Clinical Outcomes of Laparoscopic Proximal Qastrectomy with Double Tract Reconstruction in Early Stage of Siewert type II for Adenocarcinoma of Esophagogastric Junction

Objective: The aim of the current study was to investigate the surgical related complication rates, nutritional status, prognosis and the quality of daily life following laparoscopic proximal gastrectomy(LPG)with double tract reconstruction in comparisonto those of laparoscopic total gastrectomy(LTG) for Siewert type II adenocarcinoma of esophagogastric junctionin three tertiary institutions. Methods: We compared the postoperative outcomes of the two surgical approaches using a well-characterized cohort of early stage gastric carcinoma patients through a retrospective reviewbetweenJanuary2017, and December2018. Both groups were compared regarding patient characteristics, surgical results, the change of body mass index, serum hemoglobinalbumin, vitaminB12and quality of life(qol).Qol was assessed by the Chinese version ofQuality of Life Questionnaire Oesophagogastric-25(QLQ-OG25). The incidence of reux esophagitis, dumping syndrome, and retention syndrome, were also compared to evaluate postoperative restoration. Results: Both study groups were comparable with respect to general patient characteristics. No mortality and no signicant differences were found for qol and surgery- related data except operation time(p < 0.05). The LPG group was associated with a better recovery of body max index ,a fewer incidence of reux complications and better nutrition parameters (p < 0.05) than the LTG group. Conclusions: In this study, double tract reconstruction after a LPG procedure is safe for gastro esophageal junction cancer. It is superior to the LTG with respect to less incidence of reux disease,better body weight and improved postoperative nutrition status.


Introduction
The incidence of adenocarcinoma of the esophagogastric junction(AEG) has been increasing worldwide, which attracts great attention among medical professionals because of its anatomical location and unique biological behavior.A classical clinical system based on the relationship between tumor center and the area of the esophagogastric junction(EGJ)was rst established by Siewert in 1987 [1]. In this recognized system, the AEG is divided into three types: Siewert type I: the tumor center is 1 cm-5 cm above the EGJ and grows downward and invades it; Siewert type II: the tumor center is 1 cm above or 2 cm below the EGJ and invades it; Siewert type III: the tumor center is 2 cm-5 cm below the EGJ and invades it. The most frequently used therapeutic modality for AGE is surgical resection.
Asaspecialtumoracrossthethoracicandabdominalanatomicareas, AEGhascertainparticularitysurgicalpathandresectionrangeofesophagusandstomach,whichisaproblemtobeexplored. The worldwide standard recommendation for the Siewert type II and III is still total gastric resection, especially for the advanced stage of AEG. But, complications including anemia, weight loss and dumping syndrome after TG are depressing. A recent review of literature reporting proximal gastrectomy on treatment of early stage,showed an encouraging postoperative ve-year survival rate and recurrence rate [2]. As the surgical options available for the treatment of Siewert type II of AGE increase, the ability to acquire a better recovery and quality of life postoperatively takes on great importance.
An idealdigestive tract reconstruction after LPG is most likely associated with rare complications and a better quality of life. Qol is a medical recognized outcome measure in the choice of patients received differ surgical process with gastric cancer [3]. Recently, LPG with double tract reconstruction (DTR) is considered to be a less invasive surgical approach for theearly stage of Siewert type II AGE patients with a result of better nutritional status and Qol.This technique minimizes the morbidity of the re ux disease and saves partial stomach that would maintenance the normal gastro-duodenal channels.
The aim of the current study was to investigate the surgical related complication rates, nutritional status, prognosis and the quality of daily life following LPGwith DTR in three tertiary institutions. For this purpose we have used de ned and validated scoring system to evaluate postoperative functional outcomes as reported in the previous study [4,5] Materials And Methods

Double -tract reconstruction technique
Radicalresection of Siewert type II of AGE with D1 lymph node dissection was done as previous study [6]. After the proximal stomach is removed, conventional RY reconstruction was done. In general, an ideal jejuna loop must be long (35-40cm), mobile and well vascularized to reach the esophagus with no tension. We usually choose the area of the jejunum distal to the ligament of Treitz while protecting the mesenteric vessel arcade. Firstly, the anvil with a diameter of 25mm is applied at the stump of the esophagus and purse-string suture is tied, then a matched circular stapler is carefully inserted into the jejunal pouch bringing the jejuna loop in front of the transverse colon. After attaching the anvil to the central rod, the stapler device is red to complete the esophago-jejunostomy. Secondly, a side to side gastrojejunostomy is nished using ECHELON FLEX 29mmcolumnar stapler cutter at a distance about 10-15cm far from the esophagojejunostomy on the anterior wall of the great curvature of residual stomach (Fig. 1). So, the food can be divided into the remnant stomach through the duodenum and jejunummaintainingthe continuity of the digestive tract. Finally, a rouxen-y type jejunojejunostomy is performed using 25mm ETHICON circular stapler, about 15-20cm far from the gastrojejunostomy ,to maintain the intrinsic physiological biliopancreatic passage.
This technique consists of three anastomoses (Fig. 2): gastrojejunostomy is 10-15 cm below the EJA and the jejunojejunostomy is 20-25 cm below the gastrojejunostomy.Double-tract reconstruction therefore preserved the partial stomach and pylori to the conventional TG with differ reconstruction methods. Unlike jejunal interposition, this method maintains the continuity of the upper digestive tract, making it easier to perform. Furthermore, it has a dual route for food passage, reducing the incidence of delayed food emptying obstacle.

Patient selection
Eighty-seven patients diagnosed with Siewert type II of AGEat three tertiary hospitals(the Central Hospital of Wuhan/NO.1 hospital of wuhan/the Central hospital of yichang) between January2017, and December2018, were involved in this study. The inclusion and exclusion criteria in patient selection are shown in Table 1.All preoperative and postoperative data were reviewed by using institutional surgical database involved in this research.The clinical pathologic data, outcomes after surgery were shown in Table 2. Total gastrectomy with RY anastomosis or Proximal gastrectomy with double tract reconstruction was done.
No distant transfer, radical surgery was con rmed R0 resection by postoperative pathological test.
Voluntary to accept and complete the postoperative questionnaires of quality of life during the follow-up period.

Exclusion criteria
History of radiotherapy and/or chemotherapy or targeted drug therapy before surgery History of other malignant disease.
Gastrointestinal dysmotility caused by diabetes, Parkinson's disease or other diseases can in uence the GI motility. Functional outcome and nutritive data assessment

Lack of clinical data
To evaluate the quality of life after surgery, one validated and internationally accepted instruments was employed in this research for data collection: Quality of Life Questionnaire Oesophagogastric-25(QLQ-OG25). The QLQ-OG25 questionnaires were divided into the 13 categories like eating restrictions, dysphasia, re ux, pain, anxiety, body image, taste,dry mouth, and hairlossdescribedpreviously designing especially for patients with malignant diseases undergoing surgery [7,8]. In general, the higher scores in the functional scales of the QLQ-OG25 represented a poor postoperative recovery. Moreover, total plasma protein, prealbumin, serum hemoglobin, and vitaminB12 levelswere also used to evaluate nutritional condition in this research.All assessments were carried out at 1\3\6 months and 1 year after operation.Data were collected through the outpatient clinic as well as through a telephone interview.

Statistical Analyses
Variables that ful lled the criteria for a normal distribution were analysed using the Kolmogorov-Smirnov test, and normally distributed data were expressed as mean ± SD, followed by a two-tailed Student's t tests to determine the P values.Chi-square was used for enumeration data consisted of categorical variable. Statistical analyses wereperformed using SPSS software, version 21.0(SPSS, Chicago, IL, USA).A difference between groups with a pvalue of <0.05 were considered statistically signi cant.

Results
Only patients who completed the entire follow-up were included in the analysis. Forty-two patients received LPGwith DTR gastrojejunostomy, and the rest 45 patients underwent the TG with conventionalEJA reconstruction.No signi cant differences were found between groups regarding demographic or clinical characteristics ( Table 2). We considered the cohort is suitable for comparing the outcomes between the LPG with DTR and the LTG with EJA procedure. No mortality was found during the whole study cycles. Anastomotic complications werelow(5.7%). The common complications directly related to surgery were pneumonia (10.3%) ,ileus (6.9%) .No statistical signi cance was con rmed within the two differ digestive tract reconstruction styles with respect to any of the factors that were directly linked to expected operation time(260.2 ± 22.1vs 205 ± 11.8,p 0.001)Other serioussurgical complications like peritoneal abscess, pancreatic stula, were not found in our cohort, patients in general satis ed with surgical outcomes, and the vast majority of patients reiterated that they would opt for each reconstruction way again, given the similar conditions. Both the body weight changes and nutritional index show a descending trend after surgery. In practical terms, at the point of 6 month follow up, the condition of serum hemoglobin, vitamin B12 level and loss of weight was inferior in the LTG group as compared to that in the LPG with DTR procedure, and the difference was statistically signi cant (Table 3); Follow up was done through outpatient or telephone, deadline was December 2018. Of the 87 patients,82 patients were followed up with a follow-up rate of 94.3%, a follow-up time of 24 months.During the subsequent follow-up,a similar phenomenon occurred again, the BMI content in LPG group is much closer to preoperative level .Up to 2years after the operation, the serum albuminlevel in the LPGgroup exhibited a better recovery. Interestingly, all the data except vitamin B 12 related to postoperative hematologic and nutritional were improved with time in these patients, probably due to a general improvement as diet control and body adaptive capacity in the longer term (Table 3).
Forlong-term complications, we also do a survey at the last follow up point, the incidence of re ux esophagitis was rare in the LPG group compared to the LTG procedure group, although the difference was not statistically signi cant. Complaints about dumping syndrome and retention syndrome were more commonly reported in the LTG group during follow-up phone calls butnot exhibited a statistically signi cant difference compared to patients within the LPG group (Table 4).Whenconcerned about the qolof patients after surgery, the majority indicators performed better in the LPG group, although the difference was not statistically signi cantbut dietary restrictions (Table 5).

Discussion
The incidence of AEG has gradually increased in the past two decades, and the incidence of early gastric cancer has increased sharply in China as the improvement of health consciousness and promoting the endoscopic techniques in basic hospitals [9][10][11]. Guidelines are available for common surgical options for Siewert type I and III of AEG according to the consensusfrom the international tumor cooperation group [12,13]. More recently,Ivor-Lewis esophagectomywith lymph node dissection (mediastinal and partial abdominal lymph nodes)is recommended for the former,in general ,it can be treated with reference to distal esophageal cancer [14]. In the event of latter, the patient should receive a total gastrectomy with D2lymph node dissection. Treatment of Siewert type II traditionally consisted of surgical resection with proximalstomach for early stage smaller-size tumor and total gastrectomy for larger, invasive tumor. However, it is well documented that proximal gastrectomy with remnant stomachesophageal anastomosis alone usually results in high anastomotic leakage rate due to re ux esophagitis and delayed gastric emptying [15]. Thus, it is extremely important that an appropriate digestive tract reconstruction has been associated with a decrease rate of complications when underwent proximal stomach resection and is therefore reserved for early stage Siewert type II AEG patients who are not candidates for total gastectomy.
The choice of reconstruction manner after gastrectomy involves not only a continuation of the anatomical structure, but is also aimed to preserve the physiological function. The most attractive of the antrum-preserving alternatives is the double tract method,which consists of subtotal gastrectomy,creation ofthe residual stomach and preservation of the duodenal route. This original operation was described by Aikou T in 1988 in order to gain the smooth transfer of larger foods through the duodenal route [16]. In an attempt to improve functional outcomes, some points were made when carrying out the anastomosis between the residual stomach and the jejunum, maintained the physiological pancreaticocibal synchronism. One debated issue is whether DTR should be offered to young patients.Two reasons to avoid these procedure in young patients relate to the high incidence of gastric stump cancer with increasing age and the morbidity of re-operations in these potentially relapse patients.The presence of distant metastatic condition is generally a contraindication to DTR.These unfortunate patients should be managed with total stomach resection with esophago-jejunostomy(RY).
Several prospective studies have compared the surgical outcomes after LPG with DTR and LTG with RY in the treatment of AEG. No difference was found in improving re ux symptom between the two procedures. However, the increasing percentages of the serum albumin, total protein, and hemoglobin levels were signi cantly higher in patients received DTR [17][18][19]. Eiji Nomura et al from the Tokai University Hachioji Hospital reported the results of a study evaluating functional outcomes between differ types of reconstruction following LPG and TG. The post-/preoperative body weight ratios were signi cantly higher in the patients underwent DTR [20] .Takiguchi et al and Nakamura M et al conducteda propensity-score matching analysis and found double tract building was superior to conventional RY reconstruction after LTG in QoL [3]. Others, however, have reported similar results [21,22]. Since the nutritional status and QoL followed the DTR after LPG is still controversial, fewer literatureto report it in the treatment of AEG, the purpose of this study is to discuss the clinical and postoperative recovery impact of surgicaloption choice.
In this study, after analyzed the postoperative follow-up data, we nd BMI of patients who underwent LPG with DTR was higher than that of patients with LTG procedure, the possible reason was that some patients with gastric tumor had complications such as nutritional de cient diseases,many studies have demonstrated that RY reconstructive style had positive effects on weight loss. The LTG procedure cost more time and dissected more lymph node numbers. About 16 months after surgery, one gastric carcinoma recurrence (5%) was found in LPG group, this data is in agreement with those reported in literature concerned .It was noting that the cancerous rate of gastric stump in LTG maybe closely related to pathological grade and regional lymph node metastasis. In addition, this study showed that the proportion of improved nutritional status was signi cantly higher than that of LTG. Compared with RY reconstruction after LTG, DTR after LPG could guarantee residual stomach. Unlike removed the whole stomach, this method maintains the continuity of the digestive tract, making it time-saving to perform the procedure. Furthermore, it has a dual route for food passage, reducing the incidence of delayed remnant gastric emptying. Compared with LTG,we found no more serious incidence of re ux symptoms related to gastric stump in LPG (Table 4).We suspected that the fewer malnutrition rate especially low risk of vitaminB12 de ciency in LPG group can be associated with the storage function of the remnant stomach.
In our opinion, the stomach has great role in the maintentance of normal nutrition,working primarily to secret intrinsic factor and to store food so that the frequency of re ux symptoms may be limited. Thus, surgical resection of the whole stomach may lead to the loss of vitaminB 12 absorption, necessary for normal hemoglobin synthesis, result in pernicious or macrocytic anemia. Patients received total gastrectomy may require monthly administration of vitaminB 12 (nasal or intramuscular).Another advantage of preserved distal stomach is that it allows the chyme passes through the gastroduodenal channel, promoting the gastrointestinal peptide hormone exposure, avoiding potential body weight loss caused by excessive growth of intestinal bacteria, insu cient secretion of trypsin and poor absorption (Fig. 3). Postoperatively, patients underwent proximal gastrectomy are able to gain weight and return to a much better level of general nutrition. Additionally, residual stomach often means a larger reservoir than intestinal and therefore less risk for gastrointestinal motility disorder complications. In general, the results of surgical resection of proximal stomach depend on the choice of reconstruction manners. In the literature, the outcomes for patients with differ reconstruction after proximal gastrectomy has been variable. Here, we recommended preserve half of the stomach at least during the procedure of DRT after LPG. DRT has dual-output channel, one is the jejunum -remnant stomach -duodenum -jejunum, and the other is the continuity of the jejunum. Each channelcan provide energy and nutritional stores for body use (Fig). Hence, it mayavoid the risk of high intestinal obstructiondue to the recurrence of abdominal lymph node, except for the condition both the channels are packed with tumor compression.In this research, DRT indeed brings some bene ts like ideal postoperative food intake, low risk of anemia and better weight maintenance as the preservation of a partial stomach without burdening the risk of anastomotic strictures, re ux, and indigestion.Thus, the double tract technique appears to be a more physiological reconstruction.
Nowadays, because the proved excellent disease free survival rate of early-stage upper gastric cancer patients, increasing emphasis on recovery of psychological and social roles after operation drew our eyes. Increasing attention on quality of life in patients diagnosed with early stage AEG, therefore a careful survey of postoperative daily life situation is necessary.The QLQ-OG25 moduleis widely used in assessment of the quality of life of AEG patients after surgery.Although, several studies have shown the qoL of DTR after LPG was not superior to that of LTG procedure. This little study showed similar results: in term of long-term results, patients underwentDTR after LPGshowed no signi cantly postoperative recovery expect dietary restrictions, but the mechanism was still unclear.Even though, for early stage upper gastric cancer patients, we conducted that DTR after LPG may be preferred for surgical treatment.
There were certain limitations in our research. Firstly, the short follow up period-just 2 years was a limitation to elucidate the incidence rate of gastric stump carcinoma after PG. Secondly, relatively simple questionnaire was involved in data analysis, there was no doubt some other parameters might also in uence the evaluation result. Clearly, unconsolidated recognition in the perceptions of function recovery de nition may also lead to an unconscious bias on participantswhile combining data for self-assessment questionnaire form, relying on the individual understanding of these patients. Finally, this study is based on the retrospective analysis which could have resulted in a selection bias. Another potential interference factor is that the surgical procedure is nished in differ medical units, although the surgeons have acquainted anatomical knowledge and perfect technique.

Conclusion
In summary, the choice of surgical strategy for Siewert type II AEG is dependent on the stage of tumor, the anticipated functional outcomes as a result of therapy, and the risk of complications. For T1 and early T2 tumors, proximal gastrectomy with DTR may be easy to operate, less morbid and better quality of life than other digestive tract reconstruction style and therefore a superior choice. Although these results are encouraging, we cannot make any conclusion about long term outcomes until more adequately power multi-center controlled clinical trials that will hopefully provide with the answers in the near future. Schematic illustration of the residuals gastro-jejunostomy. Additional remark: residuals gastro-jejunostomy was accomplished using a 29mm circular stapler: the proximal jejunum was repositioned as to allow a side to side anastomosiswith no tension.