i tumori neuroendocrini gastro-entero-pancreatici · 2017. 1. 12. · i tumori neuroendocrini...
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I Tumori NeuroendocriniGastro-entero-pancreatici
www.fisiokinesiterapia.biz
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I TUMORI NEUROENDOCRINI PANCTREATICI
I tumori che originano dalle cellule neuroendocrine dell’apparato gastrointestinale e del pancreas presentano particolari caratteristiche diagnostiche e terapeutiche.
A differenza di altre neoplasie gastrointestinali, questi tumori possono causare sintomi dovuti ad un’eccessiva secrezione ormonale, piuttosto che a crescita invasione o effetti anatomici locali.
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Una caratteristica importante dei tumori neuroendocrini è la preservazione di funzioni cellulari altamente differenziate; le cellule tumorali contengono granuli secretori e mantengono la capacità di captare e decarbossilare precursori aminici (AminePrecursor Uptake and Decarboxylation, APUD), un processo essenziale per la produzione di neurotrasmettitori monoaminici come la serotonina, la dopamina e l’istamina.
I TUMORI NEUROENDOCRINI
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I TUMORI NEUROENDOCRINI
Sono rari ma la loro incidenza è sovente sottostimata
La diagnosi è spesso complicata nei casi asintomaticied in molti casi ritardata
La presenza di metastasi spesso anticipa i sintomi
La crescita è caratteristicamente lenta
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Distribuzione dei tumori APUD- Tratto gastroenterico Carcinoide
- Pancreas InsulinomaGlucagonomaGastrinomaVIPomaSomatostatinoma
- SNC GanglioneuroblastomaNeuroblastomaParaganglioma
- Tiroide Carcinoma midollare
- Cute Melanoma-
- Midollare del surrena Feocromocitoma
- Polmone CarcinoideCa a piccole cellule
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Epidemiologia dei T. neuroendocrini
Tipo di tumore Incidenza /mil. Local. pancreatica
Carcinoide 15 0,5%
Insulinoma 1 90%
Glucagonoma < 1 99%
Gastrinoma < 1 72%
VIPoma < 1 84%
Somatostatinoma < 1 48%
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I TUMORI NEUROENDOCRINI
T.carcinoide di diverticolo di Mekelcon metastasi epatiche multiple
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Tumori Neuroendocrini del pancreas
Sono lo 0,5 – 1,5 dei tumori del pancreas con una incidenza di circa 10 casi/anno/milione
Su 100 casi 55 Carcinoidi17 Insulinomi9 Gastrinomi2 VIPomi1 Glucagonoma1 Somatostatinoma15 T. misti
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Manifestazioni cliniche dei T. neuroendocriniTumore Peptidi secernenti Sintomatologia
Carcinoide tipico Serotonina, SP Flush + diarreaTachichinine, PG
Insulinoma Insulina, PP, VIP Convulsioni,Ipoglicemia,Obesità
Glucagonoma Glucagone, PP Eritema necroliticoCalcitonina + diabete
Gastrinoma Gastrina, VIP, PP Ulcera pepticaNeurotensina + diarrea
VIPoma VIP, PHM-42 DiarreaPHV-42 + ipocloridria
Somatostatinoma Somatostatina, PP Litiasi colecisti+ diabete
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Classificazione e caratteristiche deiT. neuroendocrini del pancreas
1) Insulinoma: T. secernente insulina, si manifesta con ipoglicemia a digiuno, nell’1% dei casi ha localizzazione extra-pancreatica ( stomaco, D. di meckel).
2) Gastrinoma: T. secernente gastrina, si manifesta con ulcere ricorrenti, steatorrea, sindrome di Zollinger Ellison, in oltre il 90% dei casi èmaligno.
3)VIPoma: T. secernente ormone VIP, si manifesta con diarrea acquosa ipopotassiemia, iposecrezione gastrica.
4)Glucagonoma: T. secernente glucagone, si manifesta con eritema necrolitico migrante, diabete mellito, anemia.
5)Somostatinoma: T. secernente somatostatina, si manifesta con diabete, steatorrea, colelitiasi, iposecrezione gastrica.
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Metastasi epatiche da carcinoide del pancreasPre-op. Post-op
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Emiepatectomia Sn. allargata per metastasi da carcinoide del pancreasEmiepatectomia Sn. allargata per
metastasi da carcinoide del pancreas
REV
VC
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Insulinoma
Tumori Neuroendocrini del pancreas
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Tumori Neuroendocrini del pancreas
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InsulinomaCefalopancreatico
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Emiepatectomia desta per metastasi da insulinoma
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Tumori Neuroendocrini del pancreas
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Tumori Neuroendocrini del pancreasEritema migratorio necrolitico in glucagonoma pancreatico
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Tumori Neuroendocrini del pancreas
Manifestazioni cutanee e glossite inGlucagonoma
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Tumori Neuroendocrini del pancreas
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Tumori Neuroendocrini del pancreasVIPoma
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Tumori Neuroendocrini del pancreasEmiepatectomia Dx allargata per VIPoma pancreatico
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Resezione Curativa di Metastasi Neuroendocrine:
Resezione Curativa di Metastasi Neuroendocrine:
Emiepatectomia9
Emiepatectomiaallargata
3
Segmentectomia2
Wedge1
Wedge multiple
3
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0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10
SOPRAVVIVENZA COM PLESSIVA
DISEASE-FREE SURVIVAL
RESEZIONI CURATIVE DI METASTASI EPATICHE DA TUMORE NEUROENDOCRINO
RESEZIONI CURATIVE DI METASTASI EPATICHE DA TUMORE NEUROENDOCRINO
Sopr
avvi
venz
a (%
)So
prav
vive
nza
(%)
Anni dalla resezione epaticaAnni dalla resezione epatica
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Don Pietro T. (1°)
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Don Pietro T. (2°)
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Don Pietro T. (3°)
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Don Pietro T. (4°)
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I TUMORI NEUROENDOCRINI
Chemio embolizzazione di metastasi epatiche diffuse da carcinoide polmonare
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.0042.004260%60%24%24%
86863535
10102929
Timing of Timing of liverliver metastasesmetastasesMetachronousMetachronous liverliver lesionlesionSynchronousSynchronous liverliver lesionlesion
.27.2748%48%30%30%
49493434
212129 29
TumorTumor functionalfunctional statusstatusFunctionalFunctional tumortumorNonfuncionalNonfuncional tumortumor
.067.06729%29%57%57%
37378383
23232626
LocationeLocatione of of primaryprimary tumortumorHead of pancreas Head of pancreas Body/Body/tailtail of pancreasof pancreas
.22.2248%48%23% 23%
58584242
28282222
SexSexMaleMaleFemaleFemale
.013.01363%63%24% 24%
66663434
993030
Treatment of liver metastasesTreatment of liver metastasesAggressive liver treatmentAggressive liver treatmentNonaggressiveNonaggressive liver metastasesliver metastases
.05.0531%31%_a_a
3737_a_a
393911 11
Status of Liver Status of Liver Presence of liver metastasesPresence of liver metastasesAbsence of liver metastasisAbsence of liver metastasis
<.0001<.000163%63%22%22%
_a_a2525
21212929
Treatment of primary tumor:Treatment of primary tumor:Resection of Primary tumorResection of Primary tumorNon resection of primary tumorNon resection of primary tumor
P valueP value55--year survivalyear survivalMedian survivalMedian survivalnnFactorsFactors
a: a: HasHas notnot beenbeen reachedreachedQuyenQuyen D. D. ChuChu, , AnnAnn SurgSurg OncologyOncology 9(9)2002:8559(9)2002:855--862, 862,
PredictivePredictive factorsfactors associatedassociated withwith longlong--termterm survivalsurvival in in patientspatientswithwith neuroendocrineneuroendocrine tumorstumors of the pancreas of the pancreas
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163 163 ptspts withwith nonnon--functionalfunctional isletislet cellcell carcinoma of the pancreascarcinoma of the pancreas
locallylocally advancedadvanced, , unresecableunresecable, , nonmetastaticnonmetastatic diseasedisease
potentiallypotentially curative curative resectionresection
P=0P=0.04.04
SolorzanoSolorzano CC, CC, SurgerySurgery 130, 130, DecDec 20012001
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8 (40%)8 (40%)PancreatoduodenectomyPancreatoduodenectomy
6 (30%)6 (30%)Liver resectionLiver resection2 (10%)2 (10%)Radiofrequency ablation for liver metastasesRadiofrequency ablation for liver metastases
3 (15%)3 (15%)Superior mesenteric vein Superior mesenteric vein recostructionrecostruction
2 (10%)2 (10%)NephrectomyNephrectomy1 (5%)1 (5%)Extensive nodal dissectionExtensive nodal dissection
2 (10%)2 (10%)Transverse Transverse colectomycolectomy
1 (5%)1 (5%)Partial Partial gastrectomygastrectomy
3 (15%)3 (15%)EnucleationEnucleation from pancreatic headfrom pancreatic head3 (15%)3 (15%)Total Total pancreasectomypancreasectomy with with splenectomysplenectomy9 (45%)9 (45%)Distal Distal pancreasectomypancreasectomy with with splenectomysplenectomy
No. (%)No. (%)ProcedureProcedure
ExtentExtent of of SurgerySurgery forfor malignantmalignant NeuroendocrineNeuroendocrine TumorsTumors in 20 in 20 patientspatients
NortonNorton JA, JA, ArchArch SurgSurg 138, 138, AugAug 20032003
90% 90% OverallOverall survivalsurvival60% 60% DeseaseDesease freefree survivalsurvival FollowFollow up 19 up 19 monthsmonths
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Morbidity, No (%)Morbidity, No (%)Pancreatic Pancreatic Fistula AbscessesFistula Abscesses
Hospital Hospital Stay MeanStay Mean
Sample Sample SizeSize
4 (20) 2 (20)4 (20) 2 (20)11.511.52020AllAll
3 (100) 03 (100) 0151533EnucleationEnucleation from pancreatic headfrom pancreatic head1 (33) 01 (33) 0151533Superior mesenteric vein Superior mesenteric vein
recostructionrecostruction
0 00 09933Total Total pancreasectomypancreasectomy1 (13) 01 (13) 0101099Distal Distal pancreatectomypancreatectomy + + splenectomysplenectomy1 (13) 1 (13)1 (13) 1 (13)14.314.388Proximal Proximal pancreatectomypancreatectomy
Complications of surgery for malignant Complications of surgery for malignant neuroendocrineneuroendocrine tumorstumors
ExtentExtent of of SurgerySurgery forfor malignantmalignant NeuroendocrineNeuroendocrine TumorsTumors in 20 in 20 patientspatients
MorbidityMorbidity and and postoperativepostoperative hospital stayhospital stay
NortonNorton JA, JA, ArchArch SurgSurg 138, 138, AugAug 20032003
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.0042.004260%60%24%24%
86863535
10102929
Timing of Timing of liverliver metastasesmetastasesMetachronousMetachronous liverliver lesionlesionSynchronousSynchronous liverliver lesionlesion
.27.2748%48%30%30%
49493434
212129 29
TumorTumor functionalfunctional statusstatusFunctionalFunctional tumortumorNonfuncionalNonfuncional tumortumor
.067.06729%29%57%57%
37378383
23232626
LocationeLocatione of of primaryprimary tumortumorHead of pancreas Head of pancreas Body/Body/tailtail of pancreasof pancreas
.22.2248%48%23% 23%
58584242
28282222
SexSexMaleMaleFemaleFemale
.013.01363%63%24% 24%
66663434
993030
Treatment of liver metastasesTreatment of liver metastasesAggressive liver treatmentAggressive liver treatmentNonaggressiveNonaggressive liver metastasesliver metastases
.05.0531%31%_a_a
3737_a_a
393911 11
Status of Liver Status of Liver Presence of liver metastasesPresence of liver metastasesAbsence of liver metastasisAbsence of liver metastasis
<.0001<.000163%63%22%22%
_a_a2525
21212929
Treatment of primary tumor:Treatment of primary tumor:Resection of Primary tumorResection of Primary tumorNon resection of primary tumorNon resection of primary tumor
P valueP value55--year survivalyear survivalMedian survivalMedian survivalnnFactorsFactors
a: a: HasHas notnot beenbeen reachedreachedQuyenQuyen D.D. ChuChu, , AnnAnn SurgSurg OncologyOncology 9(9)2002:8559(9)2002:855--862,862,
PredictivePredictive factorsfactors associatedassociated withwith longlong--termterm survivalsurvival in in patientspatientswithwith neuroendocrineneuroendocrine tumorstumors of the pancreas of the pancreas
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163 163 ptspts withwith non non functionalfunctional isletislet cellcell carcinoma of the pancreascarcinoma of the pancreas
SolorzanoSolorzano CC, CC, SurgerySurgery 130, 130, DecDec 20012001
LocalizatedLocalizated diseasediseaseat at presentationpresentation
MetastaticMetastatic diseasediseaseat at presentationpresentation
P=0P=0.001.001
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.0042.004260%60%24%24%
86863535
10102929
Timing of Timing of liverliver metastasesmetastasesMetachronousMetachronous liverliver lesionlesionSynchronousSynchronous liverliver lesionlesion
.27.2748%48%30%30%
49493434
212129 29
TumorTumor functionalfunctional statusstatusFunctionalFunctional tumortumorNonfuncionalNonfuncional tumortumor
.067.06729%29%57%57%
37378383
23232626
LocationeLocatione of of primaryprimary tumortumorHead of pancreas Head of pancreas Body/Body/tailtail of pancreasof pancreas
.22.2248%48%23% 23%
58584242
28282222
SexSexMaleMaleFemaleFemale
.013.01363%63%24% 24%
66663434
993030
Treatment of liver metastasesTreatment of liver metastasesAggressive liver treatmentAggressive liver treatmentNonaggressiveNonaggressive liver metastasesliver metastases
.05.0531%31%_a_a
3737_a_a
393911 11
Status of Liver Status of Liver Presence of liver metastasesPresence of liver metastasesAbsence of liver metastasisAbsence of liver metastasis
<.0001<.000163%63%22%22%
_a_a2525
21212929
Treatment of primary tumor:Treatment of primary tumor:Resection of Primary tumorResection of Primary tumorNon resection of primary tumorNon resection of primary tumor
P valueP value55--year survivalyear survivalMedian survivalMedian survivalnnFactorsFactors
a: a: HasHas notnot beenbeen reachedreachedQuyenQuyen D. D. ChuChu, , AnnAnn SurgSurg OncologyOncology 9(9)2002:8559(9)2002:855--862862
PredictivePredictive factorsfactors associatedassociated withwith longlong--termterm survivalsurvival in in patientspatientswithwith neuroendocrineneuroendocrine tumorstumors of the pancreas of the pancreas
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Metastasi epatiche da tumore neuroendocrinoPremessa
•• 10% 10% delledelle metastasimetastasi epaticheepatiche hannohanno origineorigine neuroendocrinaneuroendocrina
•• 90% di 90% di talitali metastasimetastasi sonosono multifocalimultifocali e e bilobaribilobari
•• 3030--32% 32% sopravvivenzasopravvivenza a 5 a 5 annianni neinei casicasi non non trattatitrattati
•• SintomiSintomi e e cattivacattiva qualitqualitàà di vitadi vita
1. Moertel CG, J Clin Oncol: 19872. Soreide O, Surgery: 1992
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•• Tumore poco frequenteTumore poco frequente
•• Caratteristiche patologiche non ben Caratteristiche patologiche non ben definitedefinite
•• Storia naturale con lenta evoluzioneStoria naturale con lenta evoluzione
•• Pochi studi riguardo al ruolo del Pochi studi riguardo al ruolo del trattamento chirurgico (Procedure trattamento chirurgico (Procedure chirurgiche maggiori)chirurgiche maggiori)
Problemi
Metastasi epatiche da tumore neuroendocrinoRuolo della chirurgia
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Resezione curativa
Metastasi epatiche da tumore neuroendocrinoRuolo della Chirurgia
Palliazione
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Metastasi epatiche da tumore neuroendocrinoDifferenti trattamenti modificano la sopravvivenza?
Chamberlain RS, J Am Coll Surg: 2000
“Hepatic metastases from neuroendocrine tumors are best managed with a multidisciplinary approach. Both HAE and surgical resection provide excellentpalliation of hormonal and pain symptoms. In select patients, surgical resection of hepatic metastases may prolong survival, but is rarely curative”.
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Sutcliffe R, Am J Surg: 2004
Metastasi epatiche da tumore neuroendocrinoManagement of neuroendocrine liver metastases
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Metastasi epatiche da tumore neuroendocrinoDoes Aggressive management improve survival?
Touzios, Ann Surg. 2005
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Touzios, Ann Surg. 2005
Metastasi epatiche da tumore neuroendocrinoDoes Aggressive management improve survival?
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“The combination of surgery, ablation and chemoembolization of hepatic metastases expands patients eligible for aggressive management and results in symptom
relief, as well as improved survival”Touzios, Ann Surg. 2005
Metastasi epatiche da tumore neuroendocrinoDoes Aggressive management improve survival?