Severe Complications After Gastrectomy for Esophagogastric Junction and Gastric Cancer: Perioperative Results and Long Term Survival
Conditions: Gastric Cancer, Esophagogastric Junction Disorder
Sponsor: Hospital Dr Sotero del Rio

Study protocol. 
 
 
Official Title of the study: 
 
Severe complications after gastrectomy for esophagogastric junction and gastric cancer. 
 
Document date: April/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 

Introduction 
 
 
Gastric cancer (GC) is the fifth most common cancer[1], with more than 900,000 
new cases every year, and the third leading cause of cancer-related death worldwide[2].  
 
 
Surgery and adjuvant treatment are the main treatment modalities for GC. 
Postoperative morbidity rates after gastrectomy vary across different studies, but total 
morbidity is more than 20–30% in most studies[3–8]. In a previous study by our group, 
morbidity was present in 31% of 1066 gastrectomies [9]. 
 
 
Data on postoperative morbidity predictors are heterogeneous. Patient (age, 
comorbidity, body mass index, serum albumin), tumor (local invasion and location), and 
surgery (open approach, total gastrectomy, lymph node dissection, and multi-organ 
resection) variables are described as potential factors for higher morbidity[3–5,8].  
 
 
In our previous study, we did not have data on complication severity because this 
type of score did not exist at the beginning of that study[9]. In the past decade, 
complication severity has gained great importance, and use of the Clavien-Dindo 
classification has been widely adopted[10]. However, only a few studies have evaluated 
postoperative morbidity predictors according to complication severity for gastrectomy[6,7]. 
 
 
The aim of this study to identify predictors of severe postoperative morbidity after 
gastrectomy for gastric cancer (GC) and esophagogastric junction (EGJ) cancer and to 
evaluate long-term survival according to complications. 
 
 

Material and methods 
 
 
This is a retrospective cohort study. We collect patients' demographics, tumor and 
surgery characteristics, and postoperative morbidity. All consecutive patients treated with a 
gastrectomy for GC or EGJ cancer are included. Only patients with stomach or EGJ 
adenocarcinoma are selected, and patients with other histology are excluded. 
 
Preoperative assessment	  
 
The preoperative assessment is an upper gastrointestinal endoscopy, biopsy, 
complete blood count, liver function tests, electrocardiogram, and nutritional evaluation. 
Preoperative imaging is a thorax-abdomen-pelvis computed tomography (CT) scan. 
 
Operative procedure 
 
Epidural analgesia is routinely employed in open surgery. Depending on the tumor’s 
location, a total or subtotal gastrectomy is indicated. Surgery includes omentectomy with 
bursectomy and D2 lymph node dissection, according to the Japanese classifications in 
patients with curative gastrectomy[11]. Multi-organ resection, including spleen, pancreas, 
colon, and liver, is performed in cases of direct tumor invasion. Partial distal 
esophagectomy with a transhiatal approach and mediastinal anastomosis is employed for 
Siewert types II and III cancers, with frozen section intraoperative biopsy to confirm an R0 
resection. Partial distal esophagectomy is considered a multi-organ resection when more 
than 2 cm of the esophagus was resected. Routine cholecystectomy is performed in curative 
cases and was not considered a multi-organ resection. A reconstruction, using Roux-en-Y, 
is performed after a total gastrectomy; Roux-en-Y or Billroth II is used for subtotal 
gastrectomy. Esophagojejunal anastomosis is performed with a circular stapler and a 
second layer of running monofilament suture. One or two prophylactic drains are used 
routinely[9]. A laparoscopic approach is employed in patients with clinical early GC who 
are not candidates for endoscopic resection and patients with advanced GC without clinical 
invasion of adjacent structures and with lymph node metastases only in the perigastric 
area[12]. 
 

Postoperative management 
 
Patients start early respiratory and physical therapy the day following surgery. An 
oral contrast study is performed on postoperative day 5–7 for total gastrectomy; after this 
study, the patient starts an oral diet and prophylactic drains are removed. 
 
 
Esophagogastric junction (EGJ) cancer is classified according to Siewert 
classification[13]. In this study, only EGJ cancer Siewert types II and III are included. 
Patients are staged using TNM Classification of Malignant Tumors, seventh edition[14].	  
 
Complication assessment 
 
Severe 30-day or in-hospital morbidity is defined as a Clavien-Dindo score ≥ 3[10]. 
The complication data is collected by each attending surgeon and together at a monthly 
conference. Complications detected upon readmission are also included in this study. 
 
 
The complications are grouped into three categories: intraabdominal, wound–
abdominal wall, and medical complication. We consider an esophagojejunostomy leak as 
the appearance of contrast outside the anastomosis, using an oral contrast study or CT scan, 
or by direct evaluation at reoperation. We consider a duodenal stump leak as the discharge 
of bile-containing liquid in drains or by direct evaluation at reoperation. A pancreatic fistula 
is considered as a drain output of any volume on or after postoperative day 3 with an 
amylase greater than three times the serum level. 
 
Follow-up 
 
Standard follow up is at three-month intervals for two years, then at six-month 
intervals for three years, and yearly thereafter. Follow-up consists of physical examination, 
a complete blood count, liver-function testing, chest x-ray, abdominal ultrasound and CT-
scanning, as clinically indicated. Patients are planned to have a minimum of 5 year follow-
up. 
 
 
Outcomes: 
 
The primary outcome of the study is severe 30-day or in-hospital morbidity. 

 
The secondary outcome is long-term 5 year survival.  
 
Sample size 
 
Using previously published data and given a 0.05 alpha level, a percentage of 
unexposed outcome of 10.8%, and OR 4.28, a sample size of 116 patients would yield at 
least 80% statistical power. 
 
Statistical analysis 
Continuous variables are described by means and standard deviations or medians 
and interquartile range. Categorical variables are described with frequencies and 
percentage. 
 
The following factors are analyzed: age, sex, comorbidity, American Society of 
Anesthesiologists (ASA) physical status, tobacco and alcohol consumption, body mass 
index (BMI), hematocrit, serum albumin level, tumor location, the use of preoperative 
chemotherapy, laparoscopic or open surgery, total or subtotal gastrectomy, duodenal stump 
closure, multi-organ resection, lymphadenectomy, reconstruction method, T status, lymph 
node metastasis, and resection margin. The T stage was grouped by T1–T2 and T3–T4 for 
analysis. Univariate and multivariate analyses are performed to identify predictors of severe 
postoperative morbidity; and predictors of long-term survival. All variables associated with 
severe morbidity with p <.05 in the univariate analysis are subsequently entered into a Cox 
multivariate regression model with backward elimination. Significance is set at two-sided p 
<.05. All analyses are performed using the statistical SPSS IBM Statistics software 
program, version 22. 
 
 
The local ethics committee approved this study. Informed consent of patients is 
waived because of the retrospective nature of the study. The study was designed in line 
with the PROCESS criteria[15]. 
 
 
 
 

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