Device-assisted enteroscopy and the need for surgery in Peutz-Jeghers syndrome: the long and winding road

One of the main goals in managing patients with Peutz-Jeghers syndrome (PJS) is to decrease the burden of small-bowel (SB) polyp-related complications, such as intestinal obstruction and bleeding [1]. Given the need for emergent surgery due to these complications, as seen in historical cohorts, enteroscopy-based preemptive approaches for resection of SB polyps have been promoted over the years, at first by means of intraoperative enteroscopy (IOE) [2], push enteroscopy [3] and, more recently, device-assisted enteroscopy (DAE) [4]. DAE removal of SB polyps larger than 10 to 15 mm is currently recommended by scientific societies [1] [4] [5].

In this issue of Endoscopy International Open, Elfeky et al. [6] retrospectively investigated the outcomes of a DAE-based approach for the prophylactic removal of SB polyps > 10 mm in PJS patients in three expert centers in the United States. Their analysis of 23 patients over 14 years (336 years of aggregated follow-up) showed a noteworthy drop in the laparotomy rate after index DAE, as only two patients underwent surgery after DAE: emergent surgery in one patient for DAE-related perforation and elective surgical removal of a large hamartoma, unreachable by DAE. Conversely, 18 patients (78%) had a positive history of emergent laparotomy for polyp-related complications prior to index DAE. Regarding safety, DAE-related severe adverse events occurred in two of 131 polypectomies (1.5%) over 46 DAE procedures (4%), in line with previous literature results [7] [8].

This well-conducted work by Elfeky and colleagues confirms the evidence gathered in recent years by similar studies regarding the safety profile of DAE and the reduction in surgical rates in both adult and pediatric PJS patients [8] [9] [10] [11] undergoing DAE for preemptive polyp removal. Nevertheless, all the available studies (including the present one from Elfeky et al.) have relevant methodological limitations such as retrospective design, low number of included patients (due to the rarity of the syndrome) and centers and, most importantly, no direct comparison with patients not undergoing DAE.

Furthermore, although the overall results of the different studies are quite consistent in emphasizing the benefit of a DAE-based preemptive approach, there are still some important open unresolved issues, which are relevant when planning a structured and effective prevention program. First of all, current guidelines recommend the interval for SB surveillance based on phenotype [1] [4] [5], whereas it is uncertain whether the strategy of removing most SB polyps by DAE might modify these surveillance intervals, especially when discrepancies (e.g., concerning polyp size, polyp location, histological examination) with other diagnostic procedures are also identified. Second, the size threshold for polyp removal is a matter for discussion: the majority of studies, as in the present paper from Elfeky et al., set the threshold for polyp removal at 10 mm [8], albeit in some other studies only those > 20 mm were resected [12]. Keeping in mind that avoidance of surgery in PJS patients is the mainstay of surveillance protocols, DAE resection of polyps > 15 mm is strongly recommended by current guidelines [4], but even smaller polyps, which do not represent per se a clear indication for DAE, should be resected when encountered during the procedure because their future growth is expected [5].

Notably, there is still uncertainty regarding the best technique for SB polyp resection in patients with PJS because the maneuverability and use of standard devices with a stable position during deep SB intubation may be challenging. On the other hand, ischemic polypectomy with detachable snares or clips seems to be a reasonable option, given its ease of use in even a limited working space [13]. Nevertheless, its efficacy (rate of amputated polyps) and safety profile (risk of delayed bleeding) have to be explored in larger cohorts. Underwater mucosal resection has also proven to be a safe technique for polyp removal in the PJS setting [14] [15]. In patients with PJS, it is crucial before planning a potentially complex and invasive procedure such as DAE to take into account the overall clinical scenario, the total number of polyps observed, their location, and also previous surgical interventions as well as the patient's condition and comorbidities. In fact, DAE requires mastery and specific technical skills because it harbors potentially cumbersome complications, particularly in the therapeutic setting such as SB polypectomy [16] [17]. Patients with PJS are expected to require multiple DAE sessions during their lives, often from both antegrade and retrograde routes because total enteroscopy could be extremely challenging due to intra-abdominal adhesions from previous surgery. Moreover, the non-uniform distribution of DAE equipment and expertise leads to the necessity for treating these patients in tertiary referral high-volume centers to achieve state-of-the-art best practice [7].

Last but not least, definite criteria for choosing between DAE polypectomy and surgery are still lacking. Because there is no standardized polyp size criterion for surgical referral, the decision to proceed with surgery using IOE should be assessed on a case-by-case basis. These evaluations should take into consideration patient characteristics (polyps exceptionally large and difficult to resect or unreachable by DAE), within the framework of a multidisciplinary team. Because patients with PJS have an increased risk of developing malignancies, even outside the gastrointestinal tract [18], the multidisciplinary team should also provide dedicated strategies for multi-organ screening programs, taking into consideration the age-dependent pattern of incidence and the increased risk of mortality [19].

The implementation of DAE-based preemptive strategies for SB polyp-related complications in PJS has changed the natural history of this disease, and the results of the paper by Elfeky et al. add to the available evidence of this trend. Nevertheless, there is a long and winding road ahead because several open issues still need to be addressed, ideally through large prospective, multicenter trials. This is essential for establishing a reliable, timely, and effective protocol for systematic pre-emptive DAE-based polypectomy in PJS patients.

Publication History

Received: 03 October 2023

Accepted: 17 October 2023

Article published online:
30 January 2024

• References

• 1 van Leerdam ME, Roos VH, van Hooft JE. et al. Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2019; 51: 877-895
• 2 Syngal S, Brand RE, Church JM. et al. ACG Clinical Guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015; 110: 223-262 quiz 263
• 3 Pennazio M, Rossini FP. Small bowel polyps in Peutz-Jeghers syndrome: management by combined push enteroscopy and intraoperative enteroscopy. Gastrointest Endosc 2000; 51: 304-308
• 4 Pennazio M, Rondonotti E, Despott EJ. et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy 2023; 55: 58-95
• 5 Yamamoto H, Sakamoto H, Kumagai H. et al. clinical guidelines for diagnosis and management of Peutz-Jeghers syndrome in children and adults. Digestion 2023; 104: 335-347
• 6 Elfeky O, Panjwani S, Cave D. et al. Device-assisted enteroscopy in the surveillance of intestinal hamartomas in Peutz-Jeghers syndrome. Endosc Int Open 2023; 11: 128-134
• 7 Pennazio M, Venezia L, Cortegoso Valdivia P. et al. Device-assisted enteroscopy: An update on techniques, clinical indications and safety. Dig Liver Dis 2019; 51: 934-943
• 8 Cortegoso Valdivia P, Rondonotti E. et al. Safety and efficacy of an enteroscopy-based approach in reducing the polyp burden in patients with Peutz-Jeghers syndrome: experience from a tertiary referral center. Ther Adv Gastrointest Endosc 2020; 13
• 9 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: 1209-1216
• 10 Sakamoto H, Yamamoto H, Hayashi Y. et al. Nonsurgical management of small-bowel polyps in Peutz-Jeghers syndrome with extensive polypectomy by using double-balloon endoscopy. Gastrointest Endosc 2011; 74: 328-333
• 11 Wang YX, Bian DJ, Zhu HY. et al. The role of double-balloon enteroscopy in reducing the maximum size of polyps in patients with Peutz-Jeghers syndrome: 12-year experience. J Dig Dis 2019; 20: 415-420
• 12 Kröner PT, Sancar A, Fry LC. et al. Endoscopic mucosal resection of jejunal polyps using double-balloon enteroscopy. GE Port J Gastroenterol 2015; 22: 137-142
• 13 Khurelbaatar T, Sakamoto H, Yano T. et al. Endoscopic ischemic polypectomy for small-bowel polyps in patients with Peutz-Jeghers syndrome. Endoscopy 2021; 53: 744-748
• 14 Pennazio M, Venezia L, Gambella A. et al. Underwater endoscopic mucosal resection of a large jejunal polyp by single-balloon enteroscopy in a patient with Peutz-Jeghers syndrome. Dig Liver Dis 2019; 51: 170-172
• 15 Suwa T, Imai K, Hotta K. et al. Underwater ischemic polypectomy for multiple small bowel polyps in a patient with Peutz-Jeghers syndrome. Am J Gastroenterol 2021; 116: 452
• 16 Rondonotti E, Spada C, Adler S. et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review. Endoscopy 2018; 50: 423-446
• 17 Yamamoto H, Despott EJ, González-Suárez B. et al. The evolving role of device-assisted enteroscopy: The state of the art as of August 2023. Best Pract Res Clin Gastroenterol 2023; (Suppl. 03) 64-65
• 18 Wagner A, Aretz S, Auranen A. et al. The management of Peutz–Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline. J Clin Med 2021; 10: 473
• 19 van Lier MGF, Westerman AM, Wagner A. et al. High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome. Gut 2011; 60: 141-147