Since the release of the 3rd edition of the Japanese Guidelines for the Treatment of Gastric Cancer in 2010 (hereinafter referred to as “the Guidelines”), it has had a great impact on the surgical treatment of gastric cancer, and the treatment of gastric cancer has become more standardized, rationalized, and standardized. In recent years, new scientific research results have twice led to the revision and reprinting of the Guidelines. 2014 Jiangsu Geriatric Hospital General Surgery Department talked about the 4th edition of the Guidelines in 2014, which revised seven major issues and introduced new evidence and standards (updated gastric surgery guidelines). The definition of gastric surgery was updated; the provisional rules and flow chart of lymph node dissection for esophagogastric cancer <4 cm were established; laparoscopic distal gastrectomy for stage I gastric cancer was determined as a routine treatment; the standards of gastroscopic treatment; the recommended chemotherapy regimen; the recommended regimen and flow chart for HER2 negative and positive gastric cancer; and the rules of surgery and chemotherapy for M1 gastric cancer and the postoperative follow-up). The 4th edition of the "Guidelines" draws on the latest scientific achievements, and provides important guidance for future clinical practice by making the basic principles and concepts of gastric cancer treatment more scientific and precise.
In October 2010, the 3rd edition of the Japanese “Guidelines for the Treatment of Gastric Cancer” (hereinafter referred to as “the Guidelines”) was released, which greatly changed the basic concept of gastric cancer treatment and brought a new era of gastric cancer treatment with new treatment principles based on high-level evidence-based medicine. In recent years, new research results have emerged, and it is urgent to supplement and update the “guidelines”.
In May 2014, the Japanese Society of Gastric Cancer revised the 3rd edition of the Guidelines and issued the 4th edition of the Guidelines, which clarifies the basic principles and concepts of gastric cancer treatment in a more scientific manner. The new treatment guidelines have been established and provide important guidance for future clinical treatment.
The main points of this revision and update are.
(1) Update the definition of gastric surgery methods;
(2) Formulate the provisional rules of lymph node dissection for esophagogastric union cancer <4cm in length and its flow chart;
(3) To determine that laparoscopic distal gastrectomy for stage I gastric cancer can be a routine treatment;
(4) Regarding gastroscopic treatment, it was established that differentiated carcinoma with undifferentiated components, <3 cm in diameter, UL(+), and pT1a were suitable for extended curative resection. In addition, the treatment of histological muc and the diagnostic criteria of UL were added;
(5) The recommended chemotherapy regimen was set, and the recommended regimen for HER2-negative and positive gastric cancer was documented and flowcharted;
(6) Seven clinical questions were set to answer and explain the treatment guidelines when M1 gastric cancer can be resected and chemotherapy when it is difficult to apply standard chemotherapy regimens;
(7) A template was created for postoperative clinical pathways and follow-up for gastric cancer.
The main contents of this update are described below.
1. Update of the definition of gastric cancer surgery
The types of surgery remain unchanged: total gastrectomy, distal gastrectomy, pylorus preserving gastrectomy, proximal gastrectomy, segmental gastrectomy, partial gastrectomy, and non-excisional surgery. However, each type of surgery is clearly defined.
(1) total gastrectomy (TG) Total gastrectomy with cardia (esophagogastric junction) and pylorus (pyloric wheel).
(2) Distal gastrectomy (DG) Gastrectomy with the pylorus, preserving the cardia, standard procedure is to remove more than 2/3 of the stomach.
(3) pylorus-preserving gastrectomy (PPG) Gastrectomy with preservation of the upper 1/3 of the stomach and the pylorus and part of the pyloric antrum.
(4)Proximal gastrectomy (PG) Gastrectomy with cardia (esophagogastric junction), preserving the pylorus.
(5) Segmental gastrectomy (SG) total circumferential resection of the stomach with preservation of the cardia and pylorus, except for those who are suitable for pylorus preservation gastrectomy.
(6) local resection (LR) non-perimeter resection of the stomach.
(7) Non-excisional surgery (anastomosis, gastric fistula and enterostomy).
For post-operative residual gastric cancer, the surgical procedures are as follows: (8) total gastrectomy (completion gastrectomy) The initial surgical procedure is not counted, and total gastrectomy of the residual stomach with cardia or pylorus is included.
(9) subtotal resection of remnant stomach (subtotal resection of remnant stomach) is a distal gastrectomy with preservation of the cardia.
2.Provisional rules and flow chart for lymph node dissection in case of esophagogastric union cancer <4cm in length
The Japanese Society of Gastric Cancer and the Japanese Society of Esophagology conducted a national survey in 2012 and 2013 on lymph node metastasis in esophagogastric union cancers less than 4 cm in length, and collected data from 3,177 cases in 273 units. In this survey, we reviewed the surgical cases from 2001 to 2010, and based on the histological findings of the resected specimens with the depth of tumor infiltration, we developed a flow chart of lymph node dissection for esophagogastric union carcinoma up to 4 cm in length, and tentatively set the benchmarks for lymph node dissection (Figure 1).
3.Laparoscopic gastrectomy
Laparoscopic gastrectomy was classified as an investigational treatment in the 3rd edition of the Guidelines because of the lack of definitive evidence of safety and long-term prognosis. This edition specifies laparoscopic surgery as an option for routine treatment of stage Ic cases that are suitable for distal gastrectomy.
The “Guidelines” of the Japanese Society of Endoscopic Surgery (2014 edition) recommend laparoscopic distal gastrectomy (recommendation B) for stage Ic gastric cancer in the “Statute for the Management of Gastric Cancer “14 and the superiority of short-term postoperative results, small prospective trials and analysis show that a phase II trial by skilled surgeons (JCOG0703) is safe, but more postoperative complications have been reported with less experience, and each unit should set benchmarks according to proficiency.
Regarding long-term outcomes, large-scale prospective studies on survival and quality of life in Japan and Korea (JCOG0912, K2ASS01) are underway, pending their results. A prospective clinical study (JLSSG0901) on the safety and long-term outcome of progressive gastric cancer is underway. Currently, there is no basis for a recommendation for laparoscopic distal gastrectomy for gastric cancer of stage IIc or higher.
There is no prospective study of laparoscopic total gastrectomy for early gastric cancer, and the Japanese Society of Endoscopic Surgery “Guidelines” (2014 edition) recommends degree C1 (can be done, but without sufficient scientific basis). The procedure should be performed with caution because of the high rate of postoperative complications in the first year. Because of the uncertainty of long-term results, patients undergoing laparoscopic surgery should be fully informed.
4. About gastroscopic treatment
(1) In the histologic classification of the Statute for the Management of Gastric Cancer14, pap, tub1, tub2 of general type of malignancy are differentiated carcinoma, and por1, por2, sig are undifferentiated carcinoma.SM When muc is present at the infiltration site of carcinoma, either differentiated carcinoma or undifferentiated carcinoma comes from, it is treated as non-curative resection.
(2) UL (ulcer) is determined by treating the ulcer seen histologically as UL(+), but the determination of UL is sometimes difficult pathologically, and the preoperative biopsy scar is sometimes treated as ulcer scar. Therefore, the clinician should ultimately make a judgment on the treatment approach based on imaging findings such as endoscopy and radiology, and the presence or absence of a preoperative biopsy. Usually biopsy scar can capture a small area of limited fibrosis under the mucosal muscle plate, and when the two cannot be distinguished as UL(+) is determined.
(3) Specify differentiated carcinoma containing undifferentiated components, under 3 cm, UL(+), pT1a suitable for extended curative resection.
5, set the recommended degree of chemotherapy regimen (recommended regimen and flow chart for HER2 negative and positive gastric cancer)
5.1 Recommended chemotherapy regimens (divided into 3 categories)
Recommendation 1: Among the regimens with superiority or non-inferiority in phase III clinical trials targeting overall survival time, those with sufficient domestic data are recommended as category 1.
Recommendation degree 2: A protocol with proven superiority or non-inferiority in phase III clinical trials, but no consensus as a category 1 recommendation, or a protocol with proven effectiveness in phase II clinical trials.
Recommendation degree 3: A protocol for which superiority, or non-inferiority, was not demonstrated in the phase III clinical trial primary evaluation program, or which did not show clinical effectiveness and sufficient evidence of safety data in Japan.
5.2 Recommended regimen for HER2-negative and positive gastric cancer
For HER2-positive gastric cancer, chemotherapy containing trastuzumab is the standard of care. It is recommended that HER2 screening should be performed prior to primary chemotherapy.
5.2.1 HER2-negative gastric cancer
The S-1+ cisplatin regimen is recommended based on the results of the Japanese phase III SPIRITS trial and the COG9912 trial. Recommendation degree 1.
Capecitabine + cisplatin therapy is one of the standard therapies overseas and is also a control for the ToGA and AVAGAST trials, and the substratum analysis of both trials in Japanese cases also showed safety and efficacy, so it is an option. Recommendation 2.
S-1+ docetaxel showed no significant difference in survival time compared to S-1 monotherapy in the primary analysis of the START trial, and additional analysis showed prolonged survival time. It is an option for limited subjects such as outpatients. Recommendation 2.
Irinotecan + cisplatin therapy and irinotecan + S-1 therapy, both of which did not demonstrate prolonged survival compared with S-1 therapy alone. Not recommended as primary chemotherapy. Recommendation level 3.
Regarding 3-drug combination therapy, the V325 trial of docetaxel + cisplatin + 5FU in Europe and the United States was effective. However, there is little experience with the balance of efficacy and toxicity in China, so clinical recommendations are not made. Recommendation 3.
The results of the phase II trial of docetaxel + cisplatin + S-1 (DOS) therapy were received in China, and the JCOG1013 trial is now underway, with DOS being the clinical trial phase at this stage.
5.2.2 HER2-positive gastric cancer
HER2-positive gastric cancer is defined as IHC3+ or FISH-positive subjects in the ToGA trial, with prolonged survival in the substrate-analysis IHC3+ , or IHC2+ and FISH-positive HER2 high-detection group. Therefore, trastuzumab-containing chemotherapy is recommended for IHC3+, or IHC2+ and FISH-positive cases. Capecitabine (or 5-FU) + cisplatin + trastuzumab therapy is recommended. Recommendation degree 1.
The 3-week schedule of S-1+ cisplatin+ trastuzumab therapy is an option based on the results of phase II trials. However, there is insufficient data on efficacy and safety.
5.2.3 The flow chart of chemotherapy for unresectable progressive gastric cancer and recurrent cancer is shown in Figure 2.
6. For gastric cancer with M1 lesions, treatment guidelines when resectable and chemotherapy issues when it is difficult to apply standard chemotherapy regimens
Question 1: When there is metastasis in the lymph nodes around the abdominal aorta of gastric cancer, is it not an indication for gastrectomy?
Answer: If there are a few lymph nodes enlargement limited to No.16a2, b1, and there are no other non-curative factors, a combination therapy including surgical resection with extended debulking can be applied selectively.
Question 2: What is the treatment policy for liver metastasis of gastric cancer?
Answer: If the number of metastases is small and there are no other non-curative factors, comprehensive treatment including surgical resection can be applied.
Question 3: What is the treatment policy for gastric cancer with positive intraperitoneal washout cytology (CY1)? What is the recommended chemotherapy regimen for CY1 cases where the primary site can be resected?
A: In the absence of other non-curative factors, a combination of treatment including standard surgery can be used. S-1 monotherapy is recommended when the primary site has been resected.
Question 4: What is the recommended chemotherapy regimen for recurrent cases during or early after the completion of postoperative adjuvant chemotherapy (within 6 months)?
A: There is no definite regimen, but most regimens other than S-1 monotherapy are chosen for routine secondary treatment of recurrent disease within 6 months.
Q5: What is the recommended treatment for patients with high peritoneal metastases who cannot consume food by mouth or who have a large amount of ascites?
A: The indication for chemotherapy is carefully determined by the systemic status. 5-FU and paclitaxel, which are less toxic, can be chosen.
Question 6: What is the recommended chemotherapy regimen for elderly people with unresectable tumor or recurrent gastric cancer?
Answer: S-1+ cisplatin is recommended for those who have good systemic status, but we should pay full attention to the side effects. S-1 single agent therapy can also be used depending on the situation.
Q7: What is the recommended chemotherapy regimen for HER2 positive gastric cancer?
Answer: The recommended regimen is paclitaxel-based anticancer agents or irinotecan. For those who have not used trastuzumab, paclitaxel and trastuzumab combination therapy may be effective for secondary chemotherapy.
7 . Clinical pathway and follow-up template after gastric cancer surgery
7.1 Addition of basic pathway additions
The basic pathways are shown in Table 1 for sharing between total gastrectomy, distal gastrectomy, and proximal gastrectomy, as well as open and laparoscopic surgery. Those with combined severe circulatory and respiratory complications, as well as liver disorders and renal dysfunction are excluded.
7.2 Post-operative follow-up for gastric cancer
The postoperative follow-up templates for gastric cancer are shown in Tables 2 and 3.