Approach to carcinoma stomach and its management

This ppt. has been made from multiple sources and is beneficial for postgraduates surgery residents. Approach and management of carcinoma stomach has been explained. Endoscopic management has been explained along with steps of gastrectomy.

1. MALIGNANCY OF STOMACH Presenter: Dr. Fatima, Dr. Sajad nazir, Dr. imtiyaz MODERATOR: Prof. Dr. Mushtaq Chalkoo (HOU SU 4)

2. Development of stomach develops from the tubular embryonic foregut. as a dilation during the fifth week of gestation in the caudal portion. its appearance and position drastically changes.

3. ROTATION OF STOMACH

4. Lesser sac

5. Parts of stomach cardia The fundus. antrum pylorus

6. Blood supply

7. Venous blood supply

8. Innervation of stomach

9. MICROSCOPIC ANATOMY

10. Lymph Node Stations According to the Japanese Classification of Gastric Carcinoma

11. Lymph node station

12. CARCINOMA STOMACH

13. EPIDEMOLOGY Worldwide gastric cancer remains the fifth most common cancer and second leading cause of cancer mortality. Substantial geographic variation. Higher occurrence in Asia and Latin America than in North America and Europe. In Kashmir, together with esophageal cancer, it accounts for more than 60% of all cancers ( Gastric cancer in K ashmir; Mariya Amin Qurieshi   1 ,  Muneer Ahmed Masoodi ,  Showkat Ahmad Kadla ,  Sheikh Zahoor Ahmad ,  P Gangadharan ). Incidence increases with age and peaks in 7 th decade.

14. EPIDEMOLOGY M:F = 2:1 Blacks > whites Incidence of tumors located distally within the stomach have decreased, whereas the incidence of more proximal gastric tumors has increased.

15. RISK FACTORS

16. TYPES OF GASTRIC CANCER

17. HEREDITARY RISK FACTORS

18. PATHOGENESIS ( The Correa hypothesis )

19. H.PYLORI PATHWAY

20. CLINICAL FEATURES Generally vague and nonspecific, contributing to its frequently advanced stage at the time of diagnosis. Clinical features depend on Length of history Age of the patient Location Extent Type of growth

21. Common clinical types INSIDIOUS TYPE Most difficult type to diagnose Tumors located in the body of stomach Presents as anorexia, weight loss, anemia, nausea, epigastric pain or discomfort Hematemesis, Malena or even perforation. OBSTRUCTIVE TYPE If growth occurs at or near GE junction patient presents with increasing dysphagia, first with solids later with fluids When pyloric region is the seat of cancer, patient presents with gastric outlet obstruction. PEPTIC ULCER TYPE One third of the patients present with a history of peptic ulcer.

22. EXTRA GASTRIC MANIFESTATIONS Acanthosis nigricans Virchow's node (trusseau) Axillary LAP (Irish) Sister Mary joseph nodule. Blummer's shelf. Krukenberg's tumor. Metastatic pleural effusion or aspiration pneumonitis. Obstructive jaundice Schnitzler's metastasis

23. HISTOLOGY WHO recognizes 10 histological types Adenocarcinoma papillary mucinous tubular signet ring cell Adenosquamous Squamous Small cell Undifferentiated others

24. Borrmann classification

25. JAPANESE CLASSIFICATION(MACROSCOPIC TYPES OF SUPERFICIAL GASTRIC CANCER)

26. BORDERS CLASSIFICATION Classified gastric carcinoma according to the degree of cellular differentiation independent of morphology GRADE 1-well differentiated GRADE 2-moderately differentiated GRADE 3-poorly differentiated GRADE 4-anaplastic

27. LAUREN CLASSIFICATION SYSTEM

28. SIEWERT CLASSIFICATION

29. DIAGNOSTIC WORKUP H&P CBC and comprehensive chemistry profile Upper GI endoscopy and biopsy Chest/abdomen/pelvic CT with oral and IV contrast FDG-PET/CT evaluation (skull base to mid-thigh) if no evidence of M1 disease and if clinically indicated Endoscopic ultrasound (EUS) if early stage disease suspected or if early versus locally advanced disease needs to be determined (preferred) Endoscopic resection (ER) is essential for the accurate staging of early-stage cancers (T1a or T1b) Biopsy of metastatic disease as clinically indicated MARKERS: CEA, CA 19-9, CA-125, and β-HCG.

30. UGI ENDOSCOPY Visualization of the tumor. provides tissue for pathologic diagnosis, treat patients with obstruction or bleeding

31. EUS NCCN guidelines as part of the staging workup for gastric cancer if there is no evidence of metastatic disease. Accurate evaluation of the depth of tumor invasion. Assessment of perigastric lymph node involvement. Sometimes identify involvement of surrounding organs or the presence of ascites

32. EUS

33. Computed tomography Inferior to EUS for T –staging More accurate for defining M-stage and for detecting ascites, peritoneal and omental deposits. LYMPH NODES(CT-SCAN) Detection of 1%of nodes <5mm 45% of nodes 5-9mm 70% of nodes >9mm

34. AJCC TNM staging

35. PET Combined PET/CT is more accurate in preoperative staging (68%) than either PET (47%) or CT (53%) alone. PET/CT is slightly better than CT alone for detection of occult metastases. Further, patients with PET-avid tumors can be monitored for a response to neoadjuvant therapy, which strongly correlates with survival. NCCN guidelines recommend considering PET/CT as part of staging for patients with greater than T1 disease without evidence of metastatic disease on initial CT.

36. Staging laparoscopy The NCCN recommends staging laparoscopic for T2 or greater gastric cancer and no prior evidence of metastases. Identify intrabdominal tumour deposits in lymph nodes, liver, or peritoneal surfaces in patients considered for curative gastrectomy To identify patients with intrabdominal tumour deposits not detected by preoperative staging To spare patients of exploratory laparotomy, having incurable disease

37. Peritoneal lavage can yield a positive cytology in 40% of the patients and almost all these go on to develop peritoneal metastasis STAGING Stage 1 No serosal involvement Stage 2 serosal invasion Stage 3 adjacent organ invasion Stage 4 distant metastasis With the use of laparoscopic contact ultrasound, staging accuracy increases Means of surgical palliation/ definitive surgery in certain patient groups

38. Management

39. Management GC is managed with curative intent when the disease is confined to stages 1-3 and palliative treatment for stage 4 disease. Broadly gastric cancer is divided into: Early gastric cancer (T1a/T1b N0/N1 M0). Locally advanced gastric cancer (resectable T2/T4 N+ M0). Advanced gastric cancer (unresectableT3/T4 N+ or M1).

40. Treatment Protocol

41. Multidisciplinary Treatment Strategy for Operable Gastric Cancer 1. The patient’s suitability to undergo curative gastrectomy 2. Accurate three-tool pretherapy staging 3. Sequence of GC therapy (surgery-first vs perioperative therapy)

42. SUITABILITY TO UNDERGO CURATIVE

43. ACCURATE THREE-TOOL PRETHERAPY STAGING EUS performed by an experienced Gastroenterologist High-resolution CT of the chest, abdomen, and pelvis, Staging laparoscopy with or without cytology.

44. SEQUENCE OF GASTRIC CANCER THERAPY SURGERY-FIRST VERSUS PERIOPERATIVE THERAPY Margin-negative (R0) gastrectomy and adequate lymphadenectomy together represent the pillars of surgical therapy for operable GC. Most patients with AJCC T2+ or N+ operable GC are offered one of the following two treatment sequences: (1) surgery-first, followed by adjuvant chemotherapy and/or chemoradiotherapy. (2) perioperative systemic therapy.

45. INTERGROUP TRIAL 116

46. CRITICS trial

47. The ARTIST trial Evaluated whether the addition of adjuvant radiotherapy would be beneficial by randomizing patients undergoing gastrectomy with D2 dissection to adjuvant chemotherapy with capecitabine and cisplatin alone or with radiotherapy. There was no difference in outcomes found between the adjuvant chemotherapy and adjuvant chemotherapy plus radiotherapy groups with 7-year follow-up.

48. ARTIST 2 A follow-up study (ARTIST 2) is ongoing to examine the benefit of radiotherapy in this patient subgroup alone. Based on presently available studies, adjuvant radiotherapy should be considered for patients with less than D2 lymphadenectomy and with positive nodal disease as part of multidisciplinary management .

49. MAGIC TRIAL a randomized study of 503 patients with stage II or higher GE cancer (372 stomach, 58 GE junction, 73 lower esophagus) that compared perioperative chemotherapy with surgery alone. The treatment group received three 3-week cycles of ECF preoperatively and three additional cycles postoperatively. More than 90% of patients who started the preoperative chemotherapy were able to complete it; The treatment group had significantly better pathologic results and long-term outcomes. The rates of local recurrence, distant metastases, and 5-year overall survival were significantly improved in the chemotherapy group compared with the surgery-only group (14.4% vs. 20.6%, 24.4% vs. 36.8%, and 36.3% vs. 23%, respectively).

50. FLOT4 study The FLOT4 study compared the regimen used in the MAGIC trial to four preoperative and four postoperative cycles of FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU). A total of 716 patients were randomized. They found that both median overall survival (50 vs. 35 months, P = 0.012) and progression-free survival (30 vs. 18 months, P = 0.004) significantly favored the FLOT regimen.

51. Treatment Recommendations It is important to recognize that these results cannot be generalized into one approach, and that the selection decisions must consider the individual characteristics of the patient’s tumor . In patients with a proximally located, diffuse-histologic subtype of cancer, perioperative chemotherapy akin to the MAGIC and CRITICS approach should generally be recommended . Conversely, in those with a distally located, intestinal histologic subtype of cancer, postoperative chemotherapy and radiation therapy akin to the Intergroup trial is more appropriate

52. Endoscopic resection The two primary modalities are: Endoscopic mucosal resection (EMR) Endoscopic submucosal dissection(ESD). Indications: Intestinal-type adenocarcinoma Tumor confined to the mucosa Absence of lymphovascular invasion Nonulcerated tumor Less than 2 cm in diameter

53. EMR

54. ESD

55. Surgical Approaches for Operable Gastric Cancer Depending on the location of the tumor in stomach, three surgeries have been defined: Proximal gastrectomy. TOTAL GASTRECTOMY SUBTOTAL GASTRECTOMY (distal).

56. Principles of radical gastrectomy Complete removal of primary tumor. Complete removal of regional nodal tissues. Histological confirmation of tumor free (R0) surgical margin. A grossly normal margin of 5 cm on either side of the gastric tumor should be aimed. Larger resection margin is required for diffuse than intestinal type( 5 vs 3cm). However tumors on either extremes, shorter distal and proximal margin are acceptable (1cm).

57. SURGERY BY SITE OF TUMOR PROXIMAL TUMORS. DISTAL TUMORS.

58. PROXIMAL TUMORS Proximal tumors have poor prognosis than distal part. Total gastrectomy is preferred over proximal gastrectomy for proximal tumors. A meta- analysis comparing proximal and total gastrectomy showed no difference in 5 year survival (61% vs 64%) but more cancer recurrences (39 vs 24%) in proximal gastrectomy group. Also the incidence of complications including anastomotic stenosis (27 vs 7%) and reflux esophagitis (20 vs 2%)was more with proximal gastrectomy.

59. Distal tumors For distal tumors preferred surgery is subtotal gastrectomy preserving cardia and fundus. Subtotal gastrectomy is associated with better nutritional status and quality of life.

60. Extent of Lymphadenectomy for Gastric Cancer

61. Extent of Lymphadenectomy for Gastric Cancer

62. D2 VS D1 ?? There are differences between East and West in nodal management of GC. In Japan, D2 lymphadenectomy has been a standard practice since 1960. Indian data from Tata Memorial hospital suggest that morbidity (<10%) and mortality (<1.5%) following D2, are low. A randomized trial from Taiwan showed a significant benefit in OS and RFS for D2 over D1.

63. Results from the Dutch Gastric Cancer Group trial demonstrated a more favorable survival benefit for spleen and pancreas preserving D2 nodal dissection. Similar results were seen in meta-analysis by Jiang L A Cochrane review meta-analysis of over 2500 patients enrolled in eight Asian and European lymphadenectomy (D1, D2, or D3) GC trials showed no difference in survival between D2 and D3 even in Asian lymphadenectomy trials. However ,D2 lymphadenectomy was associated with a significantly improved disease specific survival rate compared to D1 for T3 and T4.

64. SUMMARY D2 lymphadenectomy offers survival advantage and is the current standard of care for non metastatic, resectable T3/T4 GC. Routine pancreticosplenectomy is not recommended as a part of D2 dissection.

65. Targeted therapy in AGC Trastuzumab is approved to be as first line treatment in HER 2 positive AGC (phase 3 Toga trial). Lapatinib in combination with pacetaxel is second line treatment for AGC. Ramuciramub (anti-VEGFR2 ). Pembrolizumab is approved as third line agent in tumors expressing PD-L1.

66. Gastrectomy TYPES OF GASTRECTOMY Based on the amount of stomach removed Total Near total >90% Subtotal 80-90 % Partial 65-75 % Hemigastrectomy 50 % Antrectomy (distal gastrectomy ) 35-50%

67. Based on the method of reconstruction Billiroth 1

68. Billiroth 2

69. Roux en Y reconstructions

70. STEPS OF TOTAL GASTRECTOMY Mobilization of the greater curvature with omentectomy and division of the left gastroepiploic and short gastric vessels Infrahyoid mobilization with ligation of the right gastroepiploic vessels Suprapyloric mobilization with ligation of the right gastric vessels Duodenal transection D2 lymphadenectomy, with dissection of the porta hepatis, common hepatic artery, left gastric artery, celiac axis, and splenic artery, and ligation of left gastric vessels Gastric (or esophageal) transection Reconstruction by loop or Roux-en-Y gastrojejunostomy (or Roux- en Y esophagojejunostomy

71. POST GASTRECTOMY SYNDROMES

72. Nutritional abnormalities Weight loss Anemias Chronic calcium deficient and osteoporosis