Stomach cancer presentation with specific interest in staging of cancer and stage specific different surgical options

1. Staging and Surgery for Gastric
Carcinoma
Presentation by: Dr Happy Kagathara
20th
October, 2012
Department of Surgical Gastroenterology and Liver Transplantation
Sir Ganga Ram Hospital, New Delhi

2. Staging Evaluation
• Once the diagnosis is established, further studies are directed
at staging to assist with therapeutic decisions
• EUS and CT are primary staging modalities

3. Staging Evaluation
• EUS
– T staging - number of visceral wall layers that are disrupted
– N staging - presence and location of peri-visceral lymph nodes
or detection of malignant cells by EUS guided trans-visceral
FNA
– Less useful for M staging, due to limited depth of penetration
– However, with low frequency newer echo-endoscopes, much of
the liver can be surveyed and sampled from the stomach and
duodenum.
Roesch T. Gastrointest Endosc Clin N Am 2005;15:13-31

4. Staging Evaluation
– Accuracy for T staging - 64%
Bhandari S et al. Gastrointest Endosc 2004;59:619-26
– Sensitivity for N staging – 70 to 100%
EUS image of T1 cancer. Thick dark arrow
demonstrates mucosal tumor invading the broad white
layer of hyperechoic submucosa (white arrow) but not
disrupting the dark layer (hypoechoic) of the muscularis
propria (thin dark arrow)

5. • CT scan
– Useful in identifying distant metastases, especially in the liver
– Accuracy for T staging - 64%
Paramo JC et al. Ann Surg Oncol1999;6:379-84
– Sensitivity for N staging – 24 to 43%
Davies J et al. Gut 1997;41:314-9
CT demonstrates T4 gastric carcinoma of proximal body
with extension into perigastric fat and involvement of
splenic artery

6. Staging Evaluation
• MRI
– When CT iodinated contrast is contraindicated
– For T staging, MR is comparable or minimally superior to CT
Sohn KM et al. AJR Am J Roentgenol 2000;174:1551-7
– Improvement in detection of metastatic disease compared with
CT, when the contrast Ferumoxtran-10 is used (sensitivity
100%)
Coburn NG. J Surg Oncol 2009;99(4):199–206
Motohara T, Semelka RC. Abdom Imaging 2002;27(4):376–83

7. Staging Evaluation
• PET
– Useful in staging, recurrence detection and measuring therapy
response
– Detect node metastases before nodes are enlarged on CT
– Sensitivity for nodal staging – 23 to 73%
Yoshioka T et al. J Nucl Med 2003;44:690-9
– Limitations
• False +ve results from infectious or inflammatory processes
• Lower sensitivity for small lesions

8. Staging Evaluation
– High FDG uptake
• Associated with greater depth of invasion, size of tumor and
lymph node metastases
• Significantly lower survival rate
Mochiki E et al. World J Surg 2004;28:247-53
– Combined PET and CT (PET/CT)
• Recently introduced
• Perform both a PET and CT scan in the same session and
fuse the images.
• Excellent contrast resolution of PET
• Excellent spatial resolution of CT.
• Improved accuracy of PET/CT compared with PET alone
Antoch G et al. J Clin Oncol 2004 1;22:4357-68

9. Staging Evaluation
• Laparoscopy
– In 1985, report by Shandall and Johnson
• Detection of metastatic disease to the liver or peritoneum
• Sensitivity - 100%, specificity - 84%
• Avoidance of laparotomies - 29% of pts
– Now nodal staging is possible with laparoscopic ultrasound
– NCCN recommend laparoscoy in loco-regional gastric cancer
(M0) to guide further management
Jaffer A et al. http://www.nccn.org, v.1.2006

10. Staging Evaluation
– Implications
• In resectable pts for staging
• In unresectable pts – determination of benefits of combined
chemo-radiation (radiation may not be appropriate in
metastatic disease)
Jaffer A et al. http://www.nccn.org, v.1.2006
• Staging before entry into neo-adjuvant trials
D’Ugo DM et al. J Am Coll Surg 2003;196:965-74
– Not necessary in T1 or T2 lesions given the low incidence of
metastases
– Not indicated in the pre-op evaluation of gastric remnant
cancers, since they do not tend to develop peritonea metastasis.

12. Staging
• 2 major staging systems for gastric carcinoma
– American Joint Committee on Cancer classification
– Japanese Classification of Gastric Carcinoma
• Japanese classification uses T and M staging similar to the
AJCC system
• Nodal staging is significantly different
– The Japanese classification focuses on
• Anatomic location of the nodes, which are designated by
stations

13. Staging
– AJCC classification
• T stage based on depth of tumor (not size)
• Changes in the 7th edition of AJCC classification
– E-G junction tumors or tumors in the cardia <5cm from
E-G junction extending into E-G junction
• Staged using the TNM staging for esophageal cancer
Rüdiger et al. Ann Surg 2000; 232-353
– Tumors <5cm from E-G junction that don’t extend into
esophagus
• staged as gastric cancers

14. Staging
– In 1997, nodal classification changed from using the
location of the involved lymph nodes to the number of
lymph nodes (pN1, 1–6 nodes; pN2, 7–15 nodes; pN3,
>15 nodes)
– This requires a minimum of 15 nodes in the resection
specimen
– Avrg no. of nodes evaluated - 10, only 30% of pts have
at least 15 nodes evaluated
Coburn NG et al. Cancer 2006;107(9): 2143–51.
Schwarz RE, Smith DD. Ann Surg Oncol 2007;14(2):317–28.
Smith DD, Schwarz RR, Schwarz RE. J Clin Oncol 2005;23(28):7114–24

15. Staging
– Because of inadequate nodal evaluation
• In the 7th
edition of the AJCC classification, a
minimum of 7 nodes are required (pN1, 1–2 nodes;
pN2, 3–6 nodes; pN3, _7 nodes)
• Comparison of survival
– Using 6th
and 7th
edition in same population of pts
– Stage stratified survival difference
– This has implications for interpretation and comparison
of outcomes from studies that use 6th
vs 7th
edition
Warneke VS et al. J Clin Oncol 2011; 29: 2364

16. Staging
• Recent studies propose examining the metastatic lymph node
ratio (MLR)
– Ratio between metastatic nodes and total evaluated nodes
– More valuable in inadequate node evaluation
– Strongest negative prognostic factors for survival on
multivariate analyses
Persiani R et al. Eur J Surg Oncol 2008;34(5):519–24
Lee SY et al. Int J Oncol 2010;36(6):1461–7.
Sianesi M et al. J Gastrointest Surg 2010;14(4):614–9.

20. Surgery
• Best chance for long-term survival - complete surgical
eradication of a tumor with resection of adjacent nodes
• 6 factors determine the extent of gastric resection
– Tumor stage
– Tumor histology or type
– Tumor location
– Nodal drainage
– Peri-operative morbidity
– Long-term gastro-intestinal function

21. Surgery
• Indications for unresectability
– Distant metastases
– Invasion of a major vascular structure such as the aorta
– Encasement or occlusion of the hepatic artery or celiac
axis/proximal splenic artery
– Nodes behind or inferior to the pancreas, aorto-caval region, into
the mediastinum, or in the porta hepatis
• Distal splenic artery involvement is not an indicator of
unresectability

22. • Surgery based on tumor location
– Bulky tumor fixed to the pancreatic head
• High risk for occult metastatic disease
• Consider staging laparoscopy or neo-adjuvant chemotherapy
• Might require Whipple’s procedure

23. – Gastric cancers within the proximal stomach
• Worse prognosis
• Harrison conducted retrospective study
– 391 pts
– To determine whether the type of operation (TG vs PSG)
affects outcome
– Excluded pts who underwent esophago-gastrectomy
– No significant difference in the 5-year survival (41 vs
43%)
– Conclusion
• PSG with adequate –ve margins is oncologically
acceptable
Harrison LE et al. Surgery 1998;123(2):127–30

24. • TG is preferred by some surgeons because
– Extremely low incidence of reflux esophagitis
• Roux-en-Y reconstruction performed during TG
compared to PSG
Buhl K et al. Eur J Surg Oncol 1990; 16:404

25. – Gastric cancers within the distal stomach
• Bozzetti conducted randomized trial
– 618 pts
– Evaluation of impact of SG vs TG on the oncologic
outcome
– Conclusion
• Both procedures have a similar survival probability
• SG associated with a better nutritional status and
quality of life provided that the proximal margin falls
in healthy tissue
Bozzetti F et al. Ann Surg 1999; 230:170

26. • Gouzi conducted multi-centric post-operative controlled trial
– 169 pts
– Postoperative mortality and the 5-year survival were
compared for adenocarcinoma of antrum
– Conclusion
• TG - overall complication - 32 %, peri-operative
mortality rates - 1.3%
• SG – overall complication - 34% , peri-operative
mortality rates - 3.2%
• No difference in the 5-year survival rate (48%)
Gouzi JL et al. Ann Surg 1989; 209:162

27. – Mid-gastric lesions or infiltrative disease (linitis plastica)
• Nodal involvement is frequent
• May require TG for complete excision

28. • Extended resection for T4 disease
– Multi-organ resections - frequently indicated in T4 disease
– Assessment of adjacent organ invasion by preoperative CT or
intra-operative assessment is unreliable
– Series by Sandler
• 21 pts undergoing multi-organ resections
• only 8 (38%) had pathologically confirmed T4 disease
• Preoperative CT is inaccurate in assessing T4 lesions, with a
positive predictive value of only 50%
Sandler RS et al. Dig Dis Sci 1984;29:703-8

29. – Recent studies suggest that 5-year survival rates may be as low
as 16%
Kunisaki C et al. J Am Coll Surg 2006;202:223-30
– Regardless, it can be performed with little increased morbidity
with the expectation that long-term survival is possible in
approximately one third of patients with RO resections.

30. • Extent of nodal dissection
– Lymph node involvement - most important independent
prognostic factors
– Japanese first reported cohort studies - disease-free and overall
survival is increased with radical lymphadenectomies
Inada T et al. Anticancer Res 2002;22:291-4.
– Appropriate extent of nodal dissection - most controversial area
in gastric cancer management

31. – D1 lymphadenectomy
• Conservative node dissection
• Dissection of only the peri-gastric nodes. (stations 1-6)
– D2 lymphadenectomy
• Extended node dissection
• D1 + Removal of nodes along the hepatic, left gastric, celiac,
splenic arteries, those in the splenic hilum (stations 1-11)
– D3 dissection
• Super-extended lymphadenectomy.
• D2 + Removal of nodes within the porta hepatis, root of
mesentery regions (stations 1-16)
– D4 dissection
• D3 plus removal of para-aortic and paracolic lymph nodes

32. – Extended lymphadenectomy (D2 to D4)
• Performed by most of Japanese surgeons
• Removal of larger number of nodes
– Greater the probability of positive nodes
– More accurately stages disease extent
– Minimize stage migration (the “Okie phenomenon”,
described by Will Rodgers)
– Explain better survival results in Asian patients
Bunt AM et al. J Clin Oncol 1995; 13:19.37
de Manzoni G et al. Br J Cancer 2002; 87:171

33. – Two main arguments against the routine use of an extended
lymphadenectomy
• Higher morbidity and mortality
• Lack of a survival benefit in most large randomized trials
– Medical Research Council (MRC) trial
• Prospective randomized trial
• 400 pts undergoing curative resection to D1 or D2
lymphadenectomy
• Coclusion
– Postoperative morbidity was significantly greater in the
D2 group - 46 vs28%, operative mortality - 13 vs 6%
– Due to splenectomy and distal pancreatectomy to achieve
complete node dissection
Cuschieri A et al. Lancet 1996; 347:995

34. – Japan Clinical Oncology Group (JCOG) trial
• Multicenter randomized trial
• 523 pts randomaly assigned to D2 vs D3
• Conclusion
– Perioperative complication rate in the D3 - significantly
higher (28.1 vs 20.9 %)
– No differences in major complications
Sano T et al. J Clin Oncol 2004; 22:2767

35. • Reconstruction following TG
– Most common option
• E-S esophago-jejunostomy with distal drainage of the
duodenum by Roux-en-Y entero-enterostomy
– Meta-analysis by Gertler
• Review from 13 randomized control trials
• Assessed the value of jejunal S-pouch formation as a gastric
substitute after TG.
• Conclusion
– Pouch creation can be done safely without increased
morbidity or mortality without significantly increasing
the operative time or LOS. QOL was significantly better
in pts with pouch reconstruction
Gertler R et al. Am J Gastroenterol 2009; 104(11):2838–51

36. • Advanced procedures
– Laparoscopic resection
• Meta-analysis of 5 randomized trials and18 non-randomized
comparisons of laparoscopic versus open gastrectomy came
to following conclusions
– Mean number of lymph nodes retrieved by laparoscopic
surgery was close to that retrieved by open procedure
– Conversion rate – 0 – 3%
– Significantly less postoperative morbidity after a
laparoscopic procedure
– No difference in long term survival

37. • In the revised Japanese Gastric Cancer Treatment Guidelines
– Laparoscopy-assisted gastrectomy -eligible for stage IA
and IB cancers.
Kodera Y et al. J Am Coll Surg 2010; 211(5):677–86
• Laparoscopic gastrectomy with D2 lymphadenectomy
– Performed safely
– Less blood loss
– Lengthier operative times
Tanimura S et al. Surg Endosc 2008; 22(5):1161–4.
Kawamura H et al. World J Surg 2008;32(11):2366–70

41. – Robot assisted surgery (RAS)
• Advantages
– Provides articulated movement
– Eliminates physiologic tremor
– Steady camera platform allows more precise instrument
movement and dissections
Song J et al. Ann Surg 2009;249(6):927–32
• Series by Song
– 100 pts with early gastric cancer
– Robot-assisted gastrectomy, using the da Vinci Surgical
System
– TG – 33, SG – 67 (with D1 dissection)

42. – Operation time - 231 minutes
– Average LOS - 7.8 days
– Mean number of lymph nodes recovered - 36.7
– No mortality
Song J et al. Ann Surg 2009;249(6):927–32

43. • Palliative surgery
– Intention
• To relieve pain and suffering without increasing morbidity or
mortality
– Numerous palliative procedures
• Gastro-enterostomy (enteric bypass)
• Partial gastrectomy
• Total gastrectomy
• Esophago-gastrectomy
• Gastrostomy
– Gastric resection, endoscopic techniques (laser argon ablation,
epinephrine injection) and arterial embolization – acute
refractory hemorrhage

44. – Role for palliative total gastrectomy
• 59% felt improved their QOL
Monson JR et al. Cancer 1991;68:1863-8
– Role of palliative bypass procedures
• Palliation – infrequent
• 19% felt they benefited
ReMine WH. World J Surg 1979;3:721-9
• Peri-operative mortality – high
• Gastrostomy and jejunostomy - little role in gastric cancer
– Gastrostomy tube - benefit when frequent naso-gastric
suction for gastric outlet obstruction
– Jejunostomy - for nutritional supplementation

45. Summary
• EUS and CT are primary staging modalities
• PET useful in staging, recurrence detection and measuring therapy
response
• Laparoscoy useful in loco-regional gastric cancer (M0) to guide
further management
• Japanese classification focuses on anatomic location of the
nodes(designated by stations)
• In AJCC classification nodal stage is based on number of involved
nodes
• Proximal gastric cancers – TG preferred because of less incidence
complication

46. Summary
• Distal gastric tumors – SG preferred
• Assessment of adjacent organ invasion by preoperative CT or intra-
operative assessment is unreliable
• Extended lymphadenectomy (D2 to D4)
• More accurately stages disease extent
• Explain better survival results in Asian patients
• Higher morbidity and mortality
• Lack of a survival benefit in most large randomized trials
• QOL was significantly better in pts with pouch reconstruction
• Gastrostomy and jejunostomy - little role in gastric cancer