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Spigelman IV: can intensive cold snaring avoid duodenectomy in familial adenomatous polyposis?Referring to Takeuchi Y et al. p. 515–523
Upper gastrointestinal surveillance is recommended for patients with familial adenomatous polyposis (FAP) who develop multiple duodenal adenomas as well as colonic adenomas. It is more than three decades since the St. Mark’s Hospital group, London published a scoring system for duodenal polyposis in FAP, the “Spigelman classification” . The classification groups patients into stages from 0 to IV based on the number, size, and pathology (villosity and grade of dysplasia) of polyps, including biopsies from the duodenal ampulla and peri-ampullary area. The relevance of this system for assessing risk was demonstrated in a subsequent study where the risk over a 10-year period of duodenal cancer was only 2 %–3 % in patients with initial scores II and III, but reached 36 % at stage IV .
Therefore, when patients who were undergoing upper gastrointestinal surveillance for FAP met the criteria for stage IV, it was recommended that prophylactic pancreaticoduodenectomy be considered , or more recently, pancreas-sparing duodenectomy. These are highly morbid operations for patients who will have typically already have undergone colectomy and ileo-rectal anastomosis, and have an ileo-anal pouch or a permanent ileostomy. Understandably, therefore, groups have attempted to use endoscopic methods to “downstage” patients from Spiegelman IV to lower grades, with the assumption that this would reduce cancer risk. This is not a given outcome, however; Balmforth et al. showed a more rapid redevelopment of polyps after downstaging from stage IV compared with reported rates of primary disease progression . While endoscopic therapy has been successful in reducing polyp numbers using hot snaring or argon plasma coagulation ablation, the complication rates can be significant, with a 13 % bleeding rate and 2 % perforation rate in one recent study of 49 patients, including 11 patients needing admission for complications for a median of 3 days . This has tempered enthusiasm for extensive endoscopic therapy, with current European Society of Gastrointestinal Endoscopy guidelines recommending it be reserved for lesions ≥ 10 mm .
The study by Takeuchi et al. in this issue of Endoscopy is therefore likely to be of interest to clinicians who look after patients with FAP and manage their duodenal disease . This paper presents a follow-on study with 58 patients from their original phase I study that demonstrated the safety and feasibility of using cold snaring to resect multiple duodenal polyps, as many as 50, in a single session. Larger polyps were resected with underwater endoscopic mucosal resection. Critically, the rate of significant complications was very low despite the high resection numbers, with only one grade 3 (severe) Common Terminology Criteria for Adverse Event (CTCAE), an asymptomatic hyperamylasemia. Three patients had melena and two had a hemoglobin drop of 2 g/dL or more, but none required intervention, and were classified CTCAE grade 1 (mild). Overall, 88 % of patients with Spigelman stage IV were downstaged at the follow-up 1 year surveillance and remained stable at subsequent follow-up for a median of 37 months. No cancers developed during the follow-up period.
“There is something of a delicious irony here that by intensively applying our least invasive endoscopic method, cold snaring, we may be able to prevent our most invasive outcome, duodenectomy, for our patients with FAP.”
Can this approach be effectively translated into Western practice? The cold snares used are widely available and the technique for cold snaring is well known from colonic practice. Some features differ from approaches in the West. The patients in the Takeuchi et al. study were admitted for 5 days and were nil by mouth for the first 2 days. This would not be acceptable for many Western healthcare systems; however, the very low rate of complications suggests earlier discharge might be feasible, as is seen in some Western endoscopic submucosal dissection practice. The sedation combinations for a procedure that lasted a median of 33 minutes are also unusual for Western practice, with supplementary dexmedetomidine and haloperidol used. Propofol might be an alternative choice that is widely available. Cap-fitted, forward-viewing scopes were used, both gastroscopes and pediatric colonoscopes. The use of cap-fitted scopes is becoming more common in Western FAP surveillance practice to assist in the visualization of the ampulla without the need for a side-viewing instrument . It certainly seems possible therefore that this Japanese approach could be adapted to Western practice.
However, there is a more fundamental question: does the approach proposed by Takeuchi et al. reduce duodenal cancer risk? While 57 patients included for follow-up represents a reasonably large group for an interventional study in FAP, the follow-up is relatively short and cancer is a rare outcome, and so the study is not powered to answer this question directly; however supportive secondary outcomes that one would expect to see at follow-up if this was effective are demonstrated, including fewer polyps, smaller polyps, and lower rates of high grade dysplasia after extensive cold snare resection. A major issue here is that the duodenal ampulla is not treated. This may be important as in a recent case–control study of FAP patients with duodenal polyposis, almost half the cancers that occurred were ampullary cancers, the majority of which did not have stage IV disease . Furthermore we, and the authors of this study, may be overstaging patients with duodenal FAP by applying modern high definition, cap-fitted endoscopes with advanced endoscopic imaging to a scoring system developed with 1980 s endoscopic technology. It is likely that we are able to detect far more duodenal polyps than Spigelman and colleagues would have been able to in equivalent patients, leading to a higher risk assessment for the same underlying polyp burden with modern equipment.
Nevertheless, the current study demonstrates that intensive cold snaring is safe and leads to a stable downstaging of the Spigelman stage out to 4-year follow-up. One consequence of this might be to ask whether we should be attempting complete polyp clearance earlier in the disease process at lower Spigelman stages to stop patients reaching stage IV, and whether guidelines should be re-evaluated to recommend cold snaring of smaller lesions. This would represent a true paradigm shift to view duodenal polyposis in FAP as a preventable or reversible disease. Recent reports of new chemopreventative approaches, such as once-weekly erlotinib, suggest that use of these treatments may also become an effective and safe strategy to reduce duodenal polyposis , and perhaps in combination with intensive cold snaring endoscopy approaches might lead to profound reductions in polyp burdens.
There is something of a delicious irony here that by intensively applying our least invasive endoscopic method, cold snaring, we may be able to prevent our most invasive outcome, duodenectomy, for our patients with FAP.
Article published online:
09 February 2023
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- 1 Spigelman AD, Williams CB, Talbot IC. et al. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 1989; 2: 783-785
- 2 Groves CJ, Saunders BP, Spigelman AD. et al. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study. Gut 2002; 50: 636-641
- 3 Balmforth DC, Phillips RK, Clark SK. Advanced duodenal disease in familial adenomatous polyposis: how frequently should patients be followed up after successful therapy?. Fam Cancer 2012; 11: 553-557
- 4 Roos VH, Bastiaansen BA, Kallenberg FGJ. et al. Endoscopic management of duodenal adenomas in patients with familial adenomatous polyposis. Gastrointest Endosc 2021; 93: 457-466
- 5 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
- 6 Takeuchi Y, Hamada K, Nakahira H. et al. Efficacy and safety of intensive endoscopic intervention for multiple duodenal adenomas in patients with familial adenomatous polyposis: a prospective cohort study. Endoscopy 2023; 55: 515-523
- 7 Kallenberg FGJ, Bastiaansen BAJ, Dekker E. Cap-assisted forward-viewing endoscopy to visualize the ampulla of Vater and the duodenum in patients with familial adenomatous polyposis. Endoscopy 2017; 49: 181-185
- 8 Thiruvengadam SS, Lopez R, O’Malley M. et al. Spigelman stage IV duodenal polyposis does not precede most duodenal cancer cases in patients with familial adenomatous polyposis. Gastrointest Endosc 2019; 89: 345-354
- 9 Samadder NJ, Foster N, McMurray RP. et al. Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis. Gut 2023; 72: 256-263