According to the 2008 Global Oncology Statistics Report (GLOBOCA), gastric cancer has the fourth highest incidence rate and the second highest mortality rate worldwide, and nearly 740,000 patients die of gastric cancer each year. About 42% of the world’s gastric cancer patients are in China, and the incidence rate of gastric cancer in China is the second highest among malignant tumors, and the mortality rate is also the second highest. Although the diagnosis and treatment of gastric cancer has been greatly improved in the past 20 years, how to achieve complete radical treatment for different stages and types of gastric cancer and how to choose the best surgical reconstruction method to improve postoperative quality of life are still the hot issues we are discussing.
1.Implementation of standard radical gastric cancer surgery
Accurate preoperative staging of gastric cancer through ultrasonic endoscopy and enhanced CT can basically determine the possibility of surgical resection and the completeness of radical treatment. It has been reported that only about 60% of the initially diagnosed gastric cancer patients can be surgically resected, and about 60% of the gastric cancer patients who undergo surgery can achieve R0 resection. Radical resection through surgery is the most important part of gastric cancer treatment and is a prerequisite for gastric cancer cure. Therefore, the questions of how to consider surgery for gastric cancer as truly radical, whether the concept of radical resection is the same for early gastric cancer and progressive gastric cancer, whether it is necessary to perform D3 radical surgery, and the selection of incision in gastric fundic cardia cancer are still questions that plague us in clinical work.
(1) How to determine the radicality of surgery
The current view is that D2 radical surgery is the gold standard for the surgical treatment of gastric cancer. The origin and development of this procedure came from the Japanese gastric cancer community. In D2 radical surgery, the perigastric lymph nodes are divided into 16 stations according to their pattern of reflux metastasis, and the number of lymph node stations to be cleared is determined according to the location of the cancer. Although the AJCC and NCCN guidelines have been fine-tuned in recent years regarding the stations of D2 lymph node dissection for gastric cancer, the traditional concept of D2 dissection has been generally retained. However, in the 1990s, it was generally accepted in Western countries that D2 radical treatment was not superior to D1 radical treatment, and the results of a phase III clinical trial conducted by the Dutch Research Organization [5] found that mortality after D2 radical treatment was significantly higher and could reach 10-13%. In another clinical trial in England, it was also found that the long-term survival rate of D2 was not better than D1. Both results almost overturned the status of D2 radical surgery, but subsequent analysis concluded that the main reasons for this result were due to the low incidence of gastric cancer in Western countries, the lack of adequate experience and surgical skills of surgeons performing surgical treatment of gastric cancer in the medical centers counted, and the lack of considerable experience in the management of post-surgical complications. The results are due to the low incidence of gastric cancer in Western countries, the lack of experience and surgical skills of the surgeons performing gastric cancer surgery in the medical centers counted, and the lack of a comparable level of management of complications after surgery. The number of gastric cancer cases in the 80 medical centers in the Dutch trial was generally low, with some centers performing only a few cases of gastric cancer surgery a year. In addition, total gastrectomy for D2 radical treatment required routine removal of the tail of the pancreas and spleen at that time, so the surgical trauma and postoperative pancreatic leak caused by combined organ resection was the real cause of increased postoperative complications and mortality in D2 rather than D2 lymph node dissection. Over the next decade or so, radical D2 surgery, which preserves the pancreas and spleen and avoids combined visceral resection, has gained widespread acceptance in the Western medical community, and data published by the Dutch Research Group in 2010 showed that survival rates after radical D2 surgery were significantly higher than those after D1 surgery, without increasing the incidence of postoperative complications.
In a prospective single-blind phase II clinical trial conducted by the Italian Gastric Cancer Research Organization in 1994, D2 radical surgery with preservation of the pancreas and spleen achieved satisfactory results in 191 patients with gastric cancer, with a 3% operative mortality rate and a significantly higher 5-year postoperative survival rate than D1 surgery. Based on this result, the organization subsequently conducted a phase III clinical trial with 267 patients with gastric cancer and found that the mortality rate within 30 days after surgery was 3% in the D1 surgery group and 2.2% in the D2 group. Therefore, the safety of D2 surgery has been generally recognized.
There is no unified view on whether D2 radical surgery needs to be combined with splenectomy. According to a retrospective analysis by the Japanese Society of Clinical Oncology, 20-30% of proximal gastric cancers present with splenic hilar lymph node metastases, and combined splenectomy could theoretically achieve a more complete radical outcome. However, the results given by the Dutch Study Group that combined splenectomy increases mortality and complication rates make the retention of the spleen more controversial. For this reason, the Japanese Society of Clinical Oncology is conducting a phase III clinical trial in which 505 patients with progressive gastric cancer who had total gastrectomy were randomly divided into a spleen-preserving group and a spleen-resecting group to analyze the risks associated with spleen-resecting surgery and the impact on survival, and the final results of this trial are worth looking forward to.
(2) How to choose the surgical method for early gastric cancer
Nowadays, the majority view is that the incidence of lymph node metastasis in early gastric cancer is relatively low, the long-term prognosis is better, and excessive lymph node dissection is not necessary. Therefore, how to make patients with early gastric cancer recover quickly after surgery and preserve part of the gastric function to the greatest extent to improve the quality of life is an issue that needs to be considered in surgery.
Partial gastrectomy with preservation of the pylorus (PPG) is a considered procedure for some early gastric body cancers. According to statistics, the incidence of early gastric body cancer presenting with peripyloric lymphatic metastasis is less than 1%, which is the basis for advocating PPG surgery. 2-125px pyloric outlet preservation and intraoperative vagus nerve protection can prevent rapid emptying of food, bile reflux, gallstone formation and dumping syndrome. The advantages of this surgical approach with low postoperative complication rates are comparable to those of Birollth I style, while long-term survival rates are comparable to those of conventional surgery. In many places, radical proximal gastric cancer is also preferred because early gastric cancer within the proximal 1/3 rarely presents with metastases in the distal perigastric lymph nodes. Preserving the distal stomach can preserve part of the gastric storage function, while preserving the pylorus can serve a purpose similar to that of PPG surgery. Improving patients’ long-term quality of life is the main advantage of radical surgery for proximal gastric cancer, but the common postoperative reflux phenomenon in this type of surgery is the main reason for the current controversy about whether to use this procedure.
Laparoscopic radical gastric cancer surgery, which has been rapidly developed in the last 20 years, is considered to be the best option for the treatment of early gastric cancer, and Professor Kitano first reported the use of laparoscopic-assisted radical distal gastric surgery (LADG) to treat early gastric cancer with a low risk of lymph node metastasis. Several subsequent clinical trials with small samples have also confirmed various advantages of laparoscopic radical treatment of early gastric cancer, including features such as rapid recovery, less pain and less impact on pulmonary function, and its postoperative complication rate and mortality rate are no different from those of open surgery. In a phase III randomized clinical trial with a sample size of 1294 published in the Annals of American Surgery in 2007, the complication rate and mortality rate of laparoscopic radical gastric cancer treatment were 14.8% and 0%, which were no different from those of open surgery, and the long-term survival rate was better than that of open surgery. In the context of advocating the concept of minimally invasive and rapid recovery, laparoscopic radical gastric cancer treatment will be more widely carried out.
(3) Do PAND and LTA lead to better long-term survival?
Along with the success of D2 radical treatment, Japanese surgeons in the 1980s have started to try more aggressive radical procedures, including paraaortic lymph node dissection (PAND) without associated evidence of metastasis and radical treatment of cardia cancer using a combined left thoracoabdominal incision (LTA).
In progressive gastric cancer, the incidence of abdominal para-aortic lymph node metastasis is approximately 10-30%, and the 5-year survival rate for cases presenting with abdominal para-aortic lymph node metastasis is approximately 10-20%. Therefore, PAND has been actively performed by Japanese surgeons since the 1980s to improve the long-term survival rate of patients. The Japanese Society of Clinical Oncology designed a phase III clinical trial for 523 patients in 24 medical centers for both D2 radical treatment and PAND on top of D2 radical treatment, and found that the 5-year survival rates for the two groups were 69.2% and 70.3%, respectively, with no significant difference. The reason for this result may be caused by the low incidence of metastasis in the para-aortic lymph nodes of the abdomen. Therefore, PAND is currently not routinely recommended as a clearance procedure without evidence of metastasis.
LTA as a radical incision for cardia cancer is based on the characteristics of mediastinal lymph node metastasis. The incidence of lower mediastinal lymphatic metastases in cardia cancer has been reported to be approximately 10-40%, and the conventional approach incision cannot completely clear the lymphatic tissue in the lower mediastinum, making LTA an incisional option to consider for cardia cancer surgery. A phase III randomized clinical trial comparing radical surgery for cardia cancer with tumor invasion within 75 px of the lower esophagus by choosing a transabdominal incision and a combined left thoracoabdominal incision found that the 5-year survival rate was 52.3% in the transabdominal incision group, which was significantly higher than the 37.9% in the combined thoracoabdominal group, and the postoperative mortality rate was 4% and the complication rate was 49% with the surgical incision using LTA, with high mortality and high The existence of complication rate makes LTA less and less in clinical application.
2. Choice of GI reconstruction after resection of gastric cancer
The ideal GI reconstruction method should be as simple as possible, maintain the physiological continuity of the GI tract and reduce the incidence of postoperative complications, and enable patients to have a good long-term quality of life. At present, there are more than 60 types of GI reconstruction after total gastrectomy, and Roux-en-Y (RY) anastomosis is the most commonly used reconstruction after total gastrectomy because it can effectively prevent reflux esophagitis and is simple to perform. However, after RY GI reconstruction, patients are prone to clinical manifestations of Roux Stasis Syndrome (RSS) such as epigastric distension, nausea and vomiting, and some patients may develop dumping syndrome. Among other GI reconstruction methods, there are always more or less complicated operations, higher postoperative complication rates or poorer postoperative quality of life, so there is not yet a standard reconstruction method commonly accepted by the industry colleagues. In addition, among the debates on reconstruction modalities, the need to establish a jejunal storage pouch and preserve duodenal access are two hot issues that are constantly discussed.
(1) Establishment of jejunal storage pouch after total gastrectomy
In recent years, domestic and international studies have reported that the establishment of jejunal storage pouches, especially distal storage pouches, can significantly improve the nutritional status of patients and reduce postoperative complications, and the results of Ralf Gertler’s Meta-analysis on whether to add storage pouches after total gastrectomy found that the reconstruction method of adding storage pouches did not affect the patient’s perioperative recovery, postoperative mortality, operation time and hospital stay, but could Nakane et al. reported that the reconstruction of the GI tract with the addition of a pouch significantly increased the amount of food eaten per meal after surgery, and the amount of food eaten per meal was 50% greater than before surgery in comparison with patients without a pouch. Therefore, the establishment of a distal jejunal pouch is a very important part of the GI reconstruction process.
(2) How to preserve duodenal access
Most patients who bypass the duodenum after resection of gastric cancer will have elevated cholecystokinin levels after surgery, which can lead to rapid movement of food and intestinal fluid and failure to synchronize pancreatic fluid secretion with feeding. The main causes of elevated cholecystokinin levels are a confused feedback mechanism and rapid gastrointestinal emptying. Under normal conditions, nutrients entering the duodenum cause secretion of cholecystokinin, which slows gastrointestinal emptying, reduces the flow of nutrients through the duodenum, and feedback inhibits the secretion of cholecystokinin. Preserving the duodenal pathway can avoid the non-simultaneous nature of food and biliopancreatic fluid to a certain extent and alleviate the exocrine pancreatic dysfunction. Previous animal experiments and related studies have proved that preserving the duodenal pathway can release a certain amount of Ghrelin, which can promote appetite and increase food intake, and at the same time can coordinate gastrointestinal motility.
(3) Application of Gastrointestinal Reconstruction
In the study of the GI reconstruction modality for gastric cancer surgery in our hospital, continuous interjejunal substitution gastric surgery was designed for how to maintain the continuity of the GI tract in the reconstruction of distal gastric resection after major gastric resection that is difficult to perform Billroth I anastomosis, and how to preserve the duodenal access to improve the postoperative quality of life of patients. In the clinical work, it was found that it is difficult to perform Billroth I anastomosis directly when there is not much residual stomach left after distal gastrectomy, and Billroth II is likely to lead to reflux gastritis and anastomitis and anastomotic ulceration, while Roux-en-Y anastomosis is likely to lead to Roux retention syndrome. The use of continuous interjejunal gastric substitution is a good solution to the deficiencies in these two surgical approaches. Meanwhile, in the study of gastrointestinal hormone levels, it was found that preserving duodenal access and continuous interjejunal placement could elevate postoperative gastrin and gastrin and decrease cholecystokinin, which could effectively promote the recovery of postoperative gastrointestinal function and diet. In addition, the study of gastrointestinal myoelectricity after gastric cancer reconstruction found that continuous jejunal interposition well protected the continuity of myoelectric activity, maintained the normal pacing frequency of the gastrointestinal tract in fasting and postprandial states and improved the proportion of propagation in the antral direction, which ensured the normal peristalsis of the jejunum and facilitated the normal digestion and absorption of chyme. At present, this surgical approach has been used in clinical practice and has achieved good results.
Continuous interjejunal gastric substitution surgery: the remnant stomach and the small intestine at 500px from the flexor ligament are anastomosed end to end, and the 50px of the duodenal side of the anastomosis is ligated with a silk thread so that the intestinal fluid cannot pass, and the distal small intestine at 750px is laterally anastomosed with the duodenal stump, and the 50px of the small intestine below the anastomosis is also ligated with a silk thread so that the intestinal fluid cannot pass, and finally the small intestine at 375px from the flexor ligament is ligated with a silk thread so that the intestinal fluid cannot pass. The small intestine at 375px was laterally anastomosed with the small intestine at 250px below the duodenal-small intestine anastomosis.
3. Conclusion
The surgical treatment of gastric cancer is a process of continuous change and gradual improvement, and the proposal of new theories and the advocacy of new surgical methods are the result of the joint efforts of several generations of surgeons. At present, surgical treatment based on D2 radical treatment is still the core part of comprehensive treatment for gastric cancer, while how to better maintain the continuity of the digestive tract, preserve the storage function in the absence of stomach or semi-gastric state, and improve the long-term life treatment are the most sought-after goals of various reconstructive surgical approaches. We have reasons to believe that the hot issues encountered in gastric cancer surgery nowadays will be solved one by one in the end.