An updated Asia Pacific Consensus Recommendations on colorectal cancer screening.

OBJECTIVE: Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. DESIGN: Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. RESULTS: Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. CONCLUSIONS: Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.

The use of Pillcam Colon in assessing mucosal inflammation in ulcerative colitis: a multicenter study.

BACKGROUND AND STUDY AIM: Treatment of ulcerative colitis should be tailored to the severity of colonic inflammation, which in the past has been gauged mainly by clinical features and biochemical parameters. Recently, mucosal healing has been proposed as a standard to guide therapy. The aim of this multicenter study was to test whether mucosal appearance, as reported by colon capsule endoscopy (CCE), can be used to differentiate active from inactive ulcerative colitis. PATIENTS AND METHODS: Adult patients from Hong Kong, Singapore, and Taiwan who were suspected or known to have ulcerative colitis were included in this prospective study. CCE and conventional optical colonoscopy were offered to these patients on the same day after receiving standard bowel preparation. The primary endpoint was the accuracy of CCE in assessing colonic inflammation (defined as the presence of ulcers, erythema, erosions, edema, exudates in mucosa), using optical colonoscopy as the gold standard. RESULTS: At total of 100 patients (42 females; median age 50 years; range 22 - 68 years) were enrolled. Four cases were excluded from the analysis due to technical failure or slow transit of the capsule. In nine patients, the capsule was not excreted within 8.5 hours and required retrieval during colonoscopy. The sensitivity of CCE to detect active colonic inflammation was 89 % (95 % confidence interval [CI] 80 - 95) and specificity was 75 % (95 %CI 51 - 90). The positive and negative predictive values of CCE for colonic inflammation were 93 % (95 %CI 84 - 97) and 65 % (95 %CI 43 - 83), respectively. No serious adverse event related to the CCE procedure or preparation was reported. CONCLUSION: CCE is a safe procedure to monitor mucosal healing in ulcerative colitis. However, at this stage, CCE cannot be recommended to replace conventional colonoscopy in the management of this condition.

Value of gastrin-17 in detecting antral atrophy.

PURPOSE: Decreased plasma gastrin-17 (G-17), particularly after protein stimulation, is indicative of atrophy in the antral stomach mucosa. Available data on the value of this biomarker is inconclusive. Our study was aimed to evaluate the performance of the G-17 test in Caucasian and Asian patients for antral atrophy evaluation either in fasting state or after protein stimulation. MATERIAL/METHODS: 241 dyspeptic patients aged 55 and above from Latvia (125), Lithuania (76) and Taiwan (40) were enrolled. G-17 levels were detected in plasma samples obtained either during fasting or after a protein-rich test meal. Levels <1 pmol/L at fast and <5 pmol/L after stimulation were considered indicative of atrophy. RESULTS: The sensitivity of the test was 15.8%, its specificity 88.7%, and the overall accuracy 83% in the fasting state, and 36.8, 86.5, and 82.6%, respectively, after stimulation. In the Caucasian subgroup, the corresponding figures were 15.4, 91.5, and 86.6% in the fasting state and 30.8, 92.6, 88.6% after stimulation; but for the Asian subgroup the corresponding figures were 16.7, 73.5, and 65% (fasting) and 50, 52.9, and 52.5% (stimulated). CONCLUSIONS: The performance of G-17 was better after protein stimulation. G-17 was highly specific in the Caucasian, but not in the Asian subgroups. Still the low test sensitivity either at fast or following protein stimulation does not allow us to recommend it for wide screening purpose to diagnose antral atrophy.

Oriental HLA-A*11:90 detected in a Taiwanese cord blood sample and the haplotype in association with A*11:90 allele.

We report here an HLA-A allele, A*11:90, found in a Taiwanese cord blood sample using DNA sequence-based typing (SBT) protocol after observing an anomalous reaction pattern in a sequence-specific oligonucleotide (SSO) typing exercise. The sequence of A*11:90 is identical to A*11:01:01, the most predominant A*11 variant in Taiwanese, in exon 2 but differs from A*11:01:01 in exon 3 by two nucleotide substitutions at codon 163 (c.487C>G and c.488G>A), resulting R163E. In comparison with the sequence of A*11:02:01, the second most predominant subtype of A*11 in Taiwanese A*11:90 has one nucleotide difference at codon 19 (c.55A>G) in exon 2 resulting K19E and two nucleotides variations at codon 163 (c.487C>G and c.488G>A) in exon 3 resulting R163E. HLA-A*11:90-B*40:02-DRB1*11:01 is the deduced probable HLA haplotype in association with A*11:90. The generation of A*11:90 is thought to involve a DNA recombination event between alleles A*11:01:01 and A*80:01 where A*80:01 donated a fragment of the DNA sequence (from n.t. 487 to n.t. 497) to the recipient sequence of A*11:01:01.

Discovery of two novel HLA-B alleles, B*46:13:03 and B*15:189, in two Taiwanese volunteer bone marrow donors by sequence-based typing.

We report here two novel HLA-B alleles, B*46:13:03 and B*15:189, discovered in two Taiwanese volunteer bone marrow donors. The sequence of B*15:189 has a nucleotide sequence possibly derived from a recombination event between HLA-B*39:01:01 and B*15:01:01:01, while the origin of the sequence B*46:13:03 was less obvious to postulate, considering the low frequency of B*46:13 in the general population and the silent mutations involved. Our report here adds further HLA polymorphism to the growing lists of HLA-B*46 and HLA-B*15 and provides an additional HLA information for donor search programme for patients undergoing transplant.

Detection of two HLA-A alleles, A*31:30 and A*26:20, in two Taiwanese volunteer bone marrow donors by sequence-based typing.

We here report detection of a novel sequence of HLA-A*31:30 and a confirmatory sequence of HLA*26:20 from two Taiwanese individuals. The sequence of A*31:30 is identical to that of A*31:01:02 in exons 2 and 3, except one nucleotide (n.t.) substitution c.539T > G resulting in p.Leu180Trp. The sequence of A*26:20 is identical to A*26:01:01 in exons 2 and 3, except a segment of the sequence from n.t. 78 to n.t.102. The mismatched sequence segment is identical to a sequence segment of A*02:03:01, suggesting that the formation of A*26:20 was resulted from a DNA recombination event between A*26:01:01 and A*02:03:01 sequences. A*26:20 differs from A*26:01:01 with c.98A > T resulting in p.Tyr33Phe.

Identification of two novel HLA-B*40 alleles, B*40:137 and B*40:158, in Taiwanese individuals.

Using sequence-based typing method we discovered two new HLA-B*40 variants, B*40:137 and B*40:158, in Taiwanese individuals. The sequence of B*40:137 has three nucleotide (nt) changes from B*40:21 at nt 353 (C→T), nt 355 (C→A) and nt 369 (C→T) resulting two coding changes at residue 94 (T→I) and residue 95 (L→I), whereas the sequence of B*40:158 differs from B*40:01:01 with five nt substitutes at nt 463 (C→A), nt 477 (C→G), nt 499 (T→A), nt 512 (T→G) and nt 527 (T→A) causing five amino acid exchanges at codons 140 (Y→S), 155 (R→S), 168 (S→T), 171 (L→W) and 179 (V→E). Our hypotheses on the generation of the two novel alleles are presented.

Identification of a novel HLA-A allele, A*11:60, in a Taiwanese family.

We report the identification and sequence analysis of a new HLA-A11* variant, A*11:60 allele, found in a Taiwanese leukaemic patient and his siblings. The novel A*11 variant is identical to A*11:03 in exon 2 but differs from A*11:03 in exon 3 by one nucleotide substitution at position 527 (A→T) causing an amino acid change at codon 152 E (Glu)→V (Val) (GAG→GTG). In comparison with HLA-A*11:01:01, allele A*11:60 has two nucleotide differences in exon 3: at nt 524 (A→G) (CAT→CGT) and at nt 527 (C→T) (GCG→GTG) leading to two amino acid variations at residues 151 H (His)→R (Arg) and 152 A (Ala)→V (Val).

An HLA-A*02:01-B*13:01-DRB1*14:01:03 haplotype conserved in Taiwanese and a possible close relationship between DRB1*14:01:03 and DRB1*14:54.

We here report sequence confirmation and analysis of the variant HLA-DRB1*14:01:03 on three voluntary bone marrow donors and the conserved haplotype carrying DRB1*14:01:03 allele in Taiwanese population. In exon 2, the DNA sequence of DRB1*14:01:03 is identical to HLA-DRB1*14:01:01 except a silent nucleotide substitution at position 192. However, sequence specific primer (SSP) reaction pattern of DRB1*14:01:03 matched with the pattern of DRB1*14:54 instead of DRB1*14:01:01, 14:01:02 or 14:01:03. In exon 3, at position 421, DRB1*14:01:03 has an identical nucleotide as DRB1*14:54 but differs from DRB1*14:01:01. We think the discrepancy of the allele assignment by SSP typing protocol and by sequence-specific oligonucleotide probe (SSO) and sequence-based typing methods should be addressed. We assume DRB1*14:54 is probably the parental allele for DRB1*14:01:03.

Time trends of endoscopic and pathological diagnoses related to gastroesophageal reflux disease in a Chinese population: eight years single institution experience.

The discrepancy between Eastern and Western countries exists regarding the time trends of Barrett's esophagus (BE)/adenocarcinoma. We aimed to elucidate this issue through a retrospective review of the endoscopic and pathological diagnoses of gastroesophageal reflux disease (GERD) over time in a Chinese population. All records were analyzed from 2000 to 2007. Records included demographic data, clinical indication for endoscopy, and endoscopic findings. The total number of endoscopic procedures increased over time. The indications for referral endoscopy secondary to GERD increased from 366 cases (4.9%) in the beginning of the study to 1439 cases (14.1%) at the end. Concomitant GERD symptoms did not significantly change (range, 13-15.1%) in screening endoscopic studies. Endoscopic detection of erosive esophagitis increased in referral populations from 1546 (20.7%) to 5207 cases (51%) and by screening endoscopy from 791 (14.5%) to 1983 cases (23.5%). The prevalence of nonerosive reflux disease and BE did not change over time. BE-associated dysplasia and adenocarcinoma were rare. The detection of Los Angeles class A disease increased with time in referral endoscopy cases with a focus on erosive esophagitis composition. The endoscopic demand for GERD investigation and the GERD endoscopic diagnosis increased in our population. The results were related to a higher prevalence of low-grade erosive disease diagnosed. The incidence of BE-associated dysplasia and adenocarcinoma has been the same and the increased screening did not detect more cancers.

New allele name of some HLA-DRB1*1401: HLA-DRB1*1454.

The primary function of MHC polymorphism is considered as the foundation of self-defense mechanism of the host in surveillance against countless diverse invading pathogens. However, this biological function can also elicit undesirable immunological responses that jeopardize transplantations when compatibility between donors and recipients is unfavourable.

The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease.

BACKGROUND AND AIMS: The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease (GORD), which remains elusive, was quantified. METHODS: The population included 3669 subjects undergoing repeated upper endoscopy. Data were analysed using a three-state Markov model to estimate transition rates (according to the Los Angeles classification) regarding the natural course of the disease. Individual risk score together with the kinetic curve was derived by identifying significant factors responsible for the net force between progression and regression. RESULTS: During three consecutive study periods, 12.2, 14.9 and 17.9% of subjects, respectively, progressed from non-erosive to erosive disease, whereas 42.5, 37.3 and 34.6%, respectively, regressed to the non-erosive stage. The annual transition rate from non-erosive to class A-B disease was 0.151 per person year (95% CI 0.136 to 0.165) and from class A-B to C-D was 0.079 per person year (95% CI 0.063 to 0.094). The regression rate from class A-B to non-erosive disease was 0.481 per person year (95% CI 0.425 to 0.536). Class C-D, however, appeared to be an absorbing state when not properly treated. Being male (relative risk (RR) 4.31; 95% CI 3.22 to 5.75), smoking (RR 1.20; 95% CI 1.03 to 1.39) or having metabolic syndrome (RR 1.75; 95% CI 1.29 to 2.38) independently increased the likelihood of progressing from a non-erosive to an erosive stage of disease and/or lowered the likelihood of disease regression. The short-term use of acid suppressants (RR 0.54; 95% CI 0.39 to 0.75) raised the likelihood of regression from erosive to non-erosive disease. CONCLUSIONS: Intraoesophageal damage is a dynamic and migratory process in which the metabolic syndrome is associated with accelerated progression to or attenuated regression from erosive states. These findings have important implications for the design of effective prevention and screening strategies.

Asia Pacific consensus recommendations for colorectal cancer screening.

Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5-9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.

Subfrontal schwannoma masquerading as meningioma.

Intracranial schwannomas not associated with cranial nerves are rare and seldom encountered in the subfrontal region. We report a case of subfrontal schwannoma in a 21-year-old man who presented with seizures. Radiological features resembled an olfactory groove meningioma. The histological diagnosis of schwannoma was confirmed by immunohistochemical staining with S-100 and electron microscopy. We advocate the use of immunohistochemistry and electron microscopy as adjuncts to conventional light microscopy in differentiating schwannomas from meningiomas. Surgery remains the main therapeutic modality and complete excision is associated with cure.

Endovascular treatment of radiation-induced petrous internal carotid artery aneurysm presenting with acute haemorrhage. A report of two cases.

Haemorrhage from rupture of petrous ICA aneurysm can be life threatening and emergency treatment is required. We report 2 cases of radiation-induced petrous internal carotid artery (ICA) aneurysm presenting with acute haemorrhage (epistaxis and otorrhagia) after radiotherapy (RT) for nasopharyngeal carcinoma (NPC). Both patients had a history of RT treatment for NPC. The first patient, a 54-year-old man, presented with sudden severe epistaxis and haemorrhagic shock. The second patient, a 35-year-old man, presented with episodes of severe otorrhagia. The first patient was immediately resuscitated. Obliteration of the aneurysm was performed by endovascular occlusion of the ICA with Guglielmi detachable coils and fibered platinum coils. For the second patient, the aneurysm was treated by deploying a self-expandable stent across the aneurysm neck. In an emergency situation, ruptured petrous ICA aneurysm can be treated with endovascular occlusion of the ICA with microcoils if there is a good collateral blood flow. Alternatively, the aneurysm can be treated by deployment of a stent, which can induce stasis and eventual thrombosis of the aneurysm.

Traumatic intracranial aneurysm in infancy.

An anterior cerebral artery traumatic aneurysm in a 15-month-old infant is described. The diagnosis was confirmed by computed tomographic angiography. The patient recovered fully after successful clipping of the aneurysm. As the signs of traumatic intracranial aneurysm may be subtle especially in young children, a high degree of suspicion is essential in patients presenting with delayed neurological deterioration after head trauma.

Transvenous embolisation of spontaneous carotid-cavernous fistulas by sequential occlusion of the cavernous sinus.

SUMMARY: There are two important pathological features associated with carotid-cavernous fistula (CCF): the retrograde cortical venous drainage that can cause intracranial haemorrhage and non haemorrhagic neurological deficit and the retrograde ophthalmic venous drainage that causes orbital venous congestion and visual impairment. We propose a sequential embolisation strategy by the selective occlusion of these two pathological features as the initial steps followed by occlusion of the rest of the cavernous sinus. Eight patients with spontaneous CCF were treated by transvenous embolisation using our embolisation strategy. The clinical features, angiographic findings, embolisation procedures, and clinical and angiographic outcomes were analyzed. The follow-up period ranged from one to 21 months. Clinical cure was achieved in six patients at one to two month follow-ups. One patient with bilateral CCFs had clinical cure of the right eye and clinical improvement of the left eye at three-month follow-up. Another patient had clinical cure at one-month follow-up except residual VI nerve palsy. Two patients had complete angiographic obliteration of the fistula immediately after the embolisation procedure. Another three patients underwent follow-up angiography at one to 16 months and all showed angiographic cure. There were no immediate or late complications. Our embolisation strategy offers a safe and effective option in the embolisation of spontaneous CCF as demonstrated by the clinical results of our eight patients.

Ethyl isopropylamiloride downregulates Na,K-ATPase gene expression which confers cytotoxicity in primary proximal tubule cell cultures.

Our original attempt was to examine whether inhibition of Na/H exchange in proximal tubule would affect the expression of basolateral membrane protein Na,K-ATPase. Three amiloride analogues were tested within the range of 10(-6) M to 10(-4) M in primary cultures of proximal tubule cells. Only ethylisopropyl amiloride (EIPA) dose-dependently downregulated Na,K-ATPase activity in cultured proximal tubule cells. The time course study revealed that EIPA (10(-4) M) significantly decreased Na,K-ATPase alpha- and alpha-mRNA abundance within 4 hr and suppressed Na,K-ATPase alpha- and beta-mRNA levels by 76.3 +/- 4.5% and 85.5 +/- 5.8%, respectively, within 24 hr. The decrease in Na,K-ATPase mRNA was followed by a decrease in Na,K-ATPase activity by 22.5 +/- 10.8% and 48.8 +/- 5.9% within 12 and 24 hr, respectively, which could be reflected by a coordinate decrease in levels of both alpha- and mature beta-protein. The cell viability was not affected until 20 hr of EIPA treatment, when an increase in LDH release and cell detachment was observed. Because EIPA rapidly decreased intracellular pH (pHi) to 6.7 within 2 hr and raising pHi to 6.6 by metabolic acidosis could not elicit changes in Na,K-ATPase activity, EIPA-induced downregulation of Na,K-ATPase should not be mediated through H+. In view of the time course of EIPA effects on Na,K-ATPase subunit mRNA, protein, activity and cell toxicity, the cytotoxic effect is likely resulted from a decrease in Na,K-ATPase activity. Take together, we conclude that EIPA induces downregulation of Na,K-ATPase expression via both pre- and post-translational mechanisms, which confers cytotoxic effects on proximal tubule cells.

Lorazepam in stupor.

The use of lorazepam in relieving catatonic symptoms is illustrated by the dramatic response in a stuporous patient. The treatment allows further investigations and management. It is recommended that clinicians familiarise themselves with this simple pharmacological intervention.