Modified Double-Tract Reconstruction in Terms of postoperative quality of life of Patients with Early Adenocarcinoma of Esophagogastirc Junction after Proximal Gastrectomy

Abstract

Background

Increased reflux symptoms limited clinical application of proximal gastrectomy (PG) in the patients with early adenocarcinoma of esophagogastirc junction (AEG). The purpose of this study is to describe a method of modified double-tract reconstruction (DTR) after PG, and to evaluate the feasibility, safety, surgical outcomes, postoperative gut function and nutritional status post operation.

Methods

Prospective cohort data of 25 patients with early AEG who presented to a single tertiary hospital from Jan 2019 to Jun2019 and underwent DTR after PG were analyzed respectively. The data of this prospective cohort included: clinicopathologic characteristics, surgical outcomes, time to first flatus and defecation, Visick Score, degrees and extent of remnant gastritis, Los Angles Classification in 1-year follow-up. Another 25 early AEG patients performed TG by propensity score matching analysis from Jan 2018 to Dec 2018 were picked as control group.

Results

There was no significant difference in BMI, ASA score, tumor size, Siewert type, tumor Grade, proximal resection margin, the number of LN harvested and TNM Stage between two groups.

The operation time and hospital stay was longer, and estimated blood loss was more in DTR group. The postoperative complication rate was 8% (n = 2), which were both treated by conservative management. The volume of postoperative daily intake could reach over 700ml on 6th POD, which was much more than TG group. The weight loss of patients in DTR group remained steadily from 3^rd month after operation, which was also better than TG group. The rate of reflux symptoms was 12% (n = 3), which were classified as Visick grade II. The degree and extent of remnant gastritis in DTR group were acceptable. The incidence of residual food in remnant stomach reached 32%, but most of them were only evaluated as Grade 1.

Conclusion

The short-term outcome of this modified DTR was satisfied, which could improve the nutrition status and quality of life post operation. We believe our modified technique is one of feasible, safe, and useful choice for early AEG patients.

Introduction

The incidence of early gastric cancer (EGC) increased gradually in recent years, which may be caused by raising the self-consciousness to health care and early treatment due to cancer-screening program in our country ^[1]. And what’s more, according to our nationwide survey, the incidence of adenocarcinoma of esophagogastirc junction (AEG) has also increased in last several decades ^[2–3]. These trends have increased more interests in surgical treatments on AEG with early stage.

Proximal gastrectomy (PG) was used to be deemed as a standard surgical option for early AEG during former clinical practice, which could preserve physiological function of the remnant stomach. But conventional esophagogastrostomy after proximal gastrectomy might induce severe reflux and anastomosis site stricture post-operation which might limit its clinical application ^[4–5]. Thus total gastrectomy (TG) was widely performed on most AEG instead of PG. However, in general, TG might result in prolonged food intake restriction and long-term nutritional deficiencies ^[6]. But more and more evidence showed that, based on oncological safety, PG was more suitable to early AEG, which could associate with better nutritional status, less body weight loss, low incidence of anemia, diarrhea, dumping syndrome and better quality of life ^[7–8].

The double tract reconstruction (DTR) method following PG was first reported by Aikou ^[9] in terms of gaining the smooth transfer of larger foods through the duodenal route. But some articles argued food could not always enter the duodenum smoothly and there was no improvement in Visick score in a large portion of patients. We therefore designed some improvements to modify the alimentary tract reconstruction in DTR following PG.

Patients And Methods

Ethics Approval and Trial Registration

Ethical approval was given by local ethics regional board: Shanghai Changhai Hospital Ethics Committee (No. CHEC 2019-087). Registration with approved clinical trials registry, Chinese Clinical Trials Register, was undertaken (ChiCTR 1900024826). Ethics approval and registration were performed before trial commencement.

Patients

From Jan 2019 to June 2019, a total of 25 cases diagnosed with early AEG were preoperatively performed DTR at Shanghai Changhai Hospital, China, which is a tertiary teaching hospital with more than 2,500 beds serving 40,000 inpatients and 1,800,000 outpatients and emergencies each year. The case volumes for gastric carcinoma reach more than 1500 per year. And we retrospectively collected the data of another 25 early AEG patients performed TG by propensity score matching analysis from Jan 2018 to Dec 2018 as control group.

Preoperative assessments were carried out by endoscopy and biopsy, endoscopic ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI) if necessary. And the eligibility criteria of patients were as follows: (1) gastric cancer was confined within muscularis propria layer by echogastroscopy (T₁), (2) no lymph nodes and organs metastases in CT or MRI (N₀M₀), (3) the diameter of tumor was less than 3cm. Additional inclusion criteria were age 18 to 80 years, life expectancy >1 year, and adequate organ functions (leukocyte count >3,500/μl, platelet count >100,000/μl, hemoglobin >10.0 g/dl, serum creatinine <1.25 times upper limit of normal [ULN], transaminases and alkaline phosphatase <2.5 times ULN or <5 times ULN in patients with liver metastasis, bilirubin <1.5 times ULN, and prothrombin time <12.0 s).

The exclusion criteria of patients were as follows: (1) patients with previous history of abdominal surgery and endoscopic submucosal dissection (ESD), (2) patients with central nervous system involvement or other significant medical conditions, (3) patients chose ESD instead of operation.

Procedures for double-tract reconstruction after PG and conventional alimentary reconstruction after TG

Double-tract reconstruction after PG The decision to perform laparoscopic operation or open procedure is a judgment decision made by surgeons either before or during the operation.The basic range of surgical resection included the distal esophagus and proximal 1/3 to 1/2 stomach with D1⁺ dissection of lymph nodes (No. 1, 2, 3a, 4sa, 4sb, 7, 8a, 9 and 11p). Intraoperative frozen section examinations were performed to confirm the tumor-negative resection margins. The right gastroepiploic vessels, right gastri cartery and suprapyloric veins were preserved.

Gastrointestinal continuity was restored by double-tract method. The jejunum was divided about 15-20 cm below the Treitz ligament and esophagojejunostomy was performed with the distal jejunum by a circular stapler. Jejunojejunostomy was performed about 45 cm below the esophagojejunostomy and gastrojejunostomy was performed 10 cm below the esophagojejunostomy.

Alimentary reconstruction after TG The basic range of surgical resection included the distal esophagus and total stomach with D2 dissection of lymph nodes (No. 1, 2, 3, 4, 5, 6, 7, 8a, 9 and 11p). Intraoperative frozen section examinations were performed to confirm the tumor-negative resection margins. The jejunum was divided about 15-20 cm below the Treitz ligament and esophagojejunostomy was performed with the distal jejunum by a circular stapler. Jejunojejunostomy was performed about 40 cm below the esophagojejunostomy.

Modification in alimentary tract reconstruction in DTR

1. Shorten the distance between esophagojejunostomy and gastrojejunostomy, which was set within 10cm.
2. Gastrojejunostomy was performed on the anterior gastric wall.
3. Retrocolic gastrojejunostomy were adopted.
4. Preserve all pyloric vessels and nerves. (Including: right gastric artery (RGA), right gastric vein (RGV), right gastro-epiploic artery (RGEA), right gastro-epiploic vein (RGEV), infra-pyloric vein (IPV) and pyloric branches of vagal nerve. (Figure 1)

Enhanced Recovery After Surgery (ERAS) program post-operation

All patients underwent an ERAS program which was initially developed through a consensus meeting involving surgeons, oncologists, anesthesiologists and nutritionists. Details are as follows: Preoperative care included counseling before and after admission, avoidance of mechanical bowel preparation, a normal diet until the evening meal of the day before surgery and 1000ml oral rehydration salts intake 3h before surgery. Intraoperative care included transversus abdominis plane block (TAP-block), warming set for all intravenous infusions during operation. Postoperative care included patient controlled analgesia (PCA) in 48 hours after surgery, high flow oxygen for at least 12 hours, analgesia and antiemetic drug use if necessary (no motility agents or opioid antagonists). On postoperative day (POD) 1, nasogastric tube and urinary catheter were usually removed and patients were encouraged to get out of bed for more than 4 hours and drink water or clear soup 50ml per time. From POD 2, patients were encouraged to walk for more than 4 hours and start nutritious powder supplement 100ml per time. From POD 4, patients were encouraged to try semi-liquid diet and stepwise to normal diet. The frequency of food intake was at the patients’ discretion. Drainage tube was evaluated and removed from POD 5. Patients were discharged if they had achieved adequate pain relief and semi-liquid food tolerance, free walking ability, and exhibited normal vital signs and laboratory data. The completion of ERAS program included two categories, the first was that patient followed the aforesaid schedule and discharged within 8 days and the second was one or two days delay due to patients’ personal reason ^[10].

Clinical Analysis, Surgical Outcomes and Nutritional Status

The indicators of clinicopathological characteristics gathered were age, sex, BMI, ASA score, cancer stage, and tumor size. The surgical characteristics were operation time, estimated blood loss, proximal and distal resection margins, and number of retrieved LNs. The surgical outcomes were recovery of gut function which was measured by time to first flatus and first bowel motion, postoperative daily intake, the severity of gastroesophageal reflux symptoms (Visick score), remnant gastritis, surgical complications, and length of stay (LOS). The degrees and extent of Remnant gastritis and severity of reflux esophagitis (Los Angeles Classification) were evaluated by one same doctor by gastroscope, and the severity of early or late postopertative adverse events was classified according to Clavien-Dindo Classification System.

Follow up

All the patients enrolled were followed up 3, 6, and 12 months post-operation in outpatient department. The characteristics of the patients and their outcomes were obtained by reviewing the electronic medical records and the picture archiving and communication system.

Statistical Analysis

To minimize the influence of other confounders on outcome, we used propensity score analysis to match early AEG patients performed DTR with patients performed TG. Enrolled patients performed DTR were matched in a 1:1 ratio with patients performed TG using the nearest neighbor matching and based on gender (male or female), Siewert Type (Type Ⅰ, Ⅱ, Ⅲ), tumor Grade (well-differentiated, moderately differentiated, poorly differentiated) and TNM stage (Ⅰa, Ⅰb, Ⅱ).

Statistical analysis was performed using SPSS software (18th version, SPSS, Chicago, IL, USA). Enumeration data was presented in percentage, measurement data was presented in average number and standard deviation, abnormal distribution data was displayed by median and quartile. Continuous variables were expressed as mean±SD and compared using the t test or Mann-Whitney test. Categorical variables were compared by the χ² test or Fisher’s exact test. A probability (P) value <0.05 was considered to indicate statistical significance. All tests were two-sided.

Results

Clinicopathological characteristics of patients enrolled 

The clinicopathological characteristics of the patients enrolled were presented in Table 1. There was no significant difference in BMI, ASA score, tumor size, Siewert type, tumor Grade, proximal resection margin, the number of LN harvested and TNM Stage between two groups, which showed these two groups matched well and DTR was oncologically safe for early AEG. The operation time and hospital stay of patients performed DTR was longer than the patients in control group. The estimated blood loss in DTR was also more than control group. 

Surgical Outcomes, postoperative gut function and nutritional status of DTR patients  

In DTR group, the early postoperative complication rate was 8% (n = 2), including: wound infection (n=1) and pneumonia (n=1), which were treated by conservative management. The postoperative gut function improved gradually, and the volume of postoperative daily intake could reach over 700ml on 6th POD, which was much more than TG group (<0.01). The weight loss of patients in DTR group remained steadily from 3^rd month after operation, which was also better than TG group (<0.01). Postoperative gastrography after modified DTR reconstruction showed that contrast medium could flow to remnant stomach easily. The rate of reflux symptoms was 12% (n = 3), which were classified as Visick grade II and also verified by endoscopic evaluation at 1-year follow-up after operation. The degree and extent of remnant gastritis in DTR group were acceptable. The incidence of residual food in remnant stomach reached 32%, but most of them were only evaluated as Grade 1. (Table 2)

Discussion

Compared with TG, PG associated with a better nutritional status, which suggested to be an ideal surgical option to the patients with early AEG. As a result, interest in PG has grown in recent years ^[11]. Esophagogastrostomy was much simpler than other methods of alimentary reconstruction because it only included one anastomosis, but high incidence of reflux esophagitis post-operation limited its clinical application. Other modified esophagogastrostomy methods such as: Kamikawa and etc. were more complicated to be performed ^[12]. And digestion and absorption of many substances, such as proteins, fats, fatsoluble vitamins, most water-soluble vitamins (except vitamin B12), and selected microelements (iron, potassium) only takes place in the duodenum and initial part of the jejunum. Therefore, the maintenance of partial duodenal passage should in theory improve absorption, even in other segments of the bowel ^[13]. Therefore DTR was thought to be the best reconstruction procedure with respect to quality of life post operation and anastomosis-related late complications, especially postoperative reflux esophagitis ^[14].

There was still some concern about this kind of alimentary reconstruction during initial clinical practice. First and foremost, most dietary intake might escape into the route of jejunum which may cause these functional benefits of proximal gastrectomy might be similar with total gastrectomy ^[15]. And the incidence and grades of remnant gastritis would also increase gradually caused by erosion of gastric acid which could not be attenuated by enough foods through the duodenal route. To prevent these disadvantages, we aim to modify the anastomosis in DTR, which may allow dietary intake to pass through the remnant stomach and duodenal route more easily.

Firstly, we shorten the distance between esophagojejunostomy and gastrojejunostomy to alleviate alimentary stasis, which may be induced by relative longer jejunum between two anastomosis. Secondly, gastrojejunostomy was performed on the anterior gastric wall to reduce acid reflux and make foods enter remnant stomach more easily. Retrocolic gastrojejunostomy were adopted to fix the remnant stomach better and reduce the incidence of remnant stomach volvulus. Finally, we preserve all pyloric vessels and nerves during the process of suprapyloric lymphadenectomy to preserve autonomic pyloric function and reduce the incidence of antrum-pylorus edema.

In this study, we deemed the surgical outcomes of PG with DTR in 25 patients with early AEG were good enough to replace total gastrectomy. The rate of reflux symptoms was signficantly low, and there were no patients greater than Visick score of II. The degrees and extent of remnant gastritis in most of patients were also no severer than Grade 1. The gut function restored quickly and the volume of postoperative daily intake could reach over 700ml on 6th POD, which was much more than the TG group. Postoperative gastrography after modified DTR reconstruction showed that contrast medium flowed mainly to remnant stomach which indicated larger foods could transfer through the duodenal route easily to improve postoperative nutritional status. The weight loss also showed better postoperative nutritional status in DTR group.

In summary, the short-term outcome of this modified anastomosis technique in DTR was satisfied, which could transfer larger foods through duodenal route more smoothly and improved the nutrition status and quality of life post operation. The incidence of surgical complications was relative lower. We believe our modified technique is one of feasible, safe, and useful choice for early AEG patients.

Limitations

There was only 25 cases enrolled in DTR group, for this study was only an initial attempt of novel anastomosis technique. Another limitation is relative short follow up in this study, so we could not evaluate oncological safety of this new modified surgical operation exactly. But all modifications in our surgical procedure were in order to improve the quality of life post operation, which might not affect the oncological safety. Future prospective randomized trials with larger amount cases with long term of follow-up are warranted to validate its clinical usefulness.

Declarations

Ethical Approval

The study was approved by the Local Institutional Review Board and Human Research Ethics Committee. All patients signed an informed consent prior to the commencement of the study.

Competing interests

The authors declare there are no competing interests

Author Contributions

YK conceived and supervised the study; YK, LTH, CXS, LX , CHT, GX and ZJH performed operations; LX and GX collected the data; LTH and CXS drafted the manuscript;. All authors reviewed the results and approved the manuscript.

Conflict of Interest Statement

The authors declare that they have no conflict of interest.

Funding

This work was supported by the National Natural Science Foundation of China (Grants No. 81671886).

Availability of data and materials

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

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Tables

Table 1 Clinicopathological Characteristics of early AEG Patients performed Modified DTR or TG

Table 2 Surgical Outcomes, postoperative gut function and nutritional status of early AEG Patients performed Modified DTR or TG

* Data was collected at one year post-operation.