|Year : 2019 | Volume
| Issue : 2 | Page : 82-88
Role of a noninvasive stool-based molecular test in screening and early detection of colorectal cancers
Khalid Ahmad Al-Sindi1, Mulazim Hussain Bukhari2, Mohmed Ali Al-Hamar3
1 Professor of Pathology, Department of Pathology, Blood Bank and Laboratory Medicine, King Hamad University Hospital, Busaiteen -, Bahrain
2 Professor and Head of Pathology, Department of UCMD, University of Lahore, Lahore, Pakistan
3 Specialist Pathologist, Department of Pathology, Blood Bank and Laboratory Medicine, King Hamad University Hospital, Busaiteen -, Bahrain
|Date of Web Publication||18-Nov-2019|
Prof. Mulazim Hussain Bukhari
Department of Pathology, UCMD, University of Lahore, Lahore
Source of Support: None, Conflict of Interest: None
Background: Colonoscopy is considered the gold standard for most currently established screening programs for colorectal carcinoma (CRC), but due to its invasive nature, there were several emerging needs for the use of a substitutive, sensitive, non-invasive triaging modalities, such as utilizing immunochromatographic fecal occult blood tests (IFOBT) or molecular stool based tests such as Glycolytic M2-Pyruvate Kinase (M2-PK). Objectives: Firstly, to evaluate the sensitivity of a molecular stool based (M2PK) test, as a non-invasive, screening modality for detecting CRC and other colorectal disease (CRD). Secondary, to insight the current prevalence of CRC precursors in the Kingdom of Bahrain and recommend a customized age of enrollment in National Screening Program for CRC, once established and Thirdly, to compare the sensitivity of this fecal tumor marker based M2-PK test, as a potential replacement for the currently used IFOB test, in an attempt to promote for the need to establish a National Screening Program for Colorectal Cancer (NSPCC) based on such molecular based test or a similar platform in the kingdom, much comparable to the currently established international screening programs. Design: Prospective, cross sectional study. Duration and Place of Study: July 2012-December 2016, King Hamad University Hospital (KHUH), Bahrain. Sample Size: 2,100 (Based on Bahrain Population statistics: 1,248.348. Materials and Methods: The stool samples were collected shortly after launching a nationwide public awareness campaign against CRD in all major governmental and private sector hospitals and clinics. Out of the intended 2100 target samples, 1074 individuals managed to go through the well-structured distributed questioner and have been selected according to the inclusion/exclusion criteria and submitted their stools' samples for the detection of any CRD. A combined (molecular M2-PK and IFOBT) stool tests were used to detect any CRD in all examined stool samples. A total of 105 M2-PK' positive and 85 M2-PK'negative individuals underwent a subsequent specialist consultation and a fast track colonoscopy. Results: Out of the intended 2100 study sample, 1552 Participants were obtained during the study period and out of those, 1199 have been selected based on the inclusion and exclusion criteria. The no-show selected participants were 624 and only 575 individuals have submitted their Stool samples along with fully completed questioners. Out of those 575, only 287 stool samples were positive with M2-PK test, while 197 of the same stool samples were positive with IFOBT. Among these positive cases, only 105 of participants agreed after their medical consultation to undergo for full colonoscopies and biopsies for microscopic examination. These 105 successful full colonoscopies reveled 85 (81%) individuals negative for any neoplastic lesion and only 20 individuals (19%) showed neoplastic lesion. These 20 neoplastic findings included, 17 (85%) adenomatous polyps, 02 (10%), adenocarcinomas, and 01 (5%) was neuroendocrine carcinoma. The 17 adenomatous polyps were 09 tubular adenomas, 01 villous adenoma, and 07 tubulovillous adenomas. The colonoscopy findings in those (85) negative cases for neoplastic lesion were (6) hemorrhoids, (13) hyperplastic polyps, (10) normal mucosae with normal biopsies, (9) diverticulosis, (1) angiodysplasia, (1) inflammatory bowel disease and (1) solitary rectal ulcer. Conclusion: The screening of CRC by Stool Based molecular test such M2-PK showed high sensitivity for the detection of neoplastic Colorectal lesions compared to IFOBT. The study also found that stool based molecular (M2-PK) test, is a rapid, non-invasive, and convenient technique, which can be used as a platform for a forthcoming CRC National Screening Program in the Kingdom of Bahrain.
Keywords: Bahrain, colorectal disease, colorectal carcinoma, colorectal disease, detection, immunochromatographic fecal occult blood test, King Hamad University Hospital, M2 pyruvate kinase, noninvasive, screening, stool-based test
|How to cite this article:|
Al-Sindi KA, Bukhari MH, Al-Hamar MA. Role of a noninvasive stool-based molecular test in screening and early detection of colorectal cancers. Acta Med Int 2019;6:82-8
| Introduction|| |
Colorectal Carcinoma (CRC) ranks the third most commonly diagnosed cancer among both genders in the United States of America. CRC is a preventable disease, yet is a known major cause of cancer mortality and is considered to be greatly attributable to inappropriate lifestyle patterns. At a global level, CRC is responsible for an estimate of 8% of cancer-related deaths. There are many reports from Asia and Africa, where the incidence of CRC in the young adults, was significantly higher compared to the Western literature, and based on the cancer registry of The Gulf Cooperation Council (GCC) Countries of 1998-2007, the incidence of CRC was 40/100,000 in men and 32/100,000 in women. Compared to other GCC countries, Kingdom of Bahrain had higher incidence rates for CRC. It has also been found that more than 75% of discovered CRC cases were in advanced local, regional or systemic stages., Although Pakistan falls into the low-risk category of the worldwide for CRC, it seems that this may not be the case anymore with the increasing risk factors among the Pakistani population. Factors known to increase the risk of cancer, such as smoking, physical inactivity, obesity and bad-diet regimen have been adapted by many worldwide, thus, increasing the burden of cancer, not just globally, but also in developing countries., The rise of the incidence of CRC in many Asian, as well as Eastern European countries, may reflect the increase in the prevalence of modifiable risk factors for this cancer, which include unhealthy diet, obesity and physical inactivity, and smoking. According to a study conducted in New Zealand, the identifiable and major risk factors that played a role in CRC were excess alcohol consumption, tobacco smoking, diet containing both red and processed meats, obesity, and lack of physical activity. Furthermore, the role of cigarette smoking was identified to cause microsatellite instability (MSI) which plays a role in the pathogenesis of CRC. Likewise, it was estimated that tobacco use was responsible for approximately 21% of colon cancers related to MSI.
In Korea, there is trend for CRC screening through fecal occult blood test (FOBT) and colonoscopy, which is the gold standard technique for the diagnosis of CRC.,
Colonoscopy is an invasiveness, expensive procedure compared to FOBT, yet, FOBT is being commonly used in the screening programs for the diagnosis of CRC all over the world due to its noninvasive, more acceptable nature. According to a previous meta-analysis studies, the sensitivity, specificity, and positive predictive value of immunochromatographic FOBT (IFOBT) in CRC were 67%, 85%, and 41%, respectively.
Recent emphases on the use of stool based molecular screening tests such as M2-Pyruvate Kinase (M2-PK) has been recently considered as a screening/triaging platform for CRC. The test is based on finding an isoenzyme of PK which is mainly produced in undifferentiated and proliferating body tissues. In neoplastic cells, M2-PK regulates the synthetic balance between ATP and macromolecules, which plays an important role in neoplastic growth and glycolysis during the process of carcinogenesis. The use of M2-PK test has been proved better than IFOBT in the detection of CRC and its precursors, i.e. the adenomatous polyps, but still being expensive or not available in most remote areas.,
The objectives of the study were, Firstly, to establish the prevalence of CRC precursors in the Kingdom of Bahrain, Secondly, to investigate the validity and reliability of stool based fecal tumor biomarker (M2-PK) test and Thirdly, to compare its sensitivity to that IFOB and perhaps to recommend this or similar stool based molecular test, as a potential replacement for the currently used IFOBT.
| Materials and Methods|| |
Approvals from Ministry of Health institutional Research board (IRB) and King Hamad Hospital Directorate of Ethics and Research were obtained.
Prospective, cross sectional study.
Duration and place of study
July 2012-December 2016, King Hamad University Hospital - Kingdom of Bahrain.
2,100 (Based on the National Statistics of Bahrain Population of 1,248.348).
BD 20,000 Granted by King Hamad University Hospital research fund with the support of the Bahrain Supreme council of health.
Operational and participants flow
The study campaigning was organized in 4 Ministry of Health centers, each center represents one of the four Governorate of Bahrain (Central, Muharraq, Northern and Southern areas), alongside, three governmental hospitals and seven private sector hospitals/clinics.
Individual's consultation and sample collection stations were controlled by the study project coordinators at King Hamad University Hospital (KHUH) in coordination with the other stations for patients consultation and sample collection stations in the four Government Hospitals of Bahrain [Figure 1].
|Figure 1: King Hamad University Hospital laboratory and other stations for patients consultation and sample collection stations in Governments Hospitals of Bahrain|
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During the campaign, all participating individuals were provided with several printable educational pamphlets and illustrational audiovisual materials, followed by head to head sessions for questions and answers discussion with health care professionals, ending by escorting participants in a walk-through a giant inflatable diseased colon for further education and raising awareness about serious CRD. Interested individuals been consented for a quick professional consultation and further education about the nature of the study, the need to submit a fully completed accompanied questioners and to submit at single stool sample for testing, and to expect a call for further medical consultation about their results and whether they need to go for screening colonoscopy and biopsy taken, if positive finding is found.
All stool samples were tested within 24 hours of submission and all results were crossed checked by two senior laboratory technologists and centralized at the microbiology section computer register at KHUH Laboratories along with photo image for each result. The results were then transferred and entered in another computer software program database for further statistical analysis. All Selected individuals based on the inclusion/exclusion criteria, were contacted via the study call center in groups within days of results retrieval of their stool samples.
- Asymptomatic fit individuals, males and females
- Age: 45-74 years
- Signed consent of enrolment in the study
- Fully completed questionnaire and submission of a single stool sample.
History of diagnosed or active cases of CRC.
EQUAL CHANCE to proceed with colonoscopy was achieved via phone calls from participating government and private sector hospitals which was overseen by the study control center at King Hamad University Hospital (KHUH), so participants can attend a fast track consultant clinic for further consultations and to proceed with performing colonoscopy procedures.
The study utilized two-stool based IFOB tests; one of which was the available kit within KHUH laboratories and being utilized for clinical use and the other one was Schebo® 2 in 1 Quick™ (M2-PK + Hb) kit. The last was a commercially available, stool-based biomarker test, claimed with a superior reproducibility of 97% sensitivity and 98% specificity for detecting colorectal neoplasia at early stages.
A single STOOL SAMPLE of Participating individual was collected at KHUH within 24 hours of sample submission, according to an agreed guidelines and logistics. The Same Stool Sample was subjected for two different kinds of tests; the regular detection of IFOB Rapid (Ministry Of Health approved) test and the Metabolic fecal tumor (M2-PK 2 in 1) biomarker test. Individuals with any Positive test would be advised to undertake subsequent colonoscopy and histopathology examination (if applicable) for confirmatory diagnosis. Tumor M2-PK test (ScheBo Biotech, Giessen, Germany), a sandwich ELISA based on two monoclonal antibodies specific for tumor M2-PK 2. The test allowed the quantitative measurement of tumor M2-PK in 4 mg of stool with a lower detection limit of 2 U ml.
All analyses were carried out in the KHUH laboratory under standardized conditions.
THE COLONOSCOPY procedures were performed by participating hospitals' consultants for positive stool cases.
All colonoscopies were performed by either Consultant Gastroenterologist or a certified General Surgeons with special interest in Colonoscopy and according to the nomination by the participating hospitals.
Colonoscopy, in this study aimed mainly as a screening tool to detect presence of inert cancer or polyp, while it naturally has been used to confirm the presence of other lesions and to perform therapeutic procedures such as removing polyps etc.
Participating hospitals were agreed to be operational throughout the period of the study and be able to give an appointment for colonoscopy within 10 days of the first consultation and if this flow isn't achievable for any reason, then arrangement through the study call Centre for colonoscopy at another facility must be proceeded. Colonoscopy surveillance with or without biopsy removable of polyps or any cancerous/pre-cancerous lesions shall follow the accepted guidelines of the hospitals and out of preview of this study, i.e. Making sure that total colonoscopy with caecal intubation (visualization) is to be demonstrated in up 90% of all colonoscopy and if this cannot be achieved for anatomical reasons, virtual CT colonoscopy will be arranged.
If a suspicious lesion/polyp is found during colonoscopy, then a biopsy/polypectomy should take for histopathology verification by two independent consultant pathologists.
To assess the validity of the (M2-PK) test compared to the currently utilized IFOB, a positive and negative control groups were set up to insight the sensitivity of the new M2-PK tumor biomarker test.
Negative control group
Fifty participating individuals with negative stool (M2-PK/IFOB) tests were consented for a checkup colonoscopy and considered as Negative Control Group based on their no objection for the procedure.
Positive control group
Fifty symptomatic patients outside the study individuals, who underwent colonoscopy for various complaints and found to have CDC proved by a histopathology biopsy confirmation were asked through their concerned surgeons to collect a single stool sample each for (M2-PK/IFOB) test before their definitive surgery. Their stool samples were tested and showed positive M2-PK results, while the IFOB test showed mixed findings.
| Results|| |
There were a total of 2100 participants, who filled the questioners, but only 1700 participants were selected, according to the selection criteria. Most of the participants, among those selected persons, did not respond and only 1074 participants submitted their stool samples. The age range of the participants was wide (25–74,) but the mean age of the patients was 52.78 ± 11.52. Only 105 of participants whom their stool tests were positive for M2-PK agreed later with difficulty to undertaken colonoscopies [Table 1]. There were 64 males and 41 (with ration of 1:1.5). There were 494 (46%) persons positive for M2-PK test, while 179 (16.6%) were positive by IFOB.
|Table 1: Comparison of data for M2-pyruvate kinase and immunochromatographic fecal occult blood test, collection from different hospital of Bahrain|
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The Results for both positive and negative M2-pyruvate kinase test in 105 individuals are shown in [Figure 2].
|Figure 2: Results for positive M2-pyruvate kinase test in 105 colonoscopic patients|
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Among these positive cases, and the only 105 participants who agreed to underwent full colonoscopies, 20 showed positive lesions while 85 were found negative for neoplastic disease. Of these, 85 (81%) patients were suffering from miscellaneous lesions and only 20 (19%) cases showed neoplastic lesion. Of these neoplastic 20 findings, 17 (85%) were of adenomatous polyps, 02 (10%) adenocarcinomas, and 01 (5%) neuroendocrine carcinoma (NEC). The adenomatous polyps included 09 tubular adenomas, 01 villous adenoma, and 07 tubulovillous adenomas [Figure 3] and [Figure 4]. The morphology of 85 negative cases included a mixture of other and non-neoplastic histology. These were polyps but normal mucosa 6 cases, hemorrhoids 13 cases, hyperplastic polyps 6 cases, normal mucosa but no biopsy 31 cases, normal mucosa 10 cases, diverticulosis 9 cases, angiodysplasia 1 case, inflammatory bowel disease 1 case, and solitary rectal ulcer 1 case [Figure 5].
|Figure 3: Distribution of histopathological variants of colorectal diseases|
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|Figure 4: Distribution of histopathological variants of adenomatous polyps|
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|Figure 5: Histopathological distribution of miscellaneous lesions by colonoscopy|
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Among these 4 cases of IFOB positive but M2-PK negative whom underwent colonoscopy, no neoplastic lesion was found. Two cases were due to hemorrhoids, and other two were normal [Figure 6].
|Figure 6: Colonoscopic findings in candidates for immunochromatographic fecal occult blood positive and M2-pyruvate kinase negative|
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Twelve cases were missed by IFOB but were picked by M2-PK, 11 were adenomatous polyps and 1 was NET [Figure 7].
|Figure 7: Positive cases missed by (negative) immunochromatographic fecal occult blood but picked up by (positive) M2-pyruvate kinase|
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| Discussion|| |
CRC is a leading cause of death worldwide, including the Kingdom of Bahrain and large numbers of newly diagnosed malignant neoplasms belong to this category as in United States of America. CDC is the third most common cancer affecting both males and females., As a matter of fact, CRC is a preventable and potentially curable healthcare problem in the Kingdom of Bahrain, yet, no well-established national screening program for early detection and management of CRC. Individuals aged 50 years and above are the typical target for most exciting CRC screening programs, yet our data revealed that, once a national screening program established in the Kingdom of Bahrain, it should also consider targeting individuals at age of 40-45. This verdict has been also emphasized in other similar studies in eastern countries. Clinical examination, medical imaging, colonoscopy findings and biopsy diagnosis are the Gold standard practice for an effective CRC screening program, however, due to various limiting factors, the value of other alternative, non-invasive adjunct screening modalities are being mostly utilized.
Current Screening programs are based on periodic colonoscopy examination or stool-based detection of Fecal Occult Blood either by Guagac (g-FOB) Test or Immunological (i-FOB) Tests. The evolving principle of detecting Fecal Tumor Biomarker(s) stands in response to the limitation of the currently used fecal occult blood tests and being more specific, utilizing one stool sample instead of three consecutive samples while participating individual needs not to be on certain dietary or medication control. The faecal pyruvate kinase isoenzyme type M2 (faecal M2- PK) test recognizes a key enzyme controlling the metabolism of cells with a high proliferation rate, such as tumor cells, and thereby detects specific alterations in intestinal cells, such as polyps and cancers. This dimeric form of PK enzyme and its level increase with the developing stages of CRC from polyps. It has been claimed the same idea apply to high-risk patients with chronic Inflammatory bowel diseases (not our study subject). M2-PK is a special isoenzyme of pyruvate kinase, a key enzyme within glycolysis which catalyzes the ATP-producing conversion of phosphoenolpyruvate (PEP) to pyruvate.
Depending upon the metabolic functions of the tissues, different isoenzymes of pyruvate kinase are expressed and during tumor formation, the tissue-specific isoenzymes disappear and the pyruvate kinase isoenzyme type M2 is expressed.
The early detection by different screening methods has improved the prognosis of CRC. No doubt, the efficacy of stool-based screening methods is low compared to gold standard method, i.e. colonoscopy, but they are feasible and cost-effective techniques and the utilization of a more specific and sensitive stool based molecular techniques such M2-PK alone or in combination with the IFOB tests enhance the detection rate, providing those individuals are followed by a prompt colonoscopy examination in order to increase the screening performance for CRC at early stage.
The age range of the participants in our study was quite wide (25–74,) but the mean age of the individuals was 52.78 ± 11.52; there were 64 males and 41 females (with ration of 1:1.5). It is not consistent with the study of Kim et al., who found the mean age at the time of CRC diagnosis was 39.3 years (range 18–59 years).
In our study, there were 494 (46%) persons positive for M2- PK test, while 179 (16.6%) were positive by IFOB. Only 105 of participants who were positive either by M2-PK or IFOB or both undertook colonoscopies, It was not surprising that, out of 494 cases positive cases, only 105 of participants agreed for further colonoscopies as a line of screening for CDC, and this reflects several personal, social and educational factors, which are highlighted in the preceding text. The sensitivity of the M2- PK was found high as compared to IFOB, and our study is consistent with the other studies mentioned in literature.,
Among those 105 colonoscopy findings, 20 revealed positive lesions while 85 were found negative for neoplastic disease. The frequency of the neoplastic lesions was low as compared to other non-neoplastic lesions, whowever, these 20 neoplastic cases are quite significant. The total of 17 (85%) adenomatous polyps, 02 (10%) adenocarcinoma, and 01 (5%) Neuroendocrine tumour are detected and treated at an earlier stage. The 9 tubular adenomas, 01 villous adenoma, and 07 tubulovillous adenomas were all removed and all patients are now registered for healthcare follow up. The detection of CRD was almost 100% with the used of this combined IFOB/M2- PK kit, and the results of the variation of deferent IFOB kits will be evaluated in a different study, but what matter is that all 105 cases were found having one or other type of RCD and despite 20 cases of normal mucosa with normal biopsy, 9 diverticulosis, 1 angiodysplasia, 1 IBD, and 1 solitary rectal ulcer all were detected in subclinical stage.
The 4 cases of iFOB positive but M2-PK negative individuals who had colonoscopy performed, no neoplastic lesion was found. Two cases were of hemorrhoid, and other two were normal, therefore, when compared the specificity of both screening stool tests, the M2-PK was much better as compared to IFOB because 12 cases were missed by IFOB but were picked by M2- PK, all findings here were significant and included 11 adenomatous polyps and 1 Neuroendocrine carcinoma.
In our study, the sensitivity of M2-PK for CRC was 96%, which was superior to IFOBT (32%, P < 0.001) [Figure 8]. These findings are almost consistent with Kosset al.,
|Figure 8: Differential Diagnostic Risk-Scale for Colorectal Cancer Screening with Schebo® 2 in 1 Quick™ (M2-pyruvate kinase + haemoglobin)|
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The issue of false positivity of M2-PK must be addressed and studied further in a wider range that might also consider performing upper GIT endoscopy.
Challenges and recommendations
We experienced several difficulties to obtain major research fund, passed through variable coordination issues at all levels with many communication halts, delay and resistance. Also, finding a competent specialized data Computer system software was a major drawback with missing curtails individual information related to history and complete healthcare register, mainly due to incomplete data entry and difficult data retrieval.
Media Exposure and frequent proper cancer education programs and lack of a well-established patient education centers within major hospital is not consistent or not existing at all and mainly due to lack of specialized manpower.
Individuals prospect challenges
Colonoscopy as a screening modality of asymptomatic population is not quite acceptable in Bahrain cultures. Fear of disturbing normal lifestyle and the stigma of having diagnosed with cancer is a major personal concern, especially, the impact and drawback on their self-sponsored medical insurance cover and fear of losing job.
The Cost of treatment of CRC patients approximate BD 2.500 - BD 10.000, if not more in advanced cases. The recent statistics from Bahrain Cancer register reflects an increasing trend for CRC, therefore, it is the time to take a serous measures toward establishing a National Screening Programer for Colorectal Cancers in the Kingdom of Bahrain with all required backup support toward mass education, to ease the culture acceptance and overcome social Barriers. Providing the right employed organizational structure and fund for its success is of paramount importance, especially deployment of the most sensitive stool based platform test, i.e.: utilizing a molecular based test wither alone or in combination with the currently used IFOBT as being followed by most international established NSPCC in Europe and north America.
Our Preliminary results recommend the following: Substituting the currently used primary IFOB screening test for a population-based colorectal screening program with a new stool based tumor Biomarker test to primarily prevent the disease (Behavior Change), Secondly, to early detect the disease (by a well-structured colorectal cancer screening programs) and thirdly, to stop further disease spread (metabolic control) as tertiary prevention.
The screening may affect on prevention of CRC and to reduce mortality, stop morbidity and enhance the quality of life, through early detection and treating the precancerous polyps and early detection of CRC.
Comprehend the targeted population for evidence-based screening program and suggest further studies to start screening men and women at age of 45 with a screening interval as per the current international guidelines.
Finally, the colonoscopy must be offered to those individuals who test positive for the new biomarker tests.
| Conclusion|| |
Colonoscopy is the gold standard for diagnosis of CRC but is an invasive and time-consuming technique. The screening of CRD by a stool based molecular test such as M2-PK have shown a high sensitivity for the detection of CRC and adenomatous polyps compared to IFOBT. Fecal M2-PK is a cost-effective, easy to perform, as an adjunct a non-invasive pre-colonoscopy CRC screening test for individuals once reached age of 45 years.
We would like to thank our colleagues, who contributed toward the success of this research, namely: Dr Sanad Jassim Sanad, Consultant Gastroenterologist, Bahrain Defense Force Hospital, Dr. Zainab AL Haddad, Consultant Medical Oncologist, King Hamad University Hospital, Dr Suhail Baithun, Consultant Histopathologist, King Hamad University Hospital, Dr Omar Sharif, Consultant Gastroenterologist, King Hamad University Hospital Dr Asad Jawad, Consultant General Surgeon, King Hamad University Hospital Dr. Aysha AL-Jowdar Senior House Officer Pathologist, King Hamad University Hospital, Dr Sanjay Gupta, Consultant, General Surgeon, American Mission Hospital, Dr Rama Kreshna, Consultant, General Surgeon, American Mission Hospital, Dr Mustafa Al Abdulla, Consultant Gastroenterologist, Royal Bahrain Hospital, Dr. Suhair Al Saad, Consultant General Surgeon, Alkindi Specialist Hospital, Dr. Hamdy Al Shenawi, Consultant General Surgeon, Alkindi Specialist Hospital, Dr Jehad Gamish, Consultant Gastroenterologist, Ibn Al-Nafees Hospital, Dr Najah Al Zayani, Consultant Gastroenterologist, Bahrain Specialist Hospital, Dr Tareq Hameed, Consultant General Surgeon, Awali Hospital, Dr. Abdulwahab Mohamed, Consultant General Surgeon, Noor Specialist Hospital, Dr Abdulrahman Fakhro, Consultant General surgeon, King Abdulla medical City Hospital and Chairman of Bahrain Cancer Society. We acknowledge that without the cooperation and contribution of all above worthy stakeholders, this project was not possible to complete smoothly.
We also obliged to Bahrain Supreme council of health and the commander of King Hamad University Hospital for their upmost support and donations, The CEOs of all participating hospitals, the senior KHUH management officers for facilitating our logistics and control, joiner doctors, healthcare clinical and technical personnel as well as the participating administration staff, for their eagerness toward public support.
Finally, we extended our appreciation to the regional officers of Roche Pharma for providing the inflatable colon for the duration of the camping and ScheBo® • Biotech AG for donating 1000 free (M2PK 2-in-1) stool kits.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Authorship: Khalid Ahmad Alsindi was the principal researcher and collected the data, deigned the research Protocol and helped in designing the research protocol and supervised the project, he is also responsible for its originality and authenticity of the research work. Mulazim Hussain Bukhari, did the data analysis and helped is writing and finalizing the research work and manuscript; Afsar Saeed, gave the final touch of the manuscript; Mohmed Ali Al-Hamar also contributed toward the success of this research.
| References|| |
Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A, et al.
Colorectal cancer statistics, 2017. CA Cancer J Clin 2017;67:177-93.
Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: A quantitative overview of the epidemiological evidence. Int J Cancer 2009;125:171-80.
Gandomani HS, Yousefi SM, Aghajani M, Hafshejani AM, Tarazoj AA, Pouyesh V, et al
. Colorectal cancer in the world: Incidence, mortality and risk factors. Biomed Res Ther 2017;4:1656-75.
Arafa MA, Farhat K. Colorectal cancer in the Arab world – Screening practices and future prospects. Asian Pac J Cancer Prev 2015;16:7425-30.
Al Awadhi MA, Abulfateh NM, Abu-Hassan F, Fikree MA, Eman Janahi E, Carlo R. Cancer incidence and mortality in the Kingdom of Bahrain statistics and trends. Bahrain Med Bull 2016;38:30-4.
Bhurgri Y, Khan T, Kayani N, Ahmad R, Usman A, Bhurgri A, et al.
Incidence and current trends of colorectal malignancies in an unscreened, low risk Pakistan population. Asian Pac J Cancer Prev 2011;12:703-8.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.
Richardson A, Hayes J, Frampton C, Potter J. Modifiable lifestyle factors that could reduce the incidence of colorectal cancer in New Zealand. N
Z Med J 2016;129:13-20.
Slattery ML, Curtin K, Anderson K, Ma KN, Ballard L, Edwards S, et al.
Associations between cigarette smoking, lifestyle factors, and microsatellite instability in colon tumors. J Natl Cancer Inst 2000;92:1831-6.
Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG, Lee JS. Cancer statistics in Korea: Incidence, mortality, survival and prevalence in 2010. Cancer Res Treat 2013;45:1-4.
Zhu MM, Xu XT, Nie F, Tong JL, Xiao SD, Ran ZH. Comparison of immunochemical and guaiac-based fecal occult blood test in screening and surveillance for advanced colorectal neoplasms: A meta-analysis. J Dig Dis 2010;11:148-60.
Tonus C, Sellinger M, Koss K, Neupert G. Faecal pyruvate kinase isoenzyme type M2 for colorectal cancer screening: A meta-analysis. World J Gastroenterol 2012;18:4004-11.
Mazurek S, Grimm H, Oehmke M, Weisse G, Teigelkamp S, Eigenbrodt E. Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells. Anticancer Res 2000;20:5151-4.
Hardt PD, Ngoumou BK, Rupp J, Schnell-Kretschmer H, Kloer HU. Tumor M2-pyruvate kinase: A promising tumor marker in the diagnosis of gastro-intestinal cancer. Anticancer Res 2000;20:4965-8.
Herbst A, Kolligs FT. Detection of DNA hypermethylation in remote media of patients with colorectal cancer: New biomarkers for colorectal carcinoma. Tumour Biol 2012;33:297-305.
Leen R, Seng-Lee C, Holleran G, O'Morain C, McNamara D. Comparison of faecal M2-PK and FIT in a population-based bowel cancer screening cohort. Eur J Gastroenterol Hepatol 2014;26:514-8.
Kim J, Lee HS, Park SH, Yang SK, Ye BD, Yang DH, et al.
Pathologic 29 features of colorectal carcinomas associated with Crohn's disease in Korean population. Pathol Res Pract 2017;213:250-5.
Kim YC, Kim JH, Cheung DY, Kim TH, Jun EJ, Oh JW, et al.
The usefulness of a novel screening kit for colorectal cancer using the immunochromatographic fecal tumor M2 pyruvate kinase test. Gut Liver 2015;9:641-8.
Towler B, Irwig L, Glasziou P, Kewenter J, Weller D, Silagy C. A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, hemoccult. BMJ 1998;317:559-65.
Koss K, Maxton D, Jankowski JA. Faecal dimeric M2 pyruvate kinase in colorectal cancer and polyps correlates with tumour staging and surgical intervention. Colorectal Dis 2008;10:244-8.
McLoughlin RM, Shiel E, Sebastian SS, Ryan B, O'Connor HJ, Morain CO. The Advantages of the New ScheBo® M2-PK ™ Stool Test. Available from: http://www.dimed.at/vorteile-m2-pk-test/
. [Last retrieved on 2019 May 31].
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
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