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The Turkish Journal of Gastroenterology
Turk J Gastroenterol 2012; 23 (5): 496-502
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Double-balloon endoscopy in patients with Peutz-Jeghers syndrome
Mesut AKARSU, Funda UĐUR KANTAR, Hale AKPINAR
Department of Gastroenterology, Dokuz Eylül University, School of Medicine, Ýzmir
Keywords: Peutz-Jeghers syndrome, double-balloon endoscopy, polypectomy, surveillance.
Summary
Background/aims: Peutz-Jeghers syndrome is a rare hereditary syndrome characterized by mucocutaneous pigmentation and hamartomatous polyps of the gastrointestinal tract, especially in the small intestine. Double-balloon endoscopy is a new endoscopic technique that enables both endoscopic visualization of the entire small bowel and therapeutic interventions in a single procedure. In this study, we evaluate the efficacy and safety of double-balloon endoscopy for both treatment and surveillance of patients with Peutz-Jeghers syndrome. Materials and Methods: We retrospectively evaluated 7 consecutive patients who were referred to Dokuz Eylül University, Gastroenterology Department, with the diagnosis of Peutz-Jeghers syndrome between 2007 and 2010. Results: Patients with Peutz-Jeghers syndrome (M/F: 5/2) underwent a total 31 double-balloon endoscopy procedures: 21 by the oral route, 9 by the anal route, and 1 intraoperatively. All of the patients had a history of laparotomy and small bowel resection due to complications such as invagination and ileus. In 7 patients, we found a total of 110 polyps ≥10 mm in diameter (10-100 mm) and polypectomies were performed in all of them. The only complication was a bleeding after polypectomy, which was controlled by sclerotherapy. In 1 patient, because of the intraabdominal adhesions due to past laparotomies, polypectomy was done by intraoperative endoscopy. In 2 of our patients, we made surveillance colonoscopies, found new polyps in the small intestine, and performed polypectomies. Conclusions: Double-balloon endoscopy is an effective and safe endoscopic technique, and represents a milestone for both treatment and surveillance of patients with Peutz-Jeghers syndrome. Polypectomies made in the small intestine might decrease the complication rate due to these polyps and the need for surgery.
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • Introduction
    Peutz-Jeghers syndrome (PJS) was first described in 1921 by Peutz (1) and in 1940 by Jeghers (2) as a rare syndrome inherited in an autosomal dominant pattern. It is characterized by hamartomatous polyps of the gastrointestinal tract, mucocutaneous hyperpigmentation and intestinal and extraintestinal tumors (1,2). PJS-related polyps occur most frequently in the small intestine. The incidence of polyps in the small intestine is highest in the jejunum and progressively decreases in the ileum and duodenum. These patients may also have polyps in the colon and stomach, with a frequency of 30% and 25%, respectively. Hamartomatous polyps can also develop outside the gastrointestinal tract, such as in the uterus, nasal cavity, bladder, and lungs (3).

    Hyperpigmentation occurs as mucocutaneous macules on the lips, around the mouth, eyes, nostrils, and on the buccal mucosa, and sparsely on the fingers, soles of the feet, palms, anal area, and intestinal mucosa (4). These lesions are caused by pigment-laden macrophages on the dermis. They are evident within the first years of life (often at birth) and increase in size and number over time. Most of the pigmented lesions fade after puberty except for perioral pigmentation, which may persist throughout life. These lesions are flat, blue-grey to brown spots, which are 1-5 mm in size. Malignant degeneration of these lesions is extremely rare (5).

    The diagnosis of PJS is defined by the presence of histopathologically confirmed hamartomatous polyps and at least two of the following clinical criteria: family history, hyperpigmentation and polyps in the small bowel (6). There are many different diagnostic tools to detect these polyps in the gastrointestinal tract, such as small bowel series examination, computed tomography (CT), capsule endoscopy, magnetic resonance (MR)/CT enteroclysis, and MR/CT enterography (7). However, double-balloon endoscopy (DBE), which was introduced in clinical practice in 2001, enables both endoscopic visualization of the entire small bowel and therapeutic interventions in a single procedure. The aim of this study was to evaluate the efficacy and safety of DBE for both treatment and surveillance of patients with PJS.
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • Materials And Methods
    In this study, we retrospectively evaluated 7 consecutive patients (Male/Female: 5/2, mean age:

    29.1 years, range: 20-41) who were referred to Dokuz Eylul University, Gastroenterology Department, with the diagnosis of PJS between 2007 and 2010. Demographics, size and location of polyps, histological evaluation, and follow-up information were recorded. Epidemiological and clinical characteristics of these 7 patients are presented in Table 1. Among these 7 patients, all had a history of laparotomy and small bowel resection due to complications such as invagination and ileus. All of them had hyperpigmentation as mucocutaneous macules on the lips, around the mouth and on the buccal mucosa (Figure 1). None of our patients had extra-gastrointestinal tumor. Two patients had a family history of the disease.

    All DBE procedures were performed by the same endoscopist. DBE was performed by both the anal and oral route for each patient. To confirm the total enteroscopy, we used Indian ink tattooing of the small bowel. No specific preparation was given before oral route, but for the anal approach, bowel cleansing is required as for colonoscopy. Endoscopy was performed under conscious sedation and all patients were monitored for at least two hours at the end of the procedure. Small bowel polyps with a diameter of ≥10 mm were considered to be suitable for polypectomy. We performed polypectomy with a polypectomy snare and removed the excised polyp for histological evaluation. We repeated the DBE procedure until complete removal of all polyps greater than 10 mm, and we scheduled surveillance DBE for two years later. The DBE procedure was repeated earlier if the patient developed symptoms suggestive of small bowel obstruction or due to bleeding. Esophagogastroduodenoscopy and colonoscopy were performed in all patients before DBE, and polyps ≥10 mm in size were also removed endoscopically. Informed consent was obtained from all patients for each procedure. Fujinon EN-450T5 enteroscope was used in all procedures.

    Double-Balloon Endoscopy (DBE) Technique
    The DBE system, which was developed by Yamamoto (8), consists of a 200 cm endoscope within a 145 cm overtube. Both the endoscope and overtube have inflatable balloons at their tips, which can be controlled by an air-pump controller. DBE can be performed orally (antegrade approach) or can be introduced into the terminal ileum through the colon (retrograde approach). In the antegrade approach, the endoscope and overtube are both inserted into the stomach with balloons deflated. When the endoscope enters the second portion of the duodenum, the endoscope balloon is inflated. The overtube is advanced along the endoscope. When the distal end of the overtube reaches the end of the endoscope, the balloon of the overtube is also inflated. With both balloons inflated, gentle withdrawal of the overtube causes pleating of the intestine onto the overtube, which prevents looping of the endoscope. Next, the endoscope balloon is deflated and the endoscope is advanced further while the inflated overtube balloon holds the position within the intestine. When the endoscope cannot go any further, the balloon is inflated. The overtube balloon is then deflated and the overtube is advanced to meet the endoscope. By sequential inflating and deflating the balloons in this manner and alternately advancing and withdrawing the endoscope, the small bowel is gathered and shortened over the endoscope allowing for deep insertion of the small bowel (8,9).
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • Results
    These patients underwent a total of 31 DBE procedures (21 by the oral route and 9 by the anal route and 1 intraoperatively). Complete examination of the small bowel was achieved in all patients. In one patient, because of the intraabdominal adhesions, polypectomy was performed by intraoperative endoscopy.

    In 31 DBE procedures, we found 110 polyps ≥10 mm in diameter (Figure 2a,2b,2c,2d). The number of polyps was highest in the jejunum (n=89) followed by the ileum (n=15) and duodenum (n=6). The maximum size of the polyps was 100 mm in diameter. The only complication was a bleeding after polypectomy, which was controlled by sclerotherapy. The polyps were sent for pathological examination and were found to be hamartomatous polyps characteristic of PJS except for one polyp in the colon having microscopic foci of adenocarcinoma with no stalk invasion. In two of our patients, we made surveillance colonoscopies, found new polyps in the small intestine, and removed them by polypectomies.
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • Discussion
    Peutz-Jeghers syndrome (PJS) is an inherited autosomal disorder with variable inheritance. The prevalence of PJS is 1 in 8300 to 1 in 280000 individuals (4). It is characterized by hamartomatous polyps in the gastrointestinal tract, mostly in the small bowel and pigmented mucocutaneous lesions. Patients with PJS have a four-fold increased risk of gastrointestinal and non-gastrointestinal cancers compared with general populations. The risk of cancer is highest for gastrointestinal cancers occurring in the esophagus, stomach, small intestine, colon, and pancreas (10). In addition to gastrointestinal cancers, extra-intestinal organs at increased cancer risk include the lung, breast, uterus, cervix, ovaries, and testes.

    In PJS, hamartomatous polyps begin growing during the first decade of life, but most patients become symptomatic between the ages of 10 and 30 years. Common presenting symptoms include small bowel intussusception or obstruction (43%) and bleeding or anemia (17%), which cause the patient to undergo repeated operations often involving multiple small bowel resections and anastomoses (11). With the introduction of DBE, the obligation to surgery for management of these lifethreatening comorbidities has been decreased. DBE allows the endoscopist to visit areas of the small bowel that were previously unreachable by older techniques. DBE not only enables endoscopic visualization of the small intestine but also tissue sampling and interventional therapies such as polypectomy, so it can be applied for both treatment and surveillance of this disease (12).

    In all of our cases, endoscopic examination was performed by DBE and complete examination of the small bowel was achieved in all patients. In one of our patients, we used intraoperative DBE (IODBE) since this is the ultimate method in those patients in whom complete DBE investigation is impossible because of adhesions or other technical complications. It is suitable for those cases in which DBE could not be performed or fails to investigate the entire small intestine, especially to prevent excessive bowel resection (13,14).

    Peutz-Jeghers syndrome (PJS)-related polyps occur most frequently in the small intestine. The endoscopic polypectomy procedure performed in the small intestine has some special difficulties. The risk of perforation while working in the small intestine is high due to the thin intestinal wall. Therefore, the endoscopist who performs DBE should be trained not only in endoscopy but also in polypectomy. Another difficulty is removal of the polyps as a whole in order to make histological examination, since these polyps can be very large in size. Getting the enteroscope out of the lumen in order to carry a large polyp outside is very difficult and time-consuming. These polyps can be removed by piece-meal technique. Another solution may be taking biopsies and leaving the resected polyp in the lumen. During DBE, careful attention must be paid not to insufflate too much air in order to avoid intestinal loops, which would impede deep advancement (15). Post-surgical intraabdominal adhesions are another problem that would prevent the free motion of the small intestine within the abdominal cavity, impacting the maximal insertion at DBE. This problem can be solved by IODBE.

    The cancer risk in PJS is very high and comes close to that of other high-risk conditions in which surveillance has been recommended. According to a systematic review by van Lier et al. (16), patients with PJS develop malignancies at an average age of 42 years, and the most common malignancy is colorectal cancer. The relative cancer risks varies between 4.8 and 18 compared with the general population, with lifetime cumulative cancer risks up to 93%. On the basis of these elevated risks, there are some surveillance recommendations in order to detect malignancies in an early phase and to remove polyps that may be premalignant and cause complications (16).

    In addition to DBE, some other new surveillance techniques are becoming widely available, such as video-capsule endoscopy (VCE) and magnetic resonance imaging (MRI) enteroclysis. It has been shown that VCE and/or MRI are good alternatives to small-bowel follow-through for the detection of small bowel polyps, but they do not provide any opportunity for therapeutic intervention (17,18). DBE is clinically useful and safe for surveillance and also for therapy of polyps in PJS. All patients with PJS have to be monitored lifelong because of the risk of malignancy. It is recommended to start small bowel surveillance at the age of 10, with 2-3year intervals because of the morbidities caused by hamartomas (16). Benign complications of the polyps, such as bleeding and intussusception, predominate in the first three decades of life, whereas malignancy-related complications become more common thereafter (19). Although the mechanism of carcinogenesis is unknown, a hamartoma-adenoma-carcinoma sequence has been suggested (20). In order to decrease the risk of malignancy, small bowel polyps, which are potentially precursors of cancer, can be removed endoscopically. In our cases, the histological examination of most polyps revealed hamartomatous polyps, with a malignant transformation in one patient. In two of our patients, we performed second-year small bowel polyp surveillance. There were many polyps in both of our patients, which were removed using DBE.

    In the literature, there are a limited number of studies about the endoscopic treatment of PJS by DBE (Table 2). Ohmiya (21) reported 18 patients with the diagnosis of PJS and evaluated the usefulness of fluoroscopic enteroclysis (FE), DBE and VCE in polyp detection rates. They concluded that VCE is noninvasive and useful for detection of small bowel polyps in PJS, and DBE is safe and useful for polyp resection without laparotomy. Kopácová (22) compared intraoperative endoscopy and DBE for the diagnosis and treatment of PJS, and stated that polypectomy using DBE may obviate the need for repeated urgent operations and small bowel resections leading to short bowel syndrome. The other studies are compatible with each other encouraging the use of DBE in PJS.

    In conclusion, our experience in patients with PJS indicates that DBE represents a milestone for both the treatment and surveillance of these patients. It offers a useful and safe therapeutic option for small bowel polyps even in patients with a history of abdominal surgery. DBE is not only effective for the treatment of polyps, but also has the potential to prevent future complications like obstruction, intussusception, bleeding, and malignancy, thereby decreasing the need for surgery.
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • References
    1. Peutz JLA. Over een zeer merkwaardige, gecombineerde familiaire pollyposis van de sligmliezen van den tractus intestinalis met die van de neuskeelholte en gepaard met eigenaardige pigmentaties van huid-en slijmvliezen (Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied by peculiar pigmentations of skin and mucous membrane; in Dutch). Nederl Maandschr v Geneesk 1921; 10: 134-46.

    2. Jeghers H, McKusick VA, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits. New Engl J Med 1949; 241: 993-1005.

    3. Schreibman IR, Baker M, Amos C, McGarrity TJ. The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol 2005; 100: 476-90.

    4. Kopacova M, Tacheci I, Rejchrt S, Bures J. Peutz-Jeghers syndrome: diagnostic and therapeutic approach. World J Gastroenterol 2009; 15: 5397-408.

    5. Giardiello FM, Trimbath JD. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 2006; 4: 408-15.

    6. Gammon A, Jasperson K, Kohlmann W, Burt RW. Hamartomatous polyposis syndromes. Best Pract Res Clin Gastroenterol 2009; 23: 219-31.

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    8. Yamamoto H, Sekine Y, Sato Y, et al. Total enteroscopy with a nonsurgical steerable double-balloon method. Gastrointest Endosc 2001; 53: 216-20.

    9. Kita H, Yamamoto H. Double-balloon endoscopy for the diagnosis and treatment of small intestinal disease. Best Pract Res Clin Gastroenterol 2006; 20: 179-94.

    10. Hearle N, Schumacher V, Menko FH, et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 2006; 12: 3209-15.

    11. You YN, Wolff BG, Boardman LA, et al. Peutz-Jeghers syndrome: a study of long-term surgical morbidity and causes of mortality. Fam Cancer 2010; 9: 609-16.

    12. Terauchi S, Snowberger N, Demarco D. Double-balloon endoscopy and Peutz-Jeghers syndrome: a new look at an old disease. Proc (Bayl Univ Med Cent) 2006; 19: 335-7.

    13. Kopacova M, Bures J, Vykouril L, et al. Intraoperative enteroscopy: ten years' experience at a single tertiary center. Surg Endosc 2007; 21: 1111-6.

    14. Kopacova M, Rejchrt S, Tacheci I, Bures J. Hyperamylasemia of uncertain significance associated with oral double balloon enteroscopy. Gastrointest Endosc 2007; 66: 1133-8.

    15. Fry LC, Neumann H, Kuester D, et al. Small bowel polyps and tumours: endoscopic detection and treatment by double balloon enteroscopy. Aliment Pharmacol Ther 2008; 29: 135-42.

    16. van Lier MG, Wagner A, Mathus-Vliegen EM, et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol 2010; 105: 1258-64; author reply 1265.

    17. Caspari R, von Falkenhausen M, Krautmacher C, et al. Comparison of capsule endoscopy and magnetic resonance imaging for the detection of polyps of the small intestine in patients with familial adenomatous polyposis or with Peutz-Jeghers’ syndrome. Endoscopy 2004; 36: 1054-9.

    18. Brown G, Fraser C, Schofield G, et al. Video capsule endoscopy in Peutz-Jeghers syndrome: a blinded comparison with barium follow-through for detection of small –bowel polyps. Endoscopy 2006; 38: 385-90.

    19. Utsunomiya J, Gocho H, Miyanaga T, et al. Peutz-Jeghers syndrome: its natural course and management. Johns Hopkins Med J 1975; 136: 71-82.

    20. Gruber SB, Entius MM, Petersen GM, et al. Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome. Cancer Res 1998; 58: 5267-70.

    21. Ohmiya N, Nakamura M, Takenaka H, et al. Management of small-bowel polyps in Peutz-Jeghers syndrome by using enteroclysis, double-balloon enteroscopy, and videocapsule endoscopy Gastrointest Endosc 2010; 72: 1209-16.

    22. Kopácová M, Bures J, Ferko A, et al. Comparison of intraoperative enteroscopy and double-balloon enteroscopy for the diagnosis and treatment of Peutz-Jeghers syndrome. Surg Endosc 2010; 24: 1904-10.

    23. Ohmiya N, Taguchi A, Shirai K, et al. Endoscopic resection of Peutz-Jeghers polyps throughout the small intestine at double-balloon enteroscopy without laparotomy. Gastrointest Endosc 2005; 61: 140-7.

    24. Plum N, May AD, Manner H, Ell C. Peutz-Jeghers syndrome: endoscopic detection and treatment of small bowel polyps by double-balloon enteroscopy. Z Gastroenterol 2007; 45: 1049-55.

    25. Chen TH, Lin WP, Su MY, et al. Balloon-assisted enteroscopy with prophylactic polypectomy for Peutz-Jeghers syndrome: experience in Taiwan. Dig Dis Sci 2011; 56: 1472-5.
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • [ Summary ] [ PDF ] [ Similar Articles ] [ Mail to Author ] [ Mail to Editor ]
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