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

Tianle Ma, Lulu Sheng, Xiaodi Yang, Shuijin Zhu, Jie Zhong, Yaozong Yuan and Shihu Jiang *Ruijin Hospital affiliated to Medical School of Shanghai Jiao Tong University China* 

## **1. Introduction**

232 Inflammatory Bowel Disease – Advances in Pathogenesis and Management

Zwolińska-Wcisło, M.; Brzozowski, T.; Budak, A.; Kwiecień, S.; Sliwowski, Z.; Drozdowicz,

0867-5910.

D.; Trojanowska, D.; Rudnicka-Sosin, L.; Mach, T.; Konturek, S.J. & Pawlik, W.W. (2009). Effect of *Candida* colonization on human ulcerative colitis and the healing of inflammatory changes of the colon in the experimental model of *colitis ulcerosa* . *Journal of Physiology And Pharmacology*, Vol.60, No.1, pp. 107-118,

> Inflammatory bowel disease (IBD), comprising of Crohn's disease (CD) and ulcerative colitis (UC), is a kind of chronic relapsing disorder of unknown etiology, which is characterized clinically of abdominal pain, diarrhea, weight loss, fever, as well as endoscopic, radiologic, histopathologic findings and biochemical changes (e.g. perinuclear anti-neutrophil cytoplasm antibody (p-ANCA), anti-Saccharomyces cerevisiae antibody (ASCA) and IBD-specific p-ANCA markers) (Veluswamy et al., 2010).

> IBDs have been shown to be involved with potential factors such as genetic, immunologic, bacterial, and environmental elements; the relative strength of these factors and the importance of their interplay remain largely unknown (Edwards et al., 2008). Differences in incidence rates across age, time, and geographic areas suggest that environmental factors are involved in IBD, while only cigarette smoking and appendectomy have consistently been identified as risk factors (Colombel et al., 2007). Familial aggregation of IBD showed by an epidemiological study first suggested that genetic factors might play an important role in the pathogenesis of IBD. In 2001, the first CD susceptibility gene, NOD2/CARD15 on chromosome 16, was characterized. The gene identification should help us to understand the complex interaction between the environment and the intestinal immune system.

> The previous studies of IBD led to a complex overall impression of the disease, with some described patterns in disease prevalence. IBD was considered to be more frequent in the developed countries especially Northern Europe and the United States, usually of colder climates with increased incidence as distance from the equator increases. But now, IBD is increasingly reported in non-classical populations and in developing regions such as Asia, the Mid-East and Africa. More recent data showed significantly higher prevalence in Asians and time trend studies described an increasing trend in the incidence of UC and a similar but lower rise in CD (Goh & Xiao, 2009).

> The epidemiological changes that are taking place mirror the experience of Western countries 50 years ago. And the changes seem to occur in parallel with the rapid socioeconomic developments in Asia. It appears that certain racial groups among Asians who are more susceptible to IBD and who will demonstrate a higher frequency of IBD when exposed to putative environment.

> In recent years, with the improvement of living standard, the global incidence and prevalence are increasing year by year, which has seriously affected quality of life all over the world.

A 9-Year Retrospective Study of IBD Patients in Shanghai Rui Jin Hospital 235

The DBE devices used in the study were manufactured by Fujinon (EN 450P5/20, EN

We adopt the hierarchical analysis method. All the IBD in-patients during the last 9 years were divided into 3 groups according to the time when they were hospitalized: May 2002 to December 2004 as Group 1, January 2005 to December 2007 as Group 2, January 2008 to December 2010 as Group 3. The study made a longitudinal comparison among the 3 groups, and also made a horizontal comparison between the CD group and the UC group according

Data analysis was performed using SPSS 17.0 statistical software package (SPSS Inc., Chicago, USA). Continuous variables were summarized using means and standard deviations, while categorical variables were expressed as proportions. Variables were compared with the chi-square test. P value <0.05 was judged of statistical difference, while

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

**CD** (n=536) **UC** (n=233)

Mean age Num.

42.6±15.2 69

39.5±15.1 71

33.4±14.9 93

36.8±15.4 233

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

Num. **Sum.** 

(male: female)

(35:34)

(42:29)

(54:39)

(131:102)

Mean age

50.0±16.4 145

46.9±14.7 257

39.5±18.5 367

44.9±17.3 769

450T5/20; Fujinon Inc, Saitama, Japan).

<0.01 was judged of significantly statistical difference.

(male: female)

76 ( 46:30)

186 (119:67)

274 (166:108)

(331:205)

Table 1. Comparison of demographic characteristics among 3 groups

**Total** 536

diseases in each group.

**2.2 Statistical analysis** 

to the statistical results.

**3.1 Demographic characteristics** 

**3. Results** 

years (1-25 years).

**Group** 

Group 1 (2002-2004)

Group 2 (2005-2007)

Group 3 (2008-2010)

Because IBDs are chronic, life-long immunologic disorders that frequently require hospitalization or surgery. Such hospitalizations account for a significant portion of the estimated USD 6 billion in healthcare costs annually for IBD in the USA (Cappelman et al., 2008).

With regards to the treatments of IBD, it mainly focuses on two aims, one is to induct the ease of acute outbreak; and another is to maintain the alleviation (Domènech, 2006). The traditional drugs used for IBD mainly include 5-aminosalicylic acid, glucocorticoid, and immune inhibitors. In recent years, with the deeper understandings of IBD immunity mechanism, more biological agents have been introduced in the treatment and they have brought new dawn for IBD patients. The advantages of new biological agents in the treatment of IBD spark the clinical debate between the traditional Set-Up way and the new Set-Down strategy (Baert et al., 2007).

Clinically apparent malnutrition is more frequent among IBD admissions than those of non-IBD admissions. Its association with greater mortality and resource utilization may reflect more severe underlying disease that may lead to both malnutrition and worse outcomes. Nevertheless, diagnosable malnutrition may serve as a clinical marker of poor IBD prognosis in hospitalized patients (Nguyen et al., 2008). Therefore, nutrition support for IBD patients plays an important role in the treatment of IBD (Cao et al., 2005). Many previous studies have focused on different aspects of nutrition support, such as nutritional immunology, nutrition pharmacology and so on. The results of the current meta-analysis and multicenter randomized controlled clinical studies have lead to the conclusions that nutrition support especially the enteral nutrition support may induce illness ease, promote mucosal healings, and help maintaining the long-term stability of the disease.

Numerous studies from Europe and North America have provided a wealth of information regarding the epidemiological and clinical characteristics of IBDs in Caucasians. While large clinical material of IBD in China is still limited. The aim of this study is to systematically provide a relatively intact image of IBD patients in our hospital during the past 9 years, which may also be a valuable reference of the situation in China. The reason why we choosing this period of time is because April 2003 was the start of clinical application of double balloon enteroscopy (DBE) in our hospital, and then was also the start when the diagnostic yield of Crohn's Disease in our hospital significantly increased.

## **2. Patients and methods**

#### **2.1 Study population and data collection**

The data source of this study was from Shanghai Rui Jin Hospital another from May 2002 to December 2010. It covered all hospitalized IBD patients during a period of 9 years from department of gastroenterology, department of surgery and department of pediatrics. The diagnosis of IBD adhered to the criteria of Lennard-Jones (Lennard-Jones, 1989). Rui Jin Hospital is a tertiary level and first-class public hospital, it serves a well-defined catchment population in Shanghai. Over 96% of the medical care is provided by the public hospital system in this district. About 30% of the hospitalized patients were from the nearby provinces and all over China.

The total hospitalization number enrolled in this retrospective study was 769.The following data were collected and analyzed among the patients: the demographic characteristics (mainly included age and gender), the duration of the disease at diagnosis, the inspection methods used for diagnosis, the location of the lesions involved, the lab data of the patients, and the treatments followed by the convinced diagnosis (medical treatments and/or surgical treatments).

The DBE devices used in the study were manufactured by Fujinon (EN 450P5/20, EN 450T5/20; Fujinon Inc, Saitama, Japan).

### **2.2 Statistical analysis**

234 Inflammatory Bowel Disease – Advances in Pathogenesis and Management

Because IBDs are chronic, life-long immunologic disorders that frequently require hospitalization or surgery. Such hospitalizations account for a significant portion of the estimated USD 6 billion in healthcare costs annually for IBD in the USA (Cappelman et al., 2008). With regards to the treatments of IBD, it mainly focuses on two aims, one is to induct the ease of acute outbreak; and another is to maintain the alleviation (Domènech, 2006). The traditional drugs used for IBD mainly include 5-aminosalicylic acid, glucocorticoid, and immune inhibitors. In recent years, with the deeper understandings of IBD immunity mechanism, more biological agents have been introduced in the treatment and they have brought new dawn for IBD patients. The advantages of new biological agents in the treatment of IBD spark the clinical debate between the traditional Set-Up way and the new

Clinically apparent malnutrition is more frequent among IBD admissions than those of non-IBD admissions. Its association with greater mortality and resource utilization may reflect more severe underlying disease that may lead to both malnutrition and worse outcomes. Nevertheless, diagnosable malnutrition may serve as a clinical marker of poor IBD prognosis in hospitalized patients (Nguyen et al., 2008). Therefore, nutrition support for IBD patients plays an important role in the treatment of IBD (Cao et al., 2005). Many previous studies have focused on different aspects of nutrition support, such as nutritional immunology, nutrition pharmacology and so on. The results of the current meta-analysis and multicenter randomized controlled clinical studies have lead to the conclusions that nutrition support especially the enteral nutrition support may induce illness ease, promote

Numerous studies from Europe and North America have provided a wealth of information regarding the epidemiological and clinical characteristics of IBDs in Caucasians. While large clinical material of IBD in China is still limited. The aim of this study is to systematically provide a relatively intact image of IBD patients in our hospital during the past 9 years, which may also be a valuable reference of the situation in China. The reason why we choosing this period of time is because April 2003 was the start of clinical application of double balloon enteroscopy (DBE) in our hospital, and then was also the start when the

The data source of this study was from Shanghai Rui Jin Hospital another from May 2002 to December 2010. It covered all hospitalized IBD patients during a period of 9 years from department of gastroenterology, department of surgery and department of pediatrics. The diagnosis of IBD adhered to the criteria of Lennard-Jones (Lennard-Jones, 1989). Rui Jin Hospital is a tertiary level and first-class public hospital, it serves a well-defined catchment population in Shanghai. Over 96% of the medical care is provided by the public hospital system in this district. About 30% of the hospitalized patients were from the nearby

The total hospitalization number enrolled in this retrospective study was 769.The following data were collected and analyzed among the patients: the demographic characteristics (mainly included age and gender), the duration of the disease at diagnosis, the inspection methods used for diagnosis, the location of the lesions involved, the lab data of the patients, and the treatments followed by the convinced diagnosis (medical treatments and/or

mucosal healings, and help maintaining the long-term stability of the disease.

diagnostic yield of Crohn's Disease in our hospital significantly increased.

Set-Down strategy (Baert et al., 2007).

**2. Patients and methods** 

provinces and all over China.

surgical treatments).

**2.1 Study population and data collection** 

We adopt the hierarchical analysis method. All the IBD in-patients during the last 9 years were divided into 3 groups according to the time when they were hospitalized: May 2002 to December 2004 as Group 1, January 2005 to December 2007 as Group 2, January 2008 to December 2010 as Group 3. The study made a longitudinal comparison among the 3 groups, and also made a horizontal comparison between the CD group and the UC group according to the statistical results.

Data analysis was performed using SPSS 17.0 statistical software package (SPSS Inc., Chicago, USA). Continuous variables were summarized using means and standard deviations, while categorical variables were expressed as proportions. Variables were compared with the chi-square test. P value <0.05 was judged of statistical difference, while <0.01 was judged of significantly statistical difference.

## **3. Results**

## **3.1 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).


Table 1. Comparison of demographic characteristics among 3 groups

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.

A 9-Year Retrospective Study of IBD Patients in Shanghai Rui Jin Hospital 237

Fig. 1. Application of MSCTE, enteroscope, and CE in CD patients during the retrospective 9

Fig. 2. Application of MSCTE, enteroscope, and CE in UC patients during the retrospective 9

the lesion extensively involved the whole length of the colon and/or multiple segments of the small intestine. Then the number of patients of each scoring group was summarized,

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

years

years

respectively (Tab. 4).

more likely to involve extensively.

## **3.2 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.


Table 2. Panorama of diagnostic modalities applied in IBD during 2002-2010

The panorama of diagnostic modalities applications was summarized in Table 2. Enteroscopy (in the current study, both colonoscopy and DBE were included) was still the major diagnostic modality in IBD identification. Application of MSCTE became quite common both in CD and UC during year of 2008-2010 (Group 3), the total percentages of patients accepted MSCTE examines raised up to 63.5% (233/367) in all IBDs. Meanwhile, it was revealed that the use of CE was still limited in our hospital.

And we also analyzed the number of patient undertaken more than one single inspection: double inspections and all 3 inspections in different time groups (Tab. 3). In our hospital, the costs of each inspection method were: RMB 300 for colonoscopy, RMB 2,600 for antegrade/retrograde DBE, RMB 1,100 for MSCTE and RMB 2,800 for CE. Though a combination of different inspections may help increasing diagnostic yield, the high expense restricted its clinical application.


Table 3. Trends of modality combination during the year of 2002-2010

Figure 1 showed the trends of application of enteroscopy, MSCTE, and CE in CD patients during 2002 to 2010. 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%.

#### **3.3 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

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

> **CD** (%)

74/76 (97.4)

168/186 (90.3)

266/274 (97.1)

The panorama of diagnostic modalities applications was summarized in Table 2. Enteroscopy (in the current study, both colonoscopy and DBE were included) was still the major diagnostic modality in IBD identification. Application of MSCTE became quite common both in CD and UC during year of 2008-2010 (Group 3), the total percentages of patients accepted MSCTE examines raised up to 63.5% (233/367) in all IBDs. Meanwhile, it

And we also analyzed the number of patient undertaken more than one single inspection: double inspections and all 3 inspections in different time groups (Tab. 3). In our hospital, the costs of each inspection method were: RMB 300 for colonoscopy, RMB 2,600 for antegrade/retrograde DBE, RMB 1,100 for MSCTE and RMB 2,800 for CE. Though a combination of different inspections may help increasing diagnostic yield, the high expense

> **CD (%)** (n=186)

Double 12(15.8) 3(4.3) 31(16.7) 2(2.8) 103(37.6) 17(18.3) Triple 4(5.3) 0 0 0 0 0

Figure 1 showed the trends of application of enteroscopy, MSCTE, and CE in CD patients during 2002 to 2010. 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

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

**Group 1 Group 2 Group 3** 

**UC (%)** (n=71)

**MSCTE Enteroscopy CE** 

**UC** (%)

66/69 (95.7)

65/71 (91.5)

88/93 (94.6)

**CD** (%)

7/76

22/186 (11.8)

35/274 (12.8)

**CD (%)** (n=274)

(9.2) 0/69

**UC** (%)

1/71 (1.4)

2/93 (2.2)

**UC (%)** (n=93)

**3.2 Diagnostic modalities** 

1 4/76

2 67/186

3 210/274

restricted its clinical application.

**CD (%)** (n=76)

**Inspection** 

**3.3 Anatomic extent** 

**Group** 

our hospital during the past decade.

**CD** (%)

(5.3)

(36.1)

(76.6)

**UC** (%)

7/69 (10.1)

6/71 (8.5)

23/93 (24.7)

was revealed that the use of CE was still limited in our hospital.

**UC (%)** (n=69)

Table 3. Trends of modality combination during the year of 2002-2010

method for CD patients, the application ratio was up to 76.6%.

Table 2. Panorama of diagnostic modalities applied in IBD during 2002-2010

Fig. 1. Application of MSCTE, enteroscope, and CE in CD patients during the retrospective 9 years

Fig. 2. Application of MSCTE, enteroscope, and CE in UC patients during the retrospective 9 years

the lesion extensively involved the whole length of the colon and/or multiple segments of the small intestine. Then the number of patients of each scoring group was summarized, respectively (Tab. 4).

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.

A 9-Year Retrospective Study of IBD Patients in Shanghai Rui Jin Hospital 239

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

The result turned out that the ratios of SBO (p=0.000<0.01), anal fistula (p=0.000<0.01) and weight loss (p=0.008<0.01) in CD were significantly higher than in UC, abdominal pain (p=0.036<0.05), surgical intervention (p=0.025<0.05) and parental manifestations (p=0.043<0.05) also occurred more in CD patients. On the other hand, UC patients were much more common with mucous stool (p=0.000<0.01) and hematochezia (p=0.000<0.01)

Abdominal pain 436 (81.34) 177 (75.9) 4.399 0.036 Abdominal mass 17 (3.17) 3 (1.29) 2.276 0.131 Mucous stool 103 (19.22) 133 (57.08) 109.468 0.000 Hematochezia 175 (32.65) 191 (80.93) 158.415 0.000 Fever 143 (26.68) 59 (25.32) 0.154 0.694 SBO 56 (10.45) 5 (2.15) 15.326 0.000 Anal fistula 45 (8.39) 1 (0.43) 18.326 0.000 Weight loss 210 (39.18) 68 (29.18) 7.028 0.008 Surgery 51 (9.51) 11 (4.72) 5.035 0.025 PM 29 (5.41) 5 (2.15) 4.096 0.043

At the moment, medical treatment of IBD mainly included four kinds of pharmaceuticals: 5-aminosalicylic acid (5-ASA) or sulfasalazine, corticoids, immunosuppressant (we use

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 immunosuppressant-

azathioprine in our hospital), and tumor necrosis factor monocolonal antibody.

**UC** (n=233)

(%) *X*2 P value

**CD** (n=536) (%)

Table 6. The clinical manifestation observed in all 769 IBD patients

and etc.

(Tab. 6).

**Clinical manifestation** 

**3.6 Medical treatment** 

refractory.


Table 4. Comparison of anatomic extent in CD and UC

#### **3.4 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\*109/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, CA-125 and CA-199) 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.


Table 5. Comparison of lab index abnormalities between CD and UC in 3 groups

#### **3.5 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 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.

The result turned out that the ratios of SBO (p=0.000<0.01), anal fistula (p=0.000<0.01) and weight loss (p=0.008<0.01) in CD were significantly higher than in UC, abdominal pain (p=0.036<0.05), surgical intervention (p=0.025<0.05) and parental manifestations (p=0.043<0.05) also occurred more in CD patients. On the other hand, UC patients were much more common with mucous stool (p=0.000<0.01) and hematochezia (p=0.000<0.01) (Tab. 6).


Table 6. The clinical manifestation observed in all 769 IBD patients

## **3.6 Medical treatment**

238 Inflammatory Bowel Disease – Advances in Pathogenesis and Management

**Score CD** (%) **UC** (%) *X*2 P value 1 393 (73.3) 137 (58.8) 15.991 0.000 2 85 (15.9) 44 (18.9) 1.065 0.302 3 58 (10.8) 52 (22.3) 17.511 0.000

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\*109/L, ESR level exceeded 30mm/s, CRP over 0.8mg/L were judged of

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, CA-125 and CA-199)

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

> **CD** (%) (n=186)

**Group 1 Group 2 Group 3** 

26 (34.2) 24 (34.8) 96 (51.6) 36 (50.7) 164(59.9) 29 (31.2)

28 (36.8) 19 (27.5) 142(76.3) 38 (53.5) 143(52.2) 34 (36.6)

12 (15.8) 12 (17.4) 161(86.6) 33 (46.5) 163(59.5) 21 (22.6)

8 (10.5) 0 12 (6.5) 2 (2.8) 6 (2.2) 0

9 (11.8) 0 71 (38.1) 31 (43.7) 33 (12.0) 7 (7.5)

0 6 (8.7) 11 (5.9) 8 (11.3) 7 (2.6) 6 (6.5)

**UC** (%) (n=71)

**CD** (%) (n=274) **UC** (%) (n=93)

**Total number** 536 233 Table 4. Comparison of anatomic extent in CD and UC

no obvious difference between CD and UC in all 3 groups.

**UC** (%) (n=69)

Table 5. Comparison of lab index abnormalities between CD and UC in 3 groups

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

**CD** (%) (n=76)

**3.4 Laboratory index** 

abnormal.

in all the patients.

**Lab Index** 

PLT (>300\*109/L)

ESR (>30 mm/s)

CRP (>0.8 mg/L)

CEA (>5 ng/ml)

CA-125 (>35 U/ml)

CA-199 (>35 U/ml)

**3.5 Clinical manifestation** 

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.

A 9-Year Retrospective Study of IBD Patients in Shanghai Rui Jin Hospital 241

Infliximab is more commonly used in CD patients (especially complicated with fistula) than

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

Within all the 769 patients, 195 individuals had experiences of repeated-hospitalization (25.36%). 148 were CD and 47 were UC, accounted for the total number of each group 27.61% (148/536) and 20.17% (41/233), respectively. In CD cohort, 80 were male (54.1%) and

The times of repeated-hospitalization ranged from 2 to 22. Detailed information was listed in Table 7. The reasons for repeated-hospitalization mainly included intestinal obstruction,

**Times 2 3 4 5 >=6 Sum. N** 109 35 15 18 18\* 195 \* Within these 18 patients, 8 were hospitalized for 6 times, 3 for 7 times, 1 for 8 times, 2 for 9 times, 2 for

The interval between every 2 hospitalizations ranged from 0-94 months. And the mean

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 0.7/105 to 11.6/105 and for UC from 2.0/105 to 14.3/105. 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 3.6/105 to 7.7/105,and of UC is 4.0/105 to 44.3/105; the morbidity of CD ranges from 0.5/105 to 1/105, of CD the data is between 1/105 and 2/105 (Leong et al., 2004; Al-Ghamdi et al., 2004). In China, it is inferred that the prevalence may be 1.4/105 for CD, and 11.6/105 for UC. The difference of clinical epidemiology, diagnosis and treatment between Asia-Pacific IBDs and that of western countries may be contributed

CD (n=148) 6.29±10.71 0-92 UC (n=47) 10.04±15.39 0-94 Total (n=195) 6.94±12.13 0-94

**Mean interval (m) Range (m)** 

68 were female (45.9%). As for UC, 29 were male (61.7%) and 18 were female (38.3%).

severe GI bleeding, high temperature (>39°C) difficult to control, fistula, etc.

in UC patients.

the use of corticoids became stable.

14 times, 1 for 15 times and 1 for 22 times.

**4. Discussion** 

Table 7. Overview of repeated-hospitalization

interval of UC was longer than that of CD (Tab. 8).

Table 8. Overview of intervals between every 2 hospitalizations

**3.7 Repeated-hospitalization** 

Fig. 3. Medical treatments for CD during 2002-2010

Fig. 4. Medical treatments for UC during 2002-2010

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, 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.

## **3.7 Repeated-hospitalization**

240 Inflammatory Bowel Disease – Advances in Pathogenesis and Management

Fig. 3. Medical treatments for CD during 2002-2010

Fig. 4. Medical treatments for UC during 2002-2010

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, Within all the 769 patients, 195 individuals had experiences of repeated-hospitalization (25.36%). 148 were CD and 47 were UC, accounted for the total number of each group 27.61% (148/536) and 20.17% (41/233), respectively. In CD cohort, 80 were male (54.1%) and 68 were female (45.9%). As for UC, 29 were male (61.7%) and 18 were female (38.3%).

The times of repeated-hospitalization ranged from 2 to 22. Detailed information was listed in Table 7. The reasons for repeated-hospitalization mainly included intestinal obstruction, severe GI bleeding, high temperature (>39°C) difficult to control, fistula, etc.


\* Within these 18 patients, 8 were hospitalized for 6 times, 3 for 7 times, 1 for 8 times, 2 for 9 times, 2 for 14 times, 1 for 15 times and 1 for 22 times.

Table 7. Overview of repeated-hospitalization

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).


Table 8. Overview of intervals between every 2 hospitalizations

## **4. 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 0.7/105 to 11.6/105 and for UC from 2.0/105 to 14.3/105. 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 3.6/105 to 7.7/105,and of UC is 4.0/105 to 44.3/105; the morbidity of CD ranges from 0.5/105 to 1/105, of CD the data is between 1/105 and 2/105 (Leong et al., 2004; Al-Ghamdi et al., 2004). In China, it is inferred that the prevalence may be 1.4/105 for CD, and 11.6/105 for UC. The difference of clinical epidemiology, diagnosis and treatment between Asia-Pacific IBDs and that of western countries may be contributed

A 9-Year Retrospective Study of IBD Patients in Shanghai Rui Jin Hospital 243

laboratory indexes observed included: the number of PLT, the level of CRP and ESR, tumor markers (CEA, CA-125, CA-199). 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

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 (Colombel et al., 2007; 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

As for immunosuppressive agents (such as azathioprine, methotrexate, and 6 mercaptopurine), 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

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,

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

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

two weeks before corticosteroid tapering at the dosage of 10 mg/day.

we will convince the conclusion by collecting and analyzing the related data.

retrospective study. We will do more detailed work in our future research.

before getting more convinced conclusions.

current study, we have little to discuss here.

it in our future prospective study.

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

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 &

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

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

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

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

We chose several relatively special serologic targets in this retrospective study in IBD. The

Lakatos PL, 2007).

mechanism in IBD.

patients.

yield of CD not the UC rose significantly.

China.

laboratory indexes observed included: the number of PLT, the level of CRP and ESR, tumor markers (CEA, CA-125, CA-199). 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 (Colombel et al., 2007; 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 6 mercaptopurine), 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.

A 9-Year Retrospective Study of IBD Patients in Shanghai Rui Jin Hospital 245

Domènech E. (2006). Inflammatory bowel disease: current therapeutic options. Digestion,

Edwards, CN.; Griffith, SG.; Hennis, AJ. & Hambleton, IR. (2008). Inflammatory bowel

Inflammatory bowel diseases, Vol.14, No.10, pp. 1419-1424, ISSN 1078-0998 Feagan, BG.; Panaccione, R.; Sandborn, WJ.; D'Haens, GR.; Schreiber, S.; Rutgeerts, PJ.;

Goh, K.&Xiao, SD. (2009) .Inflammatory bowel disease: a survey of the epidemiology in Asia. Journal of digestive disease, Vol.10, No.1, pp. 1-6, ISSN 1751-2972 Hanauer, SB.; Feagan, BG.; Lichtenstein, GR.; Mayer, LF.; Schreiber, S.; Colombel, JF.;

randomised trial. Lancet, Vol.359, No.9317, pp. 1541-1549, ISSN 0023-7507 Kappelman, MD.; Rifas-Shiman, SL.; Porter, CQ.; Ollendorf, DA.; Sandler, RS.; Galanko,

Lennard-Jones, JE. (1989). Classification of inflammatory bowel disease. Scandinavian

Lakatos, L.&Lakatos, PL. (2007). Changes in the epidemiology of inflammatory bowel

Nguyen, GC.; Munsell, M. & Harris ML. (2008). Nationwide prevalence and prognostic

Sands, BE.; Anderson, FH.; Bernstein, CN.; Chey, WY.; Feagan, BG.; Fedorak, RN.; Kamm,

Sandborn, WJ.; Rutgeerts, P.; Enns, R.; Hanauer, SB.; Colombel, JF.; Panaccione, R.; D'Haens,

Annals of internal medicine, Vol.146, No.12, pp. 829-838, ISSN 0003-4819 Targan, SR.;Hanauer, SB.; van, Deventer SJ.; Mayer, L.; Present, DH.; Braakman, T.;

Journal of Medicine, Vol.350, No.9, pp. 876-885, ISSN 0028-4793

diseases. Orvosi hetilap, Vol.148, No.5, pp. 223-228, ISSN 0030-6002 Leong, RW.; Lau, JY.& Sung,JJ. (2004). The epidemiology and phenotype of Crohn's

Journal of Gastroenterology Vol.170, pp. 2-6, ISSN 0085-5928

disease: incidence, prevalence, and disease characteristics in Barbados, West Indies.

Loftus EV, Jr.; Lomax, KG.; Yu, AP.; Wu, EQ.; Chao, J.& Mulani P. (2008). Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study. Gastroenterology, Vol.135, No.5, pp. 1493-

Rachmilewitz, D.; Wolf, DC.; Olson, A.; Bao, W.; Rutgeerts, P.; & ACCENT I Study Group. (2002). Maintenance infliximab for Crohn's disease: the ACCENT I

JA.& Finkelstein, JA. (2008). Direct health care costs of Crohn's disease and ulcerative colitis in US children and adults. Gastroenterology, Vol.135, No.6, pp.

disease in the Chinese population. Inflammation Bowel Disease, Vol.10, No.5, pp.

significance of clinically diagnosable protein-calorie malnutrition in hospitalized inflammatory bowel disease patients. Inflammation Bowel Disease, Vol.14, No.8,

MA.; Korzenik, JR.; Lashner, BA.; Onken, JE.; Rachmilewitz, D.; Rutgeerts, P.; Wild, G.; Wolf, DC.;Marsters, PA.; Travers, SB. Blank, MA. & van, Deventer SJ.(2004). Infliximab maintenance therapy for fistulizing Crohn's disease. The New England

G.; Li, J.; Rosenfeld, MR.; Kent, JD.& Pollack PF.(2007). Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial.

DeWoody, KL.; Schaible, TF.& Rutgeerts PJ.(1997). A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. The New England Journal of Medicine, Vol.337,

Vol.73, No.1, pp. 67-76, ISSN 0012-2823

1499, ISSN 0016-5085

1907-1913, ISSN 0016-5085

646-651, ISSN 1078-0998

pp. 1105-1111, ISSN 1078-0998

No.15, pp. 1029-1035, ISSN 0028-4793

## **5. 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.

## **6. References**


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

Ananthakrishnan, AN.; McGinley, EL.; Binion, DG.& Saeian K.(2010). A novel risk score to

Al-Ghamdi, AS.;Al-Mofleh, IA.;Al-Rashed, RS.; Al-Amri, SM.; Aljebreen, AM.;Isnani, AC.&

Baert, F.; Caprilli, R.& Angelucci, E.(2007). Medical therapy for Crohn's disease: top-down or step-up? Digestive diseases, Vol.25, No.3, pp. 260-266, ISSN 0257-2753 Bai, A.&Peng, Z.(2010). Biological therapies of inflammatory bowel disease.

Cosnes, J.; Nion-Larmurier, I.; Beaugerie, L.; Afchain, P.; Tiret, E.& Gendre, JP.(2005). Impact

Chow, DK.; Sung, JJ.; Tsoi, KK.; Wong, VW.; Wu, JC.; Leong, RW. & Chan, FK. (2009).

Colombel, JF.; Sandborn, WJ.; Rutgeerts, P.; Enns, R.; Hanauer, SB.; Panaccione, R.;

Colombel, JF.;Vernier-Massouille, G.;Cortot, A.; Gower-Rousseau, C.&Salomez, JL.(2007).

Gastroenterology, Vol.105, No.8, pp. 1799-1807, ISSN 0002-9270

Immunotherapy, Vol.2, No.5, pp. 727-742, ISSN 1750-743X

therapeutics, Vol.29, No.8, pp. 843-854, ISSN 0269-2813

intestinal surgery. Gut, Vol.54, No.2, pp. 237-241, ISSN 0017-5749

stratify severity of Crohn's disease hospitalizations. The American Journal of

El-Badawi, R.(2004). Epidemiology and outcome of Crohn's disease in a teaching hospital in Riyadh. World Journal of Gastroenterology, Vol.10, No.9, pp. 1341-1344,

of the increasing use of immunosuppressants in Crohn's disease on the need for

Predictors of corticosteroid-dependent and corticosteroid-refractory inflammatory bowel disease: analysis of a Chinese cohort study. Alimentary pharmacology &

Schreiber, S.; Byczkowski, D.; Li, J.; Kent, JD.& Pollack PF. (2007). Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology, Vol.132, No.1, pp. 52-65, ISSN 0016-5085 Cao, Q.;Si, JM.; Gao, M.; Zhou, G.;Hu, WL.& Li JH.(2005). Clinical presentation of

inflammatory bowel disease: a hospital based retrospective study of 379 patients in eastern China. Chinese medical journalJ (Engl), Vol.118, No.9, pp. 747-752, ISSN

Epidemiology and risk factors of inflammatory bowel diseases. Bulletin de l'Académie nationale de médecine, Vol.191, No.6, pp. 1118-1123, ISSN 0001-4079

**5. Conclusion** 

**6. References** 

will contribute much to pharmacoeconomics.

ISSN 1007-9327

0366-6999


**Part 3** 

**Management of Inflammatory Bowel Disease** 

