Open Versus Laparoscopic Appendectomy: A Post Hoc Analysis of the EAST Appendicitis MUSTANG Study

Abstract

Background:

We sought to understand which factors are associated with open appendectomy as final operative approach. We hypothesize that higher American Association for the Surgery of Trauma (AAST) Emergency General Surgery (EGS) grade is associated with open appendectomy.

Patients and Methods:

Post hoc analysis of the Eastern Association for the Surgery of Trauma (EAST) Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated and Gangrenous (MUSTANG) prospective appendicitis database was performed. All adults (age >18) undergoing appendectomy were stratified by final operative approach: laparoscopic or open appendectomy (including conversion from laparoscopic). Univariable analysis was performed to compare group characteristics and outcomes, and multivariable logistic regression was performed to identify demographic, clinical, or radiologic factors associated with open appendectomy.

Results:

A total of 3,019 cases were analyzed. One hundred seventy-five (5.8%) patients underwent open appendectomy, including 127 converted from laparoscopic to open. The median age was 37 (25) years and 53% were male. Compared with the laparoscopic group, open appendectomy patients had more comorbidities, higher proportion of symptoms greater than 96 hours, and higher AAST EGS grade. Moreover, on intraoperative findings, the open appendectomy group had a higher incidence of perforated and gangrenous appendicitis with purulent contamination, abscess/phlegmon, and purulent abdominal/pelvic fluid. On multivariable analysis controlling for comorbidities, clinical and imaging AAST grade, duration of symptoms, and intra-operative findings, only AAST Clinical Grade 5 appendicitis was independently associated with open appendectomy (odds ratio [OR], 5.63; 95% confidence interval [CI], 1.24–25.55; p = 0.025).

Conclusions:

In the setting of appendicitis, generalized peritonitis (AAST Clinical Grade 5) is independently associated with greater odds of open appendectomy.

Open appendectomy was the standard procedure for appendiceal resection until the late 1980s when the laparoscopic approach was introduced by Semm.^1,2 Laparoscopic appendectomy has several advantages, including smaller incisions, decreased post-operative pain, and more rapid recovery.^3–5 Furthermore, overall outcomes, length of stay (LOS), and post-operative complications have all been reported to be superior with the laparoscopic approach.^6–14

Several studies have aimed to establish clinical and diagnostic predictors of appendicitis disease severity and have sought to identify patients at highest risk for conversion from a laparoscopic to an open approach.^15–17 However, there is a lack of high-quality evidence regarding that patients will fail laparoscopy and should undergo initial open management instead. Furthermore, there are no specific guidelines from surgical societies to facilitate the decision of optimal appendectomy approach.^18–20

Our study aims to evaluate clinical and diagnostic factors associated with open appendectomy for the surgical management of appendicitis. We hypothesize that a higher American Association for the Surgery of Trauma (AAST) Emergency General Surgery (EGS) grade is associated with open appendectomy.

Patients and Methods

This was a post hoc analysis of the Eastern Association for the Surgery of Trauma (EAST) Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated and Gangrenous (MUSTANG) study.²¹ Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed appendicitis between January 26, 2017, and June 30, 2018, were prospectively enrolled. There were 28 participating centers across the United States. Most local Institutional Review Boards granted a waiver of informed consent, whereas some required informed consent for participation in the study. For the present study, we included all patients who underwent laparoscopic or open appendectomy, including those requiring an open extended resection, and those with suspected appendicitis on presentation, even if the final pathology demonstrated normal appendix, adenocarcinoma, or neuroendocrine (carcinoid) tumor. We excluded those patients who did not have a laparoscopic or open appendectomy during the index hospitalization and those with missing data. The primary outcome was open appendectomy as the final operative approach. Additionally, we assessed patient-specific comorbid medical conditions, immunosuppressant medication use, duration of symptoms, time from symptom onset to hospital intervention, time from emergency department triage to hospital intervention, and intra-operative findings.

Patients were divided into two cohorts based on the final operative approach: laparoscopic surgery and open appendectomy (including laparoscopic converted to open appendectomy). The open surgical approach included both right lower quadrant and midline laparotomy incisions. Demographic data during index hospitalization included age, gender, body mass index (BMI), white blood cell count, comorbid medical conditions, Charlson comorbidity index (CCI), and use of steroids, chemotherapy, or other immunosuppressant medications. History of present illness data, including duration of symptoms (defined as the time from the onset of symptoms to presentation to the emergency department), time from symptom onset to initial intervention (recorded in six-hour intervals up to 96 hours), time from emergency department triage to initial intervention (recorded in six-hour intervals up to 96 hours) and the AAST appendicitis severity grading scale were measured.

The AAST grading system for acute appendicitis has five components that include descriptive, clinical, imaging, operative, and pathologic criteria.²² The grades range based on the severity from 1 through 5 for each component, representing the evolution from mild localized disease to severe, widespread disease.²² In our study, the AAST grading scale was recorded for only clinical and imaging.²² The initial intervention was defined as antibiotic agents or an operative procedure, and operative data included intra-operative findings described by the surgeon and operative approach.

Descriptive statistics were calculated for continuous and categorical variables. Categorical variables are reported as frequencies (percentages). Continuous variables are reported as mean ± standard deviation and median (interquartile range [IQR]) for parametric and non-parametric data, respectively. Categorical data were analyzed using the χ² test or Fisher exact test. Student t-test or Mann-Whitney U test was used for continuous variables, as indicated. Multivariable logistic regression models were constructed for the primary outcome, adjusting for diabetes mellitus (DM), hypercholesterolemia, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), AAST clinical and imaging grades, duration of symptoms, intra-operative findings of perforated appendicitis with purulent contamination, and perforated or gangrenous appendicitis with abscess or phlegmon. Adjusted odds ratios and 95% confidence intervals are reported for regression models. A p value <0.05 was considered statistically significant. Statistical analysis was performed using SPSS Statistics, version 28 (IBM Corp, Armonk, NY). Results are reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement per recommendations by the EQUATOR network (Supplemental Table S1).²³

Results

Of 3,597 subjects enrolled at 28 sites, 3,019 were included in our analysis. A total of 574 patients were excluded because of missing data, two patients were excluded as they underwent robotic-laparoscopic assisted appendectomy, one patient was excluded after undergoing a sigmoid colon resection, and one patient was excluded because their appendectomy was aborted with surgical drain placement instead. The median age was 37 (25) years, and most were male (52.9%). A total of 2,844 (94.2%) were treated with laparoscopic appendectomy, and 175 (5.8%) patients underwent open appendectomy, including 127 converted from laparoscopic to open. Table 1 shows the demographics of the laparoscopic and open groups. Compared with the laparoscopic group, the open surgery group had a higher percentage of patients taking steroids and with DM, CHF, COPD, and hypercholesterolemia as comorbid conditions. The CCI was also higher in the open group. There was no difference between the two groups regarding body mass index (BMI), the prevalence of coronary artery disease (CAD) or the use of chemotherapeutic or other immunosuppressant drugs (Table 1).

Table 1.

Admission Characteristics

	All (n = 3,019)	Open (n = 175)	Laparoscopic (n = 2,844)	p
Age (y)	37 (25)	49 (27)	37 (25)	< 0.001
Male (%)	52.9%	58.3%	52.6%	0.144
Tobacco use	18.4%	24.6%	18%	0.004
BMI	28.6 ± 6.6	28.8 ± 6.7	28.62 ± 6.6	0.302
WBC count (10³/mcL)	13.6 ± 4.4	14.7 ± 4.7	13.5 ± 4.4	< 0.001
Diabetes mellitus	7.5%	20.6%	6.6%	< 0.001
CAD	3.1%	5.1%	3.0%	0.111
CHF	1.2%	3.4%	1.1%	0.018
COPD	2.5%	6.3%	2.3%	0.004
Hypercholesterolemia	10.8%	20%	10.2%	< 0.001
Chemotherapy	0.6%	0.6%	0.6%	1.000
Steroids	1.9%	4.0%	1.7%	0.041
Other immunosuppressant drugs	1.7%	0.6%	1.7%	0.364
CCI	0 (1)	1 (3)	0 (1)	< 0.001

Open approach includes right lower quadrant and midline laparotomy incisions.

BMI = body mass index; WBC = white blood cell; CAD = coronary artery disease; CHF = congestive heart failure; COPD = chronic obstructive pulmonary disease; CCI = Charlson comorbidity index.

In the open group, there was a higher proportion of patients presenting with a symptom duration greater than 96 hours, higher AAST EGS clinical and imaging grades, and higher incidence of perforated and gangrenous appendicitis with local or pelvic purulent contamination, abscess or phlegmonous changes as determined by the surgeon (Table 2). The laparoscopic group had a higher incidence of intact acutely inflamed or gangrenous appendix as an intra-operative finding; however, there was no difference between the groups for normal-appearing appendix or serous abdominal/pelvic fluid.

Table 2.

Symptom Duration, History of Present Illness, Imaging Studies, and Operative Findings

	Open (n = 175)	Laparoscopic (n = 2,844)	p
Time from symptom onset to initial intervention >96 h	31.4%	9.5%	< 0.001
Symptom duration >96 h	28%	8.1%	< 0.001
Clinical AAST Grade:			< 0.001
Grade 1, 2, 3	88%	98.5%
Grade 4	2.9%	0.3%
Grade 5	9.1%	1.2%
Imaging AAST Grade:			< 0.001
Grade 1	40.6%	74.4%
Grade 2	0.6%	3.2%
Grade 3	19.4%	15.4%
Grade 4	30.3%	5.7%
Grade 5	9.1%	1.3%
Intraoperative Findings:
Acutely inflamed appendix, intact	27.4%	74.8%	< 0.001
Gangrenous appendix, intact	1.1%	4.3%	0.04
Abscess	12.6%	2.4%	< 0.001
Perforated appendix with purulent contamination	20%	3.0%	< 0.001
Perforated appendix with abscess/phlegmon	23.4%	4.2%	< 0.001
Perforated appendix with local contamination	20%	8.7%	< 0.001
Gangrenous appendix with local contamination	8.0%	3.1%	< 0.001
Gangrenous appendix with abscess/phlegmon	10.9%	1.4%	< 0.001
Gangrenous appendix with purulent contamination away from appendix	9.1%	1.3%	< 0.001
Purulent abdominal/pelvic fluid	21.7%	9.1%	< 0.001
Serous abdominal/pelvic fluid	4.6%	5.8%	0.486

AAST = American Association for the Surgery of Trauma; ED = emergency department; EGS = emergency general surgery; intervention = antibiotics or procedure.

Multiple logistic regression model

In a binomial logistic regression model controlling for DM, CHF, COPD, hypercholesterolemia, AAST Clinical and Image severity grading, duration of symptoms, and intra-operative findings, only AAST Clinical Grade 5 appendicitis, defined as generalized peritonitis, was independently associated with open appendectomy (OR, 5.63; 95% CI, 1.24–25.55; p = 0.025). Pre-existing DM, symptom duration less than 35 hours and between 48 and 53 and 72 and 77 hours, AAST Imaging Grade 2 and 3, intra-operative findings of perforated or gangrenous appendicitis with phlegmon, and intra-operative findings of perforated appendicitis with purulent contamination were associated with a decreased likelihood of open appendectomy (Table 3).

Table 3.

Multiple Logistic Regression for Open Appendectomy

	OR (95% CI)	p
Clinical AAST Grade
Grade 1, 2, 3	—	—
Grade 4	0.571 (0.254–1.287)	.177
Grade 5	5.634 (1.242–25.55)	0.025
Image AAST Grade
Grade 1	—	—
Grade 2	0.330 (0.145–0.751)	0.008
Grade 3	0.098 (0.012–0.824)	0.032
Grade 4	0.521 (0.224–1.210)	0.129
Grade 5	1.036 (0.456–2.358)	0.932
COPD	0.620 (0.280–1.372)	0.238
CHF	0.627 (0.216–1.819)	0.391
DM	0.382 (0.232–0.628)	< 0.001
Hypercholesterolemia	0.810 (0.503–1.303)	0.384
Duration of symptoms, h:
<6	—	—
6–11	0.064 (0.015–0.273)	< 0.001
12–17	0.201 (0.094–0.428)	< 0.001
18–23	0.353 (0.188–0.661)	0.001
24–29	0.142 (0.059–0.342)	< 0.001
30–35	0.407 (0.234–0.709)	0.001
36–41	0.863 (0.311–20.398)	0.778
42–47	0.000 (0.000–0.000)	0.997
48–53	0.363 (0.143–0.922)	0.033
54–59	0.583 (0.332–1.023)	0.060
60–65	0.000 (0.000–0.000)	0.999
66–71	1.798 (0.324–9.986)	0.502
72–77	0.122 (0.015–0.992)	0.049
78–83	0.566 (0.303–1.057)	0.074
84–89	1.682 (0.018–157.816)	0.822
90–96	0.000 (0.000–0.000)	0.999
>96 hours	0.571 (0.120–2.724)	0.482
Intra-operative findings: Perforated appendix with purulent contamination	0.274 (0.158–0.475)	< 0.001
Perforated appendix with abscess/phlegmon	0.416 (0.251–0.687)	< 0.001
Gangrenous appendix with abscess/phlegmon	0.275 (0.139–0.545)	< 0.001

AAST = American Association for the Surgery of Trauma; CHF = congestive heart failure; COPD = chronic obstructive pulmonary disease; DM = diabetes mellitus.

Discussion

The main finding in our study is that patients presenting with generalized peritonitis on physical examination have increased odds of requiring an open appendectomy as their final operative approach. Patients with DM and shorter symptom duration were found to have a decreased likelihood of open appendectomy. Not surprisingly, the intra-operative findings of the group requiring open surgery were more consistent with complicated appendicitis, such as perforated or gangrenous appendicitis with abscess/phlegmon.

We found that patients who underwent an open appendectomy had increased comorbidities, including CHF, COPD, and hypercholesterolemia. Although the causality of appendicitis is multifactorial, it has been suggested that in complicated appendicitis, comorbid disease processes could lead to a modification of the illness.²¹ The individual's response to the disease or even a different pathologic mechanism may be responsible.²¹ It is also possible that severe comorbidities may influence providers' pre-operative decision-making in favor of open appendectomy to reduce the exposure and physiologic impact of pneumoperitoneum.²⁴

Appendicitis is stratified into uncomplicated and complicated, with the former representing appendicitis without signs of perforation, such as mass, phlegmon, or abscess.¹⁵ Numerous studies have examined the diagnostic and clinical predictors of acute appendicitis severity, laparoscopic conversion, and appropriate operative timing, as well as comparing outcomes in laparoscopic versus open surgical management.^{14,16,25–29} Additionally, many studies have highlighted the benefits of the laparoscopic approach demonstrating decreased superficial and deep surgical site infection, wound disruption, hospital length of stay, post-operative pain, and faster return to normal activities with laparoscopic appendectomy compared to open appendectomy.^14,25 With the evolution of laparoscopy in appendicitis management in the last 40 years, this approach has been shown to be safe and effective when used in cases of both uncomplicated and complicated appendicitis.^30,31

Complicated appendicitis, as a definition, remains broad and encompasses a wide range of pathologic presentations, from perforation with or without abscess to generalized peritonitis. Although studies have demonstrated the superiority of laparoscopy in uncomplicated and complicated appendicitis, conversion to open appendectomy rates remain as high as 10%.³² We have identified a subset of patients at risk of failure of laparoscopic resection. Avoiding an initial laparoscopic attempt and proceeding with primary open appendectomy prevents prolonged operative time, general anesthetic exposure, and increased costs.³³

In a randomized controlled trial in Sweden, patients randomly assigned to open or laparoscopic appendectomy had a 12% laparoscopic conversion rate, and those converted to open had extended hospital length of stay, increased duration of sick leave, and longer time until full recovery, along with a longer operative time and general anesthesia exposure in comparison to laparoscopic and open cohorts.¹⁷

Years later, Finnerty et al.³² identified the pre-operative diagnosis of complicated appendicitis as a risk factor for conversion to open appendectomy. Patients who required conversion to an open approach had a higher number of complications, longer hospital length of stay, and higher healthcare costs compared with the laparoscopic-only or open primary approach.³² That study defined complicated appendicitis as appendicitis with either abscess or peritonitis; however, our study restricted this definition, examining patients presenting with generalized peritonitis separately from those with only abscess. Accordingly, we found that generalized peritonitis, not abscess, was independently associated with an increased risk of open appendectomy. This distinction aims to lessen the decision-making burden on the surgeon. Currently, appendicitis with abscess may be appropriately treated with initial nonoperative management with or without percutaneous drainage and with or without interval appendectomy.³⁴ Future work to prospectively compare patients at high risk for failing laparoscopy versus initial open approach is warranted.

Our study has several limitations. First, our study was a post hoc analysis of a prospective observational study and not a randomized controlled trial. Given that this was a retrospective analysis, there is the possibility of both information and selection bias. Additionally, we did not collect information regarding why each surgeon chose an open approach, or why the laparoscopic surgeries were converted to open. Furthermore, data regarding operative time were not collected and therefore we cannot determine whether operative time, particularly in cases that began laparoscopically and were converted to open, affects outcomes. Despite these limitations, our study has numerous strengths. The population used in the study was large and diverse, with data from 28 enrollment sites encompassing both urban and rural hospitals of varying sizes. Additionally, the data collected was specific for patients with appendicitis and sufficiently granular to make comparisons between groups.

Conclusions

In summary, patients requiring open appendectomy have a higher frequency of medical comorbidities, higher CCI and white blood cell count, and more severe clinical and imaging AAST grades on presentation. Patients who present with suspected or confirmed appendicitis and generalized peritonitis on physical examination have an increased likelihood of requiring open appendectomy in comparison to laparoscopy. Although these findings suggest that an initial open operative approach for patients presenting with these characteristics may be prudent, a prospective interventional study would be required to confirm these findings. Ultimately, the decision regarding the initial approach rests with the operating surgeon.

Footnotes

Acknowledgments

We are appreciative of the EAST Appendicitis Study group (alphabetically by center): Baystate Medical Center: Drs. Reginald Alouidor and Kailyn Kwong Hing; Beaumont Hospital: Drs. Victoria Sharp and Thomas Serena; Boston Medical Center: Drs. George Kasotakis and Sean Perez; Carilion Clinic: Drs. Stacie L. Allmond and Bruce Long; Cooper University Hospital: Drs. Nadine Barth and Janika San Roman; Denver Health: Drs. Ryan A. Lawless and Alexis L. Cralley; Emory University: Drs. Rondi Gelbard and Crystal Szczepanski; Essentia Health: Drs. Steven Eyer and Kaitlyn Proul; Geisinger Medical Center: Drs. Jeffrey Wild and Katelyn A.Young; Inova Fairfax: Drs. Erik J. Teicher and Elena Lita; Intermountain Medical Center: Drs. David Morris and Laura Juarez; Loma Linda University: Drs. Richard D. Catalano and David Turay; Marshfield Clinic: Drs. Daniel C. Cullinane and Jennifer C. Roberts; Massachusetts General Hospital: Drs. Haytham M.A. Kaafarani and Ahmed I. Eid; Mayo Clinic: Drs. Mohamed Ray-Zack and Tala Kana'an; Medical City Plano: Drs. Victor Portillo and Morgan Collom; Medical College of Wisconsin: Drs. Chris Dodgion and Savo Bou Zein Eddine; North Shore Medical Center: Drs. Maryam B. Tabrizi and Ahmed Elsayed Mohammed Elsharkawy; Ryder Trauma Center: Drs. D. Dante Yeh and Georgia Vasileiou; Ohio State University Wexner Medical Center: Drs. David C. Evans and Daniel E. Vazquez; St. Vincent Hospital Indianapolis: Drs. Jonathan Saxe and Lewis Jacobson; Oregon Health Sciences University: Drs. Brandon Behrens and Martin Schreiber; University of Arizona, Tucson: Drs. Bellal Joseph and Muhammad Zeeshan; University of California, Irvine: Drs. Jeffry Nahmias and Beatrice Sun; University of Florida, Jacksonville: Drs. Marie Crandall and Jennifer Mull; University of Maryland: Drs. Jason D. Pasley and Lindsay O'Meara University of Southern California: Drs. Ali Fuat Kann Gok and Jocelyn To; Walter Reed National Military Medical Center: Drs. Carlos Rodriguez and Matthew Bradley.

Authors' Contributions

Methodology: Thompson. Formal analysis: Thompson, Cohen, Wolde, Ramsey. Writing—original draft: Thompson. Writing—review and editing: Cohen, Wolde, Yeh, Ramsey, Byers, Namias, Meizoso. Resources: Yeh, Namias, Meizoso. Supervision: Yeh, Byers, Namias, Meizoso.

Funding Information

This work has not received any funding.

Author Disclosure Statement

The authors have no conflicts of interest to disclose pertaining to the published work. Dr. Meizoso receives research support from Takeda Pharmaceuticals for unrelated work. Dr. Yeh receives author royalties from UpToDate and has received an honorarium from Takeda, the Society of Critical Care Medicine (SCCM), Fresenius- Kabi and the American Society for Parenteral and Enteral Nutrition (ASPEN) for panelist participation or teaching. Dr. Namias serves on the Merck and Eli Lilly advisory board. Dr. Byers serves on the Takeda pharmaceuticals advisory board.

Supplementary Material

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