Digestive Endoscopy 2014; 26 (Suppl. 2): 30–34
doi: 10.1111/den.12255
Endoscopic diagnosis and treatment of non-ampullary superficial duodenal tumors
Duodenal adenomatosis in Japanese patients with familial adenomatous polyposis Yuji Maehata,1 Motohiro Esaki,1 Minako Hirahashi,2 Takanari Kitazono1 and Takayuki Matsumoto3 Departments of 1Medicine and Clinical Science and 2Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka and 3Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
Duodenal adenomatosis is the most frequent extracolonic manifestation of familial adenomatous polyposis (FAP), and duodenal cancer has been assumed to be the second most significant cause of death in patients with the disease. To stratify the risk of duodenal cancer, Spigelman’s classification was proposed for the staging of duodenal adenomatosis. According to Western guidelines, patients with stage IV of the classification are candidates for prophylactic duodenectomy. Since our institutional experience disclosed only 2% of duodenal or ampullary cancers among 130 patients with FAP, and because most duodenal
INTRODUCTION
F
AMILIAL ADENOMATOUS POLYPOSIS (FAP) is an autosomal dominant hereditary disease mainly caused by germline mutations of the adenomatous polyposis coli (APC) gene.1,2 As colorectal cancer occurs in most patients in the fifth decade of life, prophylactic colectomy is recommended for patients with FAP.3 However, even after prophylactic colectomy, patients are at high risk of extracolonic malignant neoplasms. Among various extracolonic tumors, duodenal and ampullary cancers are most frequent, with a 330-fold increase in the risk compared to the general population.4 Because duodenal and ampullary cancers arise from duodenal adenomatosis via the adenoma-carcinoma sequence in FAP,5 the management of duodenal adenomatosis needs to be established. However, such a high risk in the occurrence of duodenal and ampullary cancer in FAP seems debatable, because we previously demonstrated a static nature of duodenal adenomatosis from both histological and
Corresponding: Motohiro Esaki, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. Email: [email protected] Received 11 December 2013; accepted 17 January 2014.
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30
adenomatosis remains unchanged under endoscopic surveillance, it seems likely that aggressive endoscopic or surgical removal is unnecessary for most FAP patients with duodenal adenomatosis. In the present article, we demonstrate our data and present our strategy for duodenal adenomatosis of FAP. Key words: APC gene mutation, duodenal adenomatosis, endoscopic surveillance, familial adenomatous polyposis, Spigelman’s classification
endoscopic viewpoints.3,6 In the present article, we demonstrate our institutional data and discuss the management concerning the duodenal adenomatosis of FAP.
DUODENAL ADENOMATOSIS OF FAP IN OUR INSTITUTION
D
URING THE PERIOD between 1964 and 2013, the diagnosis of FAP was made in 130 patients from 101 families at our institution. The patients included 69 males and 61 females, ranging in age from 9 to 72 years (mean, 34 years) at the time of initial diagnosis of FAP. Table 1 shows the prevalence of each type of gastroduodenal lesion among our patients with FAP. As for duodenal adenomatosis, various types of duodenal lesion were endoscopically found, and we categorized them into five types: small protrusion, flat elevation, depressed lesion, nodular protrusion, and nodular aggregating lesion. Although small, whitish polyps (Fig. 1a) and flat elevation (Fig. 1b) were the most frequently found, depressed lesions sometimes occurred and they became obvious under chromoendoscopy with a dye spraying method (Fig. 1c). In patients with severe duodenal adenomatosis, duodenal adenomas were occasionally recognized as nodular protrusions (Fig. 1d) or nodular aggregating lesions (Fig. 1e).
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; 26 (Suppl. 2): 30–34
Duodenal adenomatosis of FAP 31
Table 1 Upper gastrointestinal involvement in our patients with FAP (n = 130) Gastric lesions Fundic gland polyposis Gastric adenoma Gastric cancer Duodenal lesions Ampullary adenoma Duodenal adenomatosis Ampullary cancer Duodenal cancer†
76 (58%) 40 (31%) 9 (7%) 68 (53%) 104 (80%) 2 (2%) 1 (1%)
Data are expressed as n (%). † Carcinoma of the duodenal bulb. FAP, familial adenomatous polyposis.
Based on these data, we recommend endoscopic follow up for FAP patients according to the management shown in Figure 3. At the initial diagnosis, duodenal adenomatosis should be carefully evaluated using side-viewing endoscopy. If patients have duodenal adenomatosis, surveillance endoscopy is carried out with a 2–3-year interval until the age of 35 years. Thereafter, surveillance endoscopy is done annually. In patients without duodenal adenomatosis, the interval of endoscopic surveillance is set to be longer than for patients with duodenal adenomatosis.
DISCUSSION
Of the 104 patients with duodenal adenomatosis, precise endoscopic follow-up data could be obtained in 41 patients. Table 2 summarizes Spigelman’s classification at the initial diagnosis and natural history of duodenal adenomatosis in these patients. Although 37 patients (90%) were classified as having severe duodenal adenomatosis at initial diagnosis, those lesions remained unchanged in 35 patients (85%) during the follow-up periods (median, 10.6 years, range 1.9– 38.1 years). However, duodenal adenomatosis progressed in four patients in the pedigree shown in Figure 2a, having an APC mutation at codon 1556. Ampullary and duodenal cancers were found in three patients. We could not assess the severity of duodenal adenomatosis in a patient with ampullary cancer, as we surveyed the patient after the duodenectomy. In another patient, ampullary cancer was diagnosed at the time of the initial diagnosis of FAP. The stage of adenomatosis in the patient was determined to be stage III. The remaining patient had duodenal adenomatosis of stage II both at the time of the initial diagnosis of FAP and at the time of the diagnosis of duodenal cancer. Figure 2a shows a family line of a pedigree with APC mutation at codon 1556.7 Case 1 underwent duodenectomy for his progressive duodenal adenomatosis (Fig. 2b). Histological findings of the resected specimen revealed multiple tubular adenomas with moderate to severe dysplasia. In cases 2 and 3, their duodenal adenomatosis progressed to Spigelman’s stage IV during the follow-up period (Fig. 2c,d). However, under careful endoscopic observation along with biopsy, no duodenal cancer has been confirmed. Partial resection of the duodenum was carried out for a large protrusion in case 4 (Fig. 2e), resulting in histological confirmation of tubulovillous adenoma with moderate dysplasia. Subsequently, in spite of their severe duodenal adenomatosis, no duodenal cancer has been confirmed during follow up in this pedigree.
I
N WESTERN COUNTRIES, it has been reported that duodenal adenomatosis occurs in 60–90% and duodenal cancer develops in 2–5% of FAP patients.8–12 The management of duodenal adenomatosis has thus been seriously discussed, and Spigelman’s classification has generally been applied to determine the severity.12 This classification comprises endoscopic features (number and size of adenoma) and histology of duodenal adenomas. The severity of duodenal adenomatosis is classified into five stages, in which stages III and IV imply severe duodenal adenomatosis. In particular, patients with stage IV duodenal adenomatosis are determined to be at a greater risk of malignant transformation of the duodenal adenomatosis. In recently described guidelines for FAP,13 endoscopic surveillance of the duodenum is recommended to be started at the age of 25–30 years, and to be more frequently carried out in patients with severe duodenal adenomatosis. In patients in stage IV, it is also recommended that surgery be considered. However, such aggressive intervention remains to be discussed because the natural history of duodenal adenomatosis has not been fully investigated. The natural history of duodenal adenomatosis was reported from several centers.9,14–16 In a recent European study,16 it has been reported that duodenal adenomatosis improved in 12% of patients, remained unchanged in 34% and progressed in 44%. In addition, duodenal cancer developed in 7% of the patients. In contrast, our previous study demonstrated that duodenal adenomatosis remained unchanged in 17 of 18 patients during 7 years of observation.6 The present study further confirmed the static and benign nature of duodenal adenomatosis. Duodenal adenomatosis remained unchanged in 35 of our 41 patients (85%) without any occurrence of duodenal cancer. Moreover, van Heumen et al.17 reported that duodenal cancer occurred in a minority of patients only (5.5%) with severe duodenal adenomatosis at the time of prophylactic duodenectomy. It thus seems to be inappropriate to recommend prophylactic
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
32
Y. Maehata et al.
a
d
Digestive Endoscopy 2014; 26 (Suppl. 2): 30–34
c
b
e
Figure 1 Endoscopic findings of duodenal adenomatosis in patients with familial adenomatous polyposis. (a) Small protrusion. There are minute, sessile and whitish protrusions scattered in the duodenum. (b) Flat lesion. There are innumerable flat protrusions. (c) Depressed lesion. Small, numerous, and depressed lesions are seen in the duodenum. (d) Nodular protrusion. A large, broad-based protrusion is observed. (e) Nodular aggregating lesion. Multiple nodular protrusions with a nodular surface are found in the duodenum. Table 2 Spigelman’s classification and natural history of duodenal adenomatosis in our patients followed up with electronic endoscopy† Spigelman’s classification at initial diagnosis Stage I Stage II Stage III Stage IV Natural history of duodenal adenomatosis‡ Unchanged Slowly progressive Progressive Duodenal cancer development
0 4 (10%) 36 (88%) 1 (2%) 35 (85%) 2 (5%) 4 (10%) 0
Data are expressed as n (%). † n = 41. ‡ Follow-up period was 1.9 to 38.1 years (median, 10.6 years).
duodenectomy for all FAP patients even with duodenal adenomatosis of stage IV. According to Spigelman’s classification, it was determined that most of our patients (88%) had duodenal adenomatosis of stage III. Mathus-Vliegen et al.18 demonstrated a
progressive trend in Spigelman’s score in a cohort of FAP patients evaluated between 1980 and 2009 that was mostly attributable to technological advances in endoscopy. Because the detectability of diminutive polyps depends on the resolution of endoscopy, modification of Spigelman’s classification needs to be considered. APC genotype might be another factor that needs to be considered for the determination of the risk of duodenal cancer in FAP. Although recent Western guidelines13 noted that no clear genotype–phenotype correlation was observed between APC gene mutation and duodenal adenomatosis, Björk et al.19 reported a close association of severe periampullary lesions with APC gene mutations located downstream of 1051 in exon 15. We also identified patients in the pedigree of FAP having an APC gene mutation at codon 1556 who manifested severe duodenal adenomatosis.7 Further studies with a large number of patients might confirm a possible contribution of the APC genotype to the duodenal manifestation in FAP. In conclusion, our present analysis demonstrated a static and benign nature of duodenal adenomatosis of FAP. It may not be appropriate to recommend prophylactic
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; 26 (Suppl. 2): 30–34
a
c
Duodenal adenomatosis of FAP 33
b
e
d
Figure 2 (a) Pedigrees of the family with APC gene mutation at codon 1556. Squares, male; circles, female; open symbols, no familial adenomatous polyposis (FAP); solid symbols, patients with FAP. (b) Macroscopic findings of the resected duodenum in case 1. There were multiple polypoid lesions in the duodenum. (c,d) Nodular aggregating lesions were found in the duodenum of cases 2 and 3. (e) A large nodular protrusion developed in case 4.
CONFLICT OF INTERESTS
A
UTHORS DECLARE NO conflict of interests for this article.
REFERENCES
Figure 3 Clinical management of duodenal adenomatosis in our institution.
duodenectomy to all patients with duodenal adenomatosis of Spigelman’s stage IV. However, because duodenal cancer can develop from severe duodenal adenomatosis, more sophisticated risk stratification needs to be established.
1 Nishisho I, Nakamura Y, Miyoshi Y et al. Mutation of a chromosome 5q21 gene in FAP and colorectal cancer patient. Science 1991; 253: 665–9. 2 Spirio L, Otterud B, Stauffer D et al. Linkage of a variant or attenuated form of adenomatous polyposis coli to the adenomatous polyposis coli (APC) locus. Am. J. Hum. Genet. 1992; 51: 92–100. 3 Matsumoto T, Iida M, Nakamura S et al. Natural history of ampullary adenoma in familial adenomatous polyposis: Reconfirmation of benign nature during extended surveillance. Am. J. Gastroenterol. 2000; 95: 1557–62. 4 Offerhaus GJ, Giardiello FM, Krush AL et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology 1992; 102: 1980–2. 5 Spigelman AD, Talbot IC, Penna C et al. Evidence for adenoma-carcinoma sequence in the duodenum of patients with
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
34
6
7
8
9
10
11
12
Y. Maehata et al.
familial adenomatous polyposis. The Leeds Castle Polyposis Group (Upper Gastrointestinal Committee). J. Clin. Pathol. 1994; 47: 709–10. Iida M, Yao T, Itoh H et al. Natural history of duodenal lesions in Japanese patients with familial adenomatosis coli (Gardner’s syndrome). Gastroenterology 1989; 96: 1301–6. Matsumoto T, Iida M, Kobori Y, Mizuno M, Nakamura S, Hizawa K. Progressive duodenal adenomatosis in a familial adenomatous polyposis pedigree with APC mutation at codon 1556. Dis. Colon Rectum 2002; 45: 229–33. Heiskanen I, Kellokumpu I, Järvinen H. Management of duodenal adenomas in 98 patients with familial adenomatous polyposis. Endoscopy 1999; 31: 412–6. Bülow S, Björk J, Christensen IJ et al. Duodenal adenomatosis in familial adenomatous polyposis. Gut 2004; 53: 381–6. Groves CJ, Saunders BP, Spigelman AD, Phillips RK. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study. Gut 2002; 50: 636–41. Latchford AR, Neale KF, Spigelman AD, Phillips RK, Clark SK. Features of duodenal cancer in patients with familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2009; 7: 659–63. Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 1989; 2: 783–5.
Digestive Endoscopy 2014; 26 (Suppl. 2): 30–34
13 Vasen HF, Möslein G, Alonso A et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut 2008; 57: 704–13. 14 Burke CA, Beck GJ, Church JM, van Stolk RU. The natural history of untreated duodenal and ampullary adenomas in patients with familial adenomatous polyposis followed in an endoscopic surveillance program. Gastrointest. Endosc. 1999; 49: 358–64. 15 Jaganmohan S, Lynch PM, Raju RP et al. Endoscopic management of duodenal adenomas in familial adenomatous polyposis– a single-center experience. Dig. Dis. Sci. 2012; 57: 732–7. 16 Bülow S, Christensen IJ, Hø´jen H et al. Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis. Colorectal Dis. 2012; 14: 947–52. 17 van Heumen BW, Nieuwenhuis MH, van Goor H et al. Surgical management for advanced duodenal adenomatosis and duodenal cancer in Dutch patients with familial adenomatous polyposis: A nationwide retrospective cohort study. Surgery 2012; 151: 681–90. 18 Mathus-Vliegen EM, Boparai KS, Dekker E, van Geloven N. Progression of duodenal adenomatosis in familial adenomatous polyposis: Due to ageing of subjects and advances in technology. Fam. Cancer 2011; 10: 491–9. 19 Björk J, Akerbrant H, Iselius L et al. Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: Cumulative risks and APC gene mutations. Gastroenterology 2001; 121: 1127–35.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
doi: 10.1111/den.12255
Endoscopic diagnosis and treatment of non-ampullary superficial duodenal tumors
Duodenal adenomatosis in Japanese patients with familial adenomatous polyposis Yuji Maehata,1 Motohiro Esaki,1 Minako Hirahashi,2 Takanari Kitazono1 and Takayuki Matsumoto3 Departments of 1Medicine and Clinical Science and 2Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka and 3Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
Duodenal adenomatosis is the most frequent extracolonic manifestation of familial adenomatous polyposis (FAP), and duodenal cancer has been assumed to be the second most significant cause of death in patients with the disease. To stratify the risk of duodenal cancer, Spigelman’s classification was proposed for the staging of duodenal adenomatosis. According to Western guidelines, patients with stage IV of the classification are candidates for prophylactic duodenectomy. Since our institutional experience disclosed only 2% of duodenal or ampullary cancers among 130 patients with FAP, and because most duodenal
INTRODUCTION
F
AMILIAL ADENOMATOUS POLYPOSIS (FAP) is an autosomal dominant hereditary disease mainly caused by germline mutations of the adenomatous polyposis coli (APC) gene.1,2 As colorectal cancer occurs in most patients in the fifth decade of life, prophylactic colectomy is recommended for patients with FAP.3 However, even after prophylactic colectomy, patients are at high risk of extracolonic malignant neoplasms. Among various extracolonic tumors, duodenal and ampullary cancers are most frequent, with a 330-fold increase in the risk compared to the general population.4 Because duodenal and ampullary cancers arise from duodenal adenomatosis via the adenoma-carcinoma sequence in FAP,5 the management of duodenal adenomatosis needs to be established. However, such a high risk in the occurrence of duodenal and ampullary cancer in FAP seems debatable, because we previously demonstrated a static nature of duodenal adenomatosis from both histological and
Corresponding: Motohiro Esaki, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. Email: [email protected] Received 11 December 2013; accepted 17 January 2014.
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30
adenomatosis remains unchanged under endoscopic surveillance, it seems likely that aggressive endoscopic or surgical removal is unnecessary for most FAP patients with duodenal adenomatosis. In the present article, we demonstrate our data and present our strategy for duodenal adenomatosis of FAP. Key words: APC gene mutation, duodenal adenomatosis, endoscopic surveillance, familial adenomatous polyposis, Spigelman’s classification
endoscopic viewpoints.3,6 In the present article, we demonstrate our institutional data and discuss the management concerning the duodenal adenomatosis of FAP.
DUODENAL ADENOMATOSIS OF FAP IN OUR INSTITUTION
D
URING THE PERIOD between 1964 and 2013, the diagnosis of FAP was made in 130 patients from 101 families at our institution. The patients included 69 males and 61 females, ranging in age from 9 to 72 years (mean, 34 years) at the time of initial diagnosis of FAP. Table 1 shows the prevalence of each type of gastroduodenal lesion among our patients with FAP. As for duodenal adenomatosis, various types of duodenal lesion were endoscopically found, and we categorized them into five types: small protrusion, flat elevation, depressed lesion, nodular protrusion, and nodular aggregating lesion. Although small, whitish polyps (Fig. 1a) and flat elevation (Fig. 1b) were the most frequently found, depressed lesions sometimes occurred and they became obvious under chromoendoscopy with a dye spraying method (Fig. 1c). In patients with severe duodenal adenomatosis, duodenal adenomas were occasionally recognized as nodular protrusions (Fig. 1d) or nodular aggregating lesions (Fig. 1e).
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; 26 (Suppl. 2): 30–34
Duodenal adenomatosis of FAP 31
Table 1 Upper gastrointestinal involvement in our patients with FAP (n = 130) Gastric lesions Fundic gland polyposis Gastric adenoma Gastric cancer Duodenal lesions Ampullary adenoma Duodenal adenomatosis Ampullary cancer Duodenal cancer†
76 (58%) 40 (31%) 9 (7%) 68 (53%) 104 (80%) 2 (2%) 1 (1%)
Data are expressed as n (%). † Carcinoma of the duodenal bulb. FAP, familial adenomatous polyposis.
Based on these data, we recommend endoscopic follow up for FAP patients according to the management shown in Figure 3. At the initial diagnosis, duodenal adenomatosis should be carefully evaluated using side-viewing endoscopy. If patients have duodenal adenomatosis, surveillance endoscopy is carried out with a 2–3-year interval until the age of 35 years. Thereafter, surveillance endoscopy is done annually. In patients without duodenal adenomatosis, the interval of endoscopic surveillance is set to be longer than for patients with duodenal adenomatosis.
DISCUSSION
Of the 104 patients with duodenal adenomatosis, precise endoscopic follow-up data could be obtained in 41 patients. Table 2 summarizes Spigelman’s classification at the initial diagnosis and natural history of duodenal adenomatosis in these patients. Although 37 patients (90%) were classified as having severe duodenal adenomatosis at initial diagnosis, those lesions remained unchanged in 35 patients (85%) during the follow-up periods (median, 10.6 years, range 1.9– 38.1 years). However, duodenal adenomatosis progressed in four patients in the pedigree shown in Figure 2a, having an APC mutation at codon 1556. Ampullary and duodenal cancers were found in three patients. We could not assess the severity of duodenal adenomatosis in a patient with ampullary cancer, as we surveyed the patient after the duodenectomy. In another patient, ampullary cancer was diagnosed at the time of the initial diagnosis of FAP. The stage of adenomatosis in the patient was determined to be stage III. The remaining patient had duodenal adenomatosis of stage II both at the time of the initial diagnosis of FAP and at the time of the diagnosis of duodenal cancer. Figure 2a shows a family line of a pedigree with APC mutation at codon 1556.7 Case 1 underwent duodenectomy for his progressive duodenal adenomatosis (Fig. 2b). Histological findings of the resected specimen revealed multiple tubular adenomas with moderate to severe dysplasia. In cases 2 and 3, their duodenal adenomatosis progressed to Spigelman’s stage IV during the follow-up period (Fig. 2c,d). However, under careful endoscopic observation along with biopsy, no duodenal cancer has been confirmed. Partial resection of the duodenum was carried out for a large protrusion in case 4 (Fig. 2e), resulting in histological confirmation of tubulovillous adenoma with moderate dysplasia. Subsequently, in spite of their severe duodenal adenomatosis, no duodenal cancer has been confirmed during follow up in this pedigree.
I
N WESTERN COUNTRIES, it has been reported that duodenal adenomatosis occurs in 60–90% and duodenal cancer develops in 2–5% of FAP patients.8–12 The management of duodenal adenomatosis has thus been seriously discussed, and Spigelman’s classification has generally been applied to determine the severity.12 This classification comprises endoscopic features (number and size of adenoma) and histology of duodenal adenomas. The severity of duodenal adenomatosis is classified into five stages, in which stages III and IV imply severe duodenal adenomatosis. In particular, patients with stage IV duodenal adenomatosis are determined to be at a greater risk of malignant transformation of the duodenal adenomatosis. In recently described guidelines for FAP,13 endoscopic surveillance of the duodenum is recommended to be started at the age of 25–30 years, and to be more frequently carried out in patients with severe duodenal adenomatosis. In patients in stage IV, it is also recommended that surgery be considered. However, such aggressive intervention remains to be discussed because the natural history of duodenal adenomatosis has not been fully investigated. The natural history of duodenal adenomatosis was reported from several centers.9,14–16 In a recent European study,16 it has been reported that duodenal adenomatosis improved in 12% of patients, remained unchanged in 34% and progressed in 44%. In addition, duodenal cancer developed in 7% of the patients. In contrast, our previous study demonstrated that duodenal adenomatosis remained unchanged in 17 of 18 patients during 7 years of observation.6 The present study further confirmed the static and benign nature of duodenal adenomatosis. Duodenal adenomatosis remained unchanged in 35 of our 41 patients (85%) without any occurrence of duodenal cancer. Moreover, van Heumen et al.17 reported that duodenal cancer occurred in a minority of patients only (5.5%) with severe duodenal adenomatosis at the time of prophylactic duodenectomy. It thus seems to be inappropriate to recommend prophylactic
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
32
Y. Maehata et al.
a
d
Digestive Endoscopy 2014; 26 (Suppl. 2): 30–34
c
b
e
Figure 1 Endoscopic findings of duodenal adenomatosis in patients with familial adenomatous polyposis. (a) Small protrusion. There are minute, sessile and whitish protrusions scattered in the duodenum. (b) Flat lesion. There are innumerable flat protrusions. (c) Depressed lesion. Small, numerous, and depressed lesions are seen in the duodenum. (d) Nodular protrusion. A large, broad-based protrusion is observed. (e) Nodular aggregating lesion. Multiple nodular protrusions with a nodular surface are found in the duodenum. Table 2 Spigelman’s classification and natural history of duodenal adenomatosis in our patients followed up with electronic endoscopy† Spigelman’s classification at initial diagnosis Stage I Stage II Stage III Stage IV Natural history of duodenal adenomatosis‡ Unchanged Slowly progressive Progressive Duodenal cancer development
0 4 (10%) 36 (88%) 1 (2%) 35 (85%) 2 (5%) 4 (10%) 0
Data are expressed as n (%). † n = 41. ‡ Follow-up period was 1.9 to 38.1 years (median, 10.6 years).
duodenectomy for all FAP patients even with duodenal adenomatosis of stage IV. According to Spigelman’s classification, it was determined that most of our patients (88%) had duodenal adenomatosis of stage III. Mathus-Vliegen et al.18 demonstrated a
progressive trend in Spigelman’s score in a cohort of FAP patients evaluated between 1980 and 2009 that was mostly attributable to technological advances in endoscopy. Because the detectability of diminutive polyps depends on the resolution of endoscopy, modification of Spigelman’s classification needs to be considered. APC genotype might be another factor that needs to be considered for the determination of the risk of duodenal cancer in FAP. Although recent Western guidelines13 noted that no clear genotype–phenotype correlation was observed between APC gene mutation and duodenal adenomatosis, Björk et al.19 reported a close association of severe periampullary lesions with APC gene mutations located downstream of 1051 in exon 15. We also identified patients in the pedigree of FAP having an APC gene mutation at codon 1556 who manifested severe duodenal adenomatosis.7 Further studies with a large number of patients might confirm a possible contribution of the APC genotype to the duodenal manifestation in FAP. In conclusion, our present analysis demonstrated a static and benign nature of duodenal adenomatosis of FAP. It may not be appropriate to recommend prophylactic
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; 26 (Suppl. 2): 30–34
a
c
Duodenal adenomatosis of FAP 33
b
e
d
Figure 2 (a) Pedigrees of the family with APC gene mutation at codon 1556. Squares, male; circles, female; open symbols, no familial adenomatous polyposis (FAP); solid symbols, patients with FAP. (b) Macroscopic findings of the resected duodenum in case 1. There were multiple polypoid lesions in the duodenum. (c,d) Nodular aggregating lesions were found in the duodenum of cases 2 and 3. (e) A large nodular protrusion developed in case 4.
CONFLICT OF INTERESTS
A
UTHORS DECLARE NO conflict of interests for this article.
REFERENCES
Figure 3 Clinical management of duodenal adenomatosis in our institution.
duodenectomy to all patients with duodenal adenomatosis of Spigelman’s stage IV. However, because duodenal cancer can develop from severe duodenal adenomatosis, more sophisticated risk stratification needs to be established.
1 Nishisho I, Nakamura Y, Miyoshi Y et al. Mutation of a chromosome 5q21 gene in FAP and colorectal cancer patient. Science 1991; 253: 665–9. 2 Spirio L, Otterud B, Stauffer D et al. Linkage of a variant or attenuated form of adenomatous polyposis coli to the adenomatous polyposis coli (APC) locus. Am. J. Hum. Genet. 1992; 51: 92–100. 3 Matsumoto T, Iida M, Nakamura S et al. Natural history of ampullary adenoma in familial adenomatous polyposis: Reconfirmation of benign nature during extended surveillance. Am. J. Gastroenterol. 2000; 95: 1557–62. 4 Offerhaus GJ, Giardiello FM, Krush AL et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology 1992; 102: 1980–2. 5 Spigelman AD, Talbot IC, Penna C et al. Evidence for adenoma-carcinoma sequence in the duodenum of patients with
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
34
6
7
8
9
10
11
12
Y. Maehata et al.
familial adenomatous polyposis. The Leeds Castle Polyposis Group (Upper Gastrointestinal Committee). J. Clin. Pathol. 1994; 47: 709–10. Iida M, Yao T, Itoh H et al. Natural history of duodenal lesions in Japanese patients with familial adenomatosis coli (Gardner’s syndrome). Gastroenterology 1989; 96: 1301–6. Matsumoto T, Iida M, Kobori Y, Mizuno M, Nakamura S, Hizawa K. Progressive duodenal adenomatosis in a familial adenomatous polyposis pedigree with APC mutation at codon 1556. Dis. Colon Rectum 2002; 45: 229–33. Heiskanen I, Kellokumpu I, Järvinen H. Management of duodenal adenomas in 98 patients with familial adenomatous polyposis. Endoscopy 1999; 31: 412–6. Bülow S, Björk J, Christensen IJ et al. Duodenal adenomatosis in familial adenomatous polyposis. Gut 2004; 53: 381–6. Groves CJ, Saunders BP, Spigelman AD, Phillips RK. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study. Gut 2002; 50: 636–41. Latchford AR, Neale KF, Spigelman AD, Phillips RK, Clark SK. Features of duodenal cancer in patients with familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2009; 7: 659–63. Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 1989; 2: 783–5.
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