Gastric Cancer 2014

Joshua D.I. Ellenhorn, M.D.

Gastric Cancer

•Introduction•Anatomy•Surgical approach•Lymphadenectomy•Adjuvant and neoadjuvant therapy•Minimally invasive gastric surgery

Gastric Cancer in the United States

2014

22,222 new cases

10,990 deaths

American Cancer Society

Cancer Death Rates* Among Men, US,1930-2009

Cancer Death Rates* Among Women, US,1930-2009

Gastric cancer is the second most common cause of cancer-related death in the world.

Important to Differentiate BetweenAdenocarcinoma and GIST

Small Proximal Gastric GIST Infiltrating adenocarcinoma

GIST vs Adenocarcinoma Resections EntailDifferent Considerations

GIST Adenocarcinoma

Margins • Wide margins not required • For clear margins, need a 4-cm distance from tumor

• Need 10-cm margins for diffuse-type tumors

Gastrectomy •Wedge or segmentalresection

•Distal or total gastrectomy

Lymphadenectomy •Lymphadenectomyunnecessary

• Lymphadenectomy for staging and therapeutic purposes

GIST

GIST

GIST

GIST

GIST

•Resection

•Preop Imatinib treatment for higher morbidity lesions or metastatic disease

•Adjuvant Imatinib for high risk lesions

Pathology

•95% of all malignant gastric neoplasms are adenocarcinomas

•Lauren classification• intestinal - differentiated cancer with a tendency to form glands

•Diffuse - little cell cohesion and has a predilection for extensive submucosal spread and early metastases

Risk Factors

•Helicobacter pylori - gastritis•Smoking•Previous acid reducing surgery•Genetics

•Intestinal type: - HNPCC, Li-Fraumeni•Diffuse type: - E-cadherin, Blood type A

N1 – 1-2

N2 – 3-6

N3 – 7+

Gastric Cancer Staging

Lymph nodes

Stage 0 89%

Stage IA 71%

Stage IB 57%

Stage IIA 45%

Stage IIB 33%

Stage IIIA 20%

Stage IIIB 14%

Stage IIIC 9%

Stage IV 4%

5 Year Survival

Gastric Cancer

•Introduction

•Anatomy•Surgical approach•Lymphadenectomy•Adjuvant and neoadjuvant therapy•Minimally invasive gastric surgery

Lymphadenectomy

D1 D2

Lesser omentum

Greater omentum

Gastric Cancer

•Introduction•Anatomy

•Surgical approach•Lymphadenectomy•Adjuvant and neoadjuvant therapy•Minimally invasive gastric surgery

Standard Extent of Luminal Surgical Resection

Tumor Location Type of Gastrectomy

Middle or distal Distal subtotal gastrectomy

Proximal

GE Junction

Total Gastrectomy (or proximal)

Total or proximal gastrectomydistal esophagectomy

4cm margin

Billroth I

Billroth II

Gastric Cancer

•Introduction•Anatomy•Surgical approach

•Lymphadenectomy•Adjuvant and neoadjuvant therapy•Minimally invasive gastric surgery

ResectableGastric Cancer

RANDOMIZE

D1Lymphadenectomy(n=380)

Dutch Lymphadenectomy Trial

D2Lymphadenectomy(n=331)

Bonenkamp, NEJM 340:908 1999

Hartgrink, J Clin Oncol 22:2069 2004

Hartgrink, J Clin Oncol 22:2069 2004

Dutch Lymphadenectomy Trial

Bonenkamp, NEJM 340:908 1999

Dutch Trial

D1 lymphadenectomy

D2 lymphadenectomy

4%

10%

Distal Pancreatectomy/Splenectomy

Mortality

67%

14%

ResectableGastric Cancer

RANDOMIZE

D1Lymphadenectomy(n=200)

Medical Research Council Lymphadenectomy Trial

D2Lymphadenectomy(n=200)

Cushieri A, Br J Cancer 79:1522 1999

MRC Trial

P=0.43

Cushieri A, Br J Cancer 79:1522 1999

MRC Trial

Cushieri A, Lancet 347:995 1996

D1 lymphadenectomy

D2 lymphadenectomy

6.5%

13%

Distal Pancreatectomy/Splenectomy

Mortality

65%

31%

MRC TrialSurvival with removal of spleen and pancreas

No distal panc/spleen

D2

D1

Cushieri A, Br J Cancer 79:1522 1999

ResectableGastric Cancer

RANDOMIZE

D1Lymphadenectomy(n=110)

D1 vs D3 Lymphadenectomy Trial

D3Lymphadenectomy(n=111)

Wu, Lancet Oncol. 7:309 2006

D1 – Stations 1-6D2 – Stations 7-11D3 – Stations 12-16

Wu, Lancet Oncol. 7:309 2006

D1 vs D3 Lymphadenectomy Trial

D1 lymphadenectomy

D3 lymphadenectomy

0%

0%

Distal Pancreatectomy/Splenectomy

Mortality

D1 vs D3 Lymphadenectomy Trial

Wu, Lancet Oncol 7:309 2006

13%

4%

MediastinalLN

20%

4.9%

0

148 patients

Hasegawa W J Surg 33:103, 2009

Siewert Classification

type I

type II

type III

Barbour, Ann Surg. 246:1 2007

Margin Status for GEJ

Gastric Cancer

•Introduction•Anatomy•Surgical approach•Lymphadenectomy•Adjuvant and neoadjuvant therapy•Minimally invasive gastric surgery

Resected Stage Stage IB –IVGastric CancerNo distant mets

RANDOMIZE

SurgeryN=275

Surgery+

Postop CRTN=281

Intergroup Adjuvant Chemoradiation Trial

INT 0116

Macdonald et al, N Engl J Med 345:725 2001

5FU/LV Radiation5FU/LV 5FU/LV 5FU/LV

P=0.005

Macdonald et al, N Engl J Med 345:725 2001

Intergroup Adjuvant Chemoradiation Trial

INT 0116

Stage II/IIIGastric CancerResectableNo distant mets

RANDOMIZE

Surgeryn=253

Chemo(ECF)+

Surgery+

Chemon=250

Cunningham, NEJM 355:11-20 2006

Medical Research Council Adjuvant Gastric Infusional Chemotherapy

MAGIC Trial

epirubicin (50 mg /m2) on day 1cisplatin (60 mg /m2) on day 1fluorouracil (200 mg /m2) daily for 21 days by continuous infusion

Cunningham, NEJM355:11-20 2006

3 cycles Surgery 3 cycles

Medical Research Council Adjuvant Gastric Infusional Chemotherapy

MAGIC Trial

Cunningham, NEJM 355:11-20 2006

Puli World J Gastro 14:4011 2008

EUS Accuracy

70%N stage

85%T stage

Meta-Analysis

Positive Peritoneal Cytology

Bentrem, Ann Surg Onc 12:1 2005

M1Cyt+

Positive Peritoneal Cytology

Mezhir, Ann Surg Onc 17:3173 2010

Gastrectomy in Presence of Metastatic Disease

Gold, Ann Surg Onc 14:365 2006

Gastric Cancer

•Introduction•Anatomy•Surgical approach•Lymphadenectomy•Adjuvant and neoadjuvant therapy•Minimally invasive gastric surgery

59 patientsResectable Distal cancer

RANDOMIZE

Open ResectionN=30

LaparoscopicResection

N=29

Huscher, Ann Surg 241:232-237 2005

Trial of Laparoscopic vs Open Gastrectomy

Huscher, Ann Surg 241:232-237 2005

Su

rviv

al %

Trial of Laparoscopic vs Open Gastrectomy

Distal EarlyGastric CancerT0-1

N0-1

RANDOMIZE

Laparoscopyassisted(n=82)

Opengastrectomy(n=82)

Kim, Ann Surg 248:721 2008

Laparoscopic vs Open Gastrectomy

Kim, Ann Surg 248:721 2008

•Longer operative time 252 vs. 171 minutes

•Shorter hospital stay 7.2 vs. 8.6 days

•Improved QOL

Laparoscopy

Laparoscopic vs Open Gastrectomy

Author Year Lap Open Adequacy of Resection

Results for Lap Group

Survival

Kitano 2002 14* 14 Identical Less EBL and pain, earlier recovery of bowel function

Na

Hayashi 2005 14* 14 Equally radical Shorter epidual use Na

Lee 2005 24* 23 No significant difference

Fewer pulmonary complications

No difference at 14 months

Huscher 2005 30 29 No significant difference

No difference No difference at 5 years

Kim 2008 82* 82 na Less EBL and pain medicine, shorter hospital stay, Improved QOL

na

Kim 2010 179* 161 na No difference in morbidity or mortality

na

Cai 2011 61* 62 No difference Less pulmonary infection No difference at 2 years

Laparoscopic not lap-assisted

Our patients are different

Stage Ia

Stage IIIb

Laparoscopic(n=30)

Open(n=48)

p

Surgery time (minutes), median (range) 390 (225-509) 298 <0.0001

Estimated blood loss, median (range) 200 (50-900) 382 0.0050

Length of stay (days), median (range) 7 (3-39) 10 (3-67) 0.0009

Mortality, N (%) 0 (0) 1 (2) 0.4863

Conversion 0 -

Complications, N (%) 9 (28) 22 (46) 0.4863

Guzman and Ellenhorn, Ann Surg Onc 2009

Nonrandomized Study of Laparoscopic vs. Open

Gastrectomy

Laparoscopic(n=30)

Open(n=48)

p

Negative margin 32(100) 47(98) NS

Closest margin, mean 3.77 3.6 NS

Number of lymph nodes, mean 26 26 NS

Guzman and Ellenhorn, Ann Surg Onc 2009

Nonrandomized Study of Laparoscopic vs. Open

Gastrectomy

OrVilTM Stapler

Factor Median ± SD Range N (%)

Age (yrs) 62.0 ± 17 19 – 83

BMI (kg/m2) at surgery 24.9 ± 12.8 16.4-69.5

Histology Gastric adenocarcinoma Other*

14(87.5%)2 (12.5%)

Tumor size (cm) 7.2 ± 5.7 0.0 – 22.0

Operative Time (hrs) Gastrectomy only Multi-organ resection

6.3 ± 1.48.2 ± 0

2.8 - 7.48.2

Complications Esophageal leak Esophageal stricture Delayed emptying Others None

0 (0%)

3(18.8%) 0 (0%) 4 (25%)

10(68.8%)

LOS (days) 8 ± 3.7 5 - 20

Laparoscopic Total GastrectomyFirst 16 Patients

Kachikwu and Ellenhorn, J Gastoint Surg 2011

   Age Median (range) 67 (35-96)

Gender Male 28

  Female 37

Neoadjuvant Therapy   7

Laparoscopic Gastrectomy in 65 patients

Type of Surgery Performed

Laparoscopic proximal gastrectomy 5

Laparoscopic distal gastrectomy 41

Laparoscopic total gastrectomy 19

Median Number of Lymph Nodes Retrieved

27

Median Length of Stay 7 days

Laparoscopic Gastrectomy in 65 patients

Stage I and II Gastric Cancer Survival

COH Laparoscopic Gastrectomy Series

3-year Disease-Free Survival: 68.4%

Symptom Scoring Scale:• 1: Not at All• 2: A Little • 3: Quite a Bit• 4: Very Much

Quality of Life Analysis After Laparoscopic Gastrectomy

EORTC QLQ STO-22

Global QOL at 6 months = 1.47 mean

No difference in QOL with < or > 70% gastrectomy

28 patients

Ellenhorn 2014

Conclusions

•D2 lymphadenectomy with splenic preservation should be standard

•Locally advanced gastric cancer is well suited for neoadjuvant and postoperative chemotherapy or postoperative chemoradiation

•Staging laparoscopy with peritoneal washing

•Adequate resection can be performed using a minimally invasive approach and BII for distal gastrectomy.