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Shuntaro Mukai, MD, Takao Itoi, MD, Atsushi Sofuni, MD, Fumihide Itokawa, MD, Toshio Kurihara, MD,Takayoshi Tsuchiya, MD, Kentaro Ishii, MD, Shujiro Tsuji, MD, Nobuhito Ikeuchi, MD, Reina Tanaka, MD,Junko Umeda, MD, Ryosuke Tonozuka, MD, Mitsuyoshi Honjo, MD, Fuminori Moriyasu, MD

Tokyo, Japan

EUS-guided drainage of pancreatic fluid collection is aminimally invasive procedure and has become standardtherapy worldwide for pancreatic pseudocyst and pancre-atic walled-off necrosis (WON).1-3 The conventional singletransluminal gateway technique (SGT) using transmuralplacement of single or multiple plastic or metal stents issufficient for unilocular pancreatic fluid collections. Incontrast, WON contains necrotic debris,4 and effective,prompt improvement is limited when SGT is used becausethe collections are often multiseptated. Furthermore, in-fected WON requires aggressive therapy such as directendoscopic necrosectomy (DEN) for the removal ofnecrotic tissue.5 DEN has improved the success rate ofendoscopic treatment of WON, but refractory cases remainand are resistant to treatment using SGT plus DEN.Recently, Varadarajulu et al6 advocated the usefulness ofthe EUS-guided multiple transluminal gateway technique

ns: DEN, direct endoscopic necrosectomy; MTGT, multiplel gateway technique; SEMS, self-expandable metal stent;transluminal gateway technique; SGTMD, single translumi-transcystic multiple drainages; SIR, systemic inflammatory

ON, walled-off necrosis.

E: The following authors disclosed financial relationshipsthis publication: Dr Itoi is a speaker for Taewoong and ato Xlunema. Dr Itokawa is on the speakers’ board ofll other authors disclosed no financial relationshipsthis publication. The AXIOS stents and Niti-S were providedge by Xlumena Inc and Taewoong Company, respectively.

This video can be viewed directlyfrom the GIE website or by usingthe QR code and your mobile de-vice. Download a free QR codescanner by searching “QR Scanner”in your mobile device’s app store.

2014 by the American Society for Gastrointestinal Endoscopy36.00i.org/10.1016/j.gie.2013.10.004

ly 10, 2013. Accepted October 1, 2013.

liations: Department of Gastroenterology and Hepatology,cal University, Tokyo, Japan.

uests: Takao Itoi, MD, PhD, FASGE, Department oflogy and Hepatology, Tokyo Medical University 6-7-1u, Shinjuku-ku, Tokyo 160-0023, Japan.

urnal.org

(MTGT) for complicated WON. We have also performedendoscopic treatment for refractory WON by usingMTGT. In addition to MTGT, we use a novel drainage tech-nique that we term single transluminal gateway transcysticmultiple drainage (SGTMD) for complicated multilocularWON. We retrospectively assessed the feasibility and effi-cacy of SGTMD for such patients.

PATIENTS AND METHODS

PatientsBetween March 2006 and February 2013, 68 patients

were identified who had infected pancreatic pseudocysts(nZ 14) andWON (nZ 54) at the TokyoMedical UniversityHospital. WON was diagnosed by the presence of necrotictissue in the collections, based on a history of necrotizingpancreatitis and findings on EUS, CT, and magnetic reso-nance imaging, following the revised Atlanta classification.4

Infected pseudocysts and WON were diagnosed by clinicalsigns, laboratory, fever higher than 38�C, and evidenceof systemic inflammatory response (SIR) (white blood cellcount O10,000/mL or !4000/mL and C-reactive proteinO1 mg/dL). Criteria for drainage were as follows: (1) in-fected pancreatic pseudocyst and WON and (2) sterilepancreatic pseudocyst and WON in the presence of an in-crease in size of the collection and/or worsening symptoms.Of 54 cases of WON, 5 were treated by SGTMD (Fig. 1).

SGTMD proceduresOur strategy for treating pancreatic pseudocyst and

WON is described in Figure 1. Initial drainage was per-formed by using SGT with placement of 1 or more plasticstents or a self-expandable metal stent (SEMS) (Fig. 2A,Table 1). If initial drainage was ineffective, endoscopic ne-crosectomy was performed. MTGT (Fig. 2B) or SGTMD(Fig. 2C) was performed with or without endoscopic ne-crosectomy according to the morphology and location ofcavities. Our standard SGT using multiple plastic stents(Fig. 2A) or SEMS (covered WallFlex; Boston ScientificJapan Tokyo, Japan; 10- or 16-mm AXIOS; Xlumena, Moun-tain View, Calif; 16-mm Niti-S, Taewoong Company, Seoul,Korea) alone or an SEMS with a nasocystic catheter or adouble pigtail stent (Video 1, available online at www.giejournal.org) was described previously.7-9

Volume 79, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 531

Figure 1. Treatment strategies and outcomes for pancreatic pseudocyst and walled-off necrosis.

Figure 2. Schema of single and multiple transluminal gateway techniques for EUS-guided drainage. A, Single transluminal gateway technique. B, Multipletransluminal gateway technique. C, Single transluminal gateway transcystic multiple drainages.

EUS-guided pancreatic pseudocyst drainage Mukai et al

In the case of ineffective drainage by using SGT withmultiple plastic stents or an SEMS, DEN was performedthe next day. A 15- to 20-mm dilating balloon (CRE balloon;Boston Scientific Japan) was inserted alongside the stentsand inflated to advance a standard upper GI endoscopeor ultraslim endoscope through the tract into the collec-tion. When SEMSs were used, the endoscope was directlyadvanced into the cavity without dilation of the tract.Necrotic tissue was removed by using a basket catheter,biopsy forceps, and snare forceps using CO2 insufflation.The endpoint of DEN was resolution of symptoms andSIR. Necrosectomy was limited to 1 hour per procedure.

When symptoms or SIR continued despite a decrease inthe size of the largest cavity, we assessed the location of the

532 GASTROINTESTINAL ENDOSCOPY Volume 79, No. 3 : 2014

subcavities by using CT. When located adjacent to the stom-ach or the duodenum, we used MTGT (Fig. 2B). AdditionalEUS-guided punctures of these subcavities were performedas described above for the initial session. If necessary, addi-tional DEN was performed from multiple gateways.

If the subcavities with insufficient drainage remained andconnected the main cavity by using CT (Fig. 3A), we usedSGTMD (Figs. 2C and 3B and C; Video 2, available online atwww.giejournal.org). The connectionswithin themain cavityto the subcavities were identified by using an ERCP catheterand soft guidewire (0.032-inch Radifocusl Terumo Co, Ltd,Tokyo, Japan). After the subcavities were identified, 1 ormore 7F double pigtail stents and a 5F or 6F nasocystic cath-eter were placed in the subcavities, and irrigation was

www.giejournal.org

Figure 3. Single transluminal gateway transcystic multiple drainages. A, CT revealed the subcavity (asterisk), which connected with the main cavity by anarrow tract (arrow) with insufficient drainage, causing abdominal pain and a fever spike. B, The tract from the main cavity to the subcavity was sought byusing an ERCP catheter and guidewire. C, Two 7F double pigtail stents and a 6F nasocystic catheter were deployed. D, CT revealed a decrease in thesubcavity size.

TABLE 1. Outcome of initial drainage by SGT in patients who had complicated infected WON and underwent SGTMD

Patient Age, y/sexEtiologyof AP

Maximumaxis ofmain

cavity, cm

Firstdrainageby SGT

Technicalsuccess

Clinicalsuccess

Adverseeventin first

drainage

No. ofsessions offirst DEN

Adverseeventin DEN

1 29/F Drug induced 12.8 SEMS Yes No None 2 None

2 83/M Idiopathic 6.4 SEMS Yes No None 0 N/A

3 44/M Alcohol abuse 15.4 SEMS Yes No None 2 None

4 66/M Post-ERCP 10.4 Int-PS (n Z 2),Ext-NCC (n Z 1)

Yes No None 3 None

5 56/M Alcohol abuse 7.2 Int-PS (n Z 1),Ext-NCC (n Z 1)

Yes No None 0 N/A

SGT, Single transluminal gateway; WON, walled-off necrosis; SGTMD, single transluminal gateway transcystic multiple drainages; AP, acute pancreatitis; DEN,direct endoscopic necrosectomy; F, female; SEMS, self-expandable metal stent; M, male; N/A, not applicable; Int-PS, internal plastic stent; Ext-NCC, externalnasocystic catheter.

Mukai et al EUS-guided pancreatic pseudocyst drainage

performedbyusing saline solution. Patients providedwritteninformed consent before these procedures were performed.

Evaluation of therapyTechnical success was defined as successful stent place-

ment. Clinical success was defined as the disappearance ofsymptoms or inflammation regardless of collection size. All

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adverse events were described according to the AmericanSociety for Gastrointestinal Endoscopy lexicon on endos-copy adverse events.10

After confirmation of a decrease in the size of the collec-tion by CT, SEMSs were removed and exchanged for 1 ormore double pigtail stents. If plastic stents were used,they were left in place. Repeat CT was performed every

Volume 79, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 533

TABLE 2. Outcome of SGTMD in patients with complicated infected WON

Patient

No. ofmultilocular

cavities

Maximumaxis of

subcavity,cm

Seconddrainageby SGTMD

Technicalsuccess

Clinicalsuccess

Adverseevent

in seconddrainage

ContinuousInt-PS

placementFollow-upperiod, d

Recurrenceof

inflammation

1 3 7.4 Ext-NCC (n Z 3) Yes Yes None Yes 540 No

2 4 6 Int-PS (n Z 2),Ext-NCC (n Z 1)

Yes Yes None No 150 No

3 3 12.8 Ext-NCC (n Z 1) Yes Yes None No 675 No

4 2 6.9 Int-PS (n Z 1),Ext-NCC (n Z 2)

Yes Yes None Yes 395 No

5 2 7 Ext-NCC (n Z 1) Yes Yes None Yes 1245 No

SGTMD, Single transluminal gateway transcystic multiple drainages; WON, walled-off necrosis; Int-PS, internal plastic stent; Ext-NCC, external nasocystic catheter.

EUS-guided pancreatic pseudocyst drainage Mukai et al

6 months. Stents were endoscopically removed if noadverse events occurred after 2 years.

This study was approved by our institutional reviewboard (no. 2416).

RESULTS

SGTMD was performed in 5 patients (4 males) withinfected WON (Fig. 1). The mean age was 55.6 years(range 29-83 years). The etiology was alcohol abuse in 2 pa-tients, idiopathic in 1, drug-induced in 1, and post-ERCPpancreatitis in 1. The mean maximum axis of the maincavity was 10.4 cm (range 6.4-15.4 cm). Three SEMSs or 1or 2 internal plastic stents in combination with a nasocysticcatheter were placed as initial drainage by SGT. The successrate of first drainage was 100%without any adverse event. In3 of 5 patients, DEN was performed, but eventually inflam-mation did not resolve, although there was no adverse eventduring DEN. Thus, we performed SGTMD in these patients.All patients had more than 2 cavities in addition to the maincavity (mean 2.8, range 2-4) (Table 2). The mean maximumaxis of the subcavity was 8.2 cm (range 6-12.8 cm). InSGTMD, in all patients, 1 or more nasocystic catheterswere placed for the irrigation of complicated infected sub-cavities. In 2 patients, 1 or more internal plastic stentswere simultaneously placed with a nasocystic catheter.The technical success was 100% without any adverse event.Final clinical success was achieved in all 5 patients. In 3 pa-tients, the plastic stent was placed to avoid the recurrenceof inflammation because the relatively large main cavitywas left. During the follow-up period (mean 601 days, range150-1245 days), there was no recurrence of inflammation.

DISCUSSION

To date, SGT by using multiple stents or SEMSs has al-lowed complete resolution in the setting of uncomplicated

534 GASTROINTESTINAL ENDOSCOPY Volume 79, No. 3 : 2014

pancreatic pseudocysts and WON. However, in patientswith infected WON, simple drainage by using SGT isoften not effective, and the patients usually requireDEN. DEN was first reported by Seifert et al11 in 2000as a minimally invasive endoscopic treatment for WON.They explained that the clinical response rate usingdrainage alone was approximately 40% to 50%, butdrainage plus DEN improved the response rate to 80%.Nevertheless, all cases of infected WON are not alwaystreated by drainage plus DEN. In particular, in largeand multiseptated infected WON, complete cure is pre-cluded because of the presence of undrained subcav-ities.6 These cases have historically been treated withsurgical and/or percutaneous approaches. The techniqueof a hybrid approach by using endoscopic and percuta-neous approaches has recently become popular.12,13

Unfortunately, open surgical débridement carries a mor-bidity rate of 55% and mortality rate of 14%.14 Thus,a step-up approach of combined endoscopy with apercutaneous technique is recommended for compli-cated WON rather than open necrosectomy.12,15

An alternative to endoscopic and percutaneous tech-niques is to continue with endoscopic interventions forrefractory cases. Varadarajulu et al6 developed the MTGTfor symptomatic WON and found the clinical success rateto be higher than when conventional SGT was used(91.7% vs 51.2%, P Z .018). They noted that MTGT wasnot an option for the treatment of WON that was separatefrom the GI lumen, in locations such as the perisplenicspace. When subcavities or undrained areas of the maincavity are in a location far from the stomach and duo-denum, EUS-guided intervention is not possible. In ourseries, nondrained cavities were adjacent to the stomachor duodenum in only 64% (9/15) of complicated WONcases. Previously, the percutaneous approach would havebeen used. However, we hypothesized that the multilocu-lar cavity may have originally been unilocular and onlyseparated into subcavities during the process of treatment

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Mukai et al EUS-guided pancreatic pseudocyst drainage

and collapse. As a result, tiny, narrow connections arepresent between the subcavities. We used SGTMD as atechnique for connecting the subcavities, which allowedcomplicated WON cases to be treated by using only endo-scopic interventions.

Although DEN allowed subcavities to be connected, itwas often difficult to advance the endoscope (even anultraslim endoscope) across the connected lumen. How-ever, using MTGT and SGTMD tailored to the type ofpatient allowed all patients to be effectively treated. Thereason for this is that infected subcavities might containonly small amounts of necrotic tissue. However, if aggres-sive DEN in the subcavities is needed, SGTMD may not beeffective. A percutaneous approach might be a betterapproach in these patients.

In this study, although there were no SGTMD-relatedadverse events, SGTMD involves additional drainage ofthe subcavities under fluoroscopic guidance, which carriesrisks of bleeding and perforation. In particular, if DEN isneeded for the resolution of inflammation in the subcav-ities, care should be taken because, in this study, the causeof death in 1 case was an internal hemorrhage in the cavitycaused by rupture of an aneurysm after DEN. Thus, evalu-ation of the subcavity by using CT and careful probing byusing a soft guidewire are mandatory.

The limitation of this study is that it reports experiencefrom a single center without a control group and is retro-spective in nature.

In conclusion, SGTMD appears to be useful in patientswith refractory WON in whom MTGT is not suitablebecause the subcavities are not directly accessible fromthe stomach.

ACKNOWLEDGMENTS

The authors are indebted to the medical editors andAssociate Professor Edward Barroga of the Departmentof International Medical Communications of Tokyo MedicalUniversity for the editorial review of the English inthis paper. They are grateful to Dr Todd. H. Baron ofthe Mayo Clinic, Rochester, Minnesota, for his valuable ed-iting suggestions. This work was supported in part by theResearch Committee of Intractable Pancreatic Diseases

www.giejournal.org

(Principal investigator: Tooru Shimosegawa) provided bythe Ministry of Health, Labour, and Welfare of Japan.

REFERENCES

1. Binmoeller KF, Seifert H, Walter A, et al. Transpapillary and transmuraldrainage of pancreatic pseudocysts. Gastrointest Endosc 1995;42:219-24.

2. Varadarajulu S, Christein JD, Tamhane A, et al. Prospective randomizedtrial comparing EUS and EGD for transmural drainage of pancreaticpseudocysts (with videos). Gastrointest Endosc 2008;68:1102-11.

3. Baron TH, Harewood GC, Morgan DE, et al. Outcome differences afterendoscopic drainage of pancreatic necrosis, acute pancreatic pseudo-cysts, and chronic pancreatic pseudocysts. Gastrointest Endosc2002;56:7-17.

4. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancrea-titis–2012: revision of the Atlanta classification and definitions by inter-national consensus. Gut 2013;62:102-11.

5. Seewald S, Groth S, Omar S, et al. Aggressive endoscopic therapy forpancreatic necrosis and pancreatic abscess: a new safe and effectivetreatment algorithm (videos). Gastrointest Endosc 2005;62:92-100.

6. Varadarajulu S, Phadnis M, Christein J, et al. Multiple transluminalgateway technique for EUS-guided drainage of symptomatic wall-offpancreatic necrosis. Gastrointest Endosc 2011;74:74-80.

7. Itoi T, Itokawa F, Tsuchiya T, et al. EUS-guided pancreatic pseudocystdrainage: simultaneous placement of stents and nasocystic catheterusing double-guidewire technique. Dig Endosc 2009;21(Suppl 1):S53-6.

8. Itoi T, Reddy DN, Yasuda I. New fully-covered self-expandable metalstent for EUS-guided intervention in infectious walled-off pancreaticnecrosis (with video). J Hepatobiliary Pancreat Sci 2013;20:403-6.

9. Itoi T, Binmoeller KF, Shah J, et al. Clinical evaluation of a novel lumen-apposing metal stent for endosonography-guided pancreatic pseudo-cyst and gallbladder drainage (with video). Gastrointest Endosc2012;75:870-6.

10. Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopicadverse events: report of an ASGE workshop. Gastrointest Endosc2010;71:446-54.

11. Seifert H, Werhmann T, Schmit T, et al. Retroperitoneal endoscopicdebridement for infected pancreatic necrosis. Lancet 2000;356:653-5.

12. van Santvoort HC, Besselink MG, Bakker OJ, et al. A step-up approachor open necrosectomy for necrotizing pancreatitis. N Engl J Med2010;362:1491-502.

13. Baron TH, Kozarek RA. Endotherapy for organized pancreatic necrosis:perspectives after 20 years. Clin Gastroenterol Hepatol 2012;10:1202-7.

14. Harrison S, Kakade M, Varadarajulu S, et al. Characteristics and out-comes of patients undergoing debridement of pancreatic necrosis.J Gastrointest Surg 2010;14:245-51.

15. Bakker OJ, van Santvoort HC, van Brunschot S, et al. Endoscopic trans-gastric vs surgical necrosectomy for infected necrotizing pancreatitisa randomized trial. JAMA 2012;10:1053-61.

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