Rodzinna polipowatość gruczolakowata – Rokowania, prognozy i postęp choroby

Rodzinna polipowatość gruczolakowata
Rokowania, prognozy i postęp choroby

Rodzinna polipowatość gruczolakowata (FAP) to autosomalnie dominujące schorzenie z niemal 100% ryzykiem rozwoju raka jelita grubego bez leczenia, z medianą przeżycia nieleczonych pacjentów wynoszącą 42 lata. Klasyczna postać FAP prowadzi do transformacji nowotworowej średnio w wieku 39 lat, natomiast wariant osłabiony (AFAP) cechuje się późniejszym wiekiem zachorowania (~55 lat) i mniejszą liczbą polipów (<100). Proktolektomia odtwórcza (RPC) skutecznie eliminuje ryzyko raka jelita grubego, co potwierdzają badania długoterminowe obejmujące 110 pacjentów z co najmniej 11-letnim follow-upem, u których nie stwierdzono rozwoju raka w zbiorniku jelitowym ani górnym odcinku przewodu pokarmowego. Po kolektyomii głównymi zagrożeniami pozostają guzy desmoidalne (występujące u 4-32% pacjentów, z 10-50% śmiertelnością) oraz nowotwory górnego odcinka przewodu pokarmowego, zwłaszcza rak dwunastnicy i brodawki Vatera (dotykający do 12% pacjentów), co podkreśla konieczność ścisłego nadzoru endoskopowego.

Prognozy dla pacjentów z rodzinną polipowatością gruczolakowatą

Przebieg naturalny choroby bez leczenia
Rokowanie po leczeniu chirurgicznym
Czynniki wpływające na rokowanie po leczeniu
Wpływ nadzoru i badań przesiewowych na rokowanie
Prognostyczne znaczenie ekspresji i mutacji genu APC
Znaczenie multidyscyplinarnego podejścia dla rokowania
Nowoczesne badania i perspektywy poprawy rokowania
Wnioski końcowe
Kolejne rozdziały

Prognozy dla pacjentów z rodzinną polipowatością gruczolakowatą

Rodzinna polipowatość gruczolakowata (ang. Familial adenomatous polyposis, FAP) jest autosomalnie dominującym zaburzeniem charakteryzującym się wysokim ryzykiem rozwoju nowotworów, przede wszystkim raka jelita grubego i odbytnicy. Bez odpowiedniego leczenia rokowanie w tej chorobie jest niekorzystne, jednak dzięki współczesnym metodom terapeutycznym pacjenci mogą żyć znacznie dłużej.¹²

Przebieg naturalny choroby bez leczenia

Bez odpowiedniego leczenia, ryzyko rozwoju raka jelita grubego u pacjentów z FAP wynosi blisko 100%. Większość pacjentów z klasyczną postacią FAP rozwinie raka jelita grubego przed 40 rokiem życia, a średni wiek, w którym dochodzi do transformacji nowotworowej wynosi 39 lat.³⁴⁵

Mediana przeżycia u nieleczonych pacjentów z FAP wynosi zaledwie 42 lata, co podkreśla dramatyczne znaczenie wczesnej diagnostyki i profilaktyki chirurgicznej w tej chorobie.⁶⁷

W przypadku wariantu osłabionego FAP (attenuated FAP, AFAP), średni wiek zachorowania na raka jelita grubego jest późniejszy i wynosi około 55 lat, co wynika z mniejszej liczby polipów (typowo poniżej 100) i wolniejszej progresji do raka.⁸⁹¹⁰

Rokowanie po leczeniu chirurgicznym

Proktolektomia odtwórcza (RPC) eliminuje ryzyko rozwoju raka jelita grubego u pacjentów z FAP, co stanowi fundamentalną zmianę w rokowaniu. Badania długoterminowe potwierdzają, że u pacjentów poddanych tej procedurze nie obserwuje się rozwoju raka jelita grubego w przyszłości, pod warunkiem całkowitego usunięcia zagrożonych tkanek.¹¹

W badaniu obejmującym 110 pacjentów z FAP, którzy przeszli proktolektomię odtwórczą co najmniej 11 lat wcześniej, nie zaobserwowano rozwoju raka górnego odcinka przewodu pokarmowego ani w zbiorniku jelitowym (pouch), co wskazuje na skuteczność tej metody w prewencji nowotworów jelitowych.¹²

Po odpowiednim leczeniu chirurgicznym, pacjenci z FAP mogą prowadzić normalne, długie życie. Kolektomia znacząco wydłuża oczekiwaną długość życia i przy właściwej opiece pozwala na osiągnięcie normalnej długości życia.¹³¹⁴

Czynniki wpływające na rokowanie po leczeniu

Guzy desmoidalne

Po wyeliminowaniu ryzyka raka jelita grubego, główną przyczyną zgonów i niepowodzeń leczenia u pacjentów z FAP stają się guzy desmoidalne (mezenteryczne). W cytowanym badaniu długoterminowym, spośród 110 pacjentów po RPC, u 13 rozwinęły się guzy desmoidalne, a 2 zmarło z powodu tych guzów.¹⁵

Guzy desmoidalne występują u 4-32% pacjentów z FAP, a u około 20% pacjentów mogą rozwinąć się po kolektomii. Śmiertelność związana z tymi guzami jest znacząca i wynosi 10-50%, co czyni je istotnym czynnikiem pogarszającym rokowanie.¹⁶¹⁷

Guzy desmoidalne stanowią nie tylko główną przyczynę zgonu związaną z FAP po RPC, ale także główną przyczynę niepowodzenia funkcjonowania zbiornika jelitowego (pouch failure), co bezpośrednio wpływa na jakość życia pacjentów.¹⁸

Nowotwory górnego odcinka przewodu pokarmowego

Po kolektomii, drugą najczęstszą przyczyną zgonów u pacjentów z FAP są nowotwory górnego odcinka przewodu pokarmowego, co podkreśla znaczenie programów nadzoru po leczeniu chirurgicznym.¹⁹

Najczęstszym nowotworem złośliwym występującym u pacjentów z FAP, poza rakiem jelita grubego, jest rak dwunastnicy i brodawki Vatera, który dotyka nawet 12% pacjentów.²⁰

Skumulowane prawdopodobieństwo rozwoju jakiegokolwiek nowotworu poza jelitem grubym, głównie guzów okołobrodawkowych, wynosi 11% do 50 roku życia i 52% do 75 roku życia.²¹

Inne nowotwory związane z FAP

U pacjentów z FAP mogą występować również rzadsze nowotwory, takie jak rdzeniak (zespół Turcota), hepatoblastoma, rak tarczycy, rak żołądka, rak trzustki i rak nadnerczy, które mogą wpływać na ogólne rokowanie.²²²³

Hepatoblastoma może wystąpić już przy urodzeniu, co wskazuje na potrzebę badań przesiewowych w kierunku tego nowotworu u niemowląt z rodzin z FAP, nawet przed uzyskaniem wyników testów mutacji APC.²⁴

Wpływ nadzoru i badań przesiewowych na rokowanie

Liczne badania wykazały, że nadzór kolonoskopowy od wczesnego dzieciństwa, z odpowiednio zaplanowaną kolektomią, znacząco zmniejsza zachorowalność i śmiertelność związaną z rakiem jelita grubego.²⁵

Skumulowane przeżycie pacjentów z FAP wykazało znaczącą poprawę wraz z upływem czasu i wprowadzeniem systematycznych programów nadzoru. Od czasu utworzenia Duńskiego Rejestru Polipowatości, częstość występowania raka jelita grubego znacznie się zmniejszyła, a rokowanie uległo znacznej poprawie.²⁶

Ścisły nadzór nad górnym odcinkiem przewodu pokarmowego, z wykorzystaniem endoskopu z boczną optyką, umożliwia wykrycie poważnych zmian, które można leczyć bardziej agresywnie, co poprawia rokowanie dotyczące zmian dwunastniczych i okołobrodawkowych.²⁷

Prognostyczne znaczenie ekspresji i mutacji genu APC

Mutacje genu APC, który odpowiada za rozwój FAP, mają zróżnicowany wpływ na rokowanie w różnych typach nowotworów. W niektórych przypadkach ekspresja APC może być wykorzystana jako biomarker prognostyczny.²⁸

Wykazano, że chociaż wszyscy pacjenci z mutacjami genu APC rozwiną raki jelita grubego, liczba polipów i ramy czasowe, w których stają się złośliwe, zależą od lokalizacji mutacji w genie.²⁹

Wysoki poziom ekspresji APC wiąże się z niekorzystnym rokowaniem w raku piersi (gorsze OS, DMFS, RFS i PPS), natomiast niski poziom ekspresji APC koreluje z gorszym rokowaniem dla raka płuca i raka jajnika. Wyniki te wskazują, że rola APC jako czynnika prognostycznego różni się w zależności od typu nowotworu.³⁰

Znaczenie multidyscyplinarnego podejścia dla rokowania

Opieka nad pacjentem, u którego rozwinął się guz lub rak związany z FAP, powinna być zindywidualizowana w oparciu o jego sytuację kliniczną, wywiad rodzinny oraz potrzeby monitorowania w ramach leczenia i obserwacji po leczeniu.³⁰

Strategie zarządzania ryzykiem powinny uwzględniać aktualny wiek, inne problemy zdrowotne i ryzyko raka związane z wiekiem. Korzyści i ryzyko interwencji powinny być omawiane z doświadczonym lekarzem.³¹

W przypadku pacjentów z patogennym wariantem w dwóch lub więcej genach, które predysponują do raka, podejście do zarządzania ryzykiem powinno być szczególnie zindywidualizowane.³²

Nowoczesne badania i perspektywy poprawy rokowania

FAP stanowi idealny model do badania wczesnych etapów karcynogenezy raka jelita grubego. Najnowsze analizy multimomiczne ujawniają kluczowe zdarzenia genomowe, komórkowe i molekularne podczas najwcześniejszych etapów powstawania raka jelita grubego, co może prowadzić do opracowania potencjalnych mechanizmów profilaktyki farmakologicznej.³³

Wykazano, że sygnalizacja kwasu arachidonowego ulega wzmocnieniu we wczesnym stadium formowania się polipów, przyczyniając się do stanu zapalnego. Choć aspiryna i niesteroidowe leki przeciwzapalne są powszechnie stosowane jako profilaktyka u osób z FAP, mechanizm działania i optymalne ramy czasowe tej interwencji nie są dobrze poznane.³⁴

Lepsze zrozumienie niezbędnych zmian prowadzących do transformacji nowotworowej zarówno w dziedzicznym, jak i sporadycznym raku jelita grubego, może wpłynąć na podejście do profilaktyki, wczesnego wykrywania i leczenia, poprawiając tym samym rokowanie.³⁵

Wnioski końcowe

Rodzinna polipowatość gruczolakowata jest chorobą o niemal 100% ryzyku rozwoju raka jelita grubego bez profilaktycznej kolektomii. Jednak dzięki odpowiedniemu leczeniu chirurgicznemu i ścisłemu nadzorowi, rokowanie dla pacjentów znacząco się poprawiło.³⁶³⁷

Proktolektomia odtwórcza eliminuje ryzyko raka jelita grubego, jednak pacjenci nadal wymagają nadzoru z powodu ryzyka guzów desmoidalnych oraz nowotworów górnego odcinka przewodu pokarmowego, które stają się głównymi czynnikami wpływającymi na długoterminowe rokowanie po wyeliminowaniu ryzyka raka jelita grubego.³⁸³⁹

Z właściwą opieką i regularnym nadzorem, pacjenci z FAP mogą prowadzić normalne życie, a ich oczekiwana długość życia zbliża się do populacji ogólnej, co podkreśla ogromne znaczenie wczesnej diagnostyki, profilaktycznej chirurgii i programów nadzoru w poprawie rokowania.⁴⁰⁴¹

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Materiały źródłowe

#1
https://www.omim.org/entry/175100
Familial adenomatous polyposis-1 (FAP1) is an autosomal dominant disorder characterized by predisposition to cancer. Affected individuals usually develop hundreds to thousands of adenomatous polyps of the colon and rectum, a small proportion of which will progress to colorectal carcinoma if not surgically treated. […] Colorectal cancer will develop in nearly all affected persons by the sixth decade of life if prophylactic colectomy is not performed (Giardiello et al., 2002). […] Attenuated adenomatous polyposis coli is characterized by the occurrence of fewer than 100 colonic adenomas and a later onset of colorectal cancer (age greater than 40 years) (Soravia et al., 1998).
#2 APC (Familial adenomatous polyposis) â risk management
https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma
Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by a germline pathogenic variant in the APC gene. […] Classical familial adenomatous polyposis (FAP) is defined by the presence of 100 colorectal adenomas (cumulative count), autosomal-dominant inheritance and young age of onset of polyposis (mean age approximately 15 years). […] Atypical/attenuated familial adenomatous polyposis (AFAP) is defined by the presence of 100 colorectal adenomas (cumulative count) and autosomal-dominant inheritance, with later onset of adenomas and cancer compared with classical FAP. […] The care of an individual who has developed a related tumour or cancer should be individualised based on their clinical situation, their family history and the monitoring they need as part of their treatment and post-treatment follow-up.
#3 Familial Adenomatous Polyposis (FAP): Symptoms, Diagnosis, Risks
https://my.clevelandclinic.org/health/diseases/16993-familial-adenomatous-polyposis-fap
Without treatment, the risk of developing colorectal cancer with familial adenomatous polyposis is close to 100%. […] Most people with FAP will develop cancer by their middle-age years. […] Without timely treatment, the median life expectancy is 42 years. But with appropriate care, you can live a normal life. […] Once your colon has been removed, your biggest risk is from other gastrointestinal cancers or problematic desmoid tumors. […] You can expect to have a total colectomy sometime in your early life. […] But you can live a long and healthy life after a colectomy.
#4 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/175377-overview
Patients with untreated FAP have a median life expectancy of 42 years. Life expectancy is extended greatly in those treated with colectomy. […] Upper gastrointestinal cancers and desmoid tumors are the most common causes of death in patients who have undergone colectomy. This is why surveillance programs, especially after colectomy, are essential. Colectomy only addresses the risk of colon cancer development. […] The cumulative probability of developing any type of noncolorectal cancer, mostly periampullary tumors, is 11% by age 50 years and 52% by age 75 years. […] The principal cause of mortality is colorectal cancer, which develops in all patients unless they are treated. The mean age at which colorectal cancer develops in patients with classic FAP is 39 years. […] The second reported lethal complication of FAP is diffuse mesenteric fibromatosis and is referred to as a desmoid tumor. It involves intra-abdominal organs and vessels, causing gastrointestinal obstruction and constriction of veins, arteries, and ureters. Desmoid tumors are reported in 4%-32% of patients.
#5 Familial adenomatous polyposis: MedlinePlus GeneticsLock
https://medlineplus.gov/genetics/condition/familial-adenomatous-polyposis/
Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. […] The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. […] The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years. […] In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. […] Although most people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they become malignant depend on the location of the mutation in the gene.
#6 Familial Adenomatous Polyposis (FAP): Symptoms, Diagnosis, Risks
https://my.clevelandclinic.org/health/diseases/16993-familial-adenomatous-polyposis-fap
Without treatment, the risk of developing colorectal cancer with familial adenomatous polyposis is close to 100%. […] Most people with FAP will develop cancer by their middle-age years. […] Without timely treatment, the median life expectancy is 42 years. But with appropriate care, you can live a normal life. […] Once your colon has been removed, your biggest risk is from other gastrointestinal cancers or problematic desmoid tumors. […] You can expect to have a total colectomy sometime in your early life. […] But you can live a long and healthy life after a colectomy.
#7 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/175377-overview
Patients with untreated FAP have a median life expectancy of 42 years. Life expectancy is extended greatly in those treated with colectomy. […] Upper gastrointestinal cancers and desmoid tumors are the most common causes of death in patients who have undergone colectomy. This is why surveillance programs, especially after colectomy, are essential. Colectomy only addresses the risk of colon cancer development. […] The cumulative probability of developing any type of noncolorectal cancer, mostly periampullary tumors, is 11% by age 50 years and 52% by age 75 years. […] The principal cause of mortality is colorectal cancer, which develops in all patients unless they are treated. The mean age at which colorectal cancer develops in patients with classic FAP is 39 years. […] The second reported lethal complication of FAP is diffuse mesenteric fibromatosis and is referred to as a desmoid tumor. It involves intra-abdominal organs and vessels, causing gastrointestinal obstruction and constriction of veins, arteries, and ureters. Desmoid tumors are reported in 4%-32% of patients.
#8 Familial adenomatous polyposis: MedlinePlus GeneticsLock
https://medlineplus.gov/genetics/condition/familial-adenomatous-polyposis/
Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. […] The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. […] The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years. […] In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. […] Although most people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they become malignant depend on the location of the mutation in the gene.
#9 Familial adenomatous polyposis – Wikipedia
https://en.wikipedia.org/wiki/Familial_adenomatous_polyposis
The incidence of the mutation is between 1 in 10,000 and 1 in 15,000 births. By age 35 years, 95% of individuals with FAP (100 adenomas) have polyps. Without colectomy, colon cancer is virtually inevitable. The mean age of colon cancer in untreated individuals is 39 years (range 34-43 years). […] Attenuated FAP arises when APC is defective but still somewhat functional. As a result, it retains part of its ability to suppress polyps. Therefore, attenuated FAP manifests as colorectal cancer unusually late (age 40-70, average=55), and typically with few, or at least far fewer polyps (typically 30), than the more usual version of FAP, at an age when FAP is no longer considered much of a likelihood or risk according to usual FAP epidemiology.
#10
https://www.omim.org/entry/175100
Familial adenomatous polyposis-1 (FAP1) is an autosomal dominant disorder characterized by predisposition to cancer. Affected individuals usually develop hundreds to thousands of adenomatous polyps of the colon and rectum, a small proportion of which will progress to colorectal carcinoma if not surgically treated. […] Colorectal cancer will develop in nearly all affected persons by the sixth decade of life if prophylactic colectomy is not performed (Giardiello et al., 2002). […] Attenuated adenomatous polyposis coli is characterized by the occurrence of fewer than 100 colonic adenomas and a later onset of colorectal cancer (age greater than 40 years) (Soravia et al., 1998).
#11 Long-term Outcome of Familial Adenomatous Polyposis Patients After Restorative Coloproctectomy
https://pmc.ncbi.nlm.nih.gov/articles/PMC1356236/
Restorative proctocolectomy (RPC) eliminates the risk of colorectal adenocarcinoma in familial adenomatous polyposis (FAP) patients, but desmoid tumors, duodenal, and ileal adenomas can still develop. […] RPC eliminates the risk of colorectal cancer, and close upper GI surveillance may help prevent duodenal malignancy. MDTs are the principal cause of death, once colorectal cancer has been prevented, and the main reason for worsening functional results. […] Among 110 patients with FAP that had restorative proctocolectomy at least 11 years ago, none have developed cancer of the upper gastrointestinal tract or the pouch, but 13 have developed mesenteric desmoid tumors, and 2 have died of these tumors. […] In our series, after a mean follow-up of 14 years after RPC and a minimal follow-up of 11 years, the main cause of death remains colorectal cancers discovered at the time of RPC. None of the patients who had their RPC during the time they had no invasive carcinoma of the colon or rectum have developed a metastatic cancer since their operation, and the main cause of death in these patients was mesenteric desmoid tumor.
#12 Long-term Outcome of Familial Adenomatous Polyposis Patients After Restorative Coloproctectomy
https://pmc.ncbi.nlm.nih.gov/articles/PMC1356236/
Restorative proctocolectomy (RPC) eliminates the risk of colorectal adenocarcinoma in familial adenomatous polyposis (FAP) patients, but desmoid tumors, duodenal, and ileal adenomas can still develop. […] RPC eliminates the risk of colorectal cancer, and close upper GI surveillance may help prevent duodenal malignancy. MDTs are the principal cause of death, once colorectal cancer has been prevented, and the main reason for worsening functional results. […] Among 110 patients with FAP that had restorative proctocolectomy at least 11 years ago, none have developed cancer of the upper gastrointestinal tract or the pouch, but 13 have developed mesenteric desmoid tumors, and 2 have died of these tumors. […] In our series, after a mean follow-up of 14 years after RPC and a minimal follow-up of 11 years, the main cause of death remains colorectal cancers discovered at the time of RPC. None of the patients who had their RPC during the time they had no invasive carcinoma of the colon or rectum have developed a metastatic cancer since their operation, and the main cause of death in these patients was mesenteric desmoid tumor.
#13 Familial Adenomatous Polyposis (FAP): Symptoms, Diagnosis, Risks
https://my.clevelandclinic.org/health/diseases/16993-familial-adenomatous-polyposis-fap
Without treatment, the risk of developing colorectal cancer with familial adenomatous polyposis is close to 100%. […] Most people with FAP will develop cancer by their middle-age years. […] Without timely treatment, the median life expectancy is 42 years. But with appropriate care, you can live a normal life. […] Once your colon has been removed, your biggest risk is from other gastrointestinal cancers or problematic desmoid tumors. […] You can expect to have a total colectomy sometime in your early life. […] But you can live a long and healthy life after a colectomy.
#14 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/175377-overview
Patients with untreated FAP have a median life expectancy of 42 years. Life expectancy is extended greatly in those treated with colectomy. […] Upper gastrointestinal cancers and desmoid tumors are the most common causes of death in patients who have undergone colectomy. This is why surveillance programs, especially after colectomy, are essential. Colectomy only addresses the risk of colon cancer development. […] The cumulative probability of developing any type of noncolorectal cancer, mostly periampullary tumors, is 11% by age 50 years and 52% by age 75 years. […] The principal cause of mortality is colorectal cancer, which develops in all patients unless they are treated. The mean age at which colorectal cancer develops in patients with classic FAP is 39 years. […] The second reported lethal complication of FAP is diffuse mesenteric fibromatosis and is referred to as a desmoid tumor. It involves intra-abdominal organs and vessels, causing gastrointestinal obstruction and constriction of veins, arteries, and ureters. Desmoid tumors are reported in 4%-32% of patients.
#15 Long-term Outcome of Familial Adenomatous Polyposis Patients After Restorative Coloproctectomy
https://pmc.ncbi.nlm.nih.gov/articles/PMC1356236/
Restorative proctocolectomy (RPC) eliminates the risk of colorectal adenocarcinoma in familial adenomatous polyposis (FAP) patients, but desmoid tumors, duodenal, and ileal adenomas can still develop. […] RPC eliminates the risk of colorectal cancer, and close upper GI surveillance may help prevent duodenal malignancy. MDTs are the principal cause of death, once colorectal cancer has been prevented, and the main reason for worsening functional results. […] Among 110 patients with FAP that had restorative proctocolectomy at least 11 years ago, none have developed cancer of the upper gastrointestinal tract or the pouch, but 13 have developed mesenteric desmoid tumors, and 2 have died of these tumors. […] In our series, after a mean follow-up of 14 years after RPC and a minimal follow-up of 11 years, the main cause of death remains colorectal cancers discovered at the time of RPC. None of the patients who had their RPC during the time they had no invasive carcinoma of the colon or rectum have developed a metastatic cancer since their operation, and the main cause of death in these patients was mesenteric desmoid tumor.
#16 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/175377-overview
Patients with untreated FAP have a median life expectancy of 42 years. Life expectancy is extended greatly in those treated with colectomy. […] Upper gastrointestinal cancers and desmoid tumors are the most common causes of death in patients who have undergone colectomy. This is why surveillance programs, especially after colectomy, are essential. Colectomy only addresses the risk of colon cancer development. […] The cumulative probability of developing any type of noncolorectal cancer, mostly periampullary tumors, is 11% by age 50 years and 52% by age 75 years. […] The principal cause of mortality is colorectal cancer, which develops in all patients unless they are treated. The mean age at which colorectal cancer develops in patients with classic FAP is 39 years. […] The second reported lethal complication of FAP is diffuse mesenteric fibromatosis and is referred to as a desmoid tumor. It involves intra-abdominal organs and vessels, causing gastrointestinal obstruction and constriction of veins, arteries, and ureters. Desmoid tumors are reported in 4%-32% of patients.
#17 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/175377-overview
Even after the appropriate surgical treatment of FAP, 20% of patients may develop desmoid tumors after colectomy. […] The mortality from these tumors is 10%-50%. […] The second most common malignancy in patients with FAP is adenocarcinoma of the duodenum and the papilla of Vater. It affects as many as 12% of patients. […] Rarer cancers associated with FAP include medulloblastomas (Turcot syndrome), hepatoblastoma, thyroid cancer, gastric cancer, pancreatic cancer, and adrenal cancer. […] Complications of FAP include the following: Colorectal cancer (100% in untreated patients), Duodenal or periampullary adenocarcinoma (4%-12%), Desmoid formation (as many as 20%, typically postcolectomy), Other cancers, including medulloblastoma, hepatoblastoma, thyroid cancer, gastric cancer, pancreatic cancer, and adrenal cancer, Development of rectal cancer in patients with a retained rectum.
#18 Long-term Outcome of Familial Adenomatous Polyposis Patients After Restorative Coloproctectomy
https://pmc.ncbi.nlm.nih.gov/articles/PMC1356236/
In conclusion, our results demonstrate that RPC eliminates the risk of rectal cancer, that duodenal and ampullary lesions are less worrisome than previously reported as long as close surveillance with a side-viewing instrument is used to detect severe lesions that can be treated more aggressively. Mesenteric desmoid tumors remain the primary cause of death linked to FAP after RPC, and also the principal cause of pouch failure.
#19 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/175377-overview
Patients with untreated FAP have a median life expectancy of 42 years. Life expectancy is extended greatly in those treated with colectomy. […] Upper gastrointestinal cancers and desmoid tumors are the most common causes of death in patients who have undergone colectomy. This is why surveillance programs, especially after colectomy, are essential. Colectomy only addresses the risk of colon cancer development. […] The cumulative probability of developing any type of noncolorectal cancer, mostly periampullary tumors, is 11% by age 50 years and 52% by age 75 years. […] The principal cause of mortality is colorectal cancer, which develops in all patients unless they are treated. The mean age at which colorectal cancer develops in patients with classic FAP is 39 years. […] The second reported lethal complication of FAP is diffuse mesenteric fibromatosis and is referred to as a desmoid tumor. It involves intra-abdominal organs and vessels, causing gastrointestinal obstruction and constriction of veins, arteries, and ureters. Desmoid tumors are reported in 4%-32% of patients.
#20 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/175377-overview
Even after the appropriate surgical treatment of FAP, 20% of patients may develop desmoid tumors after colectomy. […] The mortality from these tumors is 10%-50%. […] The second most common malignancy in patients with FAP is adenocarcinoma of the duodenum and the papilla of Vater. It affects as many as 12% of patients. […] Rarer cancers associated with FAP include medulloblastomas (Turcot syndrome), hepatoblastoma, thyroid cancer, gastric cancer, pancreatic cancer, and adrenal cancer. […] Complications of FAP include the following: Colorectal cancer (100% in untreated patients), Duodenal or periampullary adenocarcinoma (4%-12%), Desmoid formation (as many as 20%, typically postcolectomy), Other cancers, including medulloblastoma, hepatoblastoma, thyroid cancer, gastric cancer, pancreatic cancer, and adrenal cancer, Development of rectal cancer in patients with a retained rectum.
#21 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/175377-overview
Patients with untreated FAP have a median life expectancy of 42 years. Life expectancy is extended greatly in those treated with colectomy. […] Upper gastrointestinal cancers and desmoid tumors are the most common causes of death in patients who have undergone colectomy. This is why surveillance programs, especially after colectomy, are essential. Colectomy only addresses the risk of colon cancer development. […] The cumulative probability of developing any type of noncolorectal cancer, mostly periampullary tumors, is 11% by age 50 years and 52% by age 75 years. […] The principal cause of mortality is colorectal cancer, which develops in all patients unless they are treated. The mean age at which colorectal cancer develops in patients with classic FAP is 39 years. […] The second reported lethal complication of FAP is diffuse mesenteric fibromatosis and is referred to as a desmoid tumor. It involves intra-abdominal organs and vessels, causing gastrointestinal obstruction and constriction of veins, arteries, and ureters. Desmoid tumors are reported in 4%-32% of patients.
#22 Familial Adenomatous Polyposis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/175377-overview
Even after the appropriate surgical treatment of FAP, 20% of patients may develop desmoid tumors after colectomy. […] The mortality from these tumors is 10%-50%. […] The second most common malignancy in patients with FAP is adenocarcinoma of the duodenum and the papilla of Vater. It affects as many as 12% of patients. […] Rarer cancers associated with FAP include medulloblastomas (Turcot syndrome), hepatoblastoma, thyroid cancer, gastric cancer, pancreatic cancer, and adrenal cancer. […] Complications of FAP include the following: Colorectal cancer (100% in untreated patients), Duodenal or periampullary adenocarcinoma (4%-12%), Desmoid formation (as many as 20%, typically postcolectomy), Other cancers, including medulloblastoma, hepatoblastoma, thyroid cancer, gastric cancer, pancreatic cancer, and adrenal cancer, Development of rectal cancer in patients with a retained rectum.
#23 Familial adenomatous polyposis: MedlinePlus GeneticsLock
https://medlineplus.gov/genetics/condition/familial-adenomatous-polyposis/
Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. […] The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. […] The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years. […] In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. […] Although most people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they become malignant depend on the location of the mutation in the gene.
#24 APC (Familial adenomatous polyposis) â risk management
https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma
Familial adenomatous polyposis (FAP) is a hereditary condition with a near 100 % lifetime risk of colorectal cancer without prophylactic colectomy. […] Hepatoblastoma may present at birth, and screening for hepatoblastoma in infancy in families with FAP prior to APC mutation testing results may be warranted.
#25 APC (Familial adenomatous polyposis) â risk management
https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma
The risk management of an individual with a pathogenic variant in two or more genes that confer a predisposition to cancer should also be individualised. […] Cancer/tumour risk management guidelines: The choice of risk management strategy should take into account current age, other health issues and age-related cancer risk. […] Risks and benefits of interventions should be discussed with an experienced medical professional. […] Multiple studies have demonstrated that surveillance colonoscopy from early childhood with appropriately timed colectomy reduces CRC incidence and mortality. […] The cumulative crude survival in FAP showed substantial improvement with time. […] Since the establishment of the Danish Polyposis Register, the prevalence of colorectal cancer has decreased considerably and the prognosis has improved substantially.
#26 APC (Familial adenomatous polyposis) â risk management
https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma
The risk management of an individual with a pathogenic variant in two or more genes that confer a predisposition to cancer should also be individualised. […] Cancer/tumour risk management guidelines: The choice of risk management strategy should take into account current age, other health issues and age-related cancer risk. […] Risks and benefits of interventions should be discussed with an experienced medical professional. […] Multiple studies have demonstrated that surveillance colonoscopy from early childhood with appropriately timed colectomy reduces CRC incidence and mortality. […] The cumulative crude survival in FAP showed substantial improvement with time. […] Since the establishment of the Danish Polyposis Register, the prevalence of colorectal cancer has decreased considerably and the prognosis has improved substantially.
#27 Long-term Outcome of Familial Adenomatous Polyposis Patients After Restorative Coloproctectomy
https://pmc.ncbi.nlm.nih.gov/articles/PMC1356236/
In conclusion, our results demonstrate that RPC eliminates the risk of rectal cancer, that duodenal and ampullary lesions are less worrisome than previously reported as long as close surveillance with a side-viewing instrument is used to detect severe lesions that can be treated more aggressively. Mesenteric desmoid tumors remain the primary cause of death linked to FAP after RPC, and also the principal cause of pouch failure.
#28 A pan-cancer analysis on the carcinogenic effect of human adenomatous polyposis coli | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0265655
Adenomatous polyposis coli (APC) is the most commonly mutated gene in colon cancer and can cause familial adenomatous polyposis (FAP). […] APC promoter hypermethylation also can be a prognostic marker for breast cancer, and high expression of APC is an unfavorable prognostic biomarker for T4 gastric cancer. […] The expressed level of APC is also involved in the level of CD8+ T-cell infiltration, Tregs infiltration, and cancer-associated fibroblast infiltration. […] The results showed that the survival prognostic analysis data of the APC gene put forth completely different conclusions for different tumors. […] The overall results show that there is a correlation between the expressed level of APC and the markers of survival. […] The expression level of APC correlated with the progression of kidney renal cell carcinoma, testicular germ cell tumor, thyroid carcinoma, lung squamous cell, but not others.
#29 Familial adenomatous polyposis: MedlinePlus GeneticsLock
https://medlineplus.gov/genetics/condition/familial-adenomatous-polyposis/
Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. […] The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. […] The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years. […] In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. […] Although most people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they become malignant depend on the location of the mutation in the gene.
#30 A pan-cancer analysis on the carcinogenic effect of human adenomatous polyposis coli | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0265655
Compared with its expression in normal tissues, APC has low expression in most tumors. […] The correlation of APC expression with the pathological stages of most cancers is low, a finding that suggests that APC has persistent low expression in cancer progression. […] High expression APC and poor OS, DMFS, RFS and PPS prognosis for BRCA were highly correlated. […] In contrast, a low expression level of APC was highly correlated with poor OS, FP and PPS for LUAD and poor RFS for ovarian cancer and poor FP and PPS for gastric cancer. […] The results showed that APC mutations have no correlation with the survival prognosis of colorectal adenocarcinoma, but they are correlated with the survival prognosis of uterine corpus endometrial carcinoma. […] APC plays a central role in predicting overall survival, and there may be 0, 1, or 2 truncation mutations in APC, and each mutation will have a significantly different effect on survival. […] Our results suggest that APC expression is correlated with immune infiltration and participates in tumor regulation, but it has different regulatory effects among tumors.
#30 APC (Familial adenomatous polyposis) â risk management
https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma
Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by a germline pathogenic variant in the APC gene. […] Classical familial adenomatous polyposis (FAP) is defined by the presence of 100 colorectal adenomas (cumulative count), autosomal-dominant inheritance and young age of onset of polyposis (mean age approximately 15 years). […] Atypical/attenuated familial adenomatous polyposis (AFAP) is defined by the presence of 100 colorectal adenomas (cumulative count) and autosomal-dominant inheritance, with later onset of adenomas and cancer compared with classical FAP. […] The care of an individual who has developed a related tumour or cancer should be individualised based on their clinical situation, their family history and the monitoring they need as part of their treatment and post-treatment follow-up.
#31 APC (Familial adenomatous polyposis) â risk management
https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma
The risk management of an individual with a pathogenic variant in two or more genes that confer a predisposition to cancer should also be individualised. […] Cancer/tumour risk management guidelines: The choice of risk management strategy should take into account current age, other health issues and age-related cancer risk. […] Risks and benefits of interventions should be discussed with an experienced medical professional. […] Multiple studies have demonstrated that surveillance colonoscopy from early childhood with appropriately timed colectomy reduces CRC incidence and mortality. […] The cumulative crude survival in FAP showed substantial improvement with time. […] Since the establishment of the Danish Polyposis Register, the prevalence of colorectal cancer has decreased considerably and the prognosis has improved substantially.
#32 APC (Familial adenomatous polyposis) â risk management
https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma
The risk management of an individual with a pathogenic variant in two or more genes that confer a predisposition to cancer should also be individualised. […] Cancer/tumour risk management guidelines: The choice of risk management strategy should take into account current age, other health issues and age-related cancer risk. […] Risks and benefits of interventions should be discussed with an experienced medical professional. […] Multiple studies have demonstrated that surveillance colonoscopy from early childhood with appropriately timed colectomy reduces CRC incidence and mortality. […] The cumulative crude survival in FAP showed substantial improvement with time. […] Since the establishment of the Danish Polyposis Register, the prevalence of colorectal cancer has decreased considerably and the prognosis has improved substantially.
#33 Multiomic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis | Nature Cancer
https://www.nature.com/articles/s43018-024-00831-z
Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). […] Overall, our results reveal key genomic, cellular and molecular events during the earliest steps in CRC formation and potential mechanisms of pharmaceutical prophylaxis. […] Familial adenomatous polyposis (FAP) is an ideal system in which to study early events during CRC formation for multiple reasons. […] Third, persons with FAP have a nearly 100% lifetime risk of developing invasive adenocarcinomas and, thus, often have their entire colon removed as prophylactic treatment once the number of polyps that develop becomes unmanageable through endoscopic surveillance. […] Such information is expected to enhance our understanding of the requisite alterations for transformation in both hereditary and sporadic CRC and may inform the approach to prevention, early detection and treatment.
#34 Multiomic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis | Nature Cancer
https://www.nature.com/articles/s43018-024-00831-z
This rich open-access multiomic, multisample dataset also provides a valuable scientific resource to the community, complementing the existing datasets on sporadic CRCs. […] The transition of polyps to dysplasia was characterized by proteomic and transcriptomic alterations that were predominantly downregulated; functional enrichment was nearly entirely composed of downregulated pathways. […] Arachidonic acid signaling was also upregulated early during polyp formation, contributing to inflammation. […] While aspirin and NSAIDs are commonly used as prophylactic treatment for persons with FAP, the mechanism of action and optimal timing of this intervention are not known. […] This rich multimodal dataset illuminates the steps involved in precancer formation and transition to malignancy at unprecedented resolution and should serve as a valuable resource for the community.
#35 Multiomic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis | Nature Cancer
https://www.nature.com/articles/s43018-024-00831-z
Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). […] Overall, our results reveal key genomic, cellular and molecular events during the earliest steps in CRC formation and potential mechanisms of pharmaceutical prophylaxis. […] Familial adenomatous polyposis (FAP) is an ideal system in which to study early events during CRC formation for multiple reasons. […] Third, persons with FAP have a nearly 100% lifetime risk of developing invasive adenocarcinomas and, thus, often have their entire colon removed as prophylactic treatment once the number of polyps that develop becomes unmanageable through endoscopic surveillance. […] Such information is expected to enhance our understanding of the requisite alterations for transformation in both hereditary and sporadic CRC and may inform the approach to prevention, early detection and treatment.
#36 APC (Familial adenomatous polyposis) â risk management
https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma
Familial adenomatous polyposis (FAP) is a hereditary condition with a near 100 % lifetime risk of colorectal cancer without prophylactic colectomy. […] Hepatoblastoma may present at birth, and screening for hepatoblastoma in infancy in families with FAP prior to APC mutation testing results may be warranted.
#37 Familial Adenomatous Polyposis (FAP): Symptoms, Diagnosis, Risks
https://my.clevelandclinic.org/health/diseases/16993-familial-adenomatous-polyposis-fap
Without treatment, the risk of developing colorectal cancer with familial adenomatous polyposis is close to 100%. […] Most people with FAP will develop cancer by their middle-age years. […] Without timely treatment, the median life expectancy is 42 years. But with appropriate care, you can live a normal life. […] Once your colon has been removed, your biggest risk is from other gastrointestinal cancers or problematic desmoid tumors. […] You can expect to have a total colectomy sometime in your early life. […] But you can live a long and healthy life after a colectomy.
#38 Long-term Outcome of Familial Adenomatous Polyposis Patients After Restorative Coloproctectomy
https://pmc.ncbi.nlm.nih.gov/articles/PMC1356236/
Restorative proctocolectomy (RPC) eliminates the risk of colorectal adenocarcinoma in familial adenomatous polyposis (FAP) patients, but desmoid tumors, duodenal, and ileal adenomas can still develop. […] RPC eliminates the risk of colorectal cancer, and close upper GI surveillance may help prevent duodenal malignancy. MDTs are the principal cause of death, once colorectal cancer has been prevented, and the main reason for worsening functional results. […] Among 110 patients with FAP that had restorative proctocolectomy at least 11 years ago, none have developed cancer of the upper gastrointestinal tract or the pouch, but 13 have developed mesenteric desmoid tumors, and 2 have died of these tumors. […] In our series, after a mean follow-up of 14 years after RPC and a minimal follow-up of 11 years, the main cause of death remains colorectal cancers discovered at the time of RPC. None of the patients who had their RPC during the time they had no invasive carcinoma of the colon or rectum have developed a metastatic cancer since their operation, and the main cause of death in these patients was mesenteric desmoid tumor.
#39 Long-term Outcome of Familial Adenomatous Polyposis Patients After Restorative Coloproctectomy
https://pmc.ncbi.nlm.nih.gov/articles/PMC1356236/
In conclusion, our results demonstrate that RPC eliminates the risk of rectal cancer, that duodenal and ampullary lesions are less worrisome than previously reported as long as close surveillance with a side-viewing instrument is used to detect severe lesions that can be treated more aggressively. Mesenteric desmoid tumors remain the primary cause of death linked to FAP after RPC, and also the principal cause of pouch failure.
#40 Familial Adenomatous Polyposis (FAP): Symptoms, Diagnosis, Risks
https://my.clevelandclinic.org/health/diseases/16993-familial-adenomatous-polyposis-fap
Without treatment, the risk of developing colorectal cancer with familial adenomatous polyposis is close to 100%. […] Most people with FAP will develop cancer by their middle-age years. […] Without timely treatment, the median life expectancy is 42 years. But with appropriate care, you can live a normal life. […] Once your colon has been removed, your biggest risk is from other gastrointestinal cancers or problematic desmoid tumors. […] You can expect to have a total colectomy sometime in your early life. […] But you can live a long and healthy life after a colectomy.
#41 APC (Familial adenomatous polyposis) â risk management
https://www.eviq.org.au/cancer-genetics/adult/risk-management/178-apc-familial-adenomatous-polyposis-risk-ma
The risk management of an individual with a pathogenic variant in two or more genes that confer a predisposition to cancer should also be individualised. […] Cancer/tumour risk management guidelines: The choice of risk management strategy should take into account current age, other health issues and age-related cancer risk. […] Risks and benefits of interventions should be discussed with an experienced medical professional. […] Multiple studies have demonstrated that surveillance colonoscopy from early childhood with appropriately timed colectomy reduces CRC incidence and mortality. […] The cumulative crude survival in FAP showed substantial improvement with time. […] Since the establishment of the Danish Polyposis Register, the prevalence of colorectal cancer has decreased considerably and the prognosis has improved substantially.