Surgical anatomy of pancretico-biliary junction and significance to pancreatico-biliary disorders

Seminar- 3rd May 2010

Anand Bharathan

Outline

Embryology of PB junction Normal anatomy of PB junction Definition of APBDJ Theories of APBDJ Classification Clinical problems Mechanisms of carcinogenesis Diagnosis Treatment Summary

Embryology of PB junctionTime Event

Early 4th week

Hepatic diverticulum (HD) arises in ventral mesogastriumPrecursor of EHBR & Ventral pancreas

Late 4th week

Ventral anlage -from base of HDDorsal anlage -from dorsal mesogastrium

Early 5th week

PD & EHBR demarcateEHBR remains a solid cord of cellsProximal part of hepatic diverticulum enlarges

6th week Ventral anlage is carried away from duodenum by enlarged HDBiliary system re-canalises (proximal to distal)

7th week Duodenal rotation & fusion of ventral & dorsal anlagesBiliary re-canalisation is complete

8th week Duodenal wall thickness increasesCBD & PD enter duodenum side by side

11th week Muscles of Sphincter of Oddi- from mesenchyme around CBD

12th week MPD joins CBD, Common channel moves into duodenal muscularis propria

Modified from Matsumoto Y et al. JHBP 2002;9:45-54

Normal anatomy of PB junction

notch (a); biliary sphincter (b); transampullary septum (c); pancreatic sphincter (d); membranous septum of Boyden (e); common sphincter (f); smooth muscle of duodenal wall (g). 

Normal anatomy of P-B junction

Junction is within duodenal wall PD & CBD may have common/separate

drainage Common drainage 70-85% Separate drainage 10-13% Pancreas divisum 2%

Blumgart LH. Surgery of liver, biliary tract & pancreas, 4th ed. Pg 26

Definition of APBDJ

Junction of PD & CBD is located outside the duodenal wall radiologically

Length of common channelNormal ≤0.46 cm (Mean)PBM 1.86 cm

Funabiki T et al. Lang Arch Surg 2009;394:159-169

Theories of APBDJ

No proven concept exists Failure of normal separation of PD &

CBD.

Arrest of migration of PBJ into duodenum.

Terminal bile duct joins the duct of Wirsung & bile flows to duodenum thro’ WD.

Babbitt, 1969

Wong & Lister, 1981

Matsumoto Y et al., 2001

No common channel theory

Matsumoto Y et al. Gastrointes Endosc 2001;53:614-619

Komi classification of APBDJ

BP type

PB type

Modified fromLevy AD et al. Curr Prob Diag radiol 2003;32:233-263

Other classification of APBDJ

With biliary dilatation Without biliary dilatation

Clinical problems with APBDJ

Choledochal cyst Carcinoma gallbladder Carcinoma of extrahepatic biliary

tract GB adenomyomatous polyposis Pancreatitis Cholelithiasis

Incidence of APBDJ

Pts of H-B surgery(n=12399)

ERCP for biliary symptoms

ERCP- mostly asymptomatic

Incidence of PBM

3.3% 0.9-1.5% in japan8.7% in Taiwan1% in europe

0.03% (n= 27,076)

PBM in GBC 10.4%

PBM in BDC 4.4%

Funabiki T et al. Lang Arch Surg 2009;394:159-169

Mechanisms of carcinogenesis in APBDJ

PLA2Deconjugated

& Secondar

y bile

acids

•Reflux of pancreatic enzymes into CBD

•Activation of enzymes, Stasis, Inflammation

Hyperplasia,

Meta/dysplasi

a

•Damage to intercellular junction & CBD wall

•Recurrent inflammation

Mutations

K-ras, bcl-2P53, p14,p16

•Dilatation of CBD

•Narrowing of distal CBD

NOT precisely known

Proliferative activity in BDAgent Function/ abnormality

Ornithine decarboxylase Rate limiting enzyme in polyamine synthesis

Proliferating cell nuclear antigen

Cell kinetics marker

Ki-67 Reliable marker on cell kinetics

Mucin core protein (MUC-1) Expressed in hyperplastic/ dysplastic epithelia

Cox-2 Anti-apoptotic

VEGF Angiogenesis

8-hydroxy-2-deoxyguanosine

Oxidative DNA base modified product(suggests oxidative DNA damage)

Others TGF-α, ß-catenin, Cyclin-D1

Genetic changes in oncogenesis in APBDJ

Gene Function Early/Late

Bcl-2 Apoptosis inhibitor Early

MSI Marker of genomic stability 0% hyperplasia85.7% dysplasia80% cancer

Telemorase activity Marker of genomic stability Early

m-RNA indices Cell proliferation activity Early

K-ras point mutations Cell cycle control Most evident change

P53 mutations(Deletion, point mut., LOH)

DNA repair, Apoptosis induction Early

P14 ARF Inhibitor of p53-mdm2 interaction

Early

P16 INK4a Key factor in RB pathway ?

Modified fromFunabiki T et al. Lang Arch Surg 2009;394:159-169

Biliary malignancy incidence

PBM 17% Gen population 0.26-1.8%

Age 10 years younger Gall stone disease low

Malignancy related to APBDJ

Funabiki T et al. Lang Arch Surg 2009;394:159-169

49.4 times the population risk

800 times the population risk

Malignancy in relation to biliary dilatation

Funabiki T et al. Lang Arch Surg 2009;394:159-169

800 x population risk

Pancreatitis

Recurrent acute chronic Incidence 3-31% Pathogenesis Occlusion of PD

- Protein plugs - Stones - Associated SOD

Usually mild Rx Sphincter ablation

Diagnosis

Secretin-MRCP ERCP Biliary amylase levels

Secretin-MRCP

Increase in volume of EHBR after secretin

Problem- Bile secretion is also increased by

secretin

Bile amylase

GB bile 123.568±180.827 Bile duct bile 99.018±162.506

Kamisawa T et al. World J Gastroenterol 2008;14(43):6622-6626

Treatment- with biliary dilatation

Prophylactic bile duct & GB resection

Treatment-without biliary dilatation

Not established. Prophylactic cholecystectomy is advised

by many. Japanese consensus- recommends BD

resection - Bile duct cancer 4% vs 5.2% (dilated

vs. undilated)

- BDC 800 x population risk- Double/triple ca 45.6% occur in

undilated- Histologic & molecular changes –

same in all

Summary

APBDJ is a congenital anomaly of unclear etiology.

Incidence is highest in Japan. Detection depends on investigative

modality used. Biliary dilatation may or may not be

present. Biliary tract cancers is the major long term

concern.

Summary

GB cancer is the most common cancer. Cancer risk is same/more in undilated

biliary system. Pancreatitis is another long term issue. Sphincter ablation is recommended in

pancreatitis. Resection of bile duct & GB is

recommended irrespective of biliary ductal dilatation.