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Meta-Analysis

A Comparison of Endoscopic Versus Surgical Creation of a Cystogastrostomy to Drain Pancreatic Pseudocysts and Walled-Off Pancreatic Necrosis in 5500 Patients

Suggs, Patrick MD*; NeCamp, Timothy PhD†; Carr, John Alfred MD, FCCP, FACS‡

Author Information

From the *The Department of General Surgery, St. Joseph Mercy Medical Center, Ann Arbor, MI

†The Department of Statistics, University of Michigan, Ann Arbor, MI

‡The Department of Trauma Surgery, Mid-Michigan Medical Center, Midland, MI.

Received: 16 September 2020; Accepted 20 October 2020

Published online 20 November 2020

Disclosure: The authors declare that they have nothing to disclose.

Reprints: John Alfred Carr, MD, FCCP, FACS, The Department of Trauma Surgery, Mid-Michigan Medical Center, 4000 Wellness Drive, Midland, MI 48670. E-mail: [email protected].

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

doi: 10.1097/AS9.0000000000000024
  • Open

INTRODUCTION

Complications of pancreatitis are life threatening and frequently require complex treatment algorithms. Historically, surgical management carried a high morbidity with prolonged length of stay and risk of repeat procedures. Therefore, in 2013, the first prospective randomized trial was performed and reported that endoscopic and surgical cystogastrostomy had equal efficacy for drainage of pancreatic pseudocysts (PP).1 A subsequent study documented similar findings.2 While these initial reports dealt exclusively with the drainage of pancreatic pseudocysts, the endoscopic procedure has now been clinically extended, beyond its original intent, for drainage of infected peripancreatic fluid collections (IPFC, includes abscesses, infected pseudocysts, or infected liquefactive necrosis) and walled-off pancreatic necrosis (WON, sterile).3,4 This has marked a change in philosophy with many acute complications now being treated with internal, rather than external, drainage. While the initial results using endoscopic techniques to drain pseudocysts had been good, these expanded attempts to drain IPFCs and WON have been marred by bleeding complications, perforations, failure to adequately drain infected pseudocysts leading to sepsis, multiple reinterventions, and death.3,4 Despite these reports, endoscopic drainage of IPFC and WON has increased in volume and fewer surgical cyst-enteric drainage procedures are being performed, although a laparoscopic surgical approach has been shown to have a very short length of stay, a high safety profile, and a low cost.5

Referral patterns are evolving away from surgery due to high-perceived morbidity and mortality associated with early operation on necrotizing pancreatitis, before a walled-off or mature pseudocystic collection has formed. Previous reports documented that surgery on necrotizing pancreatitis within 72 hours resulted in mortality rates up to 65%.6,7 The surgical techniques used in these cases were distal pancreatectomies, transperitoneal approaches with debridement and packing, or transperitoneal resection with lavage.8–10 Contemporary surgeries are now carried out through videoscopic-assisted retroperitoneal debridement (VARDS), or a transgastric laparoscopic approach, with much less morbidity. Since a pseudocapsule has not yet formed early in the disease process, any attempt at a transperitoneal approach would open the lesser sac and create a vast communication between the retroperitoneum and the abdominal cavity, leading to a high rate of pancreatic fistulas and intraabdominal abscesses in these patients.11,12 It is now evident that patients who can avoid operative intervention for 12 or more days enjoy a greatly decreased mortality.13,14 This delay allows enough time for an early pseudocapsule to form within the retroperitoneum and contain the inflammatory process. If surgery can be delayed even further to 4–6 weeks, a true pseudocyst will have formed and a surgical cystogastrostomy can be created with a simultaneous debridement or necrosectomy. This procedure has a dramatically lower mortality risk than an early pancreatic necrosectomy.5

Some authors have reported that the highest success rates with endoscopic cystogastrostomy occur when there is radiographic documentation of a well-loculated, purely fluid-filled pseudocyst without any necrotic debris or infection.15,16 Infected pseudocysts often harbor thick pus and granular material that do not drain well via a small stent. Other reports have also documented that infected pseudocysts, or sterile pseudocysts that become infected after endoscopic stenting, often plug the stent with pus and debris, which allows the infection to persist, and can perpetuate ongoing sepsis and led to death.17,18 Thus, it would appear that endoscopic cystogastrostomy has proved its effectiveness for uncomplicated pseudocysts, while surgical cystogastrostomy would be more appropriate for infected pseudocysts or those with a lot of necrotic debris. Academic medical centers have standardized their approach and refer to “step up” algorithms, which match techniques to individual patient conditions.19 However, this approach is not what is always occurring in the clinical setting, and the belief that endoscopic therapy is less morbid than surgical therapy has allowed the expansive use of endoscopy for mature cystic collections of every type. Several recent reports aggregating patients from the last 10 years have documented a substantial morbidity and mortality with endoscopic cystogastrostomy for IPFCs and WON, far above what has been historically reported for surgical cystogastrostomy.15–20

Patients with pancreatitis can develop a wide-spectrum of IPFCs or WON. Each collection will vary in the amount of debris, fluid, infection, loculation, anatomical position, necrosis, and size. These patients may be hemodynamically stable or in septic shock, with varying degrees of organ failure. Research reporting on an isolated minority of homogenous fluid collections, for example, WON or PP alone, will have meaningful results that would apply to only that population, which does not reflect the variety of mature peripancreatic fluid collections that are seen in actual practice. Complicating the analysis is the fact that most published reports on endoscopic stenting of pancreatic pseudocysts include patients with infection and WON as well.17–19,21–26 Selection bias enters most comparisons as many endoscopic reports document results that are performed on stable patients in both the inpatient and outpatient settings, while surgical results contain both stable and septic patients who are hospitalized.22–26 This would, in theory, favor the endoscopic results. An appropriate way to determine the true morbidity, reintervention risk, and success of this heterogeneous group is to analyze all of the patient data together, using volume to create uniformity in the patient populations. Once the appropriate population is defined, one needs to compare analogous procedures, those being endoscopic cystogastrostomy with surgical cystogastrostomy, and to not include early pancreatic debridement or trans-peritoneal debridement.

There have been no recent reports in the last 5 years comparing the results of endoscopic therapy with surgical therapy for the drainage of all mature PP, IPFCs, and WON taken as a whole. It was the authors’ hypothesis that, based upon the myriad of case reports documenting complications from endoscopic therapy, surgical therapy, using either open or laparoscopic techniques, may actually have less morbidity with a higher success rate. With this in mind, the authors sought to review all of the reported series of patients undergoing endoscopic or surgical drainage of mature PP, IPFCs, or WON over the last 20 years, and determine the optimal approach based upon successful drainage, complications, reinterventions, and mortality.

METHODS

Data Collection

An online PubMed and internet review of all articles dealing with mature PP, IPFCs, or WON over the last 20 years were indexed. All English language articles in adult or pediatric populations were reviewed, and German, Russian, French, and Spanish articles if an English translation of the article could be procured. All series that had 5 patients or more who underwent endoscopic, laparoscopic, or open surgical therapy for mature PP, IPFCs, or WON were included. Authors who published many series containing the same patient population had only their largest series included to avoid duplications. Series that reported external catheter drainage were excluded. Case reports or series with less than 5 patients were excluded. Previously published meta-analysis or review articles were excluded. Series dealing with early pancreatic debridements, and not mature cystic collections, were excluded. Surgical reports of transperitoneal debridements were excluded since this is an outdated method and not technically comparable to endoscopic cystogastrostomy. All etiologies of pancreatic disease were included. Endoscopic and surgical reports that described any type of cystenterostomy creation, including cystogastrostomy, cystoduodenostomy, or cystojejunostomy, were included.

Since the majority of initial reports of endoscopic cystenterostomy began to be published 10 years ago, almost all of the endoscopic articles are from the last 10 years. To have a large enough comparison group and because laparoscopic and open surgical procedures have been performed for a longer time period, the surgical literature search was extended back 20 years.

Abstracts were examined for patient series of endoscopic or surgical drainage of mature PP, IPFCs, and WON since all of these disease processes are addressed by both open surgical, laparoscopic, and endoscopic methods in practice, and the authors were seeking “real world” results. After all of the abstracts were reviewed, those matching the topics of interest were isolated, and the full-length manuscript was obtained. Each article was read in its entirety, and the following information was extracted: number of patients, age, gender, etiology of pancreatitis, morbidity, and bleeding complications, resolution of the fluid collection, recurrence of fluid, reintervention, length of stay, follow-up, and mortality. Any kind of reintervention, endoscopic or surgical, to address a persistent fluid collection after the initial procedure, including postprocedure abscess or other complications such as bleeding, was counted as a reintervention. The only exception was endoscopic stent removal after successful drainage, which was not counted as a reintervention since this is a planned necessity poststenting. Resolution was defined as successful drainage and clinical improvement after a single intervention. The term “clinical resolution,” often used in the literature but having a variety of meanings, was not assumed to be true resolution unless there was associated radiographic documentation that the cyst had been drained to less than a 2-cm diameter (as suggested by other authors), and no further interventions were required because the patient was asymptomatic and without complications.27–29 If such documentation was not described in the manuscript or if no radiological follow-up was obtained in the study group, the resolution was labeled as “NR,” not reported. The number of patients in each study who had unsuccessful attempts at endoscopic drainage did not equal the number of reinterventions because many patients had reinterventions for complications, and many had more than 1 reintervention.

End Points

The primary endpoint of this study was to evaluate the efficacy (cyst resolution) and safety (complications, adverse events) of endoscopic cystenterostomy and surgical cystenterostomy. Secondary endpoints were reintervention rates, fluid or symptom recurrence, and mortality.

Definitions

According to the revised Atlanta criteria, PP were defined as collections of fluid that were observed after a period of more than 4 weeks, were encapsulated within a well-defined inflammatory wall, and contained no solid components or necrosis.30 Walled-off pancreatic necrosis (WON) was defined as a mature, encapsulated collection of pancreatic and peripancreatic necrosis that presented with a well-defined inflammatory wall and was present for more than 4 weeks, and clinically presumed to be sterile. Infected peripancreatic fluid collections (IPFCs) were PP or WON or other chronic, encapsulated, noncategorized fluid accumulations with documented infection. Many of the articles described “pseudocysts” with various amounts of necrotic debris, that is, 30% or 50% solid component, but since all of these collections were being included in this review, the exact naming of PP versus WON did not make any difference. Recurrence was defined as the presence of a new pseudocyst or reexpansion of the original cyst on imaging after successful treatment and shrinkage of the initial PP or WON.

Statistical Analysis

A statistical analysis was performed using a random effects model to account for between study heterogeneity. Specifically, we used a random intercept logistic regression model for each binary outcome of interest (bleeding, resolution, reintervention, recurrence, morbidly, and mortality).31 The model was fit using the LME-4 package in R, which uses maximum likelihood techniques.32,33 For each outcome, we obtained estimates, standard errors, and 95% confidence intervals (CI) for the mean proportion of individuals with that outcome after receiving surgery or endoscopy. We also obtained estimates, standard errors, 95% CI, and P values (testing for a difference from 0) for the log odds ratio between surgery and endoscopy for that outcome. For each continuous outcome of interest (ie, length of stay and follow-up), we estimated the overall mean using a random intercept model with inverse variance weighting for pooling each study’s mean.34 As we were unable to obtain standard deviations for all the individual studies, we used conservative estimates of the studies’ standard deviations in our analysis. The model was fit using the meta package in R.33,35 For each outcome, we obtained estimates, standard errors, and 95% confidence intervals for the mean after receiving surgery and endoscopy. We also obtained estimates, standard errors, 95% confidence intervals, and P values (testing for a difference from 0) for the difference in means between surgery and endoscopy for that outcome.

To evaluate if the endoscopic and surgery patient populations were similar, we compared the age, gender, and etiology of pancreatitis between the groups. Additional comorbidity data were very limited or absent in most of the endoscopic manuscripts, which limited further comparison of other patient characteristics. Institutional review board approval for this study was obtained from the St Joseph Mercy Health System.

RESULTS

We identified 1346 articles that covered the topics of interest, and from those, there were 27 surgical articles20,36–61 and 58 endoscopic articles15–18,20–29,59,62–104 that met criteria. From these 85 articles, we reviewed the results for 5588 patients. See Tables 1 and 2 and PRISMA flow diagram.

TABLE 1. - Results of Surgical Cystenterostomy
Author n Bleeding Resolution* Reintervention Recurrence LOS Follow-up Morbidity Mortality
Boutros 19 0 19 (100%) 0 0 7 d 31 mos NR 0
Palanivelu 100 2 (2%) 100 (100%) 2 (2%) 1 (1%) 6 d 54 mos NR 0
Yin 12 1 (8%) 12 (100%) 1 (8%) 1 (8%) NR 108 mos 3 (25%) 0
Hauters 12 0 12 (100%) 0 1 (8%) 6 d 12 mos 1 (8%) 0
Parks 28 0 28 (100%) 0 0 7 d NR 10 (36%) 0
Hindmarsh 15 0 15 (100%) 0 2 (13%) NR 37 mos 2 (13%) 0
Bansal 134 3 (2%) 128 (96%) 0 0 4 d 66 mos 14 (10%) 0
Khaled 54 0 53 (98%) 0 1 (2%) 8 d 18 mos 12 (23%) 1 (2%)
Gibson 44 1 (2%) 44 (100%) 1 (2%) 1 (2%) 6 d 74 mos 1 (2%) 0
Hamza 29 0 29 (100%) 0 2 (7%) 3 d 15 mos 1 (3%) 0
Melman 38 1 (3%) 35 (92%) 1 (3%) 1 (3%) 9 d 10 mos 10 (25%) 0
Barragan 8 0 8 (100%) 0 0 6 d NR 0 0
Obermeyer 6 0 6 (100%) 0 0 5 d 44 mos 1 (17%) 0
Mori 14 0 14 (100%) 1 (7%) 1 (7%) NR NR NR 0
Saluja 20 0 20 (100%) 0 0 5 d 24 mos 2 (10%) 0
Robin 119 2 (1.7%) 111 (93%) 4 (3.4%) 9 (7.6%) 10 d 12 mos 36 (30%) 2 (1.7%)
Martinez 111 6 (5%) 111 (100%) 0 7 (6%) NR NR 25 (23%) 2 (1%)
Marino 48 0 44 (92%) 5 (10%) 0 10 d NR 5 (10%) 0
Gerin 11 1 (9%) 11 (100%) 0 1 (9%) 16 d 10 mos 2 (18%) 0
Crisanto 20 0 19 (94%) 0 0 7 d 40 mos 1 (6%) 0
Simo 22 0 22 (100%) 0 0 14 d 2 mos 1 (4.5%) 0
Ramachandran 5 0 5 (100%) 0 0 4 d 12 mos 0 0
Oida 7 0 7 (100%) 0 0 8 d 65 mos 0 0
Kulkarni 22 0 20 (90%) 1 (4.5%) 1 (4.5%) 7 d 12 mos 7 (32%) 0
Malik 12 0 12 (100%) 0 0 4 d NR 2 (17%) 0
Yoder 13 1 (8%) 12 (92%) 1 (8%) 0 4.5 d NR 1 (8%) 0
Driedger 178 6 (3%) NR 23 (13%) 12 (7%) 8 d 21 mos 68 (38%) 4 (2%)
Total 1101
*Resolution was defined as success after a single procedure.
NR indicates not reported.

TABLE 2. - Results of Endoscopic Cystenterostomy
Author n Bleeding Resolution* Reintervention Recurrence LOS Follow-up Morbidity Mortality
Teoh 59 3 (5%) NR 20 (34%) 2 (3.4%) 11 d 11 mos 5 (8.4%) 2 (3%)
Shekhar 100 4 (4%) 89 (89%) 11 (11%) 1 (1%) NR 12 mos 9 (9%) 0
Melman 45 2 (4%) 23 (51%) 16 (36%) NR NR NR 7 (16%) 0
Rasmussen 22 NR 13 (59%) 9 (41%) 4 (18%) NR NR NR 0
Yamamoto 9 1 (11%) 7 (78%) 2 (22%) NR NR NR 2 (22%) 0
Attam 10 1 (10%) 9 (90%) 10 (100%) 2 (20%) NR NR 3 (30%) 1 (10%)
Nelsen 5 0 2 (40%) 0 3 (60%) NR 10 mos 0 0
Sharaiha 124 2 (1.6%) NR 30 (24%) 6 (5%) NR 3 mos 23 (19%) 0
Will 27 1 (4%) NR 27 (100%) NR NR NR 3 (11%) 1 (3.7%)
Ahlawat 12 0 NR 3 (25%) 2 (17%) NR 4 mos 3 (25%) 0
Xu 108 6 (5.5%) NR 8 (7%) 9 (8.3%) NR 6 mos 8 (7%) 4 (3.7%)
Gambitta 91 1 (1%) 73 (80%) 24 (26%) 17 (19%) NR NR 5 (5%) 2 (2%)
Laique 88 2 (2%) 70 (80%) 10 (11%) 6 (7%) 6 d 14 mos 19 (22%) 2 (2%)
Garg 30 3 (10%) 23 (77%) 27 (90%) 5 (17%) NR 22 mos 7 (23%) 0
Shin 27 2 (7%) NR NR 9 (30%) NR 8 mos 6 (22%) 0
Saluja 35 0 27 (78%) 6 (17%) NR 6 d 24 mos 10 (29%) 0
Yamauchi 36 NR NR NR NR NR 56 mos 20 (56%) 2 (6%)
Yao 125 5 (4%) 113(90%) 17 (14%) 3 (2.4%) NR 26 mos 24 (19%) 2 (1.6%)
Yang 205 NR 186 (91%) 19 (9%) 29 (14%) 5 d 6 mos 28 (13%) 0
Puga 41 6 (15%) NR NR NR NR 29 mos 11 (27%) 0
Venkata 116 1 (0.8%) 110 (95%) 8 (7%) 1 (0.8%) 3 d 6 mos 13 (11%) 4 (3.4%)
Brimhall 249 20 (8%) 134 (54%) 11 (4.4%) 13 (5.2%) NR NR 51 (20%) 2 (0.8%)
Ge 52 2 (4%) NR 8 (15%) NR 8 d NR 4 (8%) 0
Keane 109 2 (2%) 76 (70%) 31 (28%) 8 (7%) 4 d 11 mos 13 (12%) 0
Siddiqui 80 6 (7.5%) 72 (90%) 60 (75%) 1 (1%) NR 8 mos 13 (16%) NR
Yuan 47 NR NR NR 3 (6%) 11 d 48 mos 18 (38%) 0
Bapaye 21 1 (5%) 21 (100%) 1 (5%) 0 NR 1.5 mos 2 (10%) 0
Walter 61 4 (7%) 51 (83%) 23 (38%) NR NR NR 21 (34%) 0
Chandran 47 3 (5.5%) 36 (77%) 10 (21%) 4 (8.5%) NR 8 mos 26 (55%) 4 (8.5%)
Lin 90 4 (4%) 85 (94%) 7 (8%) 5 (5.5%) 10 d 48 mos 13 (14%) 0
Ng 61 1 (2%) 46 (75%) 13 (21%) 6 (10%) NR 11 mos 16 (26%) 0
Due 10 NR 6 (60%) 4 (40%) 4 (40%) NR 4 mos 4 (40%) 1 (10%)
Bang 122 3 (2%) 102 (84%) 21 (17%) NR NR NR 7 (6%) 1 (1%)
Mukai 89 2 (2%) 70 (79%) 37 (42%) NR NR 24 mos 11 (12%) 3 (3%)
Smoczynski 97 19 (20%) 78 (80%) 35 (36%) 19 (20%) 29 d 31 mos 29 (30%) 2 (2%)
Kato 67 NR NR 11 (16%) 16 (24%) NR 34 mos 1 (1.5%) 0
Binmoeller 14 1 (7%) 11 (79%) 5 (36%) NR NR 3 mos 3 (21%) 0
Rische 40 NR NR 106 (265%)† 4 (10%) 30 d 31 mos 14 (35%) 3 (7.5%)
Weilert 18 0 14 (78%) 8 (44%) NR NR NR 6 (33%) 3 (17%)
Fabbri 20 NR 17 (85%) 2 (10%) 1 (5%) NR 20 mos 3 (15%) 0
Puri 40 1 (2.5%) 39 (98%) 1 (2.5%) 1 (2.5%) NR 48 mos 3 (8%) 0
Seewald 80 12 (15%) 58 (73%) 22 (28%) 9 (11%) NR 31 mos 21 (26%) 0
Varadarajulu 211 3 (1%) 180 (85%) 34 (16%) NR 3 d 12 mos 17 (8%) 5 (2%)
Ahn 47 1 (2%) 42 (89%) 7 (15%) 5/41 (12%) NR 17 mos 5 (11%) 0
Gornals 19 0 NR 13 (68%) 3 (16%) NR 12 mos 5 26%) 0
Cavallini 55 2 (4%) 43 (78%) 12 (22%) 8 (14%) NR 34 mos 9 (16%) 1 (1.8%)
Sharma 144 8 (5.5%) 140 (97%) 24 (17%) 13 (9%) NR 18 mos 26 (18%) 1 (0.7%)
Petrone 67 5 (7%) NR 14 (21%) 2 (3%) NR NR 16 (24%) NR
Aburajab 47 0 44 (94%) 4 (8.5%) 4 (9%) NR NR 12 (26%) 0
Ruckert 51 2 (4%) 22 (43%) 25 (49%) 7/30 (23%) NR 42 mos 16 (31%) 3 (6%)
Wantanabe 103 2 (2%) 80 (78%) 37 (36%) 10/75(13%) NR 38 mos 15 (15%) 3 (3%)
Nabi 30 4 (13%) 28 (93%) 7 (23%) 2 (7%) NR 28 mos 10 (33%) 0
Ang 49 1 (2%) 36 (73%) 21 (43%) NR NR NR 5 (10%) 0
Vazquez 211 15 (7%) 178 (84%) 33 (16%) NR NR NR 44 (21%) NR
Thompson 60 8 (13%) 52 (86%) 21 (35%) 8 (13%) NR 17 mos NR 0
Dhir 47 NR 42 (89%) 12 (26%) 2 (4%) NR 10 mos 4 (9%) 0
Fugazza 311 22 (7%) 272 (87%) 56 (18%) 27 (9%) NR 5 mos 74 (24%) 2 (0.6%)
Parsa 306 12 (4%) 281 (92%) 45 (15%) NR 13 d 6 mos 53 (17%) 0
Total 4487
*Resolution was defined as success after a single procedure
†Every patient had at least 2 repeat interventions.
NR indicates not reported

The patients within the endoscopy and surgery groups were comparable, with similar age (surgery mean 48 years, CI, 44–52, endoscopy mean 51 years, CI, 49–53), gender (surgery males 69%, CI, 62–75%, endoscopy males 68%, CI, 65–71%), and percentage of the group having alcohol as the etiology of their pancreatitis (surgery 29%, CI, 23–35%, endoscopy 37%, CI, 32–42%). See Table 3 for results from significance tests comparing these patient populations, and see Tables 4 and 5 for raw data.

TABLE 3. - Demographics Comparison
Surgery Endoscopy P
Mean age 48, CI, 44–52 51, CI, 49–53 0.12
Male gender 69%, CI, 62–75 68%, CI, 65–71 0.87
Alcohol etiology 29%, CI, 23–35 37%, CI, 32–42 0.06

TABLE 4. - Demographics of Surgical Cystenterostomy
n Mean Age Gender % Male Alcohol Etiology(%)
Boutros 19 56 63 42
Palanivelu 100 44 70 19
Yin 12 38 64 46
Hauters 12 46 42
Parks 28 50 55 33
Hindmarsh 15 59 33 20
Bansal 134 36 86 25
Khaled 54 53 70 40
Gibson 44 54 66 32
Hamza 29 53 64 39
Melman 38 49 55
Barragan 8
Obermeyer 6 39 67 33
Mori 14 55 79 29
Saluja 20 37
Robin 119 52 90 45
Martinez 111 74
Marino 48 48
Gerin 11 61 67 23
Crisanto 20 40 54 18
Simo 22 51 65 29
Ramachandran 5 56 55 14
Oida 7 61 60 0
Kulkarni 22 51 100 71
Malik 12 52 59 14
Yoder 13 10 75 0
Driedger 178 51 64 31
Total 1101

TABLE 5. - Demographics of Endoscopic Cystenterostomy
Author n Mean age Gender % Male Alcohol Etiology (%)
Teoh 59 45 81 34
Shekhar 100 56 59 38
Melman 45 52 71
Rasmussen 22 51 59 41
Yamamoto 9
Attam 10 53 80 10
Nelsen 5 57 100
Sharaiha 124
Will 27
Ahlawat 12
Xu 108 52 56 18
Gambitta 91
Laique 88 53 60 48
Garg 30 38 73 27
Shin 27 56 81
Saluja 35 37 80 34
Yamauchi 36 54 83 47
Yao 125 48 66
Yang 205 55 63 32
Puga 41
Venkata 116 53 67 36
Brimhall 249 48 65 31
Ge 52 50 56
Keane 109 55 55 19
Siddiqui 80
Yuan 47 48 62 43
Bapaye 21 47 86 63
Walter 61
Chandran 47 51 68 38
Lin 90 49 67 16
Ng 61 49 70 66
Due 10 53 80
Bang 122 49 52 38
Mukai 89 56 81 56
Smoczynski 97
Kato 67 56 75
Binmoeller 14 50 64 50
Rische 40 56 75
Weilert 18 50 67 44
Fabbri 20 57 85 35
Puri 40 39 78 60
Seewald 80 56 61 10
Varadarajulu 211 48 58 33
Ahn 47 46 85 68
Gornals 19 57 68 32
Cavallini 55 54 55 4
Sharma 144 36 82 47
Petrone 67 59 69 12
Aburajab 47
Ruckert 51
Wantanabe 103 55 71 50
Nabi 30 73
Ang 49 53 51
Vazquez 211
Thompson 60 54 60 28
Dhir 47
Fugazza 311
Parsa 306 55 70
Total 4487

For the outcome of postprocedure bleeding complications, the percentage of surgical patients with a bleeding complication was 1.8% (CI, 0.0097–0.0342) and for endoscopy was 4.3% (CI, 0.0337–0.0558). There was a significantly decreased risk of postoperative bleeding after surgery, with a log odds ratio of –0.906 (SE 0.362, P = 0.012; see Figs. 1 and 2).

FIGURE 1.
FIGURE 1.:
Estimated odds ratio of each parameter listed for surgery compared to endoscopy.
FIGURE 2.
FIGURE 2.:
Estimated proportion of each parameter listed for surgery compared to endoscopy.

When comparing the chance of complete pseudocyst resolution after having surgery as compared to endoscopic intervention, surgical patients had complete resolution of their cyst 98.5% (CI, 0.959–0.995) of the time, compared to 83.5% (CI, 0.796–0.868) after endoscopic interventions. There was a much higher chance of having complete pseudocyst resolution after surgery, with a log odds ratio of 2.64 (SE 0.582, P < 0.0001).

In terms of repeat interventions postprocedure, including repeat interventions to drain persistent fluid collections, repeat interventions for bleeding, occluded stents, abscesses, or other complications, the risk of repeat interventions after surgical drainage was 3.9% (CI, 0.0266–0.0572) and after endoscopic procedures was 25.8% (CI, 0.1934–0.3354). This does not include repeat endoscopic intervention for planned stent removal after pseudocyst resolution, which is an expected event. Thus, surgical patients were at a greatly reduced chance of requiring any type of reintervention with a log odds ratio of –3.33 (SE 0.508; P < 0.0001).

The risk of pseudocyst recurrence, when given as a statistic, must be indexed for the length of time that a patient is followed, as the risk increases over time. Without this adjustment, the results would be skewed in favor of the group with shorter follow-up because pancreatitis tends to be a chronic and recurrent disease. Therefore, the results of pseudocyst recurrence are examined in conjunction with length of follow-up. The surgical patients had much longer follow-up, with a mean of 34.0 months (CI, 20.5–47.3). Mean endoscopic follow up was 19.4 months (CI, 15.0–23.8). The difference was small, but statistically significant (P = 0.04). However, despite the longer follow-up in the surgical group, the recurrence risk was much less at 2.3% (CI, 0.0124–0.0439) compared with the recurrence risk with endoscopic intervention, which was 8.8% (CI, 0.0679–0.1130). Thus, even taking into account the differences in follow-up, the risk of pseudocyst recurrence is much less with surgical cystogastrostomy, with a log odds ratio of –1.405 (SE 0.366, P < 0.001).

Although surgical cystogastrostomy is often cited as “more risky” than endoscopic therapy, the overall morbidity with surgery was actually less than with endoscopic stenting (13.5%, CI, 0.0934–0.1913 versus 17.8%, CI, 0.1509–0.2089). The log odds ratio slightly favored surgery at –0.326, although not statistically significant (SE 0.232, P = 0.16). Both procedures had a very low mortality, with surgery slightly less at 0.5% (CI, 0.00121–0.0201) compared with endoscopic interventions at 0.9% (CI, 0.0051–0.0157). Again the log odds ratio slightly favored surgery at –0.673 but was not significant (SE 0.943, P = 0.48).

There was no significant differences in postprocedure length of hospital stay, with a mean length of stay after surgery of 7.1 days (CI, 5.9–8.4) and a mean length of stay after endoscopic interventions of 9.4 days (CI, 4.2–14.5, P value for the difference = 0.61).

DISCUSSION

Despite the common assumption, the endoscopic therapy is safer and less morbid than surgical intervention on the pancreas; the results of this study overwhelmingly favor surgery for several important endpoints. The data could be used to challenge the assumption that surgery can always be performed if endoscopic therapy fails, as this logic is clearly flawed. Failed endoscopic therapy increases the chances of bleeding, prolongs the duration of sepsis for IPFCs, and has a greater morbidity than surgical intervention alone. Other authors have also shown that a patient’s risk of complications goes up when surgery is performed after failed endoscopic therapy, as opposed to those who went directly to surgery.36

From a pathophysiological perspective, a large surgical cystogastrostomy will allow ongoing pancreatic fluid from ductal disruption to drain into the stomach until the pancreas heals. In those patients who develop a pancreatic pseudocyst due to a significant disruption in the duct of Santorini or the duct of Wirsung, an ongoing pancreatic leak and fistula can be expected, and are slow to heal even if the duct is stented by ERCP.93 For these patients who have had a surgical cystogastrostomy or cystoduodenostomy, the ongoing fistula will continue to drain into the foregut and the output will be controlled internally. However, if these patients were treated by an endoscopic stent, the stent will need to remain in place indefinitely until the leak resolves, which can take up to 13 months or longer93,105 Some authors even recommend leaving the stents in place indefinitely.106 This is problematic since the longer a stent stays in place, the higher the complication rate from erosion into the surrounding vessels or viscera.65,67,71,75,84,88

Historically, all pseudocyst walls are biopsied at the time of cystogastrostomy creation to ensure that the pseudocyst is not really a cystadenocarcinoma of the pancreas. In all of the endoscopic series reviewed in this article, very few of the endoscopic reports described performing a biopsy at the time of cystogastrostomy creation. Other authors have recommended sampling and testing the cyst fluid for carcinoembryonic antigen or CA 19-9 to ensure no malignancy is present.94 While the risk of missing a cancer is considered low, it is not zero, and cases of pancreatic cancer are still being reported from presumed pseudocysts.95,107,108 A recent report found a 1.8% incidence of pancreatic cancer by brush cytology of WOPN, while another found a frequency of 1.25% in peripancreatic fluid collections.96,109

Many endoscopic cystogastrostomy studies document “clinical success,” which they define as symptomatic improvement only, although some authors consider “success” to be any decrease in the size of the pseudocyst by more than 1 cm.75 Other authors have defined “clinical success” to be resolution of symptoms and a decrease in the size of the pseudocyst by >40%.80 While other authors define success as the pseudocyst shrinking to less than 3 cm.67 Others think that clinical success is a size reduction of >50% or to a size <5 cm.83,110 While still other authors feel that clinical success is defined by “a distinct decrease in the size of the cyst after a drainage period of six months.”97 This variable and misleading idea of success leads to the propagation of the belief that endoscopic techniques are more successful than they actually are. We only found 5 endoscopic reports that documented follow-up CT scans or ultrasound imaging in all of their patients.22,24,91,97,98 Not surprisingly, all of these studies reported very high rates of reintervention for the persistent pseudocysts. Not only is the idea of “clinical success” misleading, but it also can be dangerous since we know from the natural history of pseudocysts that their persistence often leads to vascular erosion and hemorrhage, as one of the authors has previously reported.111 The presence of metal stents within the pseudocyst also appears to significantly increase the risk of hemorrhage.24,99,100,109

Multiple studies from the literature show that endoscopic stenting nearly always fails when there is greater than 50% parenchymal necrosis.101,112,113 Three multicenter trials in patients with primary pancreatic necrosis found that attempts at endoscopic necrosectomy had very high morbidity (26%–33%) and mortality rates (6%–11%).112–114 Another recent multicenter study involving 333 endoscopic procedures for peripancreatic fluid collections, many with a large necrotic component, found an adverse event rate of 24%.102 Thus, while endoscopic cystogastrostomy with stenting is useful for PP that are purely cystic with minimal necrotic debris, any IPFC or WON with a large solid or granular component or >50% parenchymal necrosis will be better served going directly to surgery. Surgery as primary therapy has less morbidity, mortality, recurrence, reintervention, and greater resolution than endoscopic treatments.

This study is limited by the fact that most of the reviewed articles included in the analysis were retrospective studies, and only a few were prospective trials. Thus, the analysis carries over the retrospective biases present in the original articles, including potential confounding variables and selection bias due to nonrandomization. All of the results can be interpreted as associational. However, the causal interpretation should be further assessed. Also, grouping together the disease processes into 1 large group may lead to potential bias. For example, if a majority of papers focus on a specific type of peripancreatic fluid collection, then the results will also be weighted toward results from that process. We did find, fortunately, that the results are not strongly influenced by any single paper within the study.

This article has ramifications for policy makers, administrators, and those institutions that have begun to follow a step-up approach to IPFCs, since endoscopic therapy is not a benign procedure and carries greater morbidity and mortality risk than surgery for the creation of a cystogastrostomy.

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