PANCREATITA CRONICAPANCREATITA CRONICA

Definitie:Definitie: Inflamatia cronica a pancrea - Inflamatia cronica a pancrea -sului cu distrugerea tesutului exocrin prin sului cu distrugerea tesutului exocrin prin fibroza urmata de pierderea functiei en-fibroza urmata de pierderea functiei en-docrinedocrine

Pancreatita cronica obstructivaPancreatita cronica obstructiva : : tumori, stenoze, pseudochist, ano-tumori, stenoze, pseudochist, ano-malii congenitalemalii congenitale

Pancreatita cronica calcifianta Pancreatita cronica calcifianta (95%): alcool(60-70%);(95%): alcool(60-70%);hiperparatiroidism;hiperparatiroidism;

ETIOLOGIE

• Deficit de α1 antitripsina, hemocromatoza ;

• Rare: fibroza chistica, hipercalcemie;

• Autoimuna (ciroza biliara primara, BII);

• Congenitala (autosomal dominant);

• Tropicala (toxice, malnutritie proteica);

• Idiopatica

ETIOLOGIE

FIZIOPATOLOGIEFIZIOPATOLOGIE

Procesul care initiaza inflamatia pancre-Procesul care initiaza inflamatia pancre-asului nu este complet cunoscutasului nu este complet cunoscut

Alcool precipitarea proteinelor in ducteAlcool precipitarea proteinelor in ducte

Obstructie ductala

Calcificari intraductale

(calculi)

Toxic direct

< 50g/zi

PSP- S 2-5, Citrat, pH

MORFOPATOLOGIEMORFOPATOLOGIE

Leziunile sunt distribuite parcelar, lobularLeziunile sunt distribuite parcelar, lobular

Precipitate proteice, calcificari, stricturi Precipitate proteice, calcificari, stricturi ductaleductale

Pierderea MB si atrofia epiteliului ductalPierderea MB si atrofia epiteliului ductal

Inflamatia, fibroza si atrofia tes pancreatic Inflamatia, fibroza si atrofia tes pancreatic distal de ductul stenozatdistal de ductul stenozat

Chistul pancreatic (chist de retentie)Chistul pancreatic (chist de retentie)

Pseudochist de retentiePseudochist de retentie

MANIFESTARI CLINICE

• Durere

- epigastru, CSS, CSD, iradiaza posterior

- inflamatia n. intrapancreatici, ↑pres. intraductale;

- accentuata postprandial, flexia trunchiului;

- Exacerbari pe un fond dureros cronic;

- Dispare in timp prin fibroza pancreasului.

• Malabsorbtie :

- steatoree, vit. liposolubile (A,D,E,K);

-↓ponderala, Vitamina B12;

• Diabet

- ↓insulina , glucagon

TRIADA CLASICATRIADA CLASICA

Calcificari pancreatice;Calcificari pancreatice;

SteatoreeSteatoree

Diabet zaharatDiabet zaharat

! < 1/3 din pancreatitele cronice! < 1/3 din pancreatitele cronice

EXAMEN FIZIC

• Durere : epigastru;

• Masa palpabila (pseudochist, carcinom);

• Malnutritie ;

• Icter colestatic (20%)± ciroza (10%);

• Hipertensiune portala: tromboza venei

splenice sau porte.

PROBE BIOLOGICE

• Amilaza serica

• Lipaza serica ↑ atac acut, devin N tardiv, prin fibroza pancreasului

• Bilirubina, fosfataza alcalina ↑ (20%);

• Teste hepatice;

• Hipoalbuminemia;

• Hipocalcemia, Fa ↑(vit.D);

• Tulburari de coagulare (vit K);

• Anemie macrocitara (B12);

• Glicemie ↑

Malabsorbtie

TESTE IMAGISTICE

• Rx abdominala - calcificari ductale (30%);

• Rx. cu bariu - ↑ spatiu retrogastric;

• Ecografia abdominala/ CT : dilatatii ductale, calcificari,

pseudochist, tumori ;

• Echoendoscopia;

• ERCP : stenoze ductale, calculi, dilatatii, chist; duct

principal >1cm cu stenoze intermitente (“sir lacuri”);

Ductele secundare, dilatatii si obstructii - pierderea

“acinalizarii”.

TESTE ALE FUNCTIEI PANCREATICE

• Teste directe:

- test Lundh/secretina i.v. volumul <2 ml/kg, conc bicarbonat < 90 mEq/l, prot↓;

• Teste indirecte:

- ex. microscopic fecale (grasime);

- dozare cantitativa lipide fecale ; 70g lipide /zi ; scaun / 72h; >5g/zi, >5 - 8% din lipidele ingerate;

- test oral cu trigliceride radiomarcate; - test bentiromida : PABA urina (<60%/ 6h) ;

- elastaza (fecala)<100µg/mg, tripsinogen seric <20ng/ml - insuf. severa

TRATAMENT

• Controlul durerii :

▪ abstinenta de alcool, mese fara grasimi;

▪ paracetamol, dyhidrocodeina, AINS;

▪ Feedback : enzime pancreatice (tripsina)

▪ opioide : pethidina – dependenta;

▪ plex celiac: percutan (alcool) :ameliorari tempo- rare 6 luni)

▪ Chirurgie: drenaj, pancreaticojejunostomie longitudinala sau caudala, sfincteroplastie, rezectie pancreatica

• Malabsorbtia:

▪ dieta : restrictie de lipide

▪ enzime pancreatice - lipaza 30000 U/ masa - 10 tb/ masa: Cotazim (6cp), VioKase (8cp) Creon (3cp), Zymase (3cp). pH gastric >4 -1h post-

prandial : H2 blocant, PPI (p.conventionale). Preparate enterosolubile (pH >6)

▪ Suport nutritiv : mese mici (proteine), TG lant mediu (vena porta)

• Proliferarea bacteriana: Tetraciclina 500mg/4/zi,

Metronidazol 500mg/3/zi -7-14 zile

• Diabet : doze mici de insulina

COMPLICATIICOMPLICATII

Malabsorbtia BMalabsorbtia B1212 (40%) – enz. pancreatice (40%) – enz. pancreatice

Retinopatia nondiabetica (vit.A)Retinopatia nondiabetica (vit.A)

Fistule (pleura, peritoneu, pericard)Fistule (pleura, peritoneu, pericard)

Sangerare gastrointestinala: pseudochist Sangerare gastrointestinala: pseudochist ce erodeaza duodenul, varice esofagiene ce erodeaza duodenul, varice esofagiene (gastrice)(gastrice)

Obstructie cronica :icter, colangita, ciroza Obstructie cronica :icter, colangita, ciroza biliarabiliara

Necroze subcutanate (noduli, artrite)Necroze subcutanate (noduli, artrite)

COMPLICATII

• Pseudochist - 10 % P. cr, corp/coada, asimptomatice;

- complicatii: ruptura, hemoragie, infectie;

- drenaj extern (ch/perc) intern (ch/end);

• Stricturi - dilatare endoscopica (balon);

• Calculi - litotripsie extracorporeala/ERCP;

• Ascita - octreotide, paracenteza;

- stent (ERCP),

• Fistule - pacreaticopleurala toracenteza;

• Obstructie coledoc : stent (end)/ bypass chirurgical;

• HT portala - tromboza sau compresie vs/vp decomp.ch.

PROGNOSTIC

• Mortalitate:

- 25 ani 50%;

- 20% exacerbari acute

- alte cauze sinucideri

ciroza

malnutritie

dependenta droguri

infectii

CANCERUL DE PANCREAS

• Incidenta s-a triplat in ultimii 40 ani;

• barbati, > 60 ani;

• supravietuire 1-2% dupa 5 ani; medie < 6 luni;

• anatomie patologica ADK ductale 90%

T. endocrine 5%

Alte: acinar, epidermoid

• localizare:

- cap (70%)

- corp (20 %)/coada (10%)

FACTORI DE RISC

• Dieta : carne rosie si lipide ↑;

• Fumatul de tigarete;

• Gastrectomie partiala, colecistectomie;

• Cancer colorectal ereditar nepolipozic, cancer mamar familial, Sd.Peutz- Jeger

• Pancreatita cronica (ereditara si tropicala);

• Pancreatita acuta recurenta - genetica.

• Expunere: naftylamina, benzidina, metale (praf).

MANIFESTARI CLINICE

• Initial nespecifice, : anorexie, ↓in G, greata, diaree,

tulburari psihice (depresie);

• Durere epigastrica :75%, irad post, invad n splanh.;

• Cap / corp, coada

- icter colest. progresiv/ tardiv - meta hepatice;

- obstructie duodenala /- ;

- hematemeza (stomac)/ - ;

- colangita, pancreatita acuta recurenta/ - ;

• • Diabet recent / intoleranta la glucoza.

• Tromboflebita migratorie (Trousseau)

• Poliartrita, noduli cutanati (necroza grasa)

MANIFESTARI CLINICE

SEMNE FIZICE

• Tumora palpabila (epigastru) ¼ pacienti;

• Ascita - invazie peritoneu, HT portala;

• Semn Courvoisier;

• Semn Troissier (gg. scv stg);

• Icter

• S. Paraneoplazice: TF migratorie, endocardita marantica, S. Cushing

• Necroza grasa metastatica (EN - like, artrite).

INVESTIGATII

• Markeri tumorali: CEA (50%), CA 19-9 (80%) ;

• Ecografia abd. - masa in P, dilat CBI si CBE;

• CT (spirala), RMN;

• Biopsie percutanata (aspirat citologic);

• ERCP - sensibilitate >90%, lavaj, periaj;

• Ecoendoscopia: stadializare preoperatorie;

• Angiografie: A.celiaca, AMS

• Laparoscopia - biopsie diagnostica,meta (ficat, peritoneu, epiplon)

DIAGNOSTIC DIFERENTIAL

• Carcinom ampular - 10 × mai rar, Adk;

- coledoc, pancreas, duoden, ampula;

- icter intermitent initial, apoi progresiv;

- colangita, pancreatita, sangerari digestive;

- ecografia: dilatatie CBI/CBE, obstruc. distala;

- ERCP - dublu duct : dilat. CBE si duct pancreas;

• Colangiocarcinom - icter rapid agravat, nedureros, colangita;

• Pancreatita cronica.

STADIALIZARESTADIALIZARE

Stadiul I: numai pancreasulStadiul I: numai pancreasul

Stadiul II: intereseaza P si structurile Stadiul II: intereseaza P si structurile vecinevecine

Stadiul III: gg. regionaliStadiul III: gg. regionali

Stadiul IV : metastazeStadiul IV : metastaze

Stadiile I,II si (uneori) III – Tratament Stadiile I,II si (uneori) III – Tratament chirurgicalchirurgical

TRATAMENT• Radical: chirurgical - <10%;

- Pancr.duod.ectomie (Whipple)/ P ectomie totala;

- tumori <3 cm, fara extesie locala si fara meta.

- mortalitatea op. 16%, suprav. >5ani 4 - 15%;

• Paleativ:

- Icter- nechirurgical (stent) chirurgical

ERCP PTC (perc) ambele C/J anast G/J anast

- Durere - opioide sulfat de morfina 20mg /2×zi, radioterapie externa, blocarea perc. pl.celiac.

- Chimioterapie ± radioterap., Gematabine, 5FU;

TUMORI ENDOCRINE PANCREATICETUMORI ENDOCRINE PANCREATICE

MEN - neoplazia endocrina multipla : paratiroida, MEN - neoplazia endocrina multipla : paratiroida,

hipofiza, tiroida, suprarenala, pancreashipofiza, tiroida, suprarenala, pancreas

Tumori functionale - secretie excesiva hormonala Tumori functionale - secretie excesiva hormonala

sindroame clinice variate; sindroame clinice variate;

Tumori nefunctionale : obstructii locale - cai Tumori nefunctionale : obstructii locale - cai

biliare, duoden, hemoragie digestiva, mase abd.biliare, duoden, hemoragie digestiva, mase abd.

(cromogranina A si B, hCG) (cromogranina A si B, hCG)

TumoraTumora HormoniHormoni LocalizareLocalizare Simptome si semneSimptome si semne

ACTHomACTHom ACTHACTH PancreasPancreas S. CushingS. Cushing

GastrinomGastrinom GastrinaGastrina Pancreas(60%)Pancreas(60%)

Duoden (30%) Duoden (30%) Alte(10%)Alte(10%)

Dureri abd, ulcer, Dureri abd, ulcer, diareediaree

GlucagonomGlucagonom GlucagonGlucagon PancreasPancreas Intoleranta la Intoleranta la glucoza, anemie, ↓Gglucoza, anemie, ↓G

GRFomGRFom Factor de Factor de eliberare eliberare a STHa STH

Plaman (54%), Plaman (54%),

Pancreas (30%),Pancreas (30%),

jejun (7%) alte (13%) jejun (7%) alte (13%)

AcromegalieAcromegalie

InsulinomInsulinom InsulinaInsulina PancreasPancreas Hipoglicemie (post)Hipoglicemie (post)

SomatostatinomSomatostatinom Somato-Somato-statinastatina

Pancreas (56%), Pancreas (56%), duoden/jejun (44%)duoden/jejun (44%)

Intoleranta la gluco-Intoleranta la gluco-za, diaree, calculi VBza, diaree, calculi VB

VipomVipom VIPVIP Pancreas (90%)Pancreas (90%)

alte (10%)alte (10%)

Diaree apoasa Diaree apoasa severa, flush, ↓K, severa, flush, ↓K, acidozaacidoza

DiagnosticDiagnostic

CT, RMN;CT, RMN;

Scintigrafie cu somatostatinaScintigrafie cu somatostatina

Angiografie selectivaAngiografie selectiva

EcoendoscopieEcoendoscopie

INSULINOMINSULINOM

Secretie ↑de insulina 80% unice, 10% Secretie ↑de insulina 80% unice, 10% maligne;maligne;

HipoglicemiaHipoglicemia

Dg: Glucoza si Insulina/ bazale (<40mg/dl, Dg: Glucoza si Insulina/ bazale (<40mg/dl, >6µU/ml; I ser/G ser>0,3);>6µU/ml; I ser/G ser>0,3);

EcoendoscopieEcoendoscopie

ChirurgieChirurgie

Multiple: Diazoxid, Ca blocanti, Multiple: Diazoxid, Ca blocanti, ββ- blocanti- blocanti

Streptozocin + 5-fluorouracil.Streptozocin + 5-fluorouracil.

SINDROM ZOLLINGER-ELLISONSINDROM ZOLLINGER-ELLISON

Tumori ce produc gastrina: (cistic, coledoc, Tumori ce produc gastrina: (cistic, coledoc,

duoden,gg limfatici, pancreas –”duoden,gg limfatici, pancreas –”▲gastrinomului”▲gastrinomului”

Hipersecretie acida gastrica, ulcer peptic sever, Hipersecretie acida gastrica, ulcer peptic sever,

localizat atipic ;localizat atipic ;

50% maligne;50% maligne;

Diaree (25 – 40%);Diaree (25 – 40%);

Gastrina serica > 1000 pg/ml, HCL >15m Eq/h;Gastrina serica > 1000 pg/ml, HCL >15m Eq/h;

Testul la secretina : ↑ gastrina serica;

CT, scintigrafia cu somatostatina,

echoendoscopie;

PPI: esomeprazol 40 mg/bid;

Octreotid 100 -500 µg sc/bid, 20 - 30 mg

im/lunar;

Chirurgie;

Streptozocin + 5 - FU sau doxorubicina

VIPOAMEVIPOAME

Tumori ale celulelor insulare nonTumori ale celulelor insulare nonββ pancre- pancre-atice;atice;

Secretia substantelor vasoactive intesti-Secretia substantelor vasoactive intesti-nale;nale;

50-75% maligne;50-75% maligne;

Diaree apoasa 1000 -3000ml/zi;Diaree apoasa 1000 -3000ml/zi;

Hipopotasemie, acidoza, deshidratare, Hipopotasemie, acidoza, deshidratare, aclorhidrie;aclorhidrie;

20% flush asociat episoadelor de diaree.20% flush asociat episoadelor de diaree.

Ecoendoscopie, scintigrafie cu Ecoendoscopie, scintigrafie cu

somatostatina. somatostatina.

Inlocuire hidrica si electrolitica;Inlocuire hidrica si electrolitica;

Octreotid :20/30 mg/lunarOctreotid :20/30 mg/lunar

Tratament chirurgical;Tratament chirurgical;

Streptozocin + doxorubicinaStreptozocin + doxorubicina