Small bowel polyps and tumours: endoscopic detection and treatment by double-balloon enteroscopy

Transcription

1 Alimentary Pharmacology & Therapeutics Small bowel polyps and s: endoscopic detection and treatment by double-balloon enteroscopy L. C. FRY*,1,H.NEUMANN*,1,D.KUESTER, R.KUHNà, M.BELLUTTI*,P.MALFERTHEINER*& K. MONKEMULLER* *Department of Gastroenterology, Hepatology and Infectious Diseases; Department of Pathology and àdepartment of Surgery, Otto-von- Guericke University, Magdeburg, Germany Correspondence to: Dr K. Mönkemüller, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg, Germany. 1 LCF and HN contributed equally to this study. Publication data Submitted 21 August 2008 First decision 4 September 2008 Resubmission 18 September 2008 Resubmission 29 September 2008 Accepted 29 September 2008 Epub Accepted Article 3 October 2008 SUMMARY Background Double-balloon enteroscopy has allowed us not only to inspect deeply the small bowel but also to carry out interventions for diseases of the small bowel. Aim To evaluate the utility of double-balloon enteroscopy for the diagnosis and therapy of these lesions. Methods All patients undergoing double-balloon enteroscopy for evaluation of small bowel polyps and s during a 3.75-year period at a university referral hospital were studied. The types of polyps and s as well as endoscopic technique of removal, surgery and complications were documented. Results The incidence of small bowel polyps and s in-patients undergoing DBE was 9.6%. A total of 40 double-balloon enteroscopy procedures were performed in 29 patients [13 female (44.8%), mean age 51 years, range 22 74]. The following lesions were found most frequently: adenomas in familial adenomatous polyposis syndrome, n = 8; hamartomas, n = 4 (Peutz-Jeghers and Cronkhite Canada syndromes), jejunal adenocarcinoma n = 5, neuroendocrine n = 4 and others n =6. Conclusions The incidence of small bowel s in those in-patients who were undergoing double-balloon enteroscopy was 10%. Double-balloon enteroscopy is useful for the diagnosis and treatment of small bowel polyps and s. Aliment Pharmacol Ther 29, ª 2008 The Authors 135 doi: /j x

2 136 L. C. FRY et al. INTRODUCTION The major indications for double-balloon enteroscopy are evaluation of patients with obscure gastrointestinal bleeding and suspected Crohn s disease. 1 5 Small bowel polyps and s are an important cause of small bowel pathology occurring most frequently in familial and nonfamilial polyposis syndromes. 6 8 However, other important small bowel s include adenocarcinoma, neuroendocrine s and others. 8, 9 Until recently, radiological methods and capsule endoscopy were the major methods to investigate small bowel disorders. 10, 11 However, neither radiological methods nor capsule endoscopy permits biopsy, resection or mucosal marking of polyps and s. Until only a few years ago, primary surgical resection with or without intraoperative endoscopy and polypectomy were the only available means of treating polyps in the mid-small bowel in these patients. 12 The advent of double-balloon enteroscopy has increased our diagnostic and therapeutic armamentarium for various small bowel disorders. 1 5 The aims of this study were to evaluate the feasibility and utility of double-balloon enteroscopy for the diagnosis of and therapy of these lesions. METHODS Consecutive patients who underwent double-balloon enteroscopy at the University of Magdeburg Medical Centre (Universitätsklinikum Magdeburg, Otto von Guericke University, Magdeburg, Germany) were included and their data recorded in a prospectively collected database. This study evaluated a period of 3.75 years and comprises all patients who were found to have polyps or masses of the small bowel. The study was approved by the ethics committee of the University of Magdeburg and conducted in accordance with the Helsinki Declaration. The patients provided written informed consent to undergo endoscopy with doubleballoon enteroscopy. Double-balloon enteroscopy (DBE) was performed using Fujinon enteroscopes (Fujinon FN 450P 5 20, EN-450T5, Fuji, Fujinon Corp., Japan). The characteristic technical details of double-balloon enteroscopy have been presented in detail elsewhere. 1, 5 Briefly, the depth of insertion of the endoscope into the small bowel is estimated by recording the net advancement of the endoscope for each push-and-pull manoeuvre on a standardized documentation sheet. 13 At any point during the procedure and at the end, all of the figures recorded are added and the length of small bowel that has been visualized can be estimated. During doubleballoon enteroscopy, careful attention must be given not to insufflate too much air, because this induces intestinal loop formation and impedes deep advancement. In addition, water combined with Simethicone to reduce bubble formation is used routinely. During intubation, it is important to straighten the enteroscope and resolve any loops formed during insertion. 13 Patients underwent small bowel cleansing on the day before the procedure using 2 L of a standard colon lavage solution (Kleanprep, Marburg, Germany) and then underwent the procedure after an overnight fast. A small bowel relaxant [Buscopan (butyl scopolamine), Boehringer Ingelheim, Ingelheim am Rhein, Germany] was administered if the bowel motility was increased or if a therapeutic intervention was performed. Fluoroscopy to determine the position of the enteroscope was performed using a Philips C-arm (Philips, Best, Holland). All procedures were performed using conscious sedation with propofol (Disoprivan, Propofol, Braun, Melsungen, Germany). Conscious sedation was administered by one physician. Polyps were defined as any mucosal protuberance, either sessile or pedunculated. Sessile lesions larger than 3 cm were considered masses. The polyp or mass was considered submucosal if the overlying mucosa was intact. The size of polyps and masses was estimated with the use of an open biopsy forceps. All patients with familial adenomatous polyposis syndrome underwent an additional endoscopy with the side viewing duodenoscope (Olympus, Hamburg, Germany) to evaluate the ampulla of Vater. Small bowel polyposis was defined according to the Spigelman score modified by Saurin. 14 This modified Spigelman Saurin classification takes into account the updated Vienna classification for gastrointestinal epithelial neoplasias (i.e. low or high grade dysplasia), whereas traditional Spigelman classification classifies adenomas into mild, moderate and severe dysplasia. 15 In the modified Spigelman Saurin classification, points are given for the number of polyps (1 point for one to four polyps, 2 points for five to 20 polyps and 3 points for >20 polyps), polyp size (1 point for 1 4 mm, 2 points for 5 10 mm, 3 points for >10 mm), histology (1 point for tubular adenoma, 2 points for tubolovillous and 3 points for villous adenoma) and dysplasia (1 point for low grade dysplasia, 3 points for high grade dysplasia). Stage 0: no polyp; stage I: 1 to 4 points; stage II: 5 to 6 points; stage III; 7 to 8 points;

3 DOUBLE-BALLOON ENTEROSCOPY SMALL BOWEL POLYPS AND TUMOURS 137 and stage IV: 9 t 12 points. 14, 15 Advanced adenoma (neoplasia) was defined as an adenomatous polyp >10 mm or with severe dysplasia. 14 All patients with Peutz-Jeghers syndrome and familial adenomatous polyposis syndrome received genetic counselling and genetic testing. Familial adenomatous polyposis syndrome patients underwent testing for the adenomatous polyposis coli mutation and patients with Peutz- Jeghers syndrome were tested for the STK11 germline mutation. The diagnosis of Peutz-Jeghers syndrome or familial adenomatous polyposis syndrome was based on standard criteria. 16 Determination of the primary route of insertion (oral or antegrade vs. anal or retrograde) The choice of either the oral or the anal route depended on the suspected location of the lesions within the small bowel based on the clinical manifestations, results of laboratory, radiological and previous radiological and endoscopic examinations. If a patient had undergone capsule endoscopy, we used the results of this test to guide the insertion route. Capsule endoscopy was not available at our institution until the latter part of In cases of obscure overt gastrointestinal bleeding, the route of insertion was dictated by the colour of the stool; in cases of maelena, the oral approach was preferred, whereas in the presence of haematochaezia, the anal approach was used first. If one double-balloon enteroscopy route did not yield any diagnosis, the opposite route was used for the second investigation. To confirm total enteroscopy, we performed India ink marking of the small bowel. Total enteroscopy was also confirmed if the coecum or colon could be visualized when using the oral approach. In case total enteroscopy was not possible in high risk patients with familial adenomatous polyposis syndrome, they also underwent capsule endoscopy. Complications of DBE were defined according to standard criteria. 17 Removal of polyps was performed using either mucosectomy or polypectomy techniques, but always preceded by submucosal injection of epinephrine-saline solution (1:10 000). All s were biopsied. Descriptive statistics were used to summarize baseline demographics and clinical characteristics. RESULTS During the study period, we performed a total of 402 double-balloon enteroscopies in 301 patients. Small bowel s and or polyps were detected in 29 patients (9.6%) in whom a total of 40 double-balloon enteroscopies were performed. The demographic, clinical, endoscopic and surgical findings of the study cohort are presented in Tables 1 and 2. The most common indications for double-balloon enteroscopy were obscure gastrointestinal bleeding and evaluation of small bowel polyps in-patients with familial adenomatous polyposis syndrome (Table 2). In seven patients, the double-balloon enteroscopy was performed because of suspicious finding on capsule endoscopy (Figure 1). The following polyps and s were found most frequently: adenomas in familial adenomatous polyposis syndrome, n = 8 (Figure 1); hamartomas, n = 4 (Peutz-Jeghers and Cronkhite Canada syndromes) (Figure 2) and jejunal adenocarcinoma n =5 (Figure 3), neuroendocrine n =4 (Figure 4) (Tables 1 and 2). Technical results The route for double-balloon enteroscopy in patients with positive findings was oral in 34 and anal in 6. The mean duration of the procedure was 75 min, range 25 min to 115 min. The mean radiation exposure was 185 dgy cm 2 (range 0 556). The mean small bowel insertion was 300 cm, range cm (excluding failed cases). There were two failed doubleballoon enteroscopies: in a patient with Peutz-Jeghers syndrome, jejunal intubation via the oral route was only successful to 40 cm because of multiple adhesions. In one anal double-balloon enteroscopy in a patient with neuroendocrine, it was only possible to visualize 20 cm of terminal ileum, but a submucosal lesion was detected and confirmed as a neuroendocrine during laparotomy. Endoscopic and histological results The most commonly diagnosed mass lesions were adenocarcinomas (n = 5) and neuroendocrine s (n = 4). Adenocarcinomas appeared either as a stenosing or hemicircumferential mass (Table 1) (Figure 4). In one patient with adenocarcinoma, double-balloon enteroscopy was useful to remove a lodged capsule. Neuroendocrine appeared as yellow submucosal masses, thickened folds or ulcerated actively bleeding lesions (Table 1). In two patients with neuroendocrine, endoscopic haemostatic therapy using argon plasma coagulation was employed to

4 138 L. C. FRY et al. Table 1. Clinical, demographic and endoscopic characteristics of patients diagnosed with small bowel s N Age Gender Route Indication Finding Histology Technical aspects Evolution 1 75 F Oral Anaemia, Stenosing Adenocarcinoma Extraction of CE Surgery CE: jejunal 2 72 M Oral Anaemia Hemicircumferential Adenocarcinoma Biopsies Surgery 3 56 F Oral Anaemia, CE: Tumour and capsule retention Stenosing Adenocarcinoma Biopsies but they were negative Surgery 4 72 F Oral Anaemia, CE: suspected Large mass Adenocarcinoma Biopsies + India ink marking Surgery 5 38 M Oral Maelena, Large mass Adenocarcinoma Biopsies Chemotherapy liver metastasis 6 48 M Oral Anaemia Submucosal GIST Biopsies Surgery 7 61 F Oral Maelena Submucosal GIST Biopsies Surgery 8 48 F Oral Haematochaezia Bleeding ulcerated NET Biopsies, APC, Surgery India ink marking 9 68 M Oral Haematochaezia Bleeding ulcerated NET Biopsies, India Surgery ink marking F Anal Liver Submucosal NET Biopsies negative Surgery metastasis of a NET In terminal ileum F Anal Metastatic NET Tumour with NET No biopsies could Surgery central erosion be obtained M Oral Haematochaezia, CE: small bowel with invagination Jejunal Histology negative Biopsies, India ink marking Surgery: Leiomyoma M Oral CE: suspected small bowel infiltration of lymphoma M Anal Bleeding, CE: several s Irregular mucosa suspicious of lymphoma infiltration Large mucosal s B-cell lymphoma B-celllymphoma Biopsies Biopsies Chemotherapy Chemotherapy DBE, double-balloon enteroscopy; SB, small bowel; FAP, familial adenomatous polyposis; PJS, Peutz-Jeghers syndrome; CE, capsule endoscopy, GI, gastrointestinal, GIST, gastrointestinal stromal ; NET, neuroendocrine. stop the active bleeding. Gastrointestinal stromal s appeared as large, submucosal lesions with grey rubbery surface. Both lymphomas appeared as submucosal lesions with intact overlying mucosa. Except for the patient with testicular metastasis, who expired as a result of his underlying illness, all other patients with s underwent exploratory laparotomy. The surgeon was able to locate the lesions in all patients. The polyps found in patients with familial adenomatous polyposis syndrome were adenomas of various sizes and histological grades (Table 1). The mean Spigelman Saurin score was 4.1, range 2 8. The polyps were flat with a whitish surface (Figure 1). Two patients were found to have advanced jejunal adenomas (Figure 1). Six patients were found to have mutations involving exon 15 of the adenomatous polyposis coli gene. The advanced lesions were removed with mucosectomy technique. All patients with Peutz- Jeghers syndrome and the patient with Cronkhite Canada syndrome were found to have hamartomas. All polyps larger than 15 mm were removed using snare electrocautery. Nine double-balloon enteroscopies were performed in three patients with Peutz-Jeghers syndrome. The average number of polyps removed during one session was 10 (range 3 32). The patients with diffuse small bowel polyposis and nodular lymphoid

5 DOUBLE-BALLOON ENTEROSCOPY SMALL BOWEL POLYPS AND TUMOURS 139 Table 2. Clinical, demographic and endoscopic characteristics of patients diagnosed with small bowel polyps N DBE Age Gender Route Indication* Finding Type of polyp(s) Endoscopic technical aspects 1 42 F Oral FAP Polyps in duodenum, jejunum and ileum M Oral FAP Papillary adenoma no small bowel polyps Tubulovillous adenomas with LGIN Adenomas, LGIN Polypectomy >5 polyps with snare and APC surveillance 2 Oral FAP Jejunal polyps Adenomas, LGIN APC 3 31 F Oral FAP Small bowel polyps Adenomas, LGIN APC M Oral FAP Jejunal polyps Adenomas with LGIN Mucosectomy, polypectomy + APC 2 Oral FAP Jejunal polyps APC M Oral FAP Jejunal polyps No histology APC 2 Oral FAP Jejunal polyps Advanced adenomas with LGIN Mucosectomy, polypectomy + APC M Oral FAP 1 jejunal polyp adenoma surveillance 2 Anal FAP No polyps n a surveillance 7 22 M Oral FAP Duodenal polyps adenomas surveillance 8 46 F Oral FAP Jejunal polyps adenomas with LGIN APC F Oral PJS small Hamartomas Polypectomy bowel polyps*** 2 Oral PJS 20 small bowel polyps Hamartomas Polypectomy 3 Oral PJS Small bowel polyps Hamartomas Polypectomy M Oral PJS 18 jejunal polyps*** Hamartomas Polypectomy, bleeding: epinephrine injection 2 Anal PJS Colonic polyps Hamartomas, Polypectomy adenomas M Oral PJS 12 small bowel polyps*** Hamartomas Polypectomy 2 Oral PJS 8 small bowel polyps Hamartomas Polypectomy 12 polyps 3 Oral PJS 3 small bowel polyps Hamartomas Polypectomy 4 Oral PJS 5 small bowel polyps Hamartomas polypectomy M Oral Diarrhoea Small bowel polyps NLH Medical treatment F Oral Diarrhoea Pseudopolyps Atrophy, NLH Medical treatment F Oral CCS, diarrhoea Sessile polyps, elongated villi Hamartomas, mucosal atrophy** Steroids m Oral Haematochaezia Normal 2 Anal Ileal mass*** Lipoma Surgery * Indication: FAP, surveillance; PJS, recurrent abdominal pain (intussusception) and prophylactic removal or polyps. ** The patient with CCS also had colonic polyps: serrated adenomas, juvenile polyps, pseudopolyps and hamartomas. DBE, double-balloon enteroscopy: this column indicates the number of DBEs per patient. LGIN, low grade intraepithelial neoplasia; APC, argon plasma coagulation; CCS, Cronkhite-Canada syndrome; NLH, nodular lymphoid hyperplasia. *** These patients had 1-5 polyps or lesions larger than 3 cm (per definition these were masses, see text). hyperplasia did not require any endoscopic therapeutic intervention. The only major complication was bleeding after polypectomy in a patient with Peutz-Jeghers syndrome. One patient suffered from temporary oxygen desaturation (<92%) during the procedure, which responded to increased oxygen administration.

6 140 L. C. FRY et al. Figure 1. Advanced adenoma in a patient with familial adenomatous polyposis syndrome (FAP). Note the sessile polyp with whitish mucosal discoloration. Advanced adenomas are polyps >10 mm in FAP. Figure 3. Surgical specimen demonstrating a stenosing adenocarcinoma of the small bowel. Figure 2. Large pedunculated polyp in a patient with Peutz-Jeghers syndrome. These polyps have a tendency to grow larger over time and result in bleeding or intussusception. Although we did not observe any case of pancreatitis, one patient had significant abdominal pain and bloating after the procedure, which subsided after the passage of large amounts of flatus. DISCUSSION Figure 4. Large submucosal mass diagnosed as a neuroendocrine. In this study, we found that the relative incidence of small bowel s in-patients undergoing doubleballoon enteroscopy was 9.6%. Whereas doubleballoon enteroscopy was useful for the diagnosis of various types of polyps and s its major endoscopic therapeutic impact was evident in-patients with familial adenomatous polyposis syndrome, Peutz- Jeghers syndrome and single polyps. However, even in-patients with endoscopically unresectable lesions, double-balloon enteroscopy was useful for the diagnosis and or localization of the lesion. Until only recently, primary surgical resection and intraoperative endoscopy and polypectomy were the only available possibilities to treat polyps in the midsmall bowel in-patients with polyps. 12, 15 Doubleballoon enteroscopy has changed this approach and now it is possible to not only perform endoscopic

7 DOUBLE-BALLOON ENTEROSCOPY SMALL BOWEL POLYPS AND TUMOURS 141 surveillance and diagnoses these lesions but also to resect them. 18, 19 Although there are few case reports and series documenting the feasibility of double-balloon enteroscopy in-patients with polyposis syndromes, our study has the advantage of having focused on all patients with small bowel polyps and s undergoing double-balloon enteroscopy. Knowledge of the data on the incidence and management of these lesions inpatients undergoing double-balloon enteroscopy is useful for several reasons. First, the endoscopist performing double-balloon enteroscopy should be trained and prepared to resect these polyps. Repeating double-balloon enteroscopy carries the risk of complications; albeit low, it is associated with significant morbidity and even mortality. 17, 20 Thus, in cases where a polypectomy is anticipated, double-balloon enteroscopy should be performed in a specialized centre. Second, knowledge of the incidence and management of small bowel polyps and s is important for planning the endoscopic infrastructure required for the performance of doubleballoon enteroscopy. Currently, double-balloon enteroscopy is mainly performed for obscure gastrointestinal bleeding and suspected Crohn s disease. 1 5 However, our data and those from other studies suggest that polyps and s are a major reason for performing doubleballoon enteroscopy. 21 Third, knowledge of the complications associated with small polypectomy is important. Therapeutic double-balloon enteroscopy is associated with approximately 1 5% incidence of complications, the most frequent ones being pancreatitis, bleeding and perforation. 17, 18, 20, 22 In our series, the incidence of major complications was 3%, consisting of one episode of bleeding. However, minor complications such as oxygen desaturation and abdominal discomfort can also occur as a consequence of double-balloon enteroscopy. We did not aim to investigate the utility of doubleballoon enteroscopy for the surveillance of polyposis syndromes. This topic has been addressed in recent publications. 14 Nevertheless, it is important to emphasize that patients with familial and nonfamilial polyposis syndromes are at increased risk of small bowel polyps and adenocarcinoma. In patients with familial adenomatous polyposis syndrome, the risk increases in parallel to the Spigelman Saurin score or if there are mutations in exon 15. 5, 7, 23, 24 Thus, genetic testing, as it was performed in our study, might be of help to select patients for small bowel investigation. Doubleballoon enteroscopy will allow the elimination of small bowel adenomas using either polypectomy or argon plasma coagulation. 25 In-patients with adenocarcinoma and submucosal masses such as neuroendocrine and gastrointestinal stromal s, we found that double-balloon enteroscopy was most useful for establishing a diagnosis. We want to emphasize that an important aspect about submucosal s is that endoscopic resection should not be attempted. Double-balloon enteroscopy serves the main purpose of localizing these lesions. A recent study reported on the feasibility of combined double-balloon enteroscopy and laparoscopy for the management of various small bowel disease including angiodysplasias, Meckel s diverticula, gastrointestinal stromal and adenocarcinoma. 26 It is important to stress that double-balloon enteroscopy can be a time-consuming procedure and it is not always possible to visualize the entire small bowel. Thus, capsule endoscopy may play an important role in the evaluation of patients with small bowel polyps and s. If no lesions are found, capsule endoscopy may obviate the need for an invasive double-balloon enteroscopy and if a lesion is detected, it would point to the diseased segment to be investigated with the double balloon enteroscope. Therefore, capsule endoscopy and double-balloon enteroscopy should be viewed as tests complementing each other. Our study has the potential limitations of being a single-centre study in a university setting with its associated bias and that it was not a prospective study. Because the study was not population-based, but rather reflects a consecutive series of local and referred patients, the term incidence may be a relative term. However, to our knowledge, this is the largest endoscopic experience focusing on the diagnosis and management of both small bowel polyps and s using balloon enteroscopy. In addition, the data collection was performed prospectively and thoroughly, including definition of polyps and s and usage of standard endoscopic, histological and international criteria for polyposis syndromes, including genetic testing. In summary, we have shown that the relative incidence of small bowel polyps and s in-patients undergoing double-balloon enteroscopy is 9.6%. We also demonstrated that double-balloon enteroscopy is a useful method for the diagnosis and endoscopic therapy of polyps and localization of s. ACKNOWLEDGEMENTS Declaration of personal and funding interests: None.

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