1. P ETER J. D I P ASCO, MD A SSISTANT P ROFESSOR OF S URGERY D EPARTMENT OF S URGERY – S ECTION OF S URGICAL O NCOLOGY T HE U NIVERSITY OF K ANSAS M EDICAL C ENTER F RIDAY, APRIL 4 TH, 2014 ACOS G ENERAL S URGERY I N -D EPTH R EVIEW Diagnosis & Surgical Management of Gastric Malignancies

2. Disclosure I have no disclosures

3. Epidemiology Third leading cause of cancer death worldwide Overall declining  Endemic areas persist  Refrigeration Histologic pattern is shifting from predominantly intestinal type (distal) to diffuse type (proximal / cardia)

4. Factors Increasing or Decreasing Gastric CA Increase risk Family history Diet (high in nitrates, salt, fat) Familial polyposis Gastric adenomas Hereditary nonpolyposis colorectal cancer Helicobacter pylori infection Atrophic gastritis, intestinal metaplasia, dysplasia Previous gastrectomy or gastrojejunostomy (>10 y ago) Tobacco use Ménétrier’s disease Decrease risk Aspirin Diet (high fresh fruit and vegetable intake) Vitamin C

5. Gastric Cancer Work-up/Staging  Standard  CT chest, abdomen/pelvis  PET-CT  Endoscopic Ultrasound  Controversial  Laparoscopy Peritoneal washing

6. Gastric Cancer – Surgical Controversies Resection Margins Extent of Lymphadenectomy Role of Sentinel Lymph Node Biopsy Minimally-Invasive Resection  Endoscopic Mucosal Resection (EMR)  Laparoscopic Resection

7. Surgical Margins Total vs. Subtotal Gastrectomy?  Goals  Oncologically-Sound Resection 5 - 6 cm gross margins ideal minimal 2-3 cm margins En-bloc resection if necessary partial pancreas, partial colon, spleen, etc.  Low Morbidity Avoid (if possible): total gastrectomy injury to the distal common bile duct

8. Surgical Margins Subtotal vs. Total Gastrectomy?  Factors Influencing Operation  Extent of disease  Histological type Diffuse – total gastrectomy Intestinal – potentially subtotal gastrectomy  Location (for intestinal type) Lower – subtotal gastrectomy Mid – near-total gastrectomy Upper – total gastrectomy < 2 cm of GE junction- Esophagogastrectomy

9. D1 vs. D2 Resection – Where do we stand? Definitions Theoretical Considerations Review of Clinical Trials Controversy  Japanese vs. Western Data Proposed Approaches  Conventional  Utilizing the Maruyama Index

10. Lymph Node Stations (Japanese)

11. Synopsis of Definitions - D1 vs. D2 D1 Lymphadenectomy  Lymph nodes directly adjacent gastric wall  1 & 2 – paracardial  3 & 4 – lesser and greater curvature  5 & 6 – peri-pyloric

12. Synopsis of Definitions – D1 vs. D2 D2 Lymphadenectomy (“Radical Lymphadenectomy”)  Additional tissue (en bloc):  Greater and lesser omentum  Superior leaf of mesocolon  Pancreatic capsule  Lymph nodes:  Infra/supraduodenal areas  Hepatic and common hepatic arteries  Celiac artery  Splenic artery  Organs  Distal pancreatectomy (station 11 lymph nodes)  Splenectomy (station 10 lymph nodes

13. Radical Lymphadenectomy (D2) Theoretical Considerations Pros  More Accurate Staging (Prognostic Information)  Lymph node status likely to influence adjuvant therapy  Better Locoregional Control  More extensive surgery  Removes occult nodal disease  Improved Survival  Retrospective Japanese data  No Excess Morbidity/Mortality  Japanese experience

14. Radical Lymphadenectomy (D2) Theoretical Considerations Cons  Advanced disease not amenable to more radical locoregional surgery  No “true” survival advantage  Survival advantage of radical surgery merely an artifact of more accurate staging by nodal clearance “Stage migration”  Western data does not support Japanese experience  Excess morbidity/mortality/cost  Western data

17. Minimally Invasive Resection Types  Laparoscopic  Intraperitoneal wedge resection distal gastrectomy  Intragastric  Endoscopic Mucosal Resection (EMR) Indication  Intramucosal lesion  Low-risk of lymph node involvement

18. Endoscopic Mucosal Resection Selection Criteria  Histology/Differentiation  Well and/or moderately differentiated adenocarcinoma  Or papillary adenocarcinoma  Confined to the mucosa  Without evidence of venous or lymphatic involvement  Size  Less than 2 cm if type IIA (superficially elevated)  Less than 1 cm if type IIB or IIC (superficially depressed)  Ulcer status  None grossly on endoscopy  None microscopically  No clinical evidence of lymph node involvement

19. Chemoradiation Therapy Adjuvant Chemoradiation Therapy  Landmark Intergroup 0116 Trial  556 randomized patients Vs. Surgery Alone  5-FU based regimen with concurrent XRT  Improvement: Locoregional recurrence Median survival Overall survival  Standard of care for stage IB and higher

20. Chemoradiation Therapy Neoadjuvant Chemotherapy  MAGIC Trial  503 randomized patients Vs. Surgery Alone  epirubicin, cisplatin, continuous 5-FU  Stage II or greater non-metastatic disease  Post-op chemotherapy  Improvements: Progression-free survival Overall survival Neoadjuvant chemoradiation Therapy  Ongoing Studies  Currently useful in borderline resectable patients

21. Summary Performance of oncologically-sound, low-morbid gastric resection & reconstruction  Avoid total gastrectomy and achieve microscopic (-) margins  Future Trends (early cancer)  Minimally-invasive resections  Endoscopic mucosal resections Role of “radical lymph node dissection” (D2) still controversial in Western countries  Avoid splenectomy and/or pancreatectomy  Future trends  Use of Maruyama Index (MI) Role for palliative resection for symptomatic patients Important role for chemotherapy and radiation therapy

22. CASE REPORT 58M recently admitted to OSH for abd pain and early satiety. Other complaints include post prandial pain in mid-epigastrium and a feeling of food getting stuck. EGD showed proximal gastric cancer. Diagnostic Tests? Imaging? Staging? Surgical Plan?