Br. J. Surg. 1991, Vol. 78, April, 451-452
M. Rhodes*, P. D. Chapman?, J. Burnt and A. Gunn Department of Surgery, Ashington General Hospital, Northumberland NE63 OSA and ?Regional Genetics Advisory Service, Newcastle upon Tyne NEZ 4AA, UK Correspondence to: Mr A. Gunn
Role of a regional register for familial adenomatous polyposis: experience in the Northern Region Within 36 months of its formation the Northern Region Polyposis Registry had increased the number of identified gene carriers of familial adenomatous polyposis from 56 to 65 in a population of 3.1 million and had achieved a 1.5-fold increase in the number of at-risk relatives being regularly screened. Review of the surgical records at the outset of the registry revealed that the mean age at diagnosis of those patients detected by screening was 24.7 years, whereas it was 36.6 years for those detected by symptoms. Ten of the 31 in the latter group had colorectal carcinomas whilst only one of those detected by screening had a cancer and a signqicantly higher proportion had sphincter-saving surgery. A regional registry can provide an effective screening and counselling service to surgeons treating patients with familial adenomatous polyposis. At-risk relatives are best assessed by combining results of the different screening procedures now available but the prime requirement of a successful registry is dedicated domiciliary counselling.
The possibility that colorectal adenomas could be familial was first recognized by Cripps in 1882l who described two siblings with multiple colorectal adenomas. In 1925 LockhartMummery drew attention to the risk of malignant transformation of familial large bowel adenomas’. The subsequent formation of the St. Mark’s Polyposis Registry and the writings of Dukes3 have further clarified the nature of familial adenomatous polyposis (FAP) and demonstrated the need for prophylactic surgery. A large literature has accumulated and several registers have been developed in different parts of the ~ o r l d ~but- ~as yet there are no comprehensive registers of defined geographical areas in the UK. In 1987 a regional register was established within the Northern Region of England so that surgeons could have a genetic service available to help them trace and screen at-risk relatives of patients with FAP and assess the need for surgical intervention. The results of the first 36 months of this register are presented with an emphasis on the implications for surgical management.
identification of carriers of the Subsequently all obligate gene carriers and patients at risk were seen in an ophthalmological research clinic to assess this particular clinical feature. Blood samples were obtained from all family members to assess the reliability of available gene markers. Detailed results of this aspect of the Registry’s work will be reported at a later date’. The notes of all living affected obligate gene carriers were reviewed in order to validate pathological reports and obtain details of surgical techniques employed.
Results Table I illustrates the management of F A P in the Northern Regional Health Authority of England as assessed by a review of the case records of all living patients treated at January 1987. Between January 1987 and January 1990 the number of patients detected with F A P rose from 56 to 65. Over the same period the number of at-risk relatives under review rose from 21 to 308.
Patients and methods All 72 general surgeons employed within the Northern Regional Health Authority of England (population 3.1 million) agreed to provide details of patients under their care with FAP. A part-time genetic nurse (P.D.C.) worked with a consultant clinical geneticist (J.B.) and a consultant surgeon (A.G.) to carry out a systematic search for affected families with the assistance of the surgical units involved. All families were visited, pedigrees constructed and arrangements made to compile a dedicated microcomputer register to provide a recall service for screening. Verbal permission was obtained from all patients and relatives interviewed for their inclusion in the register, and more recently written consent has been requested. The requirements of the Data Protection Act (1984) have been observed during computerization of records. Family members were recommended to attend for screening by the surgeon responsible for their aflected relative, although some flexibility was necessary in relation to the place of residence and in the situation where more than one surgeon was responsible ror different branches or the same family. During the course of the first year it became apparent that multiple areas of congenital hypertrophy of the retinal pigment epithelium, detected by indirect fundoscopy (Figure f ) , was a useful sign enabling
* Currcwt uddrrss: Depurfment u / Surgery, Roy11 Victoria Infirmary. Nmru..rtfc.upon Tvnc,, UK
0007-1323/91/040451-02
~3 199 I Butterworth-Heinemann Ltd
Figure 1 A fypicul urea of congenital hypertrophy epitkehm
of the retinalpigment
451
Regional register for familial adenomatous polyposis:
M . Rhodes et at.
Table 1 Management offamilialadenomatouspolyposis in the Northern Region ar January 1987
No. of patients Mean age at diagnosis (years) Surgery performed Colorectomy and ileorectal anastomosis Proctocolectomy and ileal reservoir Panproctocolectomy Patients with colorectal carcinoma at the time of surgery
Detected by screening
Detected by symptoms
25 24.7
31 36.6
9
11
6 5
1 13 10
1
Discussion During the first 36 months of its existence, the Northern Regional Polyposis Registry identified nine new gene carriers with FAP, a 16 per cent increase in the total of 56 identified at the initial review. The 15-fold increase in the number of relatives screened should prove important, as active identification of potential gene carriers should, in the long term, lead to early operative intervention and a subsequent reduction in morbidity and mortality rates. This belief is supported by the observation that ten of the 31 patients who were referred for surgery on the basis of symptoms (average age 36.6 years) had a colorectal carcinoma whereas only one of the 25 detected by screening (average age 24.7 years) was so affected. This, together with the lower incidence of panproctocolectomy in the population detected by screening, is encouraging, although patients undergoing rectal sparing surgery remain at risk of developing cancer of the rectal stump. However, in patients who have undergone colectomy and ileorectal anastomosis for F A P the risk of death from cancer of the rectal stump is relatively small; they are more likely to die from other diseases, particularly carcinoma of the upper gastrointestinal tract1’-’’. A regional registry responsible for tracing relatives of affected patients should also be able to advise on the use and interpretation of available screening techniques. Although large bowel endoscopy remains a fundamental screening requirement, the significance of this examination is increased if the results are correlated with age. For example, it can be estimated that a 15-year-old first-degree relative with a negative sigmoidoscopy has a 30 per cent chance of carrying the affected gene, but a 30-year-old first-degree relative without detectable colorectal adenomas has a less than 1 in 10 chance of being affectedI3. In addition, the recent localization of the FAP gene to the long arm of chromosome 5 means that analysis of blood samples by DNA probes will become an increasingly important screening procedurei4. A simple means of identifying at least 80 per cent of gene carriers is the detection of multiple areas of congenital hypertrophy of the retinal pigment epithelium by indirect fundoscopy (Figure I)’,’. These results can be combined by standard genetic risk calculations using Bayes’ theorem to give a more precise estimate of the risk of carrier status’ 5 ; for example, a 30-year-old first-degree relative with negative bowel and eye examinations and a favourable DNA pattern has less than a 1 in 1000 chance of being a gene carrier16. Family members identified as being at very low risk of carrying the gene can be offered a reduced frequency or discontinuation of large bowel endoscopy. Conversely, those shown to be at high risk can be targeted more efficiently. The combination of a consultant surgeon with an interest in colorectal disease and a consultant clinical geneticist working
452
with a genetic nurse has proved effective. Involvement with genetics is crucial and eminently feasible now that the UK has an established specialty of Clinical Genetics with NHS consultant provision in all regions. Important too are genetic nurses equipped to visit families in their homes and, where necessary, to collect blood samples. As screening methods become more sophisticated the main requirement of an effective registry is the ability to trace and counsel at-risk individuals. At its initiation the Northern Regional Registry relied on the St. Mark’s Polyposis Registry for guidance on screening policy and recommended surgical procedures. A logical and desirable development would be the establishment in each region of the UK of a polyposis registry with connections with St. Mark’s registry to permit collation of results and to allow dissemination of the rapidly growing knowledge of the most effective approaches to screening. If registries are to collate data it will be necessary to obtain consent from patients and relatives specifically for this purpose.
Acknowledgements Pamela Chapman was supported by a grant from the Northern Regional Health Authority and we are grateful to Lilian Hzath for typing the manuscript.
References I. 2. 3. 4.
5. 6.
7. 8. 9.
10. 11.
12. 13. 14. 15.
16.
Cripps WH. Two cases of disseminated polypus of the rectum. Trans Path Soc Lond 1882; 33: 165-8. Lockhart-Mummery P. Cancer and heredity. Lancet 1925; i: 427-9. Dukes CE. Familial intestinal polyposis. Ann Eugenics 1952; 17i: 1-29. Bulow S . The Danish Polyposis Register. Dis Colon Rectum 1984; 27: 351-5. Jagelman DG. Familial polyposis coli. Surg Clin Norrh Am 1983; 63: 117-28. Utsonomiya J , Iwama T . Adenomatosis coli in Japan. In: Winawer S, Schottenfeld D, Sherlock P, eds. Colorectal Cancer: Prevention, Epidemiology and Screening. New York: Raven Press. 1980: 83-95. Diaz Llopis M, Menezo JL. Congenital hypertrophy of the retinal pigment epithelium and familial polyposis of the colon. Am J Ophthalmol 1987; 103: 235. Chapman PD, Church W, Burn J, Gunn A. Congenital hypertrophy of the retinal pigment epithelium; a sign of familial adenomatous polyposis. Br Med J 1989; 298: 353-4. Burn J, Chapman P, Delhanty J et a/. The Northern Region genetic register for familial adenomatous polyposis coli: use of age of onset, CHRPE and DNA markers in risk calculations. J Med Genef (in press). Jarvinen HJ. Time and type of prophylactic surgery for familial adenomatous coli. Ann Surg 1985; 202: 93-7. Bulow S. The risk of developing rectal cancer after colectomy and ileorectal anastomosis in Danish patients with polyposis coli. Dis Colon Rectum 1984; 27: 726-9. Bussey HJR, Eyers AA, Ritchie SM, Thompson JPS. The rectum in adenomatous polyDosis: the St Mark’s policy. - .. . . Br J Surq 1985; SUPPI:S29-S35. Murdav V. Slack J. Inherited disorders associated with colorectal cancer.’Cancer Surv 1989; 8: 139-57. Bodmer WF, Bailey CJ, Bodmer J et al. Localisation of the gene for familial adenomatous polyposis on chromosome 5 . Nature 1987; 328: 614-16. Ponder BAJ, Coffey R, Gagel RF er a/. Risk estimation and screening in families of patients with medullary thyroid carcinoma. Lancet 1988; i : 397400. Houlston R, Slack J, Murday V. Risk estimates for screening adenomatous polyposis coli. Lancer 1990; i: 484 (Letter).
Paper accepted 17 October 1990
Br. J. Surg., Vol. 78, No. 4, April 1991
M. Rhodes*, P. D. Chapman?, J. Burnt and A. Gunn Department of Surgery, Ashington General Hospital, Northumberland NE63 OSA and ?Regional Genetics Advisory Service, Newcastle upon Tyne NEZ 4AA, UK Correspondence to: Mr A. Gunn
Role of a regional register for familial adenomatous polyposis: experience in the Northern Region Within 36 months of its formation the Northern Region Polyposis Registry had increased the number of identified gene carriers of familial adenomatous polyposis from 56 to 65 in a population of 3.1 million and had achieved a 1.5-fold increase in the number of at-risk relatives being regularly screened. Review of the surgical records at the outset of the registry revealed that the mean age at diagnosis of those patients detected by screening was 24.7 years, whereas it was 36.6 years for those detected by symptoms. Ten of the 31 in the latter group had colorectal carcinomas whilst only one of those detected by screening had a cancer and a signqicantly higher proportion had sphincter-saving surgery. A regional registry can provide an effective screening and counselling service to surgeons treating patients with familial adenomatous polyposis. At-risk relatives are best assessed by combining results of the different screening procedures now available but the prime requirement of a successful registry is dedicated domiciliary counselling.
The possibility that colorectal adenomas could be familial was first recognized by Cripps in 1882l who described two siblings with multiple colorectal adenomas. In 1925 LockhartMummery drew attention to the risk of malignant transformation of familial large bowel adenomas’. The subsequent formation of the St. Mark’s Polyposis Registry and the writings of Dukes3 have further clarified the nature of familial adenomatous polyposis (FAP) and demonstrated the need for prophylactic surgery. A large literature has accumulated and several registers have been developed in different parts of the ~ o r l d ~but- ~as yet there are no comprehensive registers of defined geographical areas in the UK. In 1987 a regional register was established within the Northern Region of England so that surgeons could have a genetic service available to help them trace and screen at-risk relatives of patients with FAP and assess the need for surgical intervention. The results of the first 36 months of this register are presented with an emphasis on the implications for surgical management.
identification of carriers of the Subsequently all obligate gene carriers and patients at risk were seen in an ophthalmological research clinic to assess this particular clinical feature. Blood samples were obtained from all family members to assess the reliability of available gene markers. Detailed results of this aspect of the Registry’s work will be reported at a later date’. The notes of all living affected obligate gene carriers were reviewed in order to validate pathological reports and obtain details of surgical techniques employed.
Results Table I illustrates the management of F A P in the Northern Regional Health Authority of England as assessed by a review of the case records of all living patients treated at January 1987. Between January 1987 and January 1990 the number of patients detected with F A P rose from 56 to 65. Over the same period the number of at-risk relatives under review rose from 21 to 308.
Patients and methods All 72 general surgeons employed within the Northern Regional Health Authority of England (population 3.1 million) agreed to provide details of patients under their care with FAP. A part-time genetic nurse (P.D.C.) worked with a consultant clinical geneticist (J.B.) and a consultant surgeon (A.G.) to carry out a systematic search for affected families with the assistance of the surgical units involved. All families were visited, pedigrees constructed and arrangements made to compile a dedicated microcomputer register to provide a recall service for screening. Verbal permission was obtained from all patients and relatives interviewed for their inclusion in the register, and more recently written consent has been requested. The requirements of the Data Protection Act (1984) have been observed during computerization of records. Family members were recommended to attend for screening by the surgeon responsible for their aflected relative, although some flexibility was necessary in relation to the place of residence and in the situation where more than one surgeon was responsible ror different branches or the same family. During the course of the first year it became apparent that multiple areas of congenital hypertrophy of the retinal pigment epithelium, detected by indirect fundoscopy (Figure f ) , was a useful sign enabling
* Currcwt uddrrss: Depurfment u / Surgery, Roy11 Victoria Infirmary. Nmru..rtfc.upon Tvnc,, UK
0007-1323/91/040451-02
~3 199 I Butterworth-Heinemann Ltd
Figure 1 A fypicul urea of congenital hypertrophy epitkehm
of the retinalpigment
451
Regional register for familial adenomatous polyposis:
M . Rhodes et at.
Table 1 Management offamilialadenomatouspolyposis in the Northern Region ar January 1987
No. of patients Mean age at diagnosis (years) Surgery performed Colorectomy and ileorectal anastomosis Proctocolectomy and ileal reservoir Panproctocolectomy Patients with colorectal carcinoma at the time of surgery
Detected by screening
Detected by symptoms
25 24.7
31 36.6
9
11
6 5
1 13 10
1
Discussion During the first 36 months of its existence, the Northern Regional Polyposis Registry identified nine new gene carriers with FAP, a 16 per cent increase in the total of 56 identified at the initial review. The 15-fold increase in the number of relatives screened should prove important, as active identification of potential gene carriers should, in the long term, lead to early operative intervention and a subsequent reduction in morbidity and mortality rates. This belief is supported by the observation that ten of the 31 patients who were referred for surgery on the basis of symptoms (average age 36.6 years) had a colorectal carcinoma whereas only one of the 25 detected by screening (average age 24.7 years) was so affected. This, together with the lower incidence of panproctocolectomy in the population detected by screening, is encouraging, although patients undergoing rectal sparing surgery remain at risk of developing cancer of the rectal stump. However, in patients who have undergone colectomy and ileorectal anastomosis for F A P the risk of death from cancer of the rectal stump is relatively small; they are more likely to die from other diseases, particularly carcinoma of the upper gastrointestinal tract1’-’’. A regional registry responsible for tracing relatives of affected patients should also be able to advise on the use and interpretation of available screening techniques. Although large bowel endoscopy remains a fundamental screening requirement, the significance of this examination is increased if the results are correlated with age. For example, it can be estimated that a 15-year-old first-degree relative with a negative sigmoidoscopy has a 30 per cent chance of carrying the affected gene, but a 30-year-old first-degree relative without detectable colorectal adenomas has a less than 1 in 10 chance of being affectedI3. In addition, the recent localization of the FAP gene to the long arm of chromosome 5 means that analysis of blood samples by DNA probes will become an increasingly important screening procedurei4. A simple means of identifying at least 80 per cent of gene carriers is the detection of multiple areas of congenital hypertrophy of the retinal pigment epithelium by indirect fundoscopy (Figure I)’,’. These results can be combined by standard genetic risk calculations using Bayes’ theorem to give a more precise estimate of the risk of carrier status’ 5 ; for example, a 30-year-old first-degree relative with negative bowel and eye examinations and a favourable DNA pattern has less than a 1 in 1000 chance of being a gene carrier16. Family members identified as being at very low risk of carrying the gene can be offered a reduced frequency or discontinuation of large bowel endoscopy. Conversely, those shown to be at high risk can be targeted more efficiently. The combination of a consultant surgeon with an interest in colorectal disease and a consultant clinical geneticist working
452
with a genetic nurse has proved effective. Involvement with genetics is crucial and eminently feasible now that the UK has an established specialty of Clinical Genetics with NHS consultant provision in all regions. Important too are genetic nurses equipped to visit families in their homes and, where necessary, to collect blood samples. As screening methods become more sophisticated the main requirement of an effective registry is the ability to trace and counsel at-risk individuals. At its initiation the Northern Regional Registry relied on the St. Mark’s Polyposis Registry for guidance on screening policy and recommended surgical procedures. A logical and desirable development would be the establishment in each region of the UK of a polyposis registry with connections with St. Mark’s registry to permit collation of results and to allow dissemination of the rapidly growing knowledge of the most effective approaches to screening. If registries are to collate data it will be necessary to obtain consent from patients and relatives specifically for this purpose.
Acknowledgements Pamela Chapman was supported by a grant from the Northern Regional Health Authority and we are grateful to Lilian Hzath for typing the manuscript.
References I. 2. 3. 4.
5. 6.
7. 8. 9.
10. 11.
12. 13. 14. 15.
16.
Cripps WH. Two cases of disseminated polypus of the rectum. Trans Path Soc Lond 1882; 33: 165-8. Lockhart-Mummery P. Cancer and heredity. Lancet 1925; i: 427-9. Dukes CE. Familial intestinal polyposis. Ann Eugenics 1952; 17i: 1-29. Bulow S . The Danish Polyposis Register. Dis Colon Rectum 1984; 27: 351-5. Jagelman DG. Familial polyposis coli. Surg Clin Norrh Am 1983; 63: 117-28. Utsonomiya J , Iwama T . Adenomatosis coli in Japan. In: Winawer S, Schottenfeld D, Sherlock P, eds. Colorectal Cancer: Prevention, Epidemiology and Screening. New York: Raven Press. 1980: 83-95. Diaz Llopis M, Menezo JL. Congenital hypertrophy of the retinal pigment epithelium and familial polyposis of the colon. Am J Ophthalmol 1987; 103: 235. Chapman PD, Church W, Burn J, Gunn A. Congenital hypertrophy of the retinal pigment epithelium; a sign of familial adenomatous polyposis. Br Med J 1989; 298: 353-4. Burn J, Chapman P, Delhanty J et a/. The Northern Region genetic register for familial adenomatous polyposis coli: use of age of onset, CHRPE and DNA markers in risk calculations. J Med Genef (in press). Jarvinen HJ. Time and type of prophylactic surgery for familial adenomatous coli. Ann Surg 1985; 202: 93-7. Bulow S. The risk of developing rectal cancer after colectomy and ileorectal anastomosis in Danish patients with polyposis coli. Dis Colon Rectum 1984; 27: 726-9. Bussey HJR, Eyers AA, Ritchie SM, Thompson JPS. The rectum in adenomatous polyDosis: the St Mark’s policy. - .. . . Br J Surq 1985; SUPPI:S29-S35. Murdav V. Slack J. Inherited disorders associated with colorectal cancer.’Cancer Surv 1989; 8: 139-57. Bodmer WF, Bailey CJ, Bodmer J et al. Localisation of the gene for familial adenomatous polyposis on chromosome 5 . Nature 1987; 328: 614-16. Ponder BAJ, Coffey R, Gagel RF er a/. Risk estimation and screening in families of patients with medullary thyroid carcinoma. Lancet 1988; i : 397400. Houlston R, Slack J, Murday V. Risk estimates for screening adenomatous polyposis coli. Lancer 1990; i: 484 (Letter).
Paper accepted 17 October 1990
Br. J. Surg., Vol. 78, No. 4, April 1991
