Pancreatic cancer induces a substantial global burden. We examined its global incidence/mortality rates and their correlation with socioeconomic development (Human Development Index [HDI] and Gross Domestic Product [GDP] in 2000 as proxy measures). Data on age-standardized incidence/mortality rates in 2012 were retrieved from the GLOBOCAN database. Temporal patterns in 1998-2007 were assessed for 39 countries according to gender. The Average Annual Percent Change (AAPC) of the incidence/mortality trends was evaluated using joinpoint regression analysis. The age-standardized incidence ranged between 0.8-8.9/100,000. When compared among countries, Brazil (AAPC = 10.4, 95%C.I. = 0.8,21) and France (AAPC = 4.7, 95%C.I. = 3.6,5.9) reported the highest incidence rise in men. The greatest increase in women was reported in Thailand (AAPC = 7, 95%C.I. = 2.1,12.1) and Ecuador (AAPC = 4.3, 95%C.I. = 1.3,7.3). For mortality, the Philippines (APCC = 4.3, 95%C.I. = 2,6.6) and Croatia (AAPC = 2, 95% C.I. = 0,3.9) reported the biggest increase among men. The Philippines (AAPC = 5.8, 95% C.I. 4.5,7.2) and Slovakia (AAPC = 3.1, 95% C.I. 0.9,5.3) showed the most prominent rise among women. Its incidence was positively correlated with HDI (men: r = 0.66; women: r = 0.70) and GDP (men: r = 0.29; women: r = 0.28, all p < 0.05), and similarly for mortality (men: r = 0.67; women: r = 0.72 [HDI]; men: r = 0.23; women: r = 0.28 [GDP]). In summary, the incidence and mortality of pancreatic cancer were rising in many countries, requiring regular surveillance.
Mukchun Wong Johnnyyu Jiang Liang Miaoyin Fang Yuan Yeung Ming Sze 沈祖堯
Scientific Reports
2017
Background and Aims Mucosal healing is the goal for ulcerative colitis (UC) therapy, but it needs to be confirmed via colonoscopy. Colon capsule endoscopy (CCE) is a noninvasive technique for colon investigation. Our study investigated the accuracy of second-generation CCE (CCE-2) in assessing mucosal lesions and disease activity in UC. Methods In this prospective study, CCE-2 and conventional colonoscopy were performed on the same day. CCE-2 reviewers and colonoscopists used the Mayo endoscopic subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) to assess disease activity, and they were blinded to each other's findings. Diagnostic parameters of CCE-2 for identifying mucosal lesions were evaluated by using colonoscopy as the reference. Results A total of 150 patients were enrolled. Of the 150 patients, 108 were included for per-patient analysis. CCE-2 and colonoscopy showed substantial agreement in measuring MES (intraclass correlation coefficient [ICC] 0.69; 95% confidence interval [CI], 0.46-0.81; P <.001) and UCEIS (ICC 0.64; 95% CI, 0.38-0.78; P <.001). CCE-2 had a sensitivity of 97% and 94% to detect mucosal inflammation (MES >0) and moderate to severe inflammation (MES >1), respectively. In per-segment analysis, the negative predictive values of CCE-2 to detect mucosal inflammation, including vascular pattern loss, bleeding, and erosions reached 94% to 95%. Interobserver agreement between 2 independent CCE-2 readers for both scoring systems was good (ICC >.80). The sensitivity and specificity of CCE-2 in detecting postinflammatory polyps were 100% and 91%, respectively. CCE-2 was better tolerated and preferred by patients than was colonoscopy. Conclusions CCE-2 yields high accuracy in detecting mucosal lesions and determining disease severity in UC. It represents a well-tolerated and reliable tool for disease monitoring in UC. (Clinical trial registration number: NCT02469103.)
Shi Hai Yun Francis ka leung Chan Higashimori Akira Kyaw Moe Jessica Ching Chan Heyson C.H. Chan Joey C.H. Chan Anthony W.H. Lam Tang Justin cy Wu 沈祖堯 Ng Siew C.
Gastrointestinal Endoscopy
2017
Cross-sectional studies suggest an increasing trend in incidence and relatively low recurrence rates of Clostridium difficile infections in Asia than in Europe and North America. The temporal trend of C. difficile infection in Asia is not completely understood. We conducted a territory-wide population-based observational study to investigate the burden and clinical outcomes in Hong Kong, China, over a 9-year period. A total of 15,753 cases were identified, including 14,402 (91.4%) healthcare-associated cases and 817 (5.1%) community-associated cases. After adjustment for diagnostic test, we found that incidence increased from 15.41 cases/100,000 persons in 2006 to 36.31 cases/100,000 persons in 2014, an annual increase of 26%. This increase was associated with elderly patients, for whom incidence increased 3-fold over the period. Recurrence at 60 days increased from 5.7% in 2006 to 9.1% in 2014 (p<0.001). Our data suggest the need for further surveillance, especially in Asia, which contains ≈60% of the world’s population.
Ho Jeffery Dai Rudin Z.W. Kwong Thomas Wang Xiansong Zhang Lin Margaret Ip Chan Hawkey Lam 黄至生 Gary Tse Matthew Chan Francis ka leung Chan Jun Yu Ng Siew C. 李礼舜 Justin cy Wu 沈祖堯 William ka kei Wu Sunny Wong
Emerging Infectious Diseases
2017
Background Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world. Methods We searched MEDLINE and Embase up to and including Dec 31, 2016, to identify observational, population-based studies reporting the incidence or prevalence of Crohn's disease or ulcerative colitis from 1990 or later. A study was regarded as population-based if it involved all residents within a specific area and the patients were representative of that area. To be included in the systematic review, ulcerative colitis and Crohn's disease needed to be reported separately. Studies that did not report original data and studies that reported only the incidence or prevalence of paediatric-onset inflammatory bowel disease (diagnosis at age <16 years) were excluded. We created choropleth maps for the incidence (119 studies) and prevalence (69 studies) of Crohn's disease and ulcerative colitis. We used temporal trend analyses to report changes as an annual percentage change (APC) with 95% CI. Findings We identified 147 studies that were eligible for final inclusion in the systematic review, including 119 studies of incidence and 69 studies of prevalence. The highest reported prevalence values were in Europe (ulcerative colitis 505 per 100 000 in Norway; Crohn's disease 322 per 100 000 in Germany) and North America (ulcerative colitis 286 per 100 000 in the USA; Crohn's disease 319 per 100 000 in Canada). The prevalence of inflammatory bowel disease exceeded 0·3% in North America, Oceania, and many countries in Europe. Overall, 16 (72·7%) of 22 studies on Crohn's disease and 15 (83·3%) of 18 studies on ulcerative colitis reported stable or decreasing incidence of inflammatory bowel disease in North America and Europe. Since 1990, incidence has been rising in newly industrialised countries in Africa, Asia, and South America, including Brazil (APC for Crohn's disease +11·1% [95% CI 4·8–17·8] and APC for ulcerative colitis +14·9% [10·4–19·6]) and Taiwan (APC for Crohn's disease +4·0% [1·0–7·1] and APC for ulcerative colitis +4·8% [1·8–8·0]). Interpretation At the turn of the 21st century, inflammatory bowel disease has become a global disease with accelerating incidence in newly industrialised countries whose societies have become more westernised. Although incidence is stabilising in western countries, burden remains high as prevalence surpasses 0·3%. These data highlight the need for research into prevention of inflammatory bowel disease and innovations in health-care systems to manage this complex and costly disease. Funding None.
Ng Siew C. Shi Hai Yun Hamidi Nima Underwood Fox E. Tang Whitney Benchimol Eric I. Remo Panaccione Subrata Ghosh Justin cy Wu Francis ka leung Chan 沈祖堯 Kaplan Gilaad G.
The Lancet
2017
Purpose of Review: This article serves as a critical review and summary of the role of stool- and blood-based molecular tests for colorectal cancer (CRC) screening indexed in PubMed between 2011 and early 2017. In particular, we focus on assays approved for clinical use and recent findings on novel biomarkers. The biological rationale, clinical performance characteristics, and limitations of these tools are discussed. Recent Findings: Novel miRNA markers and bacterial DNA markers have been reported and evaluated in case-controlled studies. The plasma-based SEPT9 test and the multi-target stool DNA test (mt-sDNA) have received approval for CRC screening and are available to patients. Mt-sDNA has demonstrated a high accuracy rate in detecting colorectal neoplasia. Summary: Despite the proven benefits of CRC screening, a large percentage of the eligible population remains unscreened due to suboptimal screening compliance and the limitations of current modalities. The opportunity to improve CRC screening rates has driven research to develop novel screening approaches. Stool- and blood-based molecular tests have demonstrated significant potential for improving access to CRC screening.
Wu 沈祖堯
Current Colorectal Cancer Reports
2017
Background & Aims Altered gut microbiota is implicated in development of colorectal cancer (CRC). Some intestinal bacteria have been reported to potentiate intestinal carcinogenesis by producing genotoxins, altering the immune response and intestinal microenvironment, and activating oncogenic signaling pathways. We investigated whether stool from patients with CRC could directly induce colorectal carcinogenesis in mice. Methods We obtained stored stool samples from participants in a metagenome study performed in Hong Kong. Conventional (male C57BL/6) mice were given azoxymethane to induce colon neoplasia after receiving a course of antibiotics in drinking water. Mice were gavaged twice weekly with stool from 5 patients with CRC or 5 healthy individuals (controls) for 5 weeks. Germ-free C57BL/6 mice were gavaged once with stool from 5 patients with CRC or 5 controls. We collected intestinal tissues from mice and performed histology, immunohistochemistry, expression microarray, quantitative polymerase chain reaction, immunoblot, and flow cytometry analyses. We performed 16S ribosomal RNA gene sequencing analysis of feces from mice. Results Significantly higher proportions of conventional mice fed with stool from individuals with CRC than control stool developed high-grade dysplasia (P <.05) and macroscopic polyps (P <.01). We observed a higher proportion of proliferating (Ki-67-positive) cells in colons of germ-free mice fed with stool from patients with CRC vs those fed with stool from controls (P <.05). Feces from germ-free and conventional mice fed with stool from patients with CRC vs controls contained different microbial compositions, with lower richness in mice fed with stool from patients with CRC. Intestines collected from conventional and germ-free mice fed with stool from patients with CRC had increased expression of cytokines that modulate inflammation, including C-X-C motif chemokine receptor 1, C-X-C motif chemokine receptor 2, interleukin 17A (IL17A), IL22, and IL23A. Intestines from conventional and germ-free mice fed with stool from patients with CRC contained higher proportions of T-helper 1 (Th1) cells (2.25% vs 0.44%) and Th17 cells (2.08% vs 0.31%) (P <.05 for each) than mice fed with stool from controls. Real-time polymerase chain reaction arrays revealed up-regulation of genes involved in cell proliferation, stemness, apoptosis, angiogenesis, invasiveness, and metastasis in mice fed with stool from patients with CRC. Conclusions We fed stool samples from patients with CRC and heathy individuals to germ-free mice and conventional mice with azoxymethane. We found stool from patients with CRC to increase the numbers of polyps, levels of intestinal dysplasia and proliferation, markers of inflammation, and proportions of Th1 and Th17 cells in colon, compared with stool from individuals without CRC. This study provides evidence that the fecal microbiota from patients with CRC can promote tumorigenesis in germ-free mice and mice given a carcinogen.
Wong Sunny H. Zhao Liuyang Xiang Zhang Nakatsu Geicho Han Juqiang Xu Weiqi Xiao Xue Kwong Thomas Ho yin Tsoi William ka kei Wu Zeng Ben-Hua Francis ka leung Chan 沈祖堯 Hong Wei Jun Yu
Gastroenterology
2017
Background and Aims: Endoscopic and histological healing are associated with improved clinical outcomes in ulcerative colitis [UC]. We aimed to investigate the predictive value of faecal immunochemical test [FIT] for endoscopic and histological healing in UC. Methods: We measured quantitative FIT and faecal calprotectin [FC] in 140 consecutive UC patients who underwent colonoscopy. We assessed the diagnostic accuracy of FIT for predicting endoscopic healing using the Mayo endoscopic subscore [MES 0/1] and for histological healing using the Geboes score [< 2.0] and Nancy index [grade = 1]. The predictive abilities of FIT were compared with those of FC. Results: FIT had an area under the curve [AUC] of 0.77 (95% confidence interval [CI] 0.67-0.86, p < 0.001) for endoscopic healing, an AUC of 0.77 [95% CI 0.67-0.86, p < 0.001] using the Geboes score, and 0.77 [95% CI 0.66-0.85, p < 0.001] using the Nancy Index for histological healing. The AUC of FIT was comparable to that of FC for endoscopic healing [p = 0.773] and histological healing [p = 0.767-0.960], and was comparable to colonoscopy for histological healing [p = 0.384-0.673]. FIT < 50 ng/ml predicted endoscopic healing with a sensitivity, specificity, and positive predictive value [PPV] of 72%, 68%, and 82%, respectively, and for histological healing with a sensitivity, specificity, and PPV of 73-75%, 67%, and 78-80%, respectively. Combining FIT with FC led to a higher specificity [90%] for histological healing. Over 85% of patients with FIT < 50 ng/ml and FC < 50 μg/g achieved histological healing. Conclusions: FIT is highly sensitive and accurate to predict endoscopic and histological healing in UC. It represents a promising non-invasive tool for monitoring mucosal healing in UC.
Shi Hai Yun Francis ka leung Chan Chan Anthony W.H. Higashimori Akira Kyaw Moe Jessica Ching Luk Arthur K.C. Sunny Wong Justin cy Wu 沈祖堯 Ng Siew C.
Journal of Crohn's and Colitis
2017
Background: Studies on cancer risk in inflammatory bowel disease (IBD) have yielded inconsistent results. We conducted a population-based study to determine the risk of cancer in patients with Crohn's disease (CD) and ulcerative colitis (UC). Methods: Using a territory-wide IBD registry in Hong Kong, we identified 2621 patients with IBD and no history of cancer from 1990 to 2016. We followed them from diagnosis until either September 2016, cancer development, proctocolectomy, or death. Standardized incidence ratios (SIRs) of overall cancer and site-specific cancers were calculated. Results: Of 2621 patients with IBD (1108 CD; 1603 UC; median age, 49 yr; 59.5% men) followed for 26,234 person-years, 88 patients developed cancer after IBD diagnosis. Patients with CD had an increased risk of anorectal cancers (SIR 4.11; 95% confidence interval (CI), 1.84-9.14) and hematological cancers (SIR 3.86, 95% CI, 1.61-9.27) including leukemia (SIR 5.98; 95% CI, 1.93-18.54). Nonmelanoma skin cancer was significantly increased in both CD and UC (CD: SIR 13.88; 95% CI, 1.95-98.51; UC: SIR 9.05; 95% CI, 2.26-36.19). Patients with CD had a higher risk of renal-cell carcinoma (SIR 6.89; 95% CI, 2.22-21.37), and patients with UC had a higher risk of prostate cancer (SIR 2.47; 95% CI, 1.24-4.95). Conclusions: In a population-based study, Chinese patients with CD are at an increased risk of anorectal cancers and hematological cancers compared with the general population. A higher risk of nonmelanoma skin cancer was also observed in CD and UC. Cancer surveillance should be considered.
So Jacqueline Tang Whitney Leung Wai K. Li Lo Fu Hang Wong Marc T. L. Sze Alex Shun Fung Leung Chi Man Tsang Steven Woon-Choi Shan Edwin H. S. Chan Kam Hon Lam Belsy C. Y. Aricjosun Hui Chow Wai Hung Lam Tsz Yiu Lam Vernon Lee Tsz Wai Lo Harris Ho Him Tang Ching Man Wong Cheuk Lau Justin cy Wu Francis ka leung Chan 沈祖堯 Marcus Harbord Ng Siew C.
Inflammatory Bowel Diseases
2017
Background and Aims: Mucosal healing is associated with improved long-term clinical outcomes in patients with ulcerative colitis. This population-based study assessed endoscopic and histological mucosal healing within the first year of diagnosis. Methods: Consecutive patients diagnosed with ulcerative colitis from six countries in Asia were prospectively enrolled. Clinical demographics, blood markers and inflammatory activity were assessed at baseline. Mayo score and Nancy index were used to assess endoscopic and histological activities, respectively. Clinical, endoscopic and histological evaluations were repeated at 1 year. Logistic regression was performed to identify predictors of mucosal healing. Results: Of 433 ulcerative colitis patients, 202 [46.7%] underwent colonoscopy at 1 year. In total, 68 [38.2%] achieved endoscopic mucosal healing and 35 [23.1%] achieved histological mucosal healing. On multivariate analysis, an elevated erythrocyte sedimentation rate [ESR] at diagnosis (odds ratio [OR], 0.332; 95% confidence interval (CI), 0.133-0.830; p = 0.018) was a significant negative predictor of endoscopic mucosal healing at 1 year, while histological features of ulceration [OR, 0.156; 95% CI, 0.028-0.862; p = 0.033] and being an ex-smoker [OR, 0.067; 95% CI, 0.005-0.965; p = 0.047] were significant negative predictors of histological healing at 1 year. Both endoscopic and histological mucosal healing were associated with less steroid use [p < 0.001 and p = 0.001, respectively] and hospitalization [p = 0.002 and p = 0.01, respectively]. Conclusions: Mucosal healing was achieved in fewer than half of patients with ulcerative colitis in the first year of diagnosis. An elevated ESR predicted less likelihood of endoscopic mucosal healing, while histological features of ulceration and being an ex-smoker at diagnosis predicted less likelihood of histological healing.
Leung Choy May Tang Whitney Kyaw Moe Niamul Gani Aniwan Satimai Limsrivilai Julajak Wang Yu-Fang Qin Ouyang Simadibrata Marcellus Abdullah Murdani Ong David E. Yu Hon Ho Zhang Jinwen Jessica Ching Justin cy Wu Francis ka leung Chan 沈祖堯 Ng Siew C.
Journal of Crohn's and Colitis
2017
BACKGROUND AND AIMS: Data on the natural history of elderly-onset ulcerative colitis [UC] are limited. We aimed to investigate clinical features and outcomes of patients with elderly-onset UC.METHODS: Patients with a confirmed diagnosis of UC between 1981 and 2013, from 13 hospitals within a territory-wide Hong Kong Inflammatory Bowel Disease Registry, were included. Clinical features and outcomes of elderly-onset patients, defined as age ≥ 60 years at diagnosis, were compared with those of non-elderly-onset disease [< 60 years at diagnosis].RESULTS: We identified 1225 patients, of whom 12.8% [157/1225; 56.1% male] had elderly-onset UC. Median duration of follow-up was 11 years [interquartile range, 6-16 years]. Age-specific incidence of elderly-onset UC increased from 0.1 per 100000 persons before 1991 to 1.3 per 100000 persons after 2010. There were more ex-smokers [32.2% vs. 12.2%, p < 0.001] and higher proportion of comorbidities [p < 0.001] in elderly-onset than non-elderly-onset patients. Disease extent, corticosteroids, immunosuppressants use, and colectomy rates were similar between the two groups. Elderly-onset disease was an independent risk factor for cytomegalovirus infection [odds ratio 2.9, 95% confidence interval 1.6-5.2, p < 0.001]. More elderly-onset patients had Clostridium difficile infection [11.0% vs. 5.4%, p = 0.007], hospitalisation for UC exacerbation [50.6% vs. 41.8%, p = 0.037], colorectal cancer [3.2% vs. 0.9%, p = 0.033], all-cause mortality [7.0% vs. 1.0%, p < 0.001], and UC-related mortality [1.9% vs. 0.2%, p = 0.017] than non-elderly-onset patients.CONCLUSIONS: Elderly-onset UC patients are increasing in number. These patients have higher risk of opportunistic infections, hospitalisation, colorectal cancer, and mortality than non-elderly-onset patients. Management and therapeutic strategies in this special group need careful attention.
Shi Hai Yun Francis ka leung Chan Wai keung Leung Li Leung Chi Man Sze Shun Fung Jessica Ching Lo Fu Hang Steve Tsang Shan Edwin H. S. Mak Lai Yee Lam Belsy C. Y. Aricjosun Hui Wong Sai Ho Wong Marc T. L. Ivan Hung Hui Chan Yiu Kay Chan Kam Hon Chingkong Loo Tong Raymond W. H. Chow Wai Hung Ng Carmen K. M. Lao Wai-Cheung Marcus Harbord 胡志 沈祖堯 Siew Ng
Journal of Crohn's & colitis
2016