There is little doubt that capsule endoscopy (CE) is the best method to evaluate the entire small bowel mucosa. Many studies, mostly investigating patients with gastrointestinal bleeding, demonstrate that more "abnormalities" are observed by CE than push enteroscopy or small bowel radiography (1,2,3,4). However, data on the clinical significance of the lesions and impact on patient management are rare. We report the use of CE in a cohort of patients with small bowel polyposis and demonstrate the jejunal and ileal findings and positive impact of CE on patient management.
Small intestinal polyps are the most problematic aspect of Peutz–Jeghers syndrome (PJS) and familial adenomatous polyposis (FAP). Small bowel neoplasms occur in greater than 75% of PJS and 90% of FAP patients (5,6).
Nearly, 50% of PJS patients require an operation for small bowel obstruction or intussusception, often by the third decade of life. Most series confirm that recurrent obstruction requiring relaparotomy is common and is performed between 1 and 4 times per patient (7,8,9,10). Additionally, the risk of gastrointestinal malignancy has been well described in patients with PJS. The cumulative risk of small bowel cancer is 13% in large published series (11). In order to minimize the complications of small bowel polyposis in PJS, upper endoscopy and small bowel radiographic surveillance are recommended.
In contrast to PJS, where duodenal neoplasms are uncommon, the majority of small bowel neoplasms in FAP occur in the peri-ampullary duodenum. The risk of duodenal cancer in FAP is 4% although recent studies, stratifying cancer risk on the basis of severity of duodenal polyposis, have found an incidence of 35% in those with Spigelman stage IV polyposis (12; Table 1). Forward and side-viewing endoscopy is recommended in individuals with FAP for the surveillance of gastric and duodenal polyposis. The systematic study of polyps distal to the duodenum in FAP is limited.
The aim of our study is to assess the prevalence of small bowel polyps beyond the duodenum and to evaluate the safety of CE in patients with small bowel polyposis.
METHODS
We performed an IRB approved, prospective study, in 19 patients with FAP or PJS with a history of small bowel polyposis. Patients who had undergone major abdominal surgery within the last 12 months or who had an implanted electromedical device, or symptoms suggestive of small bowel obstruction were excluded at the request of the manufacturer (Given). Patients who were due for their surveillance upper endoscopy examination were eligible for the study.
The patients ingested the capsule after an overnight fast. A single investigator (CAB) who is an experienced endoscopist and had read over 150 CE interpreted all of the videos. The location (jejunum, ileum), greatest size (1–5 mm, 6–10 mm, >10 mm), and number (1–5, 6–12, >20) of polyps detected by CE was assessed. The duodenum was designated to be the small bowel visualized up to 15 min after the capsule exited the pylorus (GET). The small bowel transit time (SBTT) was calculated to be the GET minus the time it took for the capsule to reach either the cecum, rectum, or end of capsule study. The small bowel visualized between 15 min after GET and <50% of SBTT was presumed to be jejunum and the small bowel visualized on CE >50% of SBTT was designated ileum. The size of polyps was an estimate based on experience of the investigator. Eight hours after ingestion of the capsule, upper endoscopic evaluation was performed to stage the degree of duodenal polyposis according to the Spigelman staging system (Table 1).
The major risk from CE is capsule retention and bowel obstruction. The safety of CE in this group of subjects was assessed by two methods. All subjects were instructed to contact the study staff if any gastrointestinal symptoms developed during or after CE. Subjects received a phone call 1 wk after CE and completed a standardized "pain and discomfort" assessment (none, minor, mild, severe, and intolerable).
RESULTS
Nineteen subjects, 12 female, and 7 male, were included. The mean age of the subjects was 43 yr. Fifteen patients had FAP and four had PJS. All FAP subjects had undergone major intestinal surgery including subtotal colectomy with ileorectal anastomosis (IRA) in 11 and total proctocolectomy with ileal pouch anal anastomosis (IPAA) in four. All were asymptomatic at the time of the study. All of the PJS subjects had previously undergone laparotomy for complications related to small bowel polyposis. One had anemia that was attributed to menstrual losses and all had previously experienced mild, intermittent abdominal pain not associated with abdominal distension, nausea, vomiting, or obstipation.
CE FINDINGS IN FAP
Nine (60%) FAP subjects had polyps detected beyond the duodenum (Figs. 1 and 2). The presence and location of jejunal and ileal polyps were related to the Spigelman stage of duodenal polyposis and age of the patient (Table 2). None of the four FAP subjects with stage 0 or I polyposis had small bowel polyps detected. However, polyps were detected in 75% (3/4) of stage II subjects, 100% (5/5) of stage III subjects, and 50% (1/2) of stage IV subjects. The location of polyps tended to migrate distally as the stage of polyposis advanced. The size and number of polyps also progressed as the stage of duodenal polyposis advanced (Table 3).
One patient, with stage II polyposis, who had undergone IPAA 13 months prior to CE, had no polyps detected in the jejunum or ileum. However, CE detected a circumferential appearing neoplasm just as the capsule exited the patient's anus (Fig. 3). Pouchoscopy confirmed an anal canal tubulo-villous adenoma that required examination under anesthesia and destruction of the lesion.
CE FINDINGS IN PJS
Three of four (75%) PJS subjects had polyps detected beyond the duodenum (Figs. 4 and 5). The polyps were sessile and pedunculated and ranged in sizes from 0.2 to >30 mm (Table 4). In 2 subjects, the polyposis was diffuse and in 1 subject, the polyps were noted only in the ileum.
Three of four subjects had undergone small bowel radiography within 16 months of CE. Small bowel radiography and CE were both normal in one subject. In two other subjects, the x-ray was negative, while CE detected diffuse polyposis. One subject had a small bowel x-ray that underestimated the extent of polyposis. The x-ray detected one, <1 cm polyp in the proximal jejunum. The CE revealed more than 20, >10 mm polyps diffusely in the small bowel.
In 2 subjects with PJS (50%), the findings on CE led to intraoperative endoscopy and endoscopic and surgical resection of all visualized small bowel polyps. Intraoperative endoscopy confirmed the size, number, and location of polyps as detected by CE. The small bowel polyps were all hamartomas without epithelial dysplasia.
SAFETY AND TECHNICAL ASPECTS
The capsule examination was complete to the anastomosis in 93% (14/15) of FAP subjects. In 2 FAP subjects, there were technical abnormalities. This included a loss of 2 min of data in one and poor visualization of parts of the small bowel in another subject. The capsule examination was complete in 75% (3/4) of PJS subjects. The capsule did not reach the colon in 1 subject by approximately 7 h when the storage recording device was disconnected from the patient. No regional transit abnormality was noted in this subject's CE.
No FAP or PJS subject reported complications from CE. When subjects were contacted 1 wk after the procedure, 18/19 subjects reported that they had experienced no pain or discomfort after CE, while one subject reported mild pain and discomfort.
DISCUSSION
Our study demonstrates the safety and findings of CE in subjects with FAP and PJS. It is one of the first papers of CE that demonstrates a significant clinical impact on polyposis patient management. One patient with FAP and 50% of subjects with PJS proceeded to operative management on the basis of the capsule findings. Although the number of subjects in our trial was small, it represents a large collection of individuals with the rare inherited polyposis syndromes studied at a single center.
CE was not complete in 2/19 subjects (one FAP and one PJS). In two others, technical issues precluded full evaluation of the small intestine. The clinical implications of these incomplete examinations are seemingly minor. However, the lack of visualization of all of the small bowel mucosa could lead to underestimation of the polyp burden in our study. We observed no complications from CE in our study group. One other report of CE performed in 33 individuals with polyposis failed to detect any complications (15).
In FAP, we found jejunal and ileal polyps to be common. Although we do not have histologic proof that these polyps are adenomatous, the data from others performing enteroscopy support our findings. One group found that 83% of their FAP patients undergoing small bowel enteroscopy harbored jejunal adenomas (13). Another group assessed the incidence of neoplasms in FAP patients undergoing intraoperative endoscopy and they detected adenomas in the jejunum in 29% and the ileum in 14% (14). One of our patients who had not had pouchoscopy since her IPAA was found to have an advanced neoplasm at the anal transition zone that was confirmed on pouchoscopy, and required resection.
Interestingly, we found the frequency, size, and number of polyps and the length of small bowel involvement to increase with the stage of duodenal polyposis. All polyps were less than 10 mm in size. The implication of jejunal and ileal polyps in FAP is not known. The risk of cancer distal to duodenum in FAP is much more rarely reported than duodenal and peri-ampullary carcinoma. We have detected jejunal adenocarcinomas in 2 patients with stage IV polyposis before the use of CE. Both the patients had metastatic disease. One patient presented with gastrointestinal symptoms. The other patient was asymptomatic and had a normal preoperative small bowel x-ray. The lesion was detected intraoperatively during a prophylactic, pylorus-preserving duodenectomy for stage IV polyposis.
Forward and side-viewing endoscopic surveillance for gastric and duodenal/peri-ampullary neoplasia is recommended for all individuals with FAP. The frequency of surveillance should be based on the Spigelman classification of duodenal polyposis. However, based on our personal experience, CE has become our standard pre-operative imaging modality to survey for small bowel neoplasia beyond the duodenum in FAP patients with stage IV polyposis undergoing duodenectomy. Since stage III patients have a high burden of small bowel polyps on CE, we also recommend it for surveillance in this group. More data on the prevalence of small bowel polyps detected by CE in FAP patients with advanced stage duodenal polyposis is needed to understand the utility of CE in these groups. However, we do not recommend CE for routine small bowel surveillance in FAP patients with stage 0–II disease.
In contrast to FAP, we believe CE is the method of choice for small bowel surveillance or the assessment of gastrointestinal symptoms in PJS. We found polyps in 75% of the individuals. This high prevalence is confirmed by another study of CE where polyps were detected in 90% of PJS patients (15).
All of our PJS subjects had reported mild abdominal symptoms prior to CE. It is well described that symptoms due to small bowel hamartomas may be chronic, mild, and nonspecific. Many series report that PJS patients harboring clinically significant small bowel polyps, some as large as >2 cm, may be asymptomatic (16). Small bowel radiography underestimated the polyp burden, while CE detected polyps diffusely throughout the jejunum and ileum, many greater than 20 mm in size. The results of CE led to laparotomy with intraoperative endoscopy in 50% of PJS subjects. We were pleased to confirm that the findings on CE were confirmed by intraoperative endoscopy in all patients who went to surgery.
Most guidelines suggest upper endoscopy and small bowel radiographic surveillance in patients with PJS (17,18,19,20). Endoscopic or intraoperative resection of symptomatic or large (>1 cm) polyps found on radiography is recommended to prevent obstruction and small bowel cancer. We concur with the timing and need for small bowel surveillance as set forth in published guidelines but, on the basis of our findings, recommend CE replace biennial radiographic imaging of the small bowel for polyp surveillance or for the evaluation of gastrointestinal symptoms in PJS patients.
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