Familial Cancer DOI 10.1007/s10689-015-9844-6
ORIGINAL ARTICLE
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial adenomatous polyposis: a prospective Japanese study Minori Matsumoto1 • Takeshi Nakajima1,2 • Yasuo Kakugawa1 • Taku Sakamoto1 Shiko Kuribayashi1 • Yosuke Otake1 • Takahisa Matsuda1 • Yukihide Kanemitsu3 Hirokazu Taniguchi4 • Yutaka Saito1
• •
Springer Science+Business Media Dordrecht 2015
Abstract The utility of capsule endoscopy (CE) for the surveillance of small intestinal lesions in familial adenomatous polyposis (FAP) patients has been reported. However, few studies have investigated the safety of CE in FAP patients who have undergone colon surgery. We aimed to assess the safety of surveillance CE in post-colectomy FAP patients and the endoscopic findings associated with small intestinal lesions. We assessed the safety of CE surveillance of small intestinal lesions in 41 FAP patients who had undergone colectomies. Forty-two CEs were performed in 41 patients at our facility from April 2012 to July 2014. CE was conducted safely and none of the capsules were retained, despite the inclusion of patients who had undergone several abdominal surgeries previously. Thirty-nine out of 42 capsules (93 %) were retrieved within the examination timeframe; hence, the retrieval rate was favorable. The findings from this study indicate that surveillance CE can be safely conducted in post-colectomy FAP patients. Keywords Familial adenomatous polyposis Capsule endoscopy Surveillance Small intestinal polyp
& Takeshi Nakajima [email protected] 1
Endoscopy Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
2
Department of Genetic Counseling, National Cancer Center Hospital, Tokyo, Japan
3
Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
4
Pathology Division, National Cancer Center Hospital, Tokyo, Japan
Abbreviations CE Capsule endoscopy FAP Familial adenomatous polyposis DBE Double-balloon endoscopy PC Patency capsule EGD Esophagogastroduodenoscopy
Introduction Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder caused by a mutation of the APC gene that leads to the development of multiple adenomas in the colon [1]. Various neoplastic lesions, including adenocarcinomas can develop, not only in the colon, but also in other parts of the gastrointestinal tract, including the stomach/duodenum and the jejunum/ileum [2]. Therefore, surveillance for these lesions is critical. Malignancies that develop in the duodenum, including those of the ampulla of Vater, are considered the leading cause of death in FAP patients after colorectal cancer. Thus, careful surveillance using upper gastrointestinal endoscopy is recommended according to Spigelman’s classification [3]. Cancer of the small intestine is extremely rare in FAP patients [4], and surveillance standards have not been established for the jejunum and ileum. The National Comprehensive Cancer Network guidelines recommend that in addition to computed tomography scanning or magnetic resonance imaging, diagnostic imaging of the small intestine is considered for desmoid tumor surveillance, using, for example, double-balloon endoscopy (DBE), particularly in patients with advanced duodenal
123
M. Matsumoto et al.
polyposis (http://www.nccn.org/). However, the early detection of lesions is challenging using these diagnostic imaging approaches. In westernized countries, the utility of small intestinal surveillance using capsule endoscopy (CE) has been extensively reported [5–7]. In contrast, experience in the use of CE in FAP patients in Japan including those after post total colectomy is limited [8]. Although CE surveillance of the small intestine may be effective because it is less invasive than DBE, careful assessments are necessary in relation to the unintended symptoms that are associated with capsule retention, because many FAP patients have histories of abdominal surgery or intestinal obstruction. The aim of this study was to evaluate the safety of CE in post-colectomy FAP patients, and to assess the small intestinal lesions and their associations with duodenal lesions.
Patients and methods This was a single-center pilot study conducted at our facility from April 2012 to July 2014. All patients gave their written informed consent. This study was registered after obtaining approval from our organization’s clinical ethics committee, and it was performed in accordance with the ethical principles of the Declaration of Helsinki. This study was registered in the University Hospital Medical Network Clinical Trials Registry (Clinical trial registration number: UMIN000012846). Cases were prospectively registered with a target number of 50 patients. Patient recruitment Our research administration office sent a sealed letter to each FAP patient who had undergone a colectomy. The letter contained a pamphlet that introduced the study and a questionnaire that enabled the patient to indicate whether they wished to participate in the study. If the patient was interested in participating in the study, we asked them to visit our hospital after they had sent their consent by mail. During the patient’s visit to the hospital, a physician-incharge explained the study to the patient. We additionally tried to recruit patients when they visited the outpatient department. Patients who were introduced by other patients who were already participating in the study, and the patients’ family members or acquaintances were also asked to participate in the study. After confirming the patients’ clinical histories and current symptoms, we explained the clinical aspects of the study to the patients and described the complications that may arise as a consequence of CE examinations or this study.
123
Patient selection criteria FAP was diagnosed when the patients had histories of more than 100 colorectal adenomatous polyps and/or when genetic testing proved the presence of the APC mutation. There were no restrictions in relation to the interval between the colectomies and study participation. Patients were excluded if (1) gastrointestinal tract obstruction symptoms and clinical findings were evident; (2) they had chronic abdominal symptoms, such as nausea and abdominal pains; (3) they had histories of recurrent intestinal obstruction; (4) they had a heart pacemaker implanted; (5) they were under 20 years of age; (6) their general condition, determined by a performance status score of \2, was poor; or (7) they were pregnant. If it was difficult to decide whether to include a patient with a history of intestinal obstruction because they had no symptoms at the time of inclusion, we used a patency capsule (PC) to evaluate gastrointestinal tract patency, and the patient was included in the study if patency was confirmed. All patients had undergone periodic surveillance of their stomachs and duodenums using esophagogastroduodenoscopy (EGD) at our hospital within 1 year of study participation. Moreover, patients with residual rectums underwent yearly colonoscopic surveillance. Capsule endoscopy protocol CE was performed using a Pillcam SB2 video capsule (Given Imaging Ltd., Yoqneam, Israel), which examined the small intestine. Patients were prohibited from eating for 12 h before the CE examination and were administered domperidone (10 mg) immediately before the examination to promote capsule discharge from the stomach, dimethicone (40 mg) to defoam the gastrointestinal tract fluid, and pronase for mucolysis. We did not pre-treat the patients with, for example, orally administered polyethylene glycol. Patients were prohibited from drinking water for 2 h and from eating for 4 h after capsule administration. The sensor array and recorder were detached when capsule retrieval was confirmed, or 14 h after capsule administration despite capsule discharge not being confirmed, or when the battery ran out. The data recorder was collected on the following day, and the data were downloaded onto a Rapid 6.5 workstation (Given Imaging Ltd, Yoqneam, Israel). CE findings within the duodenum, jejunum, and ileum were analyzed. Using the localization map provided by the Rapid software, the regions were defined as described next. The duodenum was defined as the area from the pylorus to the ligament of Treitz. The small intestine was defined as the area from the ligament of Treitz to the point where the villus structure of the intestinal wall disappeared and the mucosa of the large intestine was observed, or where an obvious small intestinal and
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial…
anastomotic region in the colon was observed, or where a stoma bag was imaged. The jejunum was defined as the half of the small intestine that was on the mouth side, and the ileum was defined as the half of the small intestine that was on the rectal side. Two experienced endoscopists read the imaging separately, and they discussed their analyses after cross-checking the findings to make the final diagnoses. When they did not agree on a diagnosis, they reviewed a video of the case together to build consensus about their final diagnosis. Patients visited the hospital 2 weeks after the examination to determine whether the capsule had been discharged and if they had experienced any unintentional symptoms, such as abdominal symptoms, during the examination. If a patient was unable to confirm capsule discharge and the mucosa of the large intestine could not be determined on the images, an abdominal X-ray was performed to confirm that the capsule was not retained within the small intestine. Safety assessments The study’s primary endpoint was an evaluation of safety relating to the incidence of unintended symptoms, including capsule retention, the capsule retrieval rate, nausea during the examinations, the presence of abdominal symptoms, including abdominal pains, and the capsules’ transit times through the small intestine. In this study, we thought that 1 retention case out of 50 patients was acceptable based on a retention rate of 1.62 % reported from a domestic multicenter study conducted in 2004 that used CE (unpublished Japanese data). If 2 retention cases had been observed, the study would have been terminated because of safety issues. Evaluation of duodenal lesions The sensitivity and specificity of CE for duodenal lesions were reported as 69 and 75 %, respectively, when EGD was considered the gold standard [8]. Hence, we used EGD to evaluate duodenal lesions in this study. Before they underwent CE, all of the study’s participants had undergone EGD at our hospital or at their local clinics within the preceding year. The Spigelman scores were calculated based on these results [9].
Results Patients’ characteristics Seventy-two FAP patients who had undergone colectomies were recruited for this study. Following reviews of their medical records, we excluded 5 patients with histories of repeated intestinal obstruction or intestinal obstruction within 1 year of the study beginning, 4 patients who were in poor condition in general because of old age (n = 1) or systemic colon cancer metastases (n = 3), and 4 patients who had mental disorders. Consequently, 59 post-colectomy FAP patients were invited to participate in this study. Fifty-three patients replied to the invitation, and, of these, 46 patients wished to participate in the study and 13 patients declined the invitation to participate. Direct interviews with the 46 patients who wished to undergo CE examination excluded 2 patients who had histories of intestinal obstruction within the previous year and 1 patient who was suspected of having post-colectomy anastomotic regional stenosis and had chronic abdominal symptoms. One patient who could not swallow the capsule during the examination was also excluded from the study. Thus, 42 CE examinations were performed in 41 patients, which included 1 patient who wished to undergo a secondary CE because the first capsule was retained in the jejunum (Fig. 1). Table 1 presents the characteristics of the patients who underwent CE in this study. The study cohort comprised 25 men and 16 women. The median age at the time of initial colectomy was 26 years (range 13–58 years), and the median time interval after surgery was 14 years (range 1–43 years). Thirty-two patients had undergone total colectomies with ileorectal anastomoses. Among these 32 IRA patients, 4 patients underwent additional rectal resection because of new occurrence of rectal cancer with permanent ileostomy (n = 3), or severe defecation disorder (n = 1). 9 patients had undergone total proctocolectomies with ileal J-pouch anal anastomoses. Among these 9 IPAA patients, one patients underwent additional surgery with permanent ileostomy because anastomotic leakage and necrosis (n = 1). The phenotypes of the colorectal lesions at the time of colectomy in the FAP patients were categorized as dense (n = 9) or typical (n = 32).
Evaluation of small bowel lesions The locations (jejunum or ileum), sizes (1–5, 6–14, or C15 mm), macroscopic types, and the numbers of the lesions were evaluated. The number of lesions was measured as precisely as possible to a single digit. A detailed small intestinal examination using DBE was indicated if a small intestinal lesion measuring C15 mm was detected on the capsule images.
Safety of capsule endoscopy Of 42 CEs undertaken, the capsules passed through the small intestines within the scheduled timeframe of about 8 h in 39 procedures (93 %), and the capsules were retained in the small intestines in 3 procedures (7 %). The median small intestinal transit time was 202 min (range
123
M. Matsumoto et al. Fig. 1 Patient selection for this study
79–882 min). Capsule excretion was ultimately confirmed in all of the subjects, and no capsules were retained. No minor complications, including nausea and abdominal pains, were observed during CE (Table 2). Small bowel capsule endoscopy findings Thirty-nine patients whose entire small intestines could be viewed were included in the analysis, and 20 patients (51 %) had some form of polyp in their small intestines (Table 3). The median number of small intestinal polyps was 3 (range 1–223). Ten patients had polyps in the jejunum only, 6 patients had polyps in the jejunum and ileum, and 4 patients had polyps in the ileum only. Polyps were most commonly found in the jejunum. Most of the tumors were small polyps with diameters of 1–5 mm. One patient
123
had a protruding lesion in the jejunum near the ligament of Treitz that was at least 20 mm in diameter (Fig. 2a). DBE was subsequently performed and it revealed a flat lesion in the jejunum that was 25 mm in diameter (Fig. 2b). We performed an endoscopic mucosal resection and an en bloc resection was achieved. A histopathological examination showed a well-differentiated intramucosal adenocarcinoma without any lymphovascular invasion (Fig. 2c). Association between the status of duodenal polyps and small bowel polyps The duodenal adenomas in the 39 patients who were included in the analysis were staged according to Spigelman’s staging criteria for duodenal polyposis as follows: stage 0, 16 patients; stage I, 1 patient; stage II, 10 patients;
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial… Table 1 Patient characteristics
Male:Female, n
25:16
Median age years (range)
46 (24–74)
History of open abdominal surgery, n Once Twice
30 9
C3 times
2
Median age at the time of initial colectomy, years (range)
26 (13–58)
Median time interval since initial surgery, years (range)
14 (1–43)
Phenotype Dense/typical
9/32
Type of surgery Total colectomy/ileo-rectal anastomosis
32
Total colectomy/ileal J-pouch anal anastomosis
9
Duodenal polyp Yes/no
26/15
Spigelman stage, n 0
15
I
2
II III
10 7
IV
2
V
5
Table 3 Small bowel capsule endoscopy findings
Table 2 Capsule endoscopy safety evaluation items Median total capsule endoscopy time, min (range)
489 (77–1013)
Median small intestine transit time, min (range)
202 (79–882)
Median stomach transit time, min, (range)
30 (4–1005)
Unintended symptoms including retention, n (%) No
42 (100)
Yes
0 (0)
Entire small intestine examination, n (%) Possible Impossible
39 (93) 3 (7)
Furthest point reached by capsule, n (%) Jejunum
2 (5)
Ileum
1 (2)
Stoma, pouch, rectum
39 (93)
Small intestine polyp, n (%) Yes
20 (51)
No
19 (49)
Male:Female, n (%)
12 (60):8 (40)
Median age of patients with polyps, years (range)
45 (27–74)
Median elapsed time since surgery, years (range)
12 (1–43)
Median number of lesions, n (range)
3 (1–223)
Median size of lesion, mm (range) Locations of lesions, n (%)
5 (2–25)
Jejunum only
10 (50)
Jejunum and ileum
6 (30)
Ileum only
4 (20)
Discussion stage III, 6 patients; stage IV, 1 patient; and stage V, 5 patients. Duodenal adenomas were found in 23 patients (66 %), and, of these, small intestinal adenomas were found in 13 patients (57 %). Table 4 presents the characteristics of the patients who had small intestinal lesions. The proportions of patients with Spigelman’s stage 0 and stage 1 duodenal polyposis were 25 and 0 %, respectively; however, the proportions tended to increase with the Spigelman stage (Table 5).
Capsule retention is mainly caused by gastrointestinal tract stenosis that may occur because of non-steroidal anti-inflammatory drug-associated ulcers, Crohn’s disease, neoplastic lesions, radiation-induced enteritis, or surgicallyinduced anastomotic strictures [10]. Retention rates vary depending on the disease being investigated [11–17]. To the best of our knowledge, only a few case reports have been published [18, 19] that describe capsule retention in patients after open abdominal surgery [19]. Although CE
123
M. Matsumoto et al.
Fig. 2 a A protruding lesion was detected by capsule endoscopy in the proximal jejunum. b Double-balloon endoscopy showed a flat lesion that had a diameter of 25 mm. c Histological analysis confirmed an intramucosal well-differentiated adenocarcinoma (hematoxylin and eosin stain, 9200)
can generally be performed safely, even in patients with histories of open abdominal surgery, careful assessments are needed, because gastrointestinal tract stenosis occurs in
123
a high proportion of patients after surgery. Following open abdominal surgery, gastrointestinal tract-related subjective symptoms, including chronic abdominal pain, abdominal distension, or nausea, indicate gastrointestinal tract stenosis, and the indication for CE should be carefully assessed. Furthermore, if the stricture without symptoms had been detected by surveillance colonoscopy, CE should not be done. The retention may happen although endoscope could pass through of the stenosis and patient had not been complained any symptoms [20]. In this study, the patients’ medical records were carefully reviewed, and all patients were interviewed. Consequently, CE was not performed in patients with suspected gastrointestinal tract stenosis. Before CE, gastrointestinal tract patency can be determined using a PC [21, 22]. However, capsule retention has been reported despite PC confirmation [23]. Once retention occurs, open abdominal surgery may be required to remove the capsule. Indeed, FAP patients have an increased risk of additional abdominal surgery because of adhesions; therefore, unnecessary surgery should be avoided. Several reports describe investigations of small intestinal lesions in FAP patients [24–26]. Small intestinal adenomas are found in 50–75 % of FAP patients, they are mainly found in the jejunum, and most lesions are no larger than 10 mm and do not require immediate treatment [7, 27]. The condition of the duodenal adenomas may reflect the condition of the small intestine. Patients with duodenal adenomas at advanced Spigelman stages may be at greater risk of adenoma development in the small intestine [6, 24]. However, FAP patients rarely develop cancer in the small intestine [4, 28], and few reports describe FAP and cancer of the small intestine [29]. Incidence of small intestinal cancer with FAP patients is reported 0.4 % in jejunum and 0.1 % in ileum [4]. Ishida et al. [30] reported that seven cases of jejunal carcinoma associated with FAP have been published in English journals from 1980 to 2012, including 5 cases had died. According to the database of the polyposis registry of Japan, small intestinal cancer accounted for 1.0 % of all causes of death among FAP patients [31]. These results suggest that although incidence of small intestinal cancer is low, their prognosis is poor. While the results from this study tended to concur with those that have been published, we speculate that the small intestinal neoplasm incidence rate in FAP patients is higher than suggested. Based on our current study cohort, 4 patients had small intestinal tumors, which included 2 carcinoma in situ, 2 advanced small intestinal tumors. The Spigelman stages for these cases varied from stages IV and V to stage II, but this staging did not accurately reflect the condition of the small intestinal adenomas in some cases. We think that small intestinal surveillance is necessary for FAP patients regardless of low incidence of small intestinal carcinoma in FAP patients, because, early detection is
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial… Table 4 Numbers and sizes of small-bowel polyps detected by capsule endoscopy in 20 patients with familial adenomatous polyposis Patient no.
Age (years)
Sex
Interval after colectomy (year)
Duodenal polyp
Small-bowel polyp
Spigelman stage
Number
Maximum size (mm)
Location Number
J/I
Maximum size (mm)
1
54
M
20
V
[20
17
70
70/0
\5
2
60
M
40
II
5–20
5
223
3/220
\5
3
39
M
11
III
[20
10
17
17/0
\5
4
41
M
1
0
None
–
2
2/0
\5
5
62
M
36
II
5–20
5
5
2/3
\5
6
53
M
23
II
\5
5
5
0/5
\5
7
47
F
23
II
5–20
10
3
2/1
\5
8
61
F
35
III
5–20
30
9
9/0
6
9
52
F
10
0
None
–
1
1/0
\5
10
32
F
10
III
[20
15
3
1/2
\5
11
74
M
36
0
None
–
2
2/0
\5
12
42
F
2
0
None
–
1
1/0
\5
13
49
M
6
III
[20
12
3
0/3
\5
14 15
35 41
F M
12 15
II IV
1 [20
10 10
1 3
1/0 3/0
13 \5
16
43
M
6
III
[20
2
2
1/1
\5
17
30
M
5
II
5–20
5
1
1/0
\5
18
36
F
13
III
[20
15
4
3/1
\5
19
27
M
4
V
5–20
60
1
1/0
\5
20
64
F
43
V
[20
30
1
1/0
25
M male, F female, J jejunum, I ileum
Table 5 Small intestinal lesions categorized by Spigelman stage
Spigelman stage
With polyps n (%)
Location Jejunum only
Ileum only
Jejunum and ileum
0
4/16 (25)
4
0
0
I
0/1 (0)
–
–
–
II
6/10 (60)
2
1
3
2
1
3
III
6/6 (100)
IV
1/1 (100)
1
0
0
V
3/5 (60)
1
2
0
10
4
6
Total
20/39 (51)
important due to their prognosis is poor, and that CE should be the surveillance modality used because of its low level of invasiveness [32]. Determining the inspection intervals for small intestinal surveillance in FAP patients is a topic for future investigation. The ways in which small intestinal adenomas progress in FAP patients and how they progress after their development into advanced cancers via carcinomas in situ have yet to be determined. However, some studies have
reported that even relatively large tumors can remain as adenomas pathologically [24], and that their progress can be expected to be relatively slow. Moreover, it has been reported that the frequency of small intestinal adenoma occurrence increases with time after colectomy [33]. Based on these findings, we believe that periodic surveillance should be undertaken with long intervals. In this study, the CE completion rate was 92.9 %, and reported CE completion rates are between 70 and 80 % [34–
123
M. Matsumoto et al.
36]. Hence, the study’s CE completion rate is acceptable. Examinations could not be completed in 3 cases because the capsules’ batteries ran out, and the capsule was retained in the stomach of 1 case for a long period of time. To facilitate the transit of capsules through the stomach, drugs to enhance gastrointestinal tract motility could be administered, the body posture could be changed to the left lateral decubitus position, or the capsule could be delivered to the second part of the duodenum beyond the pylorus during EGD or using an endoscopic capsule-delivery device. Inspections of the whole small intestine must be reliable if CE is to be used for surveillance, which is proposed as a topic for future investigations. This study may be subject to several limitations, one of which relates to a selection bias that may have occurred when the physicians who were in charge of testing were selecting the subjects. In relation to safety, the acceptable capsule retention rate was 0 %, and patients were carefully selected by the physicians to protect their safety. The criteria for this study enabled the safety of CE in post-colectomy FAP patients to be demonstrated. Future investigations should examine the possibility of relaxing the selection criteria to enable more FAP patients to undergo CE examinations. Acknowledgments This work was supported by a Grant-in-Aid for Health and Labor Sciences Research, the third term of comprehensive research into cancer control. Author contributions Conception and design of the study; Minori Matsumoto, Takeshi Nakajima. Analysis and interpretation of data; Minori Matsumoto, Yasuo Kakugawa, Taku Sakamoto, Yosuke Otake, Takahisa Matsuda, Yukihide Kenemitsu, Hirokazu Taniguchi, Yutaka Saito. Collection and assembly of data; Minori Matsumoto. Drafting of the article; Minori Matsumoto, Takeshi Nakajima. Critical revision of the article for important intellectual content; Minori Matsumoto, Takeshi Nakajima. Final approval of the article; Yutaka Saito Compliance with ethical standards Conflict of interest The authors have no conflict of interest directly relevant to the content of this article.
References 1. Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348(10):919–932 2. Galiatsatos P, Foulkes WD (2006) Familial adenomatous polyposis. Am J Gastroenterol 101(2):385–398 3. Brosens LA, Keller JJ, Offerhaus GJ, Goggins M, Giardiello FM (2005) Prevention and management of duodenal polyps in familial adenomatous polyposis. Gut 54(7):1034–1043 4. Jagelman DG, DeCosse JJ, Bussey HJ (1988) Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet 1(8595):1149–1151 5. Burke CA, Santisi J, Church J, Levinthal G (2005) The utility of capsule endoscopy small bowel surveillance in patients with polyposis. Am J Gastroenterol 100(7):1498–1502
123
6. Schulmann K, Hollerbach S, Kraus K, Willert J, Vogel T, Moslein G, Pox C, Reiser M, Reinacher-Schick A, Schmiegel W (2005) Feasibility and diagnostic utility of video capsule endoscopy for the detection of small bowel polyps in patients with hereditary polyposis syndromes. Am J Gastroenterol 100(1):27–37 7. Iaquinto G, Fornasarig M, Quaia M, Giardullo N, D’Onofrio V, Iaquinto S, Di Bella S, Cannizzaro R (2008) Capsule endoscopy is useful and safe for small-bowel surveillance in familial adenomatous polyposis. Gastrointest Endosc 67(1):61–67 8. Yamada A, Watabe H, Iwama T, Obi S, Omata M, Koike K (2014) The prevalence of small intestinal polyps in patients with familial adenomatous polyposis: a prospective capsule endoscopy study. Fam Cancer 13(1):23–28 9. Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK (1989) Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 2(8666):783–785 10. Cave D, Legnani P, de Franchis R, Lewis BS (2005) ICCE consensus for capsule retention. Endoscopy 37(10):1065–1067 11. Li F, Gurudu SR, De Petris G, Sharma VK, Shiff AD, Heigh RI, Fleischer DE, Post J, Erickson P, Leighton JA (2008) Retention of the capsule endoscope: a single-center experience of 1000 capsule endoscopy procedures. Gastrointest Endosc 68(1):174–180 12. Cheon JH, Kim YS, Lee IS, Chang DK, Ryu JK, Lee KJ, Moon JS, Park CH, Kim JO, Shim KN et al (2007) Can we predict spontaneous capsule passage after retention? A nationwide study to evaluate the incidence and clinical outcomes of capsule retention. Endoscopy 39(12):1046–1052 13. Goldstein JL, Eisen GM, Lewis B, Gralnek IM, Aisenberg J, Bhadra P, Berger MF (2007) Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther 25(10):1211–1222 14. Liao Z, Gao R, Xu C, Li ZS (2010) Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review. Gastrointest Endosc 71(2):280–286 15. Cheifetz AS, Kornbluth AA, Legnani P, Schmelkin I, Brown A, Lichtiger S, Lewis BS (2006) The risk of retention of the capsule endoscope in patients with known or suspected Crohn’s disease. Am J Gastroenterol 101(10):2218–2222 16. Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Rossini FP, De Franchis R (2004) Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: report of 100 consecutive cases. Gastroenterology 126(3):643–653 17. de Franchis R, Avesani EM, Abbiati C, Rondonotti E, Zatelli S, Beccari G, Primignani M, Gatti M, Cappelletti M, Carnevali A et al (2003) Unsuspected ileal stenosis causing obscure GI bleeding in patients with previous abdominal surgery–diagnosis by capsule endoscopy: a report of two cases. Dig Liver Dis 35(8):577–584 18. Majeski J (2009) Endoscopic capsule retention in an intestinal anastomosis. Int Surg 94(3):254–257 19. De Palma GD, Rega M, Puzziello A, Aprea G, Ciacci C, Castiglione F, Ciamarra P, Persico M, Patrone F, Mastantuono L et al (2004) Capsule endoscopy is safe and effective after small-bowel resection. Gastrointest Endosc 60(1):135–138 20. Durchschein F, Schreiber F, Hogenauer C (2014) Video capsule endoscopy in familial adenomatous polyposis: capsule entrapment in an anal stenosis. Endoscopy 46(Suppl 1):UCTN:E529–530 21. Spada C, Spera G, Riccioni M, Biancone L, Petruzziello L, Tringali A, Familiari P, Marchese M, Onder G, Mutignani M et al (2005) A novel diagnostic tool for detecting functional patency of the small bowel: the Given patency capsule. Endoscopy 37(9):793–800
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial… 22. Nakamura M, Hirooka Y, Yamamura T, Miyahara R, Watanabe O, Ando T, Ohmiya N, Goto H (2015) Clinical usefulness of novel tag-less Agile patency capsule prior to capsule endoscopy for patients with suspected small bowel stenosis. Dig Endosc 27(1):61–66 23. Watanabe K, Ohmiya N, Nakamura M, Fujiwara Y, Goto H, Arakawa T (2012) The investigation of the factors for confirming the patency by novel tag-less Agile patency Capsule-J for patients With Crohn’s disease and the other intestinal diseases, prospective, open-label study. Gastrointest Endosc 75(4):AB371 24. Matsumoto T, Esaki M, Yanaru-Fujisawa R, Moriyama T, Yada S, Nakamura S, Yao T, Iida M (2008) Small-intestinal involvement in familial adenomatous polyposis: evaluation by doubleballoon endoscopy and intraoperative enteroscopy. Gastrointest Endosc 68(5):911–919 25. Will OC, Man RF, Phillips RK, Tomlinson IP, Clark SK (2008) Familial adenomatous polyposis and the small bowel: a locoregional review and current management strategies. Pathol Res Pract 204(7):449–458 26. Schulz AC, Bojarski C, Buhr HJ, Kroesen AJ (2008) Occurrence of adenomas in the pouch and small intestine of FAP patients after proctocolectomy with ileoanal pouch construction. Int J Colorectal Dis 23(4):437–441 27. Wong RF, Tuteja AK, Haslem DS, Pappas L, Szabo A, Ogara MM, DiSario JA (2006) Video capsule endoscopy compared with standard endoscopy for the evaluation of small-bowel polyps in persons with familial adenomatous polyposis (with video). Gastrointest Endosc 64(4):530–537 28. Alderlieste YA, Rauws EA, Mathus-Vliegen EM, Fockens P, Dekker E (2013) Prospective enteroscopic evaluation of jejunal polyposis in patients with familial adenomatous polyposis and advanced duodenal polyposis. Fam Cancer 12(1):51–56
29. Ruys AT, Alderlieste YA, Gouma DJ, Dekker E, Mathus-Vliegen EM (2010) Jejunal cancer in patients with familial adenomatous polyposis. Clin Gastroenterol Hepatol 8(8):731–733 30. Ishida H, Kumamoto K, Amano K, Ishibashi K, Iwama T, Higashi M, Tamaru J (2013) Identification of APC gene mutations in jejunal carcinomas from a patient with familial adenomatous polyposis. Jpn J Clin Oncol 43(9):929–934 31. Iwama T, Tamura K, Morita T, Hirai T, Hasegawa H, Koizumi K, Shirouzu K, Sugihara K, Yamamura T, Muto T et al (2004) A clinical overview of familial adenomatous polyposis derived from the database of the Polyposis Registry of Japan. Int J Clin Oncol 9(4):308–316 32. Mata A, Llach J, Castells A, Rovira JM, Pellise M, Gines A, Fernandez-Esparrach G, Andreu M, Bordas JM, Pique JM (2005) A prospective trial comparing wireless capsule endoscopy and barium contrast series for small-bowel surveillance in hereditary GI polyposis syndromes. Gastrointest Endosc 61(6):721–725 33. Thompson-Fawcett MW, Marcus VA, Redston M, Cohen Z, McLeod RS (2001) Adenomatous polyps develop commonly in the ileal pouch of patients with familial adenomatous polyposis. Dis Colon Rectum 44(3):347–353 34. Rondonotti E, Herrerias JM, Pennazio M, Caunedo A, Mascarenhas-Saraiva M, de Franchis R (2005) Complications, limitations, and failures of capsule endoscopy: a review of 733 cases. Gastrointest Endosc 62(5):712–716 quiz 752, 754 35. Carey EJ, Leighton JA, Heigh RI, Shiff AD, Sharma VK, Post JK, Fleischer DE (2007) A single-center experience of 260 consecutive patients undergoing capsule endoscopy for obscure gastrointestinal bleeding. Am J Gastroenterol 102(1):89–95 36. Tatar EL, Shen EH, Palance AL, Sun JH, Pitchumoni CS (2006) Clinical utility of wireless capsule endoscopy: experience with 200 cases. J Clin Gastroenterol 40(2):140–144
123
ORIGINAL ARTICLE
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial adenomatous polyposis: a prospective Japanese study Minori Matsumoto1 • Takeshi Nakajima1,2 • Yasuo Kakugawa1 • Taku Sakamoto1 Shiko Kuribayashi1 • Yosuke Otake1 • Takahisa Matsuda1 • Yukihide Kanemitsu3 Hirokazu Taniguchi4 • Yutaka Saito1
• •
Springer Science+Business Media Dordrecht 2015
Abstract The utility of capsule endoscopy (CE) for the surveillance of small intestinal lesions in familial adenomatous polyposis (FAP) patients has been reported. However, few studies have investigated the safety of CE in FAP patients who have undergone colon surgery. We aimed to assess the safety of surveillance CE in post-colectomy FAP patients and the endoscopic findings associated with small intestinal lesions. We assessed the safety of CE surveillance of small intestinal lesions in 41 FAP patients who had undergone colectomies. Forty-two CEs were performed in 41 patients at our facility from April 2012 to July 2014. CE was conducted safely and none of the capsules were retained, despite the inclusion of patients who had undergone several abdominal surgeries previously. Thirty-nine out of 42 capsules (93 %) were retrieved within the examination timeframe; hence, the retrieval rate was favorable. The findings from this study indicate that surveillance CE can be safely conducted in post-colectomy FAP patients. Keywords Familial adenomatous polyposis Capsule endoscopy Surveillance Small intestinal polyp
& Takeshi Nakajima [email protected] 1
Endoscopy Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
2
Department of Genetic Counseling, National Cancer Center Hospital, Tokyo, Japan
3
Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
4
Pathology Division, National Cancer Center Hospital, Tokyo, Japan
Abbreviations CE Capsule endoscopy FAP Familial adenomatous polyposis DBE Double-balloon endoscopy PC Patency capsule EGD Esophagogastroduodenoscopy
Introduction Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder caused by a mutation of the APC gene that leads to the development of multiple adenomas in the colon [1]. Various neoplastic lesions, including adenocarcinomas can develop, not only in the colon, but also in other parts of the gastrointestinal tract, including the stomach/duodenum and the jejunum/ileum [2]. Therefore, surveillance for these lesions is critical. Malignancies that develop in the duodenum, including those of the ampulla of Vater, are considered the leading cause of death in FAP patients after colorectal cancer. Thus, careful surveillance using upper gastrointestinal endoscopy is recommended according to Spigelman’s classification [3]. Cancer of the small intestine is extremely rare in FAP patients [4], and surveillance standards have not been established for the jejunum and ileum. The National Comprehensive Cancer Network guidelines recommend that in addition to computed tomography scanning or magnetic resonance imaging, diagnostic imaging of the small intestine is considered for desmoid tumor surveillance, using, for example, double-balloon endoscopy (DBE), particularly in patients with advanced duodenal
123
M. Matsumoto et al.
polyposis (http://www.nccn.org/). However, the early detection of lesions is challenging using these diagnostic imaging approaches. In westernized countries, the utility of small intestinal surveillance using capsule endoscopy (CE) has been extensively reported [5–7]. In contrast, experience in the use of CE in FAP patients in Japan including those after post total colectomy is limited [8]. Although CE surveillance of the small intestine may be effective because it is less invasive than DBE, careful assessments are necessary in relation to the unintended symptoms that are associated with capsule retention, because many FAP patients have histories of abdominal surgery or intestinal obstruction. The aim of this study was to evaluate the safety of CE in post-colectomy FAP patients, and to assess the small intestinal lesions and their associations with duodenal lesions.
Patients and methods This was a single-center pilot study conducted at our facility from April 2012 to July 2014. All patients gave their written informed consent. This study was registered after obtaining approval from our organization’s clinical ethics committee, and it was performed in accordance with the ethical principles of the Declaration of Helsinki. This study was registered in the University Hospital Medical Network Clinical Trials Registry (Clinical trial registration number: UMIN000012846). Cases were prospectively registered with a target number of 50 patients. Patient recruitment Our research administration office sent a sealed letter to each FAP patient who had undergone a colectomy. The letter contained a pamphlet that introduced the study and a questionnaire that enabled the patient to indicate whether they wished to participate in the study. If the patient was interested in participating in the study, we asked them to visit our hospital after they had sent their consent by mail. During the patient’s visit to the hospital, a physician-incharge explained the study to the patient. We additionally tried to recruit patients when they visited the outpatient department. Patients who were introduced by other patients who were already participating in the study, and the patients’ family members or acquaintances were also asked to participate in the study. After confirming the patients’ clinical histories and current symptoms, we explained the clinical aspects of the study to the patients and described the complications that may arise as a consequence of CE examinations or this study.
123
Patient selection criteria FAP was diagnosed when the patients had histories of more than 100 colorectal adenomatous polyps and/or when genetic testing proved the presence of the APC mutation. There were no restrictions in relation to the interval between the colectomies and study participation. Patients were excluded if (1) gastrointestinal tract obstruction symptoms and clinical findings were evident; (2) they had chronic abdominal symptoms, such as nausea and abdominal pains; (3) they had histories of recurrent intestinal obstruction; (4) they had a heart pacemaker implanted; (5) they were under 20 years of age; (6) their general condition, determined by a performance status score of \2, was poor; or (7) they were pregnant. If it was difficult to decide whether to include a patient with a history of intestinal obstruction because they had no symptoms at the time of inclusion, we used a patency capsule (PC) to evaluate gastrointestinal tract patency, and the patient was included in the study if patency was confirmed. All patients had undergone periodic surveillance of their stomachs and duodenums using esophagogastroduodenoscopy (EGD) at our hospital within 1 year of study participation. Moreover, patients with residual rectums underwent yearly colonoscopic surveillance. Capsule endoscopy protocol CE was performed using a Pillcam SB2 video capsule (Given Imaging Ltd., Yoqneam, Israel), which examined the small intestine. Patients were prohibited from eating for 12 h before the CE examination and were administered domperidone (10 mg) immediately before the examination to promote capsule discharge from the stomach, dimethicone (40 mg) to defoam the gastrointestinal tract fluid, and pronase for mucolysis. We did not pre-treat the patients with, for example, orally administered polyethylene glycol. Patients were prohibited from drinking water for 2 h and from eating for 4 h after capsule administration. The sensor array and recorder were detached when capsule retrieval was confirmed, or 14 h after capsule administration despite capsule discharge not being confirmed, or when the battery ran out. The data recorder was collected on the following day, and the data were downloaded onto a Rapid 6.5 workstation (Given Imaging Ltd, Yoqneam, Israel). CE findings within the duodenum, jejunum, and ileum were analyzed. Using the localization map provided by the Rapid software, the regions were defined as described next. The duodenum was defined as the area from the pylorus to the ligament of Treitz. The small intestine was defined as the area from the ligament of Treitz to the point where the villus structure of the intestinal wall disappeared and the mucosa of the large intestine was observed, or where an obvious small intestinal and
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial…
anastomotic region in the colon was observed, or where a stoma bag was imaged. The jejunum was defined as the half of the small intestine that was on the mouth side, and the ileum was defined as the half of the small intestine that was on the rectal side. Two experienced endoscopists read the imaging separately, and they discussed their analyses after cross-checking the findings to make the final diagnoses. When they did not agree on a diagnosis, they reviewed a video of the case together to build consensus about their final diagnosis. Patients visited the hospital 2 weeks after the examination to determine whether the capsule had been discharged and if they had experienced any unintentional symptoms, such as abdominal symptoms, during the examination. If a patient was unable to confirm capsule discharge and the mucosa of the large intestine could not be determined on the images, an abdominal X-ray was performed to confirm that the capsule was not retained within the small intestine. Safety assessments The study’s primary endpoint was an evaluation of safety relating to the incidence of unintended symptoms, including capsule retention, the capsule retrieval rate, nausea during the examinations, the presence of abdominal symptoms, including abdominal pains, and the capsules’ transit times through the small intestine. In this study, we thought that 1 retention case out of 50 patients was acceptable based on a retention rate of 1.62 % reported from a domestic multicenter study conducted in 2004 that used CE (unpublished Japanese data). If 2 retention cases had been observed, the study would have been terminated because of safety issues. Evaluation of duodenal lesions The sensitivity and specificity of CE for duodenal lesions were reported as 69 and 75 %, respectively, when EGD was considered the gold standard [8]. Hence, we used EGD to evaluate duodenal lesions in this study. Before they underwent CE, all of the study’s participants had undergone EGD at our hospital or at their local clinics within the preceding year. The Spigelman scores were calculated based on these results [9].
Results Patients’ characteristics Seventy-two FAP patients who had undergone colectomies were recruited for this study. Following reviews of their medical records, we excluded 5 patients with histories of repeated intestinal obstruction or intestinal obstruction within 1 year of the study beginning, 4 patients who were in poor condition in general because of old age (n = 1) or systemic colon cancer metastases (n = 3), and 4 patients who had mental disorders. Consequently, 59 post-colectomy FAP patients were invited to participate in this study. Fifty-three patients replied to the invitation, and, of these, 46 patients wished to participate in the study and 13 patients declined the invitation to participate. Direct interviews with the 46 patients who wished to undergo CE examination excluded 2 patients who had histories of intestinal obstruction within the previous year and 1 patient who was suspected of having post-colectomy anastomotic regional stenosis and had chronic abdominal symptoms. One patient who could not swallow the capsule during the examination was also excluded from the study. Thus, 42 CE examinations were performed in 41 patients, which included 1 patient who wished to undergo a secondary CE because the first capsule was retained in the jejunum (Fig. 1). Table 1 presents the characteristics of the patients who underwent CE in this study. The study cohort comprised 25 men and 16 women. The median age at the time of initial colectomy was 26 years (range 13–58 years), and the median time interval after surgery was 14 years (range 1–43 years). Thirty-two patients had undergone total colectomies with ileorectal anastomoses. Among these 32 IRA patients, 4 patients underwent additional rectal resection because of new occurrence of rectal cancer with permanent ileostomy (n = 3), or severe defecation disorder (n = 1). 9 patients had undergone total proctocolectomies with ileal J-pouch anal anastomoses. Among these 9 IPAA patients, one patients underwent additional surgery with permanent ileostomy because anastomotic leakage and necrosis (n = 1). The phenotypes of the colorectal lesions at the time of colectomy in the FAP patients were categorized as dense (n = 9) or typical (n = 32).
Evaluation of small bowel lesions The locations (jejunum or ileum), sizes (1–5, 6–14, or C15 mm), macroscopic types, and the numbers of the lesions were evaluated. The number of lesions was measured as precisely as possible to a single digit. A detailed small intestinal examination using DBE was indicated if a small intestinal lesion measuring C15 mm was detected on the capsule images.
Safety of capsule endoscopy Of 42 CEs undertaken, the capsules passed through the small intestines within the scheduled timeframe of about 8 h in 39 procedures (93 %), and the capsules were retained in the small intestines in 3 procedures (7 %). The median small intestinal transit time was 202 min (range
123
M. Matsumoto et al. Fig. 1 Patient selection for this study
79–882 min). Capsule excretion was ultimately confirmed in all of the subjects, and no capsules were retained. No minor complications, including nausea and abdominal pains, were observed during CE (Table 2). Small bowel capsule endoscopy findings Thirty-nine patients whose entire small intestines could be viewed were included in the analysis, and 20 patients (51 %) had some form of polyp in their small intestines (Table 3). The median number of small intestinal polyps was 3 (range 1–223). Ten patients had polyps in the jejunum only, 6 patients had polyps in the jejunum and ileum, and 4 patients had polyps in the ileum only. Polyps were most commonly found in the jejunum. Most of the tumors were small polyps with diameters of 1–5 mm. One patient
123
had a protruding lesion in the jejunum near the ligament of Treitz that was at least 20 mm in diameter (Fig. 2a). DBE was subsequently performed and it revealed a flat lesion in the jejunum that was 25 mm in diameter (Fig. 2b). We performed an endoscopic mucosal resection and an en bloc resection was achieved. A histopathological examination showed a well-differentiated intramucosal adenocarcinoma without any lymphovascular invasion (Fig. 2c). Association between the status of duodenal polyps and small bowel polyps The duodenal adenomas in the 39 patients who were included in the analysis were staged according to Spigelman’s staging criteria for duodenal polyposis as follows: stage 0, 16 patients; stage I, 1 patient; stage II, 10 patients;
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial… Table 1 Patient characteristics
Male:Female, n
25:16
Median age years (range)
46 (24–74)
History of open abdominal surgery, n Once Twice
30 9
C3 times
2
Median age at the time of initial colectomy, years (range)
26 (13–58)
Median time interval since initial surgery, years (range)
14 (1–43)
Phenotype Dense/typical
9/32
Type of surgery Total colectomy/ileo-rectal anastomosis
32
Total colectomy/ileal J-pouch anal anastomosis
9
Duodenal polyp Yes/no
26/15
Spigelman stage, n 0
15
I
2
II III
10 7
IV
2
V
5
Table 3 Small bowel capsule endoscopy findings
Table 2 Capsule endoscopy safety evaluation items Median total capsule endoscopy time, min (range)
489 (77–1013)
Median small intestine transit time, min (range)
202 (79–882)
Median stomach transit time, min, (range)
30 (4–1005)
Unintended symptoms including retention, n (%) No
42 (100)
Yes
0 (0)
Entire small intestine examination, n (%) Possible Impossible
39 (93) 3 (7)
Furthest point reached by capsule, n (%) Jejunum
2 (5)
Ileum
1 (2)
Stoma, pouch, rectum
39 (93)
Small intestine polyp, n (%) Yes
20 (51)
No
19 (49)
Male:Female, n (%)
12 (60):8 (40)
Median age of patients with polyps, years (range)
45 (27–74)
Median elapsed time since surgery, years (range)
12 (1–43)
Median number of lesions, n (range)
3 (1–223)
Median size of lesion, mm (range) Locations of lesions, n (%)
5 (2–25)
Jejunum only
10 (50)
Jejunum and ileum
6 (30)
Ileum only
4 (20)
Discussion stage III, 6 patients; stage IV, 1 patient; and stage V, 5 patients. Duodenal adenomas were found in 23 patients (66 %), and, of these, small intestinal adenomas were found in 13 patients (57 %). Table 4 presents the characteristics of the patients who had small intestinal lesions. The proportions of patients with Spigelman’s stage 0 and stage 1 duodenal polyposis were 25 and 0 %, respectively; however, the proportions tended to increase with the Spigelman stage (Table 5).
Capsule retention is mainly caused by gastrointestinal tract stenosis that may occur because of non-steroidal anti-inflammatory drug-associated ulcers, Crohn’s disease, neoplastic lesions, radiation-induced enteritis, or surgicallyinduced anastomotic strictures [10]. Retention rates vary depending on the disease being investigated [11–17]. To the best of our knowledge, only a few case reports have been published [18, 19] that describe capsule retention in patients after open abdominal surgery [19]. Although CE
123
M. Matsumoto et al.
Fig. 2 a A protruding lesion was detected by capsule endoscopy in the proximal jejunum. b Double-balloon endoscopy showed a flat lesion that had a diameter of 25 mm. c Histological analysis confirmed an intramucosal well-differentiated adenocarcinoma (hematoxylin and eosin stain, 9200)
can generally be performed safely, even in patients with histories of open abdominal surgery, careful assessments are needed, because gastrointestinal tract stenosis occurs in
123
a high proportion of patients after surgery. Following open abdominal surgery, gastrointestinal tract-related subjective symptoms, including chronic abdominal pain, abdominal distension, or nausea, indicate gastrointestinal tract stenosis, and the indication for CE should be carefully assessed. Furthermore, if the stricture without symptoms had been detected by surveillance colonoscopy, CE should not be done. The retention may happen although endoscope could pass through of the stenosis and patient had not been complained any symptoms [20]. In this study, the patients’ medical records were carefully reviewed, and all patients were interviewed. Consequently, CE was not performed in patients with suspected gastrointestinal tract stenosis. Before CE, gastrointestinal tract patency can be determined using a PC [21, 22]. However, capsule retention has been reported despite PC confirmation [23]. Once retention occurs, open abdominal surgery may be required to remove the capsule. Indeed, FAP patients have an increased risk of additional abdominal surgery because of adhesions; therefore, unnecessary surgery should be avoided. Several reports describe investigations of small intestinal lesions in FAP patients [24–26]. Small intestinal adenomas are found in 50–75 % of FAP patients, they are mainly found in the jejunum, and most lesions are no larger than 10 mm and do not require immediate treatment [7, 27]. The condition of the duodenal adenomas may reflect the condition of the small intestine. Patients with duodenal adenomas at advanced Spigelman stages may be at greater risk of adenoma development in the small intestine [6, 24]. However, FAP patients rarely develop cancer in the small intestine [4, 28], and few reports describe FAP and cancer of the small intestine [29]. Incidence of small intestinal cancer with FAP patients is reported 0.4 % in jejunum and 0.1 % in ileum [4]. Ishida et al. [30] reported that seven cases of jejunal carcinoma associated with FAP have been published in English journals from 1980 to 2012, including 5 cases had died. According to the database of the polyposis registry of Japan, small intestinal cancer accounted for 1.0 % of all causes of death among FAP patients [31]. These results suggest that although incidence of small intestinal cancer is low, their prognosis is poor. While the results from this study tended to concur with those that have been published, we speculate that the small intestinal neoplasm incidence rate in FAP patients is higher than suggested. Based on our current study cohort, 4 patients had small intestinal tumors, which included 2 carcinoma in situ, 2 advanced small intestinal tumors. The Spigelman stages for these cases varied from stages IV and V to stage II, but this staging did not accurately reflect the condition of the small intestinal adenomas in some cases. We think that small intestinal surveillance is necessary for FAP patients regardless of low incidence of small intestinal carcinoma in FAP patients, because, early detection is
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial… Table 4 Numbers and sizes of small-bowel polyps detected by capsule endoscopy in 20 patients with familial adenomatous polyposis Patient no.
Age (years)
Sex
Interval after colectomy (year)
Duodenal polyp
Small-bowel polyp
Spigelman stage
Number
Maximum size (mm)
Location Number
J/I
Maximum size (mm)
1
54
M
20
V
[20
17
70
70/0
\5
2
60
M
40
II
5–20
5
223
3/220
\5
3
39
M
11
III
[20
10
17
17/0
\5
4
41
M
1
0
None
–
2
2/0
\5
5
62
M
36
II
5–20
5
5
2/3
\5
6
53
M
23
II
\5
5
5
0/5
\5
7
47
F
23
II
5–20
10
3
2/1
\5
8
61
F
35
III
5–20
30
9
9/0
6
9
52
F
10
0
None
–
1
1/0
\5
10
32
F
10
III
[20
15
3
1/2
\5
11
74
M
36
0
None
–
2
2/0
\5
12
42
F
2
0
None
–
1
1/0
\5
13
49
M
6
III
[20
12
3
0/3
\5
14 15
35 41
F M
12 15
II IV
1 [20
10 10
1 3
1/0 3/0
13 \5
16
43
M
6
III
[20
2
2
1/1
\5
17
30
M
5
II
5–20
5
1
1/0
\5
18
36
F
13
III
[20
15
4
3/1
\5
19
27
M
4
V
5–20
60
1
1/0
\5
20
64
F
43
V
[20
30
1
1/0
25
M male, F female, J jejunum, I ileum
Table 5 Small intestinal lesions categorized by Spigelman stage
Spigelman stage
With polyps n (%)
Location Jejunum only
Ileum only
Jejunum and ileum
0
4/16 (25)
4
0
0
I
0/1 (0)
–
–
–
II
6/10 (60)
2
1
3
2
1
3
III
6/6 (100)
IV
1/1 (100)
1
0
0
V
3/5 (60)
1
2
0
10
4
6
Total
20/39 (51)
important due to their prognosis is poor, and that CE should be the surveillance modality used because of its low level of invasiveness [32]. Determining the inspection intervals for small intestinal surveillance in FAP patients is a topic for future investigation. The ways in which small intestinal adenomas progress in FAP patients and how they progress after their development into advanced cancers via carcinomas in situ have yet to be determined. However, some studies have
reported that even relatively large tumors can remain as adenomas pathologically [24], and that their progress can be expected to be relatively slow. Moreover, it has been reported that the frequency of small intestinal adenoma occurrence increases with time after colectomy [33]. Based on these findings, we believe that periodic surveillance should be undertaken with long intervals. In this study, the CE completion rate was 92.9 %, and reported CE completion rates are between 70 and 80 % [34–
123
M. Matsumoto et al.
36]. Hence, the study’s CE completion rate is acceptable. Examinations could not be completed in 3 cases because the capsules’ batteries ran out, and the capsule was retained in the stomach of 1 case for a long period of time. To facilitate the transit of capsules through the stomach, drugs to enhance gastrointestinal tract motility could be administered, the body posture could be changed to the left lateral decubitus position, or the capsule could be delivered to the second part of the duodenum beyond the pylorus during EGD or using an endoscopic capsule-delivery device. Inspections of the whole small intestine must be reliable if CE is to be used for surveillance, which is proposed as a topic for future investigations. This study may be subject to several limitations, one of which relates to a selection bias that may have occurred when the physicians who were in charge of testing were selecting the subjects. In relation to safety, the acceptable capsule retention rate was 0 %, and patients were carefully selected by the physicians to protect their safety. The criteria for this study enabled the safety of CE in post-colectomy FAP patients to be demonstrated. Future investigations should examine the possibility of relaxing the selection criteria to enable more FAP patients to undergo CE examinations. Acknowledgments This work was supported by a Grant-in-Aid for Health and Labor Sciences Research, the third term of comprehensive research into cancer control. Author contributions Conception and design of the study; Minori Matsumoto, Takeshi Nakajima. Analysis and interpretation of data; Minori Matsumoto, Yasuo Kakugawa, Taku Sakamoto, Yosuke Otake, Takahisa Matsuda, Yukihide Kenemitsu, Hirokazu Taniguchi, Yutaka Saito. Collection and assembly of data; Minori Matsumoto. Drafting of the article; Minori Matsumoto, Takeshi Nakajima. Critical revision of the article for important intellectual content; Minori Matsumoto, Takeshi Nakajima. Final approval of the article; Yutaka Saito Compliance with ethical standards Conflict of interest The authors have no conflict of interest directly relevant to the content of this article.
References 1. Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348(10):919–932 2. Galiatsatos P, Foulkes WD (2006) Familial adenomatous polyposis. Am J Gastroenterol 101(2):385–398 3. Brosens LA, Keller JJ, Offerhaus GJ, Goggins M, Giardiello FM (2005) Prevention and management of duodenal polyps in familial adenomatous polyposis. Gut 54(7):1034–1043 4. Jagelman DG, DeCosse JJ, Bussey HJ (1988) Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet 1(8595):1149–1151 5. Burke CA, Santisi J, Church J, Levinthal G (2005) The utility of capsule endoscopy small bowel surveillance in patients with polyposis. Am J Gastroenterol 100(7):1498–1502
123
6. Schulmann K, Hollerbach S, Kraus K, Willert J, Vogel T, Moslein G, Pox C, Reiser M, Reinacher-Schick A, Schmiegel W (2005) Feasibility and diagnostic utility of video capsule endoscopy for the detection of small bowel polyps in patients with hereditary polyposis syndromes. Am J Gastroenterol 100(1):27–37 7. Iaquinto G, Fornasarig M, Quaia M, Giardullo N, D’Onofrio V, Iaquinto S, Di Bella S, Cannizzaro R (2008) Capsule endoscopy is useful and safe for small-bowel surveillance in familial adenomatous polyposis. Gastrointest Endosc 67(1):61–67 8. Yamada A, Watabe H, Iwama T, Obi S, Omata M, Koike K (2014) The prevalence of small intestinal polyps in patients with familial adenomatous polyposis: a prospective capsule endoscopy study. Fam Cancer 13(1):23–28 9. Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK (1989) Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 2(8666):783–785 10. Cave D, Legnani P, de Franchis R, Lewis BS (2005) ICCE consensus for capsule retention. Endoscopy 37(10):1065–1067 11. Li F, Gurudu SR, De Petris G, Sharma VK, Shiff AD, Heigh RI, Fleischer DE, Post J, Erickson P, Leighton JA (2008) Retention of the capsule endoscope: a single-center experience of 1000 capsule endoscopy procedures. Gastrointest Endosc 68(1):174–180 12. Cheon JH, Kim YS, Lee IS, Chang DK, Ryu JK, Lee KJ, Moon JS, Park CH, Kim JO, Shim KN et al (2007) Can we predict spontaneous capsule passage after retention? A nationwide study to evaluate the incidence and clinical outcomes of capsule retention. Endoscopy 39(12):1046–1052 13. Goldstein JL, Eisen GM, Lewis B, Gralnek IM, Aisenberg J, Bhadra P, Berger MF (2007) Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther 25(10):1211–1222 14. Liao Z, Gao R, Xu C, Li ZS (2010) Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review. Gastrointest Endosc 71(2):280–286 15. Cheifetz AS, Kornbluth AA, Legnani P, Schmelkin I, Brown A, Lichtiger S, Lewis BS (2006) The risk of retention of the capsule endoscope in patients with known or suspected Crohn’s disease. Am J Gastroenterol 101(10):2218–2222 16. Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Rossini FP, De Franchis R (2004) Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: report of 100 consecutive cases. Gastroenterology 126(3):643–653 17. de Franchis R, Avesani EM, Abbiati C, Rondonotti E, Zatelli S, Beccari G, Primignani M, Gatti M, Cappelletti M, Carnevali A et al (2003) Unsuspected ileal stenosis causing obscure GI bleeding in patients with previous abdominal surgery–diagnosis by capsule endoscopy: a report of two cases. Dig Liver Dis 35(8):577–584 18. Majeski J (2009) Endoscopic capsule retention in an intestinal anastomosis. Int Surg 94(3):254–257 19. De Palma GD, Rega M, Puzziello A, Aprea G, Ciacci C, Castiglione F, Ciamarra P, Persico M, Patrone F, Mastantuono L et al (2004) Capsule endoscopy is safe and effective after small-bowel resection. Gastrointest Endosc 60(1):135–138 20. Durchschein F, Schreiber F, Hogenauer C (2014) Video capsule endoscopy in familial adenomatous polyposis: capsule entrapment in an anal stenosis. Endoscopy 46(Suppl 1):UCTN:E529–530 21. Spada C, Spera G, Riccioni M, Biancone L, Petruzziello L, Tringali A, Familiari P, Marchese M, Onder G, Mutignani M et al (2005) A novel diagnostic tool for detecting functional patency of the small bowel: the Given patency capsule. Endoscopy 37(9):793–800
Surveillance using capsule endoscopy is safe in post-colectomy patients with familial… 22. Nakamura M, Hirooka Y, Yamamura T, Miyahara R, Watanabe O, Ando T, Ohmiya N, Goto H (2015) Clinical usefulness of novel tag-less Agile patency capsule prior to capsule endoscopy for patients with suspected small bowel stenosis. Dig Endosc 27(1):61–66 23. Watanabe K, Ohmiya N, Nakamura M, Fujiwara Y, Goto H, Arakawa T (2012) The investigation of the factors for confirming the patency by novel tag-less Agile patency Capsule-J for patients With Crohn’s disease and the other intestinal diseases, prospective, open-label study. Gastrointest Endosc 75(4):AB371 24. Matsumoto T, Esaki M, Yanaru-Fujisawa R, Moriyama T, Yada S, Nakamura S, Yao T, Iida M (2008) Small-intestinal involvement in familial adenomatous polyposis: evaluation by doubleballoon endoscopy and intraoperative enteroscopy. Gastrointest Endosc 68(5):911–919 25. Will OC, Man RF, Phillips RK, Tomlinson IP, Clark SK (2008) Familial adenomatous polyposis and the small bowel: a locoregional review and current management strategies. Pathol Res Pract 204(7):449–458 26. Schulz AC, Bojarski C, Buhr HJ, Kroesen AJ (2008) Occurrence of adenomas in the pouch and small intestine of FAP patients after proctocolectomy with ileoanal pouch construction. Int J Colorectal Dis 23(4):437–441 27. Wong RF, Tuteja AK, Haslem DS, Pappas L, Szabo A, Ogara MM, DiSario JA (2006) Video capsule endoscopy compared with standard endoscopy for the evaluation of small-bowel polyps in persons with familial adenomatous polyposis (with video). Gastrointest Endosc 64(4):530–537 28. Alderlieste YA, Rauws EA, Mathus-Vliegen EM, Fockens P, Dekker E (2013) Prospective enteroscopic evaluation of jejunal polyposis in patients with familial adenomatous polyposis and advanced duodenal polyposis. Fam Cancer 12(1):51–56
29. Ruys AT, Alderlieste YA, Gouma DJ, Dekker E, Mathus-Vliegen EM (2010) Jejunal cancer in patients with familial adenomatous polyposis. Clin Gastroenterol Hepatol 8(8):731–733 30. Ishida H, Kumamoto K, Amano K, Ishibashi K, Iwama T, Higashi M, Tamaru J (2013) Identification of APC gene mutations in jejunal carcinomas from a patient with familial adenomatous polyposis. Jpn J Clin Oncol 43(9):929–934 31. Iwama T, Tamura K, Morita T, Hirai T, Hasegawa H, Koizumi K, Shirouzu K, Sugihara K, Yamamura T, Muto T et al (2004) A clinical overview of familial adenomatous polyposis derived from the database of the Polyposis Registry of Japan. Int J Clin Oncol 9(4):308–316 32. Mata A, Llach J, Castells A, Rovira JM, Pellise M, Gines A, Fernandez-Esparrach G, Andreu M, Bordas JM, Pique JM (2005) A prospective trial comparing wireless capsule endoscopy and barium contrast series for small-bowel surveillance in hereditary GI polyposis syndromes. Gastrointest Endosc 61(6):721–725 33. Thompson-Fawcett MW, Marcus VA, Redston M, Cohen Z, McLeod RS (2001) Adenomatous polyps develop commonly in the ileal pouch of patients with familial adenomatous polyposis. Dis Colon Rectum 44(3):347–353 34. Rondonotti E, Herrerias JM, Pennazio M, Caunedo A, Mascarenhas-Saraiva M, de Franchis R (2005) Complications, limitations, and failures of capsule endoscopy: a review of 733 cases. Gastrointest Endosc 62(5):712–716 quiz 752, 754 35. Carey EJ, Leighton JA, Heigh RI, Shiff AD, Sharma VK, Post JK, Fleischer DE (2007) A single-center experience of 260 consecutive patients undergoing capsule endoscopy for obscure gastrointestinal bleeding. Am J Gastroenterol 102(1):89–95 36. Tatar EL, Shen EH, Palance AL, Sun JH, Pitchumoni CS (2006) Clinical utility of wireless capsule endoscopy: experience with 200 cases. J Clin Gastroenterol 40(2):140–144
123
