1、SPEAKER: CHENHUI NI E-email:,lymph node micrometastasis（LNMM） INadenocarcinoma of the esophagogastric junction(AEG),The incidence of adenocarcinoma of the esophagogastric junction (AEG)is increasing。 The incidence of esophageal adenocarcinoma rose from 0.13 for 1935-1971 to 0.74 for 1974-1989, and t
2、he incidence of adenocarcinoma of the esophagogastric junction rose from 0.25 to 1.34 per 100,000 person-years. whereas that of distal gastric adenocarcinoma has steadily decreased.,2,References,Cardia gastric carcinoma OR adenocarcinoma of the esophagogastric junction(AEG) ?,3,Definition & classifi
3、cation,histologyClinicalsiewert,AEG I：between 5 cm and 1 cm oral of the junctionAEG II：between 1 cm oral and 2 cm aboral of the junction AEG III ：2 cm and 5 cm aboral of the junction,4,siewert 1999 the international society for disease of the esophagus (ISDE) THE international gastric cancer associa
4、tion(IGCA),Classification,References,the clinical symptoms of these tumors are often quite vague and tend to intensify only gradually in severity over a long period of time, most patients are first diagnosed when these carcinomas already are locally advanced。The only chance for long term survival fo
5、r these patients is a complete (International Union Against Cancer UICC R0) removal of the tumor。,References,5,the importance of N statusOne of the key factors that determines the prognosis of patients with tumors throughout the gastrointestinal tract is the involvement by tumor of regional lymph no
6、des (N status)For patients with AEG, the N status has been shown to be an independent prognostic factor。,recurrence Although surgical techniques have improved, the overall prognosis for patients with these tumors remains poor primarily due to local tumor recurrence and the development of distant met
7、astases,References,7,The recurrence rates of type I, II, and III tumors were 57.1%, 44.4%, and 41.0%, respectively. The most frequent relapse site was lymphogenous in type I, hematogenous in type II, and disseminative in type III tumors. The median time-to-recurrence after surgery was 12.6 months in
8、 type I, 12.5 months in type II, and 12.7 months in type III disease, with no significant difference.,Recurrence patterns of esophagogastric junction adenocarcinoma according to Siewerts classification after radical resection；Anticancer Res. 2014 Aug;34(8):4391-7,LNMM,Micrometastasis was defined as
9、tumor cell clusters measuring from 0.2 mm to 2.0 mm in their greatest dimension，and are commonly identified by immuno-histochemistry (IHC) but can be confirmed by routine HE。isolated tumor cells (ITC) are defined as single tumor cells or small clusters of cells measuring 0.2 mm in their greatest dim
10、ension。macrometastasis，MA,lymph node micrometastasis,UICC & AJCC,Greene FL. AJCC Cancer Staging ManualM. New York : SpringerVerlag, 2002:111-119,References,8,References,9,how to find,immunohistochemistry (IHC) Ber-EP4 AE1/AE3 CK19 CD44V6(CAM5.2;E-CAD;CCR7 ；CXCR4)reverse transcription-polymerase chai
11、n reaction（RT-PCR),10,how to find,immunohistochemistry (IHC) Ber-EP4 AE1/AE3 CK19、20 CD44V6(CAM5.2;E-CAD;CCR7 ；CXCR4)reverse transcription-polymerase chain reaction（RT-PCR),11,Ber-Ep4,found in 1990 by U Latza, G Niedobitek, R Schwarting, H Nekarda, H SteinBer-Ep4 is an antibody against two glycopoly
12、peptides of 34 and 39 kD on the surface and the cytoplasm of all epithelial cells except for the superficial layers of squamous epithelia, parietal cells, and hepatocytes. The antibody does not cross-react with mesenchymal tissue including lymphoid tissue.,stomach,Mammary gland,References,12,how to
13、find,immunohistochemistry (IHC) Ber-EP4 AE1/AE3 CK19 CD44V6(CAM5.2;E-CAD;CCR7 ；CXCR4)reverse transcription-polymerase chain reaction（RT-PCR),13,RT-PCR,RT-PCR assay is thought to be far more sensitive than the immunohistochemical method。RT-PCR assay identified lymph node micrometastasis in 31.3% of p
14、atients, whereas IHC detected lymph node micrometastasis in 11.3% of patients。Several studies have reported an RT-PCR analysis to detect the positive expression of CEA, CK19, or CK20 mRNA in 5.3-23.8% of the LNs that are free from histological metastasis 。.,References,14,problems,false-positives & f
15、alse-negativessensitivity & specificity First, false-positives may be produced by RT-PCR because of the contamination or the presence of pseudogene . Second, there is a possibility of false-negatives because of the heterogeneous expression of target markers。its sensitivity and specificity were repor
16、ted as 88.9% and 96.6%,respectively。,References,15,16,sentinel node (SN) new treatment,prognostic,Clinical Significance of Lymph Node Micrometastasis,significance,intraoperation,postoperation,preoperation,lymphadenectomyintraoperative iagnostic tool,17,sentinel node (SN) new treatment,prognostic,of
17、Clinical Significance of Lymph Node Micrometastasis,significance,intraoperation,postoperation,preoperation,lymphadenectomyintraoperative iagnostic tool,If a minimally invasive surgery could be performed to treat esophageal cancer,the mortality rate after surgery and the postsurgical quality of life
18、could improve. Regarding surgical treatment, minimally invasive mucosal resection (EMR), endoscopic submucosal dissection (ESD), and blunt dissection are chosen and performed based on the stage and preoperative conditions of patients.,18,The sentinel node (SN) concept was first advocated by Morton e
19、t al. in patients with melanoma.SN biopsy for breast cancer and malignant melanoma has been accepted worldwide as a useful technique for assessment of lymph node status.,sentinel node (SN),preoperation,References,Detection of Sentinel Nodes,One day before surgery, 3 mCi (2 mL) of 99mTechnetium-tin c
20、olloid (a dioisotope (RI) colloid) was endoscopically injected into the submucosa of the esophageal wall at four sites (0.5 mL each) around the tumor using a disposable 23-gauge needle (MAJ-75, Olympus, okyo, Japan). Lymphoscintigraphy was performed 2 h after RI injection. During surgery, the uptake
21、 of RI in each lymph node was counted using Navigator GPS (TYCO HEALTHCARE, Ltd., Tokyo, Japan). After surgery, the absence of residual radioactivity was intraoperatively confirmed by Navigator GPS in the cervical,mediastinal, and abdominal fields.All dissected lymph nodes were mapped and RI uptake
22、was measured again.Lymph nodes with RI counts five times greater than background levels were classified as hot nodes and were defined as sentinel nodes (SNs).,preoperation,References,20,sentinel node (SN) new treatment,prognostic,of Clinical Significance of Lymph Node Micrometastasis,significance,in
23、traoperation,postoperation,preoperation,lymphadenectomyintraoperative iagnostic tool,Lymphatic Spread and Microinvolvement inAdenocarcinoma of the Esophago-Gastric Junction Journal of Surgical Oncology 2006;94:307315,intraoperation,Lymph nodes were sampled and grouped into three compartments: (1) me
24、diastinal lymph nodes, (2) lymph nodes adjacent to the tumor,(3) upper abdominal nodes.,intraoperation,Frequency and Clinical Impact of Lymph Node Micrometastasis and Tumor Cell Microinvolvement in Patients with Adenocarcinoma of the Esophagogastric Junction,intraoperation,References,intraoperative
25、diagnostic tool,To develop RT-PCR assay as an intraoperative diagnostic tool for the detection of LNM, RT-PCR assay needs to enable rapid analysis during operation as well as to retain high sensitivity and specificity.Yaguchi et al.recently reported the utility of one-step nucleic acid amplification
26、 (OSNA) .OSNA can take approximately 30 min to diagnose the presence or absence of lymph node metastasis.OSNA examines only CK 19 expression, the sensitivity and specificity in a study of 162 lymph node samples obtained from 32 patients with gastric cancer were 88.9 % and 96.6 %, respectively. this
27、molecular system could be a promising tool for intraoperative detection of LNM when performing minimally invasive surgery with personalized lymphadenectomy in patients .,intraoperation,References,25,sentinel node (SN) new treatment,prognostic,of Clinical Significance of Lymph Node Micrometastasis,si
28、gnificance,intraoperation,postoperation,preoperation,lymphadenectomyintraoperative iagnostic tool,postoperation,2004 and 2010,None of the patients had received preoperative chemotherapy or radiotherapy.,The presence of CK19-positive or CD44v6-positive cells was significantlyrelated to depth of invas
29、ion (P = 0.043 and P = 0.046, respectively) and Lauren classification (P = 0.019 and P = 0.007,respectively), but not to age, sex, tumour size or degree of differentiation.,Survival,30,SOME RANDOM SUBTITLE,but ome authors hold an different opinion,References,summary,1. Recurrences of adenocarcinoma
30、of the esophagogastric junction are frequent even in patients who are classified as pN0 after radical resection, suggesting that occult nodal metastases may have been missed on routine histologic examination. 2. LNMM was defined as tumor cell clusters measuring from 0.2 mm to 2.0 mm i n their greate
31、st dimension，and are commonly identified by immuno-histochemistry (IHC) but can be confirmed by routine HE。3.Findings : (IHC) Ber-EP4 AE1/AE3 CK19 CD44V6 (CAM5.2;E-cAD;CCR7 CXCR4 （ RT-PCR)4. significance : sentinel node (SN) a new treatment intraoperative iagnostic tool prognostic and lymphadenectomy,chenhui ni,THANKS,
