Present Series
A total of 12 patients with PFCs were included in this series as they met selection criteria, including 2 patients with PPC and 10 with WON. The mean age of the 12 present case series was 47.2 ± 11.9 years old with age ranged from 28 to 62 years old, including 8 males and 4 females. Regarding the etiology of acute pancreatitis, 5 cases were alcohol or hypertriglyceridemia, 6 cases were gallstone, and 1 case was idiopathic. For the location of PFCs, 2 cases were in the pancreatic head, 2 cases in the head and body, and 8 cases in the body and tail. The average maximal diameter of PFCs was 12.5 ± 4.0 cm. The symptoms of patients with PFCs were mainly abdominal pain, fever, or abdominal distention, in which 8 cases were mainly manifested by abdominal pain and fever, 2 cases were mainly manifested by abdominal distention and diarrhea, and 2 cases were found by cross-sectional image without obvious discomfort. Minimal solid debris was noted in 4 cases (33.3%), moderate solid debris in 7 cases (58.3%) and profound solid debris in 1 case (8.3%). The details of the demographic characteristics of these 12 patients are showed in Table 1.
Table 1
Characteristics of 12 patients with pancreatic fluid collections.
Characteristics | PFCs (n = 12) |
Age, year (mean ± SD) | 47.2 ± 11.9 |
Male/female | 8/4 |
Etiology of pancreatitis, n (%) | |
Alcohol or hypertriglyceridemia | 5(41.7%) |
Gallstone | 6(50.0%) |
Idiopathic | 1(8.3%) |
Complaints, n (%) | |
Abdominal pain and fever | 8(66.7%) |
Bloating and diarrhea | 2(16.7%) |
No symptoms | 2(16.7%) |
Location of fluid collection, n (%) | |
Head | 2(16.7%) |
Head and body | 2(16.7%) |
Body and tail | 8(66.7%) |
Triglycerides, mmol/L (mean ± SD) | 1.8 ± 0.9 |
Maximal diameter of PFCs, cm (mean ± SD) | 12.5 ± 4.0 |
Abbreviations: PFCs, pancreatic fluid collections; SD, standard error. |
Endoscopic debridement through LAMS was performed in 3 patients with WON, and 1 patient with WON was treated with saline cystic irrigation through LAMS. In terms of efficacy of LAMS, stents placement was technically successful in 12 patients with the technical success rate of 100%. Endoscopic therapy using the LAMS was successful in 8 of 10 patients with WON compared with 2 of 2 patients with PPC, and the clinical success rate in patients with WON and PPC was 83.3% and 100%, respectively. Treatment failure occurred in two patients, in which one patient with moderate solid debris required surgical intervention due to pseudoaneurysm and another with profound solid debris had poor drainage with cyst infection, followed by nasal cyst drainage as complementary endoscopic interventions, and the collection resolved partially across cross-sectional imaging at one month after LAMS placement.
Stent removal was performed after a median of 29.6 days (range 18–45). In terms of procedure-related adverse events, infection occurred in 1 patient with PPC and 6 patients with WON, and 1 patient with WON had a stent migration and stent blockage concurrently. Immediate bleeding or delayed bleeding was not observed in any patients. Procedural characteristics and clinical outcomes of PFCs are showed in Table 2.
Table 2
Procedural characteristics and clinical outcomes of present series
| PFCs (n = 12) | PPC (n = 2) | WON (n = 10) |
Type of LAMS, n (%) | | | |
DMHS | 7(58.3%) | 1(50.0%) | 6(60.0%) |
AXIOS | 5(41.7%) | 1(50.0%) | 4(40.0%) |
Total no. of endoscopic reinterventions | | | |
0 | 9 | 3 | 6 |
1 | 1 | 0 | 1 |
> 1 | 2 | 0 | 2 |
Cyst irrigation, n (%) | 1(8.3%) | 0 | 1(8.3%) |
Technical success, n (%) | | | |
YES | 12(100%) | 2(100%) | 10(100%) |
Clinical success, n (%) | | | |
YES | 10(83.3%) | 2(100%) | 8(80.0%) |
NO | 2(16.7%) | 0 | 2(20.0%) |
Adverse events, n (%) | | | |
Infection | 6(50%) | 1(50%) | 5(50%) |
Bleeding | 0 | 0 | 0 |
Stent migration | 1(8.3%) | 0 | 1(10.0%) |
Stent occlusion | 1(8.3%) | 0 | 1(10.0%) |
Duration of procedure, min (mean ± SD) | 65.6 ± 24.3 | 51.5 ± 23.3 | 68.4 ± 24.7 |
Hospital stay, days (mean ± SD) | 17.1 ± 8.6 | 16.5 ± 3.5 | 17.2 ± 9.4 |
Days to stent removal, days [range] | 29.6[18–45] | 27.5[27–28] | 30.1[18–45] |
Abbreviations: LAMS, lumen-apposing metal stents; PFCs, pancreatic fluid collections; PPC, pancreatic pseudocysts; WON, walled-off necrosis; SD, standard error |
Literature Search
The flowchart of the literature search process is illustrated in Fig. 1. The retrieval time was from January 2010 to January 2020. According to the search strategy, a total of 271 articles were enrolled during database searching, including 225 English articles and 46 Chinese articles. Among these articles, 39 articles were excluded due to duplicates, 203 articles were excluded after the review of title and abstract, 20 articles were excluded after full-text review for the following reason: 13 articles had no sufficient data and 7 articles targeted on other types of stents or mixed. We included 2 articles from the reference of the screened articles and a record from our center in addition. Finally, 585 patients from 12 studies were included in the meta-analysis.
Study and Population Characteristics
The studies and population characteristics in the meta-analysis are shown in Table 3. Data from our series was added to the meta-analysis as well. Among the 12 retrospective or prospective studies, the cases data came from 4 in Asia, 3 in Europe, 1 in Oceania and 4 in North America. All these treatments were implemented between the years of 2011 to 2019. Most of the used LAMS subtypes were AXIOS stents or Nagi stents (Taewoong Medical, South Korea), the rest were DMHS and HANARO stents (MI-Tech, South Korea). The definitions of clinical success used in the included individual studies are shown in Supplementary Table 2.
A total of 585 patients with PFCs were included in the meta-analysis, in which 343 patients with WON and 242 with PPC. The age of these patients were around 50 years old except for the study from Sundeep et al. The clinical success rates varied from 50–100%. Postoperative infection, bleeding, stent migration and stent occlusion were the most common complications after LAMS placement. Due to missing data in some studies, 11 patients were finally excluded for calculating clinical success, adverse events (574/585), in which four patients were lost to follow-up in Dennis et al. (1 and 3 in PPC and WON, respectively), and two patients with PPC were lost to follow-up and one patient with WON is being followed up in Rajat et al. Besides, in Daisy et al., data on four patients were limited to technical procedure and excluded from the further analysis (1 and 3 in PPC and WON, respectively).
Table 3
The characteristics of the included studies and population.
No | First author | Publication year | Country | Research period | No. of study institutes | Study design | Sample size | Study arm | LAMS subtype | Mean age | Gender, Female/Male | NOS Scores |
WON | PPC |
1 | Natsuyo et al 18 | 2013 | Japan | 2011–2012 | 2 | Retrospective | 9 | 4 | 5 | Nagi | 49 | 3/6 | 7 |
2 | Daisy et al 19 | 2015 | European countries | 2011–2012 | 15 | Prospective | 61 | 46 | 15 | AXIOS | 55 | 23/38 | 7 |
3 | Sujievvan et al 20 | 2015 | Australia | 2013 | 13 | Retrospective | 47 | 9 | 38 | Nagi | 51# | 16/32∆ | 8 |
4 | Ali A et al 21 | 2016 | US | 2012–2014 | 4 | Retrospective | 82 | 68 | 14 | AXIOS | 51 | 33/48∆ | 8 |
5 | Josep et al 22 | 2017 | US | NA | 2 | Retrospective | 25 | 22 | 3 | AXIOS | 50 | 11/14 | 9 |
6 | Shuntaro et al 23 | 2017 | Japan | 2015–2016 | 1 | Prospective | 12 | 8 | 4 | HANARO | 66 | 2/10 | 7 |
7 | Suresh et al 24 | 2017 | UK and Ireland | 2015–2016 | 11 | Prospective | 116 | 70 | 46 | AXIOS | 53 | 38/78 | 8 |
8 | Dennis et al 25 | 2018 | US | 2010–2016 | Multi-center | Retrospective | 122 | 64 | 58 | AXIOS | 60 | 43/79 | 7 |
9 | Sundeep et al 26 | 2018 | Korea | NA | NA | Prospective | 5 | 4 | 1 | Nagi | 29 | 0/5 | 6 |
10 | Maria et al 27 | 2018 | Italy | 2013–2016 | 7 | Retrospective | 67 | 23 | 44 | Nagi | 59 | 21/46 | 8 |
11 | Rajat et al 28 | 2019 | US | 2014–2017 | 1 | Retrospective | 27 | 15 | 12 | AXIOS | 54 | 15/12 | 7 |
12 | This center | NA | China | 2016–2019 | 1 | Retrospective | 12 | 10 | 2 | AXIOS and DMHS | 47 | 4/8 | NA |
Notes: # The age derived from Sujievvan et al was median age, and ages derived from other studies were mean ages. ∆ The gender distribution was derived directly from the articles or calculated from gender ratio provided from the studies, which might bring the inconsistent with the total sample size. |
Quality assessment
The included studies showed moderate to high quality. The specific scoring rules of the included trials according to NOS are showed in Supplementary Table 3. The NOS scale showed of one study with the score of 6 (moderate quality) and 10 studies were scored higher than or equal to 7 (high quality). The quality assessment showed of an acceptable quality of the included studies.
Risk ratio of technical success between WON and PPC
A total of 10 studies provided the data on the technical success rates of WON and PPC after LAMS placement. The overall risk ratio using fixed effect model (I2 = 0%, P = 0.84) was 1.04 (95%CI: 1.00-1.08) (Fig. 2). It showed no significance in technical success between WON and PPC (Z = 1.78, P = 0.08).
Clinical success rates of WON and PPC
Firstly, we summarized the overall clinical success rates of LAMS for patients with WON and PPC. As showed in Fig. 3a, the clinical success rates of LAMS for WON ranged from 50–100%, with the overall clinical success rate of 89% (95%CI: 85%-93%) in fixed effect model (I2 = 26%, P = 0.19). The clinical success rates of LAMS for PPC ranged from 83–100%, with the overall clinical success rate of 99% (95%CI: 95%-100%) in fixed effect model (I2 = 0%, P = 0.80), showed in Fig. 3b.
In order to clarify if the difference existed in the clinical success rates between LAMS in WON and PPC, the risk ratios of WON compared with PPC were calculated and showed in Fig. 4. The overall RR of WON compared with PPC was 0.92 (95%CI: 0.86–0.98) in the fixed effect model (I2 = 0%, P = 0.48). The combined Z-test value was − 2.73 (P = 0.01). The clinical effectiveness of LAMS in patients with WON was 0.92 times compared with LAMS in patients with PPC. LAMS drainage showed better clinical efficacy in PPC than that of WON.
The cumulative meta-analysis was also used on the clinical success rate (comparison of the efficacy of LAMS between PPC and WON) in the order of publication year and sample size, reflecting the dynamic trend in the included studies. In the cumulative meta-analysis of publication year, the risk ratio in the efficacy of LAMS between WON and PPC tended to be stable after the year of 2017 (Supplementary Fig. 1a). In the cumulative meta-analysis of sample size, the risk ratio between WON and PPC tended to be stable with sample size larger than 30 patients (Supplementary Fig. 1b).
The studies were divided into three subgroups: Nagi group, AXIOS group, and other group (including HANARO stents, AXIOS stents and DMHS mixed). Subgroup analysis of clinical success in different subtypes of LAMS showed the significant risk ratio in AXIOS group (RR = 0.92, 95%CI: 0.86–0.99). In Nagi and other groups, the RR showed no significance success rates in different subtypes of LAMS. The clinical efficacy of AXIOS stents in PPC were better than WON (Fig. 5).
Safety evaluation on postoperative complications
In this review, the most common adverse events included postoperative infection, bleeding, stents migration and stent occlusion. There were at least five articles provided the data on each of these four complications. The summarized proportions of adverse events were showed in Supplementary Fig. 2 and Supplementary Fig. 3. All the four complications showed no significance on the complication rates between patients with WON and PPC in fixed effect model (all the I2 < 50% and P > 0.05) (Fig. 6). As showed in Fig. 6a, the summary of RR on the postoperative infection was 1.57 (95% CI: 0.73–3.39) in fixed effect model, and no significance was found in the RR of WON cases compared with PPC cases (Z = 1.15, P = 0.25) on postoperative infection. The summary of RR on postoperative bleeding was 0.84 (95% CI: 0.34–2.09) (Fig. 6b). We also found no significance in the RR of WON cases compared with PPC cases (Z=-0.37, P = 0.71) on postoperative bleeding. The summary of RR on the complication of migration was 1.04 (95% CI: 0.51–2.12) in the fixed effect model (Fig. 6c). There was once again no significance in the RR of WON cases compared with PPC cases (Z = 0.11, P = 0.91) on stent migration. Figure 6d showed that the summary of RR on the complication of stents occlusion was 1.66 (95% CI: 0.92–2.98) in the fixed effect model. No significance was also found in the RR of WON cases compared with PPC cases (Z = 1.70, P = 0.09) on stent occlusion.
The proportion of patients undergoing DEN in WON cases
A total of 10 studies provided the information of DEN among WON cases. The summary proportion of patients undergoing DEN was 60% (95% CI: 34%-84%) in the random effect model (I2 = 94%>50%, P < 0.01). The results showed of 100% DEN proportion in the studies of Ali A et al. and Sujievvan et al (Fig. 7). Other studies with relative larger weight showed of low proportion of patients undergoing DEN in patients with WON ranged from 30–53%.
Publication bias
Finally, the publication bias was evaluated on the main outcome of RR in clinical success rates. The results of funnel plot showed that the studies distributed roughly symmetrical (Fig. 8). Statistical analysis using Egger's test confirmed that there was no evidence of publication bias in the clinical success risk ratio between WON and PPC (P = 0.07).