GE junction tumor-pptx

GE jucntion tumors

1. Gastroesophageal junction tumors Uttam Laudari MCh Resident, Second year

2. OG junction- No mans land Partly intrathoracic and partly intraabdominal Mix up AC and SCC Confusions regarding margins Extent of nodal dissection Surgical approach which is best Multimodality of treatment

3. SCC Adenoca

4. Confusion according to AJCC

5. GERD and Barrett’s Metaplasia Siewert type I tumours have a strong association with Barrett’s metaplasi Chronic GERD and Barrett’s metaplasia have been found in 70–97% of patients) Type II tumours low prevalence of Barrett’s that is slightly more than type 3 tumours Type III tumors  similar in pathology to gastric carcinoma do not have an etiologic background of Barrett’s metaplasia

6. Obesity 16% for every 1 kg/m2 increase in BMI high risk of esophageal adenocarcinoma  chronic GERD and metaplasia, Hiatus hernia also has a similar close association with GERD and esophageal adenocarcinoma Thrift AP, et al. J Natl Cancer Inst. 2014;106:dju252

7. Helicobacter pylori H. pylori infection (especially CagA strain)  adenocarcinoma of the distal stomach Siewert type III adenocarcinoma  association with H. pylori. Type I  an infection with H. pylori seems to have a protective effect for esophageal Nie S et al Dis Esophagus. 2014;27:645–53

8. Tobacco Smoking well-established and moderately strong risk factor doubled risk of adenocarcinoma compared with never smoking (OR, 1.96) twofold increased progression risk from Barrett’s esophagus to adenocarcinoma associated with tobacco smoking A similar association was reported with cardia cancer (type 2) as well Cook MB, et al. J Natl Cancer Inst. 2010;102:1344–53

9. Alcohol A large study confirmed no association between alcohol intake and increased risk of esophageal adenocarcinoma Freedman ND, et al. Gut. 2011;60:1029–37.

10. Dietary Factors good evidence for linking any conventional dietary factors with esophageal adenocarcinoma, except that vegetable intake had limited suggestive evidence for a reduced risk of adenocarcinoma Diet, nutrition, physical activity and oesophageal cancer, vol. 2018; 2018

11. Siewert Type I adenocarcinoma Distal esophageal adenocarcinoma infiltrating the EGJ and mostly associated with intestinal metaplasia i.e. Barrett’s esophagus epicentre located more between 1 and 5 cm above the EGJ

12. Siewert Type II tumors True carcinoma of the cardia arising from the epithelium of the gastro-esophageal junction and often referred to as ‘junctional carcinoma’ ( epicentre located between 1 cm above to 2 cm below the EGJ).

13. Siewert Type III tumors Subcardiac gastric carcinoma located below the EGJ and infiltrating the gastro-esophageal junction and distal esophagus ( epicentre located between 2 and 5 cm below the EGJ) an almost equal proportion of intestinal and diffuse histological types an insignificant association with reflux

14. Nishi’s Classification Both Siewert’s and Nishi’s classification clearly settled the epicenter location within 2 cm above and below the EGJ , irrespective of tumor size in the former And histological type in the latter as well as tumor extension in both. EGJ esophagogastric junction.

15. AJCC 8 th Staging Siewert type I and II   staged in the esophageal carcinoma staging schema Siewert type III tumors (2–5 cm below the EGJ) are to be staged as gastric carcinoma AJCC Cancer Staging Manual. New York: Springer; 2017. p. 185–202

16. Cavallin F. Ann Surg. 2018 AJCC8 the Edition

17. Staging

18. Staging

19. Siewert JR et al. Adenocarcinoma of the esophago-gastric junction. Scand J Surg. 2006;95:260–9. Rudiger Siewert et al. Results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg. 2000

20. Clinical Presentation Asymptomatic The majority of patients at presentation already have advanced disease Symptomatic Dysphagia (75% lumen obstructed) and odynophagia (i.e. painful swallow) Complications Hoarseness or Horner’s syndrome occur with the invasion of the recurrent laryngeal nerve or cervical ganglia ( usually inoperable) Occult or overt GI bleeding can occur especially with ulcerated tumours

21. Clinical Presentation Cervical or supraclavicular lymphadenopathy. symptoms that indicate advanced disease  chest pain, back pain, excessive weight loss (more than 10%) , long duration of dysphagia (more than 6 months) Submucosal infiltrating carcinoma at the EGJ may mimic achalasia, and as such is termed pseudoachalasia

22. Investigations endoscopy Barrett’s mucosa  extension of the salmon-pink velvety gastric mucosa proximal to the squamocolumnar junction Any visible lesion in the mucosa should be biopsied In addition four-quadrant biopsies should be taken at every 2 cm along the Barrett’s mucosa

23. At least six biopsies from non-necrotic areas of the tumour increase the yield to nearly 100%. Endoscopic views while crossing the EGJ and then the retroflexed views after entering the stomach are a good way of preoperatively subgrouping the tumors as per the Siewert classification.

24. EUS enables the endosonographer to evaluate the wall-layer pattern of the esophagus and to detect the presence of regional and celiac lymph nodes. EUS guided FNA permits directed tissue sampling of adjacent nodes the role of EUS in EGJ carcinoma found a 48% concordance between EUS uT -stage and pathologic pT -stage ( under-staged 23%, over-staged 29%) Dhupar R, et al.. Ann Thorac Surg. 2015;100:1812–6

25. EUS Frequencies of 7.5 and 12 MHz Staging: Locoregional High frequency (20 MHz) 9 layers in the esophageal wall Evaluating superficial lesions Boonstra JJ. Surg Oncol. 2009

26. Selected patients with high-grade dysplasia and early (T1a) tumors for nonsurgical treatment—For accurate T and N staging Locally advanced esophageal carcinoma— Staging of T4 tumors to determine resectability Locally advanced esophageal carcinoma— Staging for remote nodal disease and selecting out patients who may not undergo a R0 resection , e.g. upper mediastinal nodes in EGJ carcinoma Locally advanced esophageal carcinoma—To select patients for neoadjuvant therapy. Stage 2 and 3 patients are usually selected to undergo neoadjuvant treatment prior to surgery Thosani N, et  al.. Gastrointest Endosc . 2012;75:242–53. EUS is recommended to be performed in all patients with only loco-regional disease, and it may be helpful in the following clinical scenarios :

27. CT Scan CT scan of the neck, thorax, abdomen and pelvis with intravenous and oral contrast is the standard of care investigation for staging of esophageal carcinoma The fissure of the ligamentum venosum is seen on the CT separating the caudate lobe from the lateral segment of the left lobe of liver; it points directly at the EGJ

28. CECT… The key findings on CT scan include: Wall thickening greater than 5 mm (circumferential or part of the wall). Dilated esophagus proximal to an obstructing lesion Tumors infiltrating outside the wall may appear as soft tissue and fat stranding around the esophagus Locally advanced tumors may cause displacement of the tracheobronchial tree. Unfortunately loss of fat plane between the airway and the esophageal tumor cannot be used as an indication of invasion, as no fat plane is normally evident even in patients without a tumor.

29. Aortic invasion in CECT The Picus angle is the angle of contact (loss of fat plane) between the esophageal mass and aorta. Angle of contact more than 90° is highly suggestive of invasion of aorta angle less than 45° is associated with no invasion, and angle in between 45° and 90° is indeterminate Accuracy of these findings is about 80%

30. CECT… Node metastasis- mediastinal node with short axis diameter > 1cm is abnormal Sensitivity for nodal mets is low Distance metastasis

31. PET- CT Poor uptake of FDG (i.e. FDG non-avid tumours ) is usually associated diffuse Lauren type tumours small tumour size mucinous content good differentiation Up to one-third of gastric tumours can be PET non-avid

32. PET- CT Prognostic value a good correlation between higher maximum SUV ( SUVmax ) and poor overall and disease-free survival Staging is less accurate than EUS for determining the T-stage not much better than EUS or CT scan for nodal staging Uptake in the primary lesion may obscure the involved loco-regional nodes best investigation for diagnosis of unsuspected distant metastasis and extra-regional involved nodes In a meta-analysis van Vliet et al. showed that the sensitivity and specificity for detecting distant metastases by 18F-FDG PET were 71% and 93%, respectively, and by CT scan it was 52% and 91%, respectively

33. PET- CT Response assessment during neoadjuvant therapy — Early PET-CT during neoadjuvant therapy allows early recognition of non-responders and institution of salvage therapy for them. Response assessment after neoadjuvant therapy posttreatment 18F-FDG PET has good predictive value for long-term outcomes Follow-up PET can detect recurrent/metastatic disease in 8–17% of patients, sometimes even before disease can be diagnosed on standard imaging

34. Staging laparoscopy National Cancer Care Network (NCCN) recommends laparoscopic staging with peritoneal washings (lavage cytology) for patients with Siewert type 2 and type 3 advanced tumours clinical stage T3 or more or clinical node-positive tumours Changes treatment if 59.6% Avoid laparotomy- 43.8 % Bulky tumor, bulky nodal tumors, GE junction

35. SCC- ADC conceptual difference Field cancerization and lymphatic spread All etiology caused impact in whole esophagus, so entire esophagus has to be treated as SCC Lymphatic spread- proximal and distal

36. Management of SCC esophagus Irrespective of location Total esophagectomy Stomach tubes- for recon neck anastomosis Mckeown Thoracic, abdominal and cervical Transhiatal

37. Adenocarcinoma concept Need not treat entire esophagus Adequate margins only Proximal and distal margins- 3-5cm Beware of signet ring Use frozen section Adequate nodal clearance

38. Early Adenocarcinoma high-grade intraepithelial neoplasia or high-grade dysplasia and mucosal (T1a) and submucosal (T1b) carcinoma In a large study, the incidence of nodal metastasis was 0%  T1a 13%- T1b-sm1 19% -T1b-sm2 56% - T1b-sm3

39. T1m1 and T1m2 (?T1m3)-- EMR If well differentiated If not depressed If less than 2cm If final HPR- T1m3 o more- completion surgery 5 year survivial 87-90%

40. Management of Type III ADC Total Gastrectomy with D2 Dissection and lower esophageal LN

41. Type I lesion Higher lesion Clear subcarinal LN Ivor Lewis Intrathoracic anastomosis Mckeown Neck anastomosis ( often not needed in AdenoCa of OG junction)

42. Type II

43. Hulshcer Trial - Type I and Type II ADC

44. Hulshcer Trial - Type I and Type II ADC

45. Transthoracic operation Risk of complications for a possible oncologic advantage is indicated for the fit and/or younger patients Transhiatal surgery reserved for older patients with multiple comorbid conditions the early tumors wherein radical clearance in the mediastinum is considered unnecessary

46. an extended total gastrectomy including wide splitting of the diaphragmatic hiatus, transhiatal resection of the distal esophagus enbloc lymphadenectomy of the lower posterior mediastinum formal abdominal D2 lymphadenectomy Surg Oncol Clin N Am 15 (2006) 751–764

47. Dutch group, Annals of Surgery , December 2007 Transthoracic radical esophagectomy did not yield any survival benefit over a transhiatal esophagectomy

48. Lancet Oncol 2006 10 yr OS almost same

49. Left Thoracabdominal approach does not improve survival thas TH LTA leads to increased morbidity in patients with cancer of the cardia or subcardia LTA cannot be justified to treat these tumors if the length of oesophageal invasion is 3 cm or less Lancet Oncol 2006

50. Therefore, a transhiatal abdominal approach can be recommended for cases where the length of esophageal invasion is 4 cm or less , if safe excision and reconstruction are technically possible.

51. Summary of surgical management

52. Extended Lymphadenectomy Versus Standard Lymphadenectomy The extent of lymphadenectomy  abdominal, thoracic and cervical fields German guidelines, 16 nodes; UK guidelines, 15 nodes and NCCN (USA) guidelines, 15 nodes most acceptable operation in a young fit patient of EGJ adenocarcinoma is a standard two-field lymphadenectomy best done as a part of en bloc esophagectomy

53. Neoadjuvant and adjuvant in Adenoca Neoadjuvant protocols Perioperative chemotherapy Chemoradiation MAGIC protocol FLOT Protocol CROSS protocol

54. MAGIC – Stage II and III CA stomach 3 ECF SURGERY SURGERY 3 ECF Plus First adequately powered RCT Good design and conduct National and International Guidelines Minus Only 40% completed all chemo 26% OG jxn cases No updates 70% node positive ( no adju ) 13 % improvement in overall survival

55. FLOT Trial 2018/2019 55 % patient – OG junction tumors

56. 5 F u/ L eucoverin / O xaliplatin/ T axane MAGIC FLOT Med OS 35% 50% 5 yr OS 36% 45% Toxicity 27% 27% Hospitalization 26% 26%

57. Consensus Locally advanced ADC OG jn (T3/t4/N+) 4 FLOT SURGERY 4 FLOT 3 EOX SURGERY 3 EOX TOXICITY MAGIC REGIMEN

58. PROXIMAL STOMACH- CROSS TIRAL  NEOADJUVANT RADIATION LOCALLY ADVANCED OG JN TUMORS CTRT SURGERY SURGERY 75 % ADENOCARCINOMA- strong evidence CARBOPLATIN + PACLITAXEL+XRT (41.4 / Gy )--Surgery

59. PROXIMAL STOMACH- MAGIC VS CROSS VS FLOT Medial OS 5 yr Survival MAGIC 35 MONTHS 36% CROSS 49 MONTH 45% FLOT MONTHS 47 % Decision between FLOT and CROSS still no conclusion Decision by MDT

60. Awaited results of TOP Gear/ CRITICS II/ ESOPEC trials Regarding comparing CTRT VS FLOT

61. CROSS protocol- concerns Radiation field irradiates proximal stomach also – concern of vascularity or viability, as it is used in anastomosis in neck Lung toxicity Desmoplasia in irradiated patients

62. Thank you

63. References Shackelford's text book of Alimentary tract NCCN Guidelines/ Japanese Guideline of Esophagus and Esophagogastric junction cancer Japanese Gastric cancer guideline 2021 AJCC 8 th Edition Manual MAGIC/FLOT/CROSS Trials Mastery of Surgery GI Surgery Annual Volume 25 Indian Association of Surgical Gastroenterology Maingots Abdominal operation

64. Superior polar Gastrectomy Early Type III OG adeno tumors

65. Thank you

66. Siewert Type 2 extent of esophageal involvement (less or more than 3 cm) presence of mediastinal nodes the bulk of the tumour patient fitness to withstand a transthoracic procedure the experience of the surgical team to carry out adequate mediastinal clearance through the transhiatal route

67. Siewert type 2 tumours is a transhiatally extended total gastrectomy with radical resection of lower mediastinal nodes and a D2 lymphadenectomy in the abdomen alternative (e.g. transthoracic) surgical approaches may have to be chosen based on the above described factors

68. Siewert III total gastrectomy with D2 lymphadenectomy.

69. staging as based entirely on patients treated by esophagectomy alone (without preoperative or postoperative chemotherapy and/or chemoradiotherapy), the dataset used to develop the eighth edition TNM stage groupings included patients who had received preoperative induction therapy (neoadjuvant) and/or postoperative adjuvant therapy. The availability of these data led to the ability to explicitly define cTNM and ypTNM cohorts and stages

70. Tumours involving the esophagogastric junction with epicentre no more than 2 cm into the proximal stomach (originally Siewert type 1 and 2) are now to be staged as esophageal cancers tumours with epicentre located greater than 2 cm into the proximal stomach (originally Siewert type 3) are to be staged as stomach cancers even if EGJ is involved

71. A matched control study of two specialized esophageal centres comparing esophagectomy and endoscopic resection for pT1a tumours demonstrated excellent longterm survival rates (median follow-up: 4 years) in both groups but morbidity (32 vs. 0%) and mortality rates (2.6 vs. 0%) were much higher after esophagectomy [80].

72. In patients with adenocarcinoma, the depth of invasion determines the curative potential of endoscopic therapy. In case of T1a adenocarcinoma with favourable histology (absence of lymphovascular invasion or well differentiated G1 and G2 tumour ), if the margins of EMR resection are involved, then further endoscopic resection by EMR can be done multiple times till the entire lesion is resected. In general, if the post EMR T-stage is T1b or there are high-risk factors like lymphovascular invasion or poor differentiation, then surgical treatment is indicat

73. achieve this eradication of remainder of Barrett’s mucosa include complete endoscopic resection, radio-frequency ablation (RFA), cryotherapy and argon plasma coagulation (APC)

74. Surgery for Early Carcinoma multicentric disease or multiple islands of preneoplastic epithelium could be present throughout the Barrett’s mucosa in about half of the patients with early Barrett’s cancer Removal of the entire Barrett’s intestinal metaplasia in the distal esophagus therefore should be considered desirable in order to avoid recurrences. In addition adenocarcinoma invading the submucosa (T1b) has a high likelihood of local node involvement, though these are limited to lower mediastinum or lower.

75. r, endoscopic treatment has high metachronous/recurrent cancers within the Barrett’s mucosa in up to one-third of patients, thus needing lifelong surveillance and treatment [97]. The other problems of endoscopic treatment are persistent sub-epithelial islands of intestinal metaplasia and stricture rate that can approach 30%

76. The surgical options for early adenocarcinoma are as follows: Radical (transthoracic) esophagectomy (b) Transhiatal esophagectomy (most widely practiced option) (c) Minimally invasive esophagectomy (d) Vagus preserving esophagectomy (e) Merendino procedure (f) Sentinel node navigation surgery

77. Treatment of Locally Advanced Tumours Good quality surgical resection for EGJ carcinoma should aim to provide oncologic clearance with regard to the longitudinal resection margins (proximal and distal), circumferential resection margin and removal of all lymph node stations at risk of metastasis

78. Longitudinal Resection Margins it is reasonable to aim for 5 cm in vivo longitudinal resection margins (proximal and distal) and to confirm a tumour -free status with an intraoperative frozen section examination of the resection margins.

79. Circumferential Resection Margin (CRM)

80. Type II lesion Transhiatally extended total gastrectomy with radical resection of lower mediastinal nodes and a D2 lymphadenectomy in the abdomen alternative (e.g. transthoracic) surgical approaches may have to be chosen based on the above described factors Ivor Lewis/or Mckewons

81. Trans hiatal Esophagectomy ( Orringer ) Abdominal and neck incison Blunt dissection Oncological not safe

82. Mc kewon Trincisional surgery Three stage Thoracic approach- mobilize thoracic esophagus (open/MIS) Supine position – abdominal sugery Neck surgey Anastomosis in neck

83. Ivor Lewis Two stage Abdominal part- mobilize Lateral position- thoracoscopic part Thoracoscopic anastomosis