Gallbladder cancer

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  • Surgical Aspects of the Multidisciplinary Treatment of Gallbladder Cancer Eduardo A Guzman MD

  • In malignancy of the gallbladder, when a diagnosis can be made without exploration, no operation should be performed, inasmuch as it only shortens the patients life

    Alfred Blalock, 1924

  • IntroductionAggressive malignancyElderly patientsPoor prognosisMany tumors are unresectableDistant metastasisSelected patients will benefit from an aggressive surgical approach

  • EpidemiologyRare tumorIncidence 2.5 cases per 100,000 residentsMost common malignancy of the biliary tract5th most common gastrointestinal malignancy

    2 times more common in women More than 75 % are older than 65

  • Epidemiology

  • EtiologyChronic gallgladder irritation and inflammationGallstonesGallstones in 80 % GB cancerGB cancer is 7 times more common in people with gallstonesPorcelain gallbladderPrimary sclerosing cholangitisPolyp

  • Gallbladder polyp> 1 cm increased incidence of cancer

    Treatment is laparoscopic cholecystectomy

    If mass do open choelcystectomy

  • Pathology

  • Location

    Neck 10 %Body 30 %Fundus 60 %

  • Lymphatic drainage of the gallbladderCysticPericholedocalPosterior pancreaticoduodenalPeriportalCommon hepatic artery nodesCeliac, interaortocaval, SMA

  • StagingMultiple classificationsNevinJapaneseAJCC / TNM

    Recent modification of AJCC / TNM

  • AJCC / TNM 6th editionab

    T1 =Mucosal or muscular invasionT2 =Transmural invasionT3 =< 2 cm hepatic invasionT4 => 2 cm hepatic invasionN0 =No lymph node involvementN1 =Lymph node involvement within hepatoduodenal ligamentN2 =Lymph node involvement beyond hepatoduodenal ligamentM0 =No distant metastasisM1 =Distant metastasis

  • T1aT1bT2T3T4T stage

  • AJCC / TNM 6th edition Limited to gallbladder Local invasion Locally advanced Metastasis

    Stage IT1 N0 M0T2 N0 M0II T3 N0 M0T1-3 N1 M0III T4 N0 M0IVTx Nx M1

  • Other pointsStage I includes 2 different surgical therapiesT4 tumors can be resectableN2 nodes are considered metastatic disease

  • Extent of disease on initial presentation

  • Laparoscopic cholecystectomy and positive marginsMucosaSubmucosaMuscularisSerosaLiverDuring a laparoscopic cholecystectomy the plane of dissection is subserosal

  • Clinical presentationUndistinguishable from benign gallstone diseaseRight upper quadrant pain Weight lossAnorexiaAbdominal mass

    Yet, one should suspect gallbladder cancer in an elderly person with weight loss and constant pain

  • Clinical syndromes

  • DiagnosisUsually diagnosed late in the disease courseUltrasoundHeterogeneous massIrregular GB wallSensitivity 70 100 %CT scanMass replacing the gallbladder or with direct extensionMRIIdentifies plane between gallbladder mass and adjacent liverCholagiographyStricture of the common hepatic duct

  • Incidental diagnosisIt is the most common presentationIntraoperativePostoperative Pathology

    1 % of all elective cholecystectomies for cholelithiasis harbor an occult GB cancer

  • ManagementDepends on stageDo open cholecystectomy if cancer suspected pre-operativelyConvert to open procedure if cancer identified intra-operativelyAvoid bile spillage or tumor implantation into port sites

  • BiopsyRisk of seeding cancer along the needle tractWorse with core biopsyGallbladder cancer has a tendency to seed the peritoneumPercutaneous biopsy is indicated if disease has been determined to be unresectable and prior to initiation of chemotherapy

  • Staging LaparoscopyImportant considerationStaging modalityPatients with incurable disease can avoid a laparotomyYield 50 %

  • Stage IT1a Disease limited to mucosaAlmost always diagnosed following cholecystectomyNegligible probability of lymph node metastasisExcellent survival 95 %No further intervention requiredMake sure cystic duct margin is negative for tumor

  • Stage IT1bDisease limited to muscularisHigher locoregional recurrence5 year survival = 85 %Treatment remains controversialSelected patients (young and healthy) may benefit from liver resection of segment IVb and V along with local lymphadenectomy

  • Couinaud SegmentsLiver Anatomy

  • Stage IT2Transmural invasionPositive margin after cholecystectomyGood probability for lymph node positivityOptimal patient for aggressive surgical intervention. 5 yr survival 18 % Vs 61 %Liver resection of segment IVb and V and lymphadenectomyCysticPericholedochal Portal

    Right celiac Hepatic Posterior pancreaticoduodenal

  • Liver resection of segment IVb and V and lymphadenectomy

  • Stage IIT3N0 / N1 diseaseCancer invades into contiguous liver for less than 2 cm and/or has positive hepatoduodenal lymph nodesTumor is still resectable High increased incidence of lymph node metastasisIdeal patient for staging laparoscopyLiver resection of segment IVb and V and lymphadenectomy

  • Stage IIIT4N0MOCancer invades into contiguous liver for more than 2 cm and negative lymph nodesAnecdotal evidence of resectability Extended liver resectionTrisegmentectomy

  • Some other important surgical considerations

    Resect port sitesAvoid spillage of bileEn bloc resectionDo not hesitate to do CBD resectionDo anatomic liver resectionsTumors in the infundibulum may require a trisegmentectomy

  • Adjuvant Chemotherapy85 % of the recurrences occur in distant disease sitesMinimal dataRegimens5 flouroracilMitomycin CGemcitabine

  • LN+ PatientsSEER National Database 1992 - 2002Mojica, Smith and Ellenhorn 2006 Adjuvant Radiation

  • Stage IVM1N2 lymph nodesExtrahepatic metastasisChemotherapyPalliationObstructive jaundicePain

  • S Kim et al Korea29 pts inoperable GB cancerMedian age 52 yrsNo complete responses34 % partial responseTime to progression = 3 monthsOverall survival = 11 moToxicity (3 or 4) = 17 %

    Tolerable combinationModest response rates

  • SurvivalOverall 5 yr survival 15 %T1a 95 % T1b 85 %T2 Cholecystectomy 18 % Liver resection 60 %Stage IV Median survival 2 months

  • SummaryGallbladder cancer is a bad diseaseAccurate staging is criticalCholecystectomy is an inadequate operation in most of the casesT1a tumors have excellent prognosisSelected patients would obtain significant benefit from aggressive surgical interventionsNearly all patients without metastatic disease require surgical evaluation to determine resectability

  • In malignancy of the gallbladder, after careful patient selection, an aggressive surgical approach can have a significant impact in the patients life

    Eduardo Guzman, 2007

    Chronic cholecystitis 40 %Biliary colic Acute cholecystitis 20 %Pain, fever, leukocytosisMalignant biliary obstruction 30 %Jaundice, Wt loss, anorexia, painMalignant non biliary tract tumor 30 %Wt loss, anorexia, painOther GI complaint 5 %Bleeding, obstruction