Gastric cancer
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This case history involves a 55-year-old gentleman presenting with 3 months of abdominal pain. Initial investigations were normal. Further investigations were needed to determine the appropriate diagnosis and treatment. Options included fecal occult blood test, upper GI endoscopy, CT scan, H. pylori test, and serum gastrin level. Endoscopy allows direct visualization and biopsy of any lesions and is the investigation of choice.
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Gastric cancer
- 1. A Case History • AH 55 yrs gentleman from Nabhania • C/O – Abdominal pain • 3 months duration app. • O/E – Nil abnormal • Non ulcer dyspepsia Rx
- 2. A Case History • No relief after a few weeks of therapy • Next investigation of choice? – Fecal occult blood – UGI endoscopy – CT scan – Rapid serological test for H pylori – Serum gastrin level
- 4. Endoscopy • Points to remember – Allows direct visualization – Biopsy • >=10 biopsies – EUS – May miss some lesions • Two investigations are complementary Bowels MJ et al: BMJ 2001;323:1413
- 6. The Concern of The Son • The nature of the disease of his father • Is it communicable? • Why did my father get it? • Was it initially missed? • Is the incidence of cancer highest in Al- Qassim region?
- 7. Dr. Shad Salim Akhtar MBBS, MD, MRCP(UK), FRCP (Edin), FACP(USA) Member AUICC Fellows Consultant Medical Oncologist Medical Director Prince Faisal Oncology Center King Fahd Specialist Hospital Buraidah. Al-Qassim KSA Gastric Cancer The Standard Therapy
- 8. Gastric Ca In Al-Qassim 94-2000 94 = 11 95 = 9 96 = 4 97 = 11 98 = 6 99 = 8 00 = 10 01 = 12 02 = 4 Others = 2300 Gastric = 75 Year No
- 9. Lung 1,103,000 Stomach 647,000 Liver 549,000 Colon & Rectum 492,000 Breast 373,000 Esophagus 338,000 Cervix 233,000 Pancreas 213,000 Prostate 204,000 Leukemia 195,000 All sites 62,000,000 Parkin J et al. Eur J Cancer 2001; 37:S4 The Estimated Global Deaths for year 2000 (both sexes)
- 10. Changes in gastric ca related mortality in Europe Russian Fed M Russian Fed F East Europe M East Europe F XEU Solid line M (Male) XEU dashed line F (Female) Levi F etal. Ann Oncol 2004; 15:338
- 11. SEER data 1973-1999 Submitted 2001 Incidence rate of gastric ca per 100,000 (USA)
- 12. Reduced Incidence of Gastric Ca Reasons? • Better living conditions? • Increased consumption of fruits and vegetables? • Incidence of distal tumors has decreased? • Decreased intake of salted, pickled, smoked chemically preserved foods? • Decreased incidence mainly in developing countries?
- 13. Average age adjusted mortality US Males 1930-2000. Ahmedin J et al. CA Cancer J Clin 2004;54:8–29
- 14. Ahmedin J et al. CA Cancer J Clin 2004;54:8–29 Average age adjusted mortality US females 1930-2000.
- 15. Etiological Factors +ve -ve Salt Ascorbic acid Helicobactor B- Carotene Carcinogen? Risk factors include: Pernicious anemia Ch Atrophic gastritis Barrett’s esophagus Partial gastrectomy Menetrier’s disease E cadherin gene abnormality Gastric adenomatous polyposis Family history of gastric ca Blood group A Low socioeconomic status Cigarette smoking Bowels MJ et al: BMJ 2001; 323:1413
- 16. Helicobacter pylori organisms between the domes of epithelial cells
- 17. Calam J etal. BMJ 2001; 323:980 Relation of H pylori infection to UGI conditions
- 18. Autoregulation of acid secretionCalam J etal. BMJ 2001;323:980
- 19. H pylori Induced Hypoacidity • Predisposes to distal cancer • Genetically determined • Possibly due to inflammation • Reversed after eradication of H pylori • H pylori also impairs absorption of Vit. C
- 20. Hanson L etal. N Engl J Med 1996; 335:242-9 29,287 Pts 24,456 Pts
- 21. Uemura Naomi etal. N Engl J Med 2001; 345:784 Relationship of H pylori with Gastric Cancer Development
- 22. Relationship of H pylori with Gastric Cancer Development Uemura Naomi etal. N Engl J Med 2001; 345:784-9 1246 Pts 280 Pts
- 23. Gastric Cancer Location Factors Cardia Corpus Incidence Rising Declining H. pylori + ++++ Social status Upper Lower Histology Diffuse Intestinal DNA content Aneup+S phase Diploid Spread Early Hemat Late LocoReg Alberts SR etal. Ann Oncol 2003; 14:s31
- 24. Was the Diagnosis Delayed? Symptom Frequency % • Weight loss 61.6 • Abdominal Pain 51.6 • Nausea/Vomiting 34.3 • Anorexia 32.0 • Dysphagia 26.1 • Malena 20.2 • Early satiety 17.5 • Ulcer type pain 17.1 • Lower limb edema 5.9 Wanebo H etal Ann Surg 1993;218:58318365 pts with gastric cancer
- 25. Early gastric cancer Sparayed with 0.2% indigo carmine dye Burn marks around the tumour Lesion removed with 1 cm margin
- 26. Gastric Cancer Histopathology • Early cancers in eastern countries • Western experience • High grade dysplasia Cancer • No such reports from Japan & Korea • British Society of GE 1990..Hey Guys!!!! • Changes in histopathological classification needed Hohenberger P etal. The Lancet 2003; 362:305 75% Within 8 months
- 27. Category • 1 Negative for neoplasia • 2 Indefinitive for neoplasia • 3 Non invasive low grade neoplasia • 4 Non invasive high grade neoplasia – 4.1 High grade adenoma – 4.2 Non invasive carcinoma – 4.3 Suspicious for invasive carcinoma • 5 Invasive neoplasia – 5.1 Intramucosal carcinoma – 5.2 Submucosal carcinoma or beyond Woodward M et al. Eur J Gastroenterol Hepatol 2001; 13:233-7 Advances in Diagnosis Vienna Classification of Epithelial Neoplasia of GIT
- 28. Most Important Prognostic factor in Year 2004 Depth of InvasionDepth of Invasion
- 29. Most Important Prognostic Factor Depth of Invasion
- 30. Sasako M. J Clin Oncol 2003; 21:274S Incidence of Metastasis and 5-Year Survival Rate- Related to Depth of Invasion NCC Hosp Japan 1972-91
- 31. Tis=(16) T3=(464) T2=(265) T1=(168) T Stage versus Survival MSKCC Prospective Gastric CA Database
- 32. TNM Staging System N0 N1 N2 N3 M0 T1 I a I b II IV T2 I b II III a IV T3 II III a III b IV T4 III a IV IV IV M1 IV IV IV IV Hohenberger P etal. The Lancet 2003; 362:305 15 or more nodes to be examined NX <15 nodes exam; N1 1-6 +; N2 7-15 +; N3 >15 regional nodes +
- 33. Staging Investigations • Routine • Others as we know • Aim –Extent of invasion –Nodal status –Distant metastasis
- 34. Frequency of Nodal Metastasis %N+
- 35. Accuracy of Various Investigations to Assess TNM features Category CT EUS Hydro CT Lap T 25-66% 71-92% 51% 47% N 25-68% 55-87% 51% 60-90% M 65-72% 79% 80-90% Hohenberger P etal. The Lancet 2003; 362:305
- 36. • Used for 4 decades prior to 60-70s • New techniques introduced 90s • Detection of advanced cancer – CT 58% – EUS 63% –Lap 92% • Alteration in treatment plan in 30% • Best tool prior to surgery Does Laparoscopy Help? Feussner H etal. In Hohenberger P, Staging Laparoscopy 2002. 83- 95
- 37. Accuracy of Various Investigations to Assess TNM features Category CT EUS Hydro CT Lap T 25-66% 71-92% 51% 47% N 25-68% 55-87% 51% 60-90% M 65-72% 79% 80-90% Hohenberger P etal. The Lancet 2003; 362:305
- 38. Staging Laparoscopy Steps • Visual turn around of cavity – Peritoneal cavity – Liver surface • Serosal invasion – Visual – Biopsy • Open lesser sac to confirm resectability • Lavage of greater sac • Lap USG under direct vision – Sub diaphragmatic liver segments – Lymph nodes • Perigastric • coeliac axis • hepatoduodenal ligament • Biopsy any suspicious lymph nodes D’Ugo DM etal. Surg Endosc 1997; 11:1159
- 39. Back To Our Patient • Routine normal • Abdominal USG • CT scan • What was done? • What is the best treatment for such patients?
- 40. Pattern of Failure Local/Regional all 88% Distant 25% Local/Regional only 54% Gunderson etal. Int J Radioation Oncol Biol 1981; 81:1
- 41. Standard Therapy of Gastric Cancer in 2004 CURATIVECURATIVE RESECTIONRESECTION
- 42. Global Consensus-2004 GoodGood LOCAL CONTROLLOCAL CONTROL Is Essential ToIs Essential To Cure GastricCure Gastric CancerCancer
- 43. Gastric Cancer Surgery Controversies • Gastrectomy – Total vs Subtotal? • Splenectomy – To do or not to do? • Extension of lymph node dissection – D1 vs D2? • Neoadjuvant therapy (before surgery) – Role or no role?
- 44. Extent of Gastrectomy Total Gastrectomy (TG) vs Subtotal Gastrectomy Surgery Number Mortality% Morbidity% 5 yr Surv TG 93 3.2 32 48 SG 76 1.3 34 48 TG 303 2 13 62.4 SG 315 1 9 65.3 Gouzi et al. Ann Surg 1989:209:162 Bozetti et al. Ann Surg 1999;230:170 Multivariate analysis by Bozetti confirmed deleterious effects of total gastrectomy
- 45. Conclusion • Subtotal gastrectomy except if – Proximal tumor – Diffuse lesion • No splenectomy unless – Greater curvature lesion • Proximal 3rd • >=T2 – Organ invasion • Preserve pancreatic tail except if – Organ invasion Degiuli J. N Clin Oncol 1998; 16:1490 Maryuma. World J Surg 1995; 19:532
- 46. Survival in US vs Japanese Pts US 1982-1987 Japan 1971-1985 Stage No (%) 5 yr Surv (%) No (%) 5 yr Surv (%) I 2004(17.8) 50.0 1453 (45.7) 90.7 II 1976(17.5) 29.0 377 (11.9) 71.7 III 3945(35.0) 13.0 693 (21.8) 44.3 IV 3342(29.7) 3.0 653 (20.6) 9.0 Alberts SR etal. Ann Oncol 2003; 14(s2):ii31
- 47. Japanese Terms of Staging • R =Residual disease – R0 no residual disease – R1 microscopic residual tumor – R2 macroscopic residual disease • D =Extent of lymph node dissection – D1 Perigastric – D2 +Celiac axis, hep & spl art, spl hilum – D3 removes N1, N2 and N3 level nodes • Stomach is divided into three sectors – Upper third (C) – Middle third (M) – Lower third (A)
- 48. Japanese Concepts • Early gastric cancer ~ 40% • D2 is a standard procedure • D3 for advanced cancers • Retrospective data confirming superiority of these surgical procedures • Lymph node involvement is an indicator • Are we seeing a stage migration?
- 49. RCT of D1 vs D2 Resection No Morbidity Mortality 5 yr Surv D1 380 25 4 45 D2 331 43 10 47 D1 200 28 6.5 35 D2 200 46 13 33 P Value <0.001 P Value 0.004 NS Cuschieri A et al. Br J Cancer 1999; 79:1522 Bonenkamp JJ et al. N Engl J Med 1999; 340:908
- 50. Is there a survival advantage? Dutch Trial YES!!!
- 51. Is there a survival advantage? Dutch Trial YES!!!
- 52. Risk Factors for Postoperative Mortality • Kanofsky index 0.0001 • Concomitant diseases 0.0001 • Lymph node metastasis 0.001 • Tumour diameter 0.001 • Experience of the surg dept 0.001 • Age 0.028 Need for centralizing the services Bottcher et al. Chirug 1994;
- 53. Ongoing RCT Comparing Extent of Resection Type No Morbidity Mortality D1 76 11.0 1.3 D2 86 16.3 0 D1 109 7 0 D2 111 17 0 M Degiuli, Turin Italy C W Wu, Tapei Taiwan
- 54. Who Needs Extensive Dissection? Can We Know In the Year 2004? •Computerized database •Sentinel lymph node biopsy •Genomic study
- 55. Selection for Nodal Surgery • Maruyama computer program – Data from app 8000 pts – Indicators to predict nodal metastasis • Depth of infiltration • Size • Location • Grading • Type • Macroscopic appearance – Diagnostic accuracy ~74-94% Guadagani S et al. World J Surg 2000; 24:1550
- 56. Selection for Nodal Surgery Sentinel lymph node biopsy No Method Detection rate (%) Sensitivity (%) Node positive (%) 145 99 Tc Sn colloid 95 92 17 62 ICG 100 87 24 74 ICG 99 90 14 Kitagawa Y etal. Br J Surg 2002; 89:604 Ichikurs T etal. World J Surg 2002; 26:318 Hiratsuka M etal. Surgery 2001; 129:335 ICG = Indocyan green
- 57. Lymph nodes of Pts from Dutch Trial ASCO Presentation
- 58. Resected Gastric Cancer 5 years survival • Node negative 40-60% • Node positive 5-30%
- 59. Adjuvant Chemotherapy Is it effective?
- 60. Meta-analysis of Postoperative Adjuvant Trials No of trials No Patients Mortality O.R. 95% CI 11 2096 0.88 0.78-1.08 13 1990 0.80 0.66-0.97 21 3658 0.82 0.75-0.89 17 3118 0.72 0.62-0.84 Hermans J etal. J Clin Oncol 1993; 11:1441 Earle CC etal. Eur J Cancer 1999; 35:1059 Marie etal. Ann Oncol 2000 Panzini etal. Tumori 2002
- 61. • FAM • EAP+5FU • EPI+5FU/LV • FAMTX • CPT-11/CDDP • Docetaxel/CDDP/5FU • ECF • Gem/CPT-11 • 5FU CI/CDDP Adjuvant Chemotherapy Effective Drugs Available
- 62. ECF vs FAMTX ECF (111 pts) FAMTX (108 pts) CR+PR 50 (45%) 23 (21%)* CR 7 (6%) 2 (2%) PR 43 (39%) 21 (19%) SD 23 (27%) 23 (21%) Med Surv 8.7 mo 6.1 mo Webb etal. J Clin Oncol 1997; 15:261 *p value <0.002 Gastro-esophageal junction adenocarcinoma patients
- 63. PEGASUS Pan European Gastric Adjuvant Study with Uniform Surgery Surgery Chemotherapy HD Infusional 5- FU/Docetaxel/CPT-11 D1+ Lymph node dissection Preservation of spleen and pancreatic tail Observation
- 64. Post operative Adjuvant Therapy Not a standard “yet”
- 65. Site of Relapse Local and regional failure 70-90% Gunderson et al. J Clin Oncol 1995
- 66. Adjuvant Local Therapy Intra peritoneal therapy • Drugs tried – Cisplatin – Mitomycin C – 5FU+Mitomycin C • No survival benefit • Added postop morbidity and mortality Yao JC & Ajani JA. Ann Oncol 2002; s2:7
- 67. Adjuvant Chemo-radiotherapy No of pts 603; Negative margins essential; 47 ineligible for therapy
- 68. Macdonald JS. J Clin Oncol 2003; 21(23s):276s Updated results similar
- 69. Macdonald JS. J Clin Oncol 2003; 21(23s):276s Updated results similar
- 70. Post-operative Adjuvant Chemo-radiotherapy • Improves survival – Disease free (44% improvement) – Overall (28% improvement) • Acceptable toxicity – Mainly hematological • Probably standard for the surgical techniques employed outside Japan • May form the basis for future comparison
- 71. Gastric Cancer Spectrum In The West What Can Be Done? • pT3 tumors in UK study 44% • III/IV disease in German study 59% • III/IV disease in Am Col Surg 67% • Comp Res rate in adv disease <50% • Median survival at 5 yrs ~30%
- 72. Neo Adjuvant Therapy What Should It Do? • Improve resectability • Down stage the disease • Improve survival
- 73. MAGIC Trial Observation3XECF Allum W etal. Proc Am Soc Clin Oncol 2003; 22:249 (Abst 998) Operable Gastric Cancer Randomize 3XECF Surgery Surgery
- 74. MAGIC TRIAL CSC S Patients having surgery 212 (85%) 232 (92%) Median time to surgery 99 days 14 days Proportion of curative resection 79%* 69%* *p = 0.018 Allum W etal. Proc Am Soc Clin Oncol 2003; 22:249 (Abst 998)
- 75. MAGIC Trial Improvement in survival
- 76. Ongoing Adjuvant Trials Group No of pts targeted Therapy MRC 500 ECF pre & post op France 250 CDDP/CI 5-FU EORTC 360 CDDP/5-FU Swiss/Italian 250 Docetaxel/CDDP/ CI 5-FU
- 77. New Trends!!! • EGFR inhibitors • MOAB –Cetuximab (C-225) • TKIs –ZD-1839 (Iressa) –OSI-774 (Tarceva) • Flavopiridol –Pan CDK inhibitor
- 78. Improvements in Future • Minimizing morbidity – Patient selection – Organ preservation • Local control – D1+disection – Minimum 15 nodes – Centralization • Survival – Surgery – Radiotherapy – Chemotherapy
- 79. This Dream May Come True Soon
- 81. Lymph Node Metastasis Related to Depth of Tumor Invasion Sasako M. J Clin Oncol 2003; 21:274S
Editor's Notes
- Investigation of choice UGI endoscopy
- Barium meal showing an obstructing large carcinoma of the body of stomach BMJ 2001; 323:1413.
- If either Barium meal or UGI endoscope negative the other must be done. In pts with dysphagia barium swallow in addition to meal must be ordered. 10 or more biopsies taken from all parts of an ulcer reach an accuracy of near 100%. Barium may be necessary to diagnose linitis plastica which might be missed at endoscopy.
- Gastric cancer in the lesser curve
- The diagnosis of gastric ca was confirmed and while preparing the son before talking to the father, the son puts the following questions to me. And I tried to answer his queries one by one.
- World wide gastric ca is the second commonest cause of death. The incidence of the stomach cancer however, has been reported to be decreasing over the years.
- Circles= Russian Federation (filled male, open female); Squares=Eastern European (filled male, open female); Crosses= EU (solid line male, dashed line female). This graph indicates the decline in the incidence of gastric cancer related mortality in the European countries.
- Figure 99-1 Surveillance, Epidemiology, and End Results (SEER) data between 1973 and 1999 (inclusive), showing time changes in the incidence rate of gastric cancer (per 100,000 population) by gender. National Cancer Institute,DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2002 based on the November 2001 submission. Similar declining rates seen in N America.
- Better living conditions probably decreases the incidence of H pylori. The last one is wrong. Refrigerator invention may have contributed to the fall in incidence but as the next slide will show the decline had started much before the introduction of the refrigerator.
- This is the data published in Ca J for clinicians 2004 Jan showing a constantly decreasing rate of mortality due to gastric ca in males and in the next slide females.
- Risk factors for gastric cancer. Salt intake high. WHO in 1994 reported H pylori as type 1 carcinogen for humans. Nitrosamines other carcinogens? Fruits and vegetables decrease the incidence of Gastric ca. E Cadherin gene abnormality related to the inherited gastric ca, which might be prevented or cured with prophylactic gastrectomy.
- Marshall and Warren detected this organism in 1983. The spiral organisms between the junction of domes of the epithelial cells where it splits urea which leaks from the cell junction and ammonia is produced which increases the acidity.
- Relation of H pylori infection to upper gastrointestinal conditions. Various factors affect the outcome of HP infection. These include the host response, the extent and the severity of gastric inflammation and hence the amount of acid secreted. It can elevate the acid secretion in people who develop duodenal ulcer, decrease acid through gastric atrophy in those who develop gastric ulcers or cancer and leave acid secretion unchanged in those who do not develop these diseases. H pylori also impairs the bioavailability of vitamin c in these patients who may already have a poor intake. Eradication of H pylori increases secretion of vitamin C into gastric juice which might increase protection against gastric cancer.
- Autoregulation of acid secretion. Food stimulates release of gastrin from antral G cells (G). Gastrin stimulates enterochromaffin-like cells (ECL) to release histamine, which stimulates parietal cells (P) in the gastric corpus to secrete acid. Acid stimulates release of somatostatin from somatostatin cells (S) in the antrum, inhibiting further gastrin release.
- With acid hyposecretion (left), the main effect of H pylori gastritis affecting the gastric body is to suppress parietal cells, leading to low acid secretion, which is associated with gastric cancer. With acid hypersecretion (right), antral H pylori gastritis increases acid secretion by suppressing somatostatin and elevating gastrin release, increasing the risk of duodenal ulceration. Orange areas indicate extent and location of gastritis
- Swedish in patient registry study comprising 29,287 gastric ulcer pts (F Up 8.3 yrs and 24,456 pts of DU (F up 10.1 yrs). A higher incidence than normal population was noticed in initial 2 years followed by decline which continued. The incidence of diagnosing gastric cancer in G Ulcer pts continued to be high although it was highest in the initial 3 years.
- Gastric cancer developed in pts with non ulcer dyspepsia, active gastric ulcers and hyperplastic gastric polyps but no gastric cancers developed in pts with active duodenal ulcers.
- Prof Uemura followed 1526 pts prospectively for 8 years in Japan. Those who were negative did not develop cancer and as shown in the next slide those who had infection and DU or were cured did not develop cancer as well. As a result of the association of Gastric ca with H pylori we are seeing a change in the gastric cancer pattern Two definite patterns are evolving..
- LR loco regional. What else is changing in the epidemiology of gastric cancer. We are seeing more proximal cancers in people of upper social status and of diffuse histology.
- Any how a frequent question asked by the relatives and the pts alike is was the diagnosis delayed? Unfortunately the commonest symptom pain occurs late as the abdomen is a large cavity and the stomach can distend. Back ache is an indicator of advanced disease. However, in spite of this in eastern countries, Japan and Korea the disease is diagnosed in early stages.
- In Japan and Korea this is what they diagnose.. Early gastric ca. Amenable to therapy with local excesion.
- In eastern countries mainly early cancers are treated, while as in western the disease was found to be advanced at diagnosis. This difference probably contributed to the confusion in histopathological classification of disease and made the comparisons difficult. In the west, inflammatory and regenerative changes were classified as dysplasias as were well differentiated adenocarcinomas. In follow up studies people who had gastric mucosa biopsy specimens classified as high grade dysplasia upto 75% of the patients developed a cancer within a median time of 8 months. No such reports were seen from Japan, Korea or Asia. As a consequence of this finding which was reported by British Society of Gastroenterology in 1990, the Vienna classification of epithelial neoplasia of the GI was introduced in 1998. Here high grade dysplasia, noninvasive carcinoma and susp invasive ca are integrated in one term.
- The Vienna classification of epithelial neoplasia of the GI was introduced in 1998. Here high grade dysplasia, noninvasive carcinoma and susp invasive ca are integrated in one term.
- NOTE. Patients operated on between 1972 and 1991, National Cancer Center Hospital, including exploratory laparotomy. In 22 patients, tumor depth could not be obtained. Abbreviations: JCGC, Japanese Classification of Gastric Cancer; M, mucosal; SM, submucosal; MP, muscularis propria; SS, subserosa; SE, serosa exposed; SI, serosa infiltrating (neighboring organ or organs involved).
- Joint Committee on Cancer T stage. Tis (tumor in situ; n = 16) A; T1 (n = 168) B; T2 (n = 265) C; T3 (n = 464) D; T4 (not shown), n = 28. (From the Memorial Sloan-Kettering Cancer Center Department of Surgery Prospective Gastric Cancer Database.)
- In addition to T invasion the other important parts of staging are the lymphnodes. Tis Ca In situ; T1 tumour invades lamina propria (a) or submucosa (b); T2 tumour invades lamina propria or subserosa; extension into omentum or gastrohepatic ligament is considered T2 until perforation of visceral peritoneum has occurred; T3 serosa penetrated; T4 adjacent structures invaded. N0 no nodal mets, NX less than 15 nodes excised, N1 1-6 regional lymph nodes +; N2 7-15 +; N3 more than 15 regional nodes +; M1 include mets to retropancreatic, mesenteric or para - aortic nodes.
- The lymph node metastasis rate goes up to 46% in T2 lesions and may be as high as 79% in T3 tumors. The knowledge of LN status is therefore important to plan the therapy.
- EUS is considered superior to conventional CT. However, CT with gastric distention of 600-800 ml of water, hydro CT might be a complementary investigation. EUS can assess LNs close to gastric wall. Suggestive of mets on EUS rounded shape, &gt;1cm in size and hypoechoic pattern.
- The lymph node metastasis rate goes up to 46% in T2 lesions and may be as high as 79% in T3 tumors. The knowledge of LN status is therefore important to plan the therapy. Endoluminal USG can assess LNs close to the gastric wall CT scan can only define nodes and give the size as a result Lap has had a new lease of life. With advent of specialized instruments and techniques including US probes the Lap can achieve a 92% rate of detection for advanced ca. Prospectvie studies have reported that up to 30% of patients had a tumour at more advanced stage than expected needing a change in treatment strategy. A Lap performed just before treatment surgery in the hands of a skilled surgeon is the best tool to guide decisions regarding resection or palliative measures.
- EUS is considered superior to conventional CT. However, CT with gastric distention of 600-800 ml of water, hydoro CT might be a complementary investigation. EUS can assess LNs close to gastric wall. Suggestive of mets on EUS rounded shape, &gt;1cm in size and hypoechoic pattern.
- This is the sequence of a classical staging Lap and its advantages.
- There is consensus on few issues at the global level, be it Kashmir or Palestine but there does seem to be global consensus on how to cure gastric cancer!
- In spite of this consensus in principle; controversies do exist in the precise management of gastric ca.
- These two trials have looked at the advantages of total gastrectomy as compared to subtotal gastrectomy. No advantage in terms of survival. The morbidity and mortality of TG was higher. On behalf of Italian Gastrointestinal Tumour Study Group, Bozettis article also included a metaanalysis which confirmed the deleterious effects of total gastrectomy.
- However, the variation in the outcome of the cancer at same stage in US and Japan has been quite interesting to note. We started looking for answers? Let us see how Japanese work?
- N1 level nodes along splenic and left gastric artery and coeliac axis. N3 means hepatoduodenal and root of mesentery. To understand how Japanese work we need to understand their terminology.
- Surgery is the cornerstone of therapy and the surgical techniques employed have been constantly reviewed since the Japanese started reporting superior survival rates with their extended LN dissection. Indeed these superior survival rates are attributed both to the early detection as well as the extended dissection employed. In Japan 40% of the gastric ca are localized mucosal/submucosal. Extended LN dissection D2 is employed in such pts while as a D3 dissection is employed in more advanced cases (serosal involvement). But most of this data is based on retrospective data. LN involvement is an indicator of disease spread rather than a determinant (governor) of survival. Therefore extended LN dissection improves the accuracy of staging thus inducing stage migration and a better stage specific survival data becomes available.
- UK and Dutch randomized trials comparing D1 and D2 dissection. The Dutch trial was done with Japanese expertise.
- Obviously there has to be a reason for this poor outcome of D2 dissection. Looking at the Dutch trial with post op deaths excluded the difference in survival becomes obvious from 2 yrs onwards.
- Similar surv advantage becomes obvious in N1 and more so in N2 disease.
- The factor of experience is highlighted form this slide where the mortality varied according to the experience of the surgeon.
- These are two ongoing trials in Italy and Taiwan and it is obvious that the increased morbidity and mortality which we had seen in initial studies are decreasing.
- Table modified from the Lancet July 26 2003 page 312. May be relevant to small tumors in the future. Initial detection of draining lymph nodes may be as high as 100% (95-100%), but the sensitivity of detecting the nodes involved by cancer is in the range of 90%. However since Stomach has four main drainage areas; celiac, liver, mediastinum and retroperitonium more prospective trials are required before drainage direction detection revealed by blue dye or Tc colloid can be allowed to affect the deisions about removal or non removal of LNs.
- The genomic study of the lymph nodes from pts of the Dutch randomized trial showing the difference in the genomic pattern between those who were node positive and negative
- Although there is some tendency towards the decrease in the odds ratio with adjuvant therapy, the difference is not significant.
- From early days gastric cancer has been a responsive tumor out of all GI tumours and many drugs have been effective either as single agents or in combination. However, the trials have gradually moved once a favorite FAM away from the list of the most effective regimens being replaced by new drugs and new combinations. One of the important ones worth mentioning is the ECF regimen.
- This is an ongoing European trial which might give the answer to the question.
- Although we do have many effective drugs currently the adjuvant therapy is not considered standard. We are awaiting results of large randomized trials in this regard.
- Can we do something to decrease the local recurrence rate. Two important areas have been tried Intraperitoneal therapyand local radiotherapy.
- In western and non east European countries most of the pts with gastric ca present with advanced stage disease hence not amenable to complete resection. What can be done for such pts? Advanced local disease precludes curative resection hence effects the survival. Can neoadjuvant therapy be the answer?
- Many trials have been performed in the past but with inconclusive results. Probably the drugs used were not effetive
- An interesting study comparing the role of chemotherapy preoperative with no chemotherapy at all. Tumor down staged; 10% increased resectability, a 3 vs 5 cms size difference in favour of chemo. The disease free survival is in favour of chemo arm but not over all surv yet.
- The N status is according to Japanese staging indicating the nodal groups involved.