Gastric Cancer Investigations and management

detailed overview of gastric cancer staging, management.

1. DR. ARPIT BANDI GASTRIC CARCINOMA INVESTIGATIONS & MANAGEMENT

2. 5 th Most common cause of cancer death worldwide OVERVIEW

3. ANATOMY – ANTERIOR & POSTERIOR VIEW

4. T-Staging

5. Japanese classification of early carcinoma Borrmann classification of advanced gastric cancer

6. AJCC TNM STAGING

7. Investigations

8. Low hemoglobin High ESR Iron profile CEA increased in 45-50% cases. CA 19-9 elevated in about 20% cases. Blood Investigations

9. UPPER GI SCOPY & EUS - Principles for Staging Diagnostic Dye can be sprayed to delineate mucosal changes Retroversion of scope to view the cardia and fundus - J manoeuvre . U manoeuvre - to visualise lesser and greater curvature. • Tells Tumor location , Relation to GEJ for proximal tumors Multiple (6–8) biopsies, especially in ulcerated lesion. • EMR or ESD in small lesions. EMR or ESD of focal nodules ≤2 cm to assess degree of differentiation, LVI, depth of infiltration, Such excisional biopsies have the potential of being therapeutic.

10. EUS Staging EUS prior to treatment - important provides evidence of depth (T-category), abnormal or enlarged lymph nodes (N-assessment), occasionally signs of distant spread (M-category)

11. dark expansion of gastric wall layers identifies the location of tumor . layers 1–3 - infiltration of the superficial and deep mucosa plus submucosa, T1 . layers 1–4 - penetration into the muscularis propria, T2 , expansion beyond the muscularis propria that correlates with invasion of the subserosa, T3 . Loss of the bright line recognized as serosa - pT4a , and extension of the mass into surrounding organs such as the liver, pancreas, and spleen is staged as pT4b disease. T2 T1 T3 T4

12. Perigastric lymph nodes seen by EUS, if enlarged, hypoechoic (dark), homogeneous, well-circumscribed, rounded - the presence of malignant or inflammatory lymph nodes. may be confirmed with FNA C of suspicious lymph nodes Furthermore, identify presence of ascites. FNA to rule out peritoneal spread of disease.

13. Staging Workup if considered for neoadjuvant therapy

14. 16 Staging Laparoscopy Superior to radiographic studies for detecting metastatic disease. S ensitivity 86% and specificity 100% , Detects occult disease in 9% to 50% Spares unnecessary laparotomy and can begin chemotherapy earlier (19.5 vs 36.8 days) and shorter length of hospital stay. Positive cytology poor prognostic factor. Patients with initial positive cytology may have a good prognosis following neo-adjuvant treatment if the cytology results change to negative after treatment. Leake PA et al. A systematic review of the accuracy and indications for diagnostic laparoscopy prior to curative-intent resection of gastric cancer. Gastric Cancer 2012

15. 17 Ann Gastroenterol Surg. 2019  Poorly differentiated Bormanns >3 LN mets Equivocal finding in CT Linitis plastica

16. 18 Peritoneal lavage Positive peritoneal cytology in the absence of other metastatic disease (C1 ) correlate with a poor prognosis ; Median survival : 14.8 to 20.0 months Selects out up to 7% patients who are C0 disease initially and receive neoadjuvant therapy but are found to have C1 disease at the time of repeat laparoscopy, thus sparing them an unnecessary laparotomy

17. The only treatment with curative intent is represented by surgery as part of a multimodal therapy 19 Dawn of surgery

18. Japanese Guidelines, 2021

19. T1a

20. EMR and ES D EMR (Endoscopic mucosal resection) injection of a substance under the targeted lesion to act as a cushion, lesion is then removed with a snare or suctioned into a cap and snared . ESR (Endoscopic sub-mucosal resection) injection of a substance under the targeted lesion to act as a cushion, submucosa is instead dissected under the lesion with a specialized knife. This enables removal of larger and potentially deeper lesions  higher rates of R0 resections and a lower rate of local recurrence, but  technically demanding and has more adverse events .

21. T1b & Higher

22. Impact of the extent of surgical resection on survival of Distal Gastric cancer 3 small RCTs compared Total vs Partial for distal gastric cancer Overall morbidity, mortality and oncological outcomes similar Total gastrectomy associated with Inferior long term quality of life Risk of remnant gastric cancer – 0.4% to 2.5% Distal Gastric cancers – a gastric preserving R0 approach minimize the risk of sequelae of Total gastrectomy like early satiety, weight loss and need for Vit B12 supplementation.

23. Proximal vs Total Gastrectomy for Proximal Gastric cancer Meta-analyses of 1 RCT, 23 studies No significant diff in OS between two Increased reflux symptoms & anastomotic stenosis in PG LN harvest better with Total gastrectomy Risk of remnant gastric cancer – 3.6% to 9.1% Proximal Gastric cancers – although no OS difference noted Reflux symptoms, anastomotic stenosis, risk of LN mets to station 5, 6 and remnant stomach cancer, Difficult endoscopy during follow up – all these to be considered before looking for benefits of gastric preservation. Norwegian stomach cancer trial → TYPES MORTALITY MORBIDITY PROXIMAL GASTRIC RESECTION 52% 16% TOTAL GASTRIC RESECTION 38% 8%

24. Extent of lymph node dissection D1 = Perigastric nodes (station 1-6) D1+/Over D1 = D1 plus L.N. of D2 safely removed without splenectomy or pancreatectomy D2 = Common hepatic, left gastric, coeliac & splenic L.N.(7-11) D3 = Hepato-duodenal ligament & root of the mesentery (12-16) D1 D2

25. D2 D1 DISTAL RADICAL GASTRECTOMY

26. D2 D1 GASTRECTOMY FOR TUMOURS OF THE BODY

27. TOTAL GASTRECTOMY FOR TUMOURS OF THE UPPER THIRD

28. Reconstruction Procedures Billroth I Gastrectomy Billroth II Gastrectomy End to end gastroduodenal anastomosis End to side gastrojejunal anastomosis Roux en Y Gastrojejunostomy

29. Reconstruction following Total Gastrectomy

30. D1 vs D2 Lymphadenectomy (5 RCTs) 1988, Cape Town Trial 43 patients Significant morbidity with D2 5 yr OS – no difference 1994, PWH Hongkong Trial 55 patients Significant morbidity with D2 Decreased median OS with D2 2004, Italian GCSG Trial 160 patients No sig diff in operative morbidity, mortality No survival advantage with D2 MRC UK Trial, 1999 Dutch GC trial, 1999 D1 D2 D1 D2 Number 200 200 380 331 Operative mortality 6.5% 13% 4% 10% Post op Complications 28% 46% 25% 43% 5 year OS 35% 33% 45% 47% 15 year Follow up: 15 year Overall survival : 21% 29% Gastric cancer death rate : 48% 37% Loco regional recurrence rate : 22% 12% D2 dissection – Lower Locoregional recurrence rates and Gastric cancer related deaths Pancreas and Spleen preserving D2 gastrectomy is Safer and Standard

31. Extended D2? 3 RCTs Polish Study, 2007 JCOG 9501, 2008 EASOG, 2008 D2 D2 + PAND D2 D2 + PAND D2 D2 + PAND Number 141 134 263 261 134 134 Operative mortality 2.2% 4.9% 0.8% 0.8% 1 pt 5 pts Post op Complications 27.7% 21.6% 20.9% 28.1% 5 year OS NR NR 69.2% 70.3% 52.6% 55% PALN micromets 6%-33% Extended D2 is not recommended

32. SPLENECTOMY???

33. BURSECTOMY??? N=1503, T3 T4a tumors Bursectomy No bursectomy 5 year OS 76.9% 76.7% Pancreatic fistula 5% 2% Morbidity 13% 11%

34. Evolution of laparoscopic gastrectomy

35. Peri-operative Chemotherapy MAGIC trial Randomised controlled study of 503 pts. With stage II or higher gastric cancer that compared perioperative chemotherapy with surgery alone . CEF (Cisplatin, Epirubicin, 5-FU) - 3 cycles as neo-adjuvent CT - 3 cycles as adjuvent CT 5-yr survival, rate of local recurrence & distant metastasis were improved in CT group UK National Cancer Institute trial OEX ( Oxaliplatin,Epirubicin,Capecitabine ) longer overall survival than with CEF and decreased incidence of thromboembolic phenomenon by substituting oxaliplatin for cisplatin FLOT4 Trial: RCT, perioperative FLOT improved overall survival compared with perioperative ECF/ECX.

36. Intraperitoneal Chemotherapy (IPC) Recurrence following curative resection is likely due to peritoneal carcinomatosis. Systemic CT : blood-peritoneal barrier prevents the chemotherapeutic agents from achieving their cytotoxic effect. IPC : administering high doses of chemotherapy directly to the peritoneum whilst reducing the systemic effects. HIPC (hyp er thermi c Intraperitoneal Chemotherapy )  increased risk of neutropaenia and intra-abdominal abscesses .

37. HIPEC TRIALS The GYMSSA trial - 17 patients—9 in CRS + HIPEC + chemotherapy arm (GYMS) and 8 into chemotherapy only (FOLFIXIRI) arm (SA).  32  A median survival advantage of 11.3 months was seen in the experimental GYMS arm compared to 4.3 months in the SA arm. GASTRIPEC‐I‐trial – CRS + HIPEC IMPROVES SURVIVAL

38. ROLE OF CRS/HIPEC

39. Unresectable disease

40. Palliative Procedures Bleeding Endoscopic Control External Beam Radiotherapy Angiographic Embolisation Obstruction Endoscopic Enteral Stent Radiotherapy and Chemotherapy to shrink tumour Gastrojejunostomy Palliative Gastrectomy Gastrostomy

41. Thank you