Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Colorectal Neoplasms

Syndrome

Colorectal Neoplasms, Hereditary Nonpolyposis

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

Herbal and Botanical

All Drugs and Chemicals

Cola

Narrow Band Imaging

Brian Saunders, MD FRCP

The purpose of this study is to determine whether a new colonoscopic viewing technique called narrow band imaging (NBI)can help doctors detect more patients with at least one pre-cancerous area than conventional colonoscopy using white light alone in patients with genetically inherited high risk for bowel cancer (HNPCC).

Colorectal cancer is the second commonest cause of cancer death. Some people have an inherited defect in the genes which repair DNA which results in a very high risk of colorectal (bowel) cancer at a young age. This syndrome is called hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome. Colonoscopic surveillance of HNPCC patients has been shown to reduce the risk of colorectal cancer and allow detection at an earlier stage, but even with meticulous examination, some precancerous lesions or cancers are missed.

Precancerous lesions in HNPCC are difficult to see and may be advanced even if as small as a few millimeters. Endoscopists have used spraying dye on the lining of bowel (Chromoendoscopy) successfully to improve detection of abnormal areas; however this is time consuming and requires extra time and equipment and despite the benefits seen in two studies is not widely used in routine clinical practice in the UK.

Narrow Band Imaging (NBI) is a technique that relies on light to improve contrast for the smallest blood vessels in the bowel lining which shows up precancerous areas as they have a richer vascular network. It is sometimes described as "digital chromoendoscopy" as the images produced are similar to chromoendoscopy, but it is much simpler and quicker to use. With magnification it allows assessment of the fine mucosal surace pattern (pit pattern) of lesion which allows an assessment of their likelihood of being precancerous. Autofluorescence endoscopy uses short wavelength light and light filters to produce a false colour image of the bowel lining where polyps stand out. These techniques have been used with some success in the oesophagus and stomach but little work is available for the colon.

We aim to see if NBI with magnification is better than standard colonoscopy for detecting precancerous areas. This is likely as it produces images similar to chromoendoscopy which is already shown to help. If a potentially precancerous area is found we will use other types of endoscopy, in particular NBI and autofluorescence to see if these techniques are helpful for discriminating between pre-cancerous and non-cancerous areas.

Magnification Narrow Band Imaging Colonoscopy for Hereditary Non-Polyposis Colorectal Cancer Surveillance

Back-to Back Trial of Narrow Band Imaging (NBI) With Magnification Versus Standard Colonoscopy for Colonic Neoplasia Surveillance in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Patients

London North West Healthcare NHS Trust

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hereditary Breast and Ovarian Cancer Syndrome

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Neoplasms

Breast Diseases

Skin Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

For carriers with mutation genes of BRCA1, BRCA2 (both belonging to mutation genes of hereditary breast and ovarian cancer syndrome, HBOCS) and ATM, BRIP1, RAD51, RAD51C, and RAD51D (all belonging to mutation genes of other hereditary ovarian cancer syndrome), if they demand for risk-reducing surgeries, counseling, decision-making analysis, then salpingo-oophorectomy only by laparoscopy and long-term follow-up are provided.

for carriers with mutation genes of MLH1, MSH2, MSH6, PMS2, EPCAM (all belonging to mutation genes of Lynch syndromes) and STK11, , if they demand for risk-reducing surgeries, counseling, decision-making analysis, then salpingo-oophorectomy with hysterectomy by laparoscopy and long-term follow-up are provided.

For carriers with any mutation genes (BRCA1, BRCA2, ATM, BRIP1, RAD51, RAD51C, RAD51D, STK11, MLH1, MSH2, MSH6, PMS2 and EPCAM) but refusal to any risk-reducing surgeries, counseling, decision-making analysis, and then long-term follow-up are provided.

Salpingo-oophorectomy are provided for carriers with mutation genes of BRCA1, BRCA2 (both belonging to mutation genes of hereditary breast and ovarian cancer syndrome, HBOCS) and ATM, BRIP1, RAD51, RAD51C, and RAD51D (all belonging to mutation genes of other hereditary ovarian cancer syndrome). Detailed multi-disciplinary counseling, decision-making analysis before surgeries, and long-term follow-up and health management after surgeries are provided for all participants.

salpingo-oophorectomy only by laparoscopy

Salpingo-oophorectomy with hysterectomy are provided for carriers with mutation genes of MLH1, MSH2, MSH6, PMS2, EPCAM (all belonging to mutation genes of Lynch syndromes) and STK11. Detailed multi-disciplinary counseling, decision-making analysis before surgeries, and long-term follow-up and health management after surgeries are provided for all participants.

salpingo-oophorectomy with hysterectomy by laparoscopy

Detailed multi-disciplinary counseling, decision-making analysis and long-term follow-up are provided for carriers with any mutation genes but refusal to any risk-reducing gynecologic surgeries

Follow-up

Lei Li, MD

Lei L Li, MD

Ming Wu, MD

Based on studies of "Inherited Susceptible Genes Among Epithelial Ovarian Cancer" (NCT03015376, clinicaltrials.gov) and "Cohort Study of Universal Screening for Lynch Syndrome in Chinese Patients of Endometrial Cancer" (NCT03291106, clinicaltrials.gov), we provide risk-reducing surgeries of salpingo-oophorectomy with/without hysterectomy for healthy carriers with mutation genes of hereditary ovarian cancer, which is defined ovarian cancer with relevant pathogenic mutations.

Risk-Reducing Surgeries for Hereditary Ovarian Cancer

Risk-Reducing Surgeries of Salpingo-oophorectomy With/Without Hysterectomy for Carriers With Mutation Genes of Hereditary Ovarian Cancer

Precancerous lesions include serous tubal intraepithelial carcinoma (STIC) and endometrial intraepithelial neoplasia (EIN)

Incidence of primary peritoneal carcinoma after reception or refusal risk-reducing salpingo-oophorectomy

Incidence of primary uterine cancer after reception or refusal risk-reducing hysterectomy

Lei Li

Professor

Endometrial Neoplasms

Uterine Neoplasms

Uterine Diseases

immunohistochemical staining for MLH1, MSH2, MSH6 and PMS2

immunohistochemical staining

microsatellite instability in tissues of endometrial cancer

tests of microsatellite instability

Amsterdam I or II criteria and Bethesda criteria

clinical criteria of Lynch syndromes

next-generation sequencing, Sanger method or qPCR for mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM)

sequencing for mismatch repair genes

In patients diagnosed as endometrial cancer by thorough pathologic examinations, Lynch syndromes are screened by (1)immunohistochemical staining (for MLH1, MSH2, MSH6 and PMS2), (2) tests of microsatellite instability and (3) clinical criteria (Amsterdam I or II criteria and Bethesda criteria). For patients with any suspicious discoveries of Lynch syndromes from aforementioned screening methods, a molecular diagnosis with next-generation sequencing for mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) is given to confirm Lynch syndromes. For patients of Lynch syndromes and endometrial cancer, relatives of blood lineage are tested by Sanger method or qPCR to find out carriers of mutation genes of Lynch syndromes.

Study of Universal Screening for Lynch Syndrome in Chinese Patients of Endometrial Cancer

Cohort Study of Universal Screening for Lynch Syndrome in Chinese Patients of Endometrial Cancer

Distributions of specific mutation genes of Lynch syndromes will be available for other researches by officially published papers.

Proportions of patients carrying mismatch repair gene in endometrial cancer

Sensitiviy and specitiviy of immunohistochemical staining for screening Lynch syndromes

Sensitiviy and specitiviy of microsatellite instability for screening Lynch syndromes

Sensitiviy and specitiviy of clinical criteria for screening Lynch syndromes

Colonoscopy with chromoscopy

Christophe CELLIER, Pr,MD,PhD

The aim of the study is to test the hypothesis that a chromoscopy colonoscopy is able to increase by 50 % the number of pre-cancer lesions or early cancer detected in patients with HNPCC syndrome, compared to a routine colonoscopy without chromoscopy.

Patient with HNPCC syndrome confirmed by a mutation (MLH1, MSH2, MHS1) are involved in the study. Patient have 2 colonoscopy back to back. The second coloscopy is associated to chromoscopy with carmin indigo. Endoscopist are randomised for the colonoscopy with chromoscopy and are un-awarded of the result of the first colonoscopy. Histopathology of the polyp are noted. The follow up were 1 month.

CHROENDOHNPCC: Early Detection of Pre-cancer Lesions in Adults With Hereditary Nonpolyposis Colorectal Cancer Syndrome

Early Detection of Pre-cancer Lesions in Adults With Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Syndrome: Assessment of Coloscopy With Chromoscopy Benefit

Assistance Publique - Hôpitaux de Paris

Saliha DJANE

Familial Colorectal Cancer

* Patients and clinicians have access to a website with information on familial colorectal cancer risk; a risk assessment tool and decision aids
* Clinicians receive the guidelines and a risk communication tool, as well as education

Implementation aids

Control

Nicoline Hoogerbrugge, MD, PhD

Rosella PMG Hermens, PhD

The aim of this study is to improve clinicians' calculation, interpretation and communication of familial colorectal cancer risk, as well as patients' risk perception and uptake of referral for genetic counselling or for surveillance by colonoscopy for their relatives at risk.

Regular colonoscopy is effective in reducing morbidity and mortality due to colorectal cancer (CRC) in patients at increased familial CRC risk. Currently, the majority of these at-risk individuals are not properly referred for increased surveillance by colonoscopy or genetic counselling. In 2008, a national multidisciplinary evidence-based guideline on familial and hereditary CRC was launched in the Netherlands. Clinicians have new tasks in familial CRC risk calculation, interpretation and communication. A clustered randomized controlled trial including an effect, process and cost evaluation will be conducted in eighteen Dutch hospitals to determine the most cost effective way to implement these new guidelines.

Surgeons and gastroenterologists in both the intervention group and the control group will receive background information on familial colorectal cancer risk and the guidelines. Patients and clinicians in the intervention group will receive an additional intervention strategy.

The effect evaluation is done by assessing the number of CRC patients for whom correct risk calculation, interpretation and communication is performed, as well as patients' uptake of the recommended follow up policy. The actual exposure to the different elements of the implementation procedure and the experiences of users will be assessed in the process evaluation. The costs of the implementation procedure will be determined by means of a cost evaluation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Magnification Narrow Band Imaging Colonoscopy for Hereditary Non-Polyposis Colorectal Cancer Surveillance	NCT00313755	Colorectal Neop...	Narrow Band Ima...	18 Years -	London North West Healthcare NHS Trust
Risk-Reducing Surgeries for Hereditary Ovarian Cancer	NCT03294343	Hereditary Brea... Colorectal Neop... Ovariectomy Hysterectomy	salpingo-oophor... salpingo-oophor... Follow-up	35 Years -	Peking Union Medical College Hospital
Study of Universal Screening for Lynch Syndrome in Chinese Patients of Endometrial Cancer	NCT03291106	Colorectal Neop... Endometrial Neo...	immunohistochem... tests of micros... clinical criter... sequencing for ...	18 Years -	Peking Union Medical College Hospital
Magnification Narrow Band Imaging Colonoscopy for Hereditary Non-Polyposis Colorectal Cancer Surveillance	NCT00313755	Colorectal Neop...	Narrow Band Ima...	18 Years -	London North West Healthcare NHS Trust
CHROENDOHNPCC: Early Detection of Pre-cancer Lesions in Adults With Hereditary Nonpolyposis Colorectal Cancer Syndrome	NCT00224601	Colorectal Neop...	Colonoscopy wit...	25 Years - 75 Years	Assistance Publique - Hôpitaux de Paris
Risk-Reducing Surgeries for Hereditary Ovarian Cancer	NCT03294343	Hereditary Brea... Colorectal Neop... Ovariectomy Hysterectomy	salpingo-oophor... salpingo-oophor... Follow-up	35 Years -	Peking Union Medical College Hospital
Study of Universal Screening for Lynch Syndrome in Chinese Patients of Endometrial Cancer	NCT03291106	Colorectal Neop... Endometrial Neo...	immunohistochem... tests of micros... clinical criter... sequencing for ...	18 Years -	Peking Union Medical College Hospital
CHROENDOHNPCC: Early Detection of Pre-cancer Lesions in Adults With Hereditary Nonpolyposis Colorectal Cancer Syndrome	NCT00224601	Colorectal Neop...	Colonoscopy wit...	25 Years - 75 Years	Assistance Publique - Hôpitaux de Paris
Implementation of Guidelines on Hereditary or Familial Colorectal Cancer	NCT00929097	Colorectal Neop...	Implementation ... Control	18 Years - 70 Years	Radboud University Medical Center
CHROENDOHNPCC: Early Detection of Pre-cancer Lesions in Adults With Hereditary Nonpolyposis Colorectal Cancer Syndrome	NCT00224601	Colorectal Neop...	Colonoscopy wit...	25 Years - 75 Years	Assistance Publique - Hôpitaux de Paris

Spots Global Cancer Trial Database for colorectal neoplasms, hereditary nonpolyposis