Annals of the Royal College of Surgeons of England (1990) vol. 72, 181-184
Extracolonic manifestations associated with familial adenomatous polyposis T G Parks
MCh FRCS Professor of Surgical Science
Department of Surgery, Belfast City Hospital
Key words: Familial adenomatous polyposis; Extracolonic manifestations; Inheritance
Although Devic and Bussy (1) in 1912 reported a patient in whom colonic polyposis and cancer were associated with cutaneous abnormalities and bone tumours it was not until the early 1950s that Gardner and co-workers described a kindred, some members of which suffered from the triad of familial polyposis, multiple osteomas and multiple epidermoid cysts and which subsequently became known as Gardner's syndrome (2,3). Subsequently, it has become evident that a high proportion of patients with familial adenomatous polyposis have some of a wide variety of extracolonic abnormalities if carefully looked for by clinical examination, by endoscopic visualisation of the upper gastrointestinal tract and by radiological examination, particularly of the mandible. Considerable controversy has arisen, therefore, as to whether so-called Gardner's syndrome constitutes a distinct and separate entity from familial adenomatous polyposis. In his Presidential Address to the Section of Coloproctology of the Royal Society of Medicine, Sir Hugh Lockhart-Mummery discussed various lesions that may accompany colonic polyposis (4). In 1970 he and I, together with Dick Bussey, published a paper in which we classified the extracolonic manifestations of familial adenomatous polyposis according to the primary embryonic layer from which the tissue had been derived, ie ectoderm, mesoderm or endoderm (5). Table I lists a number of lesions which are generally accepted as being associated with familial adenomatous polyposis.
Lesions of ectodermal origin Epidermoid cysts are not uncommon in the general population but tend to occur with increased frequency
Correspondence to: Professor T G Parks, Professor of Surgical Science, Department of Surgery, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB
and at a younger age in patients with polyposis. Sites of predilection are the face, scalp, legs and arms. Tumours of neuroectoderm were described in association with polyposis by Turcot et al. (6) in two family members, one of whom had a medulloblastoma and the other had a frontal glioblastoma. Several other cases of the syndrome bearing the name of Turcot have been reported subsequently.
Ocular changes The association of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with familial adenomatous polyposis is now well recognised (7-11). The potential role for this ocular sign as a clinical marker has been recognised and is currently being evaluated in several centres.
The ocular lesions are discrete, darkly pigmented, round, oval or kidney shaped. They range in size from 0.1 to 1.0 or more optic disc diameters. There may be a hypopigmented halo around the periphery or depigmented lacunae within the lesions. The presence of multiple or bilateral ocular lesions are grounds for an individual to be scored as positive for CHRPE, but small solitary unilateral lesions can occur in the general population, where the incidence has been quoted as low as 2% and as high as 30%. Lesions totalling four or more, and affecting both eyes, have a specificity of approximately 98% and a sensitivity of 85% as a marker. Pigmented fungus lesions have to be ditterentiated from malignant melanoma, reactive retinal pigment epithelial hyperplasia, geographic dark posterior fundus patches and choroidal naevi.
Lesions of mesodermal origin Desmoid disease Fibromata may be encountered subcutaneously or in the musculo-aponeurotic layer of the abdominal wall,
182
T G Parks
Table I. Abnormalities of primary embryonic layers Ectodermal origin
Mesodermal origin
Epidermoid cysts Tumours of the central nervous system (Turcot's syndrome) Congenital hypertrophy of retinal pigment epithelium
Connective tissue Fibroma and fibrosarcoma Desmoid tumours Diffuse fibrosis mesenteric mesocolic retroperitoneal Excessive intra-abdominal adhesions Bone Osteoma
Exostosis Sclerosis Dental Dentigenous cyst
Endodermal origin Adenomas of: duodenum small intestine stomach Hamartomas of stomach Adenomas of: adrenal thyroid pancreas Carcinoma of: duodenum pancreas stomach thyroid adrenal
Odontoma Supernumery teeth Unerupted teeth
especially in or near laparotomy scars. Desmoid tumours of a fibrous nature which are locally invasive with illdefined margins extending into the adjacent tissue may arise particularly in the mesentery of the small bowel or in the retroperitoneum. They tend to grow slowly but can reach a massive size causing intestinal obstruction or respiratory and cardiovascular embarrassment. Extension of the fibrotic process may lead to strangulation of the mesenteric vasculature or ureteric obstruction. Occasionally patients develop dense fibrous adhesions postoperatively and intestinal obstruction is a relatively common complication. The condition may be exacerbated by operation or pregnancy. While the condition may progress relentlessly, in some instances it regresses spontaneously. The frequency with which the desmoids occur is higher in familial adenomatous polyposis than in any other medical condition. It has been estimated that the lifetime risk of developing the condition for patients with familial polyposis is 8% for males and 15% for females (12). Furthermore, females tend to develop desmoids at an earlier age than males. There is a tendency for clustering of desmoid disease to occur in some families. Desmoid tumours of the abdominal wall are excised if feasible. Intra-abdominal lesions are generally best left alone, but if operation is required, eg for obstruction, then a bypass procedure is the preferred option, since heroic attempts at removal may be followed by more desmoid tumour formation (13). At St Mark's Hospital, 215 patients underwent colectomy and ileorectal anastomosis for familial adenomatous polyposis between 1948 and 1989 and, of these, 17 patients (5 male, 12 female) developed desmoids (4 abdominal wall, 8 intra-abdominal, 5 at both sites). In
addition, 19 other polyposis patients with desmoids have been treated at St Mark's, making a total of 36 patients with the disorder of whom seven have died of their desmoid disease. Bone and dental abnormalities Osteomas may occur in the mandible, maxilla, sinuses or calvarium of the skull and less often in the long bones. Utsunomiya and Nakamura (14) described occult osteomatous changes in 93% of 29 patients in 15 polyposis families; changes were detected by panoramic radiography and not by clinical examination. They also reported that 37% of polyposis patients in their registry had impacted teeth. Exostosis may be demonstrated in the skull, digits and long bones. Localised cortical thickening occurs primarily in the long bones and less commonly in ribs, metacarpals and phalanges. Dental abnormalities include odontomas, dentigerous cysts, supernumery and unerupted teeth. The occult osteomatous, sclerotic or other dental abnormalities may antedate the development of polyps in the colorectum (15).
Lesions of endodermal origin Several publications have highlighted the increased frequency of upper gastrointestinal adenomas and carcinoma in patients with familial adenomatous polyposis (16-20). In a series of 102 patients with familial adenomatous polyposis who underwent prospective upper
Extracolonic manifestations with familial adenomatous polyposis
gastrointestinal screening by endoscopy at St Mark's and St Bartholomew's Hospitals, London, 56 had gastric polyps and 88 had duodenal polyps. Non-adenomatous fundic gland polyps predominated in the stomach, whereas adenomas were uncommon. Duodenal lesions were mostly adenomatous in nature and were sited mainly in the second and third parts with a distinct concentration in and around the duodenal papilla. The use of side viewing endoscopes together with routine biopsies confirmed a higher incidence of foregut polyposis than had previously been appreciated (16). In a recent report by Jagelman et al. (17), 57 cases of upper gastrointestinal carcinoma were identified in 1255 cases of familial adenomatous polyposis, an incidence of 4.5%. The most frequent sites were the duodenum, pancreas and the stomach. It has been estimated that individuals with polyposis may have more than a 100-fold increase in risk of developing periampullary carcinoma when compared with the general population. lida et al. (18) studied the natural history of duodenal lesions in 20 Japanese patients with familial adenomatous polyposis over a mean period of 7.1 years. Tubular adenomas of the duodenum (less than 8 mm in diameter) were present in 18 of the 20 patients (90%). Tubular adenomatous tissue of the actual duodenal papilla was recognised in 11 patients (55%). During the follow-up period, the lesions remained static in all but four cases.
Mode of inheritance It would seem that colonic polyposis and the extracolonic manifestations are controlled by the same dominant gene. It is hypothesised that a single pleiotrophic gene is responsible for the various morphological changes. Most authorities now favour the concept that patients with extracolonic manifestations merely represent a more complete phenotypic expression of the same genotype than does colonic polyposis alone. The defect responsible for familial adenomatous polyposis has recently been mapped to the long arm of chromosome 5 by linkage between the familial polyposis coli phenotype and a locus located at 5q21-22 as defined by DNA probes Cl1PIl and pi227 (21,22). The picture which has emerged is that of a genetically determined disease with a propensity for excessive tissue growth which can present in both neoplastic and hamartomatous forms in various organs and tissues of the body. The importance of extracolonic abnormalities is paramount in that upper gastrointestinal malignancy and desmoid disease carry a significant mortality. Nowadays, they are responsible for more deaths than colonic cancer in kindreds who have had appropriate treatment for the colonic element of the disease. Futhermore, the presence of extracolonic abnormalities may alert the clinician to the possibility of associated colonic disease. Where congenital hypertrophy of retinal pigment epithelium is concerned, it may aid as a clinical marker. Finally, gene probes are being evaluated and their predictive value
183
assessed so that it may be feasible to screen at-risk individuals by non-invasive methods in the future.
References I Devic A, Bussy NM. Un cas de polypose adenomateuse generalisee a tout l'intestin. Arch Mal Appar Dig 1912; 6:278-89. 2 Gardner EJ. A genetic and clinical study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum. Am 7 Hum Genet 1951;3:167-76. 3 Gardner EJ, Richards RC. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis. Am J Hum Genet 1953;5: 139-47. 4 Lockhart-Mummery HE. Intestinal polyposis: the present position. Proc R Soc Med 1967;60:381-8. 5 Parks TG, Bussey HJR, Lockhart-Mummery HE. Familial polyposis coli associated with extracolonic abnormalities. Gut 1970;11:323-9. 6 Turcot J, Despres JP, St Pierre FS. Malignant tumours of the central nervous system associated with familial polyposis of the colon. Dis Colon Rectum 1959;2:465-8. 7 Blair NP, Trempe CL. Hypertrophy of the retinal pigment epithelium associated with Gardner's syndrome. Am Jf Ophthalnol 1980;90:661-7. 8 Traboulsi EI, Krush AJ, Gardner EJ et al. Prevalence and importance of pigmented ocular fundus lesions in Gardner's syndrome. N EnglJ7 Med 1987;316:661-7. 9 Traboulsi El, Maumenee IH, Krush AJ et al. Pigmented ocular fundus lesions in the inherited gastrointestinal polyposis syndromes and in hereditary nonpolyposis colorectal cancer. Ophthalmology 1988;95:964-9. 10 Diaz-Lopez M, Menezo JL. Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis. Arch Ophthalmol 1988;106:412-13. 11 Chapman PD, Church W, Burn J, Gunn A. Congenital hypertrophy of retinal pigment epithelium: a sign of familial adenomatous polyposis. Br MedJ7 1989;298:353-4. 12 Klemmer S, Pascoe L, De Cosse J. Occurrence of desmoids in patients with familial adenomatous polyposis of the colon. Am J Med Genet 1987;28:385-92. 13 Lotfi AM, Dozois RR, Gordon H et al. Mesenteric fibromatosis complicating familial adenomatous polyposis: predisposing factors and results of treatment. Int J Color Dis 1989;4:30-6. 14 Utsunomiya J, Nakamura T. The occult osteomatous changes in the mandible in patients with familial polyposis coli. Br Jf Surg 1975;62:45-51. 15 Carl W, Sullivan MA. Dental abnormalities and bone lesions associated with familial adenomatous polyposis: report of cases. J Am Dent Assoc 1989;119: 137-9. 16 Spigelman AD, Williams CB, Talbot IC, Domizio D, Phillips RKS. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 1989;2:783-5. 17 Jagelman DG, De Cosse JJ, Bussey HJR. Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet 1988;l: 1149-50. \ 18 lida M, Yao T, Itoh H, Ohsato K, Watanabe H. Endoscopic features of adenomas of the duodenal papilla of familial polyposis of the colon. Gastrointest Endosc 1981; 27:6-8. 19 Ushio K, Sasagawa M, Doi H et al. Lesions associated with familial polyposis coli. Studies of lesions of the stomach,
184
T G Parks
duodenum, bones and teeth. Gastrointest Radiol 1976;1: 67-80. 20 Bussey HJR, Veale AMO, Morson BC. Genetics of gastrointestinal polyposis. Gastroenterology 1978;74:1325-30. 21 Bodmer WJ, Bailey CJ, Bodmer J et al. Localisation of the gene for familial adenomatous polyposis on Chromosome 5. Nature 1987;328:614-16.
22 Nakamura Y, Lathrop M, Leppert M et al. Localisation of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am J Hum Genet 1988; 43:638-44.
The foliowing papers were also presented at the Sir Hugh Lockhart-Mummery Memorial Meeting B Creamer MD FRCP W W Slack MCh FRCS B T Jackson MS FRCS
The combined medical and surgical management of Crohn's disease Historical Aspects of Serjeant-Surgeon to The Queen Lyn Lockhart-Mummery: an appreciation
Extracolonic manifestations associated with familial adenomatous polyposis T G Parks
MCh FRCS Professor of Surgical Science
Department of Surgery, Belfast City Hospital
Key words: Familial adenomatous polyposis; Extracolonic manifestations; Inheritance
Although Devic and Bussy (1) in 1912 reported a patient in whom colonic polyposis and cancer were associated with cutaneous abnormalities and bone tumours it was not until the early 1950s that Gardner and co-workers described a kindred, some members of which suffered from the triad of familial polyposis, multiple osteomas and multiple epidermoid cysts and which subsequently became known as Gardner's syndrome (2,3). Subsequently, it has become evident that a high proportion of patients with familial adenomatous polyposis have some of a wide variety of extracolonic abnormalities if carefully looked for by clinical examination, by endoscopic visualisation of the upper gastrointestinal tract and by radiological examination, particularly of the mandible. Considerable controversy has arisen, therefore, as to whether so-called Gardner's syndrome constitutes a distinct and separate entity from familial adenomatous polyposis. In his Presidential Address to the Section of Coloproctology of the Royal Society of Medicine, Sir Hugh Lockhart-Mummery discussed various lesions that may accompany colonic polyposis (4). In 1970 he and I, together with Dick Bussey, published a paper in which we classified the extracolonic manifestations of familial adenomatous polyposis according to the primary embryonic layer from which the tissue had been derived, ie ectoderm, mesoderm or endoderm (5). Table I lists a number of lesions which are generally accepted as being associated with familial adenomatous polyposis.
Lesions of ectodermal origin Epidermoid cysts are not uncommon in the general population but tend to occur with increased frequency
Correspondence to: Professor T G Parks, Professor of Surgical Science, Department of Surgery, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB
and at a younger age in patients with polyposis. Sites of predilection are the face, scalp, legs and arms. Tumours of neuroectoderm were described in association with polyposis by Turcot et al. (6) in two family members, one of whom had a medulloblastoma and the other had a frontal glioblastoma. Several other cases of the syndrome bearing the name of Turcot have been reported subsequently.
Ocular changes The association of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with familial adenomatous polyposis is now well recognised (7-11). The potential role for this ocular sign as a clinical marker has been recognised and is currently being evaluated in several centres.
The ocular lesions are discrete, darkly pigmented, round, oval or kidney shaped. They range in size from 0.1 to 1.0 or more optic disc diameters. There may be a hypopigmented halo around the periphery or depigmented lacunae within the lesions. The presence of multiple or bilateral ocular lesions are grounds for an individual to be scored as positive for CHRPE, but small solitary unilateral lesions can occur in the general population, where the incidence has been quoted as low as 2% and as high as 30%. Lesions totalling four or more, and affecting both eyes, have a specificity of approximately 98% and a sensitivity of 85% as a marker. Pigmented fungus lesions have to be ditterentiated from malignant melanoma, reactive retinal pigment epithelial hyperplasia, geographic dark posterior fundus patches and choroidal naevi.
Lesions of mesodermal origin Desmoid disease Fibromata may be encountered subcutaneously or in the musculo-aponeurotic layer of the abdominal wall,
182
T G Parks
Table I. Abnormalities of primary embryonic layers Ectodermal origin
Mesodermal origin
Epidermoid cysts Tumours of the central nervous system (Turcot's syndrome) Congenital hypertrophy of retinal pigment epithelium
Connective tissue Fibroma and fibrosarcoma Desmoid tumours Diffuse fibrosis mesenteric mesocolic retroperitoneal Excessive intra-abdominal adhesions Bone Osteoma
Exostosis Sclerosis Dental Dentigenous cyst
Endodermal origin Adenomas of: duodenum small intestine stomach Hamartomas of stomach Adenomas of: adrenal thyroid pancreas Carcinoma of: duodenum pancreas stomach thyroid adrenal
Odontoma Supernumery teeth Unerupted teeth
especially in or near laparotomy scars. Desmoid tumours of a fibrous nature which are locally invasive with illdefined margins extending into the adjacent tissue may arise particularly in the mesentery of the small bowel or in the retroperitoneum. They tend to grow slowly but can reach a massive size causing intestinal obstruction or respiratory and cardiovascular embarrassment. Extension of the fibrotic process may lead to strangulation of the mesenteric vasculature or ureteric obstruction. Occasionally patients develop dense fibrous adhesions postoperatively and intestinal obstruction is a relatively common complication. The condition may be exacerbated by operation or pregnancy. While the condition may progress relentlessly, in some instances it regresses spontaneously. The frequency with which the desmoids occur is higher in familial adenomatous polyposis than in any other medical condition. It has been estimated that the lifetime risk of developing the condition for patients with familial polyposis is 8% for males and 15% for females (12). Furthermore, females tend to develop desmoids at an earlier age than males. There is a tendency for clustering of desmoid disease to occur in some families. Desmoid tumours of the abdominal wall are excised if feasible. Intra-abdominal lesions are generally best left alone, but if operation is required, eg for obstruction, then a bypass procedure is the preferred option, since heroic attempts at removal may be followed by more desmoid tumour formation (13). At St Mark's Hospital, 215 patients underwent colectomy and ileorectal anastomosis for familial adenomatous polyposis between 1948 and 1989 and, of these, 17 patients (5 male, 12 female) developed desmoids (4 abdominal wall, 8 intra-abdominal, 5 at both sites). In
addition, 19 other polyposis patients with desmoids have been treated at St Mark's, making a total of 36 patients with the disorder of whom seven have died of their desmoid disease. Bone and dental abnormalities Osteomas may occur in the mandible, maxilla, sinuses or calvarium of the skull and less often in the long bones. Utsunomiya and Nakamura (14) described occult osteomatous changes in 93% of 29 patients in 15 polyposis families; changes were detected by panoramic radiography and not by clinical examination. They also reported that 37% of polyposis patients in their registry had impacted teeth. Exostosis may be demonstrated in the skull, digits and long bones. Localised cortical thickening occurs primarily in the long bones and less commonly in ribs, metacarpals and phalanges. Dental abnormalities include odontomas, dentigerous cysts, supernumery and unerupted teeth. The occult osteomatous, sclerotic or other dental abnormalities may antedate the development of polyps in the colorectum (15).
Lesions of endodermal origin Several publications have highlighted the increased frequency of upper gastrointestinal adenomas and carcinoma in patients with familial adenomatous polyposis (16-20). In a series of 102 patients with familial adenomatous polyposis who underwent prospective upper
Extracolonic manifestations with familial adenomatous polyposis
gastrointestinal screening by endoscopy at St Mark's and St Bartholomew's Hospitals, London, 56 had gastric polyps and 88 had duodenal polyps. Non-adenomatous fundic gland polyps predominated in the stomach, whereas adenomas were uncommon. Duodenal lesions were mostly adenomatous in nature and were sited mainly in the second and third parts with a distinct concentration in and around the duodenal papilla. The use of side viewing endoscopes together with routine biopsies confirmed a higher incidence of foregut polyposis than had previously been appreciated (16). In a recent report by Jagelman et al. (17), 57 cases of upper gastrointestinal carcinoma were identified in 1255 cases of familial adenomatous polyposis, an incidence of 4.5%. The most frequent sites were the duodenum, pancreas and the stomach. It has been estimated that individuals with polyposis may have more than a 100-fold increase in risk of developing periampullary carcinoma when compared with the general population. lida et al. (18) studied the natural history of duodenal lesions in 20 Japanese patients with familial adenomatous polyposis over a mean period of 7.1 years. Tubular adenomas of the duodenum (less than 8 mm in diameter) were present in 18 of the 20 patients (90%). Tubular adenomatous tissue of the actual duodenal papilla was recognised in 11 patients (55%). During the follow-up period, the lesions remained static in all but four cases.
Mode of inheritance It would seem that colonic polyposis and the extracolonic manifestations are controlled by the same dominant gene. It is hypothesised that a single pleiotrophic gene is responsible for the various morphological changes. Most authorities now favour the concept that patients with extracolonic manifestations merely represent a more complete phenotypic expression of the same genotype than does colonic polyposis alone. The defect responsible for familial adenomatous polyposis has recently been mapped to the long arm of chromosome 5 by linkage between the familial polyposis coli phenotype and a locus located at 5q21-22 as defined by DNA probes Cl1PIl and pi227 (21,22). The picture which has emerged is that of a genetically determined disease with a propensity for excessive tissue growth which can present in both neoplastic and hamartomatous forms in various organs and tissues of the body. The importance of extracolonic abnormalities is paramount in that upper gastrointestinal malignancy and desmoid disease carry a significant mortality. Nowadays, they are responsible for more deaths than colonic cancer in kindreds who have had appropriate treatment for the colonic element of the disease. Futhermore, the presence of extracolonic abnormalities may alert the clinician to the possibility of associated colonic disease. Where congenital hypertrophy of retinal pigment epithelium is concerned, it may aid as a clinical marker. Finally, gene probes are being evaluated and their predictive value
183
assessed so that it may be feasible to screen at-risk individuals by non-invasive methods in the future.
References I Devic A, Bussy NM. Un cas de polypose adenomateuse generalisee a tout l'intestin. Arch Mal Appar Dig 1912; 6:278-89. 2 Gardner EJ. A genetic and clinical study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum. Am 7 Hum Genet 1951;3:167-76. 3 Gardner EJ, Richards RC. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis. Am J Hum Genet 1953;5: 139-47. 4 Lockhart-Mummery HE. Intestinal polyposis: the present position. Proc R Soc Med 1967;60:381-8. 5 Parks TG, Bussey HJR, Lockhart-Mummery HE. Familial polyposis coli associated with extracolonic abnormalities. Gut 1970;11:323-9. 6 Turcot J, Despres JP, St Pierre FS. Malignant tumours of the central nervous system associated with familial polyposis of the colon. Dis Colon Rectum 1959;2:465-8. 7 Blair NP, Trempe CL. Hypertrophy of the retinal pigment epithelium associated with Gardner's syndrome. Am Jf Ophthalnol 1980;90:661-7. 8 Traboulsi EI, Krush AJ, Gardner EJ et al. Prevalence and importance of pigmented ocular fundus lesions in Gardner's syndrome. N EnglJ7 Med 1987;316:661-7. 9 Traboulsi El, Maumenee IH, Krush AJ et al. Pigmented ocular fundus lesions in the inherited gastrointestinal polyposis syndromes and in hereditary nonpolyposis colorectal cancer. Ophthalmology 1988;95:964-9. 10 Diaz-Lopez M, Menezo JL. Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis. Arch Ophthalmol 1988;106:412-13. 11 Chapman PD, Church W, Burn J, Gunn A. Congenital hypertrophy of retinal pigment epithelium: a sign of familial adenomatous polyposis. Br MedJ7 1989;298:353-4. 12 Klemmer S, Pascoe L, De Cosse J. Occurrence of desmoids in patients with familial adenomatous polyposis of the colon. Am J Med Genet 1987;28:385-92. 13 Lotfi AM, Dozois RR, Gordon H et al. Mesenteric fibromatosis complicating familial adenomatous polyposis: predisposing factors and results of treatment. Int J Color Dis 1989;4:30-6. 14 Utsunomiya J, Nakamura T. The occult osteomatous changes in the mandible in patients with familial polyposis coli. Br Jf Surg 1975;62:45-51. 15 Carl W, Sullivan MA. Dental abnormalities and bone lesions associated with familial adenomatous polyposis: report of cases. J Am Dent Assoc 1989;119: 137-9. 16 Spigelman AD, Williams CB, Talbot IC, Domizio D, Phillips RKS. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 1989;2:783-5. 17 Jagelman DG, De Cosse JJ, Bussey HJR. Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet 1988;l: 1149-50. \ 18 lida M, Yao T, Itoh H, Ohsato K, Watanabe H. Endoscopic features of adenomas of the duodenal papilla of familial polyposis of the colon. Gastrointest Endosc 1981; 27:6-8. 19 Ushio K, Sasagawa M, Doi H et al. Lesions associated with familial polyposis coli. Studies of lesions of the stomach,
184
T G Parks
duodenum, bones and teeth. Gastrointest Radiol 1976;1: 67-80. 20 Bussey HJR, Veale AMO, Morson BC. Genetics of gastrointestinal polyposis. Gastroenterology 1978;74:1325-30. 21 Bodmer WJ, Bailey CJ, Bodmer J et al. Localisation of the gene for familial adenomatous polyposis on Chromosome 5. Nature 1987;328:614-16.
22 Nakamura Y, Lathrop M, Leppert M et al. Localisation of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am J Hum Genet 1988; 43:638-44.
The foliowing papers were also presented at the Sir Hugh Lockhart-Mummery Memorial Meeting B Creamer MD FRCP W W Slack MCh FRCS B T Jackson MS FRCS
The combined medical and surgical management of Crohn's disease Historical Aspects of Serjeant-Surgeon to The Queen Lyn Lockhart-Mummery: an appreciation
