A 9-Year Retrospective Study of Hospitalized IBD Patients in Shanghai Rui Jin Hospital

(SBO), anal fistula, and manifestations (PM). mainly included episcleritis, stomatitis, erythema nodosum , pyoderma gangrenosum, peripheral arthritis and etc. This book is dedicated to inflammatory bowel disease, and the authors discuss the advances in the pathogenesis of inflammatory bowel disease, as well as several new parameters involved in the etiopathogeny of Crohn's disease and ulcerative colitis, such as intestinal barrier dysfunction and the roles of TH 17 cells and IL 17 in the immune response in inflammatory bowel disease. The book also focuses on several relevant clinical points, such as pregnancy during inflammatory bowel disease and the health-related quality of life as an end point of the different treatments of the diseases. Finally, advances in management of patients with inflammatory bowel disease are discussed, especially in a complete review of the recent literature.


Demographic characteristics
Overall, a total number of 769 hospitalized IBD patients were included in this study. Among them, 536 patients suffered CD (69.7%) and 233 patients suffered UC (30.3%), the percentage of CD was significantly higher than that of UC. Mean ages at diagnosis were 36.8±15.4 years old (range 2-88 years) in CD and 44.9±17.3 years old (range 3-83 years) in UC patients. The gender ratio (male/female) was 1.60 in CD and 1.28 in UC, there existed no statistical difference between these two groups (p>0.05). The mean duration of CD at first hospitalization was 5.6±4.7 years (1-70 years), of UC was 5.8±3.8 years (1-25 years). For each stratified period, the results were showed in Table 1. As we could see, the diagnosed numbers of both CD and UC increased with the year, while the ages at diagnosis were decreased. Number of male patients was more than that of female patients in both diseases in each group.

Diagnostic modalities
With the development and clinical applications of novel techniques for small bowel inspection, such as double balloon enteroscopy (DBE), multisliced CT enterography (MSCTE) and capsule endoscopy (CE), the diagnostic yield of IBD significantly increased in our hospital during the past decade.  Figure 2 showed the situation in UC. In the histograms, intuitive situation could be observed. During the year of 2008 to 2010, MSCTE became a screening method for CD patients, the application ratio was up to 76.6%.

Anatomic extent
In this study, we adopted a special scoring method to evaluate the anatomic extent. We scored 1 when the lesion only involved rectosigmoid colon, ileocecal or one segment of small intestine; scored 2 when the lesion extended up to left-sided colon, and scored 3 when As we can see, in Group of Score 1, CD was significantly more than UC (p=0.000<0.001), which indicated that the anatomic extent of CD is relatively limited comparing with that of UC. While in Group of Score 3, the situation was just the opposite (p=0.000<0.001), UC was more likely to involve extensively.  Table 4. Comparison of anatomic extent in CD and UC

Laboratory index
Although there are a lot of laboratory parameters believed to have certain relations with the severity of IBDs, the accurate role of each item remains controversial. In the present study, we observed 3 laboratory indexes with more confirming evidence of the clinical value. They are PLT, ESR (erythrocyte sedimentation rate) and CRP (C reactive protein). The criteria of each index were judged according to that of our hospital. PLT concentration higher than 300*10 9 /L, ESR level exceeded 30mm/s, CRP over 0.8mg/L were judged of abnormal.
Primarily research and clinical experience have presented that patients with IBD suffer higher risk of colonic cancer comparing with normal population, thus IBD patients should under the surveillance of tumor marker in order to provide information of the possibility of advancing cancer. Therefore, we also evaluated 3 tumor markers (CEA,  in all the patients. According to the results (Tab. 5), we had a rough impression that both ESR level and CRP level were higher in CD than in UC in Group 2 and Group 3. While other lab index showed no obvious difference between CD and UC in all 3 groups.

Clinical manifestation
Patients with IBD usually manifest similar clinical features, but each individual may have his own characteristic. And for CD and UC, the patterns of clinical manifestation are different in some aspect. The major clinical manifestations observed in the study www.intechopen.com included abdominal mass, abdominal pain, mucous stool, hematochezia, fever (higher than 39°C), small bowel obstruction (SBO), anal fistula, weight loss, surgical intervention and parental manifestations (PM). Parental manifestations mainly included uveitis, episcleritis, stomatitis, erythema nodosum, pyoderma gangrenosum, peripheral arthritis and etc.

Medical treatment
At the moment, medical treatment of IBD mainly included four kinds of pharmaceuticals: 5-aminosalicylic acid (5-ASA) or sulfasalazine, corticoids, immunosuppressant (we use azathioprine in our hospital), and tumor necrosis factor monocolonal antibody. 5-ASA or sulfasalazine was a base-line agent wildly used in mild IBD patients or used for maintenance therapy. For those IBD patients of active stage, we prescripted 4g/day of this kind of medicine. And the maintenance dosage dropped to 2g/day. Short-term intravenous or oral corticosteroid treatment was used in moderate-to-severe IBD patients. Methylprednisolone given intravenously usually start from the dosage of 40-60mg/day, and 7-10 days later, we changed to corticoids via oral route. The whole treatment course with corticoids was usually tapered within 12-25 weeks. Azathioprine was used as a second-line agent for corticosteroid-dependent or corticosteroid-refractory individuals. It was also used as the replacement therapy during the course of corticosteroid tapering. As for Infliximab, it only began to be used in CD and UC since 2008 and 2009 respectively. Infliximab was listed in China in September 2007, and was mainly used in IBD patients suffered from fistula or in those with corticosteroid-and/or immunosuppressantrefractory. The overview situation of the usage of four pharmaceuticals stated above in CD patients from 2002 to 2010 was shown in Figure 3. As we could see, 5-ASA/ sulfasalazine was always a base-line agent used in most patients (range from 70% to 97.6%). The percentages of patients using corticoids became rather stable since the year of 2006, about half of the hospitalized CD patients had the records of using corticoids. The same trend of AZA could be observed since the year of 2007. And that of UC was listed in Figure 4. 5-ASA/sulfasalazine also played an important role in treating UC, 94.2% to 100% patients were given the agent during 2006-2010. Since 2006 to 2010, the corticoids were also applied to more than half of UC patients; the data was a little bit higher than that of CD patients (63.1% vs 55.06%). The application of AZA was a little bit lower than that in CD. In 2010,

www.intechopen.com
Infliximab is more commonly used in CD patients (especially complicated with fistula) than in UC patients. An interesting phenomenon could be observed was the change of corticoids using in both diseases. From the year of 2002 to 2005, the trends of corticoids application were just in the opposite directions in CD and UC. In CD, it turned out to be a raising curve; while in UC, the ratio dropped from 80% to 47.4%. But after that, since the year of 2006, in both diseases the use of corticoids became stable.  The interval between every 2 hospitalizations ranged from 0-94 months. And the mean interval of UC was longer than that of CD (Tab. 8).

Discussion
Significant changes have been observed in the epidemiology of IBD in the last two decades. Traditionally, the incidence of IBD was higher in the developed, industrialized countries; as for CD it ranged from 0.7/10 5 to 11.6/10 5 and for UC from 2.0/10 5 to 14.3/10 5 . In contrast, nowadays it became more prevalent in the previously low incidence areas such as developing countries. In particular, the incidence and prevalence of IBD increased significantly in the Asia-Pacific region in recent years. Several recent studies confirmed that, in Asia, the prevalence of CD is 3.6/10 5 to 7.7/10 5 ，and of UC is 4.0/10 5 to 44.3/10 5 ; the morbidity of CD ranges from 0.5/10 5 to 1/10 5 , of CD the data is between 1/10 5 and 2/10 5 (Leong et al., 2004;Al-Ghamdi et al., 2004). In China, it is inferred that the prevalence may be 1.4/10 5 for CD, and 11.6/10 5 for UC. The difference of clinical epidemiology, diagnosis and treatment between Asia-Pacific IBDs and that of western countries may be contributed to the diversities of environment, genetic background and medical systems. Lakatos et al reported , the incidence of UC in developing countries is similar to that observed in North America and Western Europe, while the incidence of CD is still relatively low, suggesting that the environmental factors may act faster or differently in UC than in CD (Lakatos L & Lakatos PL, 2007). As stated before, Rui Jin Hospital affiliated to Shanghai Jiao Tong University is a tertiary level and first-class hospital, which is one of the largest public hospitals in China. This retrospective study enrolled all 769 hospitalized IBD patients from three departments in our hospital from May 2002 to December 2010. Thus, we can take it into granted that the current study, for the first time, systematically provide a relatively intact image of IBD patients in Shanghai during the past 9 years, which is also a valuable reference of the whole situation in China. Grossly, our study revealed that the prevalence of IBD in Shanghai gradually increased during the observing 9 years. The potential explanations for the increasing trend may be at least partially contributed to the popularity of western life style and diet habits in recent years. As we can see, with the development of economic, literature, as well as tourism, international interactions are more frequent, therefore the gap of environment, diet habit, and life style becomes lessen. The phenomenon that changes of life style and diet habit paralleling with the change of IBD prevalence also indicates the importance of environment mechanism in IBD. A second reason that may also contributed to the increasing of diagnostic yield of IBD is the improvement of inspection methods. As mentioned before, since 2003 when the DBE, MSCTE and CE became more and more popular in clinical application in our hospital, the diagnostic ratio of IBD also increased obviously. CE is a painless procedure that enables visualization of the entire small bowel and is highly acceptable to both doctors and patients. The disadvantages and limitations of this diagnostic modality include disability to control the direction, the random nature of the images, and the lack of a facility for sampling. The high cost of CE in China also precludes its use as a first-line diagnostic modality for small bowel disease. DBE was regarded as a revolutionary development for the diagnosis of small bowel diseases (Zhong et al., 2007). The entire small bowel could be visualized, usually with a combination of antegrade and retrograde approaches. DBE is used as a gold standard diagnostic modality for small bowel disease. MSCTE serves as a screening method now days in our hospital, when the relatively low cost of this modality taken into account. We failed to take enteroclysis into account, since we conducted it only in little amount of patients. Nevertheless, differ from other previous studies; our team reported a significantly higher prevalence of CD than that of UC. Among the total of 769 IBD patients enrolled in this study, 536 (69.7%) were suffered from CD and 233 (30.3%) were suffered from UC. Mean age at diagnosis in UC patients was older than in CD, duration of each disease didn't show much difference. Male patients were more than female patients in both diseases in each time-stratifying group. The main reason could be that CD involved small bowel easily, and the three novel inspection techniques mentioned above largely developed the blind spots in small bowel. And that may also give a reasonable explanation why it was the diagnostic yield of CD not the UC rose significantly. We chose several relatively special serologic targets in this retrospective study in IBD. The www.intechopen.com laboratory indexes observed included: the number of PLT, the level of CRP and ESR, tumor markers (CEA,. In our study, there existed no obvious differences of the CRP and/or ESR between UC group and CD group. Both markers were higher in CD than in UC. As for tumor indicators, CA-125 and CA-199 seemed to have some abnormal tendency comparing with normal population. But further and detailed research is necessary before getting more convinced conclusions. With the invention and development of immunomodulators and biologics, obvious changes have been introduced into IBD treatment in the past decade. Infliximab, a chimeric monoclonal antibody against tumor necrosis factor alpha, was first approved for the treatment of CD in 1998 (Hanauer et al., 2002;Sands et al., 2004;Targan et al., 1997); subsequently, three other biologic agents (Adalimumab, Certolizumab and Natalizumab) became available for induction and maintenance of remission in CD Feagan et al., 2008;Sandborn et al., 2007). Infliximab is the only biologic agent approved for the treatment of UC after demonstrating success in the ACT I and ACT II trials. In China, Infliximab was not listed until September 2007. We are now using it in more IBD patients in 2011, but since the clinical data of this year is not included within the current study, we have little to discuss here. As for immunosuppressive agents (such as azathioprine, methotrexate, and 6mercaptopurine), many studies during the last ten years have focused on their application in the treatment of both UC and CD (Ananthakrishnan et al., 2010;Cosnes et al., 2005). Azathioprine was used as a second-line agent for corticosteroid-dependent or corticosteroidrefractory individuals. And in our experience, it was more used as the replacement therapy during the course of corticosteroid tapering. Patient was usually asked to start using AZA two weeks before corticosteroid tapering at the dosage of 10 mg/day. The goals of IBD therapies can be summarized as: inducing remission, preventing complications, improving life quality, and reducing hospitalization as well as surgical rates (Bai & Peng, 2010). Thus, predicting of disease outcome is of great importance. Chow and his team reported that thrombocytosis in IBD patients at diagnosis predicted corticosteroiddependency, structuring phenotype of CD and presence of anaemia in UC predicted subsequent course of corticosteroid refractoriness (Chow et al., 2009). In the further research, we will convince the conclusion by collecting and analyzing the related data. With regard to relapsing, for hospitalized IBD patients, repeated-hospitalization may be looked on as an indicator. In our current study, about 1/5 patients suffered relapse within a mean interval about 7 months. The patients hospitalized for more than 6 times were mostly for treatment with Inflixmab. As for the predictive factors of relapse, is the defect of this retrospective study. We will do more detailed work in our future research. There are several limitations in our current study. First, we could not eliminate the possibility of referral bias. For the hospitalized IBD patients were in moderate-severe situations, which means patients suffer mild IBD may be cared by outpatient department. So the conclusion of this study maybe more reliable in reflecting the situation of moderatesevere patients. Second, the important marker of disease activity, CDAI, was not captured in this study, that would be the part included in our further study. Last but not least, data of some patients were not intact. The nutrition support, especially the enteral nutrition support, may induce illness ease, promote mucosal healings, and help maintaining the longterm stability of the disease. The lack of this part is also a pity. Nutrition therapy in patients with IBD is probably both undervalued and underused. Maybe we could try to make up for it in our future prospective study.

Conclusion
At present, large clinical material in IBD is still limited in Chinese population. This study, for the first time, systematically provided a relatively intact image of hospitalized IBD patients in Shanghai. The result is also a valuable reference of the whole situation in China. In summary, in this 9-year retrospective study, an increasing prevalence of IBD in Shanghai was observed, which is synchronized with that in the western countries. The changes of life style and diet habits, the improvement of diagnostic modalities may play important role in it. We have more options, such as biologics, for IBD treatment besides the traditional medicine of 5-ASA, corticosteroids and immunosuppressants. The combination and adjustment of medicine are of great significance in inducing remission and maintaining the long-term stability of the disease. To choose appropriate diagnostic modality for patients, to establish effective surveillance indexes, and to develop individualized treatment program will contribute much to pharmacoeconomics.