A Moroccan Colorectal Cancer Database

ISSN 2321 -9017 Volume 5, No.3, April - May 2017 Imane AllaliInternational et al., International Journal of Bio-Medical Informatics and e-Health, 5(3), April May 2017, 10- 14 Journal of Bio-Medical Informatics and– e-Health

Available Online at http://www.warse.org/IJBMIeH/static/pdf/file/ijbmieh01532017.pdf

A Moroccan Colorectal Cancer Database Imane Allali1,2, Souad Chaqsare4, Noureddine Boukhatem2, Leila Bouguenouch5, Jihane Querrach6, Mohamed Sekal7, Mohammed Adnane Tazi8, Abdelouahed Er-Raki9, Karim Ouldim5, Saaïd Amzazi1, Hassan Ghazal2,3* 1 Laboratory of Biochemistry & Immunology, Faculty of Sciences, University Mohammed V, Rabat, Morocco 2 Laboratory of Physiology and Genetics, Faculty of Sciences of Oujda, University Mohammed Premier, Oujda, Morocco 3 Polydisciplinary Faculty of Nador, University Mohammed Premier, Nador, Morocco 4 National Institute of Hygiene, Rabat, Morocco 5 Department of Molecular Genetics, University hospital Hassan II, Fez, Morocco 6 Department of Gastroenterology, University hospital Hassan II, Fez, Morocco 7 Department of Pathology, University hospital Hassan II, Fez, Morocco 8 National School of Public Health, Rabat, Morocco 9 National Institute of Oncology, Rabat, Morocco

ABSTRACT Colorectal cancer is one of the most common cancers in Morocco; the number of patients has been increasing over the last decade with the increase being attributed to different changes in the lifestyle. Here, we proposed to build a database for colorectal cancer of Moroccan patients for the purpose to capture all the data that may play a major role in cancer research and for a better managing of healthcare. This colorectal cancer database includes detailed information about family history, risk factors, eating habits and other information related to diagnoses and clinical notes. Patients with colorectal cancer were recorded between 2009 and 2013 from the National Institute of Oncology in Rabat and the Hospital University Center Hassan II in Fez. Data were collected from 525 patients; they were aged between 16–90 years, with 26.3% of colorectal cancer patients were ranging from 50 to 59 years. We observed that 46.1% of cancers were localized in the rectum, 31.1% of complaining symptoms were rectal bleeding and the most used treatment was surgery (62.2%). It is expected that this database will contribute to generating great information about colorectal cancer, provide important information for epidemiological studies and support colorectal cancer research in Morocco.

CRC in the Moroccan population. Accurate and extensive data on CRC patients are very important for the understanding of cancer etiology, clinical decisions and epidemiological studies.

The purpose of this study is to create a colorectal cancer database that will be regional and national benchmarks for colorectal cancer care in Morocco. The CRC database includes detailed information about family history, risk factors, information related to diagnoses and clinical notes.

This database is very useful for the analysis of the efficacy of diagnostic and therapeutic procedures and for the evaluation of clinical outcomes in real healthcare system that are essential for decision making in the management and the treatment. Additionally, our aim is that this database is expected to contribute to generating great information about colorectal cancer, to provide reliable records, to have easy data access with a better scientific reproducibility and interoperability between institutions in order to support colorectal cancer research in Morocco.

Keywords: Database, Colorectal cancer, Morocco.

The colorectal cancer database is a data integration platform and knowledge discovery system for the oncology and scientific research. It includes detailed information about family history, risk factors, eating habits and other information related to diagnoses and clinical notes as histopathology reports, radiotherapy and chemotherapy treatment data, administrative details such as route of admission and access to imaging information which will enable accurate cancer staging (Supplementary Figure 1).

CRC database uses MySQL (My Structured Query Language) database management system to store the data.

The PHP (Hypertext Preprocessor) and the HTML (HyperText Markup Language) programming language are used for retrieval and recording of data. For data safety, passwords were required to access the database to guarantee

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MATERIALS AND METHODS 2.1. Database

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INTRODUCTION Colorectal cancer (CRC) is the third leading cause of cancer related deaths in Morocco among cancers that affect both men and women behind breast and lung cancer [1-3].

The number of patients has been increasing over the last decade, the incidence was 10.4 per 100,000 individual in 2008 compared to 6.0 in 2005 according to the Cancer Registry of Rabat [2]. According to the same cancer registry, it estimated that 2,701 new cases must be diagnosed with CRC in 2008 in Morocco and 4,096 new cases are expected to be diagnosed in 2020 [2].

In spite of increased colorectal cancer patients, little is known about the factors that may influence the incidence of 10

Imane Allali et al., International Journal of Bio-Medical Informatics and e-Health, 5(3), April – May 2017, 10- 14 the use of the data only by authorized researchers and ID’s numbers were attributed to patients to avoid data duplication.

2.2. Population and data collection The study population (n=525) comprised all men and women who had a histological confirmation of cancer in the colon or in the rectum in the University Hospital Center Hassan II of Fez and in the National Institute of Oncology of Rabat from January 2009 to December 2013. These two institutions represent two of the largest university hospital centers in Morocco; they host mainly patients from four major regions (Tangier-Tetouan-Al Houceima, Oriental, FezMeknes and Rabat-Sale-Kenitra), the percentage of population in these four regions is approximately 47.1% compared to the whole population of Morocco according to the high commissariat of planning [4]. Each patient’s medical records were reviewed to collect the clinical characteristics, laboratory results and pathological reports. The analyzed variables were age, gender, symptoms, location of the tumor, histological type and type of treatment.

2.3. Statistical analysis Descriptive analyses of patient demographic characteristics were carried out. Simple statistical analyses were used to look for the mean, standard deviation of the data according to the nature and the distribution of the data. The data were represented in percentage and absolute numbers either in graphs or tables.

3. RESULTS 3.1. Demographic and Clinical Characteristics of Patients A total of 525 patients were identified with colorectal cancer and were included in this study; 325 patients from the University Hospital Center of Fez and 200 patients from the National Institute of Oncology of Rabat from January 2009 to December 2013. The baseline demographics and clinical characteristics of these patients are listed in (Table 1). The percentage of female with CRC is 50.7% compared to 49.3% for male.

Characteristics Colorectal Cancer (CRC) n = 525 (%) Age Range 15-19 3 ( 0.5 ) 20-29 20 ( 3.8 ) 30-39 54 ( 10.3 ) 40-49 88 ( 16.8 ) 50-59 138 ( 26.3 ) 60-69 109 ( 20.8 ) 70-79 84 ( 16.0 ) 80-90 24 ( 4.6 ) Undefined 5 ( 0.9 )

Familial History of Colorectal Cancer Yes

266 259

( 50.7 ) ( 49.3 )

175

( 33.3 )

16 334

( 3.1 ) ( 63.6 )

Zone of Origin Region Tangier – Tetouan – Al Hoceima Oriental Fez – Meknes Rabat – Sale – Kenitra Beni Mellal – Khenifra Casablanca – Settat Marrakesh – Safi Draa – Tafilalt Souss – Massa Guelmim – Oued Noun Laayoune – Sakia El Hamra Dakhla – Oued Eddahab Undefined

39 7 225 60 10 6 5 7 1 0 0 0 165

( 7.4 ) ( 1.3 ) ( 42.9 ) ( 11.5 ) ( 1.9 ) ( 1.1 ) ( 1.0 ) ( 1.3 ) ( 0.2 ) ( 0.0 ) ( 0.0 ) ( 0.0 ) ( 31.4 )

Table 1. Demographic and clinical characteristics of the studied subjects

The mean age for female is 55.0 years and for male 56.1 years (Figure 1). Most of the cases have between 50-59 years for both female and male. The percentage of young patients under 40 years is 14.6% of cases. The number of patient with colorectal cancer increases steadily with age for both sexes.

Figure 1. The number of patients per age ranges shown as female (red) and men (blue)

3.2. Histological type According to Figure 2, for female, 179 cases (69.4%) of colorectal cancers are Adenocarcinoma with no other specification (NOS), followed by 45 (17.4%) Leiberkuhnien Adenocarcinoma, 22 (8.5%) other adenocarcinomas and 12 cases (4.7%) of Carcinoma. For male, we observed similar histological type; we found that 177 (71.7%)of the cases were diagnosed with Adenocarcinoma NOS followed by 42 (17.0%) Leiberkuhnien Adenocarcinoma, 17 (6.9%), other adenocarcinomas and 11 cases (4.4%) of Carcinoma.

Gender Female Male

No Undefined

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Imane Allali et al., International Journal of Bio-Medical Informatics and e-Health, 5(3), April – May 2017, 10- 14 Characteristics

Gender (%) Female Male Age (mean ± SD) Female Male Age Range (N, %) 40> 40-49 50-59 60-69 70-79 80-90

Figure 2. Distribution of colorectal cancer histological type by sex group A. Female and B. Male

3.3. Site of Colorectal Cancer The site of colorectal cancer is shown in Figure 3. For 402 patients for whom data were available, about 60.3% of tumors were localized in the rectum especially low rectum with 16.9% and 14.2% in the recto-sigmoid junction for both sexes, 23.2% of tumors were localized in distal colon (leftsided) (17.7% of patients had a tumor in the sigmoid and 5.5% in the descending colon) whereas 16.5% of tumors were locally found in the proximal colon (right-sided) (11.2% in the cecum followed by 3.8% in the transverse colon and 1.5% in the ascending colon). The age of patients was slightly higher in the right side of the colon (Table 2). A relatively higher proportion of patients with CRC were observed for both male and female at 50-59 years. When we compared the distal colon (left-sided) and the proximal colon (right-sided), we found that the number of patients were higher at 50 years or younger in the distal colon (D=31.9% vs P=25%) while the number of patients were higher at 50 years or older in the proximal colon (D=68.1% vs P=75%).

Symptoms (%) Rectal bleeding Abdominal pain Physical tiredness Diarrhea Constipation Others Undefined

Right Colon* n = 68 N (%)

Left Colon** n = 91 N (%)

Rectum

37 (54.4) 31 (45.6)

50 (54.9) 41 (45.1)

122 (50.2) 121 (49.8)

55.6 ± 11.8 55.8 ± 11.6 55.5 ± 12.2

54.8 ± 13.8 53.9 ± 13.5 56.0 ± 14.2

54.8 ± 15.5 53.5 ± 14.4 56.1 ± 16.5

7 (10.3) 10 (14.7) 21 (30.9) 20 (29.4) 7 (10.3) 3 (4.4)

12 (13.2) 17 (18.7) 26 (28.6) 21 (23.1) 9 (9.8) 6 (6.6)

44 (18.1) 42 (17.3) 63 (25.9) 40 (16.5) 40 (16.5) 14 (5.7)

1 (1.5) 23 (33.8) 13 (19.1) 7 (10.3) 9 (13.2) 5 (7.4) 10 (14.7)

17 (18.7) 18 (19.8) 13 (14.3) 9 (9.9) 14 (15.4) 3 (3.3) 17 (18.6)

80 (32.9) 30 (12.3) 39 (16.0) 26 (10.7) 16 (6.6) 41 (16.9) 11 (4.5)

n = 243 N (%)

*Right-sided Colon: Proximal Colon, **Left-sided Colon: Distal Colon Table 2. Comparison of clinical characteristics between right-sided, left-sided colon and the rectum

3.4. Symptom of Colorectal Cancer The frequent symptoms that we have reported are rectal bleeding (31.1%), abdominal pain (16.7%) and physical tiredness (12.3%) (Figure 4). Moreover, we compared the symptoms observed in the patients with right-sided colon with those with left-sided colon and rectum (Table 2). We observed that rectal bleeding symptom was higher in rectum (32.9%) followed by left-sided colon (18.7%), however, abdominal pain, physical tiredness and constipation were more observed in patients with right-sided colon cancer. The proportion complaining symptoms associated with diarrhea was observed to be similar in right and left sided colon and in the rectum.

Figure 3. The number of tumors located in the colon and the rectum

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Imane Allali et al., International Journal of Bio-Medical Informatics and e-Health, 5(3), April – May 2017, 10- 14 previous epidemiological studies where they revealed a predilection of the rectum in CRC in both sexes [16-18].

Recently, many studies were interested to study the clinical and biological differences between right and left sided colon in the colorectal cancer [19, 20]. In our case, we found that distal colon cancer (left-sided) is more frequent in younger people while proximal colon cancer (right-sided) increases with age for both sexes which is in accordance with previous studies where they reported a dominant presence of proximal colon cancer in older people and distal colon cancer in younger people [19, 20]. Additionally, the most observed symptoms were rectal bleeding with 31.1%, which is the mainly complained symptom from CRC patients [21, 22].

In this study, we aimed to create a Moroccan database for colorectal cancer patients. We believe that it is extremely important and helpful to have a detailed database in hospitals or in oncological centers for a better management and care and to know the epidemiological profile of the population.

Having a reliable database is a great way for storing patients records, sharing those records easily between institutions and physicians and helpful in decision-making for instance in the type of treatments or in the risk of factors. This database is not perfect, we had some limitations in the process of data collecting not all the patients have all the detailed information but it is a good start to make a model for a database that can be improve with time especially there is critical issue in the process of data collection and with such as an experience we could achieve our goal to have an accurate and complete data about CRC from the National Institute of Oncology in Rabat and the University Hospital Center Hassan II of Fez as a first step and then to be extended to the all University Hospital Centers and Oncological Centers in Morocco in order to have a much better understanding of the CRC in Morocco, to provide information and to facilitate access for oncologists and physicians to the patients records for a better analysis.

5. CONCLUSION The development of such as colorectal cancer database is the necessary first step in the comprehension of a disease to improve scientific research and clinical practice. Colorectal cancer researchers across Morocco will have access to detailed clinical data including genetics characteristics, eating habits, clinical notes and treatment, which will speed up work to understand and to prevent the disease in the future especially with the advent in the gut microbiome research and personalized medicine, they will fundamentally revolutionize the way we diagnose and treat cancer.

Acknowledgments We would like to thank Prof. Mohammed El Abkari and Prof. Sidi Adil Ibrahimi (Department of Gastroenterology), Prof. Hinde El Fatemi (Department of Pathology) from the University Hospital Hassan II of Fez and Prof. Noureddine Benjaafar (Department of Radiotherapy) from National Institute of Oncology in Rabat and Mrs. Hayat Sedrati from the National School of Public Health in Rabat for their support.

*Syndrome such as familial adenomatous polyposis (FAP) or hereditary non-polyposis colon cancer (HNPCC), also known as Lynch syndrome.

Figure 4. Type of symptoms found in patients diagnosed with colorectal cancer

3.5. Treatments The first treatment envisaged in the case of colorectal cancer is surgery in 62.2% of cases, followed by a combination of surgery and chemotherapy with 14.0% then a treatment with a combination of chemotherapy and radiation therapy with 7.7% and 7.4% for a treatment based only on chemotherapy. Radiation therapy and a combination of surgery and radiotherapy are less frequent with 5.4% and 3.3% respectively.

4. DISCUSSION With an estimated of 2,701 new cases that must be diagnosed with CRC in 2008 in Morocco [2], colorectal cancer creates interest to researchers and health authorities, therefore a population database is an ideal tool for the evaluation of actual needs for the management of colorectal cancer, especially for calculating the incidence, which is an important indicator of the impact of the disease on public health.

This Colorectal cancer database represents one of the largest data set collected from the National Institute of Oncology in Rabat and from the University Hospital Center Hassan II of Fez; those two institutions cover large areas in Morocco[4]. Over this last decade, the number of patients of colorectal cancer in Morocco is increasing [1-3, 5]. Risk factors for the development of CRC include different factors such as environmental factors, inflammatory bowel disease, age, smoking, alcohol, diet and genetic factors [6-11]. The risk of developing colorectal cancer is usually low before the age of 40 years [12], in our study, only 14.6% of cases are under 40 years for both sexes, but the risk increases sharply with age, most people diagnosed were between their fifties and seventies [13]. In our study, 62.5% of female and 64.8% of male were diagnosed between 50 and 79 years. More than 90% of CRC histological type was adenocarcinomas for both sexes; it is the more common histological type in colorectal cancer [14, 15]. Most of the CRC were localized in the rectum with 60.3%; our results are in agreement with 13

Imane Allali et al., International Journal of Bio-Medical Informatics and e-Health, 5(3), April – May 2017, 10- 14 17.

REFERENCES 1.

Register-Casablanca, Register of Cancers of Casablanca (2005-2006-2007). Edition 2012.

2.

Register-Rabat, Incidence of Cancers in Rabat (2006-2008). Cancer Registry of Rabat. Edition June 2012. 2012.

3.

Register of Cancers of Casablanca (2008-2012).

Edition 2016.

4.

Regions_Morocco, High commissariat of planning in Morocco. Edition 2014.

5.

Bouchbika, Z., et al., Cancer incidence in Morocco: report from Casablanca registry 2005-2007. Pan Afr Med J, 2013. 16: p. 31.

6.

Bernstein, C.N., et al., Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer, 2001. 91(4): p. 854-62.

7.

Hannan, L.M., E.J. Jacobs, and M.J. Thun, The Association between Cigarette Smoking and Risk of Colorectal Cancer in a Large Prospective Cohort from the United States. Cancer Epidemiol Biomarkers Prev., 2009. 18(12): p. 3362-7.

8.

Ferrari, P., et al., Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer, 2007. 121(9): p.

2065-72.

9.

Fung, T.T. and L.S. Brown, Dietary Patterns and the Risk of Colorectal Cancer. Curr Nutr Rep., 2013. 2(1): p. 48-55.

10.

Kunzmann, A.T., et al., Fruit and vegetable intakes and risk of colorectal cancer and incident and recurrent adenomas in the PLCO cancer screening trial. Int J Cancer, 2016. 138(8): p. 1851-61.

11.

Sharma, S. and S.J. O'Keefe, Environmental influences on the high mortality from colorectal cancer in African Americans. Postgrad Med J, 2007.

83(983): p. 583-9.

12.

Chiang, J.M., et al., Favorable influence of age on tumor characteristics of sporadic colorectal adenocarcinoma: patients 30 years of age or younger may be a distinct patient group. Dis Colon Rectum, 2003. 46: p. 904-910.

13.

Pinsky, P.F. and R.E. Schoen, Colorectal Cancer Incidence by Age Among Patients Undergoing Surveillance Colonoscopy. JAMA Intern Med., 2015. 175(5): p. 858-860.

14.

Hugen, N., et al., Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Ann Oncol, 2014. 25(3): p. 651-657.

15.

Fleming, M., et al., Colorectal carcinoma: Pathologic aspects. J Gastrointest Oncol., 2012.

3(3): p. 153-173.

16.

Stigliano, V., et al., Early-onset colorectal cancer: A sporadic or inherited disease? World J Gastroenterol., 2014. 20(35): p. 12420-12430.

18.

19.

20.

21.

22.

O'Connell, J.B., et al., Rates of colon and rectal cancers are increasing in young adults. Am Surg., 2003. 69(10): p. 866-72.

Meyer, J.E., et al., Increasing incidence of rectal cancer in patients aged younger than 40 years: an analysis of the surveillance, epidemiology, and end results database. Cancer, 2010. 116(18): p. 4354-9.

Nawa, T., et al., Differences between right- and leftsided colon cancer in patient characteristics, cancer morphology and histology. J Gastroenterol Hepatol., 2008. 23(3): p. 418-23.

Iacopetta, B., Are there two sides to colorectal cancer? Int. J. Cancer, 2002(101): p. 403-8.

Campbell, P.T., et al., Prospective study reveals associations between colorectal cancer and type 2 diabetes mellitus or insulin use in men.

Gastroenterology, 2010. 139(4): p. 1138-46.

Astin, M., et al., The diagnostic value of symptoms for colorectal cancer in primary care: a systematic review. Br J Gen Pract., 2011. 61(586): p. 231-43.

Supplementary Material Legends Figure 1. The conceptual model of the Moroccan database, it shows entities and their attributes

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