TDs first appeared in the UICC/AJCC Tumor Staging Guide in the fifth edition of colorectal cancer staging in 1997, followed by the appearance of TDs in the 6th and 7th editions of colorectal cancer staging. However, the definition of TDs in each stage of colorectal cancer is different. The criteria and histological features of TDs have been modified several times. In the 7th edition of UICC/AJCC colorectal cancer staging, the TDs are defined as non-contiguous with the primary tumor and there is no evidence of lymphoid tissue structure, but the TDs in the lymph node drainage area, and the TDs have been included as N1c staging becomes an independent factor affecting prognosis. However, there is no evidence to suggest which version of the TDs is the most suitable for the actual survival of the patient. In gastric cancer, the TDs of the 8th edition of UICC/AJCC are classified as lymph node metastasis, the regional lymph node metastasis with no residual lymph node tissue evidence.
The pathophysiological causes of cancer nodules are still unclear, and most studies have shown that the appearance of TDs is associated with lymph node metastasis, neurovascular invasion, and microvascular system[5,8]. In terms of the cause of gastric TDs, there is no credible research report. We refer to the report of TDs in the field of colorectal cancer to study the classification of TDs. A study reported that they divided the invasive non-continuous tumor infiltration into four types, including scattered infiltration, vascular infiltration, neurological infiltration, and nodular infiltration. Subsequently, Goldstein et al. reported that the TDs were classified into three types: the nerve disseminated type, the vascular disseminated type, and the intravascular tumor. It is also reported that when the TDs are located in the mesorectum, they should be divided into intravascular, intratympanic, perineural, and isolated TDs. Some studies have found that the formation of TDs may be related to the de-interstitialization of tumor cells. The changes in the secretion of snail, twist, and epithelial cadherin promote the ability of tumors to metastasize and spread through lymph nodes. In summary, we found that the formation of TDs is associated with tumor invasive growth. In the three previous reports, the probability of developing TDs in gastric cancer patients was 17.8%, 23.9%, and 24%, respectively (sorted by publication time). It has been reported that the probability of TDs is related to tumor size, Borrmann classification, and to the extent of tumor infiltrating lymphatic vessels, lymphatic metastasis and expansion, and the survival of TDs and gastric cancer patients is significantly correlated.
In this study, we analyzed the status of TDs and the clinical physiology of patients, and found that the presence of TDs was associated with tumor infiltration (T), lymph node metastasis (N), tumor location, and neurovascular invasion, statistically significant (P <0.05). The relationship between patient age (whether greater than 61 years), gender, body mass index, pTNM stage, M stage, and degree of differentiation was not statistically significant (P < 0.05). This indicates that the TDs are related to the invasive ability of tumor cells, and the tumor cells in the TDs often have strong migration ability, which may be migration through the lymphatic pathway or sudden infiltration of tumor cells of unknown cause.
Although the overall survival rate of patients with gastric cancer has improved significantly over the past few decades, there are still many questions to be answered about histopathology and predictive factors. Studies have shown that TDs have independent prognostic value in colorectal cancer, however, only a few studies have reported the gastric TDs. Several studies have shown that the appearance of TDs predicts a poor prognosis, which is similar to our findings. Kaplan-Meier survival curves were used to map the survival of patients with positive and negative TDs. It was found that there was a significant difference between the two, which was statistically significant. Analysis of TDs and survival using multivariate Cox regression revealed that TDs positivity was not an independent risk factor for the prognosis of gastric cancer, which may be related to the presence of TDs in patients with more late stages. Using Cox regression to analyze the survival of all patients, only lymph node metastasis (N), age (more than 61 years old) were significantly different, and the other items were not significantly different. One study found that the presence or absence of TDs was not an independent factor when using Cox regression analysis. Studies have pointed out that gastric TDs are an important prognostic indicator and hope to incorporate TDs into lymph node staging. In addition, they classified TDs as metastatic lymph nodes and then re-staged patients with colorectal cancer and advanced gastric cancer using UICC/AJCC's 7th edition guidelines, and found TDs in patients with the same lymph node staging (pN). The appearance of this can lead to a worse prognosis. However, only 6 of the T1 and T2 TDs included in this study were not convincing. In a recent study, the histological typing of tumors and the extent of vascular invasion were important causes of TDs, and TDs were more common in intestinal tumors. Combined with current research, evidence for TDs in gastric cancer as an independent influencing factor is not sufficient.
We included 6,672 patients with gastric cancer surgery or gastric cancer with other pathological reports of TDs, a total of 341 cases, the TDs positive rate was 5.11%, lower than previously reported. There were 193 patients with positive deposits and 297 patients with negative deposits. Among them, 5 patients (2.59%) in stage I, 2 patients (14.51%) in stage II, 139 (72.02%) in stage III, and 21 (10.88%) in stage IV. The proportion of TDs in gastric cancer patients with a late stage is greater, suggesting that the appearance of TDs may indicate a later stage and a worse prognosis. We found that patients with the same TNM stage had a median survival of the TDs-positive group that was lower than the TDs-negative group, but there was no difference in stage IV patients. Kaplan-Meier survival curves were used to test the survival of the two groups. The prognosis of the patients with stage I TDs was worse than that of the negative group (P<0.000). The prognosis of the patients with stage II and III cancer deposits was lower than that of the negative group. The prognosis of the TDs positive group in the IV stage was better than that in the negative group, and the difference was not significant. At the same time, according to the location of the TDs suggested in the pathological report, the positive components of the TDs were the small curved group, the corpuscular group, the large curved group and the distal group. The median survival time was 37.0 months in the small curved group, the overall median survival time was 36.0 months in the corpus group, the median survival time was 15.2 months in the large curved side, and the median overall survival time was 9.9 months in the distal patient. The difference was significant and statistically significant.
It was found that when the TDs appeared on the large curved side of the stomach or the omental fat connective tissue, the patient's survival time was significantly reduced. When TDs appear on the small curved side of the stomach or on the stomach wall, there is no significant difference in survival between the two. Therefore, we believe that when the TDs appear on the small curved side of the stomach or on the stomach wall, it is limited by the anatomical positional relationship of the small omental sac and the lymphatic drainage path, and the invasion range is limited, and the possibility of distant metastasis is small. When the TDs appears in the large curved side of the stomach, the tumor cells may be transferred distally through the gastric colon ligament. When the TDs appears in the distal fat connective tissue or lymph node, it should not be considered as a N stage, but should be directly classified into the M1 stage. For patients with TDs with different TNM stages, only the Kaplan-Meier survival curves of patients with stage III were significantly different, and the Kaplan-Meier survival curves of the other three patients were not significantly different. In order to verify the influence of the location of cancer nodules on the staging of gastric cancer patients, and to find the staging that is more in line with the true survival of TDs positive patients, we made the following attempts. We compared the T-stage and N-stage of the TDs-positive small curved group with the TDs-negative group, and found that the survival curve of the TDs-positive small curved group was similar to that of the negative group of N1 and N2 staging patients. A valid conclusion is drawn. Comparing the T stage and N stage of the cancer nodule positive group and the TDs negative group, it was found that the survival curve of the TDs positive gastric group coincides with the negative group T3, T4b, N2 staging curve, we It is believed that when a TDs appears on the stomach wall, the T stage at this time should not be lower than the T3 stage, and the N stage has no conclusion.
Comparing the N staging of the TDs-positive large curved group with the cancer nodule negative group, it was found that the survival curve of the positive large curved group and the survival curve of the N3 phase of the negative group were higher, and we thought that the large curved side appeared. In the case of TDs, the N stage at this time, regardless of the number of lymph node metastases, is classified as N3. The M stage of the TDs-positive distal group and the TDs-negative group were compared, and the survival curve of the positive distal group was found to be close to the survival curve of the negative group M1. In this regard, we believe that when the pathological report suggests a TDs on the stomach (stomach wall), the T stage at this time should be no less than the T3 stage; when the TDs appears in the large curved side of the stomach, the N at this time The stage should be no less than N3; when prompted to see a cancer nodule in the distal tissue, the patient should be classified as M1.
Our study confirmed the adverse effects of TDs on the prognosis of gastric cancer. However, because this study was a single-center retrospective study, the number of cases was limited and the follow-up time was short. How to properly incorporate TDs into tumor staging still requires more large-scale clinical analysis, and also requires more in-depth basic research and exploration on the mechanism of TDs.