Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasms

Rare Diseases

Necrosis

Pancreatitis

Pancreatitis, Acute Necrotizing

Pancreatic Pseudocyst

Pancreatic Diseases

Gastrointestinal Diseases

Cysts

Pancreatic Cyst

Acute Graft Versus Host Disease

Endoscopic necrosectomy will be conducted in the same session of EUS-guided drainage (or at least within 72 hours of randomization) and be repeated until clinical success.

Step-up treatment will be conducted if a patient's condition does not improve after EUS-guided drainage. The step-up approach includes increasing the number of stents, adding another EUS-guided drainage, and performing percutaneous drainage after 72-96 hours of the initial drainage. Endoscopic necrosectomy is considered when clinical improvement is not observed even after two times of step-up treatment.

Endoscopic ultrasonography (EUS)-guided drainage will be conducted within 72 hours from randomization. A convex-type echoendoscope is advanced to the stomach or duodenum, and the walled-off necrosis (WON) is visualized and punctured under EUS guidance. A lumen-apposing metal stent (LAMS), such as Hot AXIOS system (Boston Scientific Japan, Tokyo, Japan), is recommended for the initial EUS-guided drainage.

For the immediate necrosectomy group, endoscopic necrosectomy (EN) will be performed in the same session of EUS-guided drainage using a gastroscope. The endoscope is inserted into the WON cavity through the LAMS, and necrotic tissue is removed using biopsy forceps, snare, or basket catheter. The EN procedures will be repeated until clinical improvement.

Immediate necrosectomy

Endoscopic ultrasonography (EUS)-guided drainage will be conducted within 72 hours from randomization. A convex-type echoendoscope is advanced to the stomach or duodenum, and the walled-off necrosis (WON) is visualized and punctured under EUS guidance. A lumen-apposing metal stent (LAMS), such as Hot AXIOS system (Boston Scientific Japan, Tokyo, Japan), is recommended for the initial EUS-guided drainage.

For the step-up approach group, an additional interventional procedure will be withheld for 72-96 hours after initial EUS-guided drainage. In cases without clinical improvement after 72-96 hours, additional drainage will be permitted, which includes increasing the number of stents, additional EUS-guided drainage, and performing percutaneous drainage (step-up treatment). Insufficient improvement even after two times of step-up treatment allows subsequent endoscopic necrosectomy (EN).

Step-up approach

Yousuke Nakai

Tomotaka Saito

Hiroyuki Isayama

Toshio Fujisawa

Sho Takahashi

Tadahisa Inoue

Hiroshi Ohyama

Koji Takahashi

Keisuke Iwata

Mitsuru Okuno

Akinori Maruta

Kensaku Yoshida

Takuji Iwashita

Shinya Uemura

Hideyuki Shiomi

Shogo Ota

Ryota Nakano

Hideki Kamada

Daisuke Namima

Shinichi Hashimoto

Makoto Hinokuchi

Toshiyasu Shiratori

So Nakaji

Tsuyoshi Mukai

Saburo Matsubara

Keito Nakagawa

Shinpei Doi

Nobuhiro Katsukura

Atsuhiro Masuda

Masahiro Tsujimae

Kenji Chinen

Takeshi Ogura

Atsushi Okuda

Masaki Kuwatani

Hirofumi Kogure

Kei Saito

Ichiro Yasuda

Nobuhiko Hayashi

Mamoru Takenaka

Shunsuke Omoto

Walled-off necrosis (WON) is a pancreatic fluid collection, which contains necrotic tissue after four weeks of the onset of acute pancreatitis. Interventions are required to manage patients with infected WON, for which endoscopic ultrasonography (EUS)-guided drainage has become a first-line treatment modality. For patients who are refractory to EUS-guided drainage, the step-up treatment including endoscopic necrosectomy (EN) and/or additional drainage is considered to subside the infection. Recent evidence suggests that EN immediately after EUS-guided drainage may shorten treatment duration without increasing adverse events. In this randomized trial, the investigators will compare treatment duration between EN immediately after EUS-guided drainage versus the step-up approach in patients with symptomatic WON.

Pancreatic fluid collection is a late complication of severe acute pancreatitis. According to the revised Atlanta classification, walled-off necrosis (WON) is defined as an encapsulated collection of necrotic tissue that is observed after four weeks of the onset of acute pancreatitis. Infected WON is associated with high morbidity and mortality; therefore, an appropriate treatment, including antibiotics and drainage, is mandatory. With the development of endoscopic equipment, endoscopic ultrasonography (EUS)-guided drainage has become a first-line treatment modality for infected WON. For patients who are refractory to EUS-guided drainage, endoscopic necrosectomy (EN) is a treatment option to facilitate direct removal of infected necrotic tissue within the WON. However, due to potentially lethal adverse events of EN, such as bleeding, perforation, and peritonitis, EN is usually withheld for several days after EUS-guided drainage. This strategy is known as "the step-up approach." Recently, with the accumulated evidence supporting the safety of EN, especially with the use of a dedicated lumen-apposing metal stent, it has been reported that EN immediately after EUS-guided drainage can shorten the treatment duration without increasing adverse events. Given these lines of evidence, the investigators hypothesized that immediate EN following EUS-guided drainage of WON might shorten time to clinical success compared to the step-up approach. To examine this hypothesis, the investigators planned to conduct a multicenter randomized controlled trial comparing treatment duration between EN immediately after EUS-guided drainage versus the step-up approach in patients with symptomatic WON.

Immediate Necrosectomy vs. Step-up Approach for Walled-off Necrosis

Immediate Necrosectomy vs. Step-up Approach After EUS-guided Drainage of Walled-off Necrosis: a Multicenter Randomized Controlled Trial (WONDER-01)

Clinical success is defined as 1) a decrease in the WON size to 3 cm or less and 2) an improvement of more than two out of the three following inflammatory markers; body temperature, white blood cell count, and C-reactive protein.

All procedure-related adverse events including bleeding, perforation, peritonitis, etc.

Successful placement of EUS-guided drainage including a lumen-apposing metal stent and plastic stents

Inflammatory-induced obstruction of bile duct and gastrointestinal tract

Total number of interventions and total procedure time

Indwelling period of stents and drainage tube

Success rate of surgeries associated with WON and total operation time

Total hospitalization days and total ICU stay

Total cost of interventions and total cost of hospitalization

Time from clinical success to recurrence of WON

Incidence of new-onset pancreatic pseudocyst

Total treatment period for new-onset pancreatic pseudocyst

New-onset diabetes mellitus, pancreatic cancer, and clinical symptoms associated with pancreatic exocrine insufficiency, such as steatorrhea , constipation, diarrhea, maldigestion, flatulence, and tenesmus

The start of medications for pancreatic exocrine insufficiency and the date

The presence of sarcopenia and the date of diagnosis

Change in the morphology and the volume of pancreas

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Immediate Necrosectomy vs. Step-up Approach for Walled-off Necrosis	NCT05451901	Pancreatic Flui... Walled-off Necr... Pancreatitis, A... Pancreatic Pseu...	Immediate necro... Step-up approac...	18 Years -	Tokyo University
Immediate Necrosectomy vs. Step-up Approach for Walled-off Necrosis	NCT05451901	Pancreatic Flui... Walled-off Necr... Pancreatitis, A... Pancreatic Pseu...	Immediate necro... Step-up approac...	18 Years -	Tokyo University

Spots Global Cancer Trial Database for endoscopic necrosectomy