J Gastroenterol DOI 10.1007/s00535-014-0957-8
ORIGINAL ARTICLE—LIVER, PANCREAS, AND BILIARY TRACT
Expanding endoscopic interventions for pancreatic pseudocyst and walled-off necrosis Shuntaro Mukai • Takao Itoi • Atsushi Sofuni • Fumihide Itokawa • Toshio Kurihara • Takayoshi Tsuchiya • Kentaro Ishii • Shujiro Tsuji • Nobuhito Ikeuchi • Reina Tanaka • Junko Umeda • Ryosuke Tonozuka • Mitsuyoshi Honjo • Takuji Gotoda • Fuminori Moriyasu
Received: 4 February 2014 / Accepted: 24 March 2014 Ó Springer Japan 2014
Abstract Background Recently, several endoscopists have described the usefulness of the endoscopic ultrasonography (EUS)-guided, single transluminal gateway technique (SGT) using transmural placement of single or multiple plastic stents or metal stents for a pancreatic pseudocyst (PC) and walled-off necrosis (WON). Moreover, the uses of the multiple transluminal gateway technique (MTGT) and single transluminal gateway transcystic multiple drainages (SGTMD) for complicated pancreatic walled-off necrosis have recently been reported. The aim of this study is to evaluate retrospectively the feasibility and efficacy of endotherapy for the treatment of complicated PC and WON cases. Methods Eighty-nine patients with a PC (n = 14) and WON (n = 75) were treated under EUS guidance. Results In a total of 89 cases using SGT in combination with MTGT or SGTMD, the present study showed a technical success rate of 100 %, a final clinical success rate of 97.8 %, an adverse event during procedure rate of 0 %, an early adverse event rate of 12.4 %, and a mortality rate of 2.2 %. Conclusions Even complicated WON cases can be treated using combination endotherapies, although a surgical approach as well as a percutaneous approach should be considered in the cases refractory to endoscopic therapies.
S. Mukai (&) T. Itoi A. Sofuni F. Itokawa T. Kurihara T. Tsuchiya K. Ishii S. Tsuji N. Ikeuchi R. Tanaka J. Umeda R. Tonozuka M. Honjo T. Gotoda F. Moriyasu Department of Gastroenterology and Hepatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan e-mail:
[email protected]
Keywords Endoscopic ultrasonography Pancreatic pseudocyst drainage Walled-off necrosis Abbreviations EUS Endoscopic ultrasonography SEMS Self-expandable metal stent PCD Pancreatic pseudocyst drainage DEN Direct endoscopic necrosectomy SGT Single transluminal gateway technique MTGT Multiple transluminal gateway technique SGTMD Single transluminal gateway transcystic multiple drainages ERP Endoscopic retrograde pancreatography PC Pancreatic pseudocyst WON Walled-off necrosis AE Adverse event
Introduction The revised Atlanta Classification facilitates understanding of the concept of local complications followed by acute pancreatitis: these are classified into four categories, namely, acute peripancreatic fluid collection, acute necrotic collection (sterile or infected), pancreatic pseudocyst (PC) and walled-off necrosis (WON) (sterile or infected) [1]. Of these categories, a symptomatic or infected PC and WON require various interventions, such as endotherapy, interventional radiology and surgery with or without necrosectomy. Endotherapy for PC and WON is divided into 2 types, direct endoscopic drainage using a duodenoscope and endoscopic ultrasonography (EUS)-guided drainage. Based on the outcome of numerous studies, Vosoghi et al.
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[2] claimed that the endoscopic experience, with the aid of EUS, has the lowest complication rate of all drainage procedures. Among endoscopic procedures, EUS-guided drainage is associated with the lowest recurrence rates, with comparable success and mortality rates relative to other drainage procedures. Thus, recently, EUS-guided drainage has been considered a minimally invasive therapy and has become a standard therapy for PC and WON worldwide [3–8]. Apart from the therapy of PCs, which are simply treated by only the placement of one or more plastic stents, the treatment of WON, particularly infected WON, is always challenging [9] because it is necessary not only to perform evacuation of the fluid, but also carry out the intentional removal of necrosis [1], so-called necrosectomy [10]. To date, WON treatment has traditionally been performed first using the single transluminal gateway technique (SGT) with the transmural placement of single or multiple plastic stents or metal stents for WON with or without direct endoscopic necrosectomy (DEN). Although DEN has improved the success rate of endoscopic treatment for WON, there remain refractory cases which are resistant to treatment using SGT plus DEN. Particularly, when the collections are huge or multiseptated, the use of SGT plus DEN may be limited because such refractory cases are resistant to treatment even with the use of SGT plus DEN. To overcome this situation, a new strategy, namely, the EUS-guided multiple transluminal gateway technique (MTGT) for complicated WON, was introduced by Varadarajulu et al. [11]. We have also described another novel
Fig. 1 Treatment strategies for pancreatic pseudocyst and walled-off necrosis
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technique, namely, single transluminal gateway transcystic multiple drainage (SGTMD), for complicated multiseptated WON [12]. Our hypothesis is that almost all PC and WON could be treated using various endoscopic techniques. Herein, we retrospectively evaluated the efficacy of endotherapy for the treatment of PCs and WONs followed by pancreatitis.
Patients and methods Patients We identified 89 patients who had infected PCs (n = 14) and WON (n = 75) between March 2006 and October 2013 at Tokyo Medical University Hospital. WON was diagnosed by the presence of necrotic tissue in the collections, based on the history of necrotizing pancreatitis and findings from EUS, computed tomography (CT) and magnetic resonance imaging (MRI), following the revised Atlanta Classification [1]. Infected PC and WON were diagnosed by clinical signs, laboratory results, fever ([38 °C) and evidence of a systemic inflammatory response (SIR) (WBC [ 10,000/lL or \4000/lL and CRP [ 1 mg/dL). The criteria for drainage were as follows: (1) infected PC and WON, (2) sterile PC and WON with an increase in the size of collection or worsening symptoms.
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Methods Drainage techniques Our treatment strategies for PC and WON are described in Fig. 1. Initial drainage using SGT with the placement of one or more plastic stents or a self-expandable metal stent (SEMS) is illustrated in Fig. 2a. If initial drainage was ineffective, direct endoscopic necrosectomy (DEN) was performed. MTGT (Fig. 2b) or SGTMD (Fig. 2c) was performed with or without DEN depending on the morphology and location of the cavities. Various endoscopic techniques for PCs and WONs were described previously [12]. Briefly, in terms of SGT, under
Fig. 2 Schema of single and multiple transluminal gateway techniques for endoscopic ultrasonography-guided drainage a. SGT Single transluminal gateway technique. b MTGT Multiple transluminal
EUS-guidance, a 19-gauge needle was used to puncture transgastrically into the PCs and WONs. If several cavities were separated, the largest cavity was punctured. After dilation of the tract using a rigid dilator and cautery (6-Fr Cysto Gastro Sets, Endo-Flex GmbH, Dusseldorf, Germany), or 4- to 6-mm dilating balloons (Hurricane, Boston Scientific Japan, Tokyo, Japan), one or more 7-Fr double pigtail stents and a 5-Fr or 6-Fr nasocystic catheter were simultaneously placed, or 1 SEMS (partially covered WallFlex, Boston Scientific Japan; 10- or 15-mm AXIOS, Xlumena, CA, USA; 16-mm Niti-S, Taewoong Company, Seoul, Korea; 16-mm Hanaro, MI Tech, Seoul, Korea) alone or a SEMS with a nasocystic catheter or a double pigtail stent was placed.
gateway technique. c SGTMD Single transluminal gateway transcystic multiple drainages
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Fig. 3 Single transluminal gateway transcystic multiple drainages a. CT showed huge and multiseptated walled-off necrosis. b EUSguided drainage of the largest cavity was performed with placement of two 7-Fr double pigtail plastic stents and a 6-Fr nasocystic catheter. c CT showed the sub-cavity, which were separate from the stomach
with insufficient drainage, causing abdominal pain and a fever spike. d The tract from the main cavity to the sub-cavity was sought using an ERCP catheter and guidewire. e A 6-Fr nasocystic catheter were deployed into the sub-cavity
When symptoms or inflammation continued despite the decrease in the size of the largest cavity, we assessed the location of the smaller ‘‘sub-cavities’’ using CT. If the subcavities were located adjacent to the stomach or duodenum, we used MTGT. Additional EUS-guided punctures of these sub-cavities were performed as described above for the initial session. If the sub-cavities with insufficient drainage were detected as not being adjacent to the stomach or duodenum, we used SGTMD (Fig. 3). We identified the connections within the main cavity to the sub-cavities using an endoscopic retrograde cholangiopancreatography (ERCP) catheter and a soft guidewire (0.032-in., Radifocus, Terumo Co., Ltd., Tokyo, Japan). After the subcavities were identified, 1 or more 7-Fr double pigtail
stents and a 5-Fr or 6-Fr nasocystic catheter were placed in the sub-cavities and irrigation was performed using saline.
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DEN In the case of ineffective drainage using SGT with multiple plastic stents or a SEMS, DEN was performed the following day. A 15- to 20-mm dilating balloon (CRE balloon, Boston Scientific Japan) was inserted alongside the stents and inflated to advance a standard upper GI endoscope or ultraslim endoscope through the tract into the collection. When SEMSs were used, the endoscope was directly advanced into the cavity without tract dilation. Necrotic tissue was removed using a basket catheter,
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biopsy forceps and snare forceps using CO2 insufflation. The DEN endpoint was the resolution of symptoms and inflammation. Necrosectomy was limited to 1 h per procedure. Pancreatography and transpapillary stenting When several imaging modalities revealed suspected pancreatic duct disruption, endoscopic retrograde pancreatography (ERP) was conducted after EUS-guided drainage. In the presence of PD disruption, stents were placed in the transpapillary pancreatic ducts. Evaluation of therapy Technical success was defined as having successful stent placement. Technical success of MTGT or SGTMD was defined as having successful stent placement to the dominant sub-cavity. Clinical success was defined as the disappearance of symptoms or inflammation regardless of collection size. Adverse events (AEs) were classified into 3 types: AEs during the procedure, early AEs (until 1 month after the procedure), and late AEs (over 1 month after the procedure). AEs were graded according to the ASGE lexicon’s severity grading system. All cases were divided into two groups as follows: Group A was treated using SGT alone or SGT plus DEN as the standard therapeutic course; Group B was treated using MTGT or SGTMD as a rescue therapy. In the present study, we defined Groups A and B as ‘‘uncomplicated’’ and ‘‘complicated’’ WON, respectively. After confirmation of the decrease in collection size by CT, the SEMSs were removed and exchanged with one or more double pigtail stents. In the case of plastic stent placement, stents were left in place. Repeat CT was performed every 6 months. The stents were endoscopically removed if no AEs occurred after 2 years. This study was approved by our institutional review board (No. 2445). Statistical analysis Continuous variables pertaining to baseline characteristics of the two treatment groups in the cohorts were presented as mean ± standard deviation (SD) and were compared using the Student’s t test or Wilcoxon rank-sum test as appropriate. Categorical variables were compared using the Chi squared or Fisher’s exact test. Statistical analyses were performed using StatMate III (ATMS, Tokyo, Japan). A p value of \0.05 was regarded to indicate a statistically significant difference.
Results In this study, EUS-guided drainages for symptomatic sterile/size-increasing PC cases (n = 11) or infected PC cases (n = 3), symptomatic sterile WON cases (n = 30), and infected WON cases (n = 45) were performed. Patient characteristics are shown in Table 1. All PC cases showed unilocular morphology. In contrast, half of the WON cases showed multilocular morphology (50.7 %, 38/75). The mean size of the maximum axis of the PCs was significantly smaller than those of sterile and infected WON cases (p = 0.03 and p = 0.02, respectively). PCs were treated using SGT alone. Sterile WON required MTGT in one case (3.3 %, 1/30) and infected WON required MTGT in 10 cases (22.2 %, 10/45) and SGTMD in 8 cases (17.8 %, 8/45). There was a statistically significant difference in the use of MTGT and SGTMD between PC and infected WON (p = 0.004), and between sterile WON and infected WON (p = 0.0004). In contrast, there was no statistically significant difference between PC and sterile WON. Of the 89 cases, the present study showed a technical success rate of 100 %, a final clinical success rate of 97.8 %, an AE during procedure rate of 0 %, an early AE rate of 12.4 %, and a mortality rate of 2.2 % (Table 2). AEs included SEMS migration (mild AEs, 4) and plastic stent migration (moderate AE, 1), rupture of a pseudoaneurysm (severe AEs, 2; fatal AEs, 2), mediastinal emphysema (moderate AE, 1), and perforation of the cavity during DEN (severe AE, 1). Most AEs occurred in patients with infected WON (63.6 %, 7/11). No cases required surgical intervention due to inadequate drainage. Pancreatic duct disruption was observed in ERP and transpapillary placement of pancreatic duct stent was performed after EUS-guided drainage in eight cases (9.0 %, 8/89). Treatment periods of infected WON (mean 29.4 days ± 13.2) were longer than PC (mean 13.2 days ± 6.6) or sterile WON (mean 16.5 days ± 13.2). In total, 19 (21.3 %, Group B) of 89 cases were considered resistant to treatment using SGT alone or SGT plus DEN (Table 2). Infected WON with multilocular morphology was found to be a statistically significant factor for failure to resolve using standard therapy (p \ 0.001) (Table 3). Although MTGT or SGTMD in addition to standard therapy was needed in these refractory cases, eventually, almost all cases (94.7 %, 18/19) could be treated by additional endoscopic interventions. In 18 (64 %) of 28 cases of infected WON and multilocular morphology, additional drainage with MTGT or SGTMD was required. In contrast, the remaining 10 (36 %) cases were treated by SGT and DEN. To clarify this difference between the 2 groups, we conducted measurements of the major and minor dimensions in the axial view
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J Gastroenterol Table 1 Patient characteristics Pancreatic pseudocyst (n = 14)
Sterile WON (n = 30)
Infected WON (n = 45)
Total (n = 89)
59.0 ± 19.9
49.0 ± 14.7
59.0 ± 14.1
55.8 ± 16.0
7–92
15–81
29–89
7–92
Male
9
27
36
72
Female
5
3
9
17
0 6
3 20
3 24
6 50
Drug-induced
0
1
2
3
ERCP
0
0
4
4
Post-operative pancreatic fistula
2
0
4
6
Trauma
1
0
0
1
Tumor
3
4
1
8
Idiopathic pancreatitis
2
2
7
11
Head
7
7
12
26
Body
1
11
20
32
Tail
6
12
13
31
62.6 ± 30.2
94.1 ± 38.0
95.5 ± 35.8
91.1 ± 39.3
26–214
42–200
31–187
26–187
Mean age (years) ± SD Range Gender
Etiology Gallstone Alcohol abuse
Location of main lesion
Mean size of long axis of lesion (mm) ± SD Range Morphology of cavity Unilocular
14
20
17
51
Multilocular
0
10
28
38
14
23
20
57
Therapeutic intervention SGT SGT ? DEN
0
6
7
13
MTGT ? DEN
0
1
10
11
SGTMD ? DEN
0
0
8
8
WON walled-off necrosis, SGT single transluminal gateway technique, MTGT multiple transluminal gateway technique, SGTMD single transluminal gateway transcystic multiple drainages, DEN direct endoscopic necrosectomy
of CT and the height in the coronal view of CT of all cavities of infected WON (Table 4). We could not calculate the volume of any of the cavities of WON accurately because each cavity takes on a complicated form. Therefore, we assessed the approximate volume of cavities by applying the formula for the volume of ellipse, 4/3pabc (a: half of the major dimension, b: half of the minor dimension, c: half of the height). Interestingly, we found that additional drainage with MTGT or SGTMD was performed only in the sub-cavities, in which the approximate volume was greater than 65.8 cm3 (median volume 111.1 cm3; range 65.8–654.1) (Table 4, values enclosed in rectangles). In contrast, excluding 1 case of death and 1 case of penetration from the sub-cavity to the duodenum, the subcavities in which the approximate volume was less than 69.4 cm3 (median volume 21.2 cm3; range 4.6–69.4) were
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resolved with supportive care and antibiotic therapy without the need for additional drainage.
Discussion Recently, most uncomplicated PCs and WONs can be treated by standard SGT using multiple stents or SEMSs. In fact, in the present study, all PCs, 70 % of WON and 40 % of infected WON were resolved using SGT. However, the remaining 30 % of sterile WON and 60 % of infected WON required DEN. Seifert et al. [13] described the first clinical utility of DEN as a minimally invasive endoscopic treatment for WON in 2000; the clinical response rate using drainage alone was approximately 40–50 %, but drainage plus DEN improved the response rate to 80 %.
J Gastroenterol Table 2 Outcome of EUS-guided interventions in pancreatic pseudocyst and walled-off necrosis Pseudocyst (n = 14)
Sterile WON (n = 30)
Infected WON (n = 45)
Total (n = 89)
Method of therapy SGT
14/14
23/30
20/45
57/89
1st SEMS
3
12
11
26
1st PS
11
11
9
31
N/A
6/30
7/45
13/89
1st SEMS
6
6
12
1st PS
0
1
1
Mean no. of DEN sessions
1.8
2.7
2.3
Range
1–3
1–5
1–5
SGT ? DEN
MTGT ? DEN
N/A
1st ? 2nd PS 1st ?2nd SEMS
1/30
10/45
11/89
N/A 1
4 2
4 3
1st SEMS and 2nd PS
N/A
3
3
1st ? 3rd SEMS and 2nd PS
N/A
1
1
Mean no. of sessions of DEN
2
3.6
3.5
Range
2–2
1–10
1–10
N/A
4/45
4/89
1st SEMS
2
2
1st PS
2
2
SGTMD
N/A
SGTMD ? DEN
4/45
4/89
1st SEMS
N/A
3
3
1st PS
1
1
Median no. of DEN sessions
3.5
3.5
Range
1–7
1–7
6/45
8/89
Placement of pancreatic duct stent Mean treatment periods (days) ± SD
1/14 a
N/A
1/30
13.2 ± 6.6
16.5 ± 13.2
29.4 ± 13.2
22.4 ± 14.9
Range Technical success (%)
5–24 100 (14/14)
4–54 100 (30/30)
9–69 100 (45/45)
4–69 100 (89/89)
Final clinical success (%)
100 (14/14)
100 (30/30)
93.3 (42/45)
96.6 (86/89)
Early adverse event (%)
7.1 (2/14)
6.6 (2/30)
15.6 (7/45)
12.4 (11/89)
1
2
1
4
Migration of PS
0
0
1
1
Mediastinal emphysema
0
0
1
1
Perforation of cyst
0
0
1
1
1
0
1
2
Mild Migration of SEMS Moderate
Severe Rupture of pseudoaneurysm Fatal Rupture of pseudoaneurysm Mortality (%)
0
0
2
2
0 (0/14)
0 (0/30)
6.7 (3/45)
3.4 (3/89)
EUS endoscopic ultrasonography, WON walled-off necrosis, SGT single transluminal gateway technique, MTGT multiple transluminal gateway technique, SGTMD single transluminal gateway transcystic multiple drainages, DEN direct endoscopic necrosectomy, SEMS self-expandable metal stent, PS plastic stent, N/A not available a
The patients who died were excluded
Recently, results from multi-center studies of many cases in three countries have been published [14–16]. In these studies, the success rate of treatment was 75–91 %, the rate
of complications was 26–33 %, and the mortality rate was 5.8–11 %, which was better than the treatment outcome with EUS-guided drainage alone, and suggests that DEN is
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J Gastroenterol Table 3 Comparison between standard and complicated therapeutic courses
Mean age (years) ± SD Range Gender Male Female
Case no.
Age (years)/ gender
Additional drainage
Clinical outcome
Main cavity volume (cm3)
Sub-cavity volumea (cm3)
1
35/M
MTGT
Cured
211.7
138.9
2
42/F
MTGT
Cured
280.2
82.0, 4.6
3
43/M
MTGT
Cured
132.6
99.6
4
80/F
MTGT
Cured
102.1
109.3
5
50/M
MTGT
Cured
363.0
113.0, 65.8
6
57/M
MTGT
Cured
73.6
7
70/M
MTGT
Cured
501.5
69.2, 6.3, 9.3 71.2
8
80/M
MTGT
Cured
391.9
139.4
9
68/M
MTGT
Cured
165.0
94.1
10
49/M
MTGT
Cured
1318
392.7, 31.1
11
66/M
SGTMD
Cured
160.0
98.6
12
56/M
SGTMD
Cured
292.0
118.5
0
13
29/F
SGTMD
Cured
326.6
158.8, 29.7
83/M
SGTMD
Cured
159.8
91.5, 23.6, 18.1
Group A (n = 70)
Group B (n = 19)
p value
54.9 ± 15.9
56.9 ± 17.3
0.78
7–92
29–83
58
14
12
5
Location of main cyst
0.25 0.48
Head
21
5
Body
23
9
Tail
26
5
Mean size of long axis of cavity
81 ± 42.3
106.4 ± 30.8
(mm) ± SD
26–214
0.05
65–154
Range \0.001
Diagnosis and form of cyst Pseudocyst (unilocular)
14
Table 4 Comparison of the sub-cavity sizes volume in infected multilocular walled-off necrosis
Sterile WON (unilocular)
20
0
14
Sterile WON (multilocular)
9
1
15
44/M
SGTMD
Cured
801.1
654.1, 264.0
Infected WON (unilocular)
17
0
16
89/M
SGTMD
Cured
217.2
181.5
17
55/M
SGTMD
Cured
614.6
172.6
Infected WON (multilocular)
10
18
68/F
SGTMD
Death
13.3
93.1
19
44/M
None
Cured
116.7
23.2
20
68/M
None
Cured
120.6
6.0
21
41/M
None
Cured
315.3
31.1
22
60/M
None
Cured
45.2
10.8
WON walled-off necrosis
23
62/M
None
Cured
242.9
21.2
Group A Standard therapeutic course
24
44/M
None
Cured
542.5
48.3
Group B Complicated therapeutic course
25
65/F
None
Cured
196.5
20.6, 48.5
26
66/M
None
Cured
296.9
65.9b, 69.4
27
46/M
None
Cured
302.4
20.3, 17.7
28
75/M
None
Death
259.7
377.2
Final clinical success rate (%)
97.1 (68/70)
Adverse event rate (%)
9.3 (9/70)
18 94.7(18/19) 7.1 (2/19)
0.61 0.79
safer than surgical necrosectomy. Our results were similar to the success rate of drainage plus DEN at 79 %. Thus, SGT with DEN appears to be one of the key therapies for the treatment of complicated WON. In this study, 19 (21.3 %) complicated WON cases (1 sterile WON case and 18 infected WON cases) were considered refractory to treatment as they failed to resolve using standard SGT and DEN. Interestingly, we found that the refractory cases were most often infected WON with multilocular morphology (94.7 %, 18/19). Thus, infected and multilocular WON cases are less responsive since there are undrained sub-cavities. These cases have historically been treated with surgical or percutaneous approaches. The techniques of a hybrid approach using endoscopic and percutaneous approaches have recently become popular [9, 17, 18]. Unfortunately, open surgical debridement carries a morbidity of 55 % and a mortality of 14 % [19, 20]. Thus,
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WON walled-off necrosis, MTGT multiple transluminal gateway technique, SGTMD single transluminal gateway transcystic multiple drainages, M male, F female a
Values in bold italics represent cavity volume which required additional drainage
b
The sub-cavity penetrate to duodenum
a step-up approach of combined endoscopy with percutaneous technique is recommended for complicated WON rather than open necrosectomy [21]. However, SGT with DEN is not always effective for the treatment of complicated WON, particularly multiseptated WON. Varadarajulu et al. described the usefulness of the MTGT for symptomatic WON [11] and reported that the clinical success rate was higher than when conventional
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SGT was used (91.7 % vs 51.2 %, p = 0.018). However, they suggested that MTGT was not an option for the treatment of WON which was separate from the gastrointestinal lumen, in locations such as the perisplenic space [11]. When sub-cavities or undrained areas of the main cavity are located far from the stomach and duodenum, EUS-guided intervention appears unsuitable. In the present study, non-drained cavities were adjacent to the stomach or duodenum in only 58 % (11/19) of complicated WON cases (Group B). Previously, the percutaneous approach would have been used. However, we hypothesized that the multilocular cavity may have originally been unilocular and only separated into sub-cavities during the process of treatment and collapse, and as a result, tiny, narrow connections were present between the sub-cavities [12]. We conducted SGTMD as a technique for connecting the subcavities. In the present study, however, all PCs and almost all WONs were treated by various direct endoscopic techniques, e.g. interventional EUS plus SGT, MTGT, and/ or SGTMD with or without DEN, but we should consider transpapillary and/or EUS-guided pancreatic duct access [22, 23] in addition to direct endoscopic techniques by means of EUS and ERCP for the treatment of PPC and WON caused by pancreatic duct disruption. Interestingly, we found that in cases of infected WON and multilocular morphology, the sub-cavities with an approximate volume that was greater than 65.4 cm3 required additional drainage. This number could be used to determine the need for additional drainage. On the other hand, sub-cavities that are smaller than 69.4 cm3 should improve using antibiotic therapy without additional drainage. Thus, the necessity of additional drainage depends on the size of the sub-cavity. This is similar to patients with hepatic abscesses in which drainage becomes necessary when the major axis exceeds 50 mm [24]. In the present study, the overall AE rate was 12.4 % and the mortality rate was 2.2 %. The 4 cases of pseudoaneurysm rupture were serious AEs. The cause of death in 2 cases was an internal hemorrhage in the cavity. We hypothesize that continuous peripancreatitis resulted in aneurysm formation that led to arterial bleeding. Although MTGT has comparable risks to conventional pseudocyst drainage, SGTMT involves additional drainage of the subcavities under fluoroscopic guidance, which carries risks of bleeding and perforation. Thus, evaluation of the subcavity using CT and careful probing using a soft guidewire are mandatory. In the present study, we never misdiagnosed the PC or WON as pancreatic cystic neoplasms, e.g. mucinous cystic neoplasms of the pancreas (MCN). Since at times the necrotic tissue and debris in the PCs and WONs are morphologically similar to mural nodules in the MCN, we may
perform a contrast-enhanced ultrasound for differential diagnosis before the puncture by EUS [25]. The limitations of this study are its retrospective nature performed at a single center and the absence of a control group. In conclusion, we clarified that all PC cases and most WON cases can be treated using SGT with or without DEN, and refractory WON cases can be treated using SGT plus DEN in combination with MTGT or SGTMD although a surgical approach as well as a percutaneous approach should be considered in the cases refractory to endoscopic therapies. Acknowledgments The authors are indebted to Maya Vardaman and Associate Professor Edward Barroga of the Department of International Medical Communications of Tokyo Medical University for the editorial review of the English manuscript. We are grateful to Dr. Todd. H. Baron of the Mayo Clinic, Rochester, Minnesota, USA, for his valuable editing suggestions. Conflict of interest of interest.
The authors declare that they have no conflict
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