Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
Application for Research Project Grant
To: Basic Health Research Center
Research Title: Morphological spectrum of endometrial pathology in women
presenting with atypical uterine bleeding at King Khalid Hospital, Almajmaah,
Kingdom of Saudi Arabia.
Name of the Principal Researcher:
Department: Pathology
College: MEDICINE
Mobile: +537336968
Duration of the research: 6 months
Official E-mail: a.taha@mu.edu.sa
Total Proposed Budget:
Abstract (Summary): (150 – 200 words)
This project looks at the abnormal uterine bleeding experienced by most women in their
reproductive life and it's a challenging gynecological problem caused by various endometrial
pathologies. One of the strongest risk factors is exposure to excess estrogen and/or a relative lack
of progesterone. Endometrial hyperplasia one of the serious clinical conditions among the women
in all age gropus. The overall risk of progression of hyperplasia to cancer is 5–10%, but this may
vary between individual patients according to the underlying endometrial histopathologic pattern.
This study aims to determine the different pattern of endometrial morphological changes, using the
WHO classification criteria on the reported histopathology specimens, which has a good correlation
with clinical outcome , and gives prognostic indicator by assess the over all risk of progression to
carcinoma. In addition to identify the rate of different morphological types of endometrial
pathologies among women in all age group at King Khalid Hospital, Almajmaah (2009 - 2013).
This study will be a descriptive review of all endometrial sampling in women presented with
abnormal uterine bleeding diagnosed at King Khalid Hospital (2009 - 2013). Data will be collected
by a pre tested checklist and analyze by SPSS.
Principal Researcher' Signature:
Date: 13-03-2014
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
Research Project Proposal
I. Names and Information of the Researchers
Names of Researchers*
Academic Ranking
Department
General
Specialization
Minor
Specialization
1.Ashraf Abdelfatah Deyab
2.Salah Ahmed Abdelrahim
Assistant Professor
Assistant Professor
Pathology
Pathology
Pathology
Pathology
Histopathology
Histopathology
*The first name indicates the Principal Researcher (PR) and the Second name is the Co-Researcher
designated by the PM to oblige responsibilities, in the case of the withdrawal of the PR.
Very Important Notes:
1. Only research projects could be submitted for financial support. Therefore completed or published
work will not be accepted. In case that published work has been granted, there will be a penalty
for all the teamwork, where they do not have the right to apply for research grants for a period of
2 years as well as all grants will be refunded.
2. The principal researcher and the co-researchers must hold Ph.D. degree; at least assistant
professor.
3. PR can collaborate with demonstrators, postgraduate students and undergraduate students to
carry out research projects.
4. The CV of the principal researcher should be provided.
5. This application must be submitted. Moreover, all researchers must have their own web page on
the Deanship of Scientific Research website. The researchers’ web pages must be activated and
all the required information should be provided to reflect academic activities and achievements.
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
II. Research Problem and Motivation
Endometrial hyperplasia and endometrial cancer is the most common gynecologic
problem and its one of the leading cause for abnormal uterine bleeding that affects
women of all age groups. It is the most common malignancy of the female genital tract in
the world and the seventh most common cause of death from cancer in women in
western Europe.
The disease is a common health threat in Kingdom of Saudi Arabia. In a study conducted
among cancer patients at King Fahad National Guard Hospital (KFNGH), Riyadh, it was
found that (24.1%) have endometrial cancer.
Factors that have been associated with a decreased incidence of endometrial cancer
include parity, lactation, use of combined oral contraceptives, a diet low in fat and high in
plant foods, and physical activity. Death rates from cancer of the uterine corpus have
been increasing. A lot of successful interventions are adopted associated with decreased
risk of endometrial carcinoma.
The goal of the study is to define risks of progression for different histomorphological
categories of endometrial hyperplasia in patients attending King Khalid Hospital,
Almajmaah city, Kingdom of Saudi Arabia, using the WHO classification as standardized
method for proper diagnostic handling and clinical outcome anticipation.
Also to avoid unreliable diagnosis of hyperplasia translates into inappropriate treatment,
either as a result of the under treatment of high risk lesions or the over treatment of low
risk lesions, which leads to unnecessary suffering and high treatment costs.
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
III. Research Objectives
3. Objectives:
To study endometrial hyperplasia among patients attending King Khalid hospital, Almajmaah,
Kingdom of Saudi Arabia.
3.1. Specific objectives:
1- To determine the rate of different age groups of women presented with abnormal
uterine bleeding, who underwent endometrial sampling.
2- To determine the rate of different histomorphological types seen in all endometrial
biopsies and curettages of women presented with abnormal uterine bleeding .
3- To determine the rate of different histopathology types of endometrial hyperplasia using
the World Health Organization (WHO) classification criteria.
4- To determine the rate of "premalignant" cases of endometrial hyperplasia e.g. the
atypical complex hyperplasia, atypical simple hyperplaisa and endometrial with
endometrial intraepithelial neoplasia (IEA).
5- To determine the rate of different types of endometrial cancer.
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
IV.
Literature Review
Endometrial carcinoma is the most common malignant tumor of the female genital tract and
the fourth most common cancer inwomen after carcinomas of breast, colorectum, and lung in women in
western world. In the United States, endometrial carcinoma accounts for approximately 6000 deaths
per year or 15% of all diagnosed abnormal uterine bleeding cases. (1)
The disease is a common health thread in Kingdom of Saudi Arabia. In a study conducted among cancer
patients at King Fahad National Guard Hospital (KFNGH), Riyadh, it was found that (24.1%) have
endometrial cancer. (2)
Up to 14 percent of women experience irregular or excessively heavy menstrual bleeding. This abnormal
uterine bleeding generally can be divided into anovulatory and ovulatory patterns.
Most commonly, chronic anovulation can lead to irregular bleeding, prolonged unremitting unopposed
estrogen stimulation results in endometrial hyperplasia, and increased risk of endometrial cancer. This
status of increase estrogen stimulation found to be associated with endogenous factors, e.g. polycystic
ovary syndrome, uncontrolled diabetes mellitus, thyroid dysfunction, hyperprolactinemia, and use of
drugs (exogenous) e.g. antipsychotics, Tamoxifen or antiepileptics, ect...
The overall risk of progression of hyperplasia to cancer is 5–10%, but this may vary substantially
between individual patients according to the histological pattern (3).
Endometrial hyperplasia is a relatively common gynecological condition that affects women of all age
groups, with the majority of cases presenting with abnormal uterine bleeding (4). It relates to excessive
cellular proliferation leading to increased volume of the endometrial tissue, with a ratio of endometrial
glands to stroma of more than 1:1 (5). The evolution of endometrial hyperplasia to carcinoma was first
recognized 70 years ago (6,7). In 1959, Kistner reported that hyperplasia reported that hyperplasia could
develop with use of unopposed estrogen and could be reversed by progestogen therapy (8).
Many classifications of endometrial hyperplasia have been proposed over the years. The one that is
currently preferred and which has been sanctioned by the World Health Organization (WHO) was
originally proposed by Kurman and Norris (9). It takes into account both the architectural and cytologic
features, in the sense of dividing the hyperplasias into simple and complex on the basis of the
architecture, and subdividing each into typical and atypical on the basis of their cytology. The latter
criterion is regarded as the most significant histologic type and the presence of nuclear atypia, which is
heightened cancer risk.
Risk of progression to carcinoma using the WHO classification, can be measure by the most important
indicator of the risk of endometrial carcinoma in women with endometrial hyperplasia(10).
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
V. Research Methodology
Study design:
This study will be a descriptive study design, will be done at King Khalid Hospital, Almajmaah, Kingdoms
of Saudi Arabia.
Study population:
Records of women who presented with abnormal uterine bleeding (AUB), from January 2009 to
December 2013 will be included in this study.
Study area:
Al Majma'ah is a city and a governorate in Riyad Province, Saudi Arabia. It is located at
around 25°54′14″N 45°20′44″E, and has an area of 30,000 square kilometers. The population of the
town is around 45,000, while the population of the governorate as a whole is approximately 97,349.
Al-Majma'ah Governorate borders the Eastern Province and Al-Qasim to the north, Thadig and Shaqra
to the south, Rumahto the east, and Zulfi and al-Ghat on the west.
This study will be carried out at King Khaild Hospital, Almajma'ah governorate, which is considered as a
referral hospital to all other distric hopsitals at the governorate, including Zulfi hospital, Al-Ghat
hospital, Hawtat Sudair Hospital.
Sampling:
In this study, all records of cases of abnormal uterine bleeding with reported endometrial biopsies in the
archives (2009–2013) at King Khalid Hospital, Almajmaah area, with diagnosis of endometrial
hyperplasia, polyps and endometrial carcinoma, will be selected.
Data collection:
The data will be collected by a pre-tested checklist. The check list includes demographic data and result
of histopathological diagnosis.
Data will be extract from Pathology Department's data base using manual search records of the
registered specimens, slides storage cabnit and paraffin tissue blocks filing drawers, will be obtain for
histopathologic review and characterization.
The histological type of the endometrial biopsies will be assessed using the World Health Organization
(WHO) classification criteria. The histological grade will be based on the assessment of glands to stromal
ratios and the degree of differentiation, nuclear atypia and the mitotic index.
Data Analysis:
Data will be analyzed by SPSS for windows, version 20. Quantitative data will be expressed as a
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
percentage. Comparisons between groups for quantitative variables will be performed using the t-test.
Comparisons between qualitative groups will be evaluated using the Chi square test and p <0.05 will be
considered significant.
Ethical concern:
Ethical approval will be obtained from the ethical committee, Basic Health Research Center. Permission
will be obtained from the hospital autherity. The data will be kept and used only for the purposes of this
research.
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
VI.
References
[1] Prat J1, Gallardo A, Cuatrecasas M, Catasús L. Endometrial carcinoma: pathology and genetics. 2007
Feb;39(1):72-87. PMID:17365824 [PubMed - indexed for MEDLINE]
[2] H.M. Al-Kadri, S.H. Al-Awami, A.M. Madkhali,Assessment of risk factors of uterine cancer in Saudi
patients with postmenopausal bleeding. 2004 March,7th: Saudi Med J 2004; Vol.25 (7):857-61.
(www.smj.org.sa)
[3] J P A Baak and G L Mutter, EIN and WHO9. Clin Patho. Jan 2005; 58:1-6
(doi:10.1136/jcp.2004.021071 )
[4] Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of
‘untreated’ hyperplasia in 170 patients. Cancer 1985;56:403–12.
[5] Scully RE, Bonfiglio TA, Kurman RJ, et al. Uterine corpus. In: Scully RE, Poulsen HE, Sobin LH,
editors. Histological typing of female genital tract tumors.. New York: Springer-Verlag; 1994. p. 13.
[6] Taylor Jr HC. Endometrial hyperplasia and carcinoma of the body of uterus. AmJ Obstet Gynecol
1932;23:309–32.
[7] Novak E, Yui E. Relation of endometrial hyperplasia to adenocarcinoma of uterus. Am J Obstet
Gynecol 1936;32:674–98.
[8] Kistner RW. Histological effects of progestins on hyperplasia and carcinoma in situ of the
endometrium. Cancer 1959;12:1106–22.
1. [9] Kurman RJ, Norris HJ: Endometrium. In: Henson DE, Albores-Saavedra J, ed. The pathology of
incipient neoplasia, Philadelphia: W.B. Saunders; 1986:265-277.
[10] Lacey JV Jr, Sherman ME, Rush BB, et al. Absolute risk of endometrial carcinoma during 20-year
follow-up among women with endometrial hyperplasia. J Clin Oncol 2010; 28:788.
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
VII. Detailed Budget
1- Section (1): Researchers Compensations:
Name of Researcher
1 Dr. Ashraf Abdelfatah Deyab
2 Dr. Salah Ahmed Abdelrahim
Total of Section (1)
Duration
8
8
Monthly Compensation
1200 SR Principal Researcher
1000 SR Co-Researchers
Total
09,600 SR
08,000 SR
17,600 SR
Important Notes:
1. The maximum monthly compensation for the principal researcher is SR1200 and SR1000 for the
Co-Researcher.
2. The number of Co-Researchers should not be more than one Co-researcher. However, the
council of the Deanship of Scientific Research may exempt some projects from this condition
under special circumstances based on recommendations from research centers and referees.
3. The Co-Researcher could be from outside University, and his participation in the project is
conditionally based on his contribution to the project and that he or she has publications in
ranked ISI journals. However, this requires an approval of both the research center and Deanship
of Scientific Research.
4. The duration of any research project should not exceed 12 months.
5. The duration of the project starts from the date of signing the contract.
2- Section (2): Financial Compensations for Assistants:
Assistant Type
Research Assistant
Laboratory Tech.
Statistician
University Student
Total of Section (2)
Number
1
2
1
1
Number*Compensation*Duration
1*800*4
1*400*4
1*800*2
1*400*4
Total
03,200 SR
01,600 SR
01,600 SR
01,600 SR
08,000 SR
Important Notes:
1- The role of the assistants should be defined and their participation in the project should be for a
limited period of time and should not be more than half of the duration of the project.
2- Assistants’ compensations must be calculated according to the Scientific Research Bylaws; where
master degree holder gets monthly compensation of SR800, bachelor degree holder gets
monthly compensation of SR600 and university students and technicians get monthly
compensation of SR400.
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
3- Section (3): Equipment and Materials:
Equipment and Materials
1
2
3
4
5
6
Total of Section (3)
Number
Cost
Total Cost
Important Notes:
1- You must clearly specify all the required equipment and materials that will be needed to
complete the research project and you have to provide the estimated cost for each of them.
2- In cases, where this section is not filled, this means that your research do not needs any
materials, then materials and equipments will not be provided. Furthermore, if the estimated
costs of the required equipments and materials are not inserted on the specified columns, this
may lead to reject ion of supporting the research project.
4- Section (4): Total Budget of the Research Project
Items
Cost
17,600 SR
08,000 SR
25,600 SR
1 Total of Section (1)
2 Total of Section (2)
Total Budget of the Research Project
Important Notes:
The total budget of the research project does not include the equipments and non-consumable
materials, where such items will be returned to the research center upon the research completion.
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Kingdom of Saudi Arabia
Majmaah University
Deanship of Scientific Research
RESEARCH TIMETABLE
Starting Date:
/
/ 143
H.
Items
Months
Planned processes of major tasks
Duration
1
Tool development,tool printing, logestics and communication
1
Training and pre testing
2
Data collection
3
Data entry
4
Data analysis
5
Report writing
6
11
2
3
4
5
6
7
8
9
10
11
12