Radiol Oncol 2024; 58(2): 153-169. doi: 10.2478/raon-2024-0029 153 review Endoscopic management of patients with familial adenomatous polyposis after prophylactic colectomy or restorative proctocolectomy – systematic review of the literature Aleksandar Gavric1, Liseth Rivero Sanchez2,3,4, Angelo Brunori2,3,4, Raquel Bravo3,4,5, Francesc Balaguer2,3,4, Maria Pellisé2,3,4 1 Department of Gastroenterology and Hepatology, University Medical Centre Ljubljana, Slovenia 2 Department of Gastroenterology, Hospital Clinic de Barcelona, Barcelona, Spain 3 Institut d’Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain 4 Center for Biomedical Research in the Hepatic and Digestive Diseases Network (CIBERehd), Barcelona, Spain 5 Surgery Department, Hospital Clinic de Barcelona, Barcelona, Spain Radiol Oncol 2024; 58(2): 153-169. Received 6 March 2024 Accepted 16 April 2024 Correspondence to: Maria Pellisé, M.D., Ph.D., Department of Gastroenterology Hospital Clinic de Barcelona. Institut d’Investigacions Biomediques August Pi I Sunyer (IDIBAPS). Hospital Clinic of Barcelona. Centro de Investigación Biomédica en Red de EnfermedadesHepáticas y Digestivas (CIBERehd). Universitat de Barcelona, Barcelona, Spain. E-mail: mpellise@clinic.cat Disclosure: Maria Pellise: consultant fees from Olympus and Fujifilm, speaker fees from Norgine, Mayoli and Casen recordati. Francesc Balaguer: consultant fees from Olympus, Nouscom and Norgine, editorial fees from Elsevier, endoscopic equipment on loan of FujiFilm and Olympus, research grant from FujiFilm, ZiuZ and Casen recordati, consultancy for FujiFilm, Olympus, and speakers’ fee from Olympus, Fujifilm, Norgine, IPSEN. This is an open access article distributed under the terms of the CC-BY license (https://creativecommons.org/licenses/by/4.0/). Background. Patients with familial adenomatous polyposis (FAP) develop early colorectal adenomas and if left untreated, progression to cancer is an inevitable event. Prophylactic surgery does not prevent further development of cancer in the rectal remnant, rectal cuff in patients with ileal pouch anal anastomosis (IPAA) and even on the ileal mucosa of the pouch body. The aim of this review is to assess long-term rates of cancer and adenoma development in patients with FAP after prophylactic surgery and to summarise current recommendations for endoscopic manage- ment and surveillance of these patients. Materials and methods. A systematic literature search of studies from January 1946 through to June 2023 was conducted using the PRISMA checklist. The electronic database PubMed was searched. Results. Fifty-four papers involving 5010 patients were reviewed. Cancer rate in the rectal remnant was 8.8–16.7% in the western population and 37% in the eastern population. The cumulative risk of cancer 30 years after surgery was 24%. Mortality due to cancer in the rectal remnant is 1.1–11.1% with a 5-year survival rate of 55%. The adenoma rate after primary IPAA was 9.4–85% with a cumulative risk of 85% 20 years after surgery and a cumulative risk of 12% for advanced adenomas 10 years after surgery. Cumulative risk for adenomas after ileorectal anastomosis (IRA) was 85% after 5 and 100% after 10 years. Adenomas developed more frequently after stapled (33.9–57%) compared to hand- sewn (0–33%) anastomosis. We identified reports of 45 cancers in patients after IPAA of which 30 were in the pouch body and 15 in the rectal cuff or at the anastomosis. Conclusions. There was a significant incidence of cancer and adenomas in the rectal remnant and ileal pouch of FAP patients during the long-term follow-up. Regular endoscopic surveillance is recommended, not only in IRA pa- tients, but also in pouch patients after proctocolectomy. Key words: familial adenomatous polyposis; ileorectal anastomosis; ileal pouch-anal anastomosis Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis154 Introduction Familial adenomatous polyposis (FAP) is an au- tosomal dominant inherited disease caused by pathogenic variants in the adenomatous polyposis coli (APC) gene1 with reported incidence of one in 8,000 to 12,000 live births.2 The main hallmark of the disease is the presence of multiple colorectal adenomas, leading to a 100% lifetime risk of de- veloping cancer if the colon remains in situ.3 To prevent the development of cancer, prophylactic colectomy or proctocolectomy is performed when the adenoma burden cannot be managed endo- scopically or at the age of 18–25 years old. The fol- lowing types of surgery are available4: total colec- tomy with ileorectal anastomosis (IRA) or ileosig- moid anastomosis (ISA); proctocolectomy with/ without mucosectomy and stapled ileal pouch- anal anastomosis (IPAA) or hand-sewn IPAA; and total proctocolectomy with end ileostomy. Until restorative proctocolectomy with IPAA and pouch reconstruction was described in the 1970s, colectomy with IRA or end ileostomy was the only surgical prophylactic procedure available and was associated to a considerable high CRC incidence and mortality.5 After this, proctocolectomy with pouch reconstruction (IPAA) was the technique of choice in patients with a high adenoma bur- den and was sought to eliminate the risk of CRC in FAP patients. However, since the first report of pouch cancer in 19946, there has been a substantial increase in published literature reporting rates of adenoma and cancer development after primary IPAA. The development of adenomas along life in remnant rectal mucosa is a natural phenomenon in this population. Long live periodical surveil- lance with rectoscopies is widely recommended in international guidelines as shown in Table 1.4,7-10 As there are no randomised trials comparing en- doscopic surveillance and management strategies for FAP patients with IRA and IPAA, we aimed to systematically evaluate adenoma and cancer de- velopment after prophylactic surgery, define po- tential risk factors and to summarise endoscopic practices from published series. Materials and methods Our review is reported according to the PRISMA guidelines.11 Search strategy We searched PUBMED from inception to June 2023 to identify studies evaluating long-term ad- enoma and cancer development in patients with FAP after prophylactic surgery. Deduplication was performed using Zotero software.12 Reference lists of included studies were hand-searched for ad- ditional relevant studies. The search was limited to studies, published in English. We used the fol- lowing keywords: “FAP”, “IRA”, “IPAA”, “familial adenomatous polyposis” and “proctocolectomy”. Inclusion criteria We included single-or multicentre retrospective cohort studies, prospective cohort studies and ret- rospective analyses of polyposis registries. Due to TABLE 1. Summary of recommendations from the international guidelines First author and publication date (ref.) Endoscopic surveillance – patients with IRA Indications for secondary proctectomy patients with IRA Endoscopic surveillance – patients with IPAA Vasen et al., 20087 Every 3 to 6 months Multiple large adenomas (> 5 mm) Adenomas with dysplasia Every 6 to 12 months Balmaña et al., 2013, ESMO8 Every 12 months No recommendations Every 12 months Stoffel et al., 2015, ASCO9 Every 6 to 12 months No recommendations Every 6 months to 5 years (Intervals should be determined on a case-by- case basis and may be even shorter than 1 year for some individuals) Sygnal et al., 2015, ACG10 Every 12 months No recommendations Every 12 months Herzig et al., 2017, ASCRS4 Every 12 months No recommendations Every 12 months Van Leerdam ME et al., 2019, ESGE53 Every 12 to 24 months No recommendations Every 12 to 24 months Yang J et al., 2020, ASGE54 6 months after surgery with 6 to 12 months further surveillance interval 12 months after surgery with 12 to 24 months further surveillance interval. 6 months if advance adenoma ACG = American College of Gastroenterology; ASCO = American Society of Clinical Oncology; ASCRS = American Society of Colon and Rectal Surgeons; ASGE = American Society for Gastrointestinal Endoscopy; ESGE = European Society of Gastrointestinal Endoscopy; ESMO = European Society for Medical Oncology; IPAA = ileal pouch anal anastomosis; IRA = ileorectal anastomosis Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis 155 the rarity of the events, we only considered case re- ports for inclusion when summarising reports on cancers after primary IPAA. Only the most recent series from the same institution or polyposis regis- try were included in the analysis, as some research groups regularly publish retrospective analyses of their cohorts or polyposis registries. Full-text screening and data extraction were performed by a single researcher (AG). Manuscripts of three case reports could not be obtained, data were summa- rised from the two review articles.13,14 Results Studies identified Of 97 full-text articles screened for eligibility (Figure 1), 46 met our inclusion criteria. A further 8 articles were identified by hand searching the reference lists of the included studies (6 case re- ports, 1 retrospective cohort, 1 polyposis registry analysis). We included 22 retrospective analyses, 14 case reports (carcinoma development after primary IPAA), 15 retrospective analyses of prospectively Additional records identified through hand searches of reference lists of included studies (n = 8) Database search: - PubMed Total records identified (n = 1343) Duplicates removed (n = 493) Titles and abstract screened (n = 862) Records excluded (n = 766) Full-text articles excluded (n = 44) Ineligible study type 22 Older case series 18 Case report 3 Not English 1 Studies included (n = 54) Full-text articles assessed for inclusion (n = 97 ) FIGURE 1. Flowchart of the systematic review according to the Preferred Reporting Items for Systematic Reviews (PRISMA) schema. Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis156 maintained polyposis registries and 3 prospective cohort studies. Only 5 studies were multicentre and 1 was bi-centre. The studies were published between 1994 and 2023. The studies included be- tween 1 and 925 patients. A total of 5010 patients were included in the review. Summary character- istics of the included studies are shown in Table 2. Total colectomy with ileorectal anastomosis Adenomas Five studies described the rate of adenoma devel- opment in the residual rectum (Supplementary Table 1). In 8 studies that analysed the frequency of secondary proctectomy due to endoscopically unmanageable polyposis, the rate of proctectomy ranged from 3.7% to 35%.15 Five studies described adenoma evaluated in the neoterminal ileum (Table 3), with a high variance in reported rates from 0%16 to 47.6% in patients followed-up for me- dian of > 20 years17 in one study including a paedi- atric cohort18, 2 patients required resection of the terminal ileum and construction of a new IRA, one due to low grade dysplasia (LGD) and one due to high grade dysplasia (HGD) adenoma. Rectal cancer The reported rate of cancer in the rectal remnant (Table 4) after primary IRA is 8.8%18 to 16.7%19 with a median follow-up from surgery19 of 91.1 months (3–557 months). However, studies from Japan re- port higher rates of up to 37%20, but this is due to the inclusion of in situ carcinoma in the cancer defi- nition. The same study had the longest median follow-up of 21.1 years (3–35). On the other hand, a small cohort of 21 patients from France reported zero cases of cancer during a median follow-up of 8.4 years. Jenner et al.21 only included patients with a confirmed mutation. Five studies reported a cu- mulative incidence of rectal cancer ranging from 3%22 to 17.2%19 at 5 years, 7.7%23 to 24.1%19 at 10 years, 11%22 to 23%23 at 20 years, and 24%22 at 30 years af- ter the primary IRA. In one of the largest studies24, which analysed data from 4 national registries and 776 patients, the 10-year cumulative risk of residual rectal cancer was 4.4% (95% CI, 2.6–6.2) for patients who underwent surgery before 1990 and only 2.5% (0–5.5) after the 1990. Only one study reported the time from surgery to cancer diagnosis (median 102 months [1–26 years])23; other studies reported follow-up time from surgery, but did not clearly de- fine when follow-up started nor the surveillance re- gime. Five studies reported mortality ranging from 1.6%23 to 11.1%20 in which 3 out of 27 patients died from cancer in the rectal remnant. Only one of two studies that examined long-term survival after di- agnosis of residual rectal cancer reported a 5-year survival rate of 55%.22 In a study from Japan, 5-year survival was 94%25, but the excellent survival was explained by the inclusion of carcinoma in situ de- spite the exact proportion of these was not given. Risk factors for progressive phenotype of rectal remnant Eleven studies reported nine risk factors predic- tive of the progressive rectal residual phenotype (Supplementary Table 2). Four studies analysed the genotype-phenotype relationship; The presence of a pathogenic variant between codons 1250–1464 was an independent risk factor for subsequent cancer development (HR 4.4 [1.3–15.0]23 and for the secondary proctectomy26,27 (HR 3.91 [1.45–10.51], P = 0.007). In a small study of 25 patients, all patients (n = 3) with carpeting rectal remnant polyposis had a pathogenic variant in codon 1309, but this was only descriptive data.28 An aggressive colonic phenotype with at least 500 polyps at time for sur- gery was identified as a risk factor in three stud- ies (Supplementary Table 2). Two studies15,25 have identified > 20 rectal remnant polyps at the time of surgery or during the endoscopic surveillance26 as an independent risk factor for secondary proc- tectomy (HR 30.99 [9.57–100.32] P < 0.001), while in one study a cut-off of > 10 rectal adenomas28 was associated with a more aggressive phenotype, as these patients developed a mean of 9.29 rectal re- sidual adenomas per patient per year compared with 0.67 adenomas per patient per year if they had < 5 rectal polyps at the time of surgery. Other potential risk factors included patient age at diag- nosis of rectal residual cancer, time since surgery, presence of congenital hypertrophy of the retinal pigment epithelium, and presence of colon cancer at the time of primary surgery. APC site mutation, preoperative colon phenotype, presence of duo- denal adenomas and rectal remnant phenotype on surveillance were not identified as risk factors for progressive rectal remnant disease phenotype only in one study.20 Proctocolectomy with ileal-pouch anal anastomosis Adenomas Seventeen studies (Table 5) reported on the devel- opment of adenomas after IPAA, of which eight studies differentiated between the pouch body Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis 157 TABLE 2. Characteristics of included studies First author and publication date (ref.) No. of patients Country Setting Study design Surgery performed (period) Study population Aelvoet et al., 202355 144 (111 IPAA, 33 ileostomy) The Netherlands Single Cohort/ Retrospective / IPAA, ileostomy Tatsuta et al., 202356 65 (22 IRA, 20 IPAA) Japan Single Cohort/ Retrospective 1976–2022 IRA, IPAA Anele et al., 202257 199 (199 IRA) United Kingdom Single Cohort/Retrospective 1990–2017 IRA Colletti et al., 202258 715 (715 IRA) Italy Multicentre Retrospective analysis of the Registry 1977–2021 IRA Pasquer et al., 202159 289 (197 IRA, 92 IPAA) France Multicentre Retrospective analysis of the Registry 1965–2015 IRA, IPAA Ardoino et al., 202060 925 (585 IRA, 340 IPAA) Italy Multicenter Retrospective analysis of the Registry 1947–2015 IRA, IPAA Tajika et al., 201916 47 (14 IRA, 25 IPAA, 8 ileostomy) Japan Single Cohort/Retrospective 1965–2017 IRA, IPAA and ileostomy Ganschow et al., 201861 192 Germany Singe Cohort/ Prospective and retrospective analysis of Polyposis Registry Endoscopy data collected during 2010– 2013 IPAA Kariv et al., 201762 45 Israel Single Cohort/Retrospective 1986–2013 IPAA Patel et al., 201642 21 (6 IRA, 5 IPAA, 10 intact colon) Indianapolis, USA Single Cohort/ Retrospective Endoscopies performed between 2004– 2016 IRA, IPAA and intact colon Walsh et al., 201663 1 Ireland Single Case report 1987 IPAA - cancer Maehata et al., 201520 27 Japan Single Cohort/Retrospective 1990–2004 IRA Ganschow et al., 201550 100; 50 hand- sewn and 50 stapled anastomoses Germany Single Cohort/Prospective ? Hand-sewn vs. stapled anastomosis Goldstein et al., 201563 59 Israel Single Cohort/Retrospective 1986–2013 IPAA Zahid et al., 201564 27 Australia Single Cohort/Retrospective 1984–2011 IPAA Kennedy et al., 201465 95; 85 hand- sewn and 1 stapled anastomosis Rochester, Mayo Clinic, USA Single Cohort/Retrospective 1987–2011 IPAA Koskenvuo et al., 201322 140 Finland Single Cohort/Retrospective 1963–2012 IRA Pommaret et al., 201335 118 France Single Cohort/Retrospective / IPAA and IRA Boostrom et al., 201366 117 Rochester, Mayo Clinic, USA Single Cohort/Retrospective 1972–2007 IPAA Ozdemir et al., 201337 260; 86 hand- sewn and 175 stapled anastomoses Cleveland, USA Single Analysis of polyposis registry 1983–2010 Hand-sewn vs. stapled anastomosis Wasmuth et al., 201367 61; 39 hand- sewn with mucosectomy and 22 without of which 15 were stapled and 7 hand-sewn anastomoses Norway Multicenter Analysis of polyposis registry 1986–2008 IPAA (mucosectomy vs. no- mucosectomy) Yan et al., 201268 42 (33 IPAA; 6 IRA ?) China Single Cohort/ Retrospective 1988–2008 IPAA and IRA Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis158 First author and publication date (ref.) No. of patients Country Setting Study design Surgery performed (period) Study population Makni et al., 201269 1 Tunisia Single Case report 1996 IPAA - cancer Tonelli et al., 201251 69 Italy Single Cohort/ Prospective data collection 1984–2008 IPAA von Roon et al., 201170 140; 44 hand- sewn and 76 stapled anastomoses UK Single Retrospective analysis of St. Mark’s Hospital Polyposis Registry 1978–2007 Hand-sewn vs. stapled anastomosis Banasiewicz et al., 201132 165 Poland Bicenter Bicenter/ Retrospective analysis 1985–2009 operated, Clinical data from endoscopy FUP between 2004–2009 IPAA Booij et al., 201018 43 (34 IRA) The Netherlands Single Cohort/Retrospective 1977–2005 IRA and IPAA Sinha et al., 201026 427 UK Single Retrospective analysis of St. Mark’s Hospital Polyposis Registry 1990–2008 IRA Ault et al., 200971 2 Los Angeles, USA Single Case series 1990, 1993 IPAA - cancer Nieuwenhuis et al., 200927 475 Denmark, Finland, Sweden, Netherlands Multicenter Analysis of polyposis registry / IRA Yamaguchi et al., 200925 59 Japan Single Cohort/ Retrospective 1962–2007 IRA Friederich et al., 200831 212; 71 hand- sewn with mucosectomy and 115 stapled anastomoses The Netherlands Single Analysis of National Polyposis Registry 1985–2005 IPAA Campos et al., 200819 36 Brasil Single Cohort/Retrospective 1977–2006 IRA and IPAA Bullow et al., 200824 776; 576 operated in pre-pouch period and 200 in pouch period starting in 1990 Denmark, Finland, Sweden, Netherlands Multicenter Analysis of polyposis registry 1950–2006 IRA Gleeson et al., 200830 16 Rochester, Mayo Clinic, USA Single Cohort/ Retrospective analysis 1964–2003 (Analysis of endoscopies between 1992– 2006) IPAA and IRA Lee et al., 200872 1 Korea Single Case report 1998 IPAA - cancer Linehan et al., 200773 1 Ireland Single Case report 1997 IPAA - cancer Valanzano et al., 200728 25 Italy Single Cohort/ Prospective 1986–2004 IRA Moussata et al., 200717 21 France Single Cohort/Retrospective / IPAA and IRA Ulas et al., 200674 1 Turkey Single Case report 1993 IPAA - cancer Campos et al., 200519 1 Brazil Single Case report / IPAA - cancer Groves et al., 200534 60 UK Single Retrospective analysis of St. Mark’s Hospital Polyposis Registry / IPAA Vroueraets et al., 200475 2 The Netherlands Single Case report 1990, 1991 IPAA – cancer Ooi et al., 200336 2 Cleveland, USA Single Case report / IPAA – cancer Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis 159 and the anastomosis, one study only reported the anastomotic adenoma rate, while in the remaining seven studies the authors did not precisely define the anatomical location of the adenomas. The me- dian age of patients at the time of surgery ranged from 15.4 to 34.6 years, with a median follow-up from surgery of 5.4 years to a median of 21.6 years. The reported rate of adenoma in the pouch body ranged from 9.4%29 to 76.9%.30 The proportion of HGD histology among adenomas at the polyp lev- el ranged from 5.9% 17 to 53.2%.31 In one study, the proportion of advanced adenomas on a per-patient basis was 11.2%.31 The cumulative risk of adenoma development after primary IPAA was 12% and 58% at 5 and 20 years after the surgery respective- ly.16 According to the analysis from Poland32, 50% of all patients would develop LGD 15 years after the surgery, while HGD is estimated to be present in half of the patients 17.5 years after the surgery. Six studies analysed the rate of adenoma develop- ment in the neo terminal ileum, the proportion of patients with histologically confirmed adenoma varied from 4.2%33 to 23.1%30 with at a median fol- low-up from surgery of 6.534 to 23.1 years.16 The cu- mulative risk of developing an adenoma in the neo terminal ileum was 4.4% at 20 years and increased to 36% at 30 years after the surgery as reported in the same study. The presence of pouch body ad- enomas was the only independent risk factor for the neo terminal ileum adenomas (OR, 2.16, P = 0.007).35 Cancer Since the first case report of cancer arising in the ileal pouch of a FAP patient in 19946, we have iden- tified 45 (Table 6) cancers that have developed in FAP patients after primary IPAA. Of these, 30 were located in the pouch body and 15 in the anasto- mosis/rectal cuff. The time from surgery to cancer diagnosis was reported for 22 patients and ranged from 2.336 to 33 years.37 The information about the interval since last follow-up was reported for only 15 patients. The shortest interval between normal endoscopic surveillance and cancer diagnosis was 9 months.16 Of the studies that reported the final outcome, 13 (28.9%) patients were alive at the last follow-up (range 8 months to 6 years) after surgical therapy and 9 patients died of disseminated cancer (1 month to 4 years after diagnosis), most despite an initial R0 resection. Hand-sewn vs. stapled IPAA Six studies (Supplementary Table 3) compared the rates of adenoma development at the anastomosis between hand-sewn and stapled techniques. The incidence of adenoma was lower for hand-sewn First author and publication date (ref.) No. of patients Country Setting Study design Surgery performed (period) Study population Church et al., 200338 197; 62 operated in pre-pouch period and 135 in pouch period starting in 1983 Cleveland, USA Single Analysis of polyposis registry 1950–1999 IRA Cherki et al., 200376 1 France Single Case report / IPAA - cancer Thompson-Fawcett et al., 200177 33 Canada Single Cohort/ Prospective / IPAA Church et al., 200115 213 (165 IRA) Cleveland, USA Single Analysis of polyposis registry / IRA and IPAA Brown et al., 200178 1 Singapore Single Case report / IPAA - cancer Bertario et al., 200023 371 Italy Multicenter Retrospective analysis of Hereditary tumor registry 1955–1997 IRA Vuilleumier et al., 200079 1 UK Single Case report 1990 IPAA - cancer Jenner et al., 199821 55 Australia Single Analysis of polyposis registry ?–1994 IRA Bassuini et al., 199680 1 UK Single Case report 1991 IPAA - cancer Hoehner et al., 19946 1 Iowa, USA Single Case report / IPAA - cancer FUP = follow up; IPAA = ileal pouch anal anastomosis; IRA = ileorectal anastomosis Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis160 anastomosis, ranging from 0 to 33%, and for sta- pled anastomosis, ranging from 33.9 to 57%. The 10-year cumulative risk of adenoma development is 20–22.6% for hand-sewn anastomosis and 51.1– 64% for stapled anastomosis. Risk factors for adenoma development after primary IPAA Nine studies analysed risk factors for adenoma development (Supplementary Table 4). None of the seven studies found a genotype-phenotype asso- ciation. There was no association between colon adenoma burden at the time of surgery and sub- sequent development of pouch adenomas in three out of four studies. In the only positive study, none of the patients with < 200 colon polyps developed pouch adenomas, whereas almost half of the pa- tients with > 1000 colon polyps later developed lat- er pouch adenomas. Three studies have identified age of the pouch as a risk factor, while three others found no association between time since surgery and the rate of pouch adenomas. An association between the Spigelman score and the develop- ment of pouch adenomas was not confirmed. One study identified the presence of gastric adenomas as an independent risk factor for the development of pouch adenomas. Discussion Using a systematic approach, we identified a wide range of reported adenoma and cancer rates in the rectal remnant, pouch body, at IPAA and in the neoterminal ileum. The wide range in adenoma rates is probably partly due to the wide range of included studies in terms of year of publication. The equipment and quality of optical diagnosis has improved considerably in recent years, allow- ing better detection of adenomas and more precise examination of the pouch and rectal remnants. In addition, the risk stratification of patients at the time of surgery has also improved, allowing pa- tients with a more aggressive phenotype to un- TABLE 3. Rate of adenoma development in the neoterminal ileum in patients after ileorectal anastomosis (IRA) and ileal pouch anal anastomosis (IPAA) First author and publication date (ref.) Adenomas in the neoterminal ileum – after primary IPAA; n (%) Cumulative risk for development of neoterminal adenomas Years since surgery Risk factor for adenomas in neoterminal ileum Rate of adenomas in the neoterminal ileum – after primary IRA; n (%) Years since surgery Tajika et al., 201916 4/24 (16.7) 4.4% at 20 years and 36% at 30 years after primary surgery 23.1 ± 5.8 0/14 (0.0) Boostrom et al., 201366 4/33 polyps (12.0) Pommaretet et al., 201335 9/118 (6.5) Presence of pouch adenomas (OR, 2.16, P = 0.007) Booij et al., 201018 5/34 (14.7) 2 patients had resection of neo-terminal ileum, one due to LGD and other due to HGD adenoma. Gleeson et al., 200830 3/13 (23.1) Median 6.5 (0–15) 4/16 (25.0) Median 12 (1–29) Moussata et al., 200717 Mean 17.6 +-7.8(6–35) Mean from colectomy to diagnosis: 16.4+-8.5 (5–30) 10/21 (47.6) of which 2 were advanced adenomas. Groves et al., 200534 2/20 (10.0) 6 (1–14) 1/47 (2.0%) 12 (0–39) Thompson-Fawcett et al., 200177 1/24 (4.2) Median 7 (1–19) HGD = high grade dysplasia; LGD = low grade dysplasia Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis 161 dergo primary restorative proctocolectomy while primary IRA can still be offered to patients with an attenuated phenotype or low rectal disease bur- den. Indeed, in the largest study of four European national polyposis registries, the cumulative risk of cancer in the rectal remnant (CRR) was 10% in patients operated in the ‘pre-pouch’ period and only 2% in those who were operated in the ‘pouch period.24 Similar findings have been reported from the USA38 where 8 patients operated before TABLE 4. Patient characteristics and rate of rectal remnant cancer rate in patients after ileorectal anastomosis (IRA) First author and publication date Proportion of man; n / (%) APC mutation Underwent n/ (%); Positive in; n/(%) Follow-up (years/ months) since surgery Years since surgery to cancer diagnosis Age at surgery Age at cancer diagnosis Rectal remnant cancer rate; n/ (%) Cumulative risk for rectal cancer Rectal cancer mortality Colletti et al., 202258 57.4% 93.6% / / Median of 13 years / / 47 / 715 (6.57) / 14/47 (29.8%) at median follow up of 13 years. Pasquer et al., 202159 95 (48.2) / / / / / 12 / (6.1); 1 was metastatic, 2 were resected endoscopically, 10 surgically / / Maehata et al., 201520 16 (59.3) 21 (77.8) 14 (66.7) 21.1 (3–35) / Median 27 years (9–66) / 10/27 (37.0); 6/10 cancers were TisN0M0 8% at 10 years; 19% at 20 years; 57% at 30 years 3/27 (11.1) Koskenvuo et al., 201322 59 (42.1) / Median 15 years (0–44) / Mean 36 years (18–71) Cumulative risk 2% at 40 years age; 7% at 50; 13% at 60 years age and 16 % at 70 years age. 18/140 (13%) 3% at 5 years; 4% at 10 years; 11% at 20 years; 24% at 30 years after IRA 10/140 (7%); 5-year survival 55%. Cumulative risk for death due to rectal cancer after IRA: 2% at 5 years, 3% at 10 years and 9% at 30 years. Booij et al., 201018 19 (44.2) / / / Median 16 (7–25) / 3/34 (8.8) / 2/34 (5.8) Sinha et al., 201026 232 (54.3) /311/427 (72.8) Median 15 years (7–25) / Median 21 years (11–67) / 48/427 (11.2%) / / Yamaguchi et al., 200925 35 (59.3) / Median 8.9 years / Median 30 years (13–65) / 17/59 (30%) / 5-year survival 94%; 10-year survival 94%. Nieuwenhuis et al., 200927 / / / / / / / 3.7% for group 1; 9.3% for group 2; 8.3% for group 3.% / Campos et al., 200819 / / 91.1 (3–557) / Mean 45.8 years Mean 50.6 years 6/36 (16.7) 17.2% at 5 years; 24.1% at 10 years; 43.1% after 15 years / Gleeson et al., 200830 / / FUP initiated median 12 (1–29) years after surgery / / 40 and 59 years. 2/16 (12.5) / / Bullow et al., 200824 401 (51.7) / Median 7 years (0–13). Patients were operated between 1950–2006 Median 27 (7–75) / 60/776 (7.7%) (56/576; 10% and 4/200; 2%) 10-year cumulative risk 4.4% [95% CI 2.6–6.2] in pre- pouch era; 10-year cumulative risk 2.5% [95% CI 0–5.5] in pouch era; / Moussata et al., 200717 They only watched ileal muocas above the IRA 10 (47.6) 21/21 (100.0) 14/21 (66.7) Mean 8.4 years ± 5 since colectomy / / / 0/21 (0.0) / / Church et al., 200338 92 / (46.7) / Pre-pouch era: 212 months (IQR 148 months); Pouch era: 60 months (IQR 80 months) / Median age 23 years (IQR 15.5 years pre-pouch and 17 years pouch) / 8 (12.9%) in the pre-pouch era and 0 in pouch era. / / Bertario et al., 200023 206/371 (55.5) 297/371 (80.1) 200/297 (67.3) Median 81 months Median 102 months (1–26 years) Mean 32 years / 27/371 (7.3) 10 years – 7.7% 15 years – 13.1 % 20 years – 23.0% 6/371 (1.6) Jenner et al., 199821 25/55 (45.0) 55/ (100.0) Median 10(1–31) / Mean age 30 (13–62) Median 41 7/55 (12.7) / / Colonic phenotype divided in 3 groups: (Group 1 - <100 polyps and mutation in codons 1–157, 312–412 and 1596–2843; Group 2 Hundred of polyps and mutation in codons 158–311, 413–1249 and 1465–1595; Group 3 Thousand of polyps and mutation in codon 125 APC = adenomatous polyposis coli; FUP = follow up Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis162 TABLE 5. Patient characteristics and rate of adenomas in patients after primary ileal pouch anal anastomosis (IPAA) First author and publication date Sex (man); n (%) APC mutation Underwent; n (%); Positive in; n (%) Distinguish between pouch body and rectal cuff Follow-up (months/years) Time from surgery to first adenomas (years) Age at surgery (years) Rate of adenomas (≥ 1 polyp) Size of adenomas, mm Histology of adenomas; n (%) Number of Adenomas Aelvoet AS et al., 202355 81 (56) 101 (91) 96 (86) Yes Median 152 (77–240) 15% at 5 years; 48% at 10 years; 85% at 20 years. Median 24 (18–32) Median 5 (3–15) Tubular adenomas 31 (28%), Tubulovillous 26 (23%), Villous 5 (5%) Prepouch ileum 4(2–13), Pouch body 20 (5–50), rectal cuff 6 (3–10) Tajika et al., 201926 16 (47.1) / Yes Median 21.6 (3.7–8.8) 32 (35.9) of patients showed progression of pouch adenomas during FUP Median 34.6 (17–52) 24/34 (70.6) 2–40 mm 6 advanced adenomas (25.0) 1–300 Ganschow et al., 201861 100 (52.1) 133 (69.3)) ? / 133 No Median 12.8 (9–17) for patients with pouch adenomas and (2.5–12.2) for patients without pouch adenomas; 32 (35.9) of patients showed progression of pouch adenomas during FUP 27.5 years (10.2–58.5) 90/192 (46.9) at a median of 8.5 years (0.9–25.1) after IPAA. 5 years after IPAA 84.9% patients free of adenoma; 15 years after 40.4% and 20 years after 21.9% patients were free of adenomas. 53/192 (58.9) ≤ 4 mm; 24/192 (26.7) 5 –10 mm; 13/192 (14.4) ≥ 10 mm Tubular adenomas in 69/192 (76.7); tubulovillous adenomas in 16/192 (17.8); villous in 5/192 (5.6) 46/192 (51.1) had < 4; 14/192 (15.6) 5–10; 30/192 (33.3) > 10 adenomas Goldstein et al., 201563 24 (41.0) Yes Mean 11.6 years +-14.6 years Median adenoma free time interval since surgery; Cuff 10.8 years Pouch 16.9 years Mean 30.8 years +-10.8 years 35/59 (59.0); - 20 isolated in cuff - 4 isolated in pouch body - 11 in pouch and body / All LGD / Zahid et al., 201519 14 (51.8) No Mean 9.2 years Median; 72 months (18–249) Median 31 years (14–65) 12/27 (44.0) / Only 1 polyp HGD (< 99%) / Kennedy et al., 201466 43 (45.0) Watched only anastomosis Mean 7.6 (0 – 24) Mean 15.4 (4–20) 9/95 (9.4) Pommaretet et al., 201336 110 / 139 92 / 110 (Cohort included IRA, ileostomy and IPAA patients but did not distinguish between). / Median 15 years 25 years (9−61 years) 57/118 (48.3) > 10 mm:12 94% LGD; 6% HGD 1−4: 22 5−20: 18 > 20: 17 Boostrom et al., 201366 52 (44.5) Yes 125 months (25– 423 months) 12.4 years (15–405 months) 26 years (4– 60 years) 30/117 (25.6) 5.9 mm (2 mm to 20 mm) 22 LGD, 8 tubulovillous / Wasmuth et al., 201367 34 (55.7) / Yes (body and anastomosis) Cumulative rate of adenomas at 28 years 17% for mucosectomy group and 75% at 15 years in a group without mucosectomy (P < 0.0001) 20 (10–49) Anastomosis: 4/39 (10.0) vs. 14/22 (64.0) (P < 0.0001) Pouch body: 8/39 vs. 6/22 (P 0.57) Tonelli et al., 201251 / 45 (65%) No Median 133 months (12–288 months) Mean 7 years (1–15 years) 33 years (17–63 years) 25 (36.0) Mean 3 mm (1–40 ) Adenomas, dysplasia not specified Mean 8 (1–47) Yan et al., 201268 30 (71.5) / Yes Median 7.2 (2.2–20) 29 (16–65) At the anastomosis 6/33 (18.2) / / / Banasiewicz et al., 201133 79 (47.9) / / Endoscopies performed 2–19 years since surgery. Mean 14 months to LGD; Mean 16 months to HGD. Estimated frequency LGD 15 years later 50% and for HGD 17.5 years later 50%. 21/165 (12.7) LGD - 21/32 (65.6); HGD - 11/32 (34.4) Gleeson et al., 200831 / / Yes / FUP began median 6.5 (0–15) after surgery / 13/13 (100): 10/13 pouch body; 2/13 anastomosis; 3/13 ileum above anastomosis < 5 mm / 5–30 Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis 163 1983 (12.9%) were diagnosed with CRR compared to none of those operated after 1983 when pouch surgery was introduced at the Cleveland Clinic. Recently published data from two Japanese stud- ies reporting an overall CRR rate of 30%25 – 37%20 must be interpreted with caution as carcinoma in situ was also included in the definition of cancer in their cohorts. The risk of metachronous cancer after IRA has been recognised early and these pa- tients have been advised to undergo regular sur- veillance of the rectal remnant. Traditionally, sur- veillance was recommended every 3 to 12 months. This recommendation has been maintained ever since and can be also found in the recently pub- lished international guidelines (Table 1). The French national guidelines published in 200539 are the only ones to include the genotype informa- tion, as they recommend more frequent surveil- lance if the pathogenic variant is located between codons 1250–1500. However, they were published in 2005. The main obstacle to refining recommendations for endoscopic surveillance is the lack of high- quality, prospective data. Unfortunately, we have not found a single randomised trial that has com- pared different surveillance strategies or aimed to identify factors that would allow risk stratifi- cation. Members of the International Society for Gastrointestinal Hereditary Tumors (InSiGHT)40 proposed a staging system41 and stage-specific interventions for patients with intact colon and those with IRA, but unfortunately no effort has been made to validate this staging system. Data on endoscopic treatment modalities are even more de- scriptive. In fact, in five international recommen- dations (Table 1), only Vasen et al.7 recommended endoscopic removal of all polyps with dysplasia or those larger than 5 mm. Endoscopic management of these patients has therefore been influenced by expert groups. Unfortunately, preferred methods of endoscopic management were rarely described in the reviewed studies. Maehata et al.20 recom- mend removal of all polyps larger than 8 mm. A descriptive study with a small sample size (n = 6)42 showed that large-scale cold snare polypectomy can effectively reduce the polyp burden in the rectal remnant even in cases of very high polyp numbers. The mean number of polyps removed was 78.5 (30–155). During the follow-up (mean 10.7 months), none of the patients developed rectal can- cer and there were no complications related to pol- ypectomy. This is in contrast to another study from the USA30, which advocates the use of ablative therapy with argon plasma coagulation. A similar First author and publication date Sex (man); n (%) APC mutation Underwent; n (%); Positive in; n (%) Distinguish between pouch body and rectal cuff Follow-up (months/years) Time from surgery to first adenomas (years) Age at surgery (years) Rate of adenomas (≥ 1 polyp) Size of adenomas, mm Histology of adenomas; n (%) Number of Adenomas Friederich et al., 200832 119 (56.0) / / Mean 7.9 (0.4–20.3 years) Cumulative risk of 16% at 5-years and 42.4% at 10 years for adenoma development. Cumulative risk of 12.8% at 10 years for advanced adenoma development. Mean 30.0 years (10–62.6 years) 47/212 (35%) / / / Campos et al., 200817 / / No 50.8 (5–228) 3/26 (11.5) Moussata et al., 200725 12 (57.1) 23/23 (100.0) 22/23 (95.7) Yes (only polyps in the ileal mucosa of the pouch body are described) Mean 5.4 +- 2.6 (1–11) Mean 4.7+-3.3 years (1–14) 17/23 (74.0) Mean size 5.2 mm +-3.4 mm; 3 polyps were > 10 mm. LGD 16/17 (94.1); HGD 1/17 (5.9) / Groves et al., 200535 35 (58.3) / Between pouch and above anastomosis ileum 6 years (1–17 years) / 32.5 years (13–66 years) 34/60 (57%) of which 5 were > 10 mm / 11 were advance adenomas Mean size 5 mm (1–40 mm) / Median number 4 Thompson- Fawcett et al., 200177 / 20/33 (60.6) 18/20 (90.0) Only pouch body / / / 20/33 (60.0) adenomas 1–3 mm / Median 10 (1–100) Also lymphoid hyperplasia included APC = adenomatous polyposis coli; FUP = follow up; HGD = high grade dysplasia; IRA = ileorectal anastomosis; LGD = low grade dysplasia Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis164 TABLE 6. Cancer rate after primary ileal pouch anal anastomosis (IPAA) First author and publication date (ref.) No of patients Age at cancer diagnosis (years) Time to cancer (years) Interval since last surveillance endoscopy and findings Endoscopic findings at diagnosis Location Staging of cancer and status Aelvoet et al., 202355 3/111 (2.7%) / / / / / Pouch excision Pasquer et al., 202158 1/92 (1.1) 30 / 1 month Pouch body Endoscopic resection Ganschow et al., 201861 1 / 27 / / Pouch body Resection and reconstruction of a new pouch - alive Walsh et al., 201663 1 54 / Regular annual surveillance New endoscopy due to anemia and rectal blood loos Anastomosis T3N2Mx, resection and ileostomy, alive during last FUP. Wasmuth et al., 201367 1 / 11 / / Rectal cuff Resection and ileostomy - alive Boostrom et al., 201366 1 / 23.7 / / Pouch body Transanal resection - alive Ozdemir et al., 201338 4 / Mucosectomy group; median 11.3 years (8.3–22) Without mucosecomy; 8 years Regular annual surveillance / All ATZ ? 3 underwent APR - alive 1 transanal resection – died 4 years later dissemination Makni et al., 201269 1 26 10 8 months Polyps, LGD? Pouch body? Pouch excision – died 12 months later dissemination Tonelli et al., 201251 2 2958 10 12 months, normal 6 months, normal ? IIa + IIc polyp Pouch body Pouch body Excision with ileostomy, T3N0M0, died 6 months later dissemination/ Excision with ileostomy, T2N0M0, alive after 56 month FUP voon Roon et al., 201170 1 / 13 / / Pouch body Excision of a pouch – died 2 years of disseminated disease Banasiewicz et al., 201133 5 / / / / Pouch body / Ault et al., 200971 2 6150 11 10 6, normal / Pain and blood per rectum, 3 cm mass/ Sacral pain, bleeding ulcer Pouch body / Pouch body T2N1Mx, died of AMI prior treatment / Metastatic disease, chemotherapy Tajika et al., 200983 2 55 68 8.620 9 months, normal No FUP 30x25 mm cancer / Polyposis and 25 x 25 mm polyp Pouch body/ Kock’s pouch body T4N2M0 – died 1 year later T3N?M? – died (MDS) Lee et al., 200871 1 / 7 / Ulcerating tumor Pouch body T4N1M0, APR ileostomy. Developed metastases 2 years later. Friederich et al., 200832 4 35 37 32 36 14 10.2 16.4 6.2 4.4 years, normal 2.1 years, normal No control (symptoms) 0.6 years, Tubullovilous HGD / All pouch body Dukes C Dukes B Dukes B Dukes B Linehan et al., 200772 1 40 10 / Pelvic pain, discharge Pouch body (patient had ileostomy but pouch was left in situ) Excision. At last FUP patient was well. Ulas et al., 2006 74 1 / 9 / / Anastomosis Dukes B, APR, metachronous cancer after 1 year Campos et al., 200519 1 / 12 No FUP Presented with rectal bleeding Pouch body T2N0Mx, APR and ileostomy, patient well at 6 years FUP. Vroueraets et al., 200475 2 48 36 9 10 5 years normal, then 2 and 1 years (both multiple LGD adenomas refused surgery) / Regular FUP every 2 years Presented after 1 year with rectal bleeding / Normal. Routine biopsies at subsequent FUP revealed adenoca. Anastomosis Anastomosis T2N0M0, APR, alive 1 year later / T4N0M0, APR, alive 8 months later Cherki et al., 200376 1 35 3.5 1.5 years / Pouch body T3N1M1, resection with ileostomy, died 1 month later Ooi et al., 200336 2 36/ 2 years 3 months 8 years / / Symptoms of anal bleeding/ / Anastomosis Anastomosis T3NOMO, APR, ileostomy, died 2.5 years later dissemination / T2N0M0, transanal excision with ileostomy (refused APR), died 4 years later, dissemination Brown et al., 200178 1 44 7 years 4 months Under FUP every 6 months / Anastomosis / Vuilleumier et al., 200079 1 38 7 No FUP / Anastomosis Resection with ileostomy – died 12 months later dissemination Palkar et al., 199715 1 39 4.7 3 months ? Pouch body T4NOM? - alive Kim et al., 199715 1 / / / / Pouch body? / Bassuini et al., 199680 1 31 3 No FUP / Pouch body / Von Herbay et al., 199614 1 33 8 Anastomosis T1N0M0 Hoehner et al., 19947 1 34 20 / / Anastomosis / #The data from these cases has been drawn from reviews by Tajika14 and Smith13 as full-text of the papers were not accessible. FUP = follow up; HGD = high grade dysplasia; LGD = low grade dysplasia Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis 165 practice was supported by a study published in France in 2007.17 National French guidelines pub- lished in 2005 recommend ablation with APC for small polyps (a few millimetres) and mucosectomy for larger polyps.39 Improvements in endoscopic resection tech- niques have also been applied to the treatment of large lesions in the rectal remnant. Recently two reports, both from Japan43,44, have been published of successful endoscopic submucosal dissection (ESD) of 75 mm Is + IIa adenoma and residual ad- enoma at the IRA. In our endoscopy unit (Hospital Clinic, Barcelona) we also perform advanced en- doscopic resection techniques. Figure 2 (A and B) shows a recent endoscopic mucosal resection (EMR) of an 18mm laterally spreading tumour granular type (LST-G) in the rectal remnant of a patient with FAP. There is little data on the use of advanced im- aging techniques. The study from St. Mark’s hos- pital in London45 showed no benefit of dye-based chromoendoscopy to detect additional adenomas in the rectal remnant. The European Society of Gastrointestinal Endoscopy (ESGE) guidelines46 published in 2014 did not recommend the use of advanced endoscopic imaging in patients with FAP, but did not specifically differentiate between the patients with intact colon and those after sur- gery. On the other hand, the French Society of Endoscopy39 recommended the use of dye-based chromoendoscopy with indigo carmine. We be- lieve that use of dye-based chromoendoscopy in these patients does not increase the detection of clinically relevant lesions and it is not routinely performed in our unit. Considering the data on a cumulative risk of 57% for CRR 30 years after sur- gery20 and the fact that adenoma development in the rectal remnant is an inevitable event16, regular endoscopic surveillance is mandatory. Our recom- mendations are in line with other guidelines and our patients are recommended annual endoscopic surveillance, despite alarming data from an early study published in 20015 from four European regis- tries in which 75% of patients with CRR had a neg- ative rectoscopy within 12 months and 35% within 6 months prior to diagnosis of CRR. There was no information on the endoscopy equipment used for surveillance. We believe that the high rates of neg- ative rectoscopies prior to cancer diagnosis may – to some extent - be influenced by the quality of endoscopy, which has been limited by the techni- cal aspects of the equipment used in the past. This problem needs to be addressed again in the light of developments in endoscopic equipment. When restorative proctocolectomy with IPAA was first described in 197847, it was believed that this operation would eliminate the risk of colorec- tal cancer in patients with FAP. However, a few years later, as the first pouches began to age, case reports of cancers arising in the pouch began to appear in the literature.6 Since then, reports have become more frequent and we have identified 45 cases of cancer after primary IPAA, of which 26 arose in the ileal mucosa of the pouch body and 15 at the anastomosis. Furthermore, we now know that cancer can develop even after mucosectomy down to the dentate line48, because even after re- moval of all visible rectal mucosa, some micro- scopic rectal columnar epithelium remains at the ATZ.49 In the study from the Heidelberg Polyposis FIGURE 2. Surveillance endoscopy in a 48-year old patient with FAP after colectomy with IRA revealed 18 m LST-G (A). After submucosal injection with gelofusine, indigo carmine and adrenaline, piecemeal endoscopic mucosal resection (pEMR) (B) was performed. A B Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis166 Registry with 100 patients50, rectal residual mucosa (defined as visible mucosa or detected by histology from blinded biopsies) was found in 42 (84%) cases after stapled and in 21 (42%) cases after hand-sewn anastomosis. Researchers from Japan16 found a 70% incidence of adenomas in the pouch body with one of the longest follow-up periods reported to date (> 20 years). Similarly, in a study from France, 74% of patients had at least one adenoma in the pouch, but with a mean follow-up of only 5.4 years. In contrast, one study found that isolated rectal cuff adenomas were more common than isolated pouch adenomas (49.1% vs. 6.8%), while 18.7% of patients had both pouch and rectal cuff adenomas. Cumulative 5-year, 10-year and 20-year risks for pouch adenomas were 32%, 52% and 68% in the Japanese study16, a slightly lower 5-year cumula- tive risk but a similarly high 10-year risk was ob- served in a Dutch study31; 16% and 42%, but the authors of this paper did not specifically define the exact location of the adenomas. The authors also reported a 10-year cumulative risk of developing precancerous adenomas of 12.8%. On the other hand, the adenoma rates – at least in the stapled group - seem to be higher in the studies that only looked at the anastomosis and compared hand-sewn with stapled: 0–33% vs. 33.9–57%. In view of these figures, it is essential that patients with primary IPAA also undergo regular endoscopic surveillance. Particular atten- tion should be paid to the rectal cuff and anasto- mosis, and the pouch should be examined in both forward and retroflexed position. International guidelines most commonly rec- ommend annual endoscopy examination, whereas ASCO guidelines9 advocate ‘case-by-case’ interval allocation. In 11 of only 12 studies that described a surveillance protocol, an interval of 12 months was recommended except in Brazil where endoscopy of the pouch was recommended every 2 years. Interestingly, in the Netherlands pouch endos- copy was recommended every 1 to 3 years in the late 1990s but in 2001 the protocol was changed to annual endoscopic surveillance regardless of the anastomotic technique (hand-sewn or stapled). One of the main concerns is the short interval (< 1 year) between the last normal endoscopy and the cancer diagnosis and the aggressive course of the disease despite an initial R0 resection (Supplementary Table 4). It is not entirely clear whether the adenoma-carcinoma sequence is fast- er in the ileal mucosa compared with the colon and rectum, or whether “negative” endoscopies prior to cancer diagnosis could be explained by the poor quality of pouch endoscopy. Chromoendoscopy improves the detection of diminutive adenomas31 and lymphoid hyperplastic nodules45, but its use is discouraged33,35 for the same reasons as in the examination of rectal remnants – increased of de- tection of clinically irrelevant polyps. Endoscopy should be performed with a gastroscope or pae- diatric colonoscope, as stricture can occur at the anastomosis, especially after hand suturing. There are no official recommendations for en- doscopic management of FAP patients after IPAA. We have found considerable heterogeneity in local practice. Italian authors recommend resection of FIGURE 3. Surveillance endoscopy in a 49-year old patient with FAP after proctocolectomy with IPAA revealed 25 mm LST-G mixed type lesion in the rectal cuff. Lesion was spreading from the anastomosis to the dentate line. Patient had undergone surgery five years earlier and did not show up for endoscopy follow-up since then (A). Lesion was removed with pEMR (B). A B Radiol Oncol 2024; 58(2): 153-169. Gavric A et al. / Endoscopic management in familial adenomatous polyposis 167 all adenomas > 3 mm.51 On the contrary, ablation with argon plasma coagulation is the preferred resection technique in a French study.17 Ablative techniques were also supported by the study from the Mayo Clinic.30 In a small descriptive cohort of only 5 patients42, large-scale cold snare pol- ypectomy with a mean of 110.6 (30–342) resected polyps demonstrated the efficacy of cold snare in controlling large polyp burden (> 30 polyps) with no reported polypectomy related complication. In our unit we do not use nor encourage use of argon plasma coagulation. We recommend resection of all polyps > 3 mm. Advanced resection techniques, when performed in the tertiary centres, may be a viable alternative prior to surgical resection. A case report of successful en bloc ESD of a 15 mm ‘non-lifting’ HGD adenoma in the ileal pouch has recently been published.52 Figure 3 (A and B) shows an EMR of 25 mm LST in a patient with FAP after IPAA. The polyp was located in the rectal cuff and extended from the anastomosis to the dentate line. The procedure was performed at our Endoscopy Unit. It should be emphasised that the wall of the ileum is very thin and special care must be taken when resecting larger lesions. Although there is no randomised trial compar- ing different endoscopic surveillance intervals, it is unlikely that prospective data will be available in the future. The main reason is ethical issue, as these patients are at increased risk of colorectal cancer. However, with the introduction of high quality colonoscopy and improvements in endos- copy technique, a ‘negative’ endoscopy before can- cer diagnosis should become highly unlikely if not impossible. 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