|
 |
|
ORIGINAL ARTICLE |
|
|
|
| Year : 2018 | Volume
: 14
| Issue : 3 | Page : 185-191 |
| |
Laparoscopic versus open treatment of gallbladder cancer: A systematic review and meta-analysis
Xin Zhao, Xiang Yang Li, Wu Ji
Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| Date of Submission | 17-Oct-2016 |
| Date of Acceptance | 30-May-2017 |
| Date of Web Publication | 6-Jun-2018 |
Correspondence Address:
Prof. Wu Ji
Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305, East Zhongshan Road, Xuanwu District, Nanjing 210002, Jiangsu Province
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jmas.JMAS_223_16
Background: The aim of this review was to evaluate the effect of laparoscopic surgery on the treatment of patients with gallbladder cancer (GBC).
Methods: A comprehensive search of Medline and Cochrane Library was conducted to identify relevant articles. A meta-analysis was subsequently performed.
Results: A total of 20 studies including 1217 patients met the inclusion criteria. The meta-analysis showed that the 5-year survival rate was significant higher in laparoscopic group than open group (48.4% vs. 38.5%; odds ratio [OR], 1.63; 95% confidence interval [CI], 1.22–2.19; P = 0.001). Although the scar recurrence rate was significant higher in laparoscopic group than open group (7.1% vs. 4.0%; OR, 2.10; 95% CI, 1.11–3.96; P = 0.02), the overall recurrence rates between two groups were not significant different (44.8% vs. 42.2%; OR, 0.86; 95% CI, 0.64–1.14; P = 0.29). In addition, compared with open extended cholecystectomy (EC), laparoscopic EC (LEC) was associated with less intraoperative blood loss, shorter post-operative hospital stays and insignificant less complication rate (10.0% vs. 18.3%; OR, 0.51; 95% CI, 0.15–1.73; P = 0.28).
Conclusion: Laparoscopic simple cholecystectomy does not lead to a worse prognosis when applied on patients with GBC. LEC can be performed in specialised expert centres on elective patients.
Keywords: Gallbladder cancer, laparoscopic, meta-analysis, open
How to cite this article:
Zhao X, Li XY, Ji W. Laparoscopic versus open treatment of gallbladder cancer: A systematic review and meta-analysis. J Min Access Surg 2018;14:185-91 |
| ¤ Introduction | |  |
Gallbladder cancer (GBC) is a rare malignancy and constitutes 0.6%–1.5% of all cases after cholecystectomy, but it remains the most common cancer of the biliary tract.[1],[2] The 5-year survival rates for all stages of GBC range from 5% to 20%, so it is considered to be an aggressive and highly lethal disease.[3],[4] GBC is suspected preoperatively in only 30% of patients. The other 70% are discovered incidentally by pathological examinations during or after cholecystectomy for benign diseases and termed as incidental GBC.[5],[6]
The only chance for a complete cure of GBC is by surgical resection.[7] It has been traditionally recommended that patients undergo laparotomy if they are suspected of having GBC pre-operatively.[7],[8] Using the American Joint Committee on Cancer staging system, simple cholecystectomy (SC) alone is considered definitive treatment if the histological T-stage is Tis or T1a.[9],[10] Whereas, tumours greater than stage T1b should be treated by extended cholecystectomy (EC), which including partial hepatic resection with or without lymphadenectomy and bile duct resection.[11]
Laparoscopic cholecystectomy (LC) has now replaced conventional open cholecystectomy for benign gallbladder disease, and hence many GBCs are diagnosed incidentally during or after LC.[5] However, the role of laparoscopic treatment for GBC has long been contraindicated. The most important reason for this contraindication was a higher incidence of wound metastasis after laparoscopic surgery.[12] However, recent studies suggested that LC has no adverse effects compared to open approach.[13] Hence, the doubt remains whether the initial laparoscopic surgery leads to a worsening of the prognosis, one objective of this study is to find out the answer of this question.
The development of new instruments and advanced surgical techniques has resulted in the more widespread use of laparoscopic surgery.[14],[15] Recently, laparoscopic EC (LEC) has been shown to be feasible at specialised expert centres on elective patients.[16] Considering few GBC cases are available and randomised trials are difficult to conduct, this study also conducted a pooled systematic analysis to evaluate the efficacy of laparoscopic and open EC (OEC) for GBC.
| ¤ Methods | | |
Search strategy and study selection
A systematic review of the literature was performed. Articles published up to August 2016 were identified by searching abstracts in Medline and Cochrane Library, using the keywords: Laparoscopic; gallbladder; cancer or carcinoma. The references from the included studies were also searched to identify additional studies. Two researchers independently searched for articles and compared their results. Any discrepancies were resolved by consultation with the corresponding author.
Inclusion and exclusion criteria
To be included in this analysis, studies were required to meet the following criteria: (i) the study design must be that of a comparative trial evaluating laparoscopic and open treatment of GBC; (ii) at least one outcome should be compared; (iii) the study should be a human study and written in English.
Studies were excluded from the analysis for the following reasons: (i) unpublished data, data published in an abstract form only or non-full-length articles; (ii) failure to describe the surgical methodology; (iii) only the most recent publications were included when the selected articles included the same or overlapping data in multiple publications.
Data extraction and outcome measures
Two authors independently extracted and confirmed the data and entered them into an electronic data collection form. Differences of opinion were resolved by consensus that included the corresponding author. The following data were collected: The time period, country and design of study; the procedure type of surgery; the time of follow-up; the number of GBC patients who underwent laparoscopic and open surgery; the gender and age of patients; the number of patients by T classification; the number of patients who underwent additional operation.
The primary outcome measures were the 5-year survival rate and overall recurrence rate. Secondary outcome measures included scar recurrence, intra-operative outcomes (operative time and blood loss), and post-operative outcomes (complication rate and hospital stay). The recurrence of disease was defined as any recurrence of cancer: Distant metastasis, widespread or local peritoneal seeding, or scar recurrence. The scar recurrence was defined as a suspicious mass or nodule specially described on physical examination at an incision or port site at any time in the post-operative follow-up period.
Statistical analysis
If appropriate comparisons were available, meta-analysis was conducted. Otherwise, a descriptive review of the identified evidence was carried out. The odds ratio (OR) with 95% confidence intervals (CIs) was calculated for dichotomous data and the mean difference with 95% CIs for continuous data. Heterogeneity was described with the Chi-squared test. The value of P < 0.05 was considered to indicate a difference of statistical significance. The I2 statistic was used to measure the quantity of heterogeneity, with values >50% considered to indicate significant heterogeneity. A random-effects model was used if significant heterogeneity existed, and otherwise a fixed-effects model was adopted. All statistical analyses were performed using the statistical package RevMan (Review Manager [RevMan] [Computer program]. Version 5.3. The Nordic Cochrane Centre, The Cochrane Collaboration, 2014, Copenhagen, Denmark).
The majority of the included studies in this meta-analysis enrolled a small number of patients. This meant that when an outcome was measured, there were perhaps no events occurring. It was recommended that in such situations one event was inserted into the data extraction tables to avoid division by a zero denominator. This effectively avoided eliminating small studies from consideration.[17]
| ¤ Results | | |
Baseline characteristics
Study selection and search strategy are outlined in [Figure 1]. A total of 12 studies were included in this review.[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29] There were no randomised studies and all studies were retrospective in nature. Detailed information about included studies is summarised in [Table 1].
A total of 1217 patients with GBC who underwent surgical treatment were chosen for this analysis. Seven hundred and seventy patients were in laparoscopic group, of which 730 patients underwent laparoscopic SC (LSC) and 40 patients underwent LEC. Four hundred and forty-seven patients were in open group, of which 387 patients underwent open SC (OSC) and 60 patients underwent OEC. Detailed information about these patients is shown in [Table 2]. | Table 2: Characteristics of patients in the included studies (laparoscopic vs. open)
Click here to view |
Five-year survival rate
The 5-year survival rate was reported in ten of the 12 studies (1117 patients), and all compared LSC versus OSC. There was no significant heterogeneity among these studies (χ2 = 6.68, df = 9 [P = 0.67]; I2 = 0%). Using a fixed-effects model, the 5-year survival rate was significant higher in laparoscopic group than open group (353/730, 48.4% vs. 149/387, 38.5%; OR, 1.63; 95% CI, 1.22–2.19; P = 0.001) [Figure 2].
Recurrence rate
Outcome measures reported in the included studies were summarized in [Table 3]. It was reported in ten of the 12 studies (1020 patients), of which eight studies compared LSC versus OSC and two studies compared LEC versus OEC. Thus, a subgroup analysis according to the different procedure of surgery (SC or EC) was performed. There was no significant heterogeneity among these studies (χ2 = 10.20, df = 9 [P = 0.33]; I2 = 12%), so a fixed-effects model was used. For the subgroup of SC, there was no significant difference in the rate of recurrence between the laparoscopic group and open group (282/591, 47.7% vs. 157/329, 47.7%; OR, 0.90; 95% CI, 0.67–1.20; P = 0.47). For the subgroup of EC, there was also no significant difference between two groups (1/40, 2.5% vs. 7/60, 11.7%; OR, 0.24; 95% CI, 0.04–1.35; P = 0.10). For total studies, although the recurrence rate was lower in laparoscopic group than open group, it had no significant difference (283/631, 44.8% vs. 164/389, 42.2%; OR, 0.86; 95% CI, 0.64–1.14; P = 0.29) [Figure 3]. | Table 3: Outcome measures of the included studies (laparoscopic vs. open)
Click here to view |
Scar recurrence rate
The scar recurrence rate was reported in eight of the 12 studies (965 patients), and all compared LSC versus OSC. There was no significant heterogeneity amongst these studies (χ2 = 2.87, df = 7 [P = 0.90]; I2 = 0%). Using a fixed-effects model, the scar recurrence rate was significant higher in laparoscopic group than open group (44/616, 7.1% vs. 14/349, 4.0%; OR, 2.10; 95% CI, 1.11–3.96; P = 0.02) [Figure 4].
Intra-opertive outcomes
The operative time was only reported in two of the 12 studies (100 patients), and all compared LEC versus OEC. One study reported that the operative time in laparoscopic group was significantly longer than open group (P = 0.02), but another study did not detect a significant difference (P = 0.76). Due to distinct presentation types of data, meta-analysis could not be performed.
The intraoperative blood loss was also reported in two of the 12 studies (100 patients), and all compared LEC versus OEC. Both studies reported that the intraoperative blood loss in laparoscopic group was significantly less than open group (P = 0.03 and P = 0.01, respectively). Due to distinct presentation types of data, meta-analysis could not be performed.
Post-operative outcomes
The complication rate was reported in two of the 12 studies (100 patients), and all compared LEC versus OEC. There was no significant heterogeneity amongst these studies (χ2 = 0.52, df = 1 [P = 0.47]; I2 = 0%), thus a fixed-effects model was used. Although the complication rate was lower in laparoscopic group than open group, it had no significant difference (4/40, 10.0% vs. 11/60, 18.3%; OR, 0.51; 95% CI, 0.15–1.73; P = 0.28) [Figure 5].
The post-operative hospital stay was also reported in two of the 12 studies (100 patients). One study reported that the post-operative hospital stay in laparoscopic group was significantly shorter than open group (P = 0.01), but another study did not detect a significant difference (P = 0.11). Due to distinct presentation types of data, meta-analysis could not be performed.
| ¤ Discussion | | |
Since the late 1980s, LC has been a widely accepted method for treating benign gallbladder disease.[30] However, there is controversy concerning the appropriate use of laparoscopic surgery for the treatment of GBC.[12] Since the first description of scar recurrence in 1991, it has been thought that laparoscopic surgery worsens the prognosis of GBC.[31] However, this meta-analysis showed that laparoscopic treatment for GBC had an even higher 5-year survival rate than open treatment. Although a possible explanation might be that laparoscopy was more often used to treat GBC with earlier tumour stages, the evidence from this review demonstrated that initial laparoscopic treatment did not have a measurable influence on the course of GBC.
According to previous reports, the major concern about the use of laparoscopic surgery for patients with GBC is metastatic wound implants arising from trocar holes.[13] This meta-analysis indeed detected a higher incidence of scar recurrence in laparoscopic group than the open group. However, the overall recurrence rate between two groups had no significant difference. A retrieval bag was advised by several studies in cases with perforation of gallbladder and contributed to prevent stone spillage, scar recurrence and intraperitoneal dissemination. Hence, by means of adherence to oncologic principles and use of retrieval bags, scar recurrence might not be a concern when applying laparoscopic surgery on patients with GBC.[13],[32]
The advances in instrumentation and technical improvements have resulted in the more widespread use of laparoscopic surgery to treat most cancers of digestive system, including colon, stomach, liver and even pancres. It has been demonstrated to show similar oncological outcomes with open surgery, and provide additonal benefits of minimally invasive surgery.[15],[32],[33],[34] Recently, LEC has been performed at several specialised expert centres. These centres have reported safe and feasible outcome data for T1b, T2 and even T3 tumours.[16],[35] In this analysis, two retrospective studies comparing LEC versus OEC were included. The results showed that there was no significant difference in regard to recurrence rate and complication rate between the two surgical types, but laparoscopic surgery was associated with less intraoperative blood loss and shorter post-operative hospital stay. So, based on the evidence provided by this review, it was concluded that LEC could be performed in specialised expert centres on elective patients.
This systematic review and meta-analysis had a number of limitations. First, carrying out a randomised controlled trial (RCT) that compares laparoscopic and open treatment for GBC was very difficult, and all studies included were retrospective. Second, most published studies on GBC were based on a single-centre experience with a relatively small number of patients. Third, the variable patient selections, laparoscopic and open procedures, and different outcome measures might be attributable to the heterogeneity of included studies. Forth, the follow-up period was limited to access long-term survival rate of different surgical types. Therefore, a large-sample, well-conducted, multicentre RCT including long-term follow-up will be required to further confirm the results of the present analysis.
| ¤ Conclusion | | |
The evidence from this analysis did not show that LSC leads to a worsen prognosis when applied on patients with GBC. Moreover, LEC could be performed in specialised expert centres on elective patients.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| ¤ References | | |
| 1. | Dorobisz T, Dorobisz K, Chabowski M, Pawlowski W, Janczak D, Patrzalek D, et al. Incidental gallbladder cancer after cholecystectomy: 1990 to 2014. Onco Targets Ther 2016;9:4913-6.  |
| 2. | Choi KS, Choi SB, Park P, Kim WB, Choi SY. Clinical characteristics of incidental or unsuspected gallbladder cancers diagnosed during or after cholecystectomy: A systematic review and meta-analysis. World J Gastroenterol 2015;21:1315-23. [ PUBMED] |
| 3. | Zhang WJ, Xu GF, Zou XP, Wang WB, Yu JC, Wu GZ, et al. Incidental gallbladder carcinoma diagnosed during or after laparoscopic cholecystectomy. World J Surg 2009;33:2651-6. [ PUBMED] |
| 4. | Cavallaro A, Piccolo G, Di Vita M, Zanghì A, Cardì F, Di Mattia P, et al. Managing the incidentally detected gallbladder cancer: Algorithms and controversies. Int J Surg 2014;12 Suppl 2:S108-19. |
| 5. | Tian YH, Ji X, Liu B, Yang GY, Meng XF, Xia HT, et al. Surgical treatment of incidental gallbladder cancer discovered during or following laparoscopic cholecystectomy. World J Surg 2015;39:746-52. [ PUBMED] |
| 6. | Duffy A, Capanu M, Abou-Alfa GK, Huitzil D, Jarnagin W, Fong Y, et al. Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol 2008;98:485-9. [ PUBMED] |
| 7. | Lee SE, Kim KS, Kim WB, Kim IG, Nah YW, Ryu DH, et al. Practical guidelines for the surgical treatment of gallbladder cancer. J Korean Med Sci 2014;29:1333-40. [ PUBMED] |
| 8. | Ettinger DS, Agulnik M, Cates JM, Cristea M, Denlinger CS, Eaton KD, et al. NCCN clinical practice guidelines occult primary. J Natl Compr Canc Netw 2011;9:1358-95. [ PUBMED] |
| 9. | Edge SB, Compton CC. The American Joint Committee on Cancer: The 7 th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471-4. [ PUBMED] |
| 10. | Yip VS, Gomez D, Brown S, Byrne C, White D, Fenwick SW, et al. Management of incidental and suspicious gallbladder cancer: Focus on early referral to a tertiary centre. HPB (Oxford) 2014;16:641-7. [ PUBMED] |
| 11. | Aloia TA, Járufe N, Javle M, Maithel SK, Roa JC, Adsay V, et al. Gallbladder cancer: Expert consensus statement. HPB (Oxford) 2015;17:681-90. |
| 12. | Steinert R, Nestler G, Sagynaliev E, Müller J, Lippert H, Reymond MA. Laparoscopic cholecystectomy and gallbladder cancer. J Surg Oncol 2006;93:682-9. |
| 13. | Yoon YS, Han HS, Cho JY, Choi Y, Lee W, Jang JY, et al. Is laparoscopy contraindicated for gallbladder cancer? A 10-year prospective cohort study. J Am Coll Surg 2015;221:847-53. [ PUBMED] |
| 14. | Clinical Outcomes of Surgical Therapy Study Group, Nelson H, Sargent DJ, Wieand HS, Fleshman J, Anvari M, et al. Acomparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 2004;350:2050-9. [ PUBMED] |
| 15. | Lee JH, Han HS, Lee JH. A prospective randomized study comparing open vs. laparoscopy-assisted distal gastrectomy in early gastric cancer: Early results. Surg Endosc 2005;19:168-73. [ PUBMED] |
| 16. | Shirobe T, Maruyama S. Laparoscopic radical cholecystectomy with lymph node dissection for gallbladder carcinoma. Surg Endosc 2015;29:2244-50. [ PUBMED] |
| 17. | Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 1998;17:2815-34. [ PUBMED] |
| 18. | Yoshida T, Matsumoto T, Sasaki A, Morii Y, Ishio T, Bandoh T, et al. Laparoscopic cholecystectomy in the treatment of patients with gall bladder cancer. J Am Coll Surg 2000;191:158-63. [ PUBMED] |
| 19. | Sarli L, Contini S, Sansebastiano G, Gobbi S, Costi R, Roncoroni L. Does laparoscopic cholecystectomy worsen the prognosis of unsuspected gallbladder cancer? Arch Surg 2000;135:1340-4. [ PUBMED] |
| 20. | Toyonaga T, Chijiiwa K, Nakano K, Noshiro H, Yamaguchi K, Sada M, et al. Completion radical surgery after cholecystectomy for accidentally undiagnosed gallbladder carcinoma. World J Surg 2003;27:266-71. [ PUBMED] |
| 21. | de Aretxabala XA, Roa IS, Mora JP, Orellana JJ, Riedeman JP, Burgos LA, et al. Laparoscopic cholecystectomy: Its effect on the prognosis of patients with gallbladder cancer. World J Surg 2004;28:544-7. [ PUBMED] |
| 22. | Cucinotta E, Lorenzini C, Melita G, Iapichino G, Currò G. Incidental gall bladder carcinoma: Does the surgical approach influence the outcome? ANZ J Surg 2005;75:795-8. |
| 23. | Chan KM, Yeh TS, Jan YY, Chen MF. Laparoscopic cholecystectomy for early gallbladder carcinoma: Long-term outcome in comparison with conventional open cholecystectomy. Surg Endosc 2006;20:1867-71. [ PUBMED] |
| 24. | Goetze TO, Paolucci V. Prognosis of incidental gallbladder carcinoma is not influenced by the primary access technique: Analysis of 837 incidental gallbladder carcinomas in the German Registry. Surg Endosc 2013;27:2821-8. [ PUBMED] |
| 25. | Hu L, Wang B, Liu X, Lv Y. Unsuspected gallbladder cancer: A clinical retrospective study. Arch Iran Med 2013;16:631-5. [ PUBMED] |
| 26. | Zhang WJ, Xu GF, Tian ZQ, Wu GZ, Wang H, Guan WX. Surgical approach does not influence the outcome of incidental gallbladder carcinoma. Int J Clin Exp Med 2015;8:869-75. [ PUBMED] |
| 27. | Jang JY, Heo JS, Han Y, Chang J, Kim JR, Kim H, et al. Impact of type of surgery on survival outcome in patients with early gallbladder cancer in the era of minimally invasive surgery: Oncologic safety of laparoscopic surgery. Medicine (Baltimore) 2016;95:e3675. [ PUBMED] |
| 28. | Agarwal AK, Javed A, Kalayarasan R, Sakhuja P. Minimally invasive versus the conventional open surgical approach of a radical cholecystectomy for gallbladder cancer: A retrospective comparative study. HPB (Oxford) 2015;17:536-41. [ PUBMED] |
| 29. | Itano O, Oshima G, Minagawa T, Shinoda M, Kitago M, Abe Y, et al. Novel strategy for laparoscopic treatment of pT2 gallbladder carcinoma. Surg Endosc 2015;29:3600-7. [ PUBMED] |
| 30. | Cuschieri A, Dubois F, Mouiel J, Mouret P, Becker H, Buess G, et al. The European experience with laparoscopic cholecystectomy. Am J Surg 1991;161:385-7. [ PUBMED] |
| 31. | Tantia O, Jain M, Khanna S, Sen B. Incidental carcinoma gall bladder during laparoscopic cholecystectomy for symptomatic gall stone disease. Surg Endosc 2009;23:2041-6. [ PUBMED] |
| 32. | Lacy AM, Delgado S, Castells A, Prins HA, Arroyo V, Ibarzabal A, et al. The long-term results of a randomized clinical trial of laparoscopy-assisted versus open surgery for colon cancer. Ann Surg 2008;248:1-7. [ PUBMED] |
| 33. | Han HS, Shehta A, Ahn S, Yoon YS, Cho JY, Choi Y. Laparoscopic versus open liver resection for hepatocellular carcinoma: Case-matched study with propensity score matching. J Hepatol 2015;63:643-50. [ PUBMED] |
| 34. | Boggi U, Amorese G, Vistoli F, Caniglia F, De Lio N, Perrone V, et al. Laparoscopic pancreaticoduodenectomy: A systematic literature review. Surg Endosc 2015;29:9-23. [ PUBMED] |
| 35. | Gumbs AA, Hoffman JP. Laparoscopic radical cholecystectomy and Roux-en-Y choledochojejunostomy for gallbladder cancer. Surg Endosc 2010;24:1766-8. [ PUBMED] |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]
|
