DOI: https://doi.org/10.21203/rs.3.rs-36134/v1
There is a high probability of gastroesophageal reflux after laparoscopic proximal gastrectomy of SiewertⅡAEG. Various anti-reflux anastomotic methods are emerging in clinical practice, however, none of them is widely accepted. We have innovated a new type of anti-reflux anastomotic method, named semi-embedded valve anastomosis. The aim of this study is to explore the feasibility and anti-reflux effect of the new anastomotic method.
The clinical data of 28 patients with SiewertⅡAEG were collected in this study, who were treated by semi-embedded valve anastomosis. The key point of operation is to reconstruct a simulated valve and form a similar anti-reflux barrier under physiological mechanism. GerdQ gastroesophageal reflux questionnaire and classification of gastroesophageal reflux under electron microscope were used to evaluate gastroesophageal reflux after operation.
The mean time of operation was 164.3 ± 19.0 min, the median intraoperative hemorrhage was 65 ml, the average number of lymph nodes dissected was 23 ± 2.6, the time of making valve was 15.8 ± 3.2 min, the time of anastomotic reconstruction was 35.4 ± 4.8 min, the median time of first exhaust was 3d, the median time of hospitalization was 12 days, one case with postoperative anastomotic stenosis. GerdQ score, median (range) : 2 (0–6), preoperation; 0 (0–8), 1 months postoperation; 2 (0–12), 3 months postoperation; 3 (0–12), 6 months postoperation. Wilcoxon signed rank sum test was carried out at different time after operation and the day before operation respectively, the differences were not statistically significant, P < 0.05. There was one case of grade B according to LA classification system of gastroesophageal reflux among the gastrofiberscope reexamination reports of 28 cases.
Semi-embedded valve anastomosis is safe and feasible after the proximal gastrectomy of Siewert Ⅱ AEG, and has good anti-reflux effect.
The incidence of adenocarcinoma of esophagogastric junction (AEG) has increased during the past few years in Asia, Europe and the United States [1–2]. At present, Siewert method is widely used in AEG typing [3]. The biological behavior and lymph node metastasis of type I are similar to those of esophageal cancer, and it is classified as lower esophageal cancer. Type III is classified as gastric cancer, and follows the scope of lymph node dissection of gastric cancer, and operated by general surgeons through the abdominal esophageal hiatus. Whereas type II is traditionally regarded as cardia cancer, because it locates in special anatomical region, the surgical approach, the scope of lymph node dissection, and the reconstruction method of digestive tract remain controversial [4–5].
Proximal gastrectomy (PG) or total gastrectomy (TG) is one of the arguments. After PG, the His angle was destroyed because of the removal of lower esophageal sphincter, and the anti-reflux barrier was lost, therefore, severe gastroesophageal reflux was likely to occur [6]. In the past, most experts agreed with laparoscopic total gastrectomy, but TG would cause nutrition-related complications [7–8]. Some scholars have proposed various reconstruction methods of anti-reflux anastomosis after proximal gastrectomy, such as jejunal interposition [9], double flap (Kamikawa anastomosis) [10], tubular gastric [11], but most of them have the disadvantages of complex fabrication, multiple anastomosis, time-consuming and high incidence of potential complications. By using the self-designed patent instrument(Chinese patien NO.201220661287.9), we innovated a reversed puncture method with the hand-assisted laparoscopy, and the anastomotic method is named semi-embedded valve anastomosis. This anastomotic method is safe, reliable and easy to operate. It forms a one-way valve in principle, which simulates His angle, therefore it has anti-reflux function.
Now we conduct a retrospective study to explore the anti-reflux effects of this new anastomotic method.
A retrospective study of 28 patients with Siewert Ⅱ AEG was made, who were treated with three united laparoscopic proximal gastrectomy and semi-embedded valve anastomosis in the department of gastrointestinal surgery of the second hospital of Hebei Medical University from June 2015 to February 2017. The inclusion criteria: Siewert Ⅱ AEG diagnosed and confirmed by pathological examination; TNM stage was in the stage of I-III; informed consent was signed voluntarily; proximal gastrectomy combined with semi-embedded valve anastomosis were performed. Exclusion criteria: patients with extensive tumor infiltration of nearby tissues and organs, and distant metastasis; patients with the severe combined endocrine system, immune system and mental system diseases; patients with new adjuvant treatments before operation; patients with total gastrectomy or other anastomotic methods. The staging of cancer was based on the eighth edition of the Union for International Cancer Control. This study was approved by the Ethics Committee of The second hospital of Hebei Medical University (2020-R127). Written informed consent was obtained from all patients.
Freed the stomach with the complete laparoscope in advance. After anesthesia, the patients lied down in supine position, disinfected sheet routinely, and Trocar inserted through the right lower abdomen, the lower abdomen and the left abdomen respectively with 10 mm, 5 mm and 5 mm. The stomach freeing was based on the Japanese Gastric Cancer Treatment Guidelines. The dissection of lymph nodes included 1, 2, 3, 4sa, 4sb, 4d, 7, 8a, 9, 11p, 12a, 20. According to the distance of the tumor invasion of the esophagus during the operation, the diaphragmatic angle was opened in part of Siewert Ⅱ AEG, dissected the lymph node groups of 110, 111 and 112 through the esophageal hiatus. The internal elastic ring of the patented instrument was placed in the incision that was 8 cm from the xiphoid process in the middle of upper abdomen (Fig. 1A), trimmed the external elastic ring, then the operator put the left hand in and sealed it by the surgical film and to fix, reconstructed pneumoperitoneum, and switched to the hand-assisted laparoscopy (Fig. 1B 1C).
Step 1: The surgeon pinched the lower esophagus with his assistant hand and transected the left and right vagus nerves.
Step 2: Opened a hole by the ultrasonic scalpel in the anterolateral wall of lower esophagus, and then expanded the hole upward and downward (Fig. 2A).
Step 3: The assistant held the edge of the hole to open it with the laparoscopic instrument, meanwhile, the surgeon held the anastomat head with the pre-tied string and slowly inserted it into the hole (Fig. 2B 2C).
Step 4: A horizontal 45 °oblique cutting close was made with the linear cutting closer, with a reversed puncture opening of 0.3 cm reserved at the lower right corner of the esophagus (Fig. 2D).
Step 5: The operator used the laparoscopic instrument or assisted hand to pull the string for reversed puncture ( Fig. 2E 2F).
Step 6: Removed the patented instrument, lifted the transected stomach, cut the proximal gastric specimen from the great curvature of stomach to the small curvature of stomach at about horizontal 45 ° with a cutting closer according to the location and size of the tumor.
Step 7: Opened the anterior wall of the remnant stomach under the midpoint of the oblique cutting line, and anastomosed the circular anastomat with the reversed puncture head. During the anastomosis, the operator grasped the remnant stomach with the right hand to "push" upper leftward.
The principle of anastomosis is shown in the Fig. 3 (Fig. 3).
The upper gastrointestinal angiography of one case after semi-embedded valve anastomosis is shown in Fig. 4 (Fig. 4). The reconstructed His angle, the reconstructed gastric fundus and the simulated valve structure can be seen by contrast agent filling.
The operation time, intraoperative blood loss, number of lymph node dissected, negative margin rate, time of first exhaust, hospitalization time, anastomotic complications and external anastomotic complications were collected by electronic medical record system and anesthesia records. The anastomotic time of the first anastomosis and the total time of anastomotic reconstruction were recorded during operation. The follow-up time was 2 years by regular outpatient reexamination and telephone GerdQ gastroesophageal reflux questionnaire and the classification of gastroesophageal reflux under electron microscope(LA classification system of gastroesophageal reflux).
Symptom score: 0, 1, 2 and 3 points were according to "0d", "1d", "2-3d", "4-7d" respectively as for the frequency of heartburn, reflux, pain in the central upper abdomen and nausea; Influence score: 0, 1, 2 and 3 points were according to "0d", "1d", "2-3d", "4-7d" respectively as for the frequency of sleep affected by gastroesophageal reflux, and the frequency of the anti-acid drugs administration of patients besides the prescriptions. There were six questions in total, the highest score was 18. GerdQ score ≥ 8 indicated GERD diagnosis, and scores ≥ 3 of the latter two questions indicated the influence of GERD on life quality.
The basic data of patients and the results during and after operation were shown in Table 1. From June 2015 to February 2017, a total of 58 cases of Siewert Ⅱ AEG operation were performed, 4 cases of thoracoabdominal surgery, 18 cases of total gastrectomy, 3 cases of combined multiple organ resection and 5 cases of other anastomotic methods were excluded among them, therefore, 28 cases were included. 24 males and 4 females, with an average age of 58.9 ± 9.1 (32–74); an average BMI of 23.3 ± 2.7; 2 cases of gastric cancer stage I, 12 cases of stage II and 14 cases of stage III; 27 cases of adenocarcinoma of pathological type, including 16 cases of poorly differentiated adenocarcinoma, 5 cases of moderately differentiated adenocarcinoma, 4 cases of highly differentiated adenocarcinoma, 2 cases of mucinous adenocarcinoma and 1 case of signet ring cell carcinoma. The maximum average diameter of tumor was 3.3 ± 1.3 cm.
| Variables | Result |
|---|---|
| Age, years, mean ± SD | 58.9 ± 9.1 |
| Gender, n, Male/Female | 24/4 |
| BMI, kg/m2, mean ± SD | 23.3 ± 2.7 |
| UCII stage,ⅠA/ⅠB/ⅡA/ⅡB/ⅢA | 1/1/6/6/14 |
| Diameter of tumor, cm, mean ± SD | 3.3 ± 1.3 |
| Operative time, min, mean ± SD | 164.3 ± 19.0 |
| Estimated blood loss, ml, median (range) | 65 (20–200) |
| Number of harvested lymph nodes, n, mean ± SD | 23.0 ± 2.6 |
| Gas-passing, days, median (range) | 3 (2–5) |
| Postoperative hospital stay, days, median (range) | 12 (9–21) |
| Time of making valve, min, mean ± SD | 15.8 ± 3.2 |
| Total time of anastomotic reconstruction, min, mean ± SD | 35.4 ± 4.8 |
| Anastomotic complications | |
| Anastomotic leakage | 0 |
| Anastomotic stenosis | 1 |
| Other complications | |
| Internal hernia | 1 |
| Bowel obstruction | 1 |
| Pancreatic fistula | 0 |
| Incisional infection | 0 |
| Peritoneal abscess | 0 |
| Pneumonia | 1 |
| Los Angeles grade of gastroesophageal reflux, n, A/B/C/D | 1/1/0/0 |
28 cases were successfully operated with the modified radical laparoscopic proximal gastrectomy and semi-embedded valve anastomosis. The average operation time was 164.3 ± 19.0 min, and the intraoperative blood loss was 65 ml. Due to the injury to the blood vessels around the spleen, one case was operated with the combined splenectomy. The average number of lymph nodes dissected was 23.0 ± 2.6. The upper stump tested positive under the microscope in one case, the rest were negative. The time of making valve was 15.8 ± 3.2 min, and the time of anastomotic reconstruction was 35.4 ± 4.8 min, the median time of the first exhaust was 3d, and the median time of hospitalization was 12 days.
One patient had no abnormality in eating liquid diet after operation, but complained vomit after feeding a large amount of food. Upper gastrointestinal radiography confirmed that there was anastomotic stenosis on the 18d after operation. After endoscopic dilatation treatment, all patients were cured without anastomotic leakage. One 72 year old patient with COPD developed hyperpyrexia and dyspnea 6d after operation,and lung CT confirmed inflammation in bilateral lungs accompanied by arrhythmia and then ARDS༌then transferred to ICU for treatment and discharged one week later. One patient was admitted to hospital one year later due to strangulated intestinal obstruction caused by internal hernia of small intestine, and was cured after the second operation.
The GERD score of gastroesophageal reflux was successfully evaluated in 28 patients through preoperative conversation, outpatient reexamination and telephone follow-up. The data of each group were matched at different times after the operation with that of the day before operation. The data of each group did not conform to the normal distribution through the normality test. The Wilcoxon signed rank sum test was used (Table 2). 28 patients came to the hospital for gastrofiberscope reexamination half a year after operation, and according to the LA classification system of gastroesophageal reflux, one case of grade A, and one case of grade B. The patients with reflux esophagitis regularly took acid suppressive drugs, such as PPI, and improved after conservative treatment, without grade C or grade D.
| Time | preoperation | 1 months postoperation | 3 months postoperation | 6 months postoperation |
|---|---|---|---|---|
| GerdQ Scores, median (range) | 2(0–6) | 0(0–8) | 2(0–12) | 3(0–12) |
| Z | - | -0.338b | -0.851b | -1.396b |
| P | - | 0.736 | 0.395 | 0.163 |
| b:Based on positive rank. | ||||
28 cases were followed up effectively, the follow-up time was 12–24 months, no case was lost, one case had liver metastasis in 2 years after operation, 3 cases died in half a year and 2 years respectively after operation due to tumor recurrence.
Some scholars advocated total gastrectomy for Siewert Ⅱ AEG. Reason 1: the intolerable gastroesophageal reflux may occur with high probability in esophageal gastric-remnant anastomosis after proximal gastrectomy. In the study of Nakamura M, the incidence of reflux esophagitis above grade B in the traditional esophageal gastric-remnant anastomosis group was 21.8% (12/55) [6], and the incidence was 35.3% according to the study of Chen S (12/34) [13]. Some patients needed to take acid suppressive drugs for a long time, which seriously affected the quality of life. Bile and food repeatedly stimulated the anastomosis to develop anastomotic inflammation, and further caused gastric stump cancer. Reason 2: most AEG were more malignant than other gastric cancer in biological behavior [14]. In order to achieve better radical treatment of tumor and reduce recurrence, total gastrectomy was needed.
Currently a number of researches showed that there was no advantage in the postoperative survival rate for Siewert Ⅱ AEG cases with active total gastrectomy and lymph node dissection. Recently, Yura [15] research of 202 cases revealed that the metastasis rate of NO.4d was 0.99%, NO.12a was 0.006%, NO.5 and NO.6 was 0% in T2-3 AEG. Kaixuan Zhu [16]et al. analyzed SEER database, 1584 cases were treated with proximal gastrectomy, 633 cases were treated with total gastrectomy, there was no difference in 5-year OS, and proximal gastrectomy brought more long-term survival benefits when the age was over 70 years. In this study, most of the cases were in the middle stage, including 14 cases with Ⅲ stage A, who were followed up for 24 months, and 3 cases died of tumor recurrence. We hold that it should be cautious about the proximal gastrectomy for patients with stage Ⅲ.
A disadvantage of total gastrectomy is the possibility of poor nutritional status, anemia and dumping syndrome after operation [17–18]. Due to the complete removal of gastric parietal cells, the secretion of intrinsic factors is incapable, vitamin B12 absorption is poor, which results in megaloblastic anemia. With the removal of principal cells, digestive enzymes of the stomach are lost, the nutrition-related complications aggravate further. Study of Nishigori1[19] showed that the weight loss of proximal gastrectomy was significantly less than that of total gastrectomy, and the gastrointestinal symptoms of proximal gastrectomy were also less than those of total gastrectomy. Study of Lee[8] showed that the nutritional serological indexes (albumin, total protein, hemoglobin) of proximal gastrectomy were significantly better than those of total gastrectomy two years after operation.
Physiological anti-reflux mechanism: 1.The lower esophageal sphincter (LES) is a high pressure zone under the normal condition, which forms a pressure barrier and blocks reflux. 2. The traction effect of phrenic esophageal ligament 3.The angle formed between the right posterior wall of the gastric fundus and the left side of the abdominal segment of the esophagus (His angle) is an acute angle. When the pressure in the gastric cavity increases, the expanded gastric fundus compresses the left side of the lower segment of the esophagus and makes it closed [20–21]. The proximal gastrectomy can destroy the structure above, additionally, due to the removal of the vagus nerve, the remnant stomach loses the regulation of the vagus nerve and the ability of gastric peristalsis weakens, pylorus continues to contract, which inhibits gastric emptying, and increases the probability of gastroesophageal reflux.
We were inspired by the mitral valve and tricuspid valve of the heart. When the arterial pressure is high, the blood compresses the valve root to close the opening and prevent the blood from flowing back. Why can't a valve be made manually at the junction of the esophageal and remnant stomach by surgery?
In this operation, a 45 ° oblique cutting was made with linear cutting closer at first, after cutting, the slope edge of the row of nails formed the initial valve. The reversed puncture opening was left in the lower right corner. When anastomosed the anastomat rod and the nail base, aligned the nail base vertically, and the anastomosis was oblique on the right side of the simulated valve. The operator grasped the remnant stomach and pushed it to the upper left, which made the left lower segment of the esophagus and the starting section of valve embedded deeply, and a new His angle was constructed between the left posterior wall of remnant stomach and esophagus. When food was fed through mouth, the simulated valve opened. When the pressure in the remnant stomach cavity increased and the reflux occurred, squeezed the valve root on the left side and the valve was closed. The difference was not statistically significant in GerdQ score after operation compared with that before operation in 28 patients, which preliminarily confirmed the anti-reflux effect of the new anastomotic method, but one patient scored 12 points. After operation, only one case of reflux esophagitis above grade B was confirmed by gastrofiberscope. It was a low incidence of 3.57% (1/28).
According to the principle, we divided the anti-reflux operational methods after proximal gastrectomy into two categories:
1. Method of changing the physiological digestive tract pathway: single lumen jejunum interposition, pouch interposition jejunum, double-tract reconstruction.
2. Method of the improvement of traditional esophageal gastric-remnant anastomosis: esophagogastric anterior wall anastomosis, double flap (Kamikawa) anastomosis, anastomosis of gastroesophageal side overlap and tubular gastric anastomosis.
Jejunal interposition is to insert a segment of pedicled jejunum between the esophagus and the remnant stomach. The rhythmic peristalsis of jejunum and the alkaline solution neutralize the residual gastric acid, therefore, plays a role in anti-reflux. We think jejunal interposition has some shortcomings. Firstly, the operation is complex, which needs a long operation time, and it forms three anastomosises, and has the potential incidence of anastomotic complications. The principle of Kamikawa anastomosis is similar to that of ours, which aims to form the embedded valve and construct His angle. In 33 cases of Kamikawa anastomosis reported by Kuroda[10], the number of reflux esophagitis above grade B was 0, while the average time of anastomosis reconstruction was 109 min in one year follow-up, without grade B record. We hold that Kamikawa anastomosis needs the cut of sarcoplasmic layer of "H" type at first, and insert the anastomosis into the submucous layer by hand, and then fold and cover the two layers of gastric muscle flap. The procedure of anastomosis is also complicated. If the valve overlapped too much, it is likely to cause ischemic necrosis of valve or anastomotic stenosis. Yoshito Yamashita[22] et al. reported an anti-reflux method of the anastomosis of esophageal remnant stomach side overlap via the linear cutting closer under complete laparoscopy. We believe that this method needs to reserve a long segment of lower esophageal, which can not guarantee the upper edge R0 resection of Siewert II AEG with dentate line invasion.
There was only one anastomosis in this anastomotic method. The final anastomosis was a circular anastomat one under direct vision, which required less length of the reserved lower esophageal segment and it was safer. There was no anastomotic leakage in total 28 cases. The principle of our anastomotic method is to make a one-way valve at the junction of esophageal and remnant stomach, which does not affect the circular anastomat anastomosis, therefore, we can also combine other anti-reflux surgical methods freely, such as the esophageal and gastric forearm anastomosis, tubular gastric anastomosis, to achieve a "double-guaranteed" anti-reflux effect.
Three united laparoscopic surgery was invented by us. Through patented instrument, single-port laparoscopy, complete laparoscopy and hand-assisted laparoscopy switched freely in the operation[12]. In the initial stage, complete laparoscopic surgery was used to free the stomach, and dissected the lymph nodes. Switched to hand-assisted laparoscopic surgery when anastomosing. The exposure and traction effects by hand assistance made it more convenient to place the nail base. In this study, the average time of making valve and anastomotic reconstruction was only 35.4 min, which greatly shortened the total operation time. Taking samples, anastomosis and hand assistance were all operated through the incision of patented instrument placement, which made the reasonable use of the auxiliary incision.
There are some shortcomings in this method. If the valve is too large, anastomotic stenosis may be caused due to the circular anastomat. There may be subjective bias of patients in GerdQ score in this retrospective analysis, which requires more objective impedance-24 h acid test and other experiments, On the other hand, there were fewer cases in this study, which may affect the statistical results.
Semi-embedded valve anastomosis is safe and feasible after the proximal gastrectomy of Siewert Ⅱ AEG, which has a short anastomosis time and a certain anti-reflux effect. In order to further confirm, multicenter and prospective study is needed. In addition, clinicians need to choose the most familiar method of anastomotic reconstruction according to their own conditions.
This study has been reviewed by the Ethics Committee of the second hospital of Hebei Medical University (number 2020-R127), all procedures performed in studies involving human participants were was conducted according to the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Consent for publication
Written informed consent for publication of their clinical details and clinical images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal. The principle of anastomosis was drawn by painter Minghao Li under our guidance. He agreed to publish his works.
Availability of data and materials
The datasets generated and/or analyzed during the current study are not publicly available due to protecting individual patient privacy but are available from the corresponding author on reasonable request.
Competing interests
The authors declare that they have no competing interests.
This study was funded by the Hebei Health Committee(number 20200042). The funding played a role in data collection, analysis and painting of pictures.
ZXZ suggested the method and performed the surgeries, BHW and YPW jointly wrote this draft and collected data, HJW and HQZ assisted ZXZ in performing surgeries, and critically revised this article, LTW carried out the follow-up of patients and investigated the gastroesophageal reflux questionnaire. All authors read and approved the final manuscript.
The authors thank Lei Zhang for his authentic English translation of this paper and Minghao Li for his paintings in accordance with the principle of anastomosis under the guidance of Yupeng Wu.