Biopathologic features and clinical significance of micrometatasis in the lymph node of early gastric cancer

AIM: To evaluate the biopathologic features and clinical significance of nodal micrometastasis(MI) in early gastric cancer(EGC).METHODS: Among 1022 EGC patients who underwent gastrectomy with lymphadenectomy of D1 + β or more from March 2001 to December 2005 at the Korean National Cancer Center, available nodal metastasis was found in 90 p T1N1 patients. Nodal metastasis was confirmed by immunohistochemistry(IHC) with cytokeratin and patients were classified into MI and macrometastasis(MA) groups based on the main tumor burden according to the 6th International Union Against Cancer/American Joint Committee on Cancer staging system; the main tumor burden with a diameter of greater than 0.2 mm but no greater than 2 mm as MI, and greater than 2 mm as MA of the representative metastatic node. Proliferative and apoptotic activities of the primary tumor and the nodal metastasis were measured by IHC with Ki-67 and terminal deoxynucleotidyl transferase d UTP nick end labeling, respectively. Biopathologic and clinical features of the patients were analyzed and compared between MI and MA groups. Patients with recurrence were compared with those without recurrence to identify risk factors for recurrence.RESULTS: Thirty-seven patients showed MI and the other 53 patients revealed MA in the lymph node; the incidence of patients with MI and MA was 41.1% and 58.9%. The main tumor burden was 0.9 and 4.6 mm in the representative metastatic node, respectively. Japanese N2 stations were more frequently involved in MA group(20.9%) than in MI group(10.3%) butthe difference was not statistically different(P = 0.338). Proliferative and apoptotic activities of MI were decreased than those of MA(26.7% vs 40.5%, P = 0.004 and 1.0% vs 3.0%, P < 0.001, respectively). However, nodal MI in the current study showed a relatively high proliferative activity and an equivalent apoptotic activity compared to other cancers in the previously published studies. Recurrence was observed in 6 patients during the mean follow up period of 87.6 ± 26.2 mo. The recurrence was significantly associated with the presence of MA(P = 0.041) and lymphovascular invasion of the primary tumor(P = 0.032).CONCLUSION: Lymphadenectomy of D1 + β or more might be necessary in patients with MI in sentinel node to prevent recurrence by clearing MI involving Japanese N2 station.

Predictive value of E-cadherin and Ep CAM for detection of metastatic lymph node in early gastric cancer

Objective:There has been a demand for a tumor-specific marker for metastatic lymph nodes in sentinel navigation surgery for gastric cancer.The aim of this study is to analyze protein expression in both primary tumors and metastatic lymph nodes in early gastric cancer patients.Methods:We collected primary tumors and metastatic lymph nodes from 71 patients who underwent curative gastrectomy and pathologically diagnosed with T1 N1 or T1 N2(8 th Union for International Cancer Control 8 th edition/American Joint Committee on Cancer staging system)gastric cancer.Immunohistochemistry was used to determine the expression of six cell membrane proteins,including carcinoembryonic antigen(CEA),E-cadherin,epithelial cell adhesion molecule(Ep CAM),P-cadherin,CD44 v6,and c-erb B2 in the patient samples.Results:The expression of CEA,E-cadherin,Ep CAM,P-cadherin,CD44 v6 and c-erb B2 in the evaluable primary tumor samples was 75.4%,97.1%,100%,89.9%,11.1%and 7.2%,respectively.Among cases wherein both the primary tumor and metastatic lymph nodes were evaluable,double positivity(expression in both primary tumor and metastatic lymph nodes)was observed for CEA,E-cadherin,Ep CAM,P-cadherin,CD44 v6 and c-erb B2 in 53.2%,97.9%,98.1%,76.6%,0 and 6.8%of the cases,respectively.The proportion of metastatic lymph nodes positive for CEA,E-cadherin,Ep CAM,P-cadherin,CD44 v6 and c-erb B2 was 71.4%,100%,98.1%,83.7%,0,and75%,respectively in primary tumors positive for the same markers.Conclusions:E-cadherin and Ep CAM had an overlap of 100%and 98.1%between the primary tumor and metastatic lymph nodes,respectively.Thus,E-cadherin and Ep CAM are potential molecular markers to detect metastatic lymph nodes in patients with early gastric cancer.

Recent updates and current issues of sentinel node navigation surgery for early gastric cancer

With the increase in the incidence of early gastric cancer(EGC),several endoscopic and laparoscopic approaches,such as endoscopic submucosal dissection and function-preserving gastrectomy,have been accepted as standard treatments.Sentinel node navigation surgery(SNNS)is an ideal surgical option for preservation of most parts of the stomach and consequent maintenance of normal gastric function to improve quality of life in patients with EGC.Although many previous studies and clinical trials have demonstrated the safety and feasibility of the sentinel node concept in gastric cancer,the clinical application of SNNS is debatable.Several issues regarding technical standardization and oncological safety need to be resolved.Recently several studies to resolve these problems are being actively performed,and SNNS might be an important surgical option in the treatment of gastric cancer in the future.

Factors associated with metastasis in superior mesenteric vein lymph node in subtotal gastrectomy for gastric cancer:Retrospective case control study

Objective: The revised Japanese treatment guideline for gastric cancer recommends dissection of the superior mesenteric vein lymph node(No. 14v LN) if there is metastasis in infrapyloric lymph node(No. 6 LN). However,it is still controversial whether LN dissection is necessary. The aim of this study was to investigate the factors associated with metastasis in No. 14v LN.Methods: Patients who underwent D2 lymphadenectomy between 2003 and 2010 were included. We excluded patients who underwent total gastrectomy, had multiple lesions, or had missing data about the status of metastasis in the LNs that were included in D2 lymphadenectomy. Clinicopathologic characteristics and the metastasis in regional LNs were compared between patients with No. 14v LN metastasis(14v+) and those without(14v-).Results: Five hundred sixty patients were included in this study. Univariate analysis showed that old age, larger tumor size, tumor location, differentiation, lymphatic invasion, venous invasion, perineural invasion, T classification, and N classification were related to metastasis in No. 14v LN. Multivariate analysis showed differentiation(P=0.027) and N classification(P<0.001) were independent related factors. Metastasis in infrapyloric lymph node(No. 6 LN) and proxiaml splenic lymph node(No. 11p LN) was independently associated with metastasis in No. 14v LN.Conclusions: Differentiation and N classification were independent factors associated with No. 14v LN metastasis, and No. 6 and No. 11p LN metastasis were independent risk factors for No. 14v LN metastasis.

Gastric choriocarcinoma admixed with an α-fetoprotein-producing adenocarcinoma and separated adenocarcinoma

We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adeno-carcinoma. A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduodenoscopy (EGD). Initial laboratory data showed the increased serum level of AFP and EGD revealed a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum. The patient underwent radical subtotal gastrectomywith D2 lymph node dissection and Billroth gastrojejunostomy. Histopathological evaluation confirmed double primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant chemotherapy were initiated. No recurrence or distant metastasis was observed at 4 years postoperatively.

Current status and challenges in sentinel node navigation surgery for early gastric cancer

Although a number of feasibility studies for sentinel node （SN） concepts in gastric cancer have been conducted since 2000, there remains a debate regarding detailed detection techniques and oncological safety. Two important multicenter phase II clinical trials were performed in Japan that used different methods and reached different conclusions; one confirmed acceptable results with a false-negative rate of 7%, and the other showed an unacceptably high false-negative rate of 46.4%. The Sentinel Node Oriented Tailored Approach （SENORITA） trial is a multicenter randomized controlled phase 1/I trial being performed in Korea. Patient enrollment is now complete and the long-term results are currently awaited. Recently, an image-guided SN mapping technique using infrared ray/fluorescence was introduced. This method might be a promising technology because it allows the clear visualization of SNs. With regard to the primary tumor, the non-exposed endoscopic wall-inversion surgery technique and non-exposure endolaparoscopic full-thickness resection with simple suturing technique have been reported. These methods prevent abdominal infection and tumor seeding and can be good alternatives to conventional laparoscopic gastric wedge resection. For indications, SN navigation surgery can be extended to patients who underwent non-curative endoscopic resection. Although a few studies have been performed on these patients, sentinel concepts may be beneficial to patients as they omit the need for additional gastrectomy. SN navigation surgery can lead to actual organ-preserving surgery and plays a key role in improving the quality of life of patients with early gastric cancer in the future.