Serie de Casos Prospectiva de Gastroenteroanastomosis Guiada Por Ecoendoscopia Para la obstrucción al Vaciado gástrico en Neoplasias Avanzadas Mediante la técnica Del Drenaje Nasobiliar
Conditions: Gastric Outlet Obstruction, Gastric Cancer, Pancreatic Cancer
Sponsor: Hospital del Rio Hortega

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Nasobiliary Drain Assisted EUS-guided 
Gastroenterostomies in Unresectable Malignant 
Gastric Outlet Obstruction 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1. Background  
Importance of gastric outlet obstruction in malignant disease 
Gastric outlet obstruction (GOO) counts among the most severe adverse events 
presenting in malignant tumors located in the gastrodoudenal junction. It usually 
presents with abdominal pain, nausea, vomiting and weight loss. Gastric cancer is its 
most frequent cause; it presents in 20-30% of stage IV gastric neoplasias (1). 
Restarting oral intake is a foremost priority in these patients. Due to their usually poor 
performance score and short life expectancy, the ideal procedure should be minimally 
invasive, present a low adverse event rate and have a low risk of recurrence.  
 
Management options and adverse events 
Traditional 
management 
consists 
in 
a 
gastroduodenal 
derivative 
surgery. 
Unfortunately, long hospital admissions, and relevant short term morbitidy were 
serious issues regarding this procedure, although it presents the lowest recurrence 
rates among proposed procedures (2).  
The development of endoscopic stents have allowed endoscopic stent placement to 
be considered the currently first line treatment in these patients, reaching a clinical 
success in 90% of patients in selected centers (3). Nevertheless, endoscopic stent 
placements presents some relevant drawbacks. First of all, the clinical success rates 
in less selected centers is probably lower. Secondly, adverse events during follow-up 
are relatively frequent, especially recurrent GOO due to tumoral ingrowth or, less 
frequently, to stent migration. Recurrent GOO might present in up to 30% of patients 
(3). The high recurrence rate is specially relevant, as some recent studies report 
median survivals in advanced gastric cancer of 13 months (4) Thus, we should not 
only aim at restoring bowel transit, but to keep it functioning until the patient’s death.  
 

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Novel endoscopic alternatives  
The first endoscopic approach to achieve a functional gastrojejunostomy was through 
natural orifice transluminal endoscopic surgery (NOTES), where the peritoneal cavity 
is reached throught the stomach. Once in the peritoneal cavity, a jejunal loop is 
clasped with a grasper an retrieved into the gastric cavity, suturing both hollow 
estructures (5). Although prospective prospective, proof of concept animal studies 
have shown its feasibility (6,7) and successful procedures in humans have been 
performed (8), it is a very demanding procedure even in highly skilled endoscopists. 
Endoscopic ultrasound guided gastroenterostomy (EUS-GE) is currently the preferred 
method to achieve an endoscopic gastric bypass in malignant GOO. An 
echoendoscope is used to identify the target bowel loop from the gastric cavity. To 
ease the identification of the target, different fluid solutions are injected into the bowel 
to distend it. Various methods have been proposed to reach this distention. In the 
endoscopy units taking part in the present study, the nasobiliary drain assisted EUS-
GE is used, where a nasobiliary drain is advanced through the malignant stricture into 
the distal duodenum or the jejunum, and, once in place, liquids are pumped into the 
target bowel loop. Once the target bowel loop is identified, a lumen apposing metal 
stent (LAMS) is placed across both organs. After demonstrating its feasibility in animal 
studies (9,10), , it has been extensively used in patients (11).  
 
Available results  of EUS-GE 
Self-expandable metal stents SEMS) achieve technical success in 97% of patients, 
with 87% achieving technical success, while a relevant proportion of patients present 
recurrent GOO, which presents approximately 3 months after deployment (12). A 
recent multicenter retrospective study comparing SEMS and EUS-GE observed 
similar proportions of technical and clinical success rates, while EUS-GE presented 

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lower rates of recurrent GOO and reintervention (13). Due to the low number of 
centers performing this procedure, the nasobiliary drain assisted EUS-GE has not yet 
been standardized, with significant differences among operators.  
 
 
2. Objectives 
Primary aim 
• To describe different variants in the nasobiliary drain assissted EUS-GE 
technique, offering a detailed step by step description of the procedure 
performance by different endoscopists 
Secondary aims  
• To describe the proportions of technical and clinical success.  
• To describe the adverse encountered, their severity according to ASGE 
standards and their management.  
• To describe the time elapsed between the procedure  and the initial oral intake. 
• To describe the evolution of the oral intake during the first month after the 
procedure 
• To assess the impact of the operators experience on procedure times, adverse 
events and technical issues.  
• To assess the impact of the procedure on the quality of life of the participating 
patients. 
 
4. Design 
Prospective, multicenter case-series 
 
5. Methods 

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Study population 
 
 
All consecutive patients over 18 years of age submitted to any of the 
participanting center's endoscopy units to receive a nasobiliary drain assisted EUS-GE 
for unresectable malignant GOO are eligible to participate in this study. 
 
Inclusion and exclusion criteria 
Inclusion criteria:  
• Unresectable malignant gastric outlet obstruction 
• Scheduled placement of a nasobiliary drain assisted EUS-GE 
• Age >18 years.  
Exclusion criteria:  
• Previous gastroduodenal surgery 
• Previous endoscopic or surgical treatment for gastric outlet obstruction 
• Simultaneous malignant biliary obstruction requiring endoscopic treatment 
• Unable to understand the questionnaires 
• Distal bowel obstruction 
• Ascites grade 2 or superior 
• Uncorrectable coagulation disorders (INR>1,5) or severe thrombocytopenia 
(<50000 platelets/mm3). 
 
Definitions of the outcomes employed to assess primary and secondary variables 
1. Technical success: Dichotomous variable. Defined as a correct placement of 
the LAMS, with one flange inside the gastric cavity and the other one in the 
small bowel. It should be confirmed endoscopically or fluoroscopically  

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2. Clinical success: Dichotomous variable. Defined as a GOOSS ≥2. It will be 
assessed at days +7 and +30.  
3.  
4. Recurrent GOO: Dichotomous variable. In patients achieving clinical success in 
day +7, recurrent GOO is defined as the development of nausea and vomiting 
and/or a GOOSS<2. 
5. Persistent GOO: Dichotomous variable. Continuing nausea, vomiting, and 
inability to tolerate PO intake up to or occurring within 2 weeks after the 
procedure.   
6. Major complications: life-threatening or severe complications requiring 
treatment and/or hospitalization (The adverse event severity will be graded 
according to the ASGE lexicon). 
a. Early major complications: complications occurring within 7 days after 
the intervention. 
b. Late major complications: complications occurring 7 days or later after 
the intervention.  
7. Minor complications: not life-threatening or moderate or severe complications 
that do not require hospital admission.  
8. Reintervention: Dichotomous variable. Any procedure (endoscopic, radiologic 
or surgical aiming at treating a recurrent GOO, persistent GOO or any 
procedure related adverse evento.  
9. Gastric outlet obstruction score system: Presents the following categories 0 (nil 
per os), 1(liquids), 2(soft diet), 3 (full diet or low residue diet). 
10. Target bowel loop diameter (mm): Diameter measured with the EUS of the 
dilated bowel loop. It should be measured just before placing the stent.  
 

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11. Total volume infused (ml) : Volume of saline, methilene blue solution or 
radiopaque contrast solution instiled to dilate the target bowel loop (each one 
will be individually measured).   
12. Balloon dilation: Dichotomous variable. At discretion of the endoscopist, after 
deploying the stent, it might be dilated with a controlled radial expansion 
balloon dilator.  
 
Intervention 
At inclusion 
Informed consent will be obtained. A clinical interview and a physical examination will 
be performed. The European Organization for Research and Treatment of Cancer 
QoL Questionnaire Core 30 (EORTC-QLQ-C30), which includes 30 items covering a 
global health status scale, five functional scales and ten symptom scales will be 
assessed in a telephone interview.  
 
Endoscopic procedure 
All procedures will be performed under sedation. An assistant endoscopist or research 
nurse will retrieve all data regarding the procedure. Firstly, un upper digestive 
endoscopy is performed with a conventional gastroscope. A guidewire is passed 
through the malignant lesion causing the gastric outlet obstruction. Once the guidewire 
is located in the distal duodenum/proximal jejunum, a nasobiliary drain (Nasal Biliary 
Drainage Sets, Cook medical, Indiana) is advanced over the guidewire until its distal 
end is placed in the distal duodenum/jejunum. At this point the gastroscope is 
substituted by a therapeutic echoendoscope. With the echoendoscope in place, the 
target bowel loop is filled with saline combined with methilene blue and radiopaque 
contrast. The echoendoscope is used to identify the target bowel loop. AFter 

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identifying the target, a lumen apposing metal stent (Axios, Boston Scientific, 
Massachusetts) is deployed across the gastric and bowel using its electrocautery 
enhanced deployment device. 
 
Post procedure 
Oral liquid intake can be restarted 4h after the procedure in patients presenting no 
signs or symptoms suggesting any adverse event. Pacients with an adequate 
tolerance might be discharged.  
 
Follow-up 
 
Clinical telephone interviews by an experienced research nurse will be held via 
telephone calls 1 day, 7 days and 30 days after the procedure. Oral intake and 
adverse events will be assessed every visit. Thirty days after the procedure a second 
evaluation of the EORTC-QLQ-C30 will be performed. 
 
 
Sample size 
Although EUS-GE is a rather infrequent procedure, we aim at including at least 5-10 
procedures/endoscopist, in order to present each operator’s modus operandi. Thus, 
recruitment will be active until a minimum of 5 procedures/endoscopist is reached or 
until a total sample size of 50 patients is reached, with at least 4 endoscopists 
including >5 procedures). To assess the secondary endpoint of the quality of life, 
previously published papers assessing QoL in patients with unresectable malignant 
GOO using the EORTC-QLQ-C30 reported mean global health status scores of 36.6 
(SD: 20.1) and 45 (SD: 20.3) before treatmen. To detect at least a 14-points change 

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with a 5% alfa risk and an 80% power, 33 subjects were estimated to be needed. 
Assuming a 20% of losses, 40 patients were required. 
 
Adverse events monitoring 
 
Adverse events (AE) are defined as any event preventing from completing the 
procedure, causing or lengthening a hospital admission or conditioning further 
interventions or unscheduled hospital or out-patient clinic visits. According to the time 
of diagnosis, they are classified as intraprocedure (diagnosed in the endoscopy unit 
during or immediately after the procedure), postprocedure (diagnosed in the 7 days 
following the procedure) or delayed (diagnosed beyond the first 7 days after the 
procedure). Causal relationship will be categorized into definitive (clearly related), 
probable (probably related), possible (might be related) or unlikely (there are other 
more 
likely 
causes). 
Severity 
will 
be 
assessed acording 
to 
the ASGE 
recommendations  
 
 
Severity 
 
Consequence 
Mild 
Moderate 
Severe 
Fatal 
Stop (or not even starting) a procedure 
x 
 
 
 
Post-procedure out-patient visit 
x 
 
 
 
Unplanned respiratory support during 
the procedure  
 
x 
 
 
Unplanned hospital admission for 3 
nights or less  
x 
 
 
 
Unplanned hospital admission for 4-10 
nights 
 
x 
 
 
Unplanned hospital admission for 11 or 
more nights 
 
 
x 
 
Intensive Care Unit admission for 1 night 
 
x 
 
 
Intensive Care Unit admission for 2 or 
more nights 
 
 
x 
 
Blood transfusion 
 
x 
 
 
Endoscopic procedure 
 
x 
 
 
Radiologic procedure 
 
x 
 
 

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Severity 
 
Consequence 
Mild 
Moderate 
Severe 
Fatal 
Surgical procedure 
 
 
x 
 
Permanent disability  
 
 
x 
 
Death 
 
 
 
x
 
 
 
  
The principal investigator at each center is responsible of communicating all 
adverse events (all severe or fatal adverse events, regardless of the causal 
relationship and at least possible for moderate or mild events) to the principal 
investigator.  
 
 
Data retrieval 
Data were collected and managed using the SEED Research Electronic Data 
Capture tool (REDCap), a secure, web-based application created to support data 
capture for research studies providing semiautomatic data quality control (9). Patient-
related and procedural data were included by the local investigators at stent 
deployment. Patients will be identified with a unique code. The database is password 
protected. Only the investigators have access to the database.  
Local follow-up was performed according to each center’s protocols. 
Regardless of the local follow-up, all patients underwent a centralized follow-up via 
telephone calls by an experienced research nurse, at inclusion, 1, 7 and 30 days after 
stent deployment. The EORTC-QLQ-C30 questionnaires were administered at the 
inclusion and at the 30 days telephone visits. Only in case the patient was admitted at 
the principal investigator center and preferred a personal interview, were the 
questionnaires administered in a face-to-face interview. Oral intake was evaluated 1, 7 
and 30 days after the procedure.  

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6. Statistical analysis 
Categorical variables were reported as percentages. Normally distributed 
continuous variables were reported as the mean with the standard deviation values. 
Non-normally distributed continuous variables were reported as the median and 
interquartile range. The EORTC QLQ-C30 descriptive analysis was performed with a 
specifically programmed Stata command (10). Variables regarding the procedure step 
by step analysis will only undergo a descriptive analysisDifferences between the 
different outcomes of the EORTC-QLQ-C30 will be assessed using linear mixed 
models with fixed effects for baseline values, and interaction with oncological 
treatment. The statistical analysis will be performed using the Stata package 
(StataCorp. 2013, College Station, Texas). 
 
7. Ethics  
 
Benefit risk assessment 
Patients taking part in the study will not gain any personal benefit. We consider 
taking part in the study does not increase the risks associated to the procedure. The 
study is purely observational; data retrieval will not be performed by the operator. 
Thus, we consider the procedure in participating patients should defer from those 
EUS-GE performed in other patients . Follow-up will be performed via telephone calls, 
so the patient will not have to travel to take part. The procedure associated risk are 
well documented in the published literature, with an adverse event risk of 5% The 
main risk is a hollow viscus perforation, followed by GI bleeding, and sedation 
associated procedures (aspiration pneumonia).  
 

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The study product, AXIOS ™ (Boston Scientific) 20x10mm and 15x10mm 
lumen apposing metal stents, was originally designed to create internal drains for 
pancreatic fluid collections. Currently they are used in various other indications. Their 
deployment creating EUS-GE in patients presenting malignant unresectable GOO is 
increasing, both in Europe and in the United States, with various published case 
series.  
 
8. Timeframe 
 
First year 
Recruitment of patients. Follow-up 
Second year 
Recruitment of patients. Follow-up (Recruitment will be active until the predetermined 
sample size of a minimum of 5 procedures/endoscopist is reached or until a total 
sample size of 50 patients is reached, with at least 4 endoscopists including >5 
procedures).  
Third year 
Data análisis. Presentation in scientific meetings. Manuscript redaction.  
  

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9. Bibliography  
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lumen-apposing stent: first clinical experience (with videos). Gastrointest Endosc. 
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[Epub ahead of print]