Introduction
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a
mutation in the adenomatous polyposis coli (APC) gene characterized by the presence
of more than 100 adenomatous polyps in the colorectum. The penetrance of colorectal
cancer in patients with FAP in their 40 s is approximately 50 % and rises to approximately
100 % if they are not treated before their 60 s [1]. With the exception of colorectal cancer, various neoplastic and non-neoplastic
lesions occur in other organs in patients with FAP. The most frequent cause of death
in patients with FAP is colorectal cancer, which accounts for 60.6 % of FAP-related
deaths in Japan [2]. As the prognoses of patients with FAP have improved in recent years because of
the use of prophylactic colectomy, postoperative extracolonic lesions have started
to become a more significant issue.
The causes of death in Japanese patients with FAP because of lesions outside the colon
are as follows: desmoid neoplasms in 9.9 %, duodenal cancer in 5.6 %, and gastric
cancer in 2.8 % cases [2]. Since the first report of complicating gastric lesions in patients with FAP by
Hauser in 1895 [3], a high proportion of synchronous neoplasms have been reported [2]
[4]
[5]
[6]. The types of gastric lesions associated with FAP are fundic gland polyps, gastric
adenomas, and gastric cancers. Fundic gland polyposis (FGP) associated with FAP was
first reported by Halstead et al. and is the most common gastric lesion in patients
with FAP, showing an incidence of 50 % – 60 % [7]
[8]
[9]. Gastric adenoma in patients with FAP was initially reported by Hoffman et al. [10], and several studies have reported the incidence of gastric adenoma as 2 % – 35 %
[7]
[11]
[12]
[13]. Gastric cancer related to FAP was first reported by Murphy et al. [14]. In Japan, gastric cancer is observed in 4.5 % – 13.6 % patients with FAP [15], whereas the incidence in East Asia is 2.7 % – 4.2 % [13]
[16]. In western countries, the incidence of gastric cancer associated with FAP is similar
to that of the general population [17], whereas that in East Asia is 3 – 4 times higher [15]
[16]. However, few reports about the clinical course and treatment of gastric lesions
in patients with FAP exist. Therefore, we aimed to investigate the clinical outcomes
of patients with FAP with gastric lesions and to reveal the relationships between
the incidence of gastric neoplasms and the background mucosa.
Patients and methods
We retrospectively investigated 80 patients with FAP who underwent esophagogastroduodenoscopy
(EGD) as a regular surveillance examination in 142 patients diagnosed with FAP from
October 1997 to December 2011 at the National Cancer Centre Hospital, Tokyo, Japan.
The institutional review board of the National Cancer Centre Hospital approved the
study, and we obtained informed consent from all patients. We investigated patient
characteristics, endoscopic findings of gastric lesions, treatment outcomes, and clinical
courses, and information regarding all gastric lesions was described in accordance
with the Japanese Classification of Gastric Carcinoma (JCGC) [18]. Gastric neoplasms detected over 1 year after initial endoscopic resection (ER)
or surgery were defined as metachronous gastric neoplasms (MGNs). The endoscopic extent
of gastric atrophy was diagnosed according to the Kimura – Takemoto classification,
which correlates with the histologic degree of atrophic gastritis [19]. Patients with FAP having atrophic gastritis were regarded as having a history of
Helicobacter pylori infection. The condition of the background gastric mucosa was classified into 4 groups
according to the presence of FGP and atrophic gastritis as follows: FGP with atrophic
gastritis, FGP without atrophic gastritis, no FGP with atrophic gastritis, and no
FGP without atrophic gastritis. Gastric neoplasms included invasive neoplasms and
noninvasive neoplasms; invasive neoplasms were defined as gastric cancers invading
the submucosal layer or deeper or poorly differentiated adenocarcinoma, and non-invasive
neoplasms were defined as gastric adenomas or intramucosal carcinomas. Two expert
pathologists reviewed all resected specimens at the National Cancer Center Hospital.
Histologic diagnoses were based on the Japanese Classification of Gastric Carcinoma
[18].
Treatment strategies for gastric cancers were determined by a cancer board consisting
of endoscopists, surgeons, and pathologists. Patients with gastric cancer were treated
based on the Japanese Gastric Cancer Treatment Guidelines [20]. The basic hospital policy for ER for gastric neoplasm is to resect all lesions
containing biopsy-confirmed adenocarcinoma. Therefore, all patients with FAP having
gastric adenoma underwent regular surveillance EGD and provided biopsy specimens from
gastric adenomas regardless of macroscopic changes. ER included endoscopic submucosal
dissection (ESD) and endoscopic mucosal resection (EMR) [21]
[22]
[23]
[24]. All ER procedures and surgeries were performed by skilled endoscopists and surgeons
at the National Cancer Center Hospital.
Baseline and outcomes data for patients who underwent ER were collected from electronic
medical records and prospectively collated in a computerized database. In addition,
we analyzed the proportion of patients with FAP who underwent surgical colectomy between
1972 and 2010 in cooperation with the colorectal surgery division. Pathologic information
was subsequently added after ER or surgical resection results were confirmed. All
patients with FAP were followed up every 6 months or 12 months with blood tests, EGD,
and computed tomography.
Results
Characteristics of patients with FAP
The mean age of the 80 patients (52 men and 28 women) at initial EGD was 40 ± 17 years
(mean ± SD) ([Table 1]). Of them, 42 (53 %) had an obvious family history of FAP. The median follow-up
period was 6.5 years (range, 0 – 14). Surveillance EGD was generally administered
at intervals of 12 months at the National Cancer Center Hospital, and 45 patients
(56 %) underwent EGD at this interval.
Table 1
Characteristics of patients with FAP.
|
Patient, no.
|
80
|
|
Age at initial EGD (mean ± SD, years)
|
40 ± 17
|
|
Male, no. (%)
|
52 (65)
|
|
Female
|
28 (35)
|
|
Present of familial history of FAP, no. (%)
|
42 (53)
|
|
Types of FAP, no. (%)
|
|
Classical
|
69 (86)
|
|
Profused
|
11 (14)
|
|
Treatment, no. (%)
|
|
Total colectomy
|
68 (85)
|
|
Other
|
3 (4)
|
|
Observation without surgical procedure
|
9 (11)
|
|
Follow-up period, years, median (range)
|
6.5 (0 – 14)
|
|
Follow-up interval by EGD, months
|
|
12
|
45 (56)
|
|
18
|
13 (16)
|
|
24
|
7 (9)
|
|
None
|
12 (15)
|
|
Other[1]
|
3 (4)
|
|
Fundic gland polyps, no. (%) [2]
|
|
Present
|
51 (64)
|
|
< 100
|
12 (15)
|
|
≥ 100
|
39 (49)
|
|
Absent
|
29 (36)
|
|
Gastric neoplasm, no. (%)[3]
|
22 (28)
|
FAP, familial adenomatous polyposis; EGD, esophagogastroduodenoscopy
1 The follow-up interval for 3 patients was 6 months, 36 months, and 42 months, respectively
2 Some patients had both fundic gland polyps and gastric neoplasms.
3 Gastric neoplasm included invasive neoplasm and noninvasive neoplasm.
Patient characteristics, endoscopic findings, and clinical course
FGP was observed in 51 patients (64 %) and gastric neoplasms in 22 (28 %) ([Table 1]), including noninvasive neoplasms in 20 patients and invasive neoplasms in 2.
In total, 26 gastric neoplasms in 22 patients were detected during the follow-up period,
excluding MGNs ([Table 2]). The mean age at diagnosis with gastric neoplasms was 46 ± 12 years (mean ± SD),
and 7 patients (32 %) had a family history of FAP. The median period from colectomy
to the development of gastric neoplasms was 18 years (range, 2 – 35). Regarding the
background gastric mucosa in the cases in which gastric neoplasms were detected, 11
cases (50 %) occurred in patients with no FGP with atrophic gastritis, and 8 cases
(36 %) in those with FGP without atrophic gastritis ( [Fig.1]). The number of primary gastric neoplasms was 1 in 15 patients (68 %), 2 in 4 patients
(18 %), 3 in 1 patient (5 %), and 4 or more in 2 patients (9 %). The location was
the upper two-thirds of the stomach for 19 lesions (73 %). The macroscopic type was
elevated for 17 lesions (65 %), depressed for 7 lesions (27 %), and advanced (Type
2 in JGCA) for 1 lesion (4 %). The median neoplasm size was 10 mm (range, 3 – 70)
and the histopathologicl findings revealed adenoma in 12 lesions (46 %) and differentiated-type
adenocarcinoma in 14 lesions (54 %). The depth of gastric neoplasm invasion was intramucosal
in 24 lesions (92 %) and the submucosa or deeper in two lesions (8 %).
Table 2
Characteristics and clinical outcomes of primary gastric neoplasms (22 patients with
26 lesions[1]).
|
Patient, no.
|
22
|
|
Age at the time of diagnosis with gastric neoplasm, years, mean ± SD
|
46 ± 12
|
|
Family history of FAP, no. (%)
|
7 (32)
|
|
Period from prophylactic colectomy to occurrence of gastric neoplasm, years, median
(range)
|
18 (2–35)
|
|
Findings of background gastric mucosa, no. (%)
|
|
FGP with atrophic gastritis
|
2 (9)
|
|
FGP without atrophic gastritis
|
8 (36)
|
|
Non-FGP with atrophic gastritis
|
11 (50)
|
|
Non-FGP without atrophic gastritis
|
1 (5)
|
|
Total number of gastric neoplasms[2], no. (%)
|
|
1
|
15 (68)
|
|
2
|
4 (18)
|
|
3
|
1 (5)
|
|
≥
|
2 (9)
|
|
Location, no. (%)[1]
|
|
Upper two-thirds
|
19 (73)
|
|
Lower one-third
|
7 (27)
|
|
Macroscopic type, no. (%)[1]
|
|
Elevated
|
17 (65)
|
|
Depressed
|
7 (27)
|
|
Combined
|
1 (4)
|
|
Advanced[3]
|
1 (4)
|
|
Neoplasm size, mm, median (range)
|
10 (3 – 70)
|
|
Treatment, no. (%)[1]
|
|
|
Endoscopic resection
|
11 (42)
|
|
EMR
|
7 (27)
|
|
ESD
|
4 (15)
|
|
Surgery
|
4 (15)
|
|
Observation
|
12 (46)
|
|
Histologic type, no. (%)[1]
|
|
Adenoma
|
12 (46)
|
|
Differentiated-type adenocarcinoma (tub1/tub2)
|
14 (54)
|
|
Neoplasm depth, no. (%)[1]
|
|
Intramucosal
|
24 (92)
|
|
Submucosa or deeper
|
2 (8)
|
FAP, familial adenomatous polyposis; FGP, fundic gland polyposis; EMR, endoscopic
mucosal resection; ESD, endoscopic submucosal dissection; tub1, well-differentiated
tubular adenocarcinoma; tub2, moderately differentiated tubular adenocarcinoma.
1 Two patients who had multiple gastric adenomas were excluded because the large number
of lesions were difficult to count exactly.
2 Total number of gastric neoplasms excluded metachronous neoplasms.
3 Type 2 in Japanese Gastric Cancer Treatment Guidelines.
Fig. 1 Flow diagram of the clinical courses of 80 patients with FAP who underwent EGD. The
clinical courses were classified according to the background gastric mucosa. Invasive
neoplasms were defined as gastric cancers invading deeper than the submucosal layer
and poorly differentiated adenocarcinoma, and noninvasive neoplasms were defined as
gastric adenomas and intramucosal carcinomas. FAP, familial adenomatous polyposis;
EGD, esophagogastroduodenoscopy; FGP, fundic gland polyposis; ER, endoscopic resection;
MGN, metachronous gastric neoplasm; CI, cerebral infarction.
We illustrated 2 cases of gastric neoplasms, the first case had a fundic gland polyp
developing gastric neoplasm ([Fig. 2]); and the second case had an intramucosal gastric neoplasm in the background gastric
mucosa of FGP ( [Fig. 3]). The first case was a male patient who was diagnosed with FAP at age 31 and underwent
subtotal colectomy for rectal cancer. His mother also had FAP. EGD revealed a fundic
gland polyp on the lesser curvature of the middle gastric body ([Fig. 2a]). Surveillance EGD was conducted at 18-month intervals. By age 35, lesion size had
increased ([Fig. 2b]). By age 38, the lesion had grown further, turned red, and developed an erosive
change in its center ( [Fig. 2c]). Biopsy revealed a well-differentiated adenocarcinoma (tub1) with low-grade atypia,
and ESD was performed for the elevated lesion and resulted in successful en bloc resection. Pathological result revealed Type 0-IIa, 12 mm, well-differentiated adenocarcinoma,
pT1a (M), ly(-), v(-), pHM0, pVM0 ( [Fig. 2d]). The second case was a female patient who was diagnosed with FAP and underwent
prophylactic colectomy at age 20. Her father and grandfather also had FAP. She received
annual EGD beginning at age 20. At age 26, a whitish elevated lesion was identified
on the anterior wall of the middle gastric body ([Fig. 3a] and [Fig. 3b]). The biopsy revealed a tubular adenoma, but malignancy was suspected on the basis
of the macroscopic appearance of the coalescent tendency of several polyps and its
whitish color. The pathologic result of EMR was as follows: Type 0-IIa, 10 mm, well-differentiated
adenocarcinoma, pT1a (M), ly(-), v(-), pHM0, pVM0 ( [Fig. 3c]). At age 32, a tiny depressed signet-ring cell carcinoma (sig) without atrophic
gastritis was detected in the posterior wall of the gastric antrum, and ESD was performed
([Fig. 3 d]). Pathologic result at that time was as follows: Type 0-IIc, 3 mm, sig, pT1a (M),
ly(-), v(-), pHM0, pVM0 ([Fig. 3e]).
Fig. 2 a Endoscopic findings of a male patient diagnosed as FAP at the age of 31 years. EGD
revealed a fundic gland polyp on the lesser curvature of the middle gastric body.
b By age 35, lesion size had increased. c By the age of 38, the lesion had grown further, turned red, and developed an erosive
change in its center. d Pathologic result: Type 0-IIa, 12 mm, tub1 (foveolar adenoma in WHO histological
classification), pT1a (M), ly(-), v(-), pHM0, pVM0. tub1, well-differentiated adenocarcinoma;
pT1a (M), intramucosal cancer; HM, horizontal margin; VM, vertical margin; WHO, World
Health Organization.
Fig. 3 Endoscopic findings of a female patient diagnosed with FAP at the age of 20 years.
a, b At 26 years, a whitish elevated lesion was identified on the anterior wall of the
middle gastric body in the background mucosa of FGP. c The pathological result of EMR was as follows: Type 0-IIa, 10 mm, tub1 (foveolar
adenoma in WHO histological classification), pT1a (M), ly(-), v(-), pHM0, pVM0. d At 32 years, a tiny depressed signet-ring cell carcinoma (sig) was detected in the
posterior wall of the gastric antrum. e Pathologic result was as follows: Type 0-IIc, 3 mm, sig (signet-ring cell carcinoma
in WHO histological classification), pT1a (M), ly(-), v(-), pHM0, pVM0. tub1, well-differentiated
adenocarcinoma; pT1a (M), intramucosal cancer; HM, horizontal margin; VM, vertical
margin; WHO, World Health Organization.
Treatment outcomes of gastric neoplasms
Of the 26 neoplasms, 14 primary gastric neoplasms (54 %) were treated ([Table 2]). ER was performed for 11 lesions (42 %), and surgery was conducted for 4 lesions
(15 %) although they were followed up regularly. In the 3 patients with 4 lesions
who underwent surgery, the first patient had an invasive neoplasm in the upper body
(0-IIc, 10 mm), which was diagnosed as a noninvasive neoplasm before ER and treated
by ESD, resulting in non-curative resection by histopathology with submucosal invasion
(400 μm) and lymphovascular invasion. It was then necessary to perform additional
surgery. In the second patient, 2 noninvasive neoplasms were observed in the upper
body (0-IIa + IIc, 70 mm, T1a [M]; 0-IIa, 44 mm, T1a [M]) and treated by proximal
gastrectomy because of technical difficulties in performing ER in the fornix. The
third patient had an invasive gastric neoplasm in the upper body (Type 2, 58 mm) with
liver metastases treated by partial gastrectomy and simultaneous left lateral liver
segmentectomy. After 7 years, MGN (0-IIa, 2 mm) was detected and treated by ER.
Long-term course of gastric neoplasms
Fifteen MGNs were detected in 7 patients, including 2 cases (29 %) in FGP without
atrophic gastritis and 5 (71 %) in non-FGP with atrophic gastritis ([Table 3]). The macroscopic types of MGNs were elevated for 7 lesions (47 %) and depressed
for 7 lesions (47 %). The median period from primary gastric neoplasm to MGN was 4
years (range, 2 – 12) and the median size of MGNs was 10 mm (range, 2 – 82). The site
of MGNs was the upper two-thirds of the stomach in 7 lesions (47 %), and the lower
third in 8 lesions (53 %). Ten of 15 MGNs were detected as noninvasive neoplasms (one
adenoma and nine differentiated-type adenocarcinomas) and treated by ER. One MGN was
detected as an invasive neoplasm because of histologic findings of an undifferentiated
carcinoma 3 mm in size, but was successfully treated by ER. In contrast, 4 MGNs were
observed because of histologic findings of adenoma for 3 lesions and at the patient’s
request for 1 differentiated-type adenocarcinoma.
Table 3
haracteristics and clinical outcomes of metachronous gastric neoplasms (seven patients
with 15 lesions).
|
Patient, no.
|
7
|
|
Present of family history of FAP, no. (%)
|
2 (29)
|
|
Period from primary gastric neoplasm to occurrence of metachronous neoplasms, years,
median (range)
|
4 (2 – 12)
|
|
Findings of background gastric mucosa, no. (%)
|
|
FGP with atrophic gastritis
|
0 (0)
|
|
FGP without atrophic gastritis
|
2 (29)
|
|
Non-FGP with atrophic gastritis
|
5 (71)
|
|
Non-FGP without atrophic gastritis
|
0 (0)
|
|
Total number of metachronous gastric neoplasms, no. (%)
|
|
|
1
|
4 (57)
|
|
2
|
1 (14)
|
|
3 – 5
|
1 (14)
|
|
6
|
1 (14)
|
|
Location, no. (%)
|
|
|
Upper two-thirds
|
7 (47)
|
|
Lower one-third
|
8 (53)
|
|
Macroscopic type, no. (%)
|
|
Elevated
|
7 (47)
|
|
Depressed
|
7 (47)
|
|
Combined
|
1 (7)
|
|
Advanced
|
0 (0)
|
|
Neoplasm size[1], mm, median(range)
|
10 (2 – 82)
|
|
Treatment, no. (%)
|
|
Endoscopic resection
|
11 (73)
|
|
EMR
|
2 (13)
|
|
ESD
|
9 (6)
|
|
Surgery
|
0 (0)
|
|
Observation[2]
|
4 (27)
|
|
Histologic type, no. (%)
|
|
|
Adenoma
|
4 (27)
|
|
Differentiated-type adenocarcinoma (tub1/tub2)
|
10 (67)
|
|
Undifferentiated adenocarcinoma (por/sig)
|
1 (7)
|
|
Neoplasm depth, no. (%)
|
|
Intramucosal
|
15 (100)
|
|
Submucosa or deeper
|
0 (0)
|
FAP, familial adenomatous polyposis; FGP, fundic gland polyposis; EMR, endoscopic
mucosal resection; ESD, endoscopic submucosal dissection; tub1, well-differentiated
tubular adenocarcinoma; tub2, moderately differentiated tubular adenocarcinoma; por,
poorly differentiated adenocarcinoma; sig, signet-ring cell carcinoma.
1 The largest size in multiple lesions
2 4 metachronous gastric neoplasms were observed because of the histology of adenoma
for 3 lesions and the patients request for one differentiated-type adenocarcinoma.
In the long-term follow-up period, 3 patients died of colon cancer, 1 because of a
desmoid neoplasm and 2 because of other diseases. Three patients who underwent surgical
colectomy in the past died of metachronous colon cancer or liver metastasis of colon
cancer: 1 patient in the remnant rectum 10 years later, 1 in the liver 6 months later,
and 1 in the remnant rectum and the liver 23 years later. No deaths caused by gastric
cancer occurred during the study period.
Discussion
The current study included the largest number of gastric lesions in patients with
FAP and the longest follow-up period, considering all studies of upper gastrointestinal
diseases in patients with FAP to date. The main finding was that no deaths attributable
to gastric neoplasms occurred, suggesting that early detection based on an appropriate
examination interval results in excellent prognoses.
In this study, gastric neoplasms occurred in 28 % of patients (22/80) with FAP, with
a total of 41 lesions including 15 MGNs, indicating that it is a complication with
a high incidence rate. The features of primary gastric neoplasms associated with FAP
included the macroscopic type of elevated lesions (65 %), location in the upper two-thirds
of the stomach (73 %), the presence of 1 or 2 lesions (86 %), and histologic findings
of differentiated-type adenocarcinoma (54 %) or adenoma (46 %). As for the location
of gastric neoplasms, most of the general gastric cancers occur in the lower two-thirds
of the stomach related to Helicobacter pylori infection. However, poorly differentiated adenocarcinomas develop more in the upper
gastric body than the lower two-thirds of the stomach. They also occur in the border
between the normal mucosa and atrophic mucosa associated with H. pylori infection. In general, the incidence of gastric cancers in the upper stomach was
approximately 20 %; therefore, it is possible to explain the higher incidence of neoplastic
lesion (73 %) in the proximal stomach in our study. Furthermore, eleven of 22 patients
with FAP (50 %) had complicated gastric neoplasms in non-FGP with atrophic gastritis.
However, eight of 22 patients (36 %) had gastric neoplasms in FGP without atrophic
gastritis. Therefore, not only H. pylori but also FGP may be related to the occurrence of gastric neoplasms in patients with
FAP. And high rate of well differentiated adenocarcinoma in gastric cancers of patients
with FAP was consistent with previous reports [25]
[26].
FGP was observed in 64 % (51/80) of FAP cases and was seen in the gastric body and
fundus. FGP has traditionally been recognized as hamartomatous lesions with no malignant
potential that arise from the fundic gland region. However, invasive neoplasms occurred
in two patients (5 %) and noninvasive neoplasms in 8 patients (20 %) in FGP without
atrophic gastritis, suggesting that FGP has malignant potential. Several reports have
described dysplasia in the foveolar epithelium of FAP-associated FGP [27]
[28]. Furthermore, some case reports have described high-grade dysplasia or adenocarcinoma
in association with FAP-associated FGP, suggesting that FAP-associated FGP is a potential
premalignant lesion [29]
[30]
[31]. As for genetic analysis, previous studies revealed the presence of somatic APC
mutations in FAP-associated FGP, indicating neoplastic lesions caused by the inactivation
of both alleles, similar to the mechanism of other FAP-associated neoplasms [28]
[32]. Consistent with this, 1 patient with 2 noninvasive neoplasms in FGP who underwent
proximal gastrectomy in our study had inactivation of the APC gene as previously reported
[31]. The macroscopic characteristics of FGP that developed into gastric neoplasms include
a tendency for the coalescence of individual polyps, discoloration, and flattening.
In addition, 9 of 10 patients with FAP (90 %) having gastric neoplasms in the background
gastric mucosa with FGP had more than 100 fundic gland polyps. For the treatment,
it was impractical to resect all fundic gland polyps because the number was numerous;
49 % (39/51) patients with FGP had more than 100 fundic gland polyps. Therefore, we
detected the fundic gland polyps that showed a tendency for coalescence of individual
polyp, discoloration, and flattening, suggesting the development of neoplastic lesions,
and performed endoscopic resection for the lesions diagnosed as adenocarcinoma by
biopsy. In addition, we treated the gastric neoplasms in the background of polyposis
based on the Japanese Gastric Cancer Treatment Guidelines. Similar to general gastric
cancers, intramucosal gastric neoplasms were resected by endoscopic resection (EMR/ESD)
and invasive gastric neoplasms were resected by surgery. However, we performed surgical
resection of the large noninvasive gastric neoplasms in the fornix or greater curvature
of the upper gastric body after consulting surgeon because of the technical difficulty.
Mean age at the time of diagnosis of gastric neoplasms in patients with FAP in this
study was 46 ± 12 years, which was younger than that in the general population [33]. We recommend EGD screening to be initiated at approximately age 25, because patients
with FAP had gastric adenoma starting as early as age 24 and gastric cancer as early
as age 25 in our study. EGD screening should be continued even after surgical colectomy
in patients with FAP, as the median period from surgical colectomy to the occurrence
of gastric neoplasms was 18 years (range, 2 – 35). According to the previous report,
one of the reasons for the high incidence of gastric neoplasms in our study is related
to the long-term follow-up [25]. As for the interval of surveillance EGD, most patients with FAP (73 %, 58/80),
including those with gastric neoplasms, underwent a procedure every 12 or 18 months
in this study. We consider this interval to be appropriate because none of the patients
with FAP died of gastric neoplasms, and 38 of 41 (93 %) gastric neoplasms including
MGNs were detected at the non-invasive stage. In terms of the background gastric mucosa,
we carefully observe patients with FAP in the background mucosa of FGP and/or atrophic
gastritis, in which incidence of gastric neoplasms was 95 % (21/22 patients). On the
other hand, it is difficult to decide the appropriate interval for EGD screening for
patients without FGP and atrophic gastritis in the background gastric mucosa because
there was only 1 patient who had gastric neoplasms in background gastric mucosa without
FGP and atrophic gastritis in our study. However, they should follow-up duodenal lesions
by EGD screening annually because of the high risk of duodenal neoplasia [34]. Therefore, even gastric lesions can be followed up in the same session. In addition,
the major duodenal papilla is also at risk for adenomas in patients with FAP. We reported
the risk of duodenal neoplasia (61 %, 47/77) including ampullary neoplasms (22 %,
17/77), and we recommended a short-term EGD surveillance for duodenal neoplasms including
ampullary neoplasms [34].
Patients with FAP who have primary gastric neoplasms tend to have MGNs (32 %, 7/22
patients); the rate of MGNs is higher than that in previous reports [35]
[36]. With respect to the background gastric mucosa, MGNs were correlated with atrophic
gastritis more than FGPs, demonstrated by the finding that 5 patients (71 %) had MGNs
in non-FGP with atrophic gastritis, whereas only 2 patients (29 %) had MGNs in FGP
without atrophic gastritis. The features of MGNs were as follows: located in the whole
stomach, of the depressed macroscopic type, and elevated. As for the clinical course
of MGNs, it was possible to control MGNs if regular surveillance EGD was performed
after treatment for primary gastric neoplasms because most of them (93 %, 14/15) were
detected at the noninvasive stage, excluding 1 undifferentiated adenocarcinoma.
Unfortunately, 6 of 80 patients with FAP died: colorectal cancer in 3 instances, a
desmoid neoplasm in 1, cerebral infarction in 1, and an unknown cause in 1. However,
the remaining patients are still alive, and their life expectancy is longer than it
would have been without surgical colectomy.
In the future, the risk of neoplasms other than colorectal cancer may increase. Therefore,
all neoplasms associated with FAP including gastric neoplasms should be carefully
observed. However, in this study, 24 of 26 gastric neoplasms (92 %) occurring in patients
with FAP were intramucosal cancers or adenomas, except two cases that invaded deeper
than the submucosal layer and one case of undifferentiated adenocarcinoma. Therefore,
it is obvious that the prognoses of patients with FAP with gastric neoplasms were
excellent. In addition, there remains disparity between Western and Japanese histopathologists
in the conceptual approach to histopathologic evaluation of neoplastic lesions in
the upper gastrointestinal tract because of a difference in the classification of
gastric intramucosal neoplasms between JCGC and the World Health Organization classification
[18]
[37]. Therefore, most of the gastric cancers in patients with FAP in this study were
high-grade dysplasia except for 2 invasive gastric cancers in western countries. Hence,
there may be discrepancies in the interpretation of the outcome of this study between
Japan and western countries. Furthermore, the high proportion of atrophic gastritis
in Japan may result in a higher incidence of gastric neoplasms than that in western
countries. However, we believe that early detection and treatment for gastric neoplasms
leads to better prognoses for patients with FAP. This study had a number of limitations,
as follows: this was a retrospective study conducted in a single center, using a non-integrated
follow-up method, and providing insufficient data of H. pylori infection.
Conclusion
In conclusion, FGP and atrophic gastritis in background gastric mucosa are significant
risk factors for gastric neoplasms in patients with FAP. However, the prognoses of
patients with FAP who have FGP and gastric neoplasms were satisfactory because of
appropriate intervention using EGD. We recommend annual surveillance EGD for patients
with FAP having FGP and gastric neoplasms and careful observation of these patients
while taking into consideration the macroscopic characteristics of FGP, a condition
that can develop into gastric neoplasms.
