reviewed the literature ;Multidisciplinary management of gastric cancer Yixing Jianga and Jaffer A. Ajani ; pictures taken from Sabiston textbook of surgery.

1. Review of management of gastric
cancer
Odei-Ansong Francis.

2. Overview
• Introduction
• Aetiological factors
• Pathology
• Clinical features
• Investigations
• Treatment modalities
• Conclusion

3. Introduction
• Common since the 80s, now surpassed by lung cancers
worldwide.
• Worldwide incidence contributed mostly by Japan/ Parts of
south America.
• 10th most common in US with ised incidence in the black pop.
• Risk increases with increasing age.
• Risk decreases amongst migrant pop from endemic areas
(Japan--US).
• Site of tumor now showing a shift from distal to proximal and
also an increase in incidence in whites(smoking, alc, ? H pylori
eradic.)

4. Aetiological factors
 Nutritional  Social
• Low fat or protein • Low social class
consumption  Medical
• Salted meat or fish • Prior gastric surgery
• High nitrate consumption • Helicobacter pylori infection
• High complex-carbohydrate • Gastric atrophy and gastritis
consumption • Adenomatous polyps
 Environmental • Male gender
 Medical
• Poor food preparation
(smoked, salted) • Prior gastric surgery
• Lack of refrigeration • Helicobacter pylori infection
• Gastric atrophy and gastritis
• Poor drinking water (well
water) • Adenomatous polyps
• Male gender
• Smoking

5. Pathology
Mostly adenocarcinoma (95%)
Others; squamous cell ca, adenoacanthoma , carcinoid tumors,GISTs, and lymphoma.
Adenocarcinoma can be diffuse or intestinal
Intestinal Diffuse
Environmental Familial
Gastric atrophy, , intestinal metaplasia Blood type A
Men > women Women > men
Increasing incidence with age Younger age group
Gland formation Poorly differentiated, signet ring cells
Hematogenous spread Transmural/lymphatic spread
Microsatellite instability Decreased E-cadherin
APC gene mutations
p53, p16 inactivation p53, p16 inactivation p53,

6. Pathology
• WHO of classification ;
gastric cancer is divided into five main categories: adenocarcinoma,
adenosquamous cell carcinoma, squamous cell carcinoma
,undifferentiated carcinoma, and unclassified carcinoma
Adenocarcinomas further subdivided into four types according to
their growth pattern:papillary, tubular, mucinous, and signet ring
• Borders in 1942 classified gastric carcinomas
according to the degree of cellular differentiation,
from 1 (well differentiated) to 4 (anaplastic)

7. Pathology
The Borrmann classification system developed in 1926

8. Clinical features
• Early stages are asymptomatic
• Most Px are seem in advanced stage and
symptomatic .
• Symptoms related to the location of the tumor.
• Symptoms include:-abdominal discomfort/pain;
-anorexia +/- nausea;
-weight loss;
-vomiting (pyloric lesions);
-dysphagia (lesions of cardia);
-hematemesis/ melaena

9. Clinical features
• Physical signs develop late and associated with
locally advanced or metastatic disease.
• Palpable abdominal mass, supraclavicular (Virchow’s)
or periumbilical (Sister Mary Joseph’s) lymph node,
• Rectal examination (Blumer’s shelf), or ovarian mass
(Krukenberg’s tumor).
• Hepatomegaly , jaundice, ascites, and cachexia.

10. Investigations
Diagnostic investigations Staging investigations
• Double contrast barium • LFT,
meal • EUS,
• Endoscopy + biopsy • CT scan(abdomen⁺/₋
• Endoscopy + biopsy + pelvic)
Brush cytology • CXR
General investigations
• Laparoscopy, peritoneal
• FBC cytology
• BUE& Cr, FBS • Abdominal ultrasound
• ECG etc.

11. Staging anatomy

12. Treatment modalities
• Surgery
• Chemotherapy
• Radiation
• Endoscopic dilatation and stent placement.
• Laser recanalization.

13. Surgery -review
• Traditionally been the main standard of
treatment.
• Associated with a high level of recurence
• Aimed at resection margin of 5-6cm from
macroscopic site
• Goal ; removal of the primary tumor with any direct
extension
removal of the nodal basins at risk for metastasis

14. Surgery –review(proximal tumors)
 Total vrs Proximal gastrectomy.
• Many studies advocates total gastrectomy
• Reasons;
most proximal tumours present advanced
LN dissection difficult (around pylorus)
↑ dumping, heartburn, and reduced appetite*
anastomatic stricture, local recurrence**
hypergastrinoma

15. Surgery –review(proximal tumors)
• Yoo et al. Analysis of local recurrence following proximal gastrectomy in patients
with upper third gastric cancer. Cancer Res Treat 2002;34:247-251
• revealed that the risk factors for local
recurrence following proximal gastrectomy
were diffuse type tumor, greater than 5cm in
tumor size, and serosal invasion
• Advocated for a comprehensive research on
the importance of proximal gastrectomy for
advanced ca.

16. Surgery –review(proximal tumors)
• although we can save distal stomach by performing
proximal gastrectomy for the upper third gastric
cancer, it should be considered only in early gastric
cancer because of the insufficient regional lymph
node dissection, relatively high postoperative
complication rate.
• Editorial review by Han-Kwang Yang,Issues in the Management of
the Upper Third Gastric Cancer,Cancer Research and Treatment 2004

17. Surgery –review(proximal tumors)
• Ji Yeong An et al, The American Journal of SurgeryVol 196, Issue 4 , Pg
587-591, Oct 2008
- 423 patients who underwent total or proximal gastrectomy for early gastric cancer in the upper
third of the stomach.
• Post operative complication rate
-total gastrectomy 12.6%
-proximal gastrectomy 61.8%, was significant (P < .001)
• Anastomotic stenosis and reflux esophagitis
-total gastrectomy 6.9% and 1.8%
-proximal gastrectomy 38.2% and 29.2%
• Conclusion;
that proximal gastrectomy is not a better option for upper-third early gastric cancer
than total gastrectomy

18. Surgery –review(proximal tumors)

19. Surgery –review(LN dissection)
• Reviewed by Dr Nsoh (International Society of Gastrointestinal Oncology annual meeting.
Abstract 0945. Presented October 3, 2009.)
• East favours a more extensive node dissection
• West favours a limited node dissection
• The east has more gastric surgical experience as
the dx is prevalent there
• best approach is determined by tumor, patient,
and treatment factors,
• Pxs in the east are more likely to be healthier as
they are seen earlier.

20. D2 vs D1 Lymph Node Dissection
• Dutch trial, from 1989 to 1993(N Engl J Med. 1999;340:908-
914)
 331 patients underwent D2 lymph node dissection ;43% complication rate
and a 10% postoperative mortality rate
• A study at Yonsei University in South Korea in
2002
 646 patients who underwent a D2 dissection ;17.6% complication rate
and a 0.6% postoperative mortality rate
D2 lymph node dissection favored by surgeons in the East is
Conclusion; supported by a number of factors; surgery performed safely,
better local control and thus accurate pathologic staging,
the West favors D1 lymph node dissection; They lack evidence to
support the superiority of D2 over D1 surgery.D2 has high
postoperative morbidity and mortality in Western trials.

21. Chemotherapy

22. INT-0116
Adjuvant therapy(varied results)
5fu/LV, 45Gy radiotherapy
• 603 patients randomized to either observation or combined modality therapy
after surgery.
• median follow-up of 5 years,
• 3 year relapse-free survival rates (48 vs. 31%, P<0.001)
• OS rates (50 vs. 41%,P¼0.005), median OS (36 vs. 27, P¼0.0005)
Sakuramoto S et al. N Engl J Med 2007
• A total of 1059 patients with advanced ca.
• Were randomized to either observation or 1-year oral S-1 adjuvant therapy. S-
1
• The 3-year OS was improved in the S-1 group (80.1% in S-1 group vs. 70.1% in
the observation group, P¼0.003).
• Disappointing results showed when same research was
changed b/n the west/ east.

23. • More than 30 trials comparing adjuvant
chemotherapy to surgery alone showed varied
results
• Reasons being different tumor biology.
• 5-FU/LV remains the standard care in the
United States
• CALGB 80101

24. Perioperative chemotherapy
Phase III UK MAGIC trial Cunningham D,N Engl J Med 2006
• 503 patients with resectable gastric cancer
• randomized to receive surgery with neoadjuvant ECF or surgery
alone.
• The neoadjuvant group demonstrated a significantly better OS
(hazard ratio¼
• 0.75, 95% CI 0.60–0.93, P¼0.009, 5-year survival rate of 36 vs. 23%)
and progression free survival (hazard ratio¼ 0.66, 95% CI 0.53–0.81,
P<0.001).
 Shortfalls;
• nonstandardized surgery,inaccurate preoperative staging
because of the absence of laparoscopy,

25. Preoperative chemoradiation
most of the studies have number of patients.
• Advantages
• May downstage the tumor and potentially
increase the rate of resectability
• may sterilize the operative field and thereby
reduce the risk of tumor seeding.
• may eliminate micrometastasis without delay.
• also allows better radiation field design.
More research needed to validate its importance.

26. Preoperative chemoradiation
Ajani et al.J Clin Oncol 2005
• treated 40 patients 5-FU, paclitaxel and cisplatin, radiotherapy
• Followed by surgery in 40 patients.
• The study showed a pathologic complete response rate (RR) of 20%, R0
resection rate of 78%, and median survival beyond 36 months
• A meta-analysis of 4 randomized trials also
indicated a survival benefit with preoperative
radiotherapy, compared with surgery alone
Fiorica F et al Cancer Treat Rev 2007

27. Therapy for metastatic disease
• Single active agents have included 5-FU, cisplatin,
mitomycin C, doxorubicin, epirubicin, and etoposide
 RRs(response rate) vary from 10 to 20% [38–43].
Cullinan SA, et al. JAMA 1985
Barone C, et al.two parallel randomized phase II
studies. Cancer 1998;
• 4 trials showing improved survival of 4-8 months with
combined chemotherapy
 Small studies
 QOL reported to be better
Scheithauer et al. 1995 ELF vs. BSC
Pyrhonen et al. 1995 FEMTX vs. BSC
Glimelius et al. 1997 ELF vs. BSC
Murad et al. 1999 FAMTX vs. BSC

28. Outcomes From Phase III Trials
Response Rate Median Survival
FAM 25-40% 6.9 months
FAMTX 20-30% 7.7 months
EAP 20% 6.1 months
ELF 21% 7.0 months
ECF 45% 8.9 months
Mayer ASCO 2005

29. Therapy for metastatic disease
• Conclusion; trials have showed that
chemotherapy is better than best supportive ,
combination chemotherapy with doublet is
superior than single agent, and the best
survival is achieved with three agents at the
cost of more toxicities

30. Newer Drugs.
• bevacizumab, cetuximab and trastuzumab
• Phase III Trastuzumab( for Gastric Cancer trial at the 2009 American Society of
Clinical Ontology (ASCO))
• A total of 594 patients with Her2/Neu positive
• randomized to receive either chemotherapy (cisplatin
and capecitabine or 5FU) with trastuzumab or
chemotherapy alone
• The median OS was significantly improved with the
addition of trastuzumab(13.5 vs. 11.1 months,
respectively) J Clin Oncol 2009; 27:18s

31. Newer drugs . 2nd agent
• Kang et al, At the 2010 ASCO annual meeting,
• Presented the Study of Bevacizumabin With Capecitabine and Cisplatin as
First-line Therapy in Patients With Advanced Gastric Cancer (AVAGAST);
• a total of 774 patients received chemotherapy with placebo or with
bevacizumab
• progression-free survival is significantly longer in the bevacizumab arm(6.7
months in bevacizumab arm vs. 5.3 months in the placebo arm
• The overall RR was increased from 29.5 to 38% (P¼0.012) with the
addition of bevacizumab.
J Clin Oncol 2010; 28:18s

32. Conclusion
• The challenges associated with the
management of gastric cancer has been
evolving.
• A multidisciplinary approach is required for
the management.
• Recent introduction of newer agent has been
promising yet the prognosis still remains poor.