Efficacy analysis of Cheng’s GIRAFFE reconstruction after proximal gastrectomy for adenocarcinoma of esophagogastric junction

Zhiyuan Xu,Can Hu,Yanqiang Zhang,Ling Huang,Litao Yang,Jianfa Yu,Pengfei Yu,Jiahui Chen,Yian Du,Xiangdong Cheng

1Department of Gastric Surgery,Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital),Institute of Basic Medicine and Cancer (IBMC),Chinese Academy of Sciences,Hangzhou 310022,China;2 Department of Gastrointestinal Surgery,the First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310053,China

Abstract Objective:Reconstruction of the digestive tract for adenocarcinoma of esophagogastric junction (AEG) is in dispute.This study evaluated Cheng’s gastric tube interposition esophagogastrostomy with reconstruction of His angle and fundus (Cheng’s GIRAFFE anastomosis) in laparoscopic/open proximal gastrectomy for Siewert type II AEG,which was performed at Zhejiang Cancer Hospital and the First Affiliated Hospital of Zhejiang Chinese Medical University.Here,we discuss the preliminary results of gastric emptying and anti-reflux.Methods:From a retrospective database,74 patients with advanced Siewert type II AEG underwent curative proximal gastrectomy with GIRAFFE anastomosis,and their gastric emptying and anti-reflux outcomes were evaluated by the Reflux Disease Questionnaire (RDQ) score,nuclide gastric emptying,24-h impedance-pH monitoring and gastroscopy.Results:Seventy-four patients successfully completed proximal partial gastrectomy with Cheng’s GIRAFFE esophagogastric anastomosis.RDQ score six months after the operation was 2.2±2.5.Results of nuclide gastric emptying examinations showed that the gastric half-emptying time was 67.0±21.5 min,the 1-h residual rate was(52.2±7.7)%,the 2-h residual rate was (36.4±5.1)%,and the 3-h residual rate was (28.8±3.6)%;24-h impedance-pH monitoring revealed that the mean DeMeester score was 5.8±2.9.Reflux esophagitis was observed by gastroscopy in 7 patients six months after surgery.Conclusions:Cheng’s GIRAFFE anastomosis is safe and feasible for Siewert type II AEG.

Keywords:Cheng’s GIRAFFE anastomosis;anti-reflux;Siewert type II AEG;proximal gastrectomy

Introduction

In recent years,adenocarcinoma of esophagogastric junction (AEG) has been increasing obviously in China,possibly caused by increased body weight,alcohol consumption,gastroesophageal reflux disease (GERD) and premalignant status.In Western countries,the 5-year overall survival (OS) with advanced AEG is less than 30%,which is the same as that in China (1-4).There is a significant difference in epidemiology,pathogenic mechanism,biological characteristics and prognosis between AEG and gastric antrum tumors;consequently,AEG has been defined as a kind of independent disease.To date,the scope of lymph node dissection,the selection of operative approach,the resection range and digestive tract reconstruction for the treatment of AEG have been in dispute,especially with respect to digestive tract reconstruction after surgery (5).

As there is no standard digestive tract reconstruction method for proximal gastrectomy,some studies have shown that the weight and nutritional status of patients after surgery are related to the extent of gastric resection but not to the reconstruction method.Proximal gastrectomy is superior to total gastrectomy because total gastrectomy destroys the ability to absorb vitamin B12,folic acid and iron and other factors,resulting in postoperative anemia and malnutrition (6).Because of the special position of Siewert type II AEG,compared with total gastrectomy,proximal gastrectomy can effectively prevent hypofunction of the digestive tract and anemia by using the gastric stump’s function of reserving and storing food.However,the normal physiological anti-reflux anatomical structure is destroyed because of cardia resection in proximal gastrectomy in patients with AEG.Therefore,the occurrence of esophageal reflux has become the main factor seriously affecting the postoperative quality of life of patients (7,8).

Digestive tract reconstruction for Siewert type II AEG was determined by the surgical approach.Controversy exists regarding whether reconstruction methods with low esophageal reflux should be used to treat AEG patients.Gastric tube reconstruction,antrum-preserving doubletract reconstruction and Roux-en-Y reconstruction have been the common methods (9).Some studies showed that the 24-h pH monitoring in patients with gastric tube reconstruction is similar to that in healthy people,but this may be related to the increasing incidence of gastroesophageal reflux disease in healthy people and the anti-reflux medication used in patients.Although antrumpreserving double-tract reconstruction has a good antireflux function,complicated methods and too many anastomotic stomas increase the rate of postoperative complications (10,11).The common physiological mechanism of anti-reflux is caused by the lower esophageal sphincter (LES),esophagogastric junction,His angle and so on.Therefore,we used a new reconstruction method that combines advantages of gastric tube reconstruction with rebuilding the His angle and fundus of the gastric tube.We call it Cheng’s gastric tube interposition esophagogastrostomy with reconstruction of His angle and fundus (Cheng’s GIRAFFE anastomosis) (Figure 1A?C).

Figure 1 Diagrammatic layout of GIRAFFE anastomosis.(A) Transection line of gastrectomy;(B) Complete GIRAFFE anastomosis;(C) A photo of the giraffe;(D) Esophagus was severed;(E) Methylene blue was used to draw the cutting range;(F?I) Linear staplers were used to cut off the gastric wall and a tubular stomach with a diameter of approximately 35 mm and a length of approximately 120 mm was formed;and (J?L) Reconstruction with circular stapler;(M-O) Reconstruction with linear stapler.

The aim of this study was to evaluate Cheng’s GIRAFFE anastomosis in proximal gastrectomy for Siewert type II AEG and to discuss the preliminary gastric emptying and anti-reflux results.

Materials and methods

Patients

We retrospectively analyzed the data of consecutive patients with Siewert type II AEG who underwent curative proximal gastrectomy with GIRAFFE anastomosis between February 2018 and September 2020 at the Department of Gastric Surgery,Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)and the Gastrointestinal Surgery of the First Affiliated Hospital of Zhejiang Chinese Medical University.All patients were confirmed by gastroscopy.The inclusion criteria were as follows:1) Patients with Siewert type II AEG;2) no supraclavicular lymph node or upper mediastinal node metastasis by preoperative CT and Bultrasound;and 3) laparoscopic surgery used for patients in stage cT1?3 and open operation used for patients in stage cT4.

This study was approved by the Ethics Committee of the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) and the First Affiliated Hospital of Zhejiang Chinese Medical University(No.IRB-2020-137).The study conformed to the tenets of the Declaration of Helsinki.All patients provided written informed consent before taking part in the study.

Proximal gastrectomy and lymph node dissection

According to the 3rd edition of Japanese Guidelines for the Treatment of Gastric Cancer,No.1,No.2,No.3,No.4a,No.4sb,No.7,No.8a,No.9,No.11p,No.19,No.20,No.110,No.111 and No.112 lymph nodes should be dissected.The gastrocolonic ligament was severed 1 cm below the gastroomental vascular arch,and the gastroomental vascular arch was reserved.The right gastric blood vessel and the first and second blood vessel branches at the beginning of the gastric antrum were reserved.

Reconstruction of digestive tract by GIRAFFE anastomosis

The esophagus was severed and the stomach was pulled out through an auxiliary incision (Figure 1D,Figure 2A).And the methylene blue was used to draw the cutting range(Figure 1E,Figure 2B?D).The principle are as follows:1)Ensuring that the incisal margin was 30?50 mm away from the tumor;and 2) the final tubular stomach with a diameter of approximately 35?40 mm and a length of approximately 120 mm.Firstly,the line staple was used to cut off gastric wall perpendicular to greater curvature of the stomach.Secondly,the gastric wall was severed along the greater curvature side to the fundus of the stomach,and the greater curvature side of the stomach was made into a tubular stomach with a diameter of approximately 35?40 mm and a length of approximately 120 mm (Figure 1F?H,Figure 2C?E).Thirdly,line stapler was used 60 mm away from the pyloric canal in the lesser curvature of the stomach,perpendicular to the lesser curvature side of the stomach and cutting off the gastric wall (Figure 1I,Figure 2F).Finally,the reconstruction was performed.For circular anastomosis (Figure 1J?L,Figure 2G?I),the esophagogastric anastomosis was performed with a circular stapler and the end of gastric tube was clamped with a linear stapler.For linear anastomosis (Figure 1J?L,Figure 2J?L),the esophagus was pulled to side of the stomach,roughly 40?50 mm overlap with proximal tubular stomach.The esophagogastric anastomosis was performed with a linear stapler and the entry hole of the stapler is closed by manual suture.

Figure 2 Diagrammatic layout of GIRAFFE anastomosis in surgery.(A) The esophagus was severed;(B) Methylene blue was used to draw the cutting range;(C?F) The linear staplers were used to cut off the gastric wall and a tubular stomach with a diameter of approximately 35 mm and a length of approximately 120 mm was formed;(G?I) Reconstruction with circular stapler;and (J?L) Reconstruction with linear stapler.

Reflux disease questionnaire (RDQ) scale

Patients were followed up one month after surgery,and symptoms of esophageal reflux (burning sensation behind sternum,chest pain,acid/bitter taste in the mouth,uncomfortable feeling caused by surging gastric contents)were evaluated using the RDQ scale for gastroesophageal reflux diseases.The assessment adopted the reflux symptom degree plus the reflux symptom frequency score,with the highest score of 40 points in the questionnaire,and the gastroesophageal reflux disease was considered for those with a total score ≥12 points.According to Montreal’s definition,if patients have mild reflux symptoms (mainly heartburn and reflux with symptom score ≤2) for 2?3 d in one week or moderate-to-severe symptoms (mainly heartburn and reflux with symptom score ＞2) for at least 1 d in one week,they will be highly likely to develop gastroesophageal reflux diseases.

Nuclide gastric emptying

One month after surgery,patients were followed up,and residual gastric emptying function was detected by the radionuclide gastric emptying method.Patients ingested99mTC-DTPA (2 mCi) mixed food (50 g steamed bread,1 fried egg with oil and 100 g porridge) and then were examined by abdominal pre-imaging and post-imaging at 0,8,11,15,20,25,30,60,90,120,180 and 240 min.The gastric emptying time-radiation curve and functional indicators were obtained.Patients were instructed to fast and not drink water during the monitoring,but they could engage in appropriate exercise indoors.According to the normal gastric emptying diagnostic criteria,the 1-h gastric residual rate is approximately 30%?90%,2-h gastric residual rate is approximately 10%?60%,and 3-h gastric residual rate is less than 30%.

Reflux esophagitis assessed by 24-h impedance-pH monitoring

One month after surgery,patients were followed up,and they consented to undergo 24-h impedance-pH monitoring using the ambulatory multichannel intraluminal impedance(MII) and pH monitoring system.The pH catheter electrode was calibrated in a solution of pH 4.0 and 7.0,and the electrode was inserted approximately 5 cm above the LES.An electrode ring was arranged every 2 cm between the catheter and the adjacent electrode rings to form a separate impedance channel.The catheter was connected to the recording device,and 24-h MII-pH measurements were performed.The number of acid regurgitation,weak acid regurgitation and non-acidregurgitation episodes in the orthostatic,supine and postprandial positions was assessed;regurgitation types(including liquid regurgitation,mixed regurgitation and gas regurgitation) and the DeMeester score which was a comprehensive score consisting of total of acid exposure time percentile (AET),AET in orthostatic,AET in recumbent,acid-reflux times,long acid-reflux times and longest reflux time were detected.

Reflux esophagitis assessed by gastroscopy

Patients were followed up six months after the operation,and the esophageal mucosa of patients was detected by gastroscopy.According to the Los Angeles Scale,normal was defined as no esophageal mucosal damage;Grade A was defined as one or more areas of esophageal mucosal damage with a diameter of less than 5 mm;Grade B was defined as the presence of one or more esophageal mucosal lesions with a diameter greater than 5 mm but no fusion lesions between each mucosal lesion;Grade C was defined as esophageal mucosal damage with fusion but involving less than 75% of the esophageal circumference;Grade D was defined as a broken and fused esophageal mucosa that involved at least 75% of the esophageal circumference.

Statistical analysis

GraphPad Prism 8 (GraphPad Software,Inc.,San Diego,CA,USA) and IBM SPSS Statistics (Version 20.0;IBM Corp.,New York,USA) were used for analysis,and all measurement data are expressed as.P＜0.05 was considered statistically significant.

Results

Patient characteristics

This study included 74 consecutive patients (44 males,30 females) with a mean body mass index of 23.1±3.1 kg/m2and a mean age of 61 (range,41?89) years.Among the 74 patients,43 patients were in stage I,and 31 were in stage II.Twenty-one patients underwent open surgery,while 53 patients underwent laparoscopic surgery.During the surgery,the mean anastomosis time was 39.0±4.6 min,and all patients underwent R0 resection.After operation,complications occurred in 4 patients,including anastomotic fistula in 2 patients,trouble emptying in 1 patient and anastomotic stenosis in 1 patient (Table 1).

Table 1 Patient characteristics (N=74)

Reflux esophagitis monitoring

All patients were assessed for RDQ scale scores from the day of operation to 6 months after the operation.The RDQ score was 4.4±3.0 one month after the operation,3.6±2.7 two months after the operation,3.4±2.6 three months after the operation and 2.2±2.5 six months after the operation.There was no significant difference in RDQ scores.Four patients had mild symptoms of reflux in the horizontal position,which could be changed by adjusting their position (Table 2).Fifty-seven patients underwent 24-h impedance-pH monitoring three months after the operation.The results showed that the total number of acid-reflux events was 12.6±7.8,the total number of nonacid-reflux events was 19.6±9.7,the longest reflux time was(43.8±22.7) s,and the mean DeMeester score was 5.8±2.9(Table 3).

All patients were evaluated by gastroscopy six months after the operation.Reflux esophagitis was found in 7 patients,including grade N in 3 patients,grade A in 1 patient and grade B in 3 patients (Table 4).＊,the highest score is 40 points;≥12 points means gastroesophageal reflux disease.

Table 2 Questionnaire RDQ scale

Table 3 24-h impedance-pH monitoring

Table 4 Reflux esophagitis assessed by gastroscopy (N=74)

Gastric emptying function monitoring

Fifty-seven patients underwent a radionuclide gastric emptying test three months after the operation.The results showed that the gastric half-emptying time was 67.0±21.5 min,the 1-h residual rate was (52.2±7.7)%,the 2-h residual rate was (36.4±5.1)%,and the 3-h residual rate was(28.8±3.6)% (Table 5,Figure 3).

Figure 3 Function of gastric emptying and anti-reflux after Cheng’s GIRAFFE anastomosis.(A) New gastric fundus (red arrows) had a good anti-reflux function;(B) Process of nucleotide gastric emptying;and (C) Representative reflux esophagitis evaluated by gastroscopy.

Table 5 Nuclide gastric emptying test

Discussion

AEG is a relatively distinct disease that is different from esophageal cancer and gastric cancer.Its special growth site and biological behavior have led to many controversies in the selection of surgical treatment strategies and procedures for AEG,especially regarding the reconstruction of the digestive tract after surgery.Anemia and malnutrition may occur after total gastrectomy due toimpaired absorption of vitamin B12,folic acid and iron.There is insufficient evidence that total gastrectomy provides a significant survival benefit for early Siewert type II AEG compared to proximal gastrectomy (12-14).Abdominal lymph node metastasis in Siewert type II AEG patients is mainly located at the side of the lesser curvature of the stomach and the left gastric artery.Hosodaet al.(15)showed that the right gastroomental vessel lymph nodes(No.4d),suprapyloric lymph nodes (No.5) and subpyloric lymph nodes (No.6) had a low metastasis rate in patients with Siewert type II AEG and no significant survival benefit from lymph node dissection.Gotoet al.(16)suggested that gastrectomy with distal gastric preservation could be performed for Siewert type II AEG and that distal perigastric lymph node dissection would not provide a survival benefit.However,the anatomical structure providing normal physiological anti-reflux will be destroyed by proximal partial gastrectomy in patients with Siewert type II AEG,and the occurrence of postoperative esophageal reflux has become the main issue that seriously affects the postoperative quality of life of patients.

At present,the main methods of reconstructing the digestive tract after proximal gastrectomy include esophagogastric anastomosis,interposition of the jejunum or the double channel method.Esophagogastric anastomosis has been used until now because of its simplicity and security and because it does not change the characteristics of the natural physiological channel of food.However,it has the disadvantages of insufficient residual gastric capacity and a high incidence of postoperative gastroesophageal reflux(17).In tubular gastric anastomosis,on the premise of ensuring a sufficient incision margin,the residual stomach is cut along the greater curved side,so that the lesser curved side became a tubular structure approximately 4 cm wide and was anastomosed with the esophagus.On the one hand,tubular gastric anastomosis can reduce gastric acid secretion by reducing the area of residual gastric mucosa;on the other hand,it can reduce the occurrence of esophageal reflux by expanding the gastric cavity.However,due to the long lumen of the tubular gastric anastomosis,the incidence of anastomotic leakage is increased,and the anti-reflux effect is not obvious in clinical practice (18).Therefore,Sakuramotoet al.(19) used the posterior wall of the stomach to surround the lower segment of the esophagus to reconstruct the His angle and create a false fornix,thus reducing the reflux rate of the esophagus after esophagogastric anastomosis.However,due to its complexity,this approach is not suitable for laparoscopic operation.The interposition method uses the placement of a segment of jejunum between the esophagus and the residual stomach to reduce the occurrence of esophageal reflux while restoring the continuity of the digestive tract.A reasonable jejunal length is the key to jejunum interposition.An excessively short length is not conducive to anti-reflux,and an excessively long length is not conducive to postoperative gastroscopy.Double channel jejunum interposition involves placing a segment of the jejunum between the esophagus and the residual stomach to form a continuous channel of the jejunum and a channel of the jejunum-residual stomach-duodenum-jejunum.Both dual-channel jejunal interposition and single-channel jejunal interposition have good anti-reflux effects,but they require a high length of mesentery of the small intestine and many anastomoses,which increases the risk of postoperative complications.

Therefore,a reasonable reconstruction of the digestive tract after proximal gastrectomy should include the following points.First,for safety,a sufficient blood supply,low tension at the anastomotic stoma and a minimized number of anastomotic stomas should be considered.Second,it may be better to have the function of food storage and emptying,preventing the occurrence of reflux gastritis and esophagitis,as far as possible in line with the physiological pathway.Third,we attempted to ensure the feasibility of postoperative endoscopic examination,including examination of the residual stomach,biliary tract,pancreas and so on.Fourth,a simple operation is also important because it can be used not only in open surgery but also in laparoscopy.To this end,the Department of Gastric Surgery of Zhejiang Cancer Hospital combined the above characteristics to propose Cheng’s GIRAFFE anastomosis.

In this study,a total of 74 patients with Siewert type II AEG were treated with Cheng’s GIRAFFE anastomosis.The main advantages of GIRAFFE anastomosis are as follows:First,patients had good gastric emptying function after the operation.A tubular stomach was formed,and the distal part of the stomach was retained as a storage bag in GIRAFFE anastomosis.According to the radionuclide gastric emptying examination,the gastric half-emptying time was 67.0±21.5 min 3 months after the operation,and the gastric residual rates were 52.2%?7.7%,36.4%?5.1%,and (28.8±3.6)% at 1,2 and 3 h,respectively.Compared with the diagnostic criteria of normal gastric emptying (20),it showed good function of gastric emptying.The factors that promote gastric emptying mainly include the nerve reflex caused by the mechanical stimulation of gastric contents and the release of gastrin by stimulation of the gastric antrum mucosa.One patient showed good gastric emptying in the first 2 h of the nuclide emptying examination,but the residual rate at 3 h was 34%,which may have been related to the weakened stimulation of the gastric wall after partial injury of gastric wall nerves and partial elimination of gastric contents during proximal gastrectomy.Second,the procedure yields good anti-reflux function.His angle is acute between the esophagus and the fundus of the stomach.It is a movable valve and plays an anti-reflux role.The anti-reflux function of GIRAFFE anastomosis depends on the establishment of a new gastric fundus from the storage bag and the His angle between the gastric fundus and the end of the tubular stomach.In addition,the residual stomach is made into a tubular structure with a width of 4 cm and a length of more than 5 cm,which can be regarded as a bridge between the esophagus and the residual stomach and plays an important anti-reflux role.The RDQ score of 74 patients 6 months after the operation was 2.2±2.5,which mainly manifested as the upward flow of gastric contents when overeating.The currently accepted standard for gastroesophageal reflux is abnormal acid exposure observed by 24-h impedance-pH monitoring.An esophageal pH＜4 in 24 h at a percentage＞4.2% and/or a DeMeester score ＞14.72 can be considered abnormal acid exposure.The number of acid-reflux and non-acid-reflux events in patients after GIRAFFE anastomosis was low,including the total number of acidreflux (12.6±7.8) events,total number of non-acid-reflux(19.6±9.7) events,the longest reflux times (43.8 svs.22.7 s),and DeMeester score (5.8vs.2.9 points).According to the latest GERD Lyon consensus,abnormal regurgitation is indicated when 24-h regurgitation events exceed 80 times,and physiological regurgitation is indicated when the 24-h regurgitation events are less than 40 in number.Xiaoet al.conducted impedance-pH monitoring on 70 healthy people for 24 h,and the results showed that the median total reflux was approximately 40 times (21).Moreover,all patients underwent endoscopic evaluation at 6 months postoperatively.The results showed that reflux esophagitis was found in 7 patients,including grade N in 3 patients,grade A in 1 patient and grade B in 3 patients.The rate of reflux is less than 10%.

The present study has several limitations,including the small sample size and retrospective design.A more extensive controlled study is needed to confirm the benefit of this new anastomosis for the treatment of patients with Siewert type II AEG.In addition,we are conducting a prospective clinical study to evaluate Cheng’s GIRAFFE anastomosis.This trial was registered on the ClinicalTrials network (http://www.clinicaltrial.gov) as (No.NCT 04657848).

Conclusions

Cheng’s GIRAFFE anastomosis used in patients with early Siewert type II AEG is safe and feasible.It is simple and suitable for open and laparoscopic operations,and the reconstructed digestive tract is consistent with physiological characteristics and has good anti-reflux effects,which can be used as a new anastomotic method for patients with Siewert type II AGE.

Acknowledgements

This study was supported by Diagnosis and Therapy Center of Upper Gastrointestinal Tumor (No.JBZX-202006);Key Laboratory of Prevention,Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province (No.2022E10021) and Medical Health Plan of Zhejiang Province (No.2020KY488 and No.2022KY684).

Footnote

Conflicts of Interest:The authors have no conflicts of interest to declare.