Gallbladder Cancer - SUNY Downstate Medical Cancer Manuel Molina, MD Lutheran Medical Center....

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Transcript of Gallbladder Cancer - SUNY Downstate Medical Cancer Manuel Molina, MD Lutheran Medical Center....

  • Gallbladder Gallbladder CancerCancer

    Manuel Molina, MDManuel Molina, MDLutheran Medical CenterLutheran Medical Center

  • Gallbladder CarcinomaGallbladder Carcinoma

  • EpidemiologyEpidemiology

    Most common malignancy of the Most common malignancy of the biliarybiliary system.system.55thth most common tumor of the GI tractmost common tumor of the GI tractMost common in the seventh or eighth decades Most common in the seventh or eighth decades of life.of life.Females to males: 3Females to males: 3--4:14:11.2 cases per 100,0001.2 cases per 100,000Highest rates in Native Americans and South Highest rates in Native Americans and South Americans, Polish and North IndiansAmericans, Polish and North Indians

  • PathogenesisPathogenesis

    Relationship between Relationship between cholelithiasischolelithiasis and GB and GB cancer. 80% of patients with GB cancer have cancer. 80% of patients with GB cancer have gallstones, 60% located in the gallstones, 60% located in the fundusfundus..Multistage process:Multistage process:

    Mucosal inflammationMucosal inflammationHyperplasiaHyperplasiaMetaplasiaMetaplasiaDysplasiaDysplasiaCarcinoma. Invades surrounding structuresCarcinoma. Invades surrounding structuresHematogenousHematogenous or lymphatic spread (cystic node)or lymphatic spread (cystic node)

  • PathogenesisPathogenesis

    Risk increases in direct proportion to gallstone Risk increases in direct proportion to gallstone size. RR is 2.4 if gallstones are 2 to 2.9 cm, and size. RR is 2.4 if gallstones are 2 to 2.9 cm, and 10.1 if >3.0cm10.1 if >3.0cm.(A.K. Diehl et al, JAMA 250, 1983.).(A.K. Diehl et al, JAMA 250, 1983.)Porcelain Gallbladder has been associated with Porcelain Gallbladder has been associated with GB cancer in 12.5GB cancer in 12.5--62%. Higher in selective 62%. Higher in selective mucosal calcification.mucosal calcification. (A.E. Stephen et al.,. Surgery 129, 2001).(A.E. Stephen et al.,. Surgery 129, 2001).Polyps greater than 10mm in diameter have the Polyps greater than 10mm in diameter have the greatest malignant potential. greatest malignant potential. ((M.C.AldridgeM.C.Aldridge et al., Br J et al., Br J SurgSurg &&, &&, 1990).1990).

  • PathogenesisPathogenesis

    Anomalous Anomalous pancreaticobiliarypancreaticobiliary duct junction is duct junction is associated with GB cancer; found in 17% of patients. associated with GB cancer; found in 17% of patients. This causes free back flow of pancreatic juice into the This causes free back flow of pancreatic juice into the gallbladder causing bile stasis in patients with normal gallbladder causing bile stasis in patients with normal CBD. These patients are younger and have lower CBD. These patients are younger and have lower incidence of gallstones. incidence of gallstones. (K. (K. ChijiiwaChijiiwa et al., et al., IntInt SurgSurg 80,1995)80,1995)Carcinogens like Carcinogens like methylcholanthrenemethylcholanthrene, , OO--aminoazotoluleneaminoazotolulene, nitrosamines are associated with , nitrosamines are associated with GB cancer in experimental GB cancer in experimental animals.animals.(K(K. . KowalewskiKowalewski et al, Proc Soc Exp et al, Proc Soc Exp Bio Med 136, 1971.)Bio Med 136, 1971.)

  • PathogenesisPathogenesis

    Other risk factors include obesity, estrogens, Other risk factors include obesity, estrogens, thyphoidthyphoid infection, segmental infection, segmental adenomyomatosisadenomyomatosis, chronic inflammatory bowel , chronic inflammatory bowel disease and disease and polyposispolyposis coli.coli.

  • PathologyPathology

    DysplasiaDysplasia to invasive carcinoma takes over 15 years.to invasive carcinoma takes over 15 years.Macroscopically is divided into papillary, tubular or Macroscopically is divided into papillary, tubular or nodular. Papillary less invasion to the liver and lymph nodular. Papillary less invasion to the liver and lymph nodes.nodes.Most carcinomas are Most carcinomas are adenocarcinomasadenocarcinomas 8080--95%, and 95%, and can be papillary, tubular, can be papillary, tubular, mucinousmucinous or signet cells.or signet cells.Less common types include: Less common types include: anaplasicanaplasic (2(2--7%), 7%), squamoussquamous cell (1cell (1--6%), and 6%), and adenosquamousadenosquamous (1(1--4%). 4%). CarcinoidCarcinoid, small, small--cell, malignant melanoma, lymphoma cell, malignant melanoma, lymphoma and sarcomas are particularly rare.and sarcomas are particularly rare.

  • GeneticsGenetics

    KK--rasras mutations in 39mutations in 39--59%. Increases to 5059%. Increases to 50--83% in patients with abnormal 83% in patients with abnormal pancreaticobiliarypancreaticobiliary duct junction.duct junction.P53 abnormalities are seen in 35P53 abnormalities are seen in 35--92% of GB 92% of GB cancers.cancers.(S(S. . MisraMisra et al, et al, EurEur J J SurgSurg OncolOncol 26, 2000). 26, 2000). OverOver--expression of p53 is associated with grade, expression of p53 is associated with grade, stage and presence of gallstones.stage and presence of gallstones.

  • Clinical PresentationClinical PresentationSymptomsSymptoms Proportion of patientsProportion of patients

    RUQ pain RUQ pain 82%82%Weight lossWeight loss 72%72%AnorexiaAnorexia 74%74%Nausea and vomitingNausea and vomiting 68%68%RUQ massRUQ mass 65%65%JaundiceJaundice 44%44%Abdominal distentionAbdominal distention 30%30%PruritusPruritus 20%20%HematemesisHematemesis 2%2%MelenaMelena 1%1%

  • DiagnosisDiagnosis

    Only 8Only 8--10% are diagnosed preoperatively.10% are diagnosed preoperatively.Diagnosis is often challenging, no signs and Diagnosis is often challenging, no signs and symptoms specific to gallbladder cancer.symptoms specific to gallbladder cancer.Most are incidental discovery during the OR.Most are incidental discovery during the OR.

  • DiagnosisDiagnosisUltrasonographyUltrasonography: 80% accurate; part of the : 80% accurate; part of the initial assessment. Demonstrates initial assessment. Demonstrates polypoidalpolypoidalmass without acoustic shadow with localized mass without acoustic shadow with localized thickening. Loss of GB/liver interface found in thickening. Loss of GB/liver interface found in advance cancer.advance cancer.Limitation in diagnosis of involved nodes and Limitation in diagnosis of involved nodes and staging of the diseasestaging of the diseaseEndoscopicEndoscopic ultrasound improves diagnosis of ultrasound improves diagnosis of GB cancer and predicts depth of tumor. GB cancer and predicts depth of tumor. Helpful for differential diagnosis of Helpful for differential diagnosis of polypoidpolypoidlesions.lesions.

  • DiagnosisDiagnosis

    CT Scan accurately detects GB abnormalities CT Scan accurately detects GB abnormalities and the extent of disease, direct infiltration into and the extent of disease, direct infiltration into adjacent tissues or vessels, nodal or distant adjacent tissues or vessels, nodal or distant metastasis. metastasis. MRI: tumors are MRI: tumors are hypodensehypodense in T1 images and in T1 images and hyperdensehyperdense in T2 images. Particularly useful for in T2 images. Particularly useful for visualizing invasion of the visualizing invasion of the hepatoduodenalhepatoduodenalligament, portal vein encasement and lymph ligament, portal vein encasement and lymph node involvement.node involvement.

  • DiagnosisDiagnosis

    Selective angiography is very accurate for Selective angiography is very accurate for detection of vessel encasement or detection of vessel encasement or neovascularizationneovascularization..ERCP is helpful in planning surgery, because it ERCP is helpful in planning surgery, because it can show tumor growth in the can show tumor growth in the intrahepaticintrahepatic ducts ducts or CBD.or CBD.HIDA can show CBD obstruction or cystic duct HIDA can show CBD obstruction or cystic duct obstruction (rare in GB cancer).obstruction (rare in GB cancer).FNA ultrasound or CT guided most frequently FNA ultrasound or CT guided most frequently used for used for preoppreop cytodiagnosiscytodiagnosis, has a sensitivity of , has a sensitivity of 88%.88%.

  • DiagnosisDiagnosis

    Laparoscopy and biopsy are extremely useful for Laparoscopy and biopsy are extremely useful for assessment of peritoneal metastasis, extend of assessment of peritoneal metastasis, extend of the disease and suitability of surgery in patients the disease and suitability of surgery in patients with locally advanced disease.with locally advanced disease.Markers as CA 19Markers as CA 19--9 >20U/ml have 79.4% 9 >20U/ml have 79.4% sensitivity and 79.2% specific. CEA >4mcg/L sensitivity and 79.2% specific. CEA >4mcg/L is 93% specific but only 50% sensitive.is 93% specific but only 50% sensitive.

  • StagingStaging UICC/AJCC TNMUICC/AJCC TNMPrimary tumorPrimary tumorTxTx Primary tumor cannot be assessed.Primary tumor cannot be assessed.T0 No evidence of primary tumorT0 No evidence of primary tumorTisTis Carcinoma in situCarcinoma in situT1a Tumor invade lamina T1a Tumor invade lamina propriapropriaTibTib tumor tumor invadesmuscleinvadesmuscle layerlayerT2 Tumor invades T2 Tumor invades perimuscularperimuscular connective tissue, no extension connective tissue, no extension beyongbeyong serosaserosa or into or into

    liver.liver.T3 Tumor perforates T3 Tumor perforates serosaserosa or directly invades the liver or other adjacent organs or or directly invades the liver or other adjacent organs or

    structure (stomach, duodenum, colon, pancreas, structure (stomach, duodenum, colon, pancreas, omentumomentum, , extrhepaticextrhepatic bile bile ducrsducrs))T4 Tumor invades main portal vein or hepatic a