- Email: [email protected]
Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?
HPB
http://dx.doi.org/10.1016/j.hpb.2016.10.006
ORIGINAL ARTICLE
Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant? Jarrod K.H. Tan1, Joel C.I. Goh2, Janice W.L. Lim2, Iyer G. Shridhar1, Krishnakumar Madhavan1 & Alfred W.C. Kow1 1
Division of Hepatopancreaticobiliary Surgery and Liver Transplantation, Department of Surgery, National University Health System, and 2Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Abstract Background: Studies have shown that same admission laparoscopic cholecystectomy (SALC) is superior to delayed laparoscopic cholecystectomy for acute cholecystitis (AC). While some proposed a“golden 72-hour” for SALC, the optimal timing remains controversial. The aim of the study was to compare the outcomes of SALC in AC patients with different time intervals from symptom onset. Methods: A retrospective analysis of 311 patients who underwent SALC for AC from June 2010–June 2015 was performed. Patients were divided into three groups based on the time interval between symptom onset and surgery: <4 days (E-SALC), 4–7 days (M-SALC), >7 (L-SALC). Results: The mean duration of symptoms was 2(1–3), 5(4–7) and 9 (8–13) days for E-SALC, M-SALC and L-SALC, respectively (p < 0.001). Conversion rates were higher in the L-SALC group [E-SALC, 8.2% vs M-SALC, 9.6% vs L-SALC, 21.4%] (p = 0.048). The total length of stay was longer in patients with longer symptom duration [E-SALC, 4 (2–33) vs M-SALC, 2 (2–23) vs L-SALC, 7 (2–49)] (p < 0.001). Conclusion: Patients with AC presenting beyond 7 days of symptoms have higher conversion rates and longer length of stay associated with SALC. However, patients with less than a week of symptoms should be offered SALC. Received 4 September 2016; accepted 12 October 2016
Correspondence Alfred W.C. Kow, Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, University Surgical Cluster, National University Hospital, 1E, Kent Ridge Road, NUHS Tower Block, Level 8, 119228, Singapore. E-mail: [email protected]
Introduction The management of acute cholecystitis (AC) has undergone a paradigm shift in recent years, with an increasing preference for same admission (SALC) over delayed (DLC) laparoscopic cholecystectomy.1 Existing literature has convincingly shown that compared to DLC, SALC decreases overall hospital length of stay and eliminates the risks of gallstone-related morbidity while waiting for surgery, and achieves similar conversion rates and post-operative outcomes.2–6 Nevertheless, the optimal timing of SALC based on the onset of symptoms remains controversial. Zhu et al. proposed a “golden 72 hour” period as the ideal timing for SALC, beyond which organized adhesions secondary to gallbladder inflammation form within the Calot’s triangle, rendering surgical dissection more difficult.7 While most studies remain retrospective in
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nature, early SALC from within 24–72 h of symptom onset has been associated with decreased intra-operative morbidity, with a resultant shorter hospital length of stay.8–11 With increasing proficiency in minimally invasive surgery (MIS) in recent years, SALC becomes an attractive option for patients with acute cholecystitis. Existing studies that analyze the learning curve of LC have established a significant decrease in duration of operation and post-operative morbidity over the last two to three decades.12 The higher level of expertise and experience in laparoscopic surgery has equipped surgeons with more confidence in handling the potential challenges of a difficult LC for AC in patients who present beyond 72 h of symptoms. The aim of this study was to establish the safety and effectiveness of SALC in patients with AC who presented with different time interval from symptom onset.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
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Methods
Results
A retrospective review of all patients who underwent SALC for AC from June 2010 to June 2015 in the National University Hospital of Singapore was performed. The diagnosis of AC in patients was made based on the criteria outlined in the Tokyo Guidelines, with subsequent histopathological confirmation. A total of 311 patients who underwent SALC were included in the data analysis. Patients with AC who underwent SALC were divided into three groups according to the time interval between symptom onset and surgical intervention: (i) within 3 days (E-SALC), (ii) between 4 and 7 days (M-SALC) and (iii) more than 7 days (LSALC). This was derived via existing electronic records that accurately document patient history and clinical findings. As the early symptoms of AC may be non-specific, symptoms were taken into account at their earliest onset and patients with existing symptoms of more than 2 weeks prior to LC were excluded from this study. Broad-spectrum intravenous antibiotic therapy (intravenous 3rd generation cephalosporin and metronidazole) was administered to all patients once the diagnosis of AC was made. All surgeons involved in the operations were at least consultant specialist surgeons, with extensive experience in hepatobiliary and minimally invasive surgery. The standard four-trocar technique was performed for all LC, with a 10 mm port placed through open technique in the subumbilical/transumbilical region under direct vision, and three 5 mm epigastrium and lateral working ports inserted after the establishment of pneumoperitoneum. A Kocher’s or upper midline incision was made should a conversion be required. The decision between a conversion and the performance of a subtotal cholecystectomy was left to the discretion of individual consultant surgeon based on their assessment of the Calot’s anatomy intra-operatively. Patient demographics collected include age; sex; body mass index (BMI); cardiorespiratory co-morbidities; American Society of Anesthesiologists (ASA) score and previous abdominal surgery. Intra-operative outcome parameters included duration of operation, conversion rates and injury to surrounding organ structures. Post-operative length of stay, morbidity and mortality were obtained and analyzed, with complications graded in accordance to the classification system proposed by Clavien et al.13 Resected gallbladder specimens were sent for histopathological examination, with the extent of inflammatory changes in the gallbladder wall graded accordingly.14 Upon discharge, all patients were followed up for a minimum duration of 90 days and relevant clinical information would be documented and retrieved via the electronic medical record system. Categorical variables were compared using the Pearson’s Chisquare test, while continuous variables were compared using the Kruskal–Wallis H Test. Statistical analysis was performed using the SPSS statistical package (v 19.0; IBM Corporation, Armonk, NY, USA), and all p-values reported were two-sided, with pvalues of <0.05 considered statistically significant.
Pre-operative and intra-operative variables and outcomes are shown in Tables 1 and 2, respectively. There were no patients in this cohort that required additional surgical interventions in the form of a choledochoduodenostomy or hepaticojejunostomy. Table 3 summarizes the post-operative outcomes in all three groups of patients after LC.
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Table 1 Patient demographics
p-Value
E-SALC
M-SALC
L-SALC
n
134
135
42
Median age, years (range)
53 (24–93)
57 (21–86)
60 (19–87)
0.108
73 (54.5)
70 (51.9)
23 (54.8)
0.914
25 (16–45)
26 (17–41)
0.353
16 (11.9)
5 (11.9)
0.119
0.008
Sex, n (%) Male
Median BMI, 25 (15–43) kg/m2 (range) Previous abdominal surgery, n (%)
7 (5.2)
ASA score, n (%) I
65 (48.5)
55 (40.7)
11 (26.2)
II
58 (43.3)
57 (42.2)
19 (45.2)
III
11 (8.2)
23 (17.0)
12 (28.6)
Comorbidity, n (%) Hypertension
55 (41.0)
54 (40)
24 (57.1)
0.133
Dyslipidemia
43 (32.1)
44 (32.6)
18 (42.9)
0.424
Diabetes
37 (27.6)
32 (23.7)
11 (26.2)
0.766
Ischemic heart disease
9 (6.7)
20 (14.8)
12 (28.6)
0.001
Median symptom duration, days (range) Prior to diagnosis
1 (0–3)
2 (0–7)
5 (0–13)
p < 0.001
After diagnosis
1 (0–3)
2 (0–6)
5 (0–13)
p < 0.001
Total duration
2 (1–3)
5 (4–7)
9 (8–13)
p < 0.001
13 (6–28)
0.057
Median laboratory results, unit (range) WBC, n × 109L
14 (6–34)
CRP, mg/L
102 (6–400) 105 (5–396) 156 (7–446) 0.286
Glucose, mmol/L
8 (5–29)
Amylase, u/mL
73 (30–225) 74 (30–306) 74 (30–314) 0.745
13 (4–23)
8 (3–22)
8 (5–20)
0.765
Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass index; TG, Tokyo guidelines; WBC, white blood count; CRP, Creactive protein.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
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Discussion
Table 2 Operative parameters
E-SALC
M-SALC
L-SALC
p-Value
Median operative time, minutes (range)
103 100 107 0.424 (35–209) (24–264) (46–220)
Conversion, n (%)
11 (8.2)
13 (9.6)
9 (21.4)
Intra-operative severity, n (%)
0.048 0.701
Edematous
75 (56.0)
70 (51.9)
Mucocele
3 (2.2)
4 (3.0)
20 (47.6) 3 (7.1)
Gangrenous
36 (26.9)
36 (26.7)
13 (31.0)
Empyema
20 (15.0)
25 (18.5)
6 (14.3)
Other intra-operative procedures, n (%) IOC
12 (9.0)
17 (12.6)
8 (19.0)
0.204
CBDE
2 (1.5)
1 (0.7)
1 (2.4)
0.656
Intra-operative morbidity, n (%)
0
2 (1.5)
0
0.704
Bile duct injury
0
0
0
Bowel injury
0
2 (1.5)
0
Others
0
0
0
Intra-operative mortality, n (%)
0
0
0
NA
Abbreviations: IOC, intra-operative cholangiogram; CBDE, common bile duct exploration.
Table 3 Post-operative outcomes
E-SALC
M-SALC L-SALC
p-Value
Median total length of stay, days (range)
4 (2–33)
2 (2–23)
7 (2–49)
p < 0.001
Median post-operative length of stay, days (range)
2 (1–33)
2 (1–20)
2 (1–17)
0.157
Grade of complications, n (%)
0.695
I
1 (0.7)
2 (1.5)
0 (0.0)
II
13 (9.7)
13 (9.6)
6 (14.3)
III
2 (1.5)
0 (0.0)
0 (0.0)
IV
0 (0.0)
0 (0.0)
0 (0.0)
V
0 (0.0)
1 (0.7)
Overall
16 (11.9) 16 (11.9)
0 (0.0) 6 (14.3)
Histopathological grade,a n (%)
0.456
Grade 1
42 (31.3) 53 (39.3)
18 (42.9)
Grade 2
32 (23.9) 30 (22.2)
11 (26.2)
Grade 3
60 (44.8) 52 (38.5)
13 (31.0)
a
Histopathological grade of gallbladder specimen: Grade 1 (erosive/ ulcerous inflammation); Grade 2 (phlegmonous inflammation); Grade 3 (gangrenous inflammation).
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While the use of minimally invasive surgery has gained popularity worldwide across surgical disciplines, laparoscopic cholecystectomy (LC) was once considered a relative contraindication in the presence of AC in view of increased morbidity and conversion rates.15–18 However, recent trials have shown SALC to be superior in cost effectiveness and patient quality of life as compared to DLC.1 As a result, SALC has gradually been established as the standard of care in the management of AC patients. Nonetheless, the criteria for offering SALC to patients with respect to duration of symptoms remain relatively ambiguous in existing literature. A Cochrane review outlined the benefits of SALC for AC patients with seven days of symptoms presentation,1 while various prospective studies showed similar results for same admission cholecystectomies performed within 24–96 h.19 More specifically, prevailing studies that specifically analyzed outcomes between different intervals of symptom duration prior to SALC remain largely retrospective, with varied recommendations in defining an optimal time period of symptoms beyond which patient should be considered for DLC.2–6 In recent years, several studies have proposed SALC to be performed within the “golden 72 hours” of symptom duration.7 The authors argued that operative difficulty would increase thereafter due to severe inflammatory adhesions, resulting in an increased risk of conversion and bile duct injury. Indeed, Gonzalez-Rodriguez et al. reported a significantly lower conversion rate of 7.8% vs 18.4% in patients who underwent SALC before and after 72 h of symptom onset respectively, while Zhu et al. found longer operative times in the latter group.7,20 Despite the ostensible benefits, the feasibility of performing SALC within 72 h is often questioned due to a multitude of factors.21 This is demonstrated in the current study as only 43.1% of AC patients managed to undergo SALC within 72 h of their reported symptom onset. Firstly, the non-specific nature of initial symptoms and possible attempts by patients to selfmedicate with may result in the late recognition of the condition. Secondly, the hold-up in time to diagnose AC could occur after admission, when AC might not be the initial primary diagnosis due to its diverse presenting symptoms. The time taken to obtain definitive radiological investigations is also often a ratelimiting step in the diagnosis of AC. In addition, a substantial group of patients with significant co-morbidities would require time for adequate pre-operative assessment and optimization. The aforementioned factors are apparent in the current study, which showed a longer duration of symptoms prior to and after patients are diagnosed with AC in the L-SALC group. Additional measures such as patient education in the primary healthcare setting, expedition of relevant patients to secondary care and improvement in diagnostic and intervention processes can be attempted and evaluated to shorten symptom duration prior to SALC.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
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In assessing the operative difficulty of SALC between different time intervals of symptom duration, the current study revealed a significant difference in the conversion rates between E-SALC, M-SALC and L-SALC, with reported figures of 8%, 10% and 21%, respectively. Hence, the risk of conversion in SALC increases considerably in patients with more than a week duration of symptoms. Although these results are seemingly different from previous studies supporting E-SALC,2–6 it is postulated that the higher conversion rates seen with other studies in patients with more than 72 h of symptoms can partially be contributed by a sub-group of patients that presented with symptoms beyond one week. Furthermore, the increased levels of levels of expertise in laparoscopic surgery and the emerging technique of subtotal cholecystectomy could also have potentially mitigated the challenges faced previously while performing SALC, substantiated by the similar operative times seen across all three groups in the current series. A reduction in hospital length of stay and its resultant improvement in cost effectiveness remains a major aspect in supporting the use of SALC over DLC. Various studies have shown that SALC results in hospitalization four days shorter than that of DLC.1,22 While total length of hospital stay was increased in patients with longer symptom duration, this was an expected result as L-SALC patients also had higher ASA scores, suggesting a need for workup and optimization of existing co-morbidities prior to surgery. Despite so, post-operative length of stay remained similar across all groups between three to four days, which was consistent with existing literature. Apart from a shorter hospitalization, patients with SALC also enjoy an improvement in quality of life through faster return to work whilst avoiding any gallstone-related morbidity while awaiting elective surgery, for which studies have shown up to 18% of DLC patients require emergency LC due to non-resolution of symptoms.1 The retrospective nature of this study and its resultant potential for selection bias is a limitation of this project, but there was no significant difference shown in important patient characteristics such as age, gender, previous abdominal surgery and body mass index between the three groups. This negates the presence of confounders that can inadvertently affect the various outcomes measures analyzed in this study. The presence of recall bias can also be a limitation while assessing patient symptomatology. However, majority of patients in the current study with a suspected diagnosis of AC were referred immediately to the hepatopancreaticobiliary service allowing for better standardization in patient evaluation.
purported benefits. Further prospective studies comparing DLC to SALC in patients with different interval of symptom duration should be conducted to better define management pathways in the treatment of AC.
Conclusion
13. Dindo D, Demartines N, Clavien PA. (2004) Classification of surgical
Conflict of interest and disclosure None declared.
References 1. Gurusamy KS, Davidson C, Gluud C, Davidson BR. (2013) Early versus delayed laparoscopic cholecystectomy for people with acute cholecystitis. Cochrane Database Syst Rev. CD005440. 2. Kolla SB, Aggarwal S, Kumar A, Kumar R, Chumber S, Parshad R et al. (2004) Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a prospective randomized trial. Surg Endosc 18: 1323–1327. 3. Lai PB, Kwong KH, Leung KL, Kwok SP, Chan AC, Chung SC et al. (1998) Randomized trial of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Br J Surg 85:764–767. 4. Lo CM, Liu CL, Fan ST, Lai EC, Wong J. (1998) Prospective randomized study of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Ann Surg 227:461–467. 5. Macafee DA, Humes DJ, Bouliotis G, Beckingham IJ, Whynes DK, Lobo DN. (2009) Prospective randomized trial using cost-utility analysis of early versus delayed laparoscopic cholecystectomy for acute gallbladder disease. Br J Surg 96:1031–1040. 6. Yadav RP, Adhikary S, Agrawal CS, Bhattarai B, Gupta RK, Ghimire A. (2009) A comparative study of early vs. delayed laparoscopic cholecystectomy in acute cholecystitis. Kathmandu Univ Med J 7:16–20. 7. Zhu B, Zhang Z, Wang Y, Gong K, Lu Y, Zhang N. (2012) Comparison of laparoscopic cholecystectomy for acute cholecystitis within and beyond 72 h of symptom onset during emergency admissions. World J Surg 36:2654–2658. 8. Ambe P, Weber SA, Christ H, Wassenberg D. (2014) Cholecystectomy for acute cholecystitis. How time-critical are the so called “golden 72 hours”? Or better “golden 24 hours” and “silver 25-72 hour”? A case control study. World J Emerg Surg 9:60. 9. Madan AK, Aliabadi-Wahle S, Tesi D, Flint LM, Steinberg SM. (2002) How early is early laparoscopic treatment of acute cholecystitis? Am J Surg 183:232–236. 10. Polo M, Duclos A, Polazzi S, Payet C, Lifante JC, Cotte E et al. (2015) Acute cholecystitis-optimal timing for early cholecystectomy: a French Nationwide Study. J Gastrointest Surg 19:2003–2010. 11. Stevens KA, Chi A, Lucas LC, Porter JM, Williams MD. (2006) Immediate laparoscopic cholecystectomy for acute cholecystitis: no need to wait. Am J Surg 192:756–761. 12. Lukovich P, Zsirka A, Harsanyi L. (2014) Changes in the operating time of laparoscopic cholecystectomy of the surgeons and novices between 1994-2012. Chirurgia (Bucur) 109:639–643. complications: a new proposal with evaluation in a cohort of 6336 pa-
SALC can be safely performed in AC patients presenting with less than a week of symptoms, and should be advocated in centers with MIS expertise and adequate resources in accommodating a higher emergency operating theater patient load. This would allow for more patients to be treated with SALC, and reap its
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tients and results of a survey. Ann Surg 240:205–213. 14. Schafer M, Krahenbuhl L, Buchler MW. (2001) Predictive factors for the type of surgery in acute cholecystitis. Am J Surg 182:291–297. 15. Cameron JL, Gadacz TR. (1991) Laparoscopic cholecystectomy. Ann Surg 213:1–2.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
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16. Cuschieri A. (1991) Laparoscopic cholecystectomy. Br J Hosp Med 45: 65.
20. Gonzalez-Rodriguez FJ, Paredes-Cotore JP, Ponton C, Rojo Y, Flores E, Luis-Calo ES et al. (2009) Early or delayed laparoscopic
17. Phillips EH, Carroll BJ, Fallas MJ. (1993) Laparoscopically guided cholecystectomy: a detailed report of the first 453 cases performed by one surgical team. Am Surg 59:235–242.
cholecystectomy in acute cholecystitis? Conclusions of a controlled trial. Hepatogastroenterology 56:11–16. 21. Tzovaras
18. Wilson P, Leese T, Morgan WP, Kelly JF, Brigg JK. (1991) Elective laparoscopic cholecystectomy for “all-comers”. Lancet 338:795–797. 19. Yamashita Y, Takada T, Hirata K. (2006) A survey of the timing and
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Paroutoglou G, Hatzitheofilou C. (2006) Timing of laparoscopic cholecystectomy for acute cholecystitis: a prospective non randomized study. World J Gastroenterol 12:5528–5531.
approach to the surgical management of patients with acute chole-
22. Wilson E, Gurusamy K, Gluud C, Davidson BR. (2010) Cost-utility and
cystitis in Japanese hospitals. J Hepatobiliary Pancreat Surg 13:
value-of-information analysis of early versus delayed laparoscopic
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cholecystectomy for acute cholecystitis. Br J Surg 97:210–219.
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© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
http://dx.doi.org/10.1016/j.hpb.2016.10.006
ORIGINAL ARTICLE
Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant? Jarrod K.H. Tan1, Joel C.I. Goh2, Janice W.L. Lim2, Iyer G. Shridhar1, Krishnakumar Madhavan1 & Alfred W.C. Kow1 1
Division of Hepatopancreaticobiliary Surgery and Liver Transplantation, Department of Surgery, National University Health System, and 2Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Abstract Background: Studies have shown that same admission laparoscopic cholecystectomy (SALC) is superior to delayed laparoscopic cholecystectomy for acute cholecystitis (AC). While some proposed a“golden 72-hour” for SALC, the optimal timing remains controversial. The aim of the study was to compare the outcomes of SALC in AC patients with different time intervals from symptom onset. Methods: A retrospective analysis of 311 patients who underwent SALC for AC from June 2010–June 2015 was performed. Patients were divided into three groups based on the time interval between symptom onset and surgery: <4 days (E-SALC), 4–7 days (M-SALC), >7 (L-SALC). Results: The mean duration of symptoms was 2(1–3), 5(4–7) and 9 (8–13) days for E-SALC, M-SALC and L-SALC, respectively (p < 0.001). Conversion rates were higher in the L-SALC group [E-SALC, 8.2% vs M-SALC, 9.6% vs L-SALC, 21.4%] (p = 0.048). The total length of stay was longer in patients with longer symptom duration [E-SALC, 4 (2–33) vs M-SALC, 2 (2–23) vs L-SALC, 7 (2–49)] (p < 0.001). Conclusion: Patients with AC presenting beyond 7 days of symptoms have higher conversion rates and longer length of stay associated with SALC. However, patients with less than a week of symptoms should be offered SALC. Received 4 September 2016; accepted 12 October 2016
Correspondence Alfred W.C. Kow, Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, University Surgical Cluster, National University Hospital, 1E, Kent Ridge Road, NUHS Tower Block, Level 8, 119228, Singapore. E-mail: [email protected]
Introduction The management of acute cholecystitis (AC) has undergone a paradigm shift in recent years, with an increasing preference for same admission (SALC) over delayed (DLC) laparoscopic cholecystectomy.1 Existing literature has convincingly shown that compared to DLC, SALC decreases overall hospital length of stay and eliminates the risks of gallstone-related morbidity while waiting for surgery, and achieves similar conversion rates and post-operative outcomes.2–6 Nevertheless, the optimal timing of SALC based on the onset of symptoms remains controversial. Zhu et al. proposed a “golden 72 hour” period as the ideal timing for SALC, beyond which organized adhesions secondary to gallbladder inflammation form within the Calot’s triangle, rendering surgical dissection more difficult.7 While most studies remain retrospective in
HPB 2016, -, 1–5
nature, early SALC from within 24–72 h of symptom onset has been associated with decreased intra-operative morbidity, with a resultant shorter hospital length of stay.8–11 With increasing proficiency in minimally invasive surgery (MIS) in recent years, SALC becomes an attractive option for patients with acute cholecystitis. Existing studies that analyze the learning curve of LC have established a significant decrease in duration of operation and post-operative morbidity over the last two to three decades.12 The higher level of expertise and experience in laparoscopic surgery has equipped surgeons with more confidence in handling the potential challenges of a difficult LC for AC in patients who present beyond 72 h of symptoms. The aim of this study was to establish the safety and effectiveness of SALC in patients with AC who presented with different time interval from symptom onset.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
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Methods
Results
A retrospective review of all patients who underwent SALC for AC from June 2010 to June 2015 in the National University Hospital of Singapore was performed. The diagnosis of AC in patients was made based on the criteria outlined in the Tokyo Guidelines, with subsequent histopathological confirmation. A total of 311 patients who underwent SALC were included in the data analysis. Patients with AC who underwent SALC were divided into three groups according to the time interval between symptom onset and surgical intervention: (i) within 3 days (E-SALC), (ii) between 4 and 7 days (M-SALC) and (iii) more than 7 days (LSALC). This was derived via existing electronic records that accurately document patient history and clinical findings. As the early symptoms of AC may be non-specific, symptoms were taken into account at their earliest onset and patients with existing symptoms of more than 2 weeks prior to LC were excluded from this study. Broad-spectrum intravenous antibiotic therapy (intravenous 3rd generation cephalosporin and metronidazole) was administered to all patients once the diagnosis of AC was made. All surgeons involved in the operations were at least consultant specialist surgeons, with extensive experience in hepatobiliary and minimally invasive surgery. The standard four-trocar technique was performed for all LC, with a 10 mm port placed through open technique in the subumbilical/transumbilical region under direct vision, and three 5 mm epigastrium and lateral working ports inserted after the establishment of pneumoperitoneum. A Kocher’s or upper midline incision was made should a conversion be required. The decision between a conversion and the performance of a subtotal cholecystectomy was left to the discretion of individual consultant surgeon based on their assessment of the Calot’s anatomy intra-operatively. Patient demographics collected include age; sex; body mass index (BMI); cardiorespiratory co-morbidities; American Society of Anesthesiologists (ASA) score and previous abdominal surgery. Intra-operative outcome parameters included duration of operation, conversion rates and injury to surrounding organ structures. Post-operative length of stay, morbidity and mortality were obtained and analyzed, with complications graded in accordance to the classification system proposed by Clavien et al.13 Resected gallbladder specimens were sent for histopathological examination, with the extent of inflammatory changes in the gallbladder wall graded accordingly.14 Upon discharge, all patients were followed up for a minimum duration of 90 days and relevant clinical information would be documented and retrieved via the electronic medical record system. Categorical variables were compared using the Pearson’s Chisquare test, while continuous variables were compared using the Kruskal–Wallis H Test. Statistical analysis was performed using the SPSS statistical package (v 19.0; IBM Corporation, Armonk, NY, USA), and all p-values reported were two-sided, with pvalues of <0.05 considered statistically significant.
Pre-operative and intra-operative variables and outcomes are shown in Tables 1 and 2, respectively. There were no patients in this cohort that required additional surgical interventions in the form of a choledochoduodenostomy or hepaticojejunostomy. Table 3 summarizes the post-operative outcomes in all three groups of patients after LC.
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Table 1 Patient demographics
p-Value
E-SALC
M-SALC
L-SALC
n
134
135
42
Median age, years (range)
53 (24–93)
57 (21–86)
60 (19–87)
0.108
73 (54.5)
70 (51.9)
23 (54.8)
0.914
25 (16–45)
26 (17–41)
0.353
16 (11.9)
5 (11.9)
0.119
0.008
Sex, n (%) Male
Median BMI, 25 (15–43) kg/m2 (range) Previous abdominal surgery, n (%)
7 (5.2)
ASA score, n (%) I
65 (48.5)
55 (40.7)
11 (26.2)
II
58 (43.3)
57 (42.2)
19 (45.2)
III
11 (8.2)
23 (17.0)
12 (28.6)
Comorbidity, n (%) Hypertension
55 (41.0)
54 (40)
24 (57.1)
0.133
Dyslipidemia
43 (32.1)
44 (32.6)
18 (42.9)
0.424
Diabetes
37 (27.6)
32 (23.7)
11 (26.2)
0.766
Ischemic heart disease
9 (6.7)
20 (14.8)
12 (28.6)
0.001
Median symptom duration, days (range) Prior to diagnosis
1 (0–3)
2 (0–7)
5 (0–13)
p < 0.001
After diagnosis
1 (0–3)
2 (0–6)
5 (0–13)
p < 0.001
Total duration
2 (1–3)
5 (4–7)
9 (8–13)
p < 0.001
13 (6–28)
0.057
Median laboratory results, unit (range) WBC, n × 109L
14 (6–34)
CRP, mg/L
102 (6–400) 105 (5–396) 156 (7–446) 0.286
Glucose, mmol/L
8 (5–29)
Amylase, u/mL
73 (30–225) 74 (30–306) 74 (30–314) 0.745
13 (4–23)
8 (3–22)
8 (5–20)
0.765
Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass index; TG, Tokyo guidelines; WBC, white blood count; CRP, Creactive protein.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
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Discussion
Table 2 Operative parameters
E-SALC
M-SALC
L-SALC
p-Value
Median operative time, minutes (range)
103 100 107 0.424 (35–209) (24–264) (46–220)
Conversion, n (%)
11 (8.2)
13 (9.6)
9 (21.4)
Intra-operative severity, n (%)
0.048 0.701
Edematous
75 (56.0)
70 (51.9)
Mucocele
3 (2.2)
4 (3.0)
20 (47.6) 3 (7.1)
Gangrenous
36 (26.9)
36 (26.7)
13 (31.0)
Empyema
20 (15.0)
25 (18.5)
6 (14.3)
Other intra-operative procedures, n (%) IOC
12 (9.0)
17 (12.6)
8 (19.0)
0.204
CBDE
2 (1.5)
1 (0.7)
1 (2.4)
0.656
Intra-operative morbidity, n (%)
0
2 (1.5)
0
0.704
Bile duct injury
0
0
0
Bowel injury
0
2 (1.5)
0
Others
0
0
0
Intra-operative mortality, n (%)
0
0
0
NA
Abbreviations: IOC, intra-operative cholangiogram; CBDE, common bile duct exploration.
Table 3 Post-operative outcomes
E-SALC
M-SALC L-SALC
p-Value
Median total length of stay, days (range)
4 (2–33)
2 (2–23)
7 (2–49)
p < 0.001
Median post-operative length of stay, days (range)
2 (1–33)
2 (1–20)
2 (1–17)
0.157
Grade of complications, n (%)
0.695
I
1 (0.7)
2 (1.5)
0 (0.0)
II
13 (9.7)
13 (9.6)
6 (14.3)
III
2 (1.5)
0 (0.0)
0 (0.0)
IV
0 (0.0)
0 (0.0)
0 (0.0)
V
0 (0.0)
1 (0.7)
Overall
16 (11.9) 16 (11.9)
0 (0.0) 6 (14.3)
Histopathological grade,a n (%)
0.456
Grade 1
42 (31.3) 53 (39.3)
18 (42.9)
Grade 2
32 (23.9) 30 (22.2)
11 (26.2)
Grade 3
60 (44.8) 52 (38.5)
13 (31.0)
a
Histopathological grade of gallbladder specimen: Grade 1 (erosive/ ulcerous inflammation); Grade 2 (phlegmonous inflammation); Grade 3 (gangrenous inflammation).
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While the use of minimally invasive surgery has gained popularity worldwide across surgical disciplines, laparoscopic cholecystectomy (LC) was once considered a relative contraindication in the presence of AC in view of increased morbidity and conversion rates.15–18 However, recent trials have shown SALC to be superior in cost effectiveness and patient quality of life as compared to DLC.1 As a result, SALC has gradually been established as the standard of care in the management of AC patients. Nonetheless, the criteria for offering SALC to patients with respect to duration of symptoms remain relatively ambiguous in existing literature. A Cochrane review outlined the benefits of SALC for AC patients with seven days of symptoms presentation,1 while various prospective studies showed similar results for same admission cholecystectomies performed within 24–96 h.19 More specifically, prevailing studies that specifically analyzed outcomes between different intervals of symptom duration prior to SALC remain largely retrospective, with varied recommendations in defining an optimal time period of symptoms beyond which patient should be considered for DLC.2–6 In recent years, several studies have proposed SALC to be performed within the “golden 72 hours” of symptom duration.7 The authors argued that operative difficulty would increase thereafter due to severe inflammatory adhesions, resulting in an increased risk of conversion and bile duct injury. Indeed, Gonzalez-Rodriguez et al. reported a significantly lower conversion rate of 7.8% vs 18.4% in patients who underwent SALC before and after 72 h of symptom onset respectively, while Zhu et al. found longer operative times in the latter group.7,20 Despite the ostensible benefits, the feasibility of performing SALC within 72 h is often questioned due to a multitude of factors.21 This is demonstrated in the current study as only 43.1% of AC patients managed to undergo SALC within 72 h of their reported symptom onset. Firstly, the non-specific nature of initial symptoms and possible attempts by patients to selfmedicate with may result in the late recognition of the condition. Secondly, the hold-up in time to diagnose AC could occur after admission, when AC might not be the initial primary diagnosis due to its diverse presenting symptoms. The time taken to obtain definitive radiological investigations is also often a ratelimiting step in the diagnosis of AC. In addition, a substantial group of patients with significant co-morbidities would require time for adequate pre-operative assessment and optimization. The aforementioned factors are apparent in the current study, which showed a longer duration of symptoms prior to and after patients are diagnosed with AC in the L-SALC group. Additional measures such as patient education in the primary healthcare setting, expedition of relevant patients to secondary care and improvement in diagnostic and intervention processes can be attempted and evaluated to shorten symptom duration prior to SALC.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
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In assessing the operative difficulty of SALC between different time intervals of symptom duration, the current study revealed a significant difference in the conversion rates between E-SALC, M-SALC and L-SALC, with reported figures of 8%, 10% and 21%, respectively. Hence, the risk of conversion in SALC increases considerably in patients with more than a week duration of symptoms. Although these results are seemingly different from previous studies supporting E-SALC,2–6 it is postulated that the higher conversion rates seen with other studies in patients with more than 72 h of symptoms can partially be contributed by a sub-group of patients that presented with symptoms beyond one week. Furthermore, the increased levels of levels of expertise in laparoscopic surgery and the emerging technique of subtotal cholecystectomy could also have potentially mitigated the challenges faced previously while performing SALC, substantiated by the similar operative times seen across all three groups in the current series. A reduction in hospital length of stay and its resultant improvement in cost effectiveness remains a major aspect in supporting the use of SALC over DLC. Various studies have shown that SALC results in hospitalization four days shorter than that of DLC.1,22 While total length of hospital stay was increased in patients with longer symptom duration, this was an expected result as L-SALC patients also had higher ASA scores, suggesting a need for workup and optimization of existing co-morbidities prior to surgery. Despite so, post-operative length of stay remained similar across all groups between three to four days, which was consistent with existing literature. Apart from a shorter hospitalization, patients with SALC also enjoy an improvement in quality of life through faster return to work whilst avoiding any gallstone-related morbidity while awaiting elective surgery, for which studies have shown up to 18% of DLC patients require emergency LC due to non-resolution of symptoms.1 The retrospective nature of this study and its resultant potential for selection bias is a limitation of this project, but there was no significant difference shown in important patient characteristics such as age, gender, previous abdominal surgery and body mass index between the three groups. This negates the presence of confounders that can inadvertently affect the various outcomes measures analyzed in this study. The presence of recall bias can also be a limitation while assessing patient symptomatology. However, majority of patients in the current study with a suspected diagnosis of AC were referred immediately to the hepatopancreaticobiliary service allowing for better standardization in patient evaluation.
purported benefits. Further prospective studies comparing DLC to SALC in patients with different interval of symptom duration should be conducted to better define management pathways in the treatment of AC.
Conclusion
13. Dindo D, Demartines N, Clavien PA. (2004) Classification of surgical
Conflict of interest and disclosure None declared.
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© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006