Prognostic Significance of Solitary Lymphnode Metastasis and Micrometastasis in Gastric Cancer

Mpallas, K.D.; Lagopoulos, Vasileios I.; Kamparoudis, Apostolos

doi:10.3389/fsurg.2018.00063

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…Gastric cancer is among the most common malignant digestive system tumors worldwide . Despite advances in the prevention, detection, and adjuvant treatment of gastric cancer, the number of people diagnosed with gastric cancer is increasing, and metastasis remains a major causative factor of cancer‐related death . However, the mechanism underlying metastasis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Epithelial‐mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1

Tian

et al. 2020

Cancer Medicine

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Background:Increasing numbers of studies have demonstrated that circulating tumor cells (CTCs) undergo a phenotypic change termed epithelial-mesenchymal transition (EMT), and researchers have proposed that EMT might provide CTCs with increased potential to survive in the different microenvironments encountered during metastasis through various ways, such as by increasing cell survival and early colonization. However, the exact role of EMT in CTCs remains unclear. Methods: In this study, we identified CTCs of 41 patients with gastric cancer using Cyttel-CTC and im-FISH (immune-fluorescence in situ hybridization) methods, and tested the expression of EMT markers and ULBP1 (a major member of the NKG2Dnatural killer [NK] group 2 member D-ligand family) on CTCs. Moreover, we investigated the relationship between the expression of EMT markers and ULBP1 on CTCs and gastric cancer cell lines. Results: Our results showed that the CTCs of gastric cancer patients exhibited three EMT marker subtypes, and that the expression of ULBP1 was significantly lower on mesenchymal phenotypic CTCs (M + CTCs) than on epithelial phenotypic CTCs (E + CTCs). EMT induced by TGF-β in vitro produced a similar phenomenon, and we therefore proposed that EMT might be involved in the immune evasion of CTCs from NK cells by altering the expression of ULBP1. Conclusions: Our study indicated that EMT might play a vital role in the immune invasion of CTCs by regulating the expression of ULBP1 on CTCs. These findings could provide potential strategies for targeting the immune evasion capacity of CTCs.

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Section: Introductionmentioning

confidence: 99%

Epithelial‐mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1

Tian

et al. 2020

Cancer Medicine

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“…Gastric cancer (GC) is the fourth most common malignancy worldwide; although its incidence is declining in the Western world, this disease still remains the second leading cause of cancer related death in both sexes [ 1 ]. The Japanese Gastric Cancer Association (JGCA) has recently defined the treatment guidelines of GC according to the tumor stage [ 2 ], precisely stratifying lymph node (LN) dissection according to the wideness of lymphatic resection [ 3 ]. As LN metastases occur early during the progression of the disease, JGCA highlighted the importance of collecting the higher number of epi- and peri-gastric detectable LNs [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…The Japanese Gastric Cancer Association (JGCA) has recently defined the treatment guidelines of GC according to the tumor stage [ 2 ], precisely stratifying lymph node (LN) dissection according to the wideness of lymphatic resection [ 3 ]. As LN metastases occur early during the progression of the disease, JGCA highlighted the importance of collecting the higher number of epi- and peri-gastric detectable LNs [ 3 ]. Accordingly, curative gastrectomy (with no macroscopic or microscopic residual tumor tissue) plus D2 LN dissection has been regarded as the standard surgery for potentially curable T2-4 tumors as well as cT1 N-positive tumors [ 4 ], with demonstrated decreased regional recurrence and improved long-term survival for patients [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…A retrieved LNs count of less than 16 LNs accounts for downstaging, which usually occurs in 10–25% of patients, and affects treatment plans and prognosis [ 8 , 9 , 10 , 11 , 12 ]. In fact, inadequate LN dissection can lead to residual cancer cells spreading to LNs, in the form of isolated tumor cells, micrometastasis (maximum size of 2 mm) or solitary single-LN metastasis (SLM) [ 3 ]. This results in a higher recurrence rate after surgery [ 5 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Surgeon–Pathologist Team Approach Dramatically Affects Lymph Nodes Detection and Improves Patients’ Short-Term Outcome

Ambrosio

Battini

et al. 2022

Cancers

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The downstaging of gastric cancer has recently gained particular attention in the field of gastric cancer surgery. The phenomenon is mainly due to an inappropriate sampling of lymph nodes during standard lymphadenectomy. Hence, collection of the maximum number of lymph nodes is a critical factor affecting the outcome of patients. None of the techniques proposed so far have demonstrated a real efficiency in increasing the number of identified lymph nodes. To harvest the maximum number of lymph nodes, we designed a protocol for on-site macroscopic evaluation and sampling of lymph nodes according to the Japanese Gastric Cancer Association protocol. The procedure was carried out by a surgeon/pathologist team in the operating room. We enrolled one hundred patients, 50 of whom belonged to the study group and 50 to a control group. The study group included patients who underwent lymph node dissection following the proposed protocol; the control group encompassed patients undergoing standard procedures for sampling. We compared the number and maximum diameter of lymph nodes collected in both groups, as well as some postoperative variables, the 30-day mortality and the overall survival. In the study group, the mean number of lymph nodes harvested was higher than the control one (p = 0.001). Moreover, by applying the proposed technique, we sampled lymph nodes with a very small diameter, some of which were metastatic. Noticeably, no difference in terms of postoperative course was identified between the two groups, again supporting the feasibility of an extended lymphadenectomy. By comparing the prognosis of patients, a better overall survival (p = 0.03) was detected in the study group; however, to date, no long-term follow-up is available. Interestingly, patients with metastasis in node stations number 8, 9, 11 or with skip metastasis, experienced a worse outcome and died. Based on our preliminary results, the pathologist/surgeon team approach seems to be a reliable option, despite of a slight increase in sfaff workload and technical cost. It allows for the harvesting of a larger number of lymph nodes and improves the outcome of the patients thanks to more precise staging and therapy. Nevertheless, since a higher number of patients are necessary to confirm our findings and assess the impact of this technique on oncological outcome, our study could serve as a proof-of-concept for a larger, multicentric collaboration.

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“…Cytokeratin is one component of the cytoskeleton of epithelial cells that is not present in normal lymph nodes, and its corresponding antibody is widely used to detect minute deposits of tumor cells in lymph nodes by IHC staining. Controversies remain regarding the clinical features of MI and its prognostic significance for GC (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Metastasis or Micrometastasis to the Lymph Node Along the Superior Mesenteric Vein in Gastric Carcinoma: A Retrospective Analysis

Zheng

Zhang

et al. 2021

Front. Oncol.

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BackgroundThe validity of lymphadenectomy of the lymph node along the superior mesenteric vein (LN14v) in gastric cancer remains controversial. The study investigated the characteristics and prognosis of gastric cancer with metastasis or micrometastasis to LN14v.MethodsA retrospective study of 626 patients undergoing radical gastrectomy in our center from January 2003 to December 2015 was analyzed. In total, 303 patients had lymphadenectomy of LN14v, and lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin nodes CK8/18. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis or metastasis on prognosis.ResultsThe metastatic rate of the LN14v lymph node was 15.8%, and the micrometastatic rate was 3.3%. Multivariate analysis showed site, Borrmann classification, postoperative lymph node metastasis (pN), and metastasis in LN6 and LN9 were predictive factors for LN14v micrometastasis or metastasis (P < 0.05). The 5-year survival rate in the positive group (LN14v micrometastasis or metastasis) was 12.4%. The prognosis of patients without LN14v lymph node micrometastasis was better than that of the positive group, whereas the difference between group of LN14v micrometastasis and LN14v metastasis was not obvious. In matched analysis, patients with stage III gastric cancer L/M area, pN2-3, and LN6(+) who underwent lymphadenectomy of LN14v had better survival than those without lymphadenectomy of LN14v.ConclusionLymph node micrometastasis may provide accurate prognostic information for patients with gastric cancer. Moreover, lymphadenectomy of LN14v might improve the survival of patients with stage III gastric cancer of L/M area, pN2-3, and LN6(+).

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Prognostic Significance of Solitary Lymphnode Metastasis and Micrometastasis in Gastric Cancer

Cited by 7 publications

References 43 publications

Epithelial‐mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1

Epithelial‐mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1

Surgeon–Pathologist Team Approach Dramatically Affects Lymph Nodes Detection and Improves Patients’ Short-Term Outcome

Clinical Significance of Metastasis or Micrometastasis to the Lymph Node Along the Superior Mesenteric Vein in Gastric Carcinoma: A Retrospective Analysis

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