Guz rakowiowy – Patofizjologia i mechanizm

Guz rakowiowy
Patofizjologia i mechanizm

Guzy rakowiakowe to nowotwory neuroendokrynne wywodzące się głównie z komórek enterochromafinowych przewodu pokarmowego, zwłaszcza wyrostka robaczkowego. Charakteryzują się wolnym wzrostem, ale mogą wydzielać liczne biologicznie czynne substancje, przede wszystkim serotoninę, która odgrywa kluczową rolę w patogenezie zespołu rakowiaka. Etiologia guzów wiąże się z nieprawidłowościami genetycznymi, m.in. utratą chromosomu 18 w 69% rakowiaków jelita cienkiego. Mikrośrodowisko guza, w tym fibroblasty związane z nowotworem (CAFs) i reakcja desmoplastyczna, wpływają na progresję i włóknienie. Zespół rakowiaka występuje u 30-40% pacjentów z dobrze zróżnicowanymi guzami i objawia się m.in. biegunką, zaczerwienieniem skóry oraz włóknieniem krezkowym, które może prowadzić do niedrożności jelit. Serotonina metabolizowana jest do 5-HIAA, którego podwyższony poziom koreluje z powikłaniami, w tym chorobą serca związaną z aktywacją receptora 5-HT2B i włóknieniem zastawek prawej strony serca.

Patogeneza guzów rakowiakowych

Podłoże genetyczne
Patogeneza molekularna

Mechanizm zespołu rakowiaka

Rola serotoniny
Inne mediatory zespołu rakowiaka
Mechanizm choroby sercowej w zespole rakowiaka
Mechanizm zwłóknienia pozasercowego

Patofizjologia związana z lokalizacją guza

Rakowiaki płucne
Rakowiaki jelit

Mechanizm przyczyniający się do progresji nowotworu

Rola angiogenezy
Rola receptorów somatostatynowych
Rola kryzysu rakowiaka

Mechanizmy włóknienia w zespole rakowiaka

Kaskada molekularna prowadząca do włóknienia
Strategie terapeutyczne ukierunkowane na mechanizmy włóknienia
Kolejne rozdziały

Patogeneza guzów rakowiakowych

Guzy rakowiakowe (carcinoid tumors) to nowotwory pochodzenia neuroendokrynnego, wywodzące się z komórek macierzystych znajdujących się głównie w ścianie przewodu pokarmowego, szczególnie wyrostka robaczkowego.¹² Są to wolno rosnące zmiany wywodzące się z komórek enterochromafinowych (komórki Kulchitsky’ego), które należą do rozproszonego układu komórek endokrynnych.³⁴ Guzy te mogą wydzielać liczne substancje biologicznie czynne, w tym aminy biogenne i peptydy, z których najważniejszą rolę odgrywa serotonina.⁵

Podłoże genetyczne

Dokładna etiologia guzów rakowiakowych pozostaje nieznana, jednak podejrzewa się udział nieprawidłowości genetycznych w ich rozwoju.⁶ Badania wykazały liczne zmiany chromosomalne, takie jak utrata heterozygotyczności i zaburzenia numeryczne chromosomów.⁷ W rakowiakach jelita cienkiego szczególnie często występuje utrata całego chromosomu 18 (w około 69% przypadków), podczas gdy w rakowiakach innych lokalizacji oraz guzach neuroendokrynnych trzustki obserwuje się to zjawisko znacznie rzadziej.⁸⁹

W rakowiakach nerki zaobserwowano nieprawidłowości dotyczące chromosomu 3, co sugeruje jego znaczącą rolę w patogenezie tych guzów.¹⁰ Z kolei badania nad rakowiakami wyrostka robaczkowego typu goblet cell wykazały utratę fragmentów chromosomów 11q, 16q i 18q, co sugeruje, że potencjalne lub nieznane jeszcze geny supresorowe nowotworów mogą mieć istotne znaczenie w patogenezie tych guzów.¹¹

W przeciwieństwie do guzów neuroendokrynnych trzustki, rakowiaki jelita cienkiego nie są związane z żadnym znanym zespołem genetycznym.¹² Istotne wskazówki sugerujące zespół genetyczny to: młody wiek w momencie diagnozy, występowanie wielu guzów neuroendokrynnych (lub innych nowotworów) u jednego pacjenta, występowanie podobnych lub różnych guzów neuroendokrynnych w wywiadzie rodzinnym oraz hiperplazja komórek endokrynnych i mikrogruczolaki w preparacie chirurgicznym.¹³

Patogeneza molekularna

Komórki guzów rakowiakowych produkują znaczne ilości beta-kateniny, co umożliwia adhezję komórek nowotworowych, tym samym promując przerzuty.¹⁴ Indukcja Raf1 prowadzi do zmniejszenia adhezji komórek rakowiaka i może być istotnym elementem w procesie tworzenia przerzutów.¹⁵

Mikrośrodowisko guza (TME) odgrywa kluczową rolę w progresji nowotworu i rozwoju włóknienia. W przypadku rakowiaka jelita cienkiego, mikrośrodowisko guza charakteryzuje się specyficzną reakcją desmoplastyczną i ograniczoną infiltracją leukocytarną, co odróżnia je od innych nowotworów.¹⁶ Fibroblasty związane z nowotworem (CAFs) są dominującym komórkowym składnikiem podścieliska guza i są identyfikowane przez ekspresję α-aktyny mięśni gładkich (SMA).¹⁷ W przeciwieństwie do nieaktywnych fibroblastów, CAFs mogą proliferować, produkować czynniki wzrostu i macierz pozakomórkową (ECM).¹⁸

Mechanizm zespołu rakowiaka

Zespół rakowiaka występuje u około 30-40% pacjentów z dobrze zróżnicowanymi guzami neuroendokrynnymi i jest zespołem paraneoplastycznym związanym z wydzielaniem kilku czynników humoralnych.¹⁹ Zespół ten pojawia się, gdy substancje wazoaktywne produkowane przez guz rakowiakowy omijają metabolizm wątrobowy i dostają się do krążenia ogólnego.²⁰²¹

Rola serotoniny

Serotonina jest głównym markerem związanym z zespołem rakowiaka.²² Guzy neuroendokrynne wydzielają około 40 rodzajów biologicznie aktywnych amin i peptydów, ale to właśnie serotonina odgrywa najważniejszą rolę w zespole rakowiaka.²³ W normalnych warunkach tylko 1% tryptofanu jest przekształcany w serotoninę, ale w guzach rakowiakowych może to być nawet do 70%.²⁴²⁵ Ponieważ niacyna jest syntetyzowana z tryptofanu, nadmierne wykorzystanie tryptofanu do syntezy serotoniny może prowadzić do niedoboru niacyny i związanych z tym objawów.²⁶

Nadmiar serotoniny powoduje zwiększoną motorykę przewodu pokarmowego i hipersekrecję, prowadząc do biegunki, która jest jednym z głównych objawów zespołu rakowiaka.²⁷ Serotonina jest metabolizowana do kwasu 5-hydroksyindolooctowego (5-HIAA) i wydalana z moczem.²⁸

Inne mediatory zespołu rakowiaka

Oprócz serotoniny, w patogenezie zespołu rakowiaka uczestniczą także inne substancje, takie jak histamina, kalikreina, prostaglandyny i tachykininy.²⁹³⁰ Guzy neuroendokrynne zlokalizowane w płucach produkują głównie histaminę, powodując atypowe zaczerwienienie skóry i świąd, podczas gdy tachykininy przyczyniają się do zaczerwienienia poprzez efekt wazodylatacyjny.³¹

Rakowiaki przedniej części przewodu pokarmowego (foregut) i płuc nie produkują serotoniny z powodu braku niezbędnego enzymu, natomiast rakowiaki tylnej części przewodu pokarmowego (hindgut) zazwyczaj nie wydzielają znaczących ilości hormonów.³² Guzy neuroendokrynne płuc produkują głównie histaminę, co powoduje nietypowe zaczerwienienie i świąd.³³

Mechanizm choroby sercowej w zespole rakowiaka

Dokładny mechanizm rozwoju choroby sercowej w zespole rakowiaka pozostaje niejasny, jednak istnieją silne dowody na rolę serotoniny w fibrogenezie i stymulacji wzrostu fibroblastów w chorobie sercowej związanej z rakowiakiem.³⁴ Choroba sercowa wynika z przewlekłej degeneracji włóknistej płatków zastawek sercowych.³⁵

Serotonina indukuje kardiopatię prawdopodobnie poprzez receptor 5-HT2B. Aktywacja tego receptora sprzężonego z białkiem G pośredniczy w sygnałach mitogennych fibroblastów i komórek mięśni gładkich, a także w wydzielaniu cytokin i składników macierzy pozakomórkowej.³⁶ Zmiana włóknista zazwyczaj dotyczy strony odpływowej płatków zastawkowych (tj. komorowej strony zastawki trójdzielnej i płucnej strony zastawki płucnej) oraz aparatu podzastawkowego.³⁷

Akumulacja włóknienia prowadzi do postępującego ograniczenia ruchu, retrakcji i unieruchomienia, co klinicznie objawia się jako zwężenie zastawek prawej strony serca, niedomykalność lub zmienna kombinacja obu.³⁸ Lewa strona serca jest względnie chroniona przed chorobą serca związaną z rakowiakiem, ponieważ peptydy wazoaktywne są inaktywowane podczas przechodzenia przez płuca, zanim dotrą do lewego przedsionka.³⁹⁴⁰

Mechanizm zwłóknienia pozasercowego

Zespół rakowiaka jest związany z włóknieniem skóry i włóknieniem zaotrzewnowym, które może powodować zwężenie moczowodów i wodonercze.⁴¹ Chociaż dokładne mechanizmy włóknienia pozasercowego nie zostały jeszcze w pełni wyjaśnione, serotonina i czynnik wzrostu transformujący beta (TGF-β) są uważane za możliwe mediatory.⁴²

TGF-β jest kluczowym regulatorem procesów proliferacyjnych i profibrogennych.⁴³ Sygnalizacja TGF-β ma podwójną rolę: z jednej strony działanie przeciwnowotworowe i antyproliferacyjne w stanach fizjologicznych i wczesnych nowotworowych, a z drugiej strony działanie pronowotworowe, takie jak proliferacja i inwazja w późniejszych stadiach choroby nowotworowej.⁴⁴ Stymuluje również komórki podścieliska do indukowania różnicowania miofibroblastycznego i zmienionej produkcji macierzy pozakomórkowej.⁴⁵

Kolejnym ważnym czynnikiem jest płytkopochodny czynnik wzrostu (PDGF), który ma silny efekt proliferacyjny na fibroblasty i może indukować proliferację komórek nabłonkowych nowotworów.⁴⁶ Efekty profibrogennego PDGF są zapośredniczone przez wiązanie z receptorami PDGF-α i -β.⁴⁷ W komórkach podścieliska rakowiaka jelita cienkiego receptor PDGFR został wykryty w 66-85% przypadków.⁴⁸

Czynnik wzrostu tkanki łącznej (CTGF) jest członkiem rodziny czynników wzrostu CCN, które są indukowane przez cytokiny, takie jak TGF-β, a także przez serotoninę.⁴⁹ CTGF wzmacnia profibrogeniczne działanie TGF-β, EGF i FGF, zwiększając syntezę kolagenu, proliferację fibroblastów i różnicowanie w miofibroblasty.⁵⁰

Patofizjologia związana z lokalizacją guza

Patofizjologia guzów rakowiakowych jest ściśle związana z lokalizacją guza pierwotnego.⁵¹ Guzy rakowiakowe mogą rozwijać się w różnych narządach, w tym w jelicie cienkim, wyrostku robaczkowym, okrężnicy, odbytnicy, oskrzelach, trzustce, jajnikach, jądrach, drogach żółciowych i wątrobie.⁵²

Rakowiaki płucne

Rakowiaki płucne występują zarówno w lokalizacji centralnej, jak i obwodowej, i wykazują pewne różnice w cechach kliniczno-patologicznych.⁵³ Istotną różnicą jest silny związek guza obwodowego z hiperplazją neuroendokrynną, podczas gdy taki związek w guzach centralnych jest nieistotny.⁵⁴ Lokalizacja guza może mieć znaczenie dla patobiologii rakowiaka płuc.⁵⁵

Badania wykazały, że rakowiaki typu obwodowego, niezależnie od tego, czy występują w lokalizacji obwodowej czy centralnej, wymagają dokładnego poszukiwania podstawowej hiperplazji neuroendokrynnej.⁵⁶ DIPNECH (rozlane idiopatyczne płucne nadmierne rozrastanie komórek neuroendokrynnych) charakteryzuje się hiperplazją komórek neuroendokrynnych, tumorletami i ostatecznie rakowiakami.⁵⁷

Rakowiaki jelit

Rakowiaki środkowej części przewodu pokarmowego (midgut) są szczególnie aktywnymi producentami serotoniny.⁵⁸ Pierwotna zmiana w rakowiakach środkowej części przewodu pokarmowego to zwykle mały (1 cm), płaski i włóknisty guz w płaszczyźnie podśluzówkowej jelita cienkiego, który często nie jest diagnozowany aż do operacji.⁵⁹

Inne typowe znaleziska operacyjne obejmują powiększone węzły chłonne ze związanym włóknieniem krezkowym, co prowadzi do zagięcia jelita, a tym samym do niedrożności.⁶⁰ To rozległe włóknienie krezkowe jest prawdopodobnie spowodowane uwalnianiem serotoniny i czynników wzrostu z komórek nowotworowych i może również prowadzić do otoczenia naczyń krezkowych, powodując niedokrwienie jelita.⁶¹

Zespół rakowiaka występuje typowo u pacjentów z przerzutami do wątroby/płuc, z ogólną częstością występowania 10% w rakowiakach przewodu pokarmowego, ale 20% u osób z chorobą jelita czczego i krętego.⁶²

Mechanizm przyczyniający się do progresji nowotworu

Guzy rakowiakowe są zazwyczaj wolno rosnące, jednak mogą nagle zacząć rosnąć szybko z przyczyn, które nie są dobrze poznane.⁶³ Mimo to, guzy te mogą przerzutować do regionalnych węzłów chłonnych i innych narządów, w tym wątroby, kości i ośrodkowego układu nerwowego.⁶⁴

Rola angiogenezy

Angiogeneza jest ważnym procesem w progresji guzów rakowiakowych.⁶⁵ Istnieje wiele związków o charakterze antyangiogennym, które mogą potencjalnie hamować wzrost guza.⁶⁶ Mikrośrodowisko guza jest kluczowym determinantem progresji nowotworu.⁶⁷

Rola receptorów somatostatynowych

Większość dobrze zróżnicowanych guzów rakowiakowych posiada receptory somatostatynowe na powierzchni komórek.⁶⁸ Somatostatyna jest peptydem, który hamuje wydzielanie wielu hormonów, a znaczna część guzów rakowiakowych wykazuje ekspresję receptorów somatostatynowych na powierzchni swoich komórek.⁶⁹

Analogi somatostatyny (oktreotyd i lanreotyd) oraz interferony są skutecznie stosowane do łagodzenia objawów zespołu rakowiaka u 70% pacjentów, zapewniając redukcję guza u około 5% pacjentów i stabilizację choroby u około połowy pacjentów.⁷⁰

Rola kryzysu rakowiaka

Pacjenci z zespołem rakowiaka, którzy poddawani są operacji, znieczuleniu lub chemioterapii, są narażeni na wystąpienie kryzysu rakowiaka, który jest stanem zagrażającym życiu, spowodowanym nagłym wzrostem serotoniny we krwi.⁷¹ Profilaktyczne zastosowanie ciągłego wlewu oktreotydu przed, w trakcie i po operacji zmniejsza częstość występowania kryzysów rakowiaka podczas operacji cytoredukcyjnych guzów neuroendokrynnych.⁷²

Lokalizacja	Główne mediatory	Patofizjologia	Efekty kliniczne
Jelito cienkie (midgut)	Serotonina, kalikreina	Zwiększona motoryka jelit, hipersekrecja	Biegunka, zaczerwienienie skóry, włóknienie krezkowe
Płuca (foregut)	Histamina, tachykininy	Rozszerzenie naczyń, skurcz oskrzeli	Atypowe zaczerwienienie, świąd, duszność
Jelito grube (hindgut)	Zwykle brak istotnej sekrecji hormonów	Ograniczone działanie endokrynne	Głównie objawy miejscowe
Narządy z przerzutami (najczęściej wątroba)	Serotonina i inne substancje wazoaktywne omijające metabolizm wątrobowy	Czynniki docierające do krążenia ogólnego	Pełnoobjawowy zespół rakowiaka
Serce (komplikacja systemowa)	Serotonina (via receptor 5-HT2B)	Fibrinogenna przebudowa zastawek prawej strony serca	Niedomykalność/zwężenie zastawki trójdzielnej i płucnej

Mechanizmy włóknienia w zespole rakowiaka

Włóknienie jest istotną komplikacją guzów rakowiakowych i może występować zarówno wokół guza, jak i w odległych miejscach.⁷³ Najważniejszym włóknieniem miejscowym jest włóknienie krezkowe, które występuje u 50% pacjentów z rakowiakiem jelita cienkiego.⁷⁴

Kaskada molekularna prowadząca do włóknienia

Kaskada molekularna prowadząca do włóknienia w zespole rakowiaka obejmuje kilka kluczowych czynników. Serotonina jest jednym z głównych mediatorów poprzez receptor 5-HT2B.⁷⁵ Wysokie stężenie serotoniny jest uważane za głównego mediatora biegunki, działającego bezpośrednio na receptory błony komórkowej neuronów jelitowych. Zwiększa to perystaltykę i utrudnia wchłanianie jelitowe.⁷⁶

Serotonina może również stymulować syntezę macierzy pozakomórkowej (ECM), prowadząc do włóknienia i powodując w dłuższej perspektywie niedrożność jelit oraz chorobę sercową związaną z rakowiakiem.⁷⁷ Istnieje korelacja między tymi powikłaniami a podwyższonym poziomem 5-HIAA w moczu.⁷⁸

Jak już wcześniej wspomniano, TGF-β i PDGF odgrywają istotną rolę w procesie włóknienia. TGF-β stymuluje różnicowanie fibroblastów w miofibroblasty, które następnie same wydzielają TGF-β, tworząc samopodtrzymującą się, profibrotyczną pętlę sprzężenia zwrotnego.⁷⁹

Strategie terapeutyczne ukierunkowane na mechanizmy włóknienia

Strategie terapeutyczne ukierunkowane na mechanizmy włóknienia w zespole rakowiaka obejmują inhibitory syntezy serotoniny, takie jak telotristat etyl, który jest inhibitorem hydroksylazy tryptofanu, kluczowego enzymu zaangażowanego w syntezę serotoniny.⁸⁰ Ocena telotristat etylu u pacjentów z zespołem rakowiaka opierała się na hipotezie, że zahamowanie syntezy serotoniny w guzie może skutecznie leczyć zespół rakowiaka.⁸¹

Zmniejszenie stężenia kwasu 5-hydroksyindolooctowego (5-HIAA) w moczu odzwierciedla redukcję syntezy serotoniny.⁸² Potencjalną korzyścią z obniżenia poziomu serotoniny u pacjentów z zespołem rakowiaka jest zapobieganie długoterminowym konsekwencjom wysokich poziomów.⁸³

Analogi somatostatyny, takie jak oktreotyd, działają poprzez wiązanie się z receptorami na komórkach guzów rakowiakowych i hamują produkcję i uwalnianie hormonów guza.⁸⁴ Pacjenci z guzami rakowiaka przewodu pokarmowego, których nie można usunąć chirurgicznie, mogą odnieść korzyść z comiesięcznych iniekcji syntetycznego hormonu, oktreotydu, który kontroluje objawy związane z hormonami i może potencjalnie spowolnić wzrost guza.⁸⁵

Dodatkowo, nowe terapie celowane na receptory somatostatynowe, takie jak PRRT (peptide receptor radionuclide therapy), wykorzystują radioaktywny lek o nazwie lutetium Lu 177 dotatate (Lutathera), który jest skuteczny w leczeniu guzów rakowiaka przewodu pokarmowego i trzustki posiadających receptory somatostatynowe.⁸⁶

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Materiały źródłowe

#1 Carcinoid Tumor: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/986050-overview
Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. […] The etiology of carcinoid tumors is not known, but genetic abnormalities are suspected. Reported chromosomal abnormalities include changes in chromosomes, such as loss of heterogeneity, and numerical imbalances. […] Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells, which can give rise to multiple cell lineages. […] These cells produce a significant amount of beta-catenin, which enables the tumor cell adhesion, thus promoting metastasis. Induction of Raf1 results in decreased adhesion of carcinoid cells and may be important in the metastatic process.
#2 Malignant Carcinoid Syndrome: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/282515-overview
Malignant carcinoid syndrome is characterized by an array of signs and symptoms in particular, hot, red flushing of the face; severe and debilitating diarrhea; and asthma attacks caused by vasoactive hormones secreted by metastases from carcinoid tumors. […] Carcinoid tumors are of neuroendocrine origin and derive from primitive stem cells, which can give rise to multiple cell lineages. […] Malignant carcinoid syndrome occurs in fewer than 10% of patients with a carcinoid tumor. […] Pathophysiology is closely related to the sites of the primary tumors. When these tumors spread to the liver, patients usually begin to develop malignant carcinoid syndrome. In fact, this syndrome develops when vasoactive substances produced by a carcinoid tumor escape hepatic degradation and gain access to the systemic circulation.
#3 SciELO Brazil – Carcinoid syndrome: diagnosis and medical management Carcinoid syndrome: diagnosis and medical management
https://www.scielo.br/j/abem/a/XsNGMwcFV8D6R6Lk5ZLR78j/?format=html
Gastro-intestinal carcinoids are slow growing tumors arising from enterochromaffin or Kulchitsky cells. Their clinical presentation depends on what combination of bioactive substances is secreted. Midgut carcinoid can present with the carcinoid syndrome in the presence of liver metastases. Its most typical clinical manifestations include cutaneous flushing and diarrhea. A nonspecific biochemical tumor marker for carcinoid tumors is serum chromogranin A and a specific marker for the carcinoid syndrome is the increased urinary excretion of 5-hydroxy indole acetic acid (5-HIAA). […] Carcinoids have protean clinical presentations, depending on what combination of bioactive substances is secreted. One of their main characteristics of the enterochromaffin (ECL) or Kulchitsky cells is the synthesis, storage, and secretion of serotonin. Serotonin (5-hydroxytrypamine, 5-HT) is synthesized from tryptophan through its precursor, 5-hydroxy tryptophan (5-HTP), and subsequently metabolized to 5-hydroxyindoleacetic acid (5-HIAA), which is excreted in the urine. In addition to serotonin, carcinoid tumors may also secrete other hormones such as corticotrophin (ACTH), histamine, dopamine, substance P, neurotensin, prostaglandins, kallikrein, and tachykinins.
#4 Carcinoid Tumor: Treatment, Symptoms, Meaning
https://www.medicinenet.com/carcinoid_syndrome/article.htm
Carcinoid tumors may be cancerous or benign and form largely in the lungs and gut. The clinical course of these cancers is often indolent with 5-year survival approaching 75%. […] A carcinoid tumor is a tumor that develops from enterochromaffin cells. Enterochromaffin cells are hormone- and chemical-producing cells that normally are found in the small intestine, appendix, colon, rectum, bronchi, pancreas, ovaries, testes, bile ducts, liver, as well as other organs. […] Since carcinoid tumors develop from enterochromaffin cells, they frequently retain the capability of producing the same hormones, often in large quantities. When these hormones circulate in the blood, they can cause symptoms of carcinoid syndrome, which is discussed later. […] The important characteristic of carcinoid tumors that sets them apart from other gastrointestinal tract tumors is their potential to cause carcinoid syndrome.
#5 Carcinoid syndrome: update on the pathophysiology and treatment
https://pmc.ncbi.nlm.nih.gov/articles/PMC6096975/
Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. […] More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. […] The exact mechanism underlying the development of carcinoid heart disease remains unclear. However, there is strong evidence for the role of 5-HT in the fibrogenesis and stimulation of fibroblast growth in carcinoid heart disease.
#6 Carcinoid Tumor: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/986050-overview
Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. […] The etiology of carcinoid tumors is not known, but genetic abnormalities are suspected. Reported chromosomal abnormalities include changes in chromosomes, such as loss of heterogeneity, and numerical imbalances. […] Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells, which can give rise to multiple cell lineages. […] These cells produce a significant amount of beta-catenin, which enables the tumor cell adhesion, thus promoting metastasis. Induction of Raf1 results in decreased adhesion of carcinoid cells and may be important in the metastatic process.
#7 Comparison of genetic alterations in neuroendocrine tumors: frequent loss of chromosome 18 in ileal carcinoid tumors | Modern Pathology
https://www.nature.com/articles/3800389
Carcinoid tumors and pancreatic endocrine tumors are uncommon neuroendocrine neoplasms, and their genetic alterations are not well characterized. […] We compared clinicopathological features and loss of heterozygosity of chromosomes 11q, 16q and 18, and BRAF gene mutations in 47 patients with neuroendocrine tumors including 16 with pancreatic endocrine tumors, 15 with nonileal carcinoid tumors and 16 with ileal carcinoid tumors. […] Allelic loss of chromosome 11q was present in 21% of tumors, chromosome 16q in 13%, and chromosome 18 in 30%. […] These alterations differed with the anatomical subsite of tumor: allelic loss of chromosome 18 was present in 69% of ileal carcinoid tumors, 13% of nonileal carcinoid tumors and 6% of pancreatic endocrine tumors (P=0.001). […] In contrast to pancreatic endocrine tumors and nonileal carcinoid tumors, all 11 ileal tumors with loss of chromosome 18 had complete loss of both chromosomal arms.
#8 Comparison of genetic alterations in neuroendocrine tumors: frequent loss of chromosome 18 in ileal carcinoid tumors | Modern Pathology
https://www.nature.com/articles/3800389
Carcinoid tumors and pancreatic endocrine tumors are uncommon neuroendocrine neoplasms, and their genetic alterations are not well characterized. […] We compared clinicopathological features and loss of heterozygosity of chromosomes 11q, 16q and 18, and BRAF gene mutations in 47 patients with neuroendocrine tumors including 16 with pancreatic endocrine tumors, 15 with nonileal carcinoid tumors and 16 with ileal carcinoid tumors. […] Allelic loss of chromosome 11q was present in 21% of tumors, chromosome 16q in 13%, and chromosome 18 in 30%. […] These alterations differed with the anatomical subsite of tumor: allelic loss of chromosome 18 was present in 69% of ileal carcinoid tumors, 13% of nonileal carcinoid tumors and 6% of pancreatic endocrine tumors (P=0.001). […] In contrast to pancreatic endocrine tumors and nonileal carcinoid tumors, all 11 ileal tumors with loss of chromosome 18 had complete loss of both chromosomal arms.
#9 Comparison of genetic alterations in neuroendocrine tumors: frequent loss of chromosome 18 in ileal carcinoid tumors | Modern Pathology
https://www.nature.com/articles/3800389
Our study indicates that genetic alterations vary by tumor subsite and clinicopathologic features, and ileal carcinoid tumors have distinctive clinicopathologic and genetic profiles. […] The molecular pathogenesis of pancreatic endocrine tumor and carcinoid tumor is poorly understood. […] Recent advances have been made in characterization of molecular events underlying the tumorigenesis of carcinoid tumors. […] Allelic loss of chromosomes 11q, 16q and 18q is reported in typical midgut carcinoids. […] In our study, we identified frequent complete loss of chromosome 18 in ileal carcinoid tumors compared to pancreatic endocrine tumors and nonileal carcinoid tumors. […] The findings in our study further support the concept that these three groups of tumor are fundamentally different and the tumorigenic process evolves along at least two different pathways.
#10 Oncology Letters
https://www.spandidos-publications.com/10.3892/ol_00000015
Few genetic studies of renal carcinoid tumor have been conducted thus far. […] In conclusion, we suggest that the abnormality of chromosome 3 is involved in the pathogenesis of renal carcinoid tumor. […] This study investigated the status of chromosomes 3 and 13 in four primary renal carcinoid tumors using fluorescence in situ hybridization (FISH), loss of heterozygosity (LOH) of 3p and VHL gene analysis and discussed the pathogenesis. […] Therefore, we suggest that the numerical loss of chromosome 3 plays a crucial role in the pathogenesis of primary renal carcinoid tumor. […] From the results of the present study, we can infer that LOH of chromosome 3p is involved in the pathogenesis of certain cases of renal carcinoid tumors. […] In conclusion, the abnormality of chromosome 3 may be involved in the pathogenesis of some cases of renal carcinoid tumor.
#11 Genetic Alterations in Goblet Cell Carcinoids of the Vermiform Appendix and Comparison with Gastrointestinal Carcinoid Tumors | Modern Pathology
https://www.nature.com/articles/3880905
Goblet cell carcinoid is a relatively rare neuroendocrine tumor of the vermiform appendix with poorly understood molecular pathogenesis. […] These findings suggest that allelic loss of chromosomes 11q, 16q, and 18q in goblet cell carcinoids and ileal carcinoids may have an important role in the pathogenesis of these tumors. […] Because of its rarity, little is known about the molecular pathogenesis of goblet cell carcinoid. […] Overall, these findings suggest that alterations of oncogenes and tumor suppressor genes, frequently altered in adenocarcinomas of gastrointestinal tract, do not play a role in the pathogenesis of appendiceal goblet cell carcinoid. […] The loss of chromosomes 11q, 16q, and 18q identified in the majority of these tumors suggests that putative or yet unknown tumor suppressor genes may have a major role in the pathogenesis of goblet cell carcinoids and ileal carcinoids.
#12 Genetic Causes of Neuroendocrine Tumors by Dr. Run Yu – Carcinoid Cancer Foundation
https://www.carcinoid.org/genetic-causes-neuroendocrine-tumors-dr-run-yu/
A common question that patients with neuroendocrine tumors (NETs) ask is whether their NETs are caused by inheriting a defective gene. […] Most patients with pancreatic NETs do not have a clear genetic cause. […] The most common genetic syndrome that causes pancreatic NETs is the multiple endocrine neoplasia type 1 (MEN1). […] The genetic syndromes that cause pancreatic NETs have unique and somewhat predictable clinical course. […] In contrast to pancreatic NETs, small bowel carcinoids are not associated with any known genetic syndromes. […] Important clues to a genetic syndrome are young age of diagnosis, one patient having multiple NETs (or other tumors) in one or more organs, family history of similar or different NETs, and endocrine cell hyperplasia and microadenomas in the surgical specimen.
#13 Genetic Causes of Neuroendocrine Tumors by Dr. Run Yu – Carcinoid Cancer Foundation
https://www.carcinoid.org/genetic-causes-neuroendocrine-tumors-dr-run-yu/
A common question that patients with neuroendocrine tumors (NETs) ask is whether their NETs are caused by inheriting a defective gene. […] Most patients with pancreatic NETs do not have a clear genetic cause. […] The most common genetic syndrome that causes pancreatic NETs is the multiple endocrine neoplasia type 1 (MEN1). […] The genetic syndromes that cause pancreatic NETs have unique and somewhat predictable clinical course. […] In contrast to pancreatic NETs, small bowel carcinoids are not associated with any known genetic syndromes. […] Important clues to a genetic syndrome are young age of diagnosis, one patient having multiple NETs (or other tumors) in one or more organs, family history of similar or different NETs, and endocrine cell hyperplasia and microadenomas in the surgical specimen.
#14 Carcinoid Tumor: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/986050-overview
Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. […] The etiology of carcinoid tumors is not known, but genetic abnormalities are suspected. Reported chromosomal abnormalities include changes in chromosomes, such as loss of heterogeneity, and numerical imbalances. […] Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells, which can give rise to multiple cell lineages. […] These cells produce a significant amount of beta-catenin, which enables the tumor cell adhesion, thus promoting metastasis. Induction of Raf1 results in decreased adhesion of carcinoid cells and may be important in the metastatic process.
#15 Carcinoid Tumor: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/986050-overview
Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. […] The etiology of carcinoid tumors is not known, but genetic abnormalities are suspected. Reported chromosomal abnormalities include changes in chromosomes, such as loss of heterogeneity, and numerical imbalances. […] Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells, which can give rise to multiple cell lineages. […] These cells produce a significant amount of beta-catenin, which enables the tumor cell adhesion, thus promoting metastasis. Induction of Raf1 results in decreased adhesion of carcinoid cells and may be important in the metastatic process.
#16 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
Tissue homeostasis is maintained by intricate interactions between cells and their microenvironment. […] Therefore, understanding the TME is crucial in order to decipher how SI-NETs induce fibrosis. […] The local microenvironment of cancer cells is commonly referred to as reactive stroma. […] This reactive tumour stroma consists of immune cells, fibroblasts, capillaries, basement membrane and extracellular matrix (ECM). […] The TME is crucial for tumour growth, invasion and metastasis, with both cancer-promoting as cancer-restraining actions of most components and is known to differ between cancer types. […] The tumour stroma of SI-NETs differs from other cancers with a characteristic desmoplastic reaction and limited leukocytic infiltration. […] Therefore, the pathobiological processes in the SI-NET TME differ from other cancer types. […] Moreover, because of the commonalities between pathways involved in development of fibrosis and cancer progression, insight gained in the distinct effects of different TME components in SI-NETs can result both in effective anticancer as well as antifibrotic treatment.
#17 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
Fibroblasts are the dominant cellular component of tumour stroma, next to tumour cells. […] This activated phenotype of cancer-associated fibroblasts (CAFs) is identified by expression of -smooth muscle actin (SMA). […] In contrast to quiescent fibroblasts, CAFs are able to proliferate, produce growth factors and ECM. […] This suggests that also in SI-NETs, CAFs are important regulators of fibrotic stromal programmes. […] Immune cells are another important constituent of the TME, and dysregulation of the local immune system and inflammatory response is implicated in both tumourigenesis and development of fibrosis. […] A major component of the leukocytic infiltrate in the TME is the tumour-associated macrophages (TAMs). […] TAMs have in general a tumour-promoting role, suppress the adaptive immune system and stimulate fibrosis by secretion of profibrotic factors such as TGF. […] In SI-NETs, there is less leukocytic infiltration compared to other cancers. […]
#18 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
Fibroblasts are the dominant cellular component of tumour stroma, next to tumour cells. […] This activated phenotype of cancer-associated fibroblasts (CAFs) is identified by expression of -smooth muscle actin (SMA). […] In contrast to quiescent fibroblasts, CAFs are able to proliferate, produce growth factors and ECM. […] This suggests that also in SI-NETs, CAFs are important regulators of fibrotic stromal programmes. […] Immune cells are another important constituent of the TME, and dysregulation of the local immune system and inflammatory response is implicated in both tumourigenesis and development of fibrosis. […] A major component of the leukocytic infiltrate in the TME is the tumour-associated macrophages (TAMs). […] TAMs have in general a tumour-promoting role, suppress the adaptive immune system and stimulate fibrosis by secretion of profibrotic factors such as TGF. […] In SI-NETs, there is less leukocytic infiltration compared to other cancers. […]
#19 Carcinoid syndrome: update on the pathophysiology and treatment
https://pmc.ncbi.nlm.nih.gov/articles/PMC6096975/
Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. […] More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. […] The exact mechanism underlying the development of carcinoid heart disease remains unclear. However, there is strong evidence for the role of 5-HT in the fibrogenesis and stimulation of fibroblast growth in carcinoid heart disease.
#20 Carcinoid syndrome – Wikipedia
https://en.wikipedia.org/wiki/Carcinoid_syndrome
The carcinoid syndrome occurs secondary to neuroendocrine tumors. These tumors occur mostly in the gut and less commonly in the lungs, but may also occur in other places in the body such as the pancreas, kidneys, and other organs. Neuroendocrine tumors produce several biologically active substances, mainly amines and peptides. There are over 40 substances known to be secreted by these tumors but the exact effect of each and their contribution to the carcinoid syndrome is unknown. The most common substances found to be released and contribute to the syndrome include serotonin, histamine, tachykinins, kallikrein, and prostaglandins with the greatest contribution appearing to be from serotonin. The symptoms of the carcinoid syndrome result from the action of these substances largely on the blood vessels. […] These biologic substances are often metabolized and inactivated by the liver in a process known as first pass metabolism. This is why carcinoid syndrome most often occurs in patients whom the neuroendocrine tumor has metastasized to the liver, which allows the substances to bypass the first pass metabolism. Neuroendocrine tumors arising in the bronchi may be associated with manifestations of carcinoid syndrome without liver metastases because their biologically active products reach the systemic circulation before passing through the liver and being metabolized.
#21 Malignant Carcinoid Syndrome: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/282515-overview
Malignant carcinoid syndrome is characterized by an array of signs and symptoms in particular, hot, red flushing of the face; severe and debilitating diarrhea; and asthma attacks caused by vasoactive hormones secreted by metastases from carcinoid tumors. […] Carcinoid tumors are of neuroendocrine origin and derive from primitive stem cells, which can give rise to multiple cell lineages. […] Malignant carcinoid syndrome occurs in fewer than 10% of patients with a carcinoid tumor. […] Pathophysiology is closely related to the sites of the primary tumors. When these tumors spread to the liver, patients usually begin to develop malignant carcinoid syndrome. In fact, this syndrome develops when vasoactive substances produced by a carcinoid tumor escape hepatic degradation and gain access to the systemic circulation.
#22 Carcinoid syndrome: update on the pathophysiology and treatment
https://pmc.ncbi.nlm.nih.gov/articles/PMC6096975/
Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. […] More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. […] The exact mechanism underlying the development of carcinoid heart disease remains unclear. However, there is strong evidence for the role of 5-HT in the fibrogenesis and stimulation of fibroblast growth in carcinoid heart disease.
#23 Carcinoid Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK448096/
Carcinoid syndrome arises from the release of biologically active amines and peptides into the systemic circulation, bypassing the liver’s first-pass metabolism. The liver normally inactivates these substances, but liver metastases from neuroendocrine tumors can allow these products to enter the circulation and exert systemic effects.[8][9] […] Neuroendocrine tumors secrete about 40 types of biologically active amines and peptides, with serotonin being the most significant in carcinoid syndrome. While only 1% of dietary tryptophan is normally converted to serotonin, up to 70% may be diverted in these tumors. As niacin is synthesized from dietary tryptophan, this excessive utilization of tryptophan to synthesize serotonin can result in niacin deficiency and its associated symptoms. Serotonin is metabolized to 5-HIAA and excreted in urine.
#24 Carcinoid Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK448096/
Carcinoid syndrome arises from the release of biologically active amines and peptides into the systemic circulation, bypassing the liver’s first-pass metabolism. The liver normally inactivates these substances, but liver metastases from neuroendocrine tumors can allow these products to enter the circulation and exert systemic effects.[8][9] […] Neuroendocrine tumors secrete about 40 types of biologically active amines and peptides, with serotonin being the most significant in carcinoid syndrome. While only 1% of dietary tryptophan is normally converted to serotonin, up to 70% may be diverted in these tumors. As niacin is synthesized from dietary tryptophan, this excessive utilization of tryptophan to synthesize serotonin can result in niacin deficiency and its associated symptoms. Serotonin is metabolized to 5-HIAA and excreted in urine.
#25 Carcinoid syndrome – Wikipedia
https://en.wikipedia.org/wiki/Carcinoid_syndrome
Tryptophan metabolism is altered in the carcinoid syndrome. With neuroendocrine tumors, there is a shift in conversion of tryptophan to serotonin from the normal 1% to as high as 70%. Increased amounts of serotonin lead to increased gut motility causing the diarrhea seen in carcinoid syndrome. Increased amounts of serotonin can also cause the flushing seen as the main symptom of carcinoid syndrome. Tryptophan is also needed for niacin synthesis which can be a cause for pellagra associated with carcinoid syndrome. In the pulmonary neuroendocrine tumors or metastases, histamine release and kallikrein metabolism are the vasoactive mediators of flushing and the other symptoms of carcinoid syndrome.
#26 Carcinoid Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK448096/
Carcinoid syndrome arises from the release of biologically active amines and peptides into the systemic circulation, bypassing the liver’s first-pass metabolism. The liver normally inactivates these substances, but liver metastases from neuroendocrine tumors can allow these products to enter the circulation and exert systemic effects.[8][9] […] Neuroendocrine tumors secrete about 40 types of biologically active amines and peptides, with serotonin being the most significant in carcinoid syndrome. While only 1% of dietary tryptophan is normally converted to serotonin, up to 70% may be diverted in these tumors. As niacin is synthesized from dietary tryptophan, this excessive utilization of tryptophan to synthesize serotonin can result in niacin deficiency and its associated symptoms. Serotonin is metabolized to 5-HIAA and excreted in urine.
#27 Carcinoid Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK448096/
Excess serotonin causes increased gastrointestinal motility and hypersecretion, leading to diarrhea, one of the hallmarks of carcinoid syndrome.[10] Foregut and pulmonary neuroendocrine tumors do not produce serotonin due to a lack of the necessary enzyme, while hindgut tumors typically do not secrete significant hormones. Pulmonary neuroendocrine tumors mainly produce histamine, causing atypical flushing and pruritus, while tachykinins contribute to flushing through vasodilatory effects, further complicating the clinical presentation of carcinoid syndrome.[9][11]
#28 Carcinoid Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK448096/
Carcinoid syndrome arises from the release of biologically active amines and peptides into the systemic circulation, bypassing the liver’s first-pass metabolism. The liver normally inactivates these substances, but liver metastases from neuroendocrine tumors can allow these products to enter the circulation and exert systemic effects.[8][9] […] Neuroendocrine tumors secrete about 40 types of biologically active amines and peptides, with serotonin being the most significant in carcinoid syndrome. While only 1% of dietary tryptophan is normally converted to serotonin, up to 70% may be diverted in these tumors. As niacin is synthesized from dietary tryptophan, this excessive utilization of tryptophan to synthesize serotonin can result in niacin deficiency and its associated symptoms. Serotonin is metabolized to 5-HIAA and excreted in urine.
#29 Carcinoid syndrome: update on the pathophysiology and treatment
https://pmc.ncbi.nlm.nih.gov/articles/PMC6096975/
Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. […] More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. […] The exact mechanism underlying the development of carcinoid heart disease remains unclear. However, there is strong evidence for the role of 5-HT in the fibrogenesis and stimulation of fibroblast growth in carcinoid heart disease.
#30 Carcinoid syndrome – Wikipedia
https://en.wikipedia.org/wiki/Carcinoid_syndrome
The carcinoid syndrome occurs secondary to neuroendocrine tumors. These tumors occur mostly in the gut and less commonly in the lungs, but may also occur in other places in the body such as the pancreas, kidneys, and other organs. Neuroendocrine tumors produce several biologically active substances, mainly amines and peptides. There are over 40 substances known to be secreted by these tumors but the exact effect of each and their contribution to the carcinoid syndrome is unknown. The most common substances found to be released and contribute to the syndrome include serotonin, histamine, tachykinins, kallikrein, and prostaglandins with the greatest contribution appearing to be from serotonin. The symptoms of the carcinoid syndrome result from the action of these substances largely on the blood vessels. […] These biologic substances are often metabolized and inactivated by the liver in a process known as first pass metabolism. This is why carcinoid syndrome most often occurs in patients whom the neuroendocrine tumor has metastasized to the liver, which allows the substances to bypass the first pass metabolism. Neuroendocrine tumors arising in the bronchi may be associated with manifestations of carcinoid syndrome without liver metastases because their biologically active products reach the systemic circulation before passing through the liver and being metabolized.
#31 Carcinoid Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK448096/
Excess serotonin causes increased gastrointestinal motility and hypersecretion, leading to diarrhea, one of the hallmarks of carcinoid syndrome.[10] Foregut and pulmonary neuroendocrine tumors do not produce serotonin due to a lack of the necessary enzyme, while hindgut tumors typically do not secrete significant hormones. Pulmonary neuroendocrine tumors mainly produce histamine, causing atypical flushing and pruritus, while tachykinins contribute to flushing through vasodilatory effects, further complicating the clinical presentation of carcinoid syndrome.[9][11]
#32 Carcinoid Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK448096/
Excess serotonin causes increased gastrointestinal motility and hypersecretion, leading to diarrhea, one of the hallmarks of carcinoid syndrome.[10] Foregut and pulmonary neuroendocrine tumors do not produce serotonin due to a lack of the necessary enzyme, while hindgut tumors typically do not secrete significant hormones. Pulmonary neuroendocrine tumors mainly produce histamine, causing atypical flushing and pruritus, while tachykinins contribute to flushing through vasodilatory effects, further complicating the clinical presentation of carcinoid syndrome.[9][11]
#33 Angioedema as a single manifestation of carcinoid syndrome in a bronchial carcinoid tumor | Allergologia et Immunopathologia
https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-angioedema-as-single-manifestation-carcinoid-13064930
The association of bronchial carcinoid tumors with carcinoid syndrome is extremely rare especially in the absence of metastasic disease, and the angioedema is not a typical sign of this syndrome. […] Some of them, mainly histamine, are implicated in the pathogenesis of the angioedema, possibly manifestating itself as a part of a carcinoid syndrome. […] Carcinoid tumors arising in the lung specifically produce serotonin, gastrin, adrenocorticotropic hormone and histamine, probably involved in the genesis of angioedema in this case. Therefore, bronquial carcinoid tumors could develop this syndrome, releasing tumor factors directly into the systemic circulation. […] In conclusion, we report the first case of typical bronchial carcinoid tumour, without metastasic disease, with angioedema as a single manifestation of carcinoid syndrome. So, it is very important to include complementary tests in the routine study of angioedema to reject malignant diseases.
#34 Carcinoid syndrome: update on the pathophysiology and treatment
https://pmc.ncbi.nlm.nih.gov/articles/PMC6096975/
Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. […] More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. […] The exact mechanism underlying the development of carcinoid heart disease remains unclear. However, there is strong evidence for the role of 5-HT in the fibrogenesis and stimulation of fibroblast growth in carcinoid heart disease.
#35 Complications from carcinoid syndrome: review of the current evidence – ecancer
https://ecancer.org/en/journal/article/662-complications-from-carcinoid-syndrome-review-of-the-current-evidence
An emerging body of evidence has pointed towards serotonin as the possible main causative agent of CHD. […] Serotonin-induced cardiopathy possibly occurs through 5-HT2B. Activation of this G-protein coupled receptor mediates fibroblasts and smooth muscle cells mitogenic signals, as well as secretion of cytokines and extracellular matrix components. […] Despite serotonin being important, CHD is believed to be a multifactorial phenomenon, since several other mediators have been associated with CHD. […] Regardless of the still unknown precise underlying mechanism, fibrotic plaque deposition usually affects the downstream side of the valve leaflets (i.e. ventricular aspect of tricuspid valve and pulmonary side of pulmonary valve) and subvalvular apparatus. […] The accumulation of fibrosis leads to a progressive movement restriction, retraction and fixation, which are clinically transduced to right-sided valve stenosis, regurgitation, or a variable combination of both.
#36 Complications from carcinoid syndrome: review of the current evidence – ecancer
https://ecancer.org/en/journal/article/662-complications-from-carcinoid-syndrome-review-of-the-current-evidence
An emerging body of evidence has pointed towards serotonin as the possible main causative agent of CHD. […] Serotonin-induced cardiopathy possibly occurs through 5-HT2B. Activation of this G-protein coupled receptor mediates fibroblasts and smooth muscle cells mitogenic signals, as well as secretion of cytokines and extracellular matrix components. […] Despite serotonin being important, CHD is believed to be a multifactorial phenomenon, since several other mediators have been associated with CHD. […] Regardless of the still unknown precise underlying mechanism, fibrotic plaque deposition usually affects the downstream side of the valve leaflets (i.e. ventricular aspect of tricuspid valve and pulmonary side of pulmonary valve) and subvalvular apparatus. […] The accumulation of fibrosis leads to a progressive movement restriction, retraction and fixation, which are clinically transduced to right-sided valve stenosis, regurgitation, or a variable combination of both.
#37 Complications from carcinoid syndrome: review of the current evidence – ecancer
https://ecancer.org/en/journal/article/662-complications-from-carcinoid-syndrome-review-of-the-current-evidence
An emerging body of evidence has pointed towards serotonin as the possible main causative agent of CHD. […] Serotonin-induced cardiopathy possibly occurs through 5-HT2B. Activation of this G-protein coupled receptor mediates fibroblasts and smooth muscle cells mitogenic signals, as well as secretion of cytokines and extracellular matrix components. […] Despite serotonin being important, CHD is believed to be a multifactorial phenomenon, since several other mediators have been associated with CHD. […] Regardless of the still unknown precise underlying mechanism, fibrotic plaque deposition usually affects the downstream side of the valve leaflets (i.e. ventricular aspect of tricuspid valve and pulmonary side of pulmonary valve) and subvalvular apparatus. […] The accumulation of fibrosis leads to a progressive movement restriction, retraction and fixation, which are clinically transduced to right-sided valve stenosis, regurgitation, or a variable combination of both.
#38 Complications from carcinoid syndrome: review of the current evidence – ecancer
https://ecancer.org/en/journal/article/662-complications-from-carcinoid-syndrome-review-of-the-current-evidence
An emerging body of evidence has pointed towards serotonin as the possible main causative agent of CHD. […] Serotonin-induced cardiopathy possibly occurs through 5-HT2B. Activation of this G-protein coupled receptor mediates fibroblasts and smooth muscle cells mitogenic signals, as well as secretion of cytokines and extracellular matrix components. […] Despite serotonin being important, CHD is believed to be a multifactorial phenomenon, since several other mediators have been associated with CHD. […] Regardless of the still unknown precise underlying mechanism, fibrotic plaque deposition usually affects the downstream side of the valve leaflets (i.e. ventricular aspect of tricuspid valve and pulmonary side of pulmonary valve) and subvalvular apparatus. […] The accumulation of fibrosis leads to a progressive movement restriction, retraction and fixation, which are clinically transduced to right-sided valve stenosis, regurgitation, or a variable combination of both.
#39 Complications from carcinoid syndrome: review of the current evidence – ecancer
https://ecancer.org/en/journal/article/662-complications-from-carcinoid-syndrome-review-of-the-current-evidence
Interestingly, the left side of the heart is relatively protected from CHD because the vasoactive peptides are inactivated after passing through the lungs before they reach the left atrium. […] The association between CS and skin fibrosis was first described in 1958. […] Despite its rarity, there are several reports linking carcinoid tumours with retroperitoneal fibrosis that can produce stenosis of the ureters and hydronephrosis. […] Although the precise mechanisms of extracardiac fibrosis have not yet been fully unraveled, serotonin, and TGF- are believed to be possible mediators.
#40 Carcinoid Syndrome – Neuroendocrine Disorders – Pathology – Picmonic for Medicine
https://www.picmonic.com/pathways/medicine/courses/standard/pathology-196/neuroendocrine-disorders-39305/carcinoid-syndrome_278
Wheezing caused by bronchoconstriction is a common sign of carcinoid syndrome. The exact pathogenesis of bronchoconstriction is unknown but is thought to be caused by excess serotonin. […] Carcinoid syndrome is associated with fibrotic lesions on the cardiac valves and endocardium. These typically affect the right side of the heart as the right heart receives blood from systemic circulation. This is because serotonin is broken down by monoamine oxidase, which is found in the lungs (along with the liver), with metabolism occurring before active serotonin arrives at the left heart.
#41 Complications from carcinoid syndrome: review of the current evidence – ecancer
https://ecancer.org/en/journal/article/662-complications-from-carcinoid-syndrome-review-of-the-current-evidence
Interestingly, the left side of the heart is relatively protected from CHD because the vasoactive peptides are inactivated after passing through the lungs before they reach the left atrium. […] The association between CS and skin fibrosis was first described in 1958. […] Despite its rarity, there are several reports linking carcinoid tumours with retroperitoneal fibrosis that can produce stenosis of the ureters and hydronephrosis. […] Although the precise mechanisms of extracardiac fibrosis have not yet been fully unraveled, serotonin, and TGF- are believed to be possible mediators.
#42 Complications from carcinoid syndrome: review of the current evidence – ecancer
https://ecancer.org/en/journal/article/662-complications-from-carcinoid-syndrome-review-of-the-current-evidence
Interestingly, the left side of the heart is relatively protected from CHD because the vasoactive peptides are inactivated after passing through the lungs before they reach the left atrium. […] The association between CS and skin fibrosis was first described in 1958. […] Despite its rarity, there are several reports linking carcinoid tumours with retroperitoneal fibrosis that can produce stenosis of the ureters and hydronephrosis. […] Although the precise mechanisms of extracardiac fibrosis have not yet been fully unraveled, serotonin, and TGF- are believed to be possible mediators.
#43 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
The TGF family of cytokines is a pivotal regulator of proliferative and profibrotic processes. […] TGF signalling has a dual role with on the one hand antitumourigenic and antiproliferative effects in physiological and early neoplastic conditions, and on the other hand, protumourigenic effects such as proliferation and invasion in later stages of malignant disease. […] Also, it stimulates stromal cells to induce myofibroblastic differentiation and altered ECM production. […] Once differentiated to myofibroblast, these cells secrete TGF creating a self-sustained, profibrotic feedback loop. […] Due to its profibrotic and protumourigenic effects, TGF is one of the most extensively studied growth factors in SI-NETs. […] Serotonin is a biogenic amine that can act as a neurotransmitter, hormone or growth factor. […] As a high level of serotonin secretion characterizes functional SI-NETs, this was considered as the causal agent of fibrosis. […] The ability of serotonin to have a wide array of effects is attributed to its diverse receptor system. […] Furthermore, fibroblasts are shown to express 5-HT receptors and in other fibrotic diseases, such as pulmonary and liver fibrosis, the direct proliferative effect of serotonin on fibroblasts seems to be mediated via specific 5-HT receptors. […] These results point to serotonin as the main driver of fibrosis.
#44 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
The TGF family of cytokines is a pivotal regulator of proliferative and profibrotic processes. […] TGF signalling has a dual role with on the one hand antitumourigenic and antiproliferative effects in physiological and early neoplastic conditions, and on the other hand, protumourigenic effects such as proliferation and invasion in later stages of malignant disease. […] Also, it stimulates stromal cells to induce myofibroblastic differentiation and altered ECM production. […] Once differentiated to myofibroblast, these cells secrete TGF creating a self-sustained, profibrotic feedback loop. […] Due to its profibrotic and protumourigenic effects, TGF is one of the most extensively studied growth factors in SI-NETs. […] Serotonin is a biogenic amine that can act as a neurotransmitter, hormone or growth factor. […] As a high level of serotonin secretion characterizes functional SI-NETs, this was considered as the causal agent of fibrosis. […] The ability of serotonin to have a wide array of effects is attributed to its diverse receptor system. […] Furthermore, fibroblasts are shown to express 5-HT receptors and in other fibrotic diseases, such as pulmonary and liver fibrosis, the direct proliferative effect of serotonin on fibroblasts seems to be mediated via specific 5-HT receptors. […] These results point to serotonin as the main driver of fibrosis.
#45 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
The TGF family of cytokines is a pivotal regulator of proliferative and profibrotic processes. […] TGF signalling has a dual role with on the one hand antitumourigenic and antiproliferative effects in physiological and early neoplastic conditions, and on the other hand, protumourigenic effects such as proliferation and invasion in later stages of malignant disease. […] Also, it stimulates stromal cells to induce myofibroblastic differentiation and altered ECM production. […] Once differentiated to myofibroblast, these cells secrete TGF creating a self-sustained, profibrotic feedback loop. […] Due to its profibrotic and protumourigenic effects, TGF is one of the most extensively studied growth factors in SI-NETs. […] Serotonin is a biogenic amine that can act as a neurotransmitter, hormone or growth factor. […] As a high level of serotonin secretion characterizes functional SI-NETs, this was considered as the causal agent of fibrosis. […] The ability of serotonin to have a wide array of effects is attributed to its diverse receptor system. […] Furthermore, fibroblasts are shown to express 5-HT receptors and in other fibrotic diseases, such as pulmonary and liver fibrosis, the direct proliferative effect of serotonin on fibroblasts seems to be mediated via specific 5-HT receptors. […] These results point to serotonin as the main driver of fibrosis.
#46 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
PDGF has a strong proliferative effect on fibroblasts and can induce proliferation of epithelial cancer cells. […] The profibrotic effects of PDGF are mediated by binding to the PDGF – and -receptors. […] Expression of the receptors differs between cell types and can be induced by diverse factors, such as TGF. […] In stromal cells of SI-NETs, the PDGFR was detected by IHC in 66-85%. […] The positive cells showed frequently a fibroblastic morphology with muscle actin antigen positivity, suggesting an activated phenotype characteristic of CAFs. […] CTGF is a member of the CCN family of growth factors, which are induced by cytokines such as TGF and importantly also by serotonin. […] CTGF enhances profibrotic actions of TGF, EGF and FGF by increasing collagen synthesis, fibroblast proliferation and differentiation into myofibroblasts. […] As CTGF enhances the effect of tumourgenic and profibrotic growth factors, it is a potential target for therapy.
#47 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
PDGF has a strong proliferative effect on fibroblasts and can induce proliferation of epithelial cancer cells. […] The profibrotic effects of PDGF are mediated by binding to the PDGF – and -receptors. […] Expression of the receptors differs between cell types and can be induced by diverse factors, such as TGF. […] In stromal cells of SI-NETs, the PDGFR was detected by IHC in 66-85%. […] The positive cells showed frequently a fibroblastic morphology with muscle actin antigen positivity, suggesting an activated phenotype characteristic of CAFs. […] CTGF is a member of the CCN family of growth factors, which are induced by cytokines such as TGF and importantly also by serotonin. […] CTGF enhances profibrotic actions of TGF, EGF and FGF by increasing collagen synthesis, fibroblast proliferation and differentiation into myofibroblasts. […] As CTGF enhances the effect of tumourgenic and profibrotic growth factors, it is a potential target for therapy.
#48 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
PDGF has a strong proliferative effect on fibroblasts and can induce proliferation of epithelial cancer cells. […] The profibrotic effects of PDGF are mediated by binding to the PDGF – and -receptors. […] Expression of the receptors differs between cell types and can be induced by diverse factors, such as TGF. […] In stromal cells of SI-NETs, the PDGFR was detected by IHC in 66-85%. […] The positive cells showed frequently a fibroblastic morphology with muscle actin antigen positivity, suggesting an activated phenotype characteristic of CAFs. […] CTGF is a member of the CCN family of growth factors, which are induced by cytokines such as TGF and importantly also by serotonin. […] CTGF enhances profibrotic actions of TGF, EGF and FGF by increasing collagen synthesis, fibroblast proliferation and differentiation into myofibroblasts. […] As CTGF enhances the effect of tumourgenic and profibrotic growth factors, it is a potential target for therapy.
#49 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
PDGF has a strong proliferative effect on fibroblasts and can induce proliferation of epithelial cancer cells. […] The profibrotic effects of PDGF are mediated by binding to the PDGF – and -receptors. […] Expression of the receptors differs between cell types and can be induced by diverse factors, such as TGF. […] In stromal cells of SI-NETs, the PDGFR was detected by IHC in 66-85%. […] The positive cells showed frequently a fibroblastic morphology with muscle actin antigen positivity, suggesting an activated phenotype characteristic of CAFs. […] CTGF is a member of the CCN family of growth factors, which are induced by cytokines such as TGF and importantly also by serotonin. […] CTGF enhances profibrotic actions of TGF, EGF and FGF by increasing collagen synthesis, fibroblast proliferation and differentiation into myofibroblasts. […] As CTGF enhances the effect of tumourgenic and profibrotic growth factors, it is a potential target for therapy.
#50 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
PDGF has a strong proliferative effect on fibroblasts and can induce proliferation of epithelial cancer cells. […] The profibrotic effects of PDGF are mediated by binding to the PDGF – and -receptors. […] Expression of the receptors differs between cell types and can be induced by diverse factors, such as TGF. […] In stromal cells of SI-NETs, the PDGFR was detected by IHC in 66-85%. […] The positive cells showed frequently a fibroblastic morphology with muscle actin antigen positivity, suggesting an activated phenotype characteristic of CAFs. […] CTGF is a member of the CCN family of growth factors, which are induced by cytokines such as TGF and importantly also by serotonin. […] CTGF enhances profibrotic actions of TGF, EGF and FGF by increasing collagen synthesis, fibroblast proliferation and differentiation into myofibroblasts. […] As CTGF enhances the effect of tumourgenic and profibrotic growth factors, it is a potential target for therapy.
#51 Malignant Carcinoid Syndrome: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/282515-overview
Malignant carcinoid syndrome is characterized by an array of signs and symptoms in particular, hot, red flushing of the face; severe and debilitating diarrhea; and asthma attacks caused by vasoactive hormones secreted by metastases from carcinoid tumors. […] Carcinoid tumors are of neuroendocrine origin and derive from primitive stem cells, which can give rise to multiple cell lineages. […] Malignant carcinoid syndrome occurs in fewer than 10% of patients with a carcinoid tumor. […] Pathophysiology is closely related to the sites of the primary tumors. When these tumors spread to the liver, patients usually begin to develop malignant carcinoid syndrome. In fact, this syndrome develops when vasoactive substances produced by a carcinoid tumor escape hepatic degradation and gain access to the systemic circulation.
#52 Carcinoid Tumor: Treatment, Symptoms, Meaning
https://www.medicinenet.com/carcinoid_syndrome/article.htm
Carcinoid tumors may be cancerous or benign and form largely in the lungs and gut. The clinical course of these cancers is often indolent with 5-year survival approaching 75%. […] A carcinoid tumor is a tumor that develops from enterochromaffin cells. Enterochromaffin cells are hormone- and chemical-producing cells that normally are found in the small intestine, appendix, colon, rectum, bronchi, pancreas, ovaries, testes, bile ducts, liver, as well as other organs. […] Since carcinoid tumors develop from enterochromaffin cells, they frequently retain the capability of producing the same hormones, often in large quantities. When these hormones circulate in the blood, they can cause symptoms of carcinoid syndrome, which is discussed later. […] The important characteristic of carcinoid tumors that sets them apart from other gastrointestinal tract tumors is their potential to cause carcinoid syndrome.
#53
https://link.springer.com/article/10.1007/s12022-018-9530-y
Pulmonary carcinoid tumors occur in both central and peripheral locations, and some differences in clinico-pathological features have long been observed. […] An important difference was a strong association of the peripheral tumor with neuroendocrine hyperplasia while such an association in central tumors was negligible. The tumor location might be relevant for pathobiology of lung carcinoid tumors. […] It has long been known that there are some clinical and pathological differences between carcinoid tumors arising in the bronchus and those located in the periphery of the lung. […] The findings in our study confirm that the so-called central and peripheral carcinoid tumors are a subtype of carcinoid tumor with distinct clinical and pathological characteristics. A notable difference is a strong association of the peripheral carcinoid with neuroendocrine hyperplasia, which indicates a different pathogenesis. Histologic features of carcinoid tumor of peripheral type, whether occurring in the peripheral or central location, would require thorough search for underlying neuroendocrine hyperplasia.
#54
https://link.springer.com/article/10.1007/s12022-018-9530-y
Pulmonary carcinoid tumors occur in both central and peripheral locations, and some differences in clinico-pathological features have long been observed. […] An important difference was a strong association of the peripheral tumor with neuroendocrine hyperplasia while such an association in central tumors was negligible. The tumor location might be relevant for pathobiology of lung carcinoid tumors. […] It has long been known that there are some clinical and pathological differences between carcinoid tumors arising in the bronchus and those located in the periphery of the lung. […] The findings in our study confirm that the so-called central and peripheral carcinoid tumors are a subtype of carcinoid tumor with distinct clinical and pathological characteristics. A notable difference is a strong association of the peripheral carcinoid with neuroendocrine hyperplasia, which indicates a different pathogenesis. Histologic features of carcinoid tumor of peripheral type, whether occurring in the peripheral or central location, would require thorough search for underlying neuroendocrine hyperplasia.
#55
https://link.springer.com/article/10.1007/s12022-018-9530-y
Pulmonary carcinoid tumors occur in both central and peripheral locations, and some differences in clinico-pathological features have long been observed. […] An important difference was a strong association of the peripheral tumor with neuroendocrine hyperplasia while such an association in central tumors was negligible. The tumor location might be relevant for pathobiology of lung carcinoid tumors. […] It has long been known that there are some clinical and pathological differences between carcinoid tumors arising in the bronchus and those located in the periphery of the lung. […] The findings in our study confirm that the so-called central and peripheral carcinoid tumors are a subtype of carcinoid tumor with distinct clinical and pathological characteristics. A notable difference is a strong association of the peripheral carcinoid with neuroendocrine hyperplasia, which indicates a different pathogenesis. Histologic features of carcinoid tumor of peripheral type, whether occurring in the peripheral or central location, would require thorough search for underlying neuroendocrine hyperplasia.
#56
https://link.springer.com/article/10.1007/s12022-018-9530-y
Pulmonary carcinoid tumors occur in both central and peripheral locations, and some differences in clinico-pathological features have long been observed. […] An important difference was a strong association of the peripheral tumor with neuroendocrine hyperplasia while such an association in central tumors was negligible. The tumor location might be relevant for pathobiology of lung carcinoid tumors. […] It has long been known that there are some clinical and pathological differences between carcinoid tumors arising in the bronchus and those located in the periphery of the lung. […] The findings in our study confirm that the so-called central and peripheral carcinoid tumors are a subtype of carcinoid tumor with distinct clinical and pathological characteristics. A notable difference is a strong association of the peripheral carcinoid with neuroendocrine hyperplasia, which indicates a different pathogenesis. Histologic features of carcinoid tumor of peripheral type, whether occurring in the peripheral or central location, would require thorough search for underlying neuroendocrine hyperplasia.
#57 Carcinoid Tumors | CancerIndex
http://www.cancerindex.org/clinks6d.htm
DIPNECH is characterized by neuroendocrine cell hyperplasia, tumorlets, and eventually carcinoid tumors. Although it is regarded by some authors as a preneoplastic condition, this issue is controversial. New pathologic criteria have recently been proposed for the diagnosis of DIPNECH, and a subgroup of carcinoid tumors expressing developing neural transcription factors (DNTFs), with clinicopathologic features similar to those of DIPNECH, has been recognized. […] The prophylactic use of a preoperative, intraoperative, and postoperative high-dose continuous octreotide acetate infusion was evaluated for its ability to minimize the incidence of carcinoid crises during neuroendocrine tumor (NET) cytoreductive surgeries. […] A continuous high-dose infusion of octreotide acetate intraoperatively minimizes the incidence of carcinoid crisis.
#58 A PECULIAR CASE OF PSYCHOSIS ASSOCIATED WITH NEUROENDOCRINE CARCINOID CANCER OF THE APPENDIX – SHM Abstracts | Society of Hospital Medicine
https://shmabstracts.org/abstract/a-peculiar-case-of-psychosis-associated-with-neuroendocrine-carcinoid-cancer-of-the-appendix/
Carcinoids are neuroendocrine malignancies derived from cells characterized by their ability to produce and secrete vasoactive substances such as serotonin. […] Midgut tumors are especially active serotonin producers. Excess serotonin can cause carcinoid syndrome, which can present as diarrhea, skin flushing, heart valve dysfunction, bronchospasm, pellagra and uncommonly with psychiatric symptoms. […] Neuroendocrine malignancies of the midgut such as appendix are especially active serotonin producers. Carcinoid syndrome due to excess serotonin production is more likely with metastatic carcinoid cancer. The mechanism precipitating psychosis in carcinoid syndrome is not fully understood but includes hormonal effect from the tumor; niacin deficiency due to metabolic diversion of its precursor tryptophan to form serotonin. […] The recognition of psychosis as a presenting and unusual symptom of carcinoid syndrome is essential for proper treatment and management of this complicated and uncommon condition.
#59 Management of gastrointestinal carcinoid tumours-10 years experience at a district general hospital – Dronamraju – Journal of Gastrointestinal Oncology
https://jgo.amegroups.org/article/view/271/568
GICTs account for approximately 75% of all neuro-endocrine tumours and according to a recent large population based survey there has been a significant increase in the annual age adjusted incidence rates of carcinoids tumours. Based on their embryonic origin, GICTs are classified as foregut, midgut and hindgut carcinoids. They are slow growing lesions and as a result, patients usually complain of a wide variety of non-specific abdominal pains/symptoms which eventually progress to episodes of small bowel obstruction or rarely gastrointestinal bleeding. Furthermore, in a significant proportion of these patients, the diagnosis is not revealed until after emergency surgery. […] The primary lesion in midgut carcinoids is usually a small (1 cm), flat and fibrotic tumour in the submucosal plane of the ileum and is frequently not diagnosed until surgical exploration. Other operative findings usually include enlarged lymph nodes with associated adjacent mesenteric fibrosis leading to kinking of the bowel and thus obstruction. This extensive mesenteric stranding and fibrosis is probably secondary to the release of serotonin and growth factors from tumour cells and can also lead to the encasement of mesenteric vessels leading to ischemia of the bowel.
#60 Management of gastrointestinal carcinoid tumours-10 years experience at a district general hospital – Dronamraju – Journal of Gastrointestinal Oncology
https://jgo.amegroups.org/article/view/271/568
GICTs account for approximately 75% of all neuro-endocrine tumours and according to a recent large population based survey there has been a significant increase in the annual age adjusted incidence rates of carcinoids tumours. Based on their embryonic origin, GICTs are classified as foregut, midgut and hindgut carcinoids. They are slow growing lesions and as a result, patients usually complain of a wide variety of non-specific abdominal pains/symptoms which eventually progress to episodes of small bowel obstruction or rarely gastrointestinal bleeding. Furthermore, in a significant proportion of these patients, the diagnosis is not revealed until after emergency surgery. […] The primary lesion in midgut carcinoids is usually a small (1 cm), flat and fibrotic tumour in the submucosal plane of the ileum and is frequently not diagnosed until surgical exploration. Other operative findings usually include enlarged lymph nodes with associated adjacent mesenteric fibrosis leading to kinking of the bowel and thus obstruction. This extensive mesenteric stranding and fibrosis is probably secondary to the release of serotonin and growth factors from tumour cells and can also lead to the encasement of mesenteric vessels leading to ischemia of the bowel.
#61 Management of gastrointestinal carcinoid tumours-10 years experience at a district general hospital – Dronamraju – Journal of Gastrointestinal Oncology
https://jgo.amegroups.org/article/view/271/568
GICTs account for approximately 75% of all neuro-endocrine tumours and according to a recent large population based survey there has been a significant increase in the annual age adjusted incidence rates of carcinoids tumours. Based on their embryonic origin, GICTs are classified as foregut, midgut and hindgut carcinoids. They are slow growing lesions and as a result, patients usually complain of a wide variety of non-specific abdominal pains/symptoms which eventually progress to episodes of small bowel obstruction or rarely gastrointestinal bleeding. Furthermore, in a significant proportion of these patients, the diagnosis is not revealed until after emergency surgery. […] The primary lesion in midgut carcinoids is usually a small (1 cm), flat and fibrotic tumour in the submucosal plane of the ileum and is frequently not diagnosed until surgical exploration. Other operative findings usually include enlarged lymph nodes with associated adjacent mesenteric fibrosis leading to kinking of the bowel and thus obstruction. This extensive mesenteric stranding and fibrosis is probably secondary to the release of serotonin and growth factors from tumour cells and can also lead to the encasement of mesenteric vessels leading to ischemia of the bowel.
#62 Management of gastrointestinal carcinoid tumours-10 years experience at a district general hospital – Dronamraju – Journal of Gastrointestinal Oncology
https://jgo.amegroups.org/article/view/271/568
Carcinoid syndrome is typically seen in patients with liver/lung metastases with an overall incidence of 10% in GICTs but 20% in those with jejuno-ileal disease. Typical symptoms of carcinoid syndrome include flushing, diarrhoea, tachycardia, hypotension, bronchospasm and right heart failure; carcinoid heart disease is a late and potentially fatal complication presumed to be secondary to endocardial fibrosis of right side heart valves leading to pulmonary stenosis and tricuspid insufficiency. […] Somatostatin is a peptide that inhibits the secretion of a number of hormones and a significant proportion of GICTs have been shown to express somatostatin receptors on their cell surfaces. As a result, somatostatin analogues (Octreotide and Lanreotide) as well as interferons have been used to effectively palliate the symptoms of carcinoid syndrome in up to 70% of patients, to provide tumour reduction in around 5% of patients and to stabilise the disease in approximately half of the patients.
#63 Gastrointestinal Carcinoid Tumors | Memorial Sloan Kettering Cancer Center
https://www.mskcc.org/cancer-care/types/gastrointestinal-neuroendocrine/gastrointestinal-carcinoid-tumors
Carcinoid tumors are the most common type of neuroendocrine tumor. An estimated 11,000 to 12,000 people are diagnosed with a carcinoid tumor each year in the United States. About two-thirds of all carcinoid tumors appear in the gastrointestinal system, particularly in the small intestine, rectum, stomach, colon, and liver. […] Carcinoid tumors usually grow slowly over many years. Neuroendocrine tumors that grow slowly are called low-grade tumors. However, even low-grade carcinoid tumors can begin to grow rapidly, for reasons that are not well understood. […] Many carcinoid tumors produce a hormone called serotonin, which can lead to a variety of symptoms known as carcinoid syndrome. […] Patients with carcinoid syndrome who undergo surgery, anesthesia, or chemotherapy are at risk of experiencing a carcinoid crisis, which is a life-threatening condition caused by a sudden surge of serotonin into the bloodstream.
#64
https://link.springer.com/article/10.1007/s11864-002-0031-2
Carcinoids are rare endocrine tumors that can develop in several organs in the body. […] Most carcinoid tumors are indolent but can metastasize to regional lymph nodes and to other organs, including the liver, bone, and the central nervous system. […] Overall, 5- and 10-year survival rates in patients with metastatic disease are favorable, although tumors can be resistant to most forms of medical or surgical therapy.
#65 Carcinoid Tumors and the Carcinoid Syndrome: What’s new in the therapeutic pipeline – Carcinoid Cancer Foundation
https://www.carcinoid.org/for-patients/videos/carcinoid-tumors-and-the-carcinoid-syndrome-whats-new-in-the-therapeutic-pipeline/
The tumors on the Octreoscan are shown here as the dark black spots. […] We have been talking a lot about small bowel carcinoids because that is, in my practice, and in the practice of people who specialize in this, the most common site of the primary tumor. […] The anaplastic carcinoid tumors are the tumors that when we look under the microscope have lots of cells that are dividing. These are tumors that are faster growing. […] Most of these well-differentiated tumors are somatostatin receptor positive meaning they have receptors on the surface of the cell. Most of the poorly differentiated tumors are somatostatin receptor negative. […] The initial evidence that Sandostatin, although it causes tumor shrinkage uncommonly, does result in prolongation of life because of the growth inhibitory effect on the tumor cells. […] The process is called angiogenesis. There are a number of compounds that are anti-angiogenic in nature. […] We are also going to be evaluating a new drug called Epothilone-B and that is going before our scientific review committee on Monday.
#66 Carcinoid Tumors and the Carcinoid Syndrome: What’s new in the therapeutic pipeline – Carcinoid Cancer Foundation
https://www.carcinoid.org/for-patients/videos/carcinoid-tumors-and-the-carcinoid-syndrome-whats-new-in-the-therapeutic-pipeline/
The tumors on the Octreoscan are shown here as the dark black spots. […] We have been talking a lot about small bowel carcinoids because that is, in my practice, and in the practice of people who specialize in this, the most common site of the primary tumor. […] The anaplastic carcinoid tumors are the tumors that when we look under the microscope have lots of cells that are dividing. These are tumors that are faster growing. […] Most of these well-differentiated tumors are somatostatin receptor positive meaning they have receptors on the surface of the cell. Most of the poorly differentiated tumors are somatostatin receptor negative. […] The initial evidence that Sandostatin, although it causes tumor shrinkage uncommonly, does result in prolongation of life because of the growth inhibitory effect on the tumor cells. […] The process is called angiogenesis. There are a number of compounds that are anti-angiogenic in nature. […] We are also going to be evaluating a new drug called Epothilone-B and that is going before our scientific review committee on Monday.
#67 The role of serotonin inhibition within the treatment of carcinoid syndrome in: Endocrine Oncology Volume 3 Issue 1 (2023)
https://eo.bioscientifica.com/view/journals/eo/3/1/EO-22-0077.xml
Carcinoid syndrome is the most frequent hormonal complication associated with neuroendocrine neoplasms. It is caused by the secretion of several vasoactive substances, the most prominent being serotonin, which play a pathophysiological role in the clinical symptoms which characterise carcinoid syndrome. […] The major acute life-threatening complication of CS is carcinoid crisis. CS has been shown to have a significant impact on patients QoL. The aim of CS treatment is to reduce 5-HT production, control symptoms and improve QoL. […] The tumour microenvironment has been recognised as a critical determinant of tumour progression. […] Seven 5-HT receptor classes (5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7) have been identified and are widely expressed throughout the body. […] A high 5-HT is thought to be the main mediator of diarrhoea by acting directly on cell membrane receptors of enteric neurons. This increases peristalsis and impedes intestinal absorption. 5-HT may stimulate the synthesis of extracellular matrix (ECM), leading to fibrosis and resulting in bowel obstruction and carcinoid heart disease in the long term. There is a correlation between these complications and raised urine 5-HIAA. […] The focus of carcinoid syndrome treatment is to reduce serotonin production and hence improve the patients quality of life.
#68 Carcinoid Tumors and the Carcinoid Syndrome: What’s new in the therapeutic pipeline – Carcinoid Cancer Foundation
https://www.carcinoid.org/for-patients/videos/carcinoid-tumors-and-the-carcinoid-syndrome-whats-new-in-the-therapeutic-pipeline/
The tumors on the Octreoscan are shown here as the dark black spots. […] We have been talking a lot about small bowel carcinoids because that is, in my practice, and in the practice of people who specialize in this, the most common site of the primary tumor. […] The anaplastic carcinoid tumors are the tumors that when we look under the microscope have lots of cells that are dividing. These are tumors that are faster growing. […] Most of these well-differentiated tumors are somatostatin receptor positive meaning they have receptors on the surface of the cell. Most of the poorly differentiated tumors are somatostatin receptor negative. […] The initial evidence that Sandostatin, although it causes tumor shrinkage uncommonly, does result in prolongation of life because of the growth inhibitory effect on the tumor cells. […] The process is called angiogenesis. There are a number of compounds that are anti-angiogenic in nature. […] We are also going to be evaluating a new drug called Epothilone-B and that is going before our scientific review committee on Monday.
#69 Management of gastrointestinal carcinoid tumours-10 years experience at a district general hospital – Dronamraju – Journal of Gastrointestinal Oncology
https://jgo.amegroups.org/article/view/271/568
Carcinoid syndrome is typically seen in patients with liver/lung metastases with an overall incidence of 10% in GICTs but 20% in those with jejuno-ileal disease. Typical symptoms of carcinoid syndrome include flushing, diarrhoea, tachycardia, hypotension, bronchospasm and right heart failure; carcinoid heart disease is a late and potentially fatal complication presumed to be secondary to endocardial fibrosis of right side heart valves leading to pulmonary stenosis and tricuspid insufficiency. […] Somatostatin is a peptide that inhibits the secretion of a number of hormones and a significant proportion of GICTs have been shown to express somatostatin receptors on their cell surfaces. As a result, somatostatin analogues (Octreotide and Lanreotide) as well as interferons have been used to effectively palliate the symptoms of carcinoid syndrome in up to 70% of patients, to provide tumour reduction in around 5% of patients and to stabilise the disease in approximately half of the patients.
#70 Management of gastrointestinal carcinoid tumours-10 years experience at a district general hospital – Dronamraju – Journal of Gastrointestinal Oncology
https://jgo.amegroups.org/article/view/271/568
Carcinoid syndrome is typically seen in patients with liver/lung metastases with an overall incidence of 10% in GICTs but 20% in those with jejuno-ileal disease. Typical symptoms of carcinoid syndrome include flushing, diarrhoea, tachycardia, hypotension, bronchospasm and right heart failure; carcinoid heart disease is a late and potentially fatal complication presumed to be secondary to endocardial fibrosis of right side heart valves leading to pulmonary stenosis and tricuspid insufficiency. […] Somatostatin is a peptide that inhibits the secretion of a number of hormones and a significant proportion of GICTs have been shown to express somatostatin receptors on their cell surfaces. As a result, somatostatin analogues (Octreotide and Lanreotide) as well as interferons have been used to effectively palliate the symptoms of carcinoid syndrome in up to 70% of patients, to provide tumour reduction in around 5% of patients and to stabilise the disease in approximately half of the patients.
#71 Gastrointestinal Carcinoid Tumors | Memorial Sloan Kettering Cancer Center
https://www.mskcc.org/cancer-care/types/gastrointestinal-neuroendocrine/gastrointestinal-carcinoid-tumors
Carcinoid tumors are the most common type of neuroendocrine tumor. An estimated 11,000 to 12,000 people are diagnosed with a carcinoid tumor each year in the United States. About two-thirds of all carcinoid tumors appear in the gastrointestinal system, particularly in the small intestine, rectum, stomach, colon, and liver. […] Carcinoid tumors usually grow slowly over many years. Neuroendocrine tumors that grow slowly are called low-grade tumors. However, even low-grade carcinoid tumors can begin to grow rapidly, for reasons that are not well understood. […] Many carcinoid tumors produce a hormone called serotonin, which can lead to a variety of symptoms known as carcinoid syndrome. […] Patients with carcinoid syndrome who undergo surgery, anesthesia, or chemotherapy are at risk of experiencing a carcinoid crisis, which is a life-threatening condition caused by a sudden surge of serotonin into the bloodstream.
#72 Carcinoid Tumors | CancerIndex
http://www.cancerindex.org/clinks6d.htm
DIPNECH is characterized by neuroendocrine cell hyperplasia, tumorlets, and eventually carcinoid tumors. Although it is regarded by some authors as a preneoplastic condition, this issue is controversial. New pathologic criteria have recently been proposed for the diagnosis of DIPNECH, and a subgroup of carcinoid tumors expressing developing neural transcription factors (DNTFs), with clinicopathologic features similar to those of DIPNECH, has been recognized. […] The prophylactic use of a preoperative, intraoperative, and postoperative high-dose continuous octreotide acetate infusion was evaluated for its ability to minimize the incidence of carcinoid crises during neuroendocrine tumor (NET) cytoreductive surgeries. […] A continuous high-dose infusion of octreotide acetate intraoperatively minimizes the incidence of carcinoid crisis.
#73 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
Another hallmark of SI-NETs is the ability to induce fibrosis. The fibrosis can occur around the tumour or at distant sites. […] Carcinoid heart disease is associated with metastatic disease and carcinoid syndrome, suggesting an etiological role for circulating tumour-secreted factors. […] However, in this review, we will focus on local fibrotic complications, of which mesenteric fibrosis (MF) is most notable and occurs in up to 50% of SI-NET patients. […] It is caused by a metastatic lesion circumscribed by an extensive fibrotic reaction in the mesentery. […] MF leads in a significant percentage of patients to intestinal obstruction, oedema and ischaemia, which causes abdominal pain, cachexia and often necessitates surgery. […] Because survival of patients improved since the development of targeted and more effective therapies for carcinoid syndrome and tumour growth control, there is increased need for advancements in treatment options for MF. […] As improved knowledge of the pathogenesis of fibrosis is key to the development of new therapies, we assessed in this review literature on putative mediators of MF in SI-NETs and treatments targeting these factors.
#74 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
Another hallmark of SI-NETs is the ability to induce fibrosis. The fibrosis can occur around the tumour or at distant sites. […] Carcinoid heart disease is associated with metastatic disease and carcinoid syndrome, suggesting an etiological role for circulating tumour-secreted factors. […] However, in this review, we will focus on local fibrotic complications, of which mesenteric fibrosis (MF) is most notable and occurs in up to 50% of SI-NET patients. […] It is caused by a metastatic lesion circumscribed by an extensive fibrotic reaction in the mesentery. […] MF leads in a significant percentage of patients to intestinal obstruction, oedema and ischaemia, which causes abdominal pain, cachexia and often necessitates surgery. […] Because survival of patients improved since the development of targeted and more effective therapies for carcinoid syndrome and tumour growth control, there is increased need for advancements in treatment options for MF. […] As improved knowledge of the pathogenesis of fibrosis is key to the development of new therapies, we assessed in this review literature on putative mediators of MF in SI-NETs and treatments targeting these factors.
#75 Complications from carcinoid syndrome: review of the current evidence – ecancer
https://ecancer.org/en/journal/article/662-complications-from-carcinoid-syndrome-review-of-the-current-evidence
Patients with well-differentiated neuroendocrine tumours may develop carcinoid syndrome (CS), which is characterised by flushing, abdominal cramps, diarrhoea, and bronchospasms. […] current evidence suggests the pathogenesis of such fibrogenic complications relies on signalling through 5-HT2B and TGF-1. […] Although the precise pathogenesis remains elusive, these substances are implicated in the development of CS. Tumour metastatic spread to the liver circumvents the hepatic inactivation of these substances and leads to CS development. […] CHD results from chronic fibrotic degeneration of the cardiac valve leaflets. Despite the fact that the precise pathways involved in this complication remain largely unknown, it was proposed that the vasoactive substances produced and secreted by the tumours induce myofibroblast proliferation and local deposition of extracellular matrix, ultimately leading to the emergence of endocardial plaques composed of matrix-rich fibrous tissues.
#76 The role of serotonin inhibition within the treatment of carcinoid syndrome in: Endocrine Oncology Volume 3 Issue 1 (2023)
https://eo.bioscientifica.com/view/journals/eo/3/1/EO-22-0077.xml
Carcinoid syndrome is the most frequent hormonal complication associated with neuroendocrine neoplasms. It is caused by the secretion of several vasoactive substances, the most prominent being serotonin, which play a pathophysiological role in the clinical symptoms which characterise carcinoid syndrome. […] The major acute life-threatening complication of CS is carcinoid crisis. CS has been shown to have a significant impact on patients QoL. The aim of CS treatment is to reduce 5-HT production, control symptoms and improve QoL. […] The tumour microenvironment has been recognised as a critical determinant of tumour progression. […] Seven 5-HT receptor classes (5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7) have been identified and are widely expressed throughout the body. […] A high 5-HT is thought to be the main mediator of diarrhoea by acting directly on cell membrane receptors of enteric neurons. This increases peristalsis and impedes intestinal absorption. 5-HT may stimulate the synthesis of extracellular matrix (ECM), leading to fibrosis and resulting in bowel obstruction and carcinoid heart disease in the long term. There is a correlation between these complications and raised urine 5-HIAA. […] The focus of carcinoid syndrome treatment is to reduce serotonin production and hence improve the patients quality of life.
#77 The role of serotonin inhibition within the treatment of carcinoid syndrome in: Endocrine Oncology Volume 3 Issue 1 (2023)
https://eo.bioscientifica.com/view/journals/eo/3/1/EO-22-0077.xml
Carcinoid syndrome is the most frequent hormonal complication associated with neuroendocrine neoplasms. It is caused by the secretion of several vasoactive substances, the most prominent being serotonin, which play a pathophysiological role in the clinical symptoms which characterise carcinoid syndrome. […] The major acute life-threatening complication of CS is carcinoid crisis. CS has been shown to have a significant impact on patients QoL. The aim of CS treatment is to reduce 5-HT production, control symptoms and improve QoL. […] The tumour microenvironment has been recognised as a critical determinant of tumour progression. […] Seven 5-HT receptor classes (5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7) have been identified and are widely expressed throughout the body. […] A high 5-HT is thought to be the main mediator of diarrhoea by acting directly on cell membrane receptors of enteric neurons. This increases peristalsis and impedes intestinal absorption. 5-HT may stimulate the synthesis of extracellular matrix (ECM), leading to fibrosis and resulting in bowel obstruction and carcinoid heart disease in the long term. There is a correlation between these complications and raised urine 5-HIAA. […] The focus of carcinoid syndrome treatment is to reduce serotonin production and hence improve the patients quality of life.
#78 The role of serotonin inhibition within the treatment of carcinoid syndrome in: Endocrine Oncology Volume 3 Issue 1 (2023)
https://eo.bioscientifica.com/view/journals/eo/3/1/EO-22-0077.xml
Carcinoid syndrome is the most frequent hormonal complication associated with neuroendocrine neoplasms. It is caused by the secretion of several vasoactive substances, the most prominent being serotonin, which play a pathophysiological role in the clinical symptoms which characterise carcinoid syndrome. […] The major acute life-threatening complication of CS is carcinoid crisis. CS has been shown to have a significant impact on patients QoL. The aim of CS treatment is to reduce 5-HT production, control symptoms and improve QoL. […] The tumour microenvironment has been recognised as a critical determinant of tumour progression. […] Seven 5-HT receptor classes (5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7) have been identified and are widely expressed throughout the body. […] A high 5-HT is thought to be the main mediator of diarrhoea by acting directly on cell membrane receptors of enteric neurons. This increases peristalsis and impedes intestinal absorption. 5-HT may stimulate the synthesis of extracellular matrix (ECM), leading to fibrosis and resulting in bowel obstruction and carcinoid heart disease in the long term. There is a correlation between these complications and raised urine 5-HIAA. […] The focus of carcinoid syndrome treatment is to reduce serotonin production and hence improve the patients quality of life.
#79 Small intestinal neuroendocrine tumours and fibrosis: an entangled conundrum in: Endocrine-Related Cancer Volume 25 Issue 3 (2018)
https://erc.bioscientifica.com/view/journals/erc/25/3/ERC-17-0380.xml
The TGF family of cytokines is a pivotal regulator of proliferative and profibrotic processes. […] TGF signalling has a dual role with on the one hand antitumourigenic and antiproliferative effects in physiological and early neoplastic conditions, and on the other hand, protumourigenic effects such as proliferation and invasion in later stages of malignant disease. […] Also, it stimulates stromal cells to induce myofibroblastic differentiation and altered ECM production. […] Once differentiated to myofibroblast, these cells secrete TGF creating a self-sustained, profibrotic feedback loop. […] Due to its profibrotic and protumourigenic effects, TGF is one of the most extensively studied growth factors in SI-NETs. […] Serotonin is a biogenic amine that can act as a neurotransmitter, hormone or growth factor. […] As a high level of serotonin secretion characterizes functional SI-NETs, this was considered as the causal agent of fibrosis. […] The ability of serotonin to have a wide array of effects is attributed to its diverse receptor system. […] Furthermore, fibroblasts are shown to express 5-HT receptors and in other fibrotic diseases, such as pulmonary and liver fibrosis, the direct proliferative effect of serotonin on fibroblasts seems to be mediated via specific 5-HT receptors. […] These results point to serotonin as the main driver of fibrosis.
#80 Advances in the Management of Patients With Carcinoid Syndrome â Hematology & Oncology
https://www.hematologyandoncology.net/archives/april-2017/advances-in-the-management-of-patients-with-carcinoid-syndrome/
Carcinoid tumors have the ability to secrete peptides and hormones, such as serotonin. […] It is thought that fibrosis is caused by serotonin that is secreted by the tumor. […] The association between serotonin secretion and carcinoid syndrome has been known for a long time. […] Telotristat ethyl (Xermelo, Lexicon Pharmaceuticals) is an inhibitor of tryptophan hydroxylase, a key enzyme involved in serotonin synthesis. […] The evaluation of telotristat ethyl in patients with carcinoid syndrome was based on the hypothesis that inhibition of the synthesis of serotonin in the tumor could effectively treat carcinoid syndrome. […] Decreases in urinary 5-HIAA reflect reductions in serotonin synthesis. […] This decrease in urinary 5-HIAA validated the mechanism of action of telotristat ethyl. […] A potential benefit of decreasing serotonin levels in patients with carcinoid syndrome relates to the long-term consequences of high levels.
#81 Advances in the Management of Patients With Carcinoid Syndrome â Hematology & Oncology
https://www.hematologyandoncology.net/archives/april-2017/advances-in-the-management-of-patients-with-carcinoid-syndrome/
Carcinoid tumors have the ability to secrete peptides and hormones, such as serotonin. […] It is thought that fibrosis is caused by serotonin that is secreted by the tumor. […] The association between serotonin secretion and carcinoid syndrome has been known for a long time. […] Telotristat ethyl (Xermelo, Lexicon Pharmaceuticals) is an inhibitor of tryptophan hydroxylase, a key enzyme involved in serotonin synthesis. […] The evaluation of telotristat ethyl in patients with carcinoid syndrome was based on the hypothesis that inhibition of the synthesis of serotonin in the tumor could effectively treat carcinoid syndrome. […] Decreases in urinary 5-HIAA reflect reductions in serotonin synthesis. […] This decrease in urinary 5-HIAA validated the mechanism of action of telotristat ethyl. […] A potential benefit of decreasing serotonin levels in patients with carcinoid syndrome relates to the long-term consequences of high levels.
#82 Advances in the Management of Patients With Carcinoid Syndrome â Hematology & Oncology
https://www.hematologyandoncology.net/archives/april-2017/advances-in-the-management-of-patients-with-carcinoid-syndrome/
Carcinoid tumors have the ability to secrete peptides and hormones, such as serotonin. […] It is thought that fibrosis is caused by serotonin that is secreted by the tumor. […] The association between serotonin secretion and carcinoid syndrome has been known for a long time. […] Telotristat ethyl (Xermelo, Lexicon Pharmaceuticals) is an inhibitor of tryptophan hydroxylase, a key enzyme involved in serotonin synthesis. […] The evaluation of telotristat ethyl in patients with carcinoid syndrome was based on the hypothesis that inhibition of the synthesis of serotonin in the tumor could effectively treat carcinoid syndrome. […] Decreases in urinary 5-HIAA reflect reductions in serotonin synthesis. […] This decrease in urinary 5-HIAA validated the mechanism of action of telotristat ethyl. […] A potential benefit of decreasing serotonin levels in patients with carcinoid syndrome relates to the long-term consequences of high levels.
#83 Advances in the Management of Patients With Carcinoid Syndrome â Hematology & Oncology
https://www.hematologyandoncology.net/archives/april-2017/advances-in-the-management-of-patients-with-carcinoid-syndrome/
Carcinoid tumors have the ability to secrete peptides and hormones, such as serotonin. […] It is thought that fibrosis is caused by serotonin that is secreted by the tumor. […] The association between serotonin secretion and carcinoid syndrome has been known for a long time. […] Telotristat ethyl (Xermelo, Lexicon Pharmaceuticals) is an inhibitor of tryptophan hydroxylase, a key enzyme involved in serotonin synthesis. […] The evaluation of telotristat ethyl in patients with carcinoid syndrome was based on the hypothesis that inhibition of the synthesis of serotonin in the tumor could effectively treat carcinoid syndrome. […] Decreases in urinary 5-HIAA reflect reductions in serotonin synthesis. […] This decrease in urinary 5-HIAA validated the mechanism of action of telotristat ethyl. […] A potential benefit of decreasing serotonin levels in patients with carcinoid syndrome relates to the long-term consequences of high levels.
#84 Carcinoid Tumor: Treatment, Symptoms, Meaning
https://www.medicinenet.com/carcinoid_syndrome/article.htm
Although carcinoid tumors may also cause these local symptoms, they may also produce and release the substances that cause the carcinoid syndrome. […] Carcinoid syndrome is a combination of symptoms caused by the hormones and other chemical substances released by the tumors into the bloodstream. […] The common hormones released are serotonin, bradykinin, histamine, and chromogranin A. […] The presence of carcinoid syndrome usually means that the tumor is malignant and has spread to the liver. […] The most important treatment modality for carcinoid syndrome is octreotide, a synthetic hormone similar in structure to the naturally-occurring hormone, somatostatin. […] Octreotide, like somatostatin, binds to receptors on the cells of carcinoid tumors and inhibits the manufacture and release of tumor hormones.
#85 Gastrointestinal Carcinoid Tumors | Memorial Sloan Kettering Cancer Center
https://www.mskcc.org/cancer-care/types/gastrointestinal-neuroendocrine/gastrointestinal-carcinoid-tumors
Patients with gastrointestinal carcinoid tumors that cannot be surgically removed may benefit from monthly injections of a synthetic hormone, octreotide, which controls hormone-related symptoms and may have the potential to slow tumor growth. […] Chemotherapy is usually reserved for patients whose carcinoid tumors begin to grow during treatment with octreotide. […] Some neuroendocrine tumors absorb a hormone called norepinephrine. These tumors may respond to a nuclear medicine technique called MIBG radiolabeled therapy. […] PRRT is a new nuclear medicine therapy. This treatment uses a radioactive drug called lutetium Lu 177 dotatate (Lutathera), which is given through an IV. The drug is effective against gastrointestinal and pancreatic carcinoid tumors that have proteins called somatostatin receptors.
#86 Gastrointestinal Carcinoid Tumors | Memorial Sloan Kettering Cancer Center
https://www.mskcc.org/cancer-care/types/gastrointestinal-neuroendocrine/gastrointestinal-carcinoid-tumors
Patients with gastrointestinal carcinoid tumors that cannot be surgically removed may benefit from monthly injections of a synthetic hormone, octreotide, which controls hormone-related symptoms and may have the potential to slow tumor growth. […] Chemotherapy is usually reserved for patients whose carcinoid tumors begin to grow during treatment with octreotide. […] Some neuroendocrine tumors absorb a hormone called norepinephrine. These tumors may respond to a nuclear medicine technique called MIBG radiolabeled therapy. […] PRRT is a new nuclear medicine therapy. This treatment uses a radioactive drug called lutetium Lu 177 dotatate (Lutathera), which is given through an IV. The drug is effective against gastrointestinal and pancreatic carcinoid tumors that have proteins called somatostatin receptors.