Analysis and suggestion of endoscopic non curative resection for early gastric cancer

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Gastric (early) cancer (EGC) is defined as the infiltration of the tumor is confined to the mucosa or submucosa, regardless of the size of l

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Gastric (early) cancer (EGC) is defined as the infiltration of the tumor is confined to the mucosa or submucosa, regardless of the size of lesions and lymph node metastasis. The prognosis of this type of gastric cancer is good, no matter the endoscopic or surgical treatment, 5 year survival rate of more than 90%. However, compared with traditional surgery, endoscopic treatment of EGC has the advantages of small trauma, low cost, fewer complications, fast recovery and high quality of life of patients with postoperative survival, has become the first choice for treatment of EGC. However, endoscopic treatment of EGC is to achieve the same therapeutic effect as surgery, the premise is that the early lesions must be completely removed, and the risk of lymph node metastasis without disease, that is to achieve the standard of curative resection. In clinical practice, patients with EGC may be treated with endoscopic therapy, but we can not achieve the standard of curative resection by pathological evaluation of the pathological changes. With the development of minimally invasive endoscopic treatment technology and is widely applied, the increasing number of cases of non curative resection of the clinical encounter, but the current lack of analysis of curative resection, the treatment strategy of further controversy. Therefore, we according to the domestic and foreign existing research results, the non curative resection and the pathological features of further treatment and prognosis are discussed, hoping to provide a useful reference for further treatment strategies for EGC endoscopic resection of non healing.

First, EGC endoscopic treatment of the relevant concepts

According to the Japanese gastric cancer treatment guidelines (2010), for the possibility of lymph node metastasis in very low EGC, ESD syndrome is an absolute diameter less than 2 cm, with better differentiation of ulcer mucosa cancer. At the same time, the guidelines are also given in the ESD treatment of EGC relative indications, including: (1) differentiated mucosal cancer, if the surface is not formed in ulcer size can be more than 2 cm; (2) differentiated mucosal cancer, if the surface has formed ulcer, in diameter less than 3 cm (3; undifferentiated type) mucosa carcinoma, surface ulceration, and lesion diameter less than 2 cm; (4) differentiation and invasion and submucosa, invasion depth of not more than 500 m.

EGC endoscopic complete resection is a complete excision of the lesion, and the pathological changes of the horizontal and vertical margins are negative. Curative resection is to meet the standard of complete resection of EGC, and to evaluate the risk of lymph node metastasis. According to the Japanese gastric cancer treatment guidelines for absolute indications to meet the requirements of complete resection, tumor diameter less than 2 cm, differentiated cancer, depth is pT1a, the horizontal and vertical negative margins, and no lymph and blood vessel invasion. One of them is to meet the following four requirements for the relative indications: (1) no more than 2 cm differentiated pT1a ulcer ulcer type; (2) differentiated pT1a within 3 cm; (3) within 2 cm without ulcer undifferentiated pT1a; (4) below 3 cm depth and differentiation type pT1b-SM1 (infiltrating the muscularis mucosa is less than 500 m), and the horizontal and vertical negative margins, and no lymph vessel invasion. Does not meet any of the above 4 cases of non healing. EGC's curative resection is undoubtedly the ultimate goal of endoscopic treatment, and the key is the need for clinicians to fully understand the indications for endoscopic treatment. However, postoperative pathology confirmed that some of the EGC did not reach the standard of curative resection after endoscopic treatment.

Cho et al. In recent years, the relevant literatures about the therapeutic effect of ESD on EGC in eastern and Western countries were analyzed. The results showed that the total resection rate was 92% to 97%, and the cure rate was about 73.6%. The results show that non curative resection is still a certain proportion in the postoperative pathological evaluation.

Two, EGC endoscopic non curative resection analysis

Non curative resection of the situation mainly includes 2 aspects: (1) incomplete resection, including non resection and (or) positive margin; (2) there is risk of lymph node metastasis risk factors, such as the depth of submucosal invasion and more than 500 mu m, vascular invasion and tumor differentiation.

(I) incomplete excision

1 en bloc resection: EGC endoscopic treatment consists of the following 2 approaches, namely EMR and ESD. Facciorusso et al. 1916 patients with EGC treated by ESD were compared with those of treated by EMR. The results showed that the rate of ESD en bloc resection was significantly higher than that of EMR. The maximum diameter of EMR was about 2 cm, for more than 2 cm lesions require multi block resection, i.e. non ESD en bloc resection; mucosal ring dissection, is not affected by the size of the lesion, the theory can be en bloc, so as to improve the objectivity of pathological diagnosis margin.

In Japan, ESD is the most commonly used safe and effective treatment in clinic. Meta analysis of ESD and EMR in 2013 and 2 published in China in the year of 2015 showed that the effective rates of ESD en bloc resection rate, complete resection rate, curative resection rate and recurrence rate were significantly better than those of EGC (EMR). At present, ESD has replaced EMR as the main treatment of EGC in clinic. But it is worth noting that, compared with the ESD, the technical difficulty is small, the operator is more easy to grasp, for the 2 cm lesions, EMR can still be used as a safe and effective method for clinical application. In addition, in 2010, the guidelines for the treatment of gastric cancer in Japan, said the use of EMR for treatment, but for multiple block resection, if the differentiated cancer and meet other conditions of curative resection can be considered for further closer observation.

2 the level of incisal margin and (or) vertical margin was positive: complete resection of the EGC requires the removal of intact cells on the basis of en bloc resection, horizontal margins (lateral margins), and vertical margins (basal margins). Nagano of 726 cases of endoscopic therapy (including ESD and EMR) of the EGC patients were divided into two groups, group A with the level of margin of mucosal cancer positive (n=309), B group of cancer submucosal infiltration depth is less than 500 m and higher degree of differentiation (n=14), C group of cancer submucosal invasion depth of more than 500 m and vertical negative margin (n=15), D group of vertical positive margin (n=10), the results showed that A group additional surgery rate was 6.8%, while B, C and D group were 21.4%, 73.3% and 100%; no tumor recurrence in patients with follow-up and group A had no additional surgery in after treatment, endoscopic cancer cell survival rate was 5.8%, no lymph node metastasis, while in B, C, D group after endoscopic treatment of cancer cell survival rate were 7.1%, 13.3% and 40%, the rate of lymph node metastasis were 14.3%, 6.7% and 10%. Thus, Nagano proposed for mucosa cancer with the level of margin positive patients (A group), cancer cell survival rate and lymph node metastasis rate is low, can close follow-up again or endoscopic treatment; for cancer cells infiltrating the submucosa and vertical margin positive patients, metastasis rate significantly increased cancer cell survival rate and the lymph nodes, additional surgical resection should be. Lee were analyzed in 28 cases of patients with endoscopic non curative resection and additional surgical resection, simple horizontal margin and simple vertical margin positive postoperative residual cancer cells were 25% and 33.3%, with vertical margin level of positive margin postoperative cancer cell survival rate was 66.7%, the recommended level of margin patients with positive close follow-up, and suggested that combined vertical cut edge positive patients added further surgery.

The results of a non - surgical resection of a positive, positive, positive margin were also observed in the 2010 guidelines for the treatment of gastric cancer in japan. Kim of 55 cases of postoperative pathology confirmed for patients with positive margins of up to 23 months of follow-up, 20 cases were found among them (36.4%) developed local recurrence, local recurrence rate and pointed out that the lesion size of the lesion and the level of correlation between the length of cutting edge positive, positive margin level is more than 6 mm in length independent risk factors for local recurrence of the disease.

In summary, the vertical positive margin because of the high transfer rate and the rate of residual lymph nodes after surgery, the need for additional surgery for further treatment of radical operation; the level of margin of mucosal cancer patients with a positive rate of residual cancer cells, and the lymph node metastasis rate is low, if the patient refused or because of physical conditions do not allow additional surgery. You can choose the level of close follow-up, positive margin length can be an additional criterion for further treatment, study the large sample size is needed to confirm. In addition, the study found that the level of positive margin is mainly attributed to the ESD marking scope is not accurate enough, so it can be considered again for ESD 15, but the effectiveness of the research two ESD operation still need large sample further support.

(two) risk factors associated with lymph node metastasis

After EGC surgery, the 5 year survival rate of patients without lymph node metastasis was from 85% to 100%, while the survival rate of patients with lymph node metastasis was less than 72% ~ 93.5%. Thus, whether or not lymph node metastasis is the key factor to determine the prognosis and the treatment strategy. However, EGC lymph node metastasis rate is low, if all surgery, excessive treatment of suspected. According to the research of lymph node metastasis and degree of differentiation of cancer cells, submucosal invasion depth, vascular invasion and whether there are relevant factors, analysis of these factors can help determine the risk of lymph node metastasis size, which can choose different treatment strategies.

1 cancer cells of submucosal invasion and vascular invasion and related research findings: the mucosa cancer lymph node metastasis rate is l% ~ 3%, once the cancer cell invasion and submucosa, its metastatic rate is increased to 11% ~ 20%. Hoteya according to the depth of invasion in EGC cancer cells after ESD in pathological examination 818 cases of patients with EGC (977 EGC lesions) were divided into 3 groups, group M (cancer cell infiltration of the mucosa), SM1 group (cancer cell infiltration and submucosa depth < 500 m and group SM2 (tumor cell invasion of mucosa the lower and the depth > 500 m) group, M resection rate was as high as 92.6%, SM1 group the curative resection rate was 63.8% (48 / 77), M group and SM1 group of non curative resection in patients with vascular invasion and only 1 cases, SM2 group of non curative resection in patients with midrib invasion and up tube 65%. They suggest that submucosal infiltration is an important factor leading to vascular invasion, and local vascular invasion is an important step in lymph node metastasis. In addition, the study also proposes "the volume index of submucosal" (i.e. submucous infiltration area * submucous infiltration depth) of this new concept, that is not all submucosal invasive carcinoma require additional resection, can be judged according to the volume index of mucous membrane, but need further study in the test.

Traditionally, if confirmed after endoscopic resection and vascular invasion, need regular additional surgical resection, which is determining the local vascular infiltration and lymph node metastasis rate and a positive correlation based on the research results. But according to the latest research results, like the concept of "volume index" submucous, researchers put forward the concept of "lymph node metastasis index", according to a large number of research data, the submucosa cancer cell invasion depth, width and volume of tumor thrombus considered, so that the fluctuation range is similar to the "norms", to guide the clinical treatment.

To sum up, some researchers believe that the invasion of the submucosa is the first cause of local infiltration of the vessel, which leads to an increase in the rate of lymph node metastasis. It is worth noting that the endoscopic resection and surgical resection specimens of submucosa thickness compared to the difference is very large. This difference is due to endoscopic resection specimens before fixing often need to fully stretch to the specimen flattening, excessive retraction will result in submucosal layer deformation, thus affecting the submucosal infiltration of cancer cells determine the depth, so the specimen processing process standardization is the first step to determine the submucosa cancer cell invasion depth. According to the guidelines for treatment of EGC in Japan, patients with submucosal invasion depth of more than 500 m are at higher risk of lymph node metastasis, and do not meet the criteria for EGC endoscopic treatment, often requiring further treatment. However, in the above study, the patients with lymph node metastasis or tumor recurrence were found rarely. Therefore, the patients with negative margin and relative contraindication were considered to be followed up closely. The submucosal volume index, lymph node index "equivalent new concept was proposed to calculate the probability, whether lymph node metastasis or recurrence of cancer cells according to the submucosa infiltration volume, so as to determine the need for further treatment, and further research confirmed.

2 the degree of pathological differentiation and vascular invasion: in Japan, clinically referred to the poor degree of differentiation usually include low differentiated adenocarcinoma and signet ring cell carcinoma. Generally, endoscopic treatment is based on postoperative pathology. Pathological differentiation of tumor invasion and easy local vessels, leading to lymph node metastasis, pathological differentiation degree is worse, the higher the degree of malignant disease, local vascular invasion and more widely, the risk of lymph node metastasis is greater.

Lee of 847 cases confined to the mucosal layer and the surgical EGC patients were divided into two groups according to postoperative pathology, 215 cases with poorly differentiated or undifferentiated components in patients with postoperative pathology was analyzed and found to contain the postoperative pathological mucosal cancer patients with poorly differentiated or undifferentiated components, the lymph node metastasis rate significantly higher than the differentiated mucosal cancer patients (5.1% vs 0.5%, P < 0.001), undifferentiated or poorly differentiated components and with lymph node metastasis was positively correlated (OR=4.39, 95%CI:1.08 ~ 17.89), and when it exists with other risk factors, such as lesion diameter > 2 cm, with its lymph node ulcer. The transfer rate can be increased to 10%. In the study of Oda 25 in 298 cases of non curative resection in cases can be attributed to the poor differentiation of the 45 cases, including 12 cases of radical surgical treatment, postoperative lymph node metastasis rate was 6.3%, local recurrence was observed in other patients.

Bang summarize the data of endoscopic therapy, the differentiation degree of poor EGC Meta analysis, pointed out that the poorly differentiated EGC cancer cells in the mucosa hyperplasia in the area are not continuous distribution and exists in the middle of a layer of mucosa but not exposed to the mucosal surface, which makes the horizontal extension after accurate measurement of cancer cells the depth of invasion and greatly increased the difficulty of. Typically, ESD expanded to the degree of pathological differentiation syndrome mainly refers to the assessment of postoperative histopathology, and the pathology of ESD before operation is also very important, Bang pointed out that ESD preoperative and postoperative pathological differences can be used as a measure of the risk of lymph node metastasis index.

3 other: in fact, in addition to the above two points, female, age, tumor located in stomach in the lower, larger tumors, depression type tumors, ulceration, diffuse type of organization and other factors may be EGC risk factors for lymph node metastasis. Shin suggested that for gastroscopy in the treatment of EGC, can be divided into two steps: the first step is to evaluate the patients with endoscopic lesions and biopsy and imaging evaluation before treatment, selection of appropriate patients; the second step is to evaluate the operation and risk analysis and further necessary sample pathology after treatment, especially about the size of the tumor, histological type, depth of invasion and vascular invasion and the situation. This requires close cooperation between the endoscopic surgeon, pathologist and surgeon.

Three, summary

Pathological data research and analysis of the EGC of the surgical operation after the discovery, about 1 / 3 of the patients with the indication of endoscopic therapy and surgery; endoscopic treatment group to meet the relative fitness of mucosal cancer syndrome occurred only 5.2% lymph node metastasis. To a certain extent, this data indicates the great potential of clinical application of endoscopic therapy. With the endoscopic treatment technology especially the continuous improvement and development of ESD technology, more and more EGC underwent endoscopic treatment, to be sure, at the same time there will be more and more patients with postoperative pathologic evaluation for non curative resection. The research at home and abroad for the non curative resection is additional surgical radical surgery treatment is controversial, at present there is evidence to support on the part of non curative resection in patients with conservative treatment and close follow-up can. In addition, there are more and more research provides a more accurate method to evaluate the risk of lymph node metastases, believe that with the development of relevant research, we can get the treatment more and more accurate and more feasible to guide the clinical objective clinical evidence. In conclusion, EGC endoscopic treatment will be more and more popular, and the selection of non curative resection of the further treatment strategies for endoscopic, to improve the prognosis of patients, to avoid further surgical trauma and reduce the medical burden will be of great significance.

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