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GI & Liver Malignancies Bushra Ibnauf Sulieman, MD MS Consultant, Gastroenterology & Hepatology Department of Medicine Kin...
Question <ul><li>A 45 year old man was referred by his PCP because of new onset of dysphagia of 4 weeks duration. The pati...
Question <ul><li>A 45 year old man was referred by his PCP because of new onset of dysphagia of 4 weeks duration. The pati...
Pathogenesis of Adenocarcinoma GERD Reflux Esophagitis Intestinal metaplasia (Barrett’s esophagus) Dysplasia Adenocarcinoma
Barrett’s HGD
Barrett’s Esophagus <ul><li>Intestinal metaplasia of the esophagus : Replacement of the stratified squamous mucosa by spec...
 
Epidemiology of Esophageal Cancer in the US <ul><li>  Squamous   Adeno </li></ul><ul><li>New cases per year   ~ 6000 ~ 600...
Esophageal AdenoCa: Risk Factors <ul><li>Barrett’s mucosa: most significant (40 fold) </li></ul><ul><li>GERD </li></ul><ul...
Esophageal SCCA: Risk Factors <ul><li>Diet: </li></ul><ul><ul><li>N-nitroso compounds </li></ul></ul><ul><ul><li>Alcohol <...
Clinical Presentation & Symptoms <ul><li>Dysphagia:  </li></ul><ul><ul><li>Most common </li></ul></ul><ul><ul><li>Initiall...
Esophageal Cancer: Diagnosis <ul><li>Endoscopy: </li></ul><ul><ul><li>Location: Distal vs. proximal </li></ul></ul><ul><ul...
Esophageal Cancer: Diagnosis
Question <ul><li>You performed an EGD, with biopsy of the mass. The results confirm your suspicions. You now wish to begin...
Staging Classification: TNM <ul><li>T : Primary tumor </li></ul><ul><ul><li>Tis: Carcinoma in situ / high grade dysplasia ...
Esophageal Cancer Staging <ul><li>Stage 0:  Tis, N0, M0 </li></ul><ul><li>Stage I:  T1, N0, M0 </li></ul><ul><li>Stage II:...
Esophageal Cancer: Survival <ul><li>STAGE   5-Year Survival </li></ul><ul><li>Stage 0:   75% </li></ul><ul><li>Stage I:  5...
Staging Tools <ul><li>Endoscopic Ultrasound (EUS) </li></ul><ul><ul><li>Best modality for locoregional staging </li></ul><...
EUS: Esophageal Cancer <ul><li>T & N staging </li></ul><ul><li>Metastasis: </li></ul><ul><ul><li>Celiac lymph nodes </li><...
7.5 / 12 MHz. 7.5 MHz. UC-30P UM-130 Mechanical Radial Scanning Curved Linear Array Scanning
EUS: Gastrointestinal Wall Mucosa Submucosa Muscularis propria Serosa Lumen Scope
T2N0 T3N0 T4N0
Treatment: Early Disease <ul><li>Stages: T is , I and IIA </li></ul><ul><li>Surgery: </li></ul><ul><ul><li>Mainstay of tre...
Treatment: Locally advanced Disease <ul><li>Stages IIB and III </li></ul><ul><li>Difficult and controvercial </li></ul><ul...
Treatment: Metastatic Disease <ul><li>Palliative  </li></ul><ul><li>Chemotherapy +/- XRT: </li></ul><ul><ul><li>Potential ...
Endoscopic Therapy <ul><li>Limited role </li></ul><ul><li>Endoscopic Mucosal resection </li></ul><ul><li>Coagulation thera...
Palliative Treatment <ul><li>XRT </li></ul><ul><li>Chemotherapy </li></ul><ul><li>Endoscopic dilation </li></ul><ul><li>En...
Screening & Prevention <ul><li>Aggressive treatment of GERD </li></ul><ul><ul><li>Medical  </li></ul></ul><ul><ul><li>Surg...
Question <ul><li>A 72 year old man presents with 10 kg weight loss, early </li></ul><ul><li>satiety and melena. He has a g...
Gastric Cancer <ul><li>Lung (1.4 million deaths) </li></ul><ul><li>Stomach (740 000 deaths) </li></ul><ul><li>Liver (700 0...
Gastric Cancer  <ul><li>Environmental : preserved meats, nitrates </li></ul><ul><li>Genetics: First degree relatives 2-3x ...
Gastric Cancer - Diagnosis
Gastric Cancer- Staging & Prognosis TNM
Other Gastric Tumors
Case  <ul><li>55 y.o. male w/ chronic active HBV, decompensated Child B cirrhosis </li></ul><ul><li>Abdominal pain and jau...
Hepatocellular Carcinoma <ul><li>One million new cases yearly worldwide; 15,000 new cases in the US </li></ul><ul><li>One ...
<ul><li>Clinical Features </li></ul><ul><li>Asymptomatic 23% </li></ul><ul><li>Abdominal pain 32% </li></ul><ul><li>Malais...
Etiology <ul><li>Cirrhosis (60-90%) </li></ul><ul><li>Alcohol </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>Cardiac ...
Risk of HCC in Cirrhosis High >15% HCV HBV +iron Moderate Alcohol Low <5% Wilson PBC Autoimmune
Diagnosis <ul><li>AFP </li></ul><ul><ul><li>AFP > 20 ng/mL in > 70% w/ HCC </li></ul></ul><ul><ul><li>AFP 10-500 ng/mL in ...
Trabecular pattern, increased N:C ratio Abnormal nuclei Microtrabecular pattern, irregular hepatocytes Gastroenterology.  ...
Acinar structures, bile  Mixed acinar, trabecular structures Mitros F. Atlas of Liver Pathology. Virtual Hospital
Central vein and portal triad involvement of HCC  Bizzare hepatocyte giant cell Mitros F. Atlas of Liver Pathology. Virtua...
Histology FNH Adenoma Regenerative Nodule Well-differentiated HCC can be confused with FNH, adenoma, and macroregenrative ...
Imaging in HCC <ul><li>Multiple forms </li></ul><ul><ul><li>Rapid enhancement </li></ul></ul><ul><ul><li>Enhancing rim cap...
Radiographics.  2002; 22: 1023-1039   Axial T2, fat-sat, fast spin echo Axial T1, in-phase, gradient echo Axial T1, arteri...
Axial portal phase dynamic enhanced Coronal contrast enhanced Radiographics.  2002; 22: 1023-1039
Early arterial Portal venous Delayed FNH Adenoma Pre-contrast Early contrast No contrast Early contrast Portal venous Dela...
Management <ul><li>Resection </li></ul><ul><li>Tumor ablation </li></ul><ul><ul><li>Radiofrequency ablation </li></ul></ul...
Factors Influencing Treatment <ul><li>Tumor size, number and distribution </li></ul><ul><ul><li>Artery or venous proximity...
Surgical Resection <ul><li>Indications </li></ul><ul><ul><li>Ability to remove all the tumor </li></ul></ul><ul><ul><li>We...
CW Pinson, AASLD 1999, post-grad course
CW Pinson, AASLD 1999, post-grad course
Chemoembolization <ul><li>Technique </li></ul><ul><li>Requires hepatic arteriogram </li></ul><ul><li>Chemo agents: doxorub...
Chemoembolization <ul><li>Applications </li></ul><ul><ul><li>Tumor downsizing for resection </li></ul></ul><ul><ul><li>Pal...
Complications of TACE (197 procedures) Fever 74% Abdominal pain 45% Nausea/emesis 59% Bleeding or hematoma 7% GI bleeding ...
POST- TACE PRE- TACE CW Pinson, AASLD 1999, post-grad course
61 RCT 1 º  treatment of HCC 26 RCT  adequate control arm 14 RCT  Sample size adequate 7 RCT  TAE/TACE 7 RCT  tamoxifen He...
Prospective RCTs of TAE/TACE   #   % Child A   % response   1/2 yr    survival Lin et al. (1988) ? TAE  21    13(70%)   42...
Hepatology.  2003; 37:429-442   <ul><li>TAE improves 2-yr survival – 41% vs 27% (OR 0.53: 95% confidence interval 0.32-0.8...
<ul><li>Technique </li></ul><ul><li>Percutaneous, laparoscopic or open  </li></ul><ul><li>U/S guided probe placement </li>...
Radio-frequency Ablation <ul><li>Well tolerated and safe </li></ul><ul><li>Side effects  </li></ul><ul><li>13% complicatio...
<ul><ul><li>Radiology. 2000; 217(3):633-46 </li></ul></ul>POST-RFA PRE-RFA
Liver Transplantation in HCC <ul><li>Theoretic best treatment  </li></ul><ul><ul><li>Widest resection margins </li></ul></...
<ul><li>Current indications </li></ul><ul><li>Child B/C cirrhosis </li></ul><ul><li>TNM, stage I/II </li></ul><ul><li>Cont...
Liver Transplant for Small HCC in Patients with Cirrhosis N Engl J Med.  1996; 334(11):693-699  <ul><li>Exclusions </li></...
<ul><li>Results </li></ul><ul><li>Overall mortality 17% </li></ul><ul><li>Explanted liver examined </li></ul><ul><ul><li>P...
OLT for HCC <ul><li>Regalia et al. (2001),  122 pts   </li></ul><ul><ul><li>Single tumor <5, 3 tumors < 3cm </li></ul></ul...
Model for End Stage Liver Disease MELD Score = (0.957 x Log e (creatinine mg/dL)  + 0.378 x Log e (bilirubin mg/dL) + 1.12...
(MELD) and Allocation of Donor Livers <ul><li>3437 adult liver transplant candidates  </li></ul><ul><ul><li>Listed as 2A o...
MELD Provisions for HCC <ul><li>UNOS policy 3.6.1 (2/2002) </li></ul><ul><ul><li>T1- MELD score = 15% 3 mo pre-transplant ...
Hepatocellular Cancer Single tumor <5cm 3 tumors, each <3cm Consider liver transplant Resection Local ablation TACE Large ...
SAMA www.sama-sd.org
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GI and Liver Malignancies

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by Bushra Ibnauf as part of SAMA's Visiting Faculty Program in SMSB on July 11th 2011.

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Transcript of "GI and Liver Malignancies"

  1. 1. GI & Liver Malignancies Bushra Ibnauf Sulieman, MD MS Consultant, Gastroenterology & Hepatology Department of Medicine King Faisal Specialist Hospital & Research Center - Jeddah
  2. 2. Question <ul><li>A 45 year old man was referred by his PCP because of new onset of dysphagia of 4 weeks duration. The patient has had a history of smoking, 5-pack years, in high school and a history of heartburn self medicated with OTC antiacids. An UGI study showed a mass lesion in the distal esophagus. Which of the following statements is INCORRECT? </li></ul><ul><li>The lesion is most likely produced by a metastatic cancer </li></ul><ul><li>The patient probably has had Barrett’s esophagus </li></ul><ul><li>Biopsy specimens from the gastroesophageal junction of this patient would show adenocarcinoma </li></ul><ul><li>Squamous cell cancer is unlikely in this location </li></ul><ul><li>Most patients with this cancer would likely be male </li></ul>
  3. 3. Question <ul><li>A 45 year old man was referred by his PCP because of new onset of dysphagia of 4 weeks duration. The patient has had a history of smoking , 5-pack years, in high school and a history of heartburn self medicated with OTC antiacids. An UGI study showed a mass lesion in the distal esophagus. </li></ul><ul><li>Which of the following statements is INCORRECT? </li></ul><ul><li>The lesion is most likely produced by a metastatic cancer </li></ul><ul><li>The patient probably has had Barrett’s esophagus </li></ul><ul><li>Biopsy specimens from the gastroesophageal junction of this patient would show adenocarcinoma </li></ul><ul><li>Squamous cell cancer is unlikely in this location </li></ul><ul><li>Most patients with this cancer would likely be male </li></ul>
  4. 4. Pathogenesis of Adenocarcinoma GERD Reflux Esophagitis Intestinal metaplasia (Barrett’s esophagus) Dysplasia Adenocarcinoma
  5. 5. Barrett’s HGD
  6. 6. Barrett’s Esophagus <ul><li>Intestinal metaplasia of the esophagus : Replacement of the stratified squamous mucosa by specialized columnar cells </li></ul>
  7. 8. Epidemiology of Esophageal Cancer in the US <ul><li> Squamous Adeno </li></ul><ul><li>New cases per year ~ 6000 ~ 6000 </li></ul><ul><li>Male-to-female ratio 3:1 7:1 </li></ul><ul><li>Black-to-white ratio 6:1 1:4 </li></ul><ul><li>Major risk factors smoking Barrett’s </li></ul><ul><li>Alcohol esophagus </li></ul><ul><li>Socioeconomic class lower high </li></ul><ul><li>Geography SE Asia western / </li></ul><ul><li>Africa industrial </li></ul><ul><li>Iran </li></ul>
  8. 9. Esophageal AdenoCa: Risk Factors <ul><li>Barrett’s mucosa: most significant (40 fold) </li></ul><ul><li>GERD </li></ul><ul><li>AC is largely a disease of Caucasians and males </li></ul><ul><li>Obesity has been associated with AC but not SCC </li></ul><ul><li>Smoking probably increases the risk of AC </li></ul><ul><ul><li>Development of HGD in Barrett’s </li></ul></ul><ul><li>Alcohol is probably not an important risk factor </li></ul>Cameron A, et al. Gastroenterology 1995; 109: 1541. Lagergren et al. NEJM 1999; 340:825.
  9. 10. Esophageal SCCA: Risk Factors <ul><li>Diet: </li></ul><ul><ul><li>N-nitroso compounds </li></ul></ul><ul><ul><li>Alcohol </li></ul></ul><ul><ul><li>Hot tea </li></ul></ul><ul><li>Tobacco </li></ul><ul><li>HPV 16 </li></ul><ul><li>Lye induced strictures </li></ul><ul><li>Chronic esophagitis </li></ul><ul><li>Associated diseases: </li></ul><ul><ul><li>Head & neck cancer </li></ul></ul><ul><ul><li>Achalasia </li></ul></ul><ul><ul><li>Plummer-Vinson syndrome </li></ul></ul><ul><ul><li>Tylosis </li></ul></ul><ul><ul><li>Celiac disease </li></ul></ul><ul><ul><li>Gastrectomy </li></ul></ul><ul><ul><li>Radiation therapy </li></ul></ul>Axelard A, et al. In Sleizenger & Fordtran’s Gastro & Liver Dis, 6 th Ed.
  10. 11. Clinical Presentation & Symptoms <ul><li>Dysphagia: </li></ul><ul><ul><li>Most common </li></ul></ul><ul><ul><li>Initially intermittent </li></ul></ul><ul><ul><li>Solids then liquids </li></ul></ul><ul><li>History of GERD (AdenoCa): </li></ul><ul><ul><li>Esophagitis / Barrett’s in 50% on presentation </li></ul></ul><ul><li>Food intolerance, anorexia and wt. Loss </li></ul><ul><li>Odynophagia and back pain: </li></ul><ul><ul><li>Mediastinal involvement </li></ul></ul><ul><li>Hoarseness </li></ul><ul><li>Esophago-pulmonary fistula </li></ul><ul><li>Liver / diaphragm / airway mets </li></ul>
  11. 12. Esophageal Cancer: Diagnosis <ul><li>Endoscopy: </li></ul><ul><ul><li>Location: Distal vs. proximal </li></ul></ul><ul><ul><li>Associated Barrett’s </li></ul></ul><ul><ul><li>Appearance: Flat vs. polypoid </li></ul></ul><ul><li>Endoscopic biopsy: Most valuable </li></ul><ul><ul><li>Sensitivity of 6-8 bxies: 98% </li></ul></ul><ul><ul><li>Sensitivity of cytology and bx: 100% </li></ul></ul><ul><li>Radiology: </li></ul><ul><ul><li>Esophagogram: Filling defect </li></ul></ul><ul><ul><li>CAT scan: Thickening </li></ul></ul>
  12. 13. Esophageal Cancer: Diagnosis
  13. 14. Question <ul><li>You performed an EGD, with biopsy of the mass. The results confirm your suspicions. You now wish to begin to stage the mass. </li></ul><ul><li>Which of the following would be the first procedure of choice? </li></ul><ul><li>PET scan </li></ul><ul><li>CT of the chest and abdomen </li></ul><ul><li>EUS, with FNA of lymph nodes, if present </li></ul><ul><li>Video assissted thoracosocpy, with biopsy </li></ul>
  14. 15. Staging Classification: TNM <ul><li>T : Primary tumor </li></ul><ul><ul><li>Tis: Carcinoma in situ / high grade dysplasia </li></ul></ul><ul><ul><li>T1: Mucosa and submucosa </li></ul></ul><ul><ul><li>T2: Muscularis propria </li></ul></ul><ul><ul><li>T3: Transmural / periesophageal </li></ul></ul><ul><li>N : Regional lymph nodes </li></ul><ul><ul><li>N0: No adenopathy </li></ul></ul><ul><ul><li>N1: Regional nodal metastasis </li></ul></ul><ul><li>M : Distant metastasis </li></ul><ul><ul><li>M0 vs. M1 </li></ul></ul>
  15. 16. Esophageal Cancer Staging <ul><li>Stage 0: Tis, N0, M0 </li></ul><ul><li>Stage I: T1, N0, M0 </li></ul><ul><li>Stage II: </li></ul><ul><ul><li>IIA: T2/3, N0, M0 </li></ul></ul><ul><ul><li>IIB: T1/2, N1 , M0 </li></ul></ul><ul><li>Stage III: </li></ul><ul><ul><li>T3, N1 , M0 </li></ul></ul><ul><ul><li>T4 , N1, M0 </li></ul></ul><ul><li>Stage IV: Any T, any N, M1 </li></ul>
  16. 17. Esophageal Cancer: Survival <ul><li>STAGE 5-Year Survival </li></ul><ul><li>Stage 0: 75% </li></ul><ul><li>Stage I: 50% </li></ul><ul><li>S tage IIA: 40% </li></ul><ul><li>Stage IIB: 20% </li></ul><ul><li>Stage III: 15% </li></ul><ul><li>Stage IV: < 5% </li></ul>
  17. 18. Staging Tools <ul><li>Endoscopic Ultrasound (EUS) </li></ul><ul><ul><li>Best modality for locoregional staging </li></ul></ul><ul><ul><li>Limited role in distant metastasis </li></ul></ul><ul><li>CAT scan: </li></ul><ul><ul><li>T staging: no role </li></ul></ul><ul><ul><li>Nodal staging: very low sensitivity </li></ul></ul><ul><ul><li>Detection of metastasis </li></ul></ul><ul><li>PET scan: </li></ul><ul><ul><li>Whole body survey </li></ul></ul><ul><ul><li>Helpful in diagnosing metastatic disease </li></ul></ul><ul><ul><li>Limited role in T / local staging </li></ul></ul>Flamen P, et al. J Clin Oncol 2000; 18: 3202.
  18. 19. EUS: Esophageal Cancer <ul><li>T & N staging </li></ul><ul><li>Metastasis: </li></ul><ul><ul><li>Celiac lymph nodes </li></ul></ul><ul><ul><li>Liver lesions </li></ul></ul><ul><li>Change in management decisions </li></ul><ul><li>Prognostic information </li></ul>
  19. 20. 7.5 / 12 MHz. 7.5 MHz. UC-30P UM-130 Mechanical Radial Scanning Curved Linear Array Scanning
  20. 21. EUS: Gastrointestinal Wall Mucosa Submucosa Muscularis propria Serosa Lumen Scope
  21. 22. T2N0 T3N0 T4N0
  22. 23. Treatment: Early Disease <ul><li>Stages: T is , I and IIA </li></ul><ul><li>Surgery: </li></ul><ul><ul><li>Mainstay of treatment </li></ul></ul><ul><ul><li>Surgery alone </li></ul></ul><ul><ul><li>Best outcome: </li></ul></ul><ul><ul><ul><li>T is & HGD: cure rate of 100% </li></ul></ul></ul><ul><ul><ul><li>Stages I & IIA: cure rate ~ 80% </li></ul></ul></ul>Steup W, et al. J Thorac Cardiovasc Surg 1996; 5:S17-26.
  23. 24. Treatment: Locally advanced Disease <ul><li>Stages IIB and III </li></ul><ul><li>Difficult and controvercial </li></ul><ul><li>Surgery alone: 10% cure! </li></ul><ul><li>Neoadjuvant chemo or XRT: No difference </li></ul><ul><li>Neoadjuvant chemo and radiation: </li></ul><ul><ul><li>Greatest chance for prolonged survival </li></ul></ul><ul><ul><li>Cisplatin and 5-Fluorouracil </li></ul></ul><ul><li>Patient and Dr.’s decision!!! </li></ul>Lightdale C. Am J Gastro 1999; 94: 20.
  24. 25. Treatment: Metastatic Disease <ul><li>Palliative </li></ul><ul><li>Chemotherapy +/- XRT: </li></ul><ul><ul><li>Potential prolongation of life? </li></ul></ul><ul><ul><li>Fit and willing patient </li></ul></ul>Lightdale C. Am J Gastro 1999; 94: 20.
  25. 26. Endoscopic Therapy <ul><li>Limited role </li></ul><ul><li>Endoscopic Mucosal resection </li></ul><ul><li>Coagulation therapy (Barrett’s HGD): </li></ul><ul><ul><ul><li>Photodynamic therapy </li></ul></ul></ul><ul><ul><ul><li>Bipolar / heat coagulation </li></ul></ul></ul><ul><ul><ul><li>Laser </li></ul></ul></ul>
  26. 27. Palliative Treatment <ul><li>XRT </li></ul><ul><li>Chemotherapy </li></ul><ul><li>Endoscopic dilation </li></ul><ul><li>Endoscopic stenting </li></ul><ul><li>Photodynamic therapy </li></ul><ul><li>Endoscopic laser therapy </li></ul><ul><li>Access for nutritional support </li></ul>
  27. 28. Screening & Prevention <ul><li>Aggressive treatment of GERD </li></ul><ul><ul><li>Medical </li></ul></ul><ul><ul><li>Surgical </li></ul></ul><ul><li>Screening of target population : </li></ul><ul><ul><li>Barrett’s metaplasia </li></ul></ul><ul><ul><li>High incidence areas </li></ul></ul><ul><li>Tools: </li></ul><ul><ul><li>Endoscopy </li></ul></ul><ul><ul><li>Balloon cytology </li></ul></ul><ul><ul><li>Endoscopic ultrasound </li></ul></ul><ul><ul><li>Biomarkers </li></ul></ul>
  28. 29. Question <ul><li>A 72 year old man presents with 10 kg weight loss, early </li></ul><ul><li>satiety and melena. He has a great fear of gastric </li></ul><ul><li>cancer because his father died of it at age 59. EGD was </li></ul><ul><li>Done and revealed a large ulcer with raised edges. You recommend: </li></ul><ul><li>Imatinib to shrink the tumor </li></ul><ul><li>Radiotherapy and Chemotherapy </li></ul><ul><li>Eradication of H Pylori to reverse </li></ul><ul><li>the condition </li></ul><ul><li>Surgical resection </li></ul><ul><li>Laser therapy </li></ul>
  29. 30. Gastric Cancer <ul><li>Lung (1.4 million deaths) </li></ul><ul><li>Stomach (740 000 deaths) </li></ul><ul><li>Liver (700 000 deaths) </li></ul><ul><li>Colorectal (610 000 deaths) </li></ul><ul><li>Breast (460 000 deaths). </li></ul>WHO 2008
  30. 31. Gastric Cancer <ul><li>Environmental : preserved meats, nitrates </li></ul><ul><li>Genetics: First degree relatives 2-3x </li></ul><ul><li>H Pylori Infection more related to distal stomach cancers </li></ul><ul><li>Pernicious anemia </li></ul><ul><li>? Partial gastrectomy for benign disease </li></ul><ul><li>Gastric polyps </li></ul><ul><li>95% adenocarcinoma </li></ul><ul><li>5% lymphoma, sarcoma, carcinoiud </li></ul><ul><li>Linitis plastica 10% of adenoacarcinomas </li></ul>
  31. 32. Gastric Cancer - Diagnosis
  32. 33. Gastric Cancer- Staging & Prognosis TNM
  33. 34. Other Gastric Tumors
  34. 35. Case <ul><li>55 y.o. male w/ chronic active HBV, decompensated Child B cirrhosis </li></ul><ul><li>Abdominal pain and jaundice </li></ul><ul><li>AFP 400’s </li></ul><ul><li>MRI- 3 enhancing liver nodules 1.5cm, 1cm and 9mm (segments III, V, VIII) </li></ul><ul><li>Diagnosis/Treatment? </li></ul>
  35. 36. Hepatocellular Carcinoma <ul><li>One million new cases yearly worldwide; 15,000 new cases in the US </li></ul><ul><li>One million deaths yearly worldwide </li></ul><ul><li>Peak age </li></ul><ul><ul><li>Industrialized nations: 6-7 th decade </li></ul></ul><ul><ul><li>Fibrolamellar subtype (3-10%): <40 yr </li></ul></ul><ul><ul><li>High incidence areas: 30-40 yr </li></ul></ul><ul><ul><li>Children: <5yr </li></ul></ul><ul><li>Median survival 2-10 months; 5 year survival <3% </li></ul>Gastroenterology. 2002; 122:1609-1619
  36. 37. <ul><li>Clinical Features </li></ul><ul><li>Asymptomatic 23% </li></ul><ul><li>Abdominal pain 32% </li></ul><ul><li>Malaise 9% </li></ul><ul><li>Fever 8% </li></ul><ul><li>Ascites 8% </li></ul><ul><li>Jaundice 6% </li></ul><ul><li>Anorexia 6% </li></ul><ul><li>Weight Loss 4% </li></ul><ul><li>Hemorrhage 2% </li></ul><ul><li>Encephalopathy 2% </li></ul><ul><li>(461 Patients) </li></ul>Gastroenterology. 2002; 122:1609-1619 Paraneoplastic Syndromes Sexual precocity Gynecomastia Feminization Carcinoid Syndrome Hypertrophic arthropathy Hypercholesterolemia Hypoglycemia Hypercalcemia Erythrocytosis Vitiligo Thrombophlebitis
  37. 38. Etiology <ul><li>Cirrhosis (60-90%) </li></ul><ul><li>Alcohol </li></ul><ul><li>Hemochromatosis </li></ul><ul><li>Cardiac </li></ul><ul><li>Biliary atresia </li></ul><ul><li>Hepatitis B/C (~15%) </li></ul><ul><li>Carcinogens </li></ul><ul><li>Aflatoxin </li></ul><ul><li>Siderosis </li></ul><ul><li>Androgens </li></ul><ul><li>Thorotrast </li></ul><ul><li>Inborn errors of metabolism </li></ul><ul><li>Alph-1-antitrypsin </li></ul><ul><li>Galactosemia </li></ul><ul><li>Type I glycogen storage disease (von Gierke) </li></ul><ul><li>Wilson disease </li></ul><ul><li>Tyrosinosis </li></ul>
  38. 39. Risk of HCC in Cirrhosis High >15% HCV HBV +iron Moderate Alcohol Low <5% Wilson PBC Autoimmune
  39. 40. Diagnosis <ul><li>AFP </li></ul><ul><ul><li>AFP > 20 ng/mL in > 70% w/ HCC </li></ul></ul><ul><ul><li>AFP 10-500 ng/mL in necroinflammatory conditions -> Viral hepatitis </li></ul></ul><ul><ul><li>Sensitivity (39-64%), Specificity (76-91%) </li></ul></ul><ul><li>Liver Biopsy </li></ul><ul><ul><li>Not needed in everyone (AFP 500, cirrhosis) </li></ul></ul><ul><ul><li>Needle track spread of HCC (1%) </li></ul></ul>Gastroenterology. 2002; 122:1609-1619
  40. 41. Trabecular pattern, increased N:C ratio Abnormal nuclei Microtrabecular pattern, irregular hepatocytes Gastroenterology. 2002; 122:1609-1619
  41. 42. Acinar structures, bile Mixed acinar, trabecular structures Mitros F. Atlas of Liver Pathology. Virtual Hospital
  42. 43. Central vein and portal triad involvement of HCC Bizzare hepatocyte giant cell Mitros F. Atlas of Liver Pathology. Virtual Hospital
  43. 44. Histology FNH Adenoma Regenerative Nodule Well-differentiated HCC can be confused with FNH, adenoma, and macroregenrative nodules
  44. 45. Imaging in HCC <ul><li>Multiple forms </li></ul><ul><ul><li>Rapid enhancement </li></ul></ul><ul><ul><li>Enhancing rim capsule </li></ul></ul><ul><ul><li>Heterogenous (fat, hemorrhage, fibrosis) </li></ul></ul><ul><ul><li>PV thrombosis </li></ul></ul><ul><li>Ultrasound (86-99% sens, 90-93% spec) </li></ul><ul><ul><li>Mixed echogenicity (60%): tumor necrosis </li></ul></ul><ul><ul><li>Hypechoic (30%): solid tumor </li></ul></ul><ul><ul><li>Hyperechoic (10%): fatty change </li></ul></ul>Radiographics. 2002; 22: 1023-1039
  45. 46. Radiographics. 2002; 22: 1023-1039 Axial T2, fat-sat, fast spin echo Axial T1, in-phase, gradient echo Axial T1, arterial phase
  46. 47. Axial portal phase dynamic enhanced Coronal contrast enhanced Radiographics. 2002; 22: 1023-1039
  47. 48. Early arterial Portal venous Delayed FNH Adenoma Pre-contrast Early contrast No contrast Early contrast Portal venous Delayed Hemangioma
  48. 49. Management <ul><li>Resection </li></ul><ul><li>Tumor ablation </li></ul><ul><ul><li>Radiofrequency ablation </li></ul></ul><ul><ul><li>Chemoembolization </li></ul></ul><ul><ul><li>Percutaneous alcohol injection </li></ul></ul><ul><ul><li>Cryoablation </li></ul></ul><ul><ul><li>Microwave ablation </li></ul></ul><ul><ul><li>Laser ablation </li></ul></ul><ul><li>Liver transplant </li></ul><ul><li>Chemotherapy </li></ul>Gastroenterology. 2002; 122:1609-1619
  49. 50. Factors Influencing Treatment <ul><li>Tumor size, number and distribution </li></ul><ul><ul><li>Artery or venous proximity or invasion </li></ul></ul><ul><li>Extrahepatic metastatic disease </li></ul><ul><li>Liver function/reserve </li></ul><ul><li>Comorbid conditions </li></ul><ul><li>Local expertise and resources </li></ul>Gastroenterology. 2002; 122:1609-1619
  50. 51. Surgical Resection <ul><li>Indications </li></ul><ul><ul><li>Ability to remove all the tumor </li></ul></ul><ul><ul><li>Well compensated Child A or B cirrhosis </li></ul></ul><ul><ul><li>Non-cirrhotic with HCC </li></ul></ul><ul><li>Contraindications </li></ul><ul><ul><li>Extrahepatic metastasis </li></ul></ul><ul><ul><li>Excessive comorbid conditions </li></ul></ul><ul><li>Disadvantages </li></ul><ul><ul><li>No improvement in liver function </li></ul></ul><ul><ul><li>HCC risk remains </li></ul></ul><ul><li>Only 5-30% are candidates </li></ul>Gastroenterology. 2002; 122:1609-1619 CW Pinson, AASLD 1999, post-grad course
  51. 52. CW Pinson, AASLD 1999, post-grad course
  52. 53. CW Pinson, AASLD 1999, post-grad course
  53. 54. Chemoembolization <ul><li>Technique </li></ul><ul><li>Requires hepatic arteriogram </li></ul><ul><li>Chemo agents: doxorubicin, cisplatin, others </li></ul><ul><li>Occlusive agent: gelfoam, lipiodol </li></ul><ul><li>Extensive tumor necrosis achieved in ~80% </li></ul>Radiographics. 2002; 20:9-27 Gastroenterology. 2002; 122:1609-1619
  54. 55. Chemoembolization <ul><li>Applications </li></ul><ul><ul><li>Tumor downsizing for resection </li></ul></ul><ul><ul><li>Palliative therapy </li></ul></ul><ul><ul><li>Neoadjuvant therapy for transplant </li></ul></ul><ul><li>Contraindications: </li></ul><ul><ul><li>Diffuse tumor involvement, </li></ul></ul><ul><ul><li>Encephalopathy </li></ul></ul><ul><ul><li>Borderline liver function </li></ul></ul><ul><ul><li>Absent hepatopedal blood flow, portal vein thrombosis </li></ul></ul>
  55. 56. Complications of TACE (197 procedures) Fever 74% Abdominal pain 45% Nausea/emesis 59% Bleeding or hematoma 7% GI bleeding 3% Positive blood culture 2% Development of ascites 1% Hepatic encephalopathy 1% Variceal bleeding 1% Acalculous cholecystitis .5% Liver abscess .5% Splenic abscess .5% Cancer. 2002; 94:1747-52
  56. 57. POST- TACE PRE- TACE CW Pinson, AASLD 1999, post-grad course
  57. 58. 61 RCT 1 º treatment of HCC 26 RCT adequate control arm 14 RCT Sample size adequate 7 RCT TAE/TACE 7 RCT tamoxifen Hepatology. 2003; 37:429-442
  58. 59. Prospective RCTs of TAE/TACE # % Child A % response 1/2 yr survival Lin et al. (1988) ? TAE 21 13(70%) 42 25 TAE + IV 5-FU 21 10(48%) 20 20 IV 5-FU 21 2(10%) 13 13 Pelletier et al. (1990) ? TACE 21 7(33) 24 NA Conservative tx 21 0 33 NA Group d’etude (1995) 100 TACE 50 7(16) 62 38 Conservative tx 46 2(5) 43 26 Bruix et al. (1998) 82 TAE + coils 40 22(55) 70 49 Conservative tx 40 0 72 50 Pelletier et al. (1998 ) 76 TACE + tamoxifen 37 9(24) 51 24 Tamoxifen 36 2(5) 55 26 Lo et al. (2002) ? TACE 40 11(27) 57 31 Conservative tx 39 1(3) 31 11 Llovet et al. (2002) 70 TAE 37 16(43) 75 50 TACE 40 14(35) 82 63 Conservative tx 35 0 63 27 Hepatology. 2003; 37:429-442
  59. 60. Hepatology. 2003; 37:429-442 <ul><li>TAE improves 2-yr survival – 41% vs 27% (OR 0.53: 95% confidence interval 0.32-0.89) </li></ul><ul><li>TACE w/ cisplatin or doxorubicin better than TAE alone </li></ul><ul><li>Objective response in 35% (16-61%) </li></ul><ul><li>No survival benefit with tamoxifen </li></ul>
  60. 61. <ul><li>Technique </li></ul><ul><li>Percutaneous, laparoscopic or open </li></ul><ul><li>U/S guided probe placement </li></ul><ul><li>Thermal induced coagulation necrosis </li></ul><ul><li>Indications </li></ul><ul><li>Small unresectable tumors </li></ul><ul><li>Tumor downstaging for transplant </li></ul>Radiographics. 2002; 20:9-27 Radio-frequency Ablation
  61. 62. Radio-frequency Ablation <ul><li>Well tolerated and safe </li></ul><ul><li>Side effects </li></ul><ul><li>13% complications (14/110) </li></ul><ul><li>Ascites, hydropneumothorax, pleural effusion, fever, abdominal pain, bleeding, transient jaundice </li></ul><ul><li>Needle track seading? </li></ul><ul><li>4/32 patients all with tumors < 1cm from capsule </li></ul><ul><li>Cooled electrode tip used </li></ul><ul><ul><li>Ann Surg 2000 Sep;232(3):381-91 </li></ul></ul>
  62. 63. <ul><ul><li>Radiology. 2000; 217(3):633-46 </li></ul></ul>POST-RFA PRE-RFA
  63. 64. Liver Transplantation in HCC <ul><li>Theoretic best treatment </li></ul><ul><ul><li>Widest resection margins </li></ul></ul><ul><ul><li>Restores hepatic function </li></ul></ul><ul><ul><li>Removes remaining liver at high risk of de novo HCC formation </li></ul></ul><ul><li>Early results were poor </li></ul><ul><ul><li>3 year survival 21-47% </li></ul></ul><ul><ul><li>Recurrence rate 29-54% </li></ul></ul>Gastroenterology. 2002; 122:1609-1619
  64. 65. <ul><li>Current indications </li></ul><ul><li>Child B/C cirrhosis </li></ul><ul><li>TNM, stage I/II </li></ul><ul><li>Contraindications </li></ul><ul><li>Extrahepatic spread </li></ul><ul><li>Advanced stage </li></ul>Gastroenterology. 2002; 122:1609-1619
  65. 66. Liver Transplant for Small HCC in Patients with Cirrhosis N Engl J Med. 1996; 334(11):693-699 <ul><li>Exclusions </li></ul><ul><li>Vascular invasion </li></ul><ul><li>Extrahepatic metastasis </li></ul>48 Transplanted <ul><li>Criteria for OLTx </li></ul><ul><li>One tumor <5cm </li></ul><ul><li>3 tumors <3cm </li></ul><ul><li>bx confirmed or AFP >300 </li></ul>21 Child B 12 Child A 15 Child C F/U 26 mo (9-54mo) 26 Chemoembolization Iodized oil + Doxarubicin 14; Iodized oil +Mitoxantrone 12 No TACE
  66. 67. <ul><li>Results </li></ul><ul><li>Overall mortality 17% </li></ul><ul><li>Explanted liver examined </li></ul><ul><ul><li>Predetermined criteria met in 35 patients (73%) </li></ul></ul><ul><li>TNM status, # of tumors, AFP level, pre-OLTx TACE not correlated with survival </li></ul>N Engl J Med. 1996; 334(11):693-699 4-yr survival 75% 4-yr survival 83% 4-yr survival 85% 4-yr survival 92% Recurrence free survival > overall survival: cancer recurrence excluded at autopsy in some
  67. 68. OLT for HCC <ul><li>Regalia et al. (2001), 122 pts </li></ul><ul><ul><li>Single tumor <5, 3 tumors < 3cm </li></ul></ul><ul><ul><li>5 year survival 80% </li></ul></ul><ul><li>Yao et al. (2001), 70 pts </li></ul><ul><ul><li>25% had single tumor 5-6.5 cm or <3 tumors, all < 4.5cm w/ total diameter <8 cm </li></ul></ul><ul><ul><li>One and 5 year mortality 90% and 75% </li></ul></ul><ul><ul><li>No difference in survival in patients w/ larger tumors </li></ul></ul>Am J Surg . 2002; 183:309-316.
  68. 69. Model for End Stage Liver Disease MELD Score = (0.957 x Log e (creatinine mg/dL) + 0.378 x Log e (bilirubin mg/dL) + 1.120 x Log e (INR) + 0.643) X 10 Range 6-40 <ul><li>Superior to CTP in predicting mortality </li></ul><ul><ul><li>Elective TIPS </li></ul></ul><ul><li>Equivalent to CTP </li></ul><ul><ul><li>Acute variceal hemorrhage </li></ul></ul>www.unos.org
  69. 70. (MELD) and Allocation of Donor Livers <ul><li>3437 adult liver transplant candidates </li></ul><ul><ul><li>Listed as 2A or 2B between 11/99-12/01 </li></ul></ul><ul><ul><li>3-month mortality 412 (12%) </li></ul></ul><ul><ul><li>MELD score <9 -> 1.9% mortality </li></ul></ul><ul><ul><li>MELD score >40 -> 71.3% mortality </li></ul></ul><ul><ul><li>C-statistic (ROC) curve </li></ul></ul><ul><ul><ul><li>AUC 0.83 MELD vs. 0.76 CTP, P <0.001 </li></ul></ul></ul>Gastroenterology. 2003; 124:91-96
  70. 71. MELD Provisions for HCC <ul><li>UNOS policy 3.6.1 (2/2002) </li></ul><ul><ul><li>T1- MELD score = 15% 3 mo pre-transplant risk of death </li></ul></ul><ul><ul><li>T2- MELD score = 30% </li></ul></ul><ul><ul><li>Additional MELD points awarded Q 3mo (= to 10% increase mortality) </li></ul></ul>UNOS 2002, policy 3.6, www.unos.org
  71. 72. Hepatocellular Cancer Single tumor <5cm 3 tumors, each <3cm Consider liver transplant Resection Local ablation TACE Large tumor >5cm or More than 3 tumors Resection Local ablation techniques No treatment Longer waiting list Liver Transplant Short waiting list 3-6 months Am J Surg . 2002; 183:309-316.
  72. 73. SAMA www.sama-sd.org

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