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Serrated polyps of the colon and rectum

Hazewinkel, Y.

Publication date 2014 Document Version Final published version

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Citation for published version (APA): Hazewinkel, Y. (2014). Serrated polyps of the colon and rectum.

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Download date:02 Oct 2021 6 Yield of screening colonoscopy in first-degree relatives of patients with serrated polyposis syndrome

Y Hazewinkel, JJ Koornstra, KS Boparai, TA van Os, KM Tytgat, S van Eeden, P Fockens and E Dekker

J Clin Gastroenterol. 2014 Mar 6 [Epub ahead of print]

This study was supported by grants of the Dutch Cancer Society 88 Chapter 6 Background aims study and individuals. with patients of these for program screening relatives a colonoscopy warranting substantial, is first-degree polyposis serrated in colonoscopy screening single a of yield The Conclusions 3. WHO-criterion SPS met also sibling one whom of 2, WHO-criterion SPS fulfilled relatives first-degree (14%) Eleven (≥5). polyps multiple had relatives (9%) first-degree Seven polyps. of detection the in observed were relationship familial or der significant more gen age, on based or differences No relatives. One first-degree of 43% in detected were diagnosed. polyps not was cancer Colorectal 41-60). inter range y; quartile 52 age (median colonoscopy underwent relatives first-degree Seventy-seven Results pathologist. expert one by reviewed were specimens Tissue polyps. hyperplastic proximal and adenoma/polyps serrated sessile adenomas, serrated traditional adenomas, defined were polyps nificant least at Sig with relatives. first-degree included relatives of number total the to first-degree relative polyp of significant one number the by expressed The was colonoscopy. yield undergo diagnostic to invited were SPS with patients of relatives First-degree Methods polyposis. serrated with patients of relatives first-degree in colonoscopies screening of yield diagnostic the evaluate to group. aimed this We in justified are copies colonos screening whether to investigate to and useful inheritance of be mode possible would a evaluate information This scarce. however are group this screening in of yield colonoscopies the evaluating studies Prospective SPS. and cancer colorectal both for risk increased an have inheritance patients these of Although relatives cancer. first-degree unknown, are colorectal patterns for risk increased an at are SPS with Patients Part II|Serrated polyposissyndrome A bstract - - - - yield of screening colonoscopies in first-degree relatives of patients with SPS. with patients of relatives first-degree in colonoscopies screening of yield diagnostic the evaluate to was study this of aim The individuals. these in lesions of tion distribu and type prevalence, the first- assess of adequately to series necessary large are relatives in degree studies screening Prospective estimates. risk the inflated have may which bias, ascertainment to prone are designs study Such ascertained. spectively ily members of patients with SPS compared with the general population. general the with compared SPS with fam patients of first-degree members in ily cancer colorectal of demonstrated incidence studies increased 5-fold cohort approximately an retrospective recent two Moreover, cancer. colorectal with relative first-degree a have SPS with patients of 50% to up that report cancer. series Case colorectal developing of risk increased an have syndrome the with patients of an estimated prevalence of 1:150 to 300. to 1:150 of prevalence estimated an with screening, cancer colorectal (FIT)-based testing immunochemical fecal undergoing than 20 serrated polyps distributed throughout the colorectum. the throughout distributed polyps 20 serrated than more 3) or SPS with relative first-degree a has who individual an in proximal colon sigmoid the polyps to serrated of number any 2) or diameter, in mm 10 than larger 2 which of colon, sigmoid the to proximal lesions serrated diagnosed histologically 5 least at 1) follows: as (WHO) Organization Health the World by defined was condition the 2010, In histopathology. with combination in findings endoscopic on based therefore is SPS of diagnosis The unknown. is disease the of defect genetic underlying the syndromes, sis number or size of lesions, is not feasible. not is lesions, of size or number the of because e.g. burden, surveillance. polyp the of control endoscopic endoscopic when frequent indicated is undergo Surgery to advised are patients growth, invasive stance familial adenomatous polyposis (1:13.000). polyposis adenomatous familial stance in for than occurrence in frequent more is which 1:1800, be to estimated is prevalence with an increased colorectal cancer risk. cancer colorectal increased an with is associated and colon the throughout distributed polyps serrated by numerous terized is charac syndrome, polyposis hyperplastic formerly (SPS), syndrome polyposis Serrated members has been described in previous reports. previous in described been has members diagnosis of SPS reported in the family member. family the in reported SPS of diagnosis of time at age the than younger years 5-10 age an at or years 35-50 age at starting tives rela first-degree all for years 6 or 5 every colonoscopies advise authorities most reason, I ntrod Although most SPS cases seem non-familial, presence of the disease in multiple family family in multiple of disease the presence non-familial, seem cases SPS most Although The above-mentioned recommendations are based on data that were mainly retro mainly were that data on based are recommendations above-mentioned The u ction 1-3 9 4,5 SPS is a relatively common finding in patients patients in finding common relatively a is SPS In an average risk screening population the the population screening risk average an In 12,13,15,16 6,7 Screening colonoscopy inFDRsofpatients withSPS 10-12 In contrast with most other polypo other most with contrast In In addition, first-degree relatives relatives first-degree addition, In 8 To from polyps prevent 10-14 For this this For ------89 Chapter 6 90 Chapter 6 Invitation population and hyperplastic polyp, sessile serrated adenoma/polyp or traditional serrated adenoma adenoma serrated forserrated in the WHO classification incorporated recently traditional criteria on based histological or adenoma/polyp serrated sessile polyp, hyperplastic as classified were polyps Serrated pathology. special a gastrointestinal in with expertise (SvE) and interest pathologist one by reviewed were specimens tissue available All Histopathology cecum). and colon ascending transverse, (descending, sigmoid to as proximal defined was colon proximal The ileum). the of intubation or orifice appendix valve, (cecal landmarks cecal the of documentation by confirmed was intubation Cecal a diet. fibre low and fluids with transparent of L 2-4 additional an with solution prepared PEG hypertonic were L 2 a or Subjects solution (PEG) glycol polyethylene location. L 4 a including colonic preparation, bowel and standard size polyp document to and assessment histological for polyps detected all retrieve and remove to instructed were colonoscopists All Netherlands. the across institutions referral tertiary and hospitals nity commu both at fentanyl and/or midazolam with sedation conscious were under Procedures performed used. not were chromoendoscopy, or imaging techniques, narrow-band imaging as such Advanced colonoscopy. light white high-resolution or standard a either underwent relatives first-degree eligible all consent, informed providing After Colonoscopic procedure NTR3253). number trial (www.trialregister.nl; Register Trial Dutch the in registered analyses. data further from excluded were visible) mucosa colonic 90% (< tion prepara bowel poor or colonoscopy incomplete an with Subjects characteristics. polyp and intubation cecal preparation, bowel of quality the demographics, clinical regarding a years. 3 previous the undergone in had colonoscopy they if or polyposis had serrated or they cancer if colorectal excluded of were history Relatives personal choice. their of hospital or hospital local colonoscopy a their at offered subsequently were SPS, with diagnosed was patient index the at which age the than younger 5 years age an from or years, 35 of age the from sponders Re patient. index the by relative the to given was that invitation of letter standard a of means by colonoscopy undergo to invited were subjects these of children) and siblings (parents, relatives First-degree Groningen). Center, Medical University the and sterdam Am Center, Medical Academic (the Netherlands the in hospitals referral tertiary two in forSPS weretheidentified or criteria WHO-1 WHO-3 fulfilling patients) (index Individuals Part II|Serrated polyposissyndrome M Ethical approval was obtained from our institutional review board and the study was was study the and board review institutional our from obtained was approval Ethical data obtain to institutions all from collected were reports histology and Endoscopy et h ods - - - - the term “unclassified serrated polyp” was used. polyp” was serrated term “unclassified the sampling poor or artefacts cautery severe orientation, poor to due e.g. ser subtypes, different rated the between differentiate to possible not was it When nuclei. elongated located centrally or cytoplasm eosinophilic abundant configura having cells villiform columnar with tions distorted with pattern growth pedunculated or protuberant a by defined were adenomas crypt a or serrated “L” “boot” the as Traditional of appears shape. often that portion basal the of branching or dilation including crypts, distorted and ≥ 10 mm, with villous structure or with high grade dysplasia. grade high with or structure villous with mm, 10 ≥ Clinical colonoscopy and characteristics analysis. for used was 19.0.1 version USA) IL, (Chicago, software for Windows SPSS significant. statistically as considered were 0.05 in than less confidence of p-values 95% Two-sided tervals. with risk relative as expressed were Differences groups. between differences significant test to used was test chi-square A relatives. first-degree included of number total the to relative polyp significant one least at with relatives first-degree of number the by expressed was yield diagnostic the finding Consequently, colonoscopy. significant during clinical a as defined were polyps hyperplastic proximal and polyps adenomas/ serrated sessile adenomas, serrated traditional cancer. Adenomas, colorectal 8] and tradi adenomas advanced 7] 5] mm 10 < adenoma/polyps adenomas tubular 6] serrated adenoma serrated sessile tional 4] polyps hyperplastic proximal 3] hyperplastic polyps distal 2] polyps no 1] colonoscopy: at found lesion advanced most the of found. was polyp one least at whom in relatives first-degree of proportion the as defined was rate Prevalence istics. character polyp and population study the describe to used were statistics Descriptive Outcome statistical measuresand analysis polyps. ing 77 first-degree relatives were all asymptomatic and underwent their procedure at procedure their underwent and asymptomatic all were relatives first-degree 77 ing remain The (n=3). colonoscopy incomplete of an or because (n=2) preparation procedure bowel the inadequate after excluded were relatives Five 2012. October and 2008 patients. index 36 the of first-degree participating 1-5). (range 2 of was 31 patient index number per relatives siblings, median (56%) The (4%). 43 parents of 3 consisted and and (40%) children families 36 to belong relatives included The R es To express the diagnostic yield, patients were classified into 8 groups on the basis basis the on groups 8 into classified were patients yield, diagnostic the express To A total of 82 eligible first-degree relatives underwent colonoscopy between October October between colonoscopy underwent relatives first-degree eligible 82 of total A u lts 8 A sessile serrated adenoma/polyp was defined by predominantly disorganized disorganized predominantly by defined was adenoma/polyp serrated sessile A Table 1 Table 15 Advanced adenomas were adenomas adenomas were adenomas Advanced Screening colonoscopy inFDRsofpatients withSPS outlines the clinical characteristics characteristics clinical the outlines ------91 Chapter 6 92 Chapter 6 polyps were ≥ 10 mm and 80 (58%) lesions were located proximal to the sigmoid. the to proximal werelocated lesions (58%) 80 and mm 10 were≥ polyps (6%) 8 2-5mm); (IQR mm 3 was size polyp median polyp. The juvenile (1%) lesions’1 and (33%) adenomas, 17 (12%) sessile 3 serrated adenomas/polyps, (2%) 46 ‘unclassifiedserrated polyps, hyperplastic (52%) 72 demonstrated: Histopathology used. was local pathologist the by diagnosis sign-out original the in specimens remaining 6 performed the for was polyps; 133 specimens pathology of Review detected. were cancers colorectal no and polyps 139 of total a relatives, first-degree the in colonoscopy screening During Polyp characteristics range,IQR: interquartile colorectal CRC: cancer, FDR:first-degree relative Number ofFDRsindex patients (%) withCRC Parents (%) Children (%) Siblings (%) (%) Male ageinyearsMedian (IQR) Table oftheincludedfirst-degree 2.Clinicalcharacteristics relatives (n=77) in shown are relatives first-degree 77 included the of characteristics Clinical hospitals. community different 17 at procedures (26%) 20 and center colonoscopy single one at procedures (23%) 18 institutions, referral tertiary two at performed were colonoscopies (51%) Thirty-nine hospitals. different 20 range,IQR: interquartile colorectal CRC: cancer 10 mmindiameter. WHO 3:≥20serrated polypsdistributed throughout thecolorectum * WHO 1: ≥ 5 histologically diagnosed serrated lesions proximal to the sigmoid colon, of which 2 larger than numberofFDRsperindex patientMedian (range) Number ofpatients (%) withCRC numberofadenomas(IQR) Median numberofproximalMedian serrated polyps(IQR) numberofserratedMedian polyps(IQR) Combined (1and3) 3 1 (%)* WHO criteria (%) Male ageinyearsMedian (IQR) Table ofindex patients 1.Baselinecharacteristics withserrated polyposis(n=36) Part II|Serrated polyposissyndrome Table2 . 25 (14-36) 64 (59-71) 52 (41-60) 12 (5-22) 16 (44) 17 (47) 12 (33) 19 (53) 41 (53) 31 (40) 43 (56) 37 (48) 2 (1-5) 4 (1-9) 7 (20) 3 (4) Prevalence (%) Table 3.Numberandprevalence ofpolyps, stratified by gender, familial relation andage adenomas/polyps respectively. serrated relatives, first-degree (6%) 5 and sessile (12%) 9 in detected were proximal and polyps hyperplastic Proximal tively. respec relatives, first-degree (36%) 28 and (9%) 7 (36%), 28 in detected was adenoma in is age shown and relationship familial gender, by stratified polyps of number and Prevalence Prevalence andnumber ofpolyps Yield ofcolonoscopy relatives are listed in are listed 7 relatives these of characteristics pedigree and polyp Clinical, children. 2 and siblings 5 bands; pro different 7 from relatives first-degree (9%) 7 in detected were 5) (≥ polyps Multiple First-degree relatives with multiple (≥5) polyps 0.84-2.52). 95% 1.46 (RR years 50 < between ≥ 50and years relatives first-degree or between 0.64-1.81), 95% 0.77-2.18) (RR 1.30 and female male 95% 1.07 (RR children) and (parents (brothers non-siblings and siblings sisters) between and polyps significant of detection the in seen was difference significant No polyp. hyperplastic proximal a 2 in and adenoma/polyp serrated sessile a 3 in mm, 10 < adenoma tubular a 22 in adenoma, advanced an was finding advanced most the relatives 6 In first-degree was detected. polyp) or hyperplastic a polyp proximal adenoma/ serrated sessile adenoma, serrated traditional polyp’asanadenoma, (defined one least ‘significant at (43%) 33 other the In found. were polyps hyperplastic distal only listed is age and relation ial by gender, famil stratified lesion, to theadvanced mostaccording findings Colonoscopy yield;findingsaccordingDiagnostic to themostadvanced lesiondetected at colonoscopy Number ofpolyps(%) Adenoma Traditional serrated adenoma Hyperplastic polyp Hyperplastic serratedSessile adenoma/polyp 0 1 ≥ 5 2-4 Table 3 Table . At least one hyperplastic polyp, sessile serrated adenoma/polyp or or adenoma/polyp serrated sessile polyp, hyperplastic one least At . Table 5 Table 4 . Four of the seven first-degree relatives with multiple polyps polyps multiple with relatives . Four of first-degree the seven Combined 28 (36) 28 (36) 30 (39) 19 (25) 21 (27) n=77 0 (0) 7 (9) 7 (9) . In 44 (57%) first-degree relatives either no lesions or lesions no either relatives first-degree (57%) 44 In . 16 (43) 16 (43) 10 (27) 11 (30) 12 (32) 4 (11) 4 (11) n=37 Male 0 (0) Female 12 (30) 12 (30) 20 (50) 8 (20) 9 (23) n=40 0 (0) 3 (8) 3 (8) Screening colonoscopy inFDRsofpatients withSPS Siblings 14 (33) 21 (48) 12 (28) 11 (26) 15 (35) 5 (12) n=43 4 (9) 0 (0) siblings 14 (41) 18 (53) 7 (21) 8 (24) 6 (18) n=34 Non- 3 (9) 0 (0) 2 (6) 11 (31) 19 (54) 7 (20) 6 (17) 8 (23) <50 y n=35 2 (6) 0 (0) 2 (6) 17 (40) 21 (50) 11 (26) 13 (31) 13 (31) ≥ 50y n= 42 5 (12) 5 (12) 0 (0) - - - 93 Chapter 6 94 Chapter 6 Distal hyperplastic polyp(%) No polyps(%) polyps orno(%) Number ofFDRswithdistalhyperplastic Proximal hyperplastic polyp(%) Sessile serratedSessile adenoma/polyp(%) Traditional serrated adenoma(%) Advanced adenoma(%) Tub. Adenoma ≤10mm(%) Colorectal cancer (%) than 10 mm in diameter, this individual did not meet the WHO-criterion 1. WHO-criterion the meet not did individual this diameter, in mm 10 than were larger polyps serrated proximal of the none Since 5 and adenomas. polyps serrated 2, (FDR child One 1. WHO-criterion satisfied relatives first-degree the of None colon). the throughout spread polyps serrated 20 than (more 3 In 43% of first-degree relatives at least one significant polyp (defined as an adenoma, adenoma, an as (defined polyp significant one least at relatives first-degree of 43% In diagnosed. not was cancer Colorectal polyposis. serrated with patients of relatives gree first-de in colonoscopies screening of yield diagnostic the evaluated prospectively We a in of relative sigmoid with patient SPS) and 1first-degree (FDR 1, the to proximal polyps serrated of number (any 2 WHO-criterion fulfilled them of all criteria; theWHO of one least at met relatives first-degree (14%) 11 of total A First-degree relatives fulfillingtheWHO-criteria polyps. more or 5 had them of none study; present the in screened were families 7 same the from relatives other Twelve identified. were adenomas/polyps serrated sessile 4 FDR4) and in 2 of (FDR3 whom adenoma/polyp, serrated sessile one at least harboured Tub.: tubularFDRs:First-degree relatives adenoma 8]colorectal cancer advanced 7] mm 10 < adenoma tubular 6] adenoma/polyps serrated sessile 5] adenoma serrated ditional sion found at colonoscopy: 1] no polyps 2] distal hyperplastic polyps 3] proximal hyperplastic polyps 4] Tra - To express the diagnostic yield, patients were classified into 8 groups on the basis of the most advanced le by gender, familialrelation andage Table 4. Part II|Serrated polyposissyndrome significant polyp(%) Number ofFDRswithat leastone D isc u Diagnostic yield; colonoscopy findings according to the most advanced lesion detected, stratified ssion 14 (18) 30 (39) 44 (57) 22 (29) 33 (43) n=77 Total 2 (3) 3 (4) 0 (0) 6 (8) 0 (0) 10 (27) 19 (51) 11 (30) 18 (49) 9 (24) 5 (14) n=37 Male 1 (3) 1 (3) 0 (0) 0 (0) Female 20 (50) 25 (62) 11 (28) 15 (38) 5 (13) n=40 1 (3) 2 (5) 0 (0) 1 (3) 0 (0) Table 5 Table 5 Table Siblings 12 (28) 24 (56) 12 (28) 19 (44) 8 (19) 6 (14) n=43 2 (5) 3 (7) 0 (0) 0 (0) ) also fulfilled WHO-criterion ) also WHO-criterion fulfilled ) had 14 polyps; 9 proximal proximal 9 polyps; 14 had ) siblings 18 (53) 20 (59) 14 (41) 14 (41) n=34 Non- 2 (6) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 19 (54) 23 (66) 10 (29) 12 (34) 4 (11) <50 y n=35 1 (3) 0 (0) 0 (0) 1 (3) 0 (0) 11 (26) 21 (50) 10 (24) 12 (29) 21 (50) ≥ 50y n= 42 5 (12) 1 (2) 3 (7) 0 (0) 0 (0) - - Table 5. First-degree relatives with multiple (≥ 5) polyps detected by screening colonoscopy FDR 1 FDR 2 FDR 3 FDR 4 FDR 5 FDR 6 FDR 7 Age at endoscopy (y) 38 44 58 65 58 55 60 Sex Female Male Male Female Male Female male Relation Sibling Non-sibling (son) Non-sibling (son) Sibling Sibling (brother) Sibling Sibling (brother) (sister) (sister) (sister) Colonoscopy findings 21 polyps 14 polyps 7 polyps 7 polyps 7 polyps 5 polyps 5 polyps

21 HP (9 prox) 8 HP (8 prox) 1 HP (0 prox) 2 HP (1 prox) 3 HP (2 prox) 3 HP (1 prox) 1 HP (0 prox) multiple distal HPs 1 USP (1 prox) 4 SSA/P (4 prox) 4 SSA/P (3 prox) 1 SSA/P (0 prox) 2 SSA/P (2 prox) 4 AD (3 prox) still in situ 5 AD (5 prox) 2 AD (0 prox) 1 AD (1 prox) 3 AD (3 prox) Advanced adenoma No No No No Yes No Yes Tub. AD ≥ 10 mm Tub. Vil. AD > 20 mm HGD Fulfils WHO criteria WHO-2 and 3 WHO-2 WHO-2 WHO-2 WHO-2 WHO-2 None Index case characteristics 45 y, male 74 y, female 85 y, female 69 y, male 63 y, male 59 y, male 54 y, male WHO 1 and 3 WHO-3 WHO-3 WHO-1 WHO-1 WHO-3 WHO-1 and 3 Screening colonoscopy inFDRsofpatients withSPS CRC: no CRC: yes CRC: yes CRC: yes CRC: yes CRC: no CRC: yes Other FDRs who None None 1 sibling 2 children 3 siblings 3 siblings 3 siblings underwent screening in 1) 2 HPs, 1 AD 1) no lesions 1) 1 HP; 1 AD 1) 1 HP 1) 3 AD the current study 2) no lesions 2) 1 HP 2) no lesions 2) 1 AD (relation to index) 3) no lesions 3) no lesions 3) no lesions FDR: first-degree relative, Y: years, HP: hyperplastic polyp, USP: unclassified serrated polyp, SSA/P: sessile serrated adenoma/polyp, AD: adenoma, Tub: tubular, Vil: villous, HGD: high-grade dysplasia, WHO: World Health Organization, CRC: colorectal cancer 95 Chapter 6 96 Chapter 6 frequently found in a non-familial context. non-familial a in found frequently also are lesions these that shows clearly 12%) (approximately population general the in lesions serrated proximal of prevalence high observed recently the but true, be might rational This SPS. with patient a of relative first-degree a in polyps serrated of numbers ofsmaller significance the to elevate in the criteria WHO incorporated was initially terion cri excessive. This somewhat 2 is WHO-criterion meeting solely relatives for surveillance annual that believe but 3 or 1 WHO-criteria meeting relatives for regimen this support these all WHO the theofWe criteria. one WHO fulfil they as to surveillance annual undergo should According individuals WHO-critierion-3. fulfilled also sibling one polyposis) whom serrated of with patient a of relative first-degree a in sigmoid the to proximal age. young relatively a from commence should and siblings non- and siblings to offered These be should this non-siblings. advised, is screening versus if that suggest siblings findings in lesions significant of detection the in observed was difference no addition, In years. 50 than less to those compared age of years 50 over relatives first-degree in polyps significant of detection the in difference no observed we Remarkably, lesion. significant one least at had relatives first-degree (43%) Thirty-three colonoscopy. undergoing relatives of number total the to relative polyp significant one least at with relatives first-degree of number the as calculated then was hyperplastic yield diagnostic proximal and The colonoscopy. screening during finding adenomas/polyps significant clinical a as defined were serrated polyps) (sessile polyps adenomas both serrated reason, both this and For that SPS. with patients illustrating in relevant sequence, clinically are pathways adenoma-carcinoma traditionally the follows ably (32%) first-degree relatives fulfilled one of the WHO-criteria compared with 11 (14%) in (14%) 11 with compared WHO-criteria the of one fulfilled relatives first-degree (32%) plastic polyps) and one fulfilled the WHO criteria for SPS. for criteria WHO the fulfilled one and polyps) plastic hyper distal (including polyp one least at had them of (59%) 10 colonoscopy; screening risk. cancer greater no likely with polyps serrated sporadic small few a or one with those from risk familial increased suspected a with relatives delineate to necessary therefore serrated polyposis arises via the serrated neoplasia pathway. neoplasia serrated the via arises polyposis serrated 3. WHO-criterion SPS met also sibling one whom of 2, had relatives SPS WHO-criterion fulfilled relatives (9%) first-degree (14%) 11 of A total (≥5). polyps first-degree multiple Seven polyps. significant were of relationship detection the familial in or observed gender age, on based differences No found. was polyp) hyperplastic proximal or adenoma/polyp serrated sessile adenoma, serrated traditional Part II|Serrated polyposissyndrome from Spain, 78 first-degree relatives of patients with SPS were screened. were SPS with patients of relatives first-degree 78 Spain, from 50 of below years age. In in a our of group study of recent relatives polyps detection high the with corresponds which 50, of age the under were polyps with relatives first-degree Eleven first-degree relatives met SPS WHO-criterion-2 (any number of serrated polyps polyps serrated of number (any SPSWHO-criterion-2 met relatives first-degree Eleven In a study from Portugal, 17 first-degree relatives of patients with SPS underwent a underwent SPS with patients of relatives first-degree 17 Portugal, from study a In Studies demonstrate that approximately half of all colorectal cancers in patients with with patients in cancers colorectal all of half approximately that demonstrate Studies 19,20 A more stringent WHO-criterion 2 seems seems 2 WHO-criterion stringent more A 11 Interestingly, 7 out of the 10 10 the of out 7 Interestingly, 17,18 The other half presum half other The 16 A total of 25 25 of total A - - - other 12 relatives from the same 7 pedigrees had multiple polyps ( polyps multiple had pedigrees 7 same the from relatives 12 other the of none and proband SPS the in presence cancer colorectal or/and one phenotype WHO with associated not was polyps multiple of finding The polyps. 5-10 with siblings, were 4 whom of relatives, 5 and polyps of 10) (> number extensive an with non-sibling, relatives ( relatives other 4 in polyps) hyperplastic proximal and adenomas/polyps serrated sessile multiple ( not were who well, as polyps 10 than more with 2 of relatives relatives presence the Still, report. present the in included second-degree investigate to necessary be might question it this in a insight or more no gain to which Moreover, in exists. cases component other inheritable by distinct swamped be might SPS of forms inherited as mode inheritance possible a postulate to difficult it makes This subcategorized. further yet not sub-conditions of group a represents WHO, the by defined currently as syndrome, the that believe experts most and diversity phenotypic substantial a with presents SPS that fact the to due likely most is This inheritance. of mode one with consistent not are ings mode with lower penetrance. lower with mode dominant or recessive autosomal with consistent mode inheritance an suggest reports our believe we polyposis, relevant. clinical are serrated findings or cancer colorectal of history personal a without individuals screen-naïve are practice clinical in with confronted relatives first-degree of majority vast the that considering Still, beforehand. excluded are abnormalities colonic known with relatives as approach polyposis, serrated of this risk familial true that the underestimate might emphasized be to of needs risk it hand the other minimize the On to bias. relatives ascertainment these exclude to decided We differences. observed these explain may, part, in series our in polyposis serrated or cancer colorectal of history personal a with relatives first-degree of exclusion The cohort. our in relative (1%) 1 only with or3 compared WHO-criterion-1 fulfilled study Spanish in the relatives study. Six our knowledged. An important question to answer is whether our detection rates are higher are higher rates detection our is whether to answer question An important knowledged. ac be to need that limitations also has study Our cancer. colorectal of history family or ofa personal irrespective toparticipate, asked were patients index identified all that fact the and pathologist expert one by specimens polyp all of revision the relatives, degree inheritance. of mode the explore further to and lesions additional developing of risk longitudinal the quantify to individuals these on focus should studies more Further future. a the in develop burden polyp will extensive relatives these whether see to interesting be will It role. a played have might all of combination a or factors environmental genes, penetrance low or more one of involvement inheritance, of mode co-dominant a or recessive autosomal An Table 5 Table Regarding the mode of inheritance, occasionally reported affected siblings in previous in previous siblings affected reported occasionally the of mode inheritance, Regarding Strengths of this study are the prospective design, the large number of included first- included of number large the design, prospective the are study this of Strengths : FDR 1 and 2) and an intermediate SPS phenotype of 5-10 polyps (including (including polyps 5-10 of phenotype SPS intermediate an and 2) and 1 FDR : Table 5 Table : FDR 3, 4, 5 and 6) could suggest a familial component in these cases. cases. these in component familial a suggest could 6) and 5 4, 3, FDR : 10-12 We found 2 first-degree relatives, one sibling and one one and sibling one relatives, first-degree 2 found We Screening colonoscopy inFDRsofpatients withSPS Table 5 Table ). These find These ). - - 97 Chapter 6 98 Chapter 6 and to observe the longitudinal risk of colorectal cancer in this group. this in cancer colorectal of interval risk longitudinal the surveillance observe to and optimal the evaluate to necessary are studies prospective future However, years. 6 or 5 of interval maximum a with polyps of detection the on based are intervals surveillance Subsequent family. the in reported SPS of diagnosis of time at age lowest the than younger years 5 or years 35 of age the at non-siblings, and siblings both relatives, in first-degree surveillance to we start advise in series, our of polyps onset early ous studies justify screening colonoscopies in this group. this in colonoscopies screening justify studies ous previ in reported cancer colorectal of incidence increased observed the and relatives of with colonoscopists by experience. of level different Netherlands The throughout spread hospitals different 20 in performed were colonoscopies that is study the of weakness possible a Finally, results. biased generate to likely seem not does this Nonetheless, study. our in participate not did relatives many how know precisely not do we patients, index the by relative the to given was that letter a by total invited were relatives the As screening. for eligible represent was that group fully not may relatives first-degree participating of group is our shortcoming that potential second A Netherlands. the in program screening currently is primary there no as concerns ethical raised have certainly would however, This, data. our of interpretation the for value additional of been have would hospitals same the colonoscopy in screening undergoing persons asymptomatic of group control matched a Therefore, scarce. are polyps multiple and adenomas/polyps serrated sessile of rates prevalence on data prospective reliable addition, In cancer. and colorectal of gender history age, family to respect with ours with comparable not are cohorts study these of with SPS. We a believe with average risk was comparison persons as not appropriate most relative a first-degree without persons asymptomatic in rates detections with compared Part II|Serrated polyposissyndrome We believe that the high yield theof lesions, offinding significant polypsin multiple 9% 12,13 Considering the observed observed the Considering -

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programmes. Gut. 2013; Gut. programmes. screening cancer colorectal FIT-based in syndrome polyposis serrated of prevalence High al. et S, Carballal M, Pellisé L, Moreira Gut.2013; programme. screening cancer bowel NHS the in polyposis) (serrated syndrome polyposis hyperplastic of prevalence High al. et R, Guy AJ, Ellis S, Biswas 62: ​ 2013; Gut. neoplasia. colorectal of development relentless and rapid polyposis: Serrated al. et LM, Hylind JE, Axilbund DL, Edelstein e11636. 2010; one. PloS clinics. genetics from series case cross-sectional a polyps: serrated multiple with patients in cancer colorectal for factors Risk al. et M, Drini K, Sweet DD, Buchanan 2010; Gut. study. cohort multicentre a syndrome: polyposis hyperplastic with patients in follow-up during risk cancer colorectal Increased al. et JJ, Koornstra EMH, Mathus-Vliegen KS, Boparai and the risk of colorectal cancer. Gut. 2012; Gut. cancer. colorectal of risk the and syndrome polyposis Hyperplastic J. Orlowska 1994; Mutat. Hum rate. mutation and penetrance, (FAP):frequency, polyposis adenomatous Familial al. et S, Bülow K, Fenger ML, Bisgaard digestive system. Lyon 2010 160 2010 Lyon system. digestive the of tumours of classification WHO eds. R, F, T,Hruban Carneiro Bosman In: polyposis. serrated and rectum and colon the of polyps Serrated al. et R, D,Burt Ahnen DC, Snover 470 25 ogy. 2006; ogy. Gastroenterol MYH. and MBD4 of role the and presentations phenotypic syndrome: polyposis Hyperplastic al. et E, Lynch L, Lipton E, Chow 2008; Am. North Clin Gastroenterol ment. manage clinical and history, natural genetics, molecular classification, colon: the of adenomas serrated and polyps hyperplastic syndromic and BP, Sporadic JR. Saunders Jass JE, East ‑ ​404 46 ‑ 1; author reply 471 reply author 1; ​3: ‑ ​121 8. ​59: ​131: ‑ 5.

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syndrome. Gut. 2010; Gut. syndrome. polyposis hyperplastic with patients of relatives first-degree in risk cancer colorectal Increased al. V, et Lemmens JB, Reitsma KS, Boparai 1779 2004; Gastroenterol. J Am study. clinical a on based guidelines future for contribution a relatives: first-degree at-risk of screening and polyposis hyperplastic with patients Portuguese of Management al. et ,R P, Sousa Lage M, Cravo polyposis. Am J Gastroenterol. 2012; Gastroenterol. J Am polyposis. serrated with patients of relatives for risks Cancer al. et DD Buchanan RJ, Walters AK, Win 164 2011; Rectum. Colon Dis syndrome. polyposis hyperplastic in risk cancer and phenotypes Defining al. et B, Leach A, MF, Jarrar Kalady 1330. 2012; Gastroenterol. J Am panel. expert an from recommendations and review colorectum: the of lesions rated Ser al. et JA, Baron DJ, Ahnen DK, Rex Polyposis. Am J Surg Pathol. 2013; Pathol. Surg J Am Polyposis. Serrated With Individuals in Carcinomas Colorectal of Heterogeneity Molecular and Multiplicity al. et RJ, MD, C, Walsh Walters Rosty 28 2013; Hepatol. Gastroenterol J Eur relatives. first-degree of study prospective polyposis: Serrated al. et A, Pueyo A, Guerra S, Oquiñena Clin Gastroenterol Hepatol 2011; Hepatol Gastroenterol Clin colonoscopy. screening during polyps serrated colon proximal of detection variable and Prevalence al. et DL, Norton DG, Hewett CJ, Kahi 2011; Pathol. J Am syndrome. polyposis hyperplastic with patients in pathway WNT classic the over predominates pathway cancer colorectal serrated A al. et MM, Polak E, Dekker KS, Boparai trial. Gut. 2012; Gut. trial. controlled randomised programme: screening cancer colorectal a in CT-colonography cathartic non- to compared colonoscopy of Burden al. et EM, Stoop MC, Haan De TR, De Wijkerslooth Screening colonoscopy inFDRsofpatients withSPS ‑ 32. ‑ 70. ‑ ​178: 84. ​2700 ‑ ​61: 7. ​1552 ​59: ​107: ‑ 9. ​1222 ​1315 ‑ 5. ‑ 29; quiz 1314, 1314, quiz 29; ​9: ​37: ​42 ​107: ​434 ‑ - 6. ​770 ‑ 42. ​ ​99: ​ ​25: ‑ 8. ​ ​54: 99 Chapter 6