Finnish National Esophago-Gastric Cancer Cohort (FINEGO) for studying outcomes after oesophageal and gastric cancer surgery: a protocol for a retrospective, population-based, nationwide cohort study in Finland

1 KauppilaJH, e al. BMJ Open 2019;9:e024094. doi:10.1136/bmjopen-2018-024094 Open access Finnish Na ional Esophago-Gas ic Cance Coho (FINEGO) o s udying ou comes a e oesophageal and gas ic cance su ge y: a p o ocol o a e ospec i e, popula ion-based, na ionwide coho s udy in Finland Joonas H Kauppila,1,2 Pasi Oh onen,3 Tuomo J Ka unen,4 A o Kokkola,5 Simo Laine,6 Tuomo Ran anen,7 A i Ris imäki,8 Ja i V Räsänen,9 Juha Saa nio,3 Ee o Sih o,10 Vesa Toikkanen,11 Tuula Ty äinen12 To ci e: KauppilaJH, Oh onenP, Ka unenTJ, e al. Finnish Na ional Esophago-Gas ic Cance Coho (FINEGO) o s udying ou comes a e oesophageal and gas ic cance su ge y: a p o ocol o a e ospec i e, popula ion- based, na ionwide coho s udy in Finland. BMJ Open 2019;9:e024094. doi:10.1136/ bmjopen-2018-024094 ►P epublica ion his o y and addi ional ma e ial o his pape a e a ailable online. To iew hese iles, please isi he jou nal online (h p:// dx. doi. o g/ 10. 1136/ bmjopen- 2018- 024094). Recei ed 9 May 2018 Re ised 10 Oc obe 2018 Accep ed 16 No embe 2018 Fo numbe ed a ilia ions see end o a icle. Co espondence o D Joonas HKauppila; joonas. kauppila@ oulu. i P o ocol © Au ho (s) (o hei employe (s)) 2019. Re-use pe mi ed unde CC BY-NC. No comme cial e-use. See igh s and pe missions. Published by BMJ. Abs AC In oduc ion Su ge y o oesophageal and gas ic cance s is associa ed wi h high mo bidi y, mo ali y and poo quali y o li e pos ope a i ely. The Finnish Na ional Esophago-Gas ic Cance Coho has been es ablished wi h he aim o iden i ying ac o s ha could con ibu e o imp o ed ou comes in oesophago-gas ic cance . Me hods and analysis All pa ien s wi h oesophageal and gas ic cance diagnosed in Finland be ween 1987 and 2015 will be iden i ied om he Finnish na ional egis ies. The Finnish Cance Regis y and Finnish Pa ien Regis y will be used o iden i y pa ien s ha ul il he inclusion c i e ia o he s udy: (1) diagnosis o oesophageal, gas o- oesophageal junc ion, o gas ic cance , (2) any su gical ea men o he diagnosed cance and (3) age o 18 o o e a he ime o diagnosis. Clinical a iables and complica ion in o ma ion will be e ie ed in ex ensi e da a collec ion om he medical eco ds o he ele an Finnish hospi als and comple e ollow-up o i al s a us om S a is ics Finland. P ima y endpoin is o e all all-cause mo ali y and seconda y endpoin s include complica ions, eope a ions, medica ion use and sick lea es. Sub-s udies will be implemen ed wi hin he coho o in es iga e speci ic popula ions unde going oesophageal and gas ic cance su ge y. The ini ial es ima ed sample size is 1800 pa ien s wi h su gically ea ed oesophageal cance and 7500 pa ien s wi h su gically ea ed gas ic cance . E hics and dissemina ion The s udy has been app o ed by he E hical Commi ee in No he n Os obo hnia, Finland and The Na ional Ins i u e o Heal h and Wel a e, Finland. S udy indings will be dissemina ed ia p esen a ions a con e ences and publica ions in pee - e iewed jou nals. In oduC Ion Gas ic cance is he hi d, and oesophageal cance he six h, leading cause o cance dea h wo ldwide.1 The incidence o oesoph- ageal adenoca cinoma is inc easing, while ha o oesophageal squamous cell ca cinoma and gas ic cance is dec easing in Finland,2 simila o o he Wes e n coun ies.3 The inci- dence o gas ic cance is slowly dec easing in majo i y o he coun ies ac oss he globe.4 Howe e , bo h cance s a e cha ac e ised by poo su i al e en a e cu a i ely in ended su ge y5–8 and a ‘ ex book ou come’ may be achie ed in less han hal o he pa ien s unde going oesophago-gas ic cance su ge y.9 S udies on sick lea es,10 o pos op- e a i e use o opioids as an ou come a e oesophageal and gas ic cance su ge y a e lacking, while hese a e impo an ou comes o he pa ien s. I has been shown ha sick lea es a ec o example job e en ion in pa ien s wi h cance .11 Randomised ials in oesophageal and gas ic cance ha e p o ided quali y s eng hs and limi a ions o his s udy ►The main s eng h o he s udy is he popula- ion-based design wi h comple e and accu a e as- ce ainmen and ollow-up o all pa ien s diagnosed wi h oesophageal o gas ic cance in Finland, coun- e ac ing selec ion bias. ►The inclusion o mul iple po en ial con ounding ac- o s om he egis ies and pa ien eco ds allows accu a e analysis o a a ie y o exposu es and end poin s. ►The sample size will la ge enough o enable obus su i al and eg ession analyses in smalle sub- g oups o pa ien s. ►The main limi a ions o he s udy a e he exclusion o pa ien s no unde going su ge y and in o ma ion lag o up o 2 yea s. on 28 Ap il 2019 by gues . P o ec ed by copy igh .h p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2018-024094 on 15 Janua y 2019. Downloaded om 2KauppilaJH, e al. BMJ Open 2019;9:e024094. doi:10.1136/bmjopen-2018-024094 Open access e idence ha neoadju an —and adju an he apies inc ease su i al12–15 and ha minimally in asi e su gical app oaches educe, o a leas do no inc ease compli- ca ions.16 17 Despi e hei good in e nal alidi y and lack o bias, andomised con olled s udies in gene al ha e limi ed ex e nal alidi y and applicabili y o gene al popu- la ion, and hus need o be complemen ed by quali y obse a ional s udies o eliably assess he e ec s o imple- men a ion o ial esul s in o p ac ice.18 Addi ionally, obse a ional s udies can p o ide e idence on ques ions ha ha e no , o canno , be e alua ed in andomised ials.18 In Finland, high-quali y egis y da a on hese cance s is eadily a ailable.19 Despi e he good a ailabili y, he exposu e and ou come da a in he egis ies a e no de ailed enough o su gical esea ch. Because o small popula ion (5.5 million) spa sely popula ing Finland, he hospi als a e many, and he single-cen e coho s con aining de ailed in o ma ion a e small, no neces- sa ily gene alisable and ha e po en ial selec ion bias. The e a e no p e ious coo dina ed na ionwide popula- ion-based esea ch e o s wi h de ailed clinical da a on oesophago-gas ic cance in Finland. To o e come hese challenges, an ex ensi e e ospec i e na ionwide da a collec ion om he pa ien medical eco ds is needed. The Finnish Na ional Esophago-Gas ic Cance Coho (FINEGO) was es ablished as a esea che -led e o o coo dina e his e ospec i e da abase. objec i es The speci ic objec i es o he FINEGO a e: ►To es ablish impo an baseline da a on na ional and egional ends and changes o e ime in oesophageal and gas ic cance su ge y, pos ope a i e mo bidi y and long- e m ou comes in Finland. ►To in es iga e associa ions be ween su geon and hospi al olume and pos ope a i e mo bidi y and mo ali y in oesophago-gas ic cance s. ►To assess he ele ance o clinical cha ac e is ics, modi iable isk ac o s, such as p eope a i e eeding, su gical app oach, ype o neoadju an ea men , o me hod o analgesia in ela ion o mo ali y and mo bidi y ou comes, as well as cance su i o ship, such as pos ope a i e medica ion use in oesopha- go-gas ic cance . ►To in es iga e whe he his ological assessmen could be used o p edic ion o p ognosis in oesophageal and gas ic cance . ME hods A mul icen e FINEGO-collabo a i e has been es ablished o conduc la ge-scale epidemiological, clinical and clini- copa hological s udies in oesophago-gas ic cance s. The collabo a i e includes one o wo senio consul an s uppe gas oin es inal o ho acic su geons as he local p incipal in es iga o s (PIs) om all academic cen es conduc ing oesophageal and gas ic cance su ge y in Finland, as well as senio consul an oesophago-gas ic pa hologis s and bios a is icians. The pa icipa ing esea che s will sign he needed p o essional con iden iali y consen s o be allowed access o pa ien da a ob ained om he egis ies. s udy design This s udy is a popula ion-based, na ionwide, e ospec i e coho s udy in Finland. The ini ial s udy pe iod is om 1 Janua y 1987 o 31 Decembe 2015, wi h ollow-up un il 31 Decembe 2016. The s udy pe iod will be expanded e e y 5 yea s o keep he coho upda ed o he mos ecen da a. Inclusion and exclusion c i e ia The pa ien s ul illing he ollowing inclusion c i e ia a e included in he s udy: 1. P ima y cance o epi helial o igin in he oesophagus, he gas o-oesophageal junc ion o he s omach. 2. Pa ien ecei es su gical ea men o he cance , in- cluding cu a i e, pallia i e, escue su ge y ha is, su - ge y a e cu a i e chemo adia ion, o endoscopic cu- a i e su ge y, such as endoscopic mucosal esec ion and endoscopic submucosal dissec ion. 3. Age a leas o o e 18 yea s du ing he ime o diagnosis. Iden i ica ion o he s udy pa icipan s The immu able, 11-digi pe sonal iden i ica ion numbe assigned o each esiden in he coun y allows eliable iden i ica ion and combining he egis y da a wi h pa ien eco ds.20 The pa ien s will be iden i ied h ough he Finnish Cance Regis y, and he Finnish Pa ien Regis y by sea ching hese egis ies o cance diag- noses (online supplemen a y able 1) and ope a ion s a us and ope a ions codes (online supplemen a y able 2). The iden i ica ion h ough bo h egis ies is done o ensu e nea 100% comple eness on oesophago-gas ic cance diagnosis. The pa ien s unde going oesophageal o gas ic cance su ge y will be iden i ied using he ope - a ions codes in he Finnish Pa ien Regis y. The Finnish Pa ien Regis y will p o ide he hospi al names and ope - a ion da es, based on which he ele an pa ien eco ds will be e ie ed om he a chi es o he hospi als in all 21 hospi al dis ic s in Finland. da a collec ion Regis y da a will be collec ed om The Finnish Cance Regis y, The Finnish Pa ien Regis y, The Popula ion Regis e Cen e, S a is ics Finland and The Social Insu ance Ins i u ion (Kela)- egis y ( able 1). The quali y o da a in hese egis- ies is known o be e y high21–24 and epo ing o he egis ies is manda o y by he Finnish Law. These egis y da a include he iden i ying in o ma ion, he a iables ela ed o he socio-economy, and will be used o calcu- la e he well- alida ed Cha lson’s Como bidi y Index (online supplemen a y able 3)25 and annual hospi al olumes. All egis y da a-de i ed a iables a e calcula ed by a bios a is ician. The pa ien eco ds o he included pa ien s iden i ied om he egis ies will be sc u inised by on 28 Ap il 2019 by gues . P o ec ed by copy igh .h p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2018-024094 on 15 Janua y 2019. Downloaded om 3 KauppilaJH, e al. BMJ Open 2019;9:e024094. doi:10.1136/bmjopen-2018-024094 Open access he s udy nu ses and he in es iga o s using s anda dised o ms o clinical a iables, including pa ien cha ac e is- ics and su geon, ou come and complica ion in o ma ion ( able 1 and online supplemen a y ex 1). The clinical a iables ha e been decided on by he in es iga o s in he FINEGO g oup. Key a iables, such as hose om he ope a ions cha s will be ex ac ed by one o he in es iga- o s, while he nu se ex ac s in o ma ion no conside ed p one o e o s, such as adminis a i e da a and labo a o y esul s. All eco ds and he co esponding da a collec ion o ms will be scanned and sa ed o la e use. The his o- logical samples will be collec ed om he biobanks. These o iginal, p ospec i ely collec ed diagnos ic slides om he p eope a i e gas oscopy and he su gical specimen will be sough om he biobanks’ a chi es o he s udy pa ien s. The sample slides a e e ie ed acco ding o he biobank policies, and scanned and digi ised in o a pic u e o m o assessmen and e iew o he his ological pa am- e e s and neoadju an ea men esponse ( able 1). The iden i ying in o ma ion o he selec ed pa ien s om each hospi al dis ic will be p o ided o he espec- i e PIs and adminis a i e pe sonnel o ob aining he pa ien eco ds da a om he heal hca e en i ies’ a chi es. The ob ained egis y da a, medical and heal h eco ds da a, as well as he digi ised his ological samples, will be en e ed in o he s udy da abase and pseudonymised using s udy iden i ie s a e he comple ion o he da a collec ion. The ha d copies o some o he s udy da a will be kep in a sa e deposi on he p emises o Uni e si y o Oulu. The iden i ica ion a iables om he egis ies will be kep in an enc yp ed and passwo d-p o ec ed ile wi h limi ed access g an ed o only he main bios a is ician and he PI o he p ojec . The pseudonymised coho wi hou iden i ying in o ma ion is a ailable o he membe s o he collabo a i e o sub-s udies wi hin he amewo k speci ied below. da a managemen and analysis plan The da a managemen and analyses in his s udy will be supe ised and conduc ed by an expe bios a is ician (PO). A e inishing he da a collec ion, a coho p o ile will be published. Fo he coho p o ile, numbe o new yea ly cance cases and he yea ly numbe o ope a ed cance s will be calcula ed based on he egis y da a. The baseline cha ac e is ics, ha is, numbe o pa ien s in each g oup o selec ed a iables will be epo ed in ables. O e all all-cause mo ali y will be epo ed o each cance ype based on he li e able me hod26 and depic ed using Kaplan-Meie cu es. Each o he sub-s udies will be planned in he collabo- a i e wi h a de ailed a p io i s udy p o ocol desc ibing he a ionale, aims, hypo hesis and s a is ical analysis plan including app op ia e me hods, po en ial con ounding and biases o he pa icula esea ch ques ion, as well as he bios a is ician in ol ed in he analysis. da a quali y assessmen The da a quali y in he egis ies will be checked h ough compa ing he collec ed clinical da a agains he da a, namely ype o su ge y and umou s age ob ained om he egis ies. In e nal audi , whe e a andom sample Table 1 Da a sou ces and da ase in o ma ion Da a sou ce Va iables The Finnish Cance Regis y Pe sonal iden i ica ion numbe (age, sex) Diagnosis numbe Da e o cance diagnosis Tumou s age The Finnish Pa ien Regis y Pe sonal iden i ica ion numbe (age, sex) Hospi al admissions da a ►Admi ing hospi al ►Da es o admission and discha ge ►Diagnosis codes ►Ope a ions codes The Popula ion Regis e Cen e Ma i al s a us S a is ics Finland Educa ion le el Da e o dea h Causes o dea h TheSocial Insu ance Ins i u ion(Kela) egis y Dispensed d ugs ►Type (Ana omical The apeu ic Chemical (ATC)-code) ►Da e dispensed ►Amoun o dispensed d ug Sick lea e (s a da e, end da e) Pension in o ma ion (s a da e) Pa ien eco ds Tumou s age in o ma ion Anaes hesia in o ma ion ►Type o anaes hesia ►ASA classi ica ion* Su ge y in o ma ion ►Type o su ge y ►Su geon olume ►Bleeding ►Ope a ion du a ion Complica ions ►Acco ding o he Esophagec omy Complica ions Consensus G oup ►Cla ien-Dindo classi ica ion Oncological ea men ►Neoadju an and adju an ea men ►T ea men modali y ►Complica ions Pa hology ►Tumou loca ion and s age ►Lymph node yield and esec ion adicali y Hospi al and in ensi e ca e uni s ay Biobanks Scans o o iginal diagnos ic slides on 28 Ap il 2019 by gues . P o ec ed by copy igh .h p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2018-024094 on 15 Janua y 2019. Downloaded om 4KauppilaJH, e al. BMJ Open 2019;9:e024094. doi:10.1136/bmjopen-2018-024094 Open access o he pa ien eco ds o 50 pa ien s wi h oesophageal cance and 50 pa ien s wi h gas ic cance will be e- e- iewed by ano he in es iga o , and he di e ences be ween he wo assessmen s will be checked agains he o iginal da a collec ion. I he e a e signs o di icul ies in he assessmen o ce ain a iables o sys ema ic e o s, hese a iables will be audi ed in mo e de ail. As o now, no ex e nal audi is planned, bu all s udy p o ocols, da a iles, s a is ical syn ax used o ob ain he esul s and he end-p oduc will be kep o u he po en ial audi s. sample size One o he main s eng hs is he la ge sample size o he s udy. I is es ima ed ha a leas 6000 oesophageal and 25 000 pa ien s wi h gas ic cance will be ound in sc eening du ing he s udy pe iod. O hese pa ien s, es i- ma ed 30% ha e been ope a ed o hei cance , yielding es ima es o 1800 oesophageal and 7500 pa ien s wi h gas ic cance o he s udy. Wi h 1800 pa ien s wi h oesophageal cance , he es i- ma ed powe would be >80% o eliably de ec weak associa ions (HR =1.15), gi en an equal dis ibu ion o pa ien s in he exposu e g oups. Wi h 7500 pa ien s wi h gas ic cance , he powe would be >80 o de ec an associ- a ion a he le el HR=1.07. Pe missions and egis a ion Rele an local pe missions and egis a ions a e ob ained by he collabo a i e om all he 21 hospi al dis ic s, namely he Lapland Hospi al dis ic , Länsi-Pohja Hospi al Dis ic , Kainuun Social and Heal h Ca e Join Au ho i y, The Hospi al dis ic o No he n Os obo hnia, Soi e, The Hospi al Dis ic o Sou h Os obo hnia, Pi kanmaa Hospi al Dis ic , Kan a-Häme Hospi al Dis ic , Vaasa Hospi al Dis ic , Sa akun a Hospi al Dis ic , Hospi al Dis ic o Sou hwes Finland, Ålands hälso- och sjuk å d, Join Au ho i y o he Helsinki and Uusimaa Hospi al Dis ic , Päijä -Häme Hospi al Dis ic , Kymenlaakso Social and Heal h Se ices Ca e, Sou h Ka elia Social and Heal h Ca e Dis ic (Ekso e), No h Ka elia Cen al Hospi al and Honkalampi Cen e, Eas Sa o Hospi al Dis ic , Sou h Sa o Social and Heal h Se ices, Kuopio Uni e si y Hospi al Dis ic and The Cen al Finland Hospi al Dis ic , as well as he ele an Biobanks, namely Au ia Biobank, Helsinki Biobank, Biobank o Eas e n Finland, Cen al Finland Biobank, No he n Finland Biobank Bo ealis and Finnish Clinical Biobank Tampe e. Indi idual in o med consen will no be sough om he pa ien s whose da a a e used in his obse a ional s udy. Ob aining he in o med consen has been wai ed by he Finnish law. The s udy will be conduc ed in acco - dance wi h he Decla a ion o Helsinki. Pa ien and public in ol emen Pa ien s o public we e no in ol ed in he de elopmen o he esea ch ques ion and s udy design o conduc ing he p esen s udy. dIsCussIon Oesophageal and gas ic cance s ha e poo p ognosis, e en a e cu a i e su ge y.5 6 The p esen popula- ion-based, na ionwide e ospec i e coho s udy will p o ide in o ma ion on he ecen ime ends in he ea men o oesophageal and gas ic cance and iden i y new, and e i y p e iously iden i ied, modi iable ac o s ela ed o mo bidi y, mo ali y and su i o ship a e oesophageal and gas ic cance su ge y. The s eng hs o he FINEGO-coho include i s popu- la ion-based design wi h comple e and accu a e asce - ainmen and ollow-up o all pa ien s diagnosed wi h oesophageal o gas ic cance in Finland, coun e ac ing selec ion bias. The combined use o egis y and pa ien eco ds da a educes in o ma ion bias. The inclusion o mul iple po en ial con ounding ac o s om he egis ies and pa ien eco ds allows accu a e analysis o a a ie y o exposu es and end poin s. The sample size will la ge enough o enable obus su i al and eg ession analyses in smalle sub-g oups o pa ien s. Compa ed wi h some global collabo a i es, such as he Wo ldwide Esophageal Cance Collabo a ion27 o Esophagec omy Complica ions Consensus G oup,28 he FINEGO can con ibu e o he scien i ic communi y by p oducing esul s in a eal-li e se ing including all pa ien s ope a ed o oesophageal and gas ic cance s in he coun y, while he collabo a- i es ypically include a sample o pa ien s ope a ed in high- olume cen es. Fu he mo e, he abo e-men ioned collabo a i es include only oesophageal cance , while he p esen s udy includes bo h oesophageal and gas ic cance . The e a e also limi a ions in he p esen s udy. The e ospec i e s udy design is po en ially weake in da a quali y, compa ed wi h a p ospec i e s udy. Howe e , he e ospec i e design enables ob aining a la ge numbe o pa ien s mo e quickly han a p ospec i e da a collec- ion, and he da a quali y in he egis ies he coho is based on is known o be e y high, and he manually collec ed pa ien eco ds da a will be igo ously checked and alida ed o quali y. Fu he mo e, a na ional quali y egis y o hese pa ien s is going o be es ablished, and he p ospec i e clinical da a collec ed in ha quali y egis y can be la e used in he upda es o he FINE- GO-coho o po en ially imp o e he quali y o he mo e ecen da a. All pa ien s no unde going su ge y will be excluded, because examining he pa ien eco ds o all he pa ien s would inc ease he numbe o in ol ed heal hca e en i ies signi ican ly o o e 250, educing he easibili y o he da a collec ion. Pa ien s unde going cu a i ely in ended o pallia i e chemo he apy and/o adio he apy will be excluded, educing he possibili ies o s udy pa ien s wi h dissemina ed disease o no eligible o any ype o su ge y. The coho is planned o be upda ed e e y 5 yea s, and he e is a lag o up o 2 yea s, including quali y checks and con ols, be o e he egis y da a is made a ailable o esea ch, p e en ing he s udy g oup om ge ing he mos ecen da a o analysis e en du ing he coho upda es. Howe e , his lag will on 28 Ap il 2019 by gues . P o ec ed by copy igh .h p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2018-024094 on 15 Janua y 2019. Downloaded om 5 KauppilaJH, e al. BMJ Open 2019;9:e024094. doi:10.1136/bmjopen-2018-024094 Open access no educe he ela i e sample size conside ably and he e ec on ollow-up in pe son-yea s is minimal due o high mo ali y a es o he cance s. Fu he mo e, he e a e some a iables, including smoking his o y and alcohol use, ha a e no eco ded in he egis ies and canno be eliably e ie ed om he pa ien eco ds, as hey a e no ou inely eco ded by he heal hca e pe sonnel in a s uc- u ed way. Howe e , he da a quali y and missing da a will be me iculously checked be o e unning he sub-s udies, and he missing da a will be aken in o accoun by using mul iple impu a ion me hods in he analyses o educe bias om missing da a. Taken oge he , his popula ion-based, na ionwide e ospec i e coho s udy will p o ide new e idence ega ding a ious unanswe ed ques ions in oesophageal and gas ic cance su ge y by combining epidemiolog- ical and clinical da a, as well as complemen andomised clinical ials by assessing hei indings in an unselec ed popula ion. Au ho a ilia ions 1Cance and T ansla ional Medicine Resea ch Uni , Uni e si y o Oulu and Oulu Uni e si y Hospi al, Oulu, Finland 2Uppe Gas oin es inal Su ge y, Depa men o Molecula Medicine and Su ge y, Ka olinska Ins i u e and Ka olinska Uni e si y Hospi al, S ockholm, Sweden 3Depa men o Su ge y, Oulu Uni e si y Hospi al, Oulu, Finland 4Depa men o Pa hology, Oulu Uni e si y Hospi al and Uni e si y o Oulu, Oulu, Finland 5Depa men o Su ge y, Uni e si y o Helsinki and Helsinki Uni e si y Hospi al, Helsinki, Finland 6The Di ision o Diges i e Su ge y and U ology, Tu ku Uni e si y Hospi al, Tu ku, Finland 7Depa men o Su ge y, Uni e si y o Eas e n Finland and Kuopio Uni e si y Hospi al, Kuopio, Finland 8Depa men o Pa hology and HUSLAB, Uni e si y o Helsinki and Helsinki Uni e si y Hospi al, Helsinki, Finland 9Depa men o Gene al Tho acic and Oesophageal Su ge y, Hea and Lung Cen e, Uni e si y o Helsinki and Helsinki Uni e si y Hospi al, Helsinki, Finland 10Depa men o Su ge y, Cen al Finland Cen al Hospi al, Jy askyla, Finland 11Depa men o Ca dio ho acic Su ge y, Hea Cen e , Tampe e Uni e si y Hospi al and Uni e si y o Tampe e, Tampe e, Tampe e, Finland 12Depa men o Gas oen e ology and Alimen a y T ac Su ge y, Tampe e Uni e si y Hospi al, Tampe e, Finland Con ibu o s JHK de eloped he s udy idea, concep and design, ini ia ed he collabo a i e p ojec , de eloped da a collec ion ools, ob ained pe missions and unding and d a ed he s udy p o ocol. PO was in ol ed in he s a is ical design, made subs an ial e isions o he p o ocol and was in ol ed in he o iginal concep , s udy design and implemen a ion. TJK was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. AK was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. SL was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. TR was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. AR was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. JVR was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. JS was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. ES was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. VT was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. TT was in ol ed in design and implemen a ion o he s udy, and e ised he p o ocol. JHK is he gua an o . Funding This wo k is suppo ed by esea ch g an s om he Sig id Jusélius Founda ion (Sig id Juséliuksen Sää iö), The Finnish Cance Founda ion (Syöpäsää iö) and O ion Resea ch Founda ion (O ionin Tu kimussää iö). The unding sou ces ha e no ole in he design and conduc o he s udy; collec ion, managemen , analysis and in e p e a ion o he da a; p epa a ion, e iew, o app o al o he manusc ip ; o decision o submi he s udy p o ocol o publica ion. Compe ing in e es s None decla ed. Pa ien consen o publica ion No equi ed. E hics app o al The E hical Commi ee in No he n Os h obo nia; The Na ional Ins i u e o Heal h and Wel a e; S a is ics Finland and he O ice o he Da a P o ec ion Ombudsman. P o enance and pee e iew No commissioned; ex e nally pee e iewed. open access This is an open access a icle dis ibu ed in acco dance wi h he C ea i e Commons A ibu ion Non Comme cial (CC BY-NC 4.0) license, which pe mi s o he s o dis ibu e, emix, adap , build upon his wo k non-comme cially, and license hei de i a i e wo ks on di e en e ms, p o ided he o iginal wo k is p ope ly ci ed, app op ia e c edi is gi en, any changes made indica ed, and he use is non-comme cial. See: h p:// c ea i ecommons. o g/ licenses/ by- nc/ 4. 0/. EFE EnCEs 1. Fi zmau ice C, Allen C, Ba be RM, e al. Global Bu den o Disease Cance Collabo a ion. Global, Regional, and Na ional Cance Incidence, Mo ali y, Yea s o Li e Los , Yea s Li ed Wi h Disabili y, and Disabili y-Adjus ed Li e-yea s o 32 Cance G oups, 1990 o 2015: A Sys ema ic Analysis o he Global Bu den o Disease S udy. JAMA Oncol 2017;3:524–48. 2. Weide pass E, Pukkala E. Time ends in socioeconomic di e ences in incidence a es o cance s o gas o-in es inal ac in Finland. BMC Gas oen e ol 2006;6:41. 3. Malho a GK, Yanala U, Ra ipa i A, e al. Global ends in esophageal cance . J Su g Oncol 2017;115:564–79. 4. Luo G, Zhang Y, Guo P, e al. Global pa e ns and ends in s omach cance incidence: Age, pe iod and bi h coho analysis. In J Cance 2017;141:1333–44. 5. Lage g en J, Smy h E, Cunningham D, e al. Oesophageal cance . Lance 2017;390:2383–96. 6. Van Cu sem E, Sagae X, Topal B, e al. Gas ic cance . Lance 2016;388:2654–64. 7. Kauppila JH, Ma sson F, B usselae s N, e al. P ognosis o oesophageal adenoca cinoma and squamous cell ca cinoma ollowing su ge y and no su ge y in a na ionwide Swedish coho s udy. BMJ Open 2018;8:e021495. 8. Asplund J, Kauppila JH, Ma sson F, e al. Su i al T ends in Gas ic Adenoca cinoma: A Popula ion-Based S udy in Sweden. Ann Su g Oncol 2018;25:2693–702. 9. an de Kaaij RT, de Rooij MV, an Coe o den F, e al. Using ex book ou come as a measu e o quali y o ca e in oesophagogas ic cance su ge y. B J Su g 2018;105:561–9. 10. Endo M, Ha uyama Y, Takahashi M, e al. Re u ning o wo k a e sick lea e due o cance : a 365-day coho s udy o Japanese cance su i o s. J Cance Su i 2016;10:320–9. 11. Veens a CM, Regenbogen SE, Hawley ST, e al. Associa ion o Paid Sick Lea e Wi h Job Re en ion and Financial Bu den Among Wo king Pa ien s Wi h Colo ec al Cance . JAMA 2015;314:2688–90. 12. Shapi o J, an Lanscho JJB, Hulsho M, e al. CROSS s udy g oup. Neoadju an chemo adio he apy plus su ge y e sus su ge y alone o oesophageal o junc ional cance (CROSS): long- e m esul s o a andomised con olled ial. Lance Oncol 2015;16:1090–8. 13. Cunningham D, Allum WH, S enning SP, e al. Pe iope a i e chemo he apy e sus su ge y alone o esec able gas oesophageal cance . N Engl J Med 2006;355:11–20. 14. Macdonald JS, Smalley SR, Benede i J, e al. Chemo adio he apy a e su ge y compa ed wi h su ge y alone o adenoca cinoma o he s omach o gas oesophageal junc ion. N Engl J Med 2001;345:725–30. 15. Kelsen DP, Win e KA, Gunde son LL, e al. Radia ion The apy Oncology G oupUSA In e g oup. Long- e m esul s o RTOG ial 8911 (USA In e g oup 113): a andom assignmen ial compa ison o chemo he apy ollowed by su ge y compa ed wi h su ge y alone o esophageal cance . J Clin Oncol 2007;25:3719–25. 16. Bie e SS, an Be ge Henegouwen MI, Maas KW, e al. Minimally in asi e e sus open oesophagec omy o pa ien s wi h oesophageal cance : a mul icen e, open-label, andomised con olled ial. Lance 2012;379:1887–92. 17. Kim HH, Hyung WJ, Cho GS, e al. Mo bidi y and mo ali y o lapa oscopic gas ec omy e sus open gas ec omy o gas ic cance : an in e im epo –a phase III mul icen e , p ospec i e, andomized T ial (KLASS T ial). Ann Su g 2010;251:417–20. on 28 Ap il 2019 by gues . P o ec ed by copy igh .h p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2018-024094 on 15 Janua y 2019. Downloaded om 6KauppilaJH, e al. BMJ Open 2019;9:e024094. doi:10.1136/bmjopen-2018-024094 Open access 18. Boo h CM, Tannock IF. Randomised con olled ials and popula ion- based obse a ional esea ch: pa ne s in he e olu ion o medical e idence. B J Cance 2014;110:551–5. 19. Ma e -Ouda J, Tao W, Wahlin K, e al. No dic egis y-based coho s udies: Possibili ies and pi alls when combining No dic egis y da a. Scand J Public Heal h 2017;45:14–19. 20. Lud igsson JF, O e blad-Olausson P, Pe e sson BU, e al. The Swedish pe sonal iden i y numbe : possibili ies and pi alls in heal hca e and medical esea ch. Eu J Epidemiol 2009;24:659–67. 21. Sund R. Quali y o he Finnish Hospi al Discha ge Regis e : a sys ema ic e iew. Scand J Public Heal h 2012;40:505–15. 22. Leinonen MK, Mie inen J, Heikkinen S, e al. Quali y measu es o he popula ion-based Finnish Cance Regis y indica e sound da a quali y o solid malignan umou s. Eu J Cance 2017;77:31–9. 23. Lah i RA, Pen ilä A. The alidi y o dea h ce i ica es: ou ine alida ion o dea h ce i ica ion and i s e ec s on mo ali y s a is ics. Fo ensic Sci In 2001;115:15–32. 24. Fu u K, We e ma k B, Ande sen M, e al. The No dic coun ies as a coho o pha macoepidemiological esea ch. Basic Clin Pha macol Toxicol 2010;106:86–94. 25. A mi age JN, an de Meulen JH. Royal College o Su geons Co- mo bidi y Consensus G oup. Iden i ying co-mo bidi y in su gical pa ien s using adminis a i e da a wi h he Royal College o Su geons Cha lson Sco e. B J Su g 2010;97:772–81. 26. Cu le SJ, Ede e F. Maximum u iliza ion o he li e able me hod in analyzing su i al. J Ch onic Dis 1958;8:699–712. 27. Rice TW, Rusch VW, Appe son-Hansen C, e al. Wo ldwide esophageal cance collabo a ion. Dis Esophagus 2009;22:1–8. 28. Low DE, Alde son D, Cecconello I, e al. In e na ional Consensus on S anda diza ion o Da a Collec ion o Complica ions Associa ed Wi h Esophagec omy: Esophagec omy Complica ions Consensus G oup (ECCG). Ann Su g 2015;262:286–94. on 28 Ap il 2019 by gues . P o ec ed by copy igh .h p://bmjopen.bmj.com/BMJ Open: i s published as 10.1136/bmjopen-2018-024094 on 15 Janua y 2019. Downloaded om