Carcinoma of Gallbladder

CARCINOMA OF GALLBLADDER

Prof. Amitabha SarkarProfessor

Dept. of General SurgeryIPGME&R – SSKM HOSPITAL

INTESTINE

1. Mucosa –epithelium, lamina propria, muscularis mucosa

2. Submucosa3. Muscularis propria (muscle layer)

Outer –longitudial Inner –circular

4. Serosa

GALL BLADDER

1. Mucosa- Single layer, highly folded, tall columnar epithelium

2. Lamina propria (epithelial support)3. Muscle layer4. Perimuscular subserosa5. Serosa

No muscularis mucosa / submucosa

Figure 1. Normal gallbladder.

Levy A D et al. Radiographics 2001;21:295-314

©2001 by Radiological Society of North America

TUMOR ORIGIN

• Fundus- 60%• Body- 30%• Neck- 10%

GROSS MORPHOLOGY

• Papillary:Minimally invasive or noninvasiveGood prognosis

• Nodular:Difficult to distinguish from sclerosing cholangitisPropensity to infiltrate tissue

• Infiltrative:Spread along the ducts

• Combind nodular infiltrativeDifficult to distinguish from chr. Inflammatory condition.

Figure 2. (a) Well-differentiated adenocarcinoma.



Figures 8. (8) Poorly differentiated adenocarcinoma.



Figures 9. (9) Papillary adenocarcinoma.



LYMPHATIC DRAINAGE

Cystic Pericholedochal

retroportal Sup. Mesenteric

celiac post sup pancreatico duodenal

Interaortocaval nodes

Gall bladderN1

N2

IW

RISK FACTORS

• Cholelithiasis• Choledochal cysts• Anomalous Pancreatobiliary duct junction

(A.P.B.D.J)• Carcinogens- nitrosamine, rubber industry• Primary sclerosing cholangitis• Typhoid carrier• Porcelain gallbladder (10% at diagnosis)

RISK FACTORS

• Adenomatous gallbladder polyps- >1cm, broad based, sessile –highest

• Obesity• Estrogens• Asian population- Pakistan & North West India,

Chile, Japan, Israel, Native American IndianCholesterol & inflammatory polyps – No potential

for malignant transformation or degeneration

CLASSIFICATION

• Malignant epithelialAdenocacinomaSquamousAdeno squamousOat cell carcinoma

• MesenchymalEmbryonal rhabdomyosacomaLeiomyosarcomaMalignant fibrous histiocytomaangiosarcoma

CLASSIFICATION

• Adenocarcinoma – 90%• Papillary features – 6% (localised to GB)• At diagnosis Localised- 25%Regional lymph node / other organ- 35%Distant metastasis – 40%

CLASSIFICATION

• Adenocarcinoma:Well differentiated – papillary, intestinal type,

pleomorphic giant cellsPoorly differentiated – small cell, giant ring

type, clear cell, oat cell, colloid, choriocarcinoma like area

CLASSIFICATION• Adenocarcinoma: Carcinoma of glandular epithelium-1. Intestinal type adenocarcinoma- morphologicaly similar

to GIT 2. Signet ring cell CA- Diffuse infiltration of individual cells3. Mucinous adenocarcinoma- secration, stromal

deposition4. Adenosquamous- glandular and squamous

differentiation5. Clear cell CA- morphologically like RCC

CLASSIFICATION

• Adenocarcinoma:Non glandular type-

These lack glands, mucin & papilla, undifferentiated & sarcomatoid carcinoma

1. Small cell CA- alike lung CA, high gr neuroendocrine tumor marker like chromogranin, synaptophysin present.

2. Large cell neuroendocrine CA

STAGING Stage Tumor Node Mets 5yr survival

0 Tis N0 M0 100

I T1 N0 M0 85

II T2 N0 M0 25-65

IIIA*IIIB

T1-2T3

N1*N0-1

M0M0

1010

IVA*IVB

T1-4T1-4

N2*N0-2

M0M1

22

STAGING • Tis – ca in situ• T1 – tumour limited to mucosa, muscularis• T2 – tumour invades serosa• T3 – tumour invades liver (<2cm)/1 ad organ• T4 – tumour invades liver (>2cm)/ 2or more ad organ involved

• N0 – No nodal involvement• N1 – nodes along cystic, bile duct, hilar l.n• N2 – other lymph node involvement

• M0 – no distant metastasis• M1 – distant mets

NEVIN’S STAGING• Stage I – Confined to mucosa• Stage II – Breaches muscularis• Stage III – extends through muscularis• Stage IV – Involves cystic duct node• Stage V – Involves liver/ other organ

• Stg I – in situ CA• Stg II – mucosal / muscular invasion• Stg III – transmural direct liver invasion• Stg IV – lymph node metastasis• Stg V – distant metastasis

DIAGNOSIS

• History• Clinical examination• investigation

CLINICAL PRESENTATION• Asymptomatic – most of the cases• When symptoms occur it is like biliary colic or chr

cholecystitis.• Pre op diagnosis often difficult – incidental GB CA found in

cholecystectomy specimen• Careful history may revealed constant RUQ pain in an elderly

patient with wt loss and anorexia – should be suspicious. • Wt loss , anorexia, jaundice- signs of advanced disease.• Presence of palpable lump predicts high rate of

unresectability.

Cancer of the Gall Bladder

Lab INVESTIGATION

• Generally not helpful except for advanced disease- anemia, hypoalbuminemia, leucocytosis, and elevated alk. Phsphatase or high bilirubin.

• Tumour markersCEA (carcinoembryonic antigen)

sensitivity-50%, specificity-90%CA 19-9

both sensitivity&specificity -75%Helpful for follow up ? Recurrence.

INVESTIGATIONS

• Ultrasonography 70-100% sensitive• CT Scan / Spiral CT• Doppler assessment• CT / MRI Angigraphy• Invasive cholangiography

Figure 10. Porcelain gallbladder containing carcinoma and a fistula to the duodenum.



Figure 12. Moderately well-differentiated adenocarcinoma in a 70-year-old woman with right upper quadrant pain and a history of gallstones.



Figure 16. Moderately well-differentiated adenocarcinoma in a 55-year-old man.



Figure 20. Intrahepatic and periportal extension of adenocarcinoma in a 53-year-old woman.



Figure 21. Spectrum of ERCP findings in gallbladder carcinoma.



SURGICAL RESECTION

• Cholecystectomy• Extended cholecystectomy

Wide resection of GB bed lymph node removal of porta hepatis, hepatoduodenal ligament, ant & inf peripancreatic lymph node 2cm portion of hepatic parenchyma surrounding GB fossa.

• Major liver resection, l.n removal, pancreaticoduodenectomy, extrahepatic bile duct, portal vein, adjacent adherent organ.

• Formal rt hepatic lobectomy is considered inadequate.

PALLIATION

• P.T.B.D. – STENT (GB in situ)• Narcotic therapy• Ext. beam radiation• Percutaneous celiac ganglion nerve block

Mean survival <6 months

CHEMOTHERAPY

• Frequently used – 5FU, Mitomycin-C <20% pts responds

• Others – DoxorubicinNitrosoureaCis platingemcitabine

THANK YOU

Carcinoma of Gallbladder

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