- Email: [email protected]
Is port-site resection necessary in the surgical management of gallbladder cancer?
Journal of Visceral Surgery (2013) 150, 277—284
Available online at www.sciencedirect.com
ORIGINAL ARTICLE
Is port-site resection necessary in the surgical management of gallbladder cancer? D. Fuks a, J.-M. Regimbeau a,∗, P. Pessaux b, P. Bachellier b, A. Raventos c, G. Mantion d, J.-F. Gigot e, L. Chiche f, G. Pascal g, D. Azoulay g, A. Laurent h, C. Letoublon i, E. Boleslawski j, M. Rivoire k, J.-Y. Mabrut l, M. Adham m, Y.-P. Le Treut n, J.-R. Delpero o, F. Navarro p, A. Ayav q, K. Boudjema r, G. Nuzzo s, M. Scotte t, O. Farges u a
Département de chirurgie digestive et métabolique, université de Picardie, hôpital Nord-Amiens, CHU d’Amiens, place Victor-Pauchet, 80054 Amiens cedex 01, France b Département de chirurgie digestive, Strasbourg, France c Département de chirurgie digestive, Barcelona, Spain d Département de chirurgie digestive, Besanc¸on, France e Département de chirurgie digestive, Bruxelles, Belgium f Département de chirurgie digestive, Caen, France g Département de chirurgie digestive, Villejuif, France h Département de chirurgie digestive, Créteil, France i Département de chirurgie digestive, Grenoble, France j Département de chirurgie digestive, Lille, France k Département de chirurgie digestive, hôpital Léon-Bérard, Lyon, France l Département de chirurgie digestive, hôpital de la Croix-Rousse, Lyon, France m Département de chirurgie digestive, hôpital Édouard-Herriot, Lyon, France n Département de chirurgie digestive, hôpital de la Conception, Marseille, France o Département de chirurgie digestive, hôpital Paoli-Calmettes, Marseille, France p Département de chirurgie digestive, Montpellier, France q Département de chirurgie digestive, Nancy, France r Département de chirurgie digestive, Rennes, France s Département de chirurgie digestive, Roma, Italy t Département de chirurgie digestive, Rouen, France u Département de chirurgie digestive, Clichy, France
KEYWORDS Gallbladder cancer; Port-sites; Long-term survival
∗
Summary Introduction: Gallbladder carcinoma is frequently discovered incidentally on pathologic examination of the specimen after laparoscopic cholecystectomy (LC) performed for presumed ‘‘benign’’ disease. The objective of the present study was to assess the role of excision of port-sites from the initial LC for patients with incidental gallbladder carcinoma (IGBC) in a French registry.
Abbreviations: PS, Port-site; PSE, Port-site excision; NPSE, No port-site excision. Corresponding author. Tel.: +33 3 22 66 83 01; fax: +33 3 22 66 86 80. E-mail address: [email protected] (J.-M. Regimbeau).
1878-7886/$ — see front matter © 2013 Published by Elsevier Masson SAS. http://dx.doi.org/10.1016/j.jviscsurg.2013.03.006
278
D. Fuks et al. Methods: Data on patients with IGBC identified after LC between 1998 and 2008 were retrospectively collated in a French multicenter database. Among those patients undergoing re-operation with curative intent, patients with port-site excision (PSE) were compared with patients without PSE and analyzed for differences in recurrence patterns and survival. Results: Among 218 patients with IGBC after LC (68 men, 150 women, median age 64 years), 148 underwent re-resection with curative intent; 54 patients had PSE and 94 did not. Both groups were comparable with regard to demographic data (gender, age > 70, co-morbidities), surgical procedures (major resection, lymphadenectomy, main bile duct resection) and postoperative morbidity. In the PSE group, depth of tumor invasion was T1b in six, T2 in 24, T3 in 22, and T4 in two; this was not significantly different from patients without PSE (P = 0.69). Port-site metastasis was observed in only one (2%) patient with a T3 tumor who died with peritoneal metastases 15 months after resection. PSE did not improve the overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively) compared to patients with no PSE (78%, 55%, 33% at 1, 3, 5 years, respectively, P = 0.37). Eight percent of patients developed incisional hernia at the port-site after excision. Conclusion: In patients with IGBC, PSE was not associated with improved survival and should not be considered mandatory during definitive surgical treatment. © 2013 Published by Elsevier Masson SAS.
Introduction Gallbladder carcinoma is the fifth most frequent cancer of the digestive tract [1,2]. Prognosis is poor in the absence of treatment with 5-year survival ranging from 5 to 20% [1—5]. Gallbladder carcinoma is suspected preoperatively in only 30% of patients [1,2], while the other 70% are discovered incidentally on pathologic examination of the gallbladder specimen after cholecystectomy for benign disease (stones, acute cholecystitis, gallbladder polyps) [6—8]. Incidental gallbladder carcinoma (IGBC) is found in 0.2-3% of all cholecystectomies, a non-infrequent event [9]. Prognosis of gallbladder carcinoma is essentially determined by the degree of tumor infiltration and by the possibility of obtaining a tumor-free resection margin (R0) [10]. For tumors with extension deeper than the lamina propria (≥ T1b), definitive resection should include a minimal hepatic resection centered on the gallbladder bed associated with regional lymphadenectomy [11,12]. There is consensual agreement regarding several technical points, such as the extension of hepatectomy, resection of the main bile duct and the extent of lymphadenectomy. On the other hand, routine port-site excision (PSE) is widely debated [13,14]. The prevalence of tumor seeding in port-sites after laparoscopic cholecystectomy is very variable in published series (between 0 and 40%) and seems higher in case of gallbladder perforation [13,15—18]. The Memorial SloanKettering Cancer Center recently underscored that port-site seeding was a poor prognostic factor and seemed associated with the existence or the onset of peritoneal carcinomatosis [16,19,20]. However, PSE did not improve survival or disease-free survival in this series. The authors therefore concluded that routine PSE was not warranted during secondary resection of IGBC [21]. The principal goal of this study was to evaluate the value and the specific morbidity of PSE in patients undergoing secondary resection for IGBC in a French multicenter series.
Patients and methods Selection of patients The AFC-CVB-2009 group was created in 2009 under the auspices of the Association Franc ¸aise de Chirurgie (French
Association of Surgery) with the goal of establishing a retrospective registry of patients undergoing operation for gallbladder carcinoma. Twenty-one centers were asked to identify patients undergoing curative or palliative resection for histologically proven gallbladder carcinoma (biliary tract adenocarcinoma) between 1998 and 2008 and to fill in a questionnaire (based on available clinical data) these were collated in June 2009. Among the 429 patients with gallbladder carcinoma, 211 were suspected preoperatively while 218 were incidental diagnoses. This study involved the 148 (68%) patients who underwent a re-operation for resection with curative intent for IGBC and the primary endpoint was the value of PSE (Fig. 1).
Surgical procedures Re-operation with curative intent was performed in patients with gallbladder carcinoma graded as greater or equal to T1b on the pathology report for cholecystectomy. As data collection was retrospective, surgical procedures (extent of the hepatectomy, of lymphadenectomy, of resection of the main bile duct and PSE) were not standardized within the different centers. Segment IV and inferior V bisegmentectomy associated with lymphadenectomy of the hepatic pedicle, and without excision of the main bile duct, was performed in 52.3% of patients. Main bile duct resection was performed only in case of tumoral involvement of the cystic duct on the initial pathology report or because of macroscopic involvement detected intraoperatively during the second operation. PSE was left to the surgeon’s discretion and was not performed routinely. Likewise, the technique of PSE was not standardized. Non-absorbable sutures were used for wound closure.
Postoperative course After resection, adjuvant treatment was proposed case by case, mainly for patients with advanced carcinoma. Patients were followed postoperatively according to the recommendations of the thesaurus of digestive tract carcinology; this included a physical examination with hepatic sonography every three months during the first postoperative year, and every 6 months thereafter. Abdominal CT scan was performed according to the results of sonography and a chest X-ray performed every year [22].
Is port-site resection necessary in the surgical management of gallbladder cancer?
Figure 1.
279
Synopsis of the study.
Criteria studied The main objective of this study was to assess the value of PSE during secondary resection with regard to short-term (specific complications) and long-term (specific complications, recurrence, overall survival) outcome, particularly focused on long-term survival of patients after secondary resection for IGBC identified in this French multicenter series.
Verification of data and statistical analysis Data were coded, checked several times and a copy of the pathology report was recorded. The different centers were contacted when there were missing answers found in the questionnaire, information on the pathology report and the questionnaire were inconsistent, or if survival was less than 6 months. Non-parametric data were expressed as medians (range) and qualitative data were given as frequency or proportions (%). Categorical data were analyzed with Pearson’s v2 test. The Mann-Whitney U test was used for data that did not follow a normal distribution. Survival curves were traced according to the Kaplan-Meier method and the log-rank test was used to compare prognostic variables. The threshold of statistical significance was set at P < 0.05. All statistical analyses were performed with SPSS software, version 18.0 for Windows (SPSS Inc, Chicago, IL).
Results
vs. 21%, P = 0.0001) and required fewer blood transfusions (15 vs. 31%, P = 0.02). There was no statistically significant difference found in terms of T-stage or lymph node involvement. The median number of port-sites excised was not recorded. Overall postoperative mortality was 3.3% (n = 5) with no difference according to whether PSE had been performed or not (4% vs. 3%, P = 0.65). Nor did overall morbidity (37%) differ between the two groups (30% vs. 41%, respectively, P = 0.29). Resection margins were tumor-free (R0) in 51 (94%) patients in the PSE group versus 83 (88%) in the NPSE group (P = 0.03). Adjuvant chemotherapy was administered in 17 (31%) patients in the PSE group (T3 tumor n = 10, N1 n = 6) and in 23 (24%) NPSE patients (P = 0.09).
Tumor involvement of port-sites Port-site involvement was identified histologically in one (2%) patient bearing a T3N0 tumor treated with IV-V bisegmentectomy and hepatic pedicle lymphadenectomy without resection of the main bile duct. A peritoneal carcinomatosis nodule was resected during the same operation. No information was available as to the exact location of the involved port-site, whether a sac was used for gallbladder extraction, or whether gallbladder perforation occurred during cholecystectomy. Resection margins were not involved and this patient did not receive adjuvant chemotherapy. Generalized peritoneal carcinomatosis was discovered 7 months later and the patient died 15 months after re-operation. Analysis of factors associated with port-site involvement was not possible because of the small number of patients (n = 1).
Selected population Follow-up, survival and recurrence Among the 148 patients undergoing re-operation with curative intent, there were 100 women and 48 men, with a median age of 61 years (31—81). The median delay between cholecystectomy and re-operation was 48 (2—245) days and 29 patients (20%) underwent secondary resection within 30 days of the initial operation. Of these 148 patients, 54 (36%) had PSE while 94 patients (64%) did not (NPSE). Demographic data and co-morbidities were comparable between the two groups (Table 1). During secondary resection, the PSE group underwent major hepatectomy more often (24 vs. 6%, P = 0.006), had more adjacent organ resection (48
During median follow-up of 26 months (6—109), 10 patients (19%) in the PSE group developed an incisional hernia: two patients had incisional hernia located in the right subcostal incision, whereas incisional hernia was located at the site of PSE in eight (15%) patients (Fig. 2). Seven of these patients underwent incisional hernia repair. In the group without PSE, four patients developed subcostal incisional hernia; all underwent repair. Overall 1, 3, and 5 year-survival was 77%, 56% and 29%, respectively among the 148 patients undergoing resection.
280
D. Fuks et al.
Table 1 Comparison between patients undergoing re-operation for gallbladder carcinoma discovered incidentally with or without port-site excision (n = 148). Port-site excision n (%)
No port-site excision n (%)
n = 54
n = 94
P
O 33 (35) 21 (22) 10 (11)
0.33 0.50 0.09
Co-morbidities Diabetes Arterial hypertension Ischemic cardiac disease Chronic obstructive bronchopulmonary disease Kidney failure Dyslipidemia Antecedent cancer
4 14 0 0 0 6 5
(7) (26) (0) (0) (0) (11) (9)
10 24 4 3 1 9 7
(11) (26) (4) (3) (1) (10) (7)
0.40 0.44 0.17 0.27 0.65 0.42 0.14
Surgical procedures Major hepatectomy Pedicular lymphadenenectomy Resection adjacent organs Resection hepatic artery branch Resection portal vein branch Resection main biliary duct Vascular clampage Blood transfusion
13 47 26 0 1 20 16 8
(24) (87) (48) (0) (2) (37) (30) (15)
6 81 20 1 2 43 39 29
(6) (86) (21) (1) (2) (46) (41) (31)
0.006 0.07 0.0001 0.65 0.72 0.35 0.16 0.02
Pathology Stage T T1b T2 T3 Stage N N0 N1 Resection margins R0 R1 R2 Adjuvant therapy Chemotherapy
0.97 3 (6) 25 (46) 26 (48)
8 (8) 44 (47) 42 (45)
42 (78) 12 (22)
82 (87) 12 (13)
51 (94) 3 (6) 0
83 (88) 10 (11) 1 (1)
17 (31)
23 (24)
0.11
0.03
0.09
Figure 2. A. Abdomen of a patient having undergone re-operation for incidental gallbladder carcinoma discovered on the cholecystectomy specimen with port-site excision (immediately postoperative). B. Abdomen of another patient having undergone re-operation 23 months previously for incidental gallbladder carcinoma discovered on the cholecystectomy specimen with port-site excision consulting for multiple port-site incisional hernia.
Pronostic factors in patients undergoing two-stage resection (n = 148) (uni- and multivariable analysis).
Variables
Survival 1 year (%)
Survival 3 years (%)
Survival 5 years (%)
Gender Male Female
82 73
48 55
38 43
Symptomatic No Yes
78 73
54 55
42 44
Major hepatectomy No Yes
80 53
59 27
44 27
Resection main bile duct No Yes
84 66
74 42
58 34
Port-site excision No Yes
78 77
55 58
33 21
Lymphadenectomy No Yes
46 78
23 56
0 45
Adjuvant chemotherapy No Yes
81 65
61 34
46 29
pT T1 T2 T3 T4
100 97 65 50
— 71 30 25
— 65 24 0
pN N0 N1
81 43
58 21
44 0
Resection margins R0 R1
83 50
53 0
43 0
Residual tumor No Yes
97 67
81 30
69 24
P (univariate)
OR (95% CI)
P (multivariable)
0.03
1.35 (0.06—30.51)
0.84
0.01
0.24 (0.05—1.17)
0.07
0.02
0.76 (0.13—4.34)
0.76
0.0001
6.74 (1.13—40.08)
0.03
0.005
2.95 (0.18—46.74)
0.44
1.94 (0.41—9.13)
0.40
0.83
0.59
0.34
0.10
Is port-site resection necessary in the surgical management of gallbladder cancer?
Table 2
0.45
0.0001
281
282
D. Fuks et al.
Figure 3. Overall survival of the 54 patients with PSE (green curve) and 94 patients without PSE (blue curve) (Kaplan-Meier) (P = 0.37).
1 year 3 years 5 years Port-site excision (n = 54) Overall survival (%) Patients at risk (n) No port-site excision (n = 94) Overall survival (%) Patients at risk (n)
77 24
58 11
21 4
78 52
55 28
33 12
Disease-free 1, 3, and 5-year survival was 51%, 34% and 20%, respectively. T stage was the only independent prognostic factor found in multivariable analysis (OR 6.74 [1.13—40.08], P = 0.03) (Table 2). Port-site excision did not improve overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively), compared to patients without PSE (78%, 55%, 33% at 1, 3, and 5 years, respectively, P = 0.37) (Fig. 3). Among the patients undergoing R0 resection, PSE did not improve survival (79%, 60%, 24% vs. 82%, 63%, 35% respectively, P = 0.29) (Fig. 4). Diseasefree survival was not modified by the performance of PSE. In the PSE group, 19 (35%) patients had a recurrence, seven of which were peritoneal carcinomatosis, comparable to the 37 (39%) patients with recurrence in the group without PSE, nine of which were peritoneal carcinomatosis.
Discussion In the 2009 AFC report on gallbladder carcinoma, 5-year survival was 27% irrespective of treatment modalities [23]. Incidental gallbladder carcinoma discovered on the specimen after cholecystectomy for benign disease represents a privileged situation for which re-operation with curative intent should be proposed [24] in that long-term survival is better than when cancer is suspected preoperatively [23]. ‘‘Radical cholecystectomy’’ consists of hepatic resection centered on the gallbladder bed associated with regional lymphadenectomy without routine resection of the main bile duct.
Figure 4. Overall survival of 51 patients with port-site excision (green curve) and 83 patients without port-site excision (blue curve) having undergone R0 resection (Kaplan-Meier) (P = 0.29).
1 year 3 years 5 years Port-site excision (n = 51) Overall survival (%) Patients at risk (n) No port-site excision (n = 83) Overall survival (%) Patients at risk (n)
79 23
60 10
24 3
82 50
63 25
35 9
The peritoneal tropism associated with gallbladder carcinoma seems to be aggravated by the laparoscopic route, the most common approach for cholecystectomy today. Several mechanisms have been suggested to explain the increased incidence: intraoperative perforation [15,16,24,25], CO2 pneumoperitoneum, repeated passages of instruments through the trocars, increased abdominal pressure, tumoral manipulation and the relative diminution of cellular immunity induced by pneumoperitoneum [24]. However, in spite of these suggested mechanisms, routine PSE remains controversial. In our series, of 218 patients with incidental gallbladder carcinoma, 68% underwent re-resection with curative intent, compared to 37% of the 435 patients in the series originating from MSKCC. Conversely, 70% of patients undergoing resection had PSE in the North American series compared with only 36% in our population. In our study, the incidence of port-site involvement in patients with IGBC was 2%, corresponding to the lower limit of the range reported in the literature (from 2 to 29%) [15,18,21]. The median interval to onset of port-site metastases ranged from four to 10 months after laparoscopic cholecystectomy [15,16,20,26,27] and involved all portsites indifferently [21]. The incidence was 19% in the MSKCC series [21]. However, among the 13 patients with histologically proven port-site metastasis, seven had macroscopically incomplete resections (R2) because of concomitant peritoneal carcinomatosis, found in 86% of cases. Port-site involvement seems to be a factor of poor prognosis. In the MSKCC series, of the six patients with R0 resection of their involved port-site, only one was still alive at 3
Is port-site resection necessary in the surgical management of gallbladder cancer?
Figure 5. awl.
283
Intraoperative view of the technique of port-site excision. The cylindrical resection is guided by the insertion of a Redon drain
years. In this series, disease-free survival was considerably reduced in patients with port-site involvement. Conversely, overall survival was unchanged, probably because of the small number of patients. ‘‘Poor’’ prognosis seems related to several factors. First, these are advanced-stage tumors: port-site involvement was never observed for T1b tumors in these two series. Likewise, lymph node involvement was present in 100% and 92% of patients in both of these series, respectively. Lastly, port-site involvement seems to be associated with concomitant peritoneal carcinomatosis (six of 13 patients in the MSKCC series). In the MSKCC series, all patients with port-site involvement had tumor recurrence, most often peritoneal, irrespective of the tumor margin status. In our series, the only patient with histologically proven port-site involvement, having undergone en bloc resection of a carcinomatosis nodule, died of peritoneal recurrence 15 months after initial cholecystectomy. We therefore confirmed the results of the MSKCC series, showing that port-site excision does not improve overall survival, disease-free survival or the delay between initial cholecystectomy and recurrence (irrespective of margin status). Of note, among the NPSE patients, between 2 and 29% had microscopic involvement. In our series, PSE was more likely to be performed in association with major hepatectomies and adjacent organ resections. Even if the R0 margin rate was significantly higher, survival did not differ between the two groups. Similar results were observed in the R0 resection subgroup. From a technical point of view, PSE is difficult and often incorrectly performed. One possible explanation for the absence of difference between the two groups might be that a PSE centered only on the skin scar may leave tumor behind
if the trocar had been inserted in an oblique direction. To this end, we propose insertion of a thin drain trocar joining the two scars (skin and peritoneal) to guide the PSE (Fig. 5). Lastly, 8% of our patients presented with a specific complication of PSE, i.e. incisional hernia. This rate is comparable with that observed in the MSKCC series (nine patients of 69) and should be taken into consideration in the therapeutic strategy. Our multicenter study was retrospective, and therefore contained several biases including a measurement bias (small sample, low percentage of patients undergoing PSE). However, the low incidence of port-site involvement makes it improbable if not impossible to perform a therapeutic trial on the subject. In conclusion, we confirmed that PSE need not be routinely performed during secondary resection with curative intent for IGBC discovered after cholecystectomy. We would rather propose a frozen section examination of the peritoneum surrounding the peritoneal trocar orifices for all gallbladder carcinoma greater or equal to T2.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
References [1] Varshney S, Buttirini G, Gupta R, et al. Incidental carcinoma of the gallbladder. Eur J Surg Oncol 2002;28:4—10.
284 [2] Wullstein C, Woeste G, Barkhausen S, Gross E, Hopt UT, et al. Do complications related to laparoscopic cholecystectomy influence the prognosis of gallbladder cancer? Surg Endosc 2002;16:828—32. [3] Benoist S, Panis Y, Fagniez PL, et al. Long-term results after curative resection for carcinoma of the gallbladder. Am J Surg 1998;175:118—22. [4] Cubertafond P, Gainant A, Cuchiaro G, et al. Surgical treatment of 724 carcinomas of the gallbladder. Results of the French Surgical Association survey. Ann Surg 1994;219:275—80. [5] Regimbeau JM, Fuks D, Le Treut YP, et al. Surgery for hilar cholangiocarcinoma: a multi-institutional update on practice and outcome by the AFC-HC study group. J Gastrointest Surg 2011;15:480—8. [6] Box JC, Edge SB. Laparoscopic cholecystectomy and unsuspected gallbladder carcinoma. Semin Surg Oncol 1999;16:327—31. [7] Pawlik TM, Gleisner AL, Vigano L, et al. Incidence of finding residual disease for incidental gallbladder carcinoma: implications for re-resection. J Gastrointest Surg 2007;11:1478—86. [8] Goetze TO, Paolucci V. Adequate extent in radical re-resection of incidental gallbladder carcinoma: analysis of the German Registry. Surg Endosc 2010;24:2156—64. [9] Romano F, Franciosi C, Caprotti R, et al. Laparoscopic cholecystectomy and unsuspected gallbladder cancer. Eur J Surg Oncol 2001;27:225—8. [10] Suzuki K, Kimura T, Ogawa H. Long-term prognostic of gallbladdder cancer diagnosed after laparosopic cholecystectomy. Surg Endosc 2000;14:712—6. [11] Goetze TO, Paolucci V. Benefits of reoperation of T2 and more advanced incidental gallbladder carcinoma: analysis of the German Registry. Ann Surg 2008;247:104—8. [12] Goetze TO, Paolucci V. Immediate re-resection of T1 incidental gallbladder carcinomas: a survival analysis of the German Registry. Surg Endosc 2008;22:2462—5. [13] Hu JB, Sun XN, Xu J, He C. Port site and distant metastases of gallbladder cancer after laparoscopic cholecystectomy diagnosed by positron emission tomography. World J Gastroenterol 2008;14:6428—31. [14] Giuliante F, Ardito F, Vellone M, Clemente G, Nuzzo G. Port-sites excision for gallbladder cancer incidentally found
D. Fuks et al.
[15]
[16]
[17]
[18]
[19]
[20] [21]
[22] [23]
[24] [25]
[26]
[27]
after laparoscopic cholecystectomy. Am J Surg 2006;191: 114—6. Lundberg O, Kristoffersson A. Port site metastases from gallbladdercancer after laparoscopic cholecystectomy. Results of a Swedish survey and review of published reports. Eur J Surg 1999;165:215—22. Z’Graggen K, Birrer S, Maurer CA, Wehrli H, Klaiber C, Baer HU. Incidence of port site recurrence after laparoscopic cholecystectomy for preoperatively unsuspected gallbladder carcinoma. Surgery 1998;124:831—8. Weiland ST, Mahvi DM, Niederhuber JE, Heisey DM, Chicks DS, Rikkers LF. Should suspected early gallbladder cancer be treated laparoscopically? J Gastrointest Surg 2002;6:50—6. Zhang WJ, Xu GF, Zou XP, et al. Incidental gallbladder carcinoma diagnosed during or after laparoscopic cholecystectomy. World J Surg 2009;33:2651—6. Fong Y, Brennan MF, Turnbull A, Colt DG, Blumgart LH. Gallbladder cancer discovered during laparoscopic surgery. Potential for iatrogenic tumor dissemination. Arch Surg 1993;128:1054—6. Ricardo AE, Feig BW, Ellis LM, et al. Gallbladder cancer and trocar site recurrences. Am J Surg 1997;174:619—22. Maker AV, Butte JM, Oxenberg J, et al. Is port site resection necessary in the surgical management of gallbladder cancer? Ann Surg Oncol 2012;19:409—17. http://www.snfge.asso.fr/01-Bibliotheque/0G-Thesauruscancerologie/publication5/sommaire-thesaurus.asp Regimbeau JM, Pruvot FR, Farges O, editors. Chirurgie des cholangiocarcinomes intrahépatiques, hilaires et vésiculaires. France: Arnette Wolker Kluver; 2009. Chiche L, Metairie S. Fortuitous discovery of gallbladder cancer. J Chir (Paris) 2001;138:336—41. Wibbenmeyer LA, Wade TP, Chen RC, Meyer RC, Turgeon RP, Andrus CH. Laparoscopic cholecystectomy can disseminate in situ carcinoma of the gallbladder. J Am Coll Surg 1995;181:504—10. Paolucci V, Schaeff B, Schneider M, Gutt C. Tumor seeding following laparoscopy: international survey. World J Surg 1999;23:989—95. Paolucci V. Port site recurrences after laparoscopic cholecystectomy. J Hepatobiliary Pancreat Surg 2001;8:535—43.
Available online at www.sciencedirect.com
ORIGINAL ARTICLE
Is port-site resection necessary in the surgical management of gallbladder cancer? D. Fuks a, J.-M. Regimbeau a,∗, P. Pessaux b, P. Bachellier b, A. Raventos c, G. Mantion d, J.-F. Gigot e, L. Chiche f, G. Pascal g, D. Azoulay g, A. Laurent h, C. Letoublon i, E. Boleslawski j, M. Rivoire k, J.-Y. Mabrut l, M. Adham m, Y.-P. Le Treut n, J.-R. Delpero o, F. Navarro p, A. Ayav q, K. Boudjema r, G. Nuzzo s, M. Scotte t, O. Farges u a
Département de chirurgie digestive et métabolique, université de Picardie, hôpital Nord-Amiens, CHU d’Amiens, place Victor-Pauchet, 80054 Amiens cedex 01, France b Département de chirurgie digestive, Strasbourg, France c Département de chirurgie digestive, Barcelona, Spain d Département de chirurgie digestive, Besanc¸on, France e Département de chirurgie digestive, Bruxelles, Belgium f Département de chirurgie digestive, Caen, France g Département de chirurgie digestive, Villejuif, France h Département de chirurgie digestive, Créteil, France i Département de chirurgie digestive, Grenoble, France j Département de chirurgie digestive, Lille, France k Département de chirurgie digestive, hôpital Léon-Bérard, Lyon, France l Département de chirurgie digestive, hôpital de la Croix-Rousse, Lyon, France m Département de chirurgie digestive, hôpital Édouard-Herriot, Lyon, France n Département de chirurgie digestive, hôpital de la Conception, Marseille, France o Département de chirurgie digestive, hôpital Paoli-Calmettes, Marseille, France p Département de chirurgie digestive, Montpellier, France q Département de chirurgie digestive, Nancy, France r Département de chirurgie digestive, Rennes, France s Département de chirurgie digestive, Roma, Italy t Département de chirurgie digestive, Rouen, France u Département de chirurgie digestive, Clichy, France
KEYWORDS Gallbladder cancer; Port-sites; Long-term survival
∗
Summary Introduction: Gallbladder carcinoma is frequently discovered incidentally on pathologic examination of the specimen after laparoscopic cholecystectomy (LC) performed for presumed ‘‘benign’’ disease. The objective of the present study was to assess the role of excision of port-sites from the initial LC for patients with incidental gallbladder carcinoma (IGBC) in a French registry.
Abbreviations: PS, Port-site; PSE, Port-site excision; NPSE, No port-site excision. Corresponding author. Tel.: +33 3 22 66 83 01; fax: +33 3 22 66 86 80. E-mail address: [email protected] (J.-M. Regimbeau).
1878-7886/$ — see front matter © 2013 Published by Elsevier Masson SAS. http://dx.doi.org/10.1016/j.jviscsurg.2013.03.006
278
D. Fuks et al. Methods: Data on patients with IGBC identified after LC between 1998 and 2008 were retrospectively collated in a French multicenter database. Among those patients undergoing re-operation with curative intent, patients with port-site excision (PSE) were compared with patients without PSE and analyzed for differences in recurrence patterns and survival. Results: Among 218 patients with IGBC after LC (68 men, 150 women, median age 64 years), 148 underwent re-resection with curative intent; 54 patients had PSE and 94 did not. Both groups were comparable with regard to demographic data (gender, age > 70, co-morbidities), surgical procedures (major resection, lymphadenectomy, main bile duct resection) and postoperative morbidity. In the PSE group, depth of tumor invasion was T1b in six, T2 in 24, T3 in 22, and T4 in two; this was not significantly different from patients without PSE (P = 0.69). Port-site metastasis was observed in only one (2%) patient with a T3 tumor who died with peritoneal metastases 15 months after resection. PSE did not improve the overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively) compared to patients with no PSE (78%, 55%, 33% at 1, 3, 5 years, respectively, P = 0.37). Eight percent of patients developed incisional hernia at the port-site after excision. Conclusion: In patients with IGBC, PSE was not associated with improved survival and should not be considered mandatory during definitive surgical treatment. © 2013 Published by Elsevier Masson SAS.
Introduction Gallbladder carcinoma is the fifth most frequent cancer of the digestive tract [1,2]. Prognosis is poor in the absence of treatment with 5-year survival ranging from 5 to 20% [1—5]. Gallbladder carcinoma is suspected preoperatively in only 30% of patients [1,2], while the other 70% are discovered incidentally on pathologic examination of the gallbladder specimen after cholecystectomy for benign disease (stones, acute cholecystitis, gallbladder polyps) [6—8]. Incidental gallbladder carcinoma (IGBC) is found in 0.2-3% of all cholecystectomies, a non-infrequent event [9]. Prognosis of gallbladder carcinoma is essentially determined by the degree of tumor infiltration and by the possibility of obtaining a tumor-free resection margin (R0) [10]. For tumors with extension deeper than the lamina propria (≥ T1b), definitive resection should include a minimal hepatic resection centered on the gallbladder bed associated with regional lymphadenectomy [11,12]. There is consensual agreement regarding several technical points, such as the extension of hepatectomy, resection of the main bile duct and the extent of lymphadenectomy. On the other hand, routine port-site excision (PSE) is widely debated [13,14]. The prevalence of tumor seeding in port-sites after laparoscopic cholecystectomy is very variable in published series (between 0 and 40%) and seems higher in case of gallbladder perforation [13,15—18]. The Memorial SloanKettering Cancer Center recently underscored that port-site seeding was a poor prognostic factor and seemed associated with the existence or the onset of peritoneal carcinomatosis [16,19,20]. However, PSE did not improve survival or disease-free survival in this series. The authors therefore concluded that routine PSE was not warranted during secondary resection of IGBC [21]. The principal goal of this study was to evaluate the value and the specific morbidity of PSE in patients undergoing secondary resection for IGBC in a French multicenter series.
Patients and methods Selection of patients The AFC-CVB-2009 group was created in 2009 under the auspices of the Association Franc ¸aise de Chirurgie (French
Association of Surgery) with the goal of establishing a retrospective registry of patients undergoing operation for gallbladder carcinoma. Twenty-one centers were asked to identify patients undergoing curative or palliative resection for histologically proven gallbladder carcinoma (biliary tract adenocarcinoma) between 1998 and 2008 and to fill in a questionnaire (based on available clinical data) these were collated in June 2009. Among the 429 patients with gallbladder carcinoma, 211 were suspected preoperatively while 218 were incidental diagnoses. This study involved the 148 (68%) patients who underwent a re-operation for resection with curative intent for IGBC and the primary endpoint was the value of PSE (Fig. 1).
Surgical procedures Re-operation with curative intent was performed in patients with gallbladder carcinoma graded as greater or equal to T1b on the pathology report for cholecystectomy. As data collection was retrospective, surgical procedures (extent of the hepatectomy, of lymphadenectomy, of resection of the main bile duct and PSE) were not standardized within the different centers. Segment IV and inferior V bisegmentectomy associated with lymphadenectomy of the hepatic pedicle, and without excision of the main bile duct, was performed in 52.3% of patients. Main bile duct resection was performed only in case of tumoral involvement of the cystic duct on the initial pathology report or because of macroscopic involvement detected intraoperatively during the second operation. PSE was left to the surgeon’s discretion and was not performed routinely. Likewise, the technique of PSE was not standardized. Non-absorbable sutures were used for wound closure.
Postoperative course After resection, adjuvant treatment was proposed case by case, mainly for patients with advanced carcinoma. Patients were followed postoperatively according to the recommendations of the thesaurus of digestive tract carcinology; this included a physical examination with hepatic sonography every three months during the first postoperative year, and every 6 months thereafter. Abdominal CT scan was performed according to the results of sonography and a chest X-ray performed every year [22].
Is port-site resection necessary in the surgical management of gallbladder cancer?
Figure 1.
279
Synopsis of the study.
Criteria studied The main objective of this study was to assess the value of PSE during secondary resection with regard to short-term (specific complications) and long-term (specific complications, recurrence, overall survival) outcome, particularly focused on long-term survival of patients after secondary resection for IGBC identified in this French multicenter series.
Verification of data and statistical analysis Data were coded, checked several times and a copy of the pathology report was recorded. The different centers were contacted when there were missing answers found in the questionnaire, information on the pathology report and the questionnaire were inconsistent, or if survival was less than 6 months. Non-parametric data were expressed as medians (range) and qualitative data were given as frequency or proportions (%). Categorical data were analyzed with Pearson’s v2 test. The Mann-Whitney U test was used for data that did not follow a normal distribution. Survival curves were traced according to the Kaplan-Meier method and the log-rank test was used to compare prognostic variables. The threshold of statistical significance was set at P < 0.05. All statistical analyses were performed with SPSS software, version 18.0 for Windows (SPSS Inc, Chicago, IL).
Results
vs. 21%, P = 0.0001) and required fewer blood transfusions (15 vs. 31%, P = 0.02). There was no statistically significant difference found in terms of T-stage or lymph node involvement. The median number of port-sites excised was not recorded. Overall postoperative mortality was 3.3% (n = 5) with no difference according to whether PSE had been performed or not (4% vs. 3%, P = 0.65). Nor did overall morbidity (37%) differ between the two groups (30% vs. 41%, respectively, P = 0.29). Resection margins were tumor-free (R0) in 51 (94%) patients in the PSE group versus 83 (88%) in the NPSE group (P = 0.03). Adjuvant chemotherapy was administered in 17 (31%) patients in the PSE group (T3 tumor n = 10, N1 n = 6) and in 23 (24%) NPSE patients (P = 0.09).
Tumor involvement of port-sites Port-site involvement was identified histologically in one (2%) patient bearing a T3N0 tumor treated with IV-V bisegmentectomy and hepatic pedicle lymphadenectomy without resection of the main bile duct. A peritoneal carcinomatosis nodule was resected during the same operation. No information was available as to the exact location of the involved port-site, whether a sac was used for gallbladder extraction, or whether gallbladder perforation occurred during cholecystectomy. Resection margins were not involved and this patient did not receive adjuvant chemotherapy. Generalized peritoneal carcinomatosis was discovered 7 months later and the patient died 15 months after re-operation. Analysis of factors associated with port-site involvement was not possible because of the small number of patients (n = 1).
Selected population Follow-up, survival and recurrence Among the 148 patients undergoing re-operation with curative intent, there were 100 women and 48 men, with a median age of 61 years (31—81). The median delay between cholecystectomy and re-operation was 48 (2—245) days and 29 patients (20%) underwent secondary resection within 30 days of the initial operation. Of these 148 patients, 54 (36%) had PSE while 94 patients (64%) did not (NPSE). Demographic data and co-morbidities were comparable between the two groups (Table 1). During secondary resection, the PSE group underwent major hepatectomy more often (24 vs. 6%, P = 0.006), had more adjacent organ resection (48
During median follow-up of 26 months (6—109), 10 patients (19%) in the PSE group developed an incisional hernia: two patients had incisional hernia located in the right subcostal incision, whereas incisional hernia was located at the site of PSE in eight (15%) patients (Fig. 2). Seven of these patients underwent incisional hernia repair. In the group without PSE, four patients developed subcostal incisional hernia; all underwent repair. Overall 1, 3, and 5 year-survival was 77%, 56% and 29%, respectively among the 148 patients undergoing resection.
280
D. Fuks et al.
Table 1 Comparison between patients undergoing re-operation for gallbladder carcinoma discovered incidentally with or without port-site excision (n = 148). Port-site excision n (%)
No port-site excision n (%)
n = 54
n = 94
P
O 33 (35) 21 (22) 10 (11)
0.33 0.50 0.09
Co-morbidities Diabetes Arterial hypertension Ischemic cardiac disease Chronic obstructive bronchopulmonary disease Kidney failure Dyslipidemia Antecedent cancer
4 14 0 0 0 6 5
(7) (26) (0) (0) (0) (11) (9)
10 24 4 3 1 9 7
(11) (26) (4) (3) (1) (10) (7)
0.40 0.44 0.17 0.27 0.65 0.42 0.14
Surgical procedures Major hepatectomy Pedicular lymphadenenectomy Resection adjacent organs Resection hepatic artery branch Resection portal vein branch Resection main biliary duct Vascular clampage Blood transfusion
13 47 26 0 1 20 16 8
(24) (87) (48) (0) (2) (37) (30) (15)
6 81 20 1 2 43 39 29
(6) (86) (21) (1) (2) (46) (41) (31)
0.006 0.07 0.0001 0.65 0.72 0.35 0.16 0.02
Pathology Stage T T1b T2 T3 Stage N N0 N1 Resection margins R0 R1 R2 Adjuvant therapy Chemotherapy
0.97 3 (6) 25 (46) 26 (48)
8 (8) 44 (47) 42 (45)
42 (78) 12 (22)
82 (87) 12 (13)
51 (94) 3 (6) 0
83 (88) 10 (11) 1 (1)
17 (31)
23 (24)
0.11
0.03
0.09
Figure 2. A. Abdomen of a patient having undergone re-operation for incidental gallbladder carcinoma discovered on the cholecystectomy specimen with port-site excision (immediately postoperative). B. Abdomen of another patient having undergone re-operation 23 months previously for incidental gallbladder carcinoma discovered on the cholecystectomy specimen with port-site excision consulting for multiple port-site incisional hernia.
Pronostic factors in patients undergoing two-stage resection (n = 148) (uni- and multivariable analysis).
Variables
Survival 1 year (%)
Survival 3 years (%)
Survival 5 years (%)
Gender Male Female
82 73
48 55
38 43
Symptomatic No Yes
78 73
54 55
42 44
Major hepatectomy No Yes
80 53
59 27
44 27
Resection main bile duct No Yes
84 66
74 42
58 34
Port-site excision No Yes
78 77
55 58
33 21
Lymphadenectomy No Yes
46 78
23 56
0 45
Adjuvant chemotherapy No Yes
81 65
61 34
46 29
pT T1 T2 T3 T4
100 97 65 50
— 71 30 25
— 65 24 0
pN N0 N1
81 43
58 21
44 0
Resection margins R0 R1
83 50
53 0
43 0
Residual tumor No Yes
97 67
81 30
69 24
P (univariate)
OR (95% CI)
P (multivariable)
0.03
1.35 (0.06—30.51)
0.84
0.01
0.24 (0.05—1.17)
0.07
0.02
0.76 (0.13—4.34)
0.76
0.0001
6.74 (1.13—40.08)
0.03
0.005
2.95 (0.18—46.74)
0.44
1.94 (0.41—9.13)
0.40
0.83
0.59
0.34
0.10
Is port-site resection necessary in the surgical management of gallbladder cancer?
Table 2
0.45
0.0001
281
282
D. Fuks et al.
Figure 3. Overall survival of the 54 patients with PSE (green curve) and 94 patients without PSE (blue curve) (Kaplan-Meier) (P = 0.37).
1 year 3 years 5 years Port-site excision (n = 54) Overall survival (%) Patients at risk (n) No port-site excision (n = 94) Overall survival (%) Patients at risk (n)
77 24
58 11
21 4
78 52
55 28
33 12
Disease-free 1, 3, and 5-year survival was 51%, 34% and 20%, respectively. T stage was the only independent prognostic factor found in multivariable analysis (OR 6.74 [1.13—40.08], P = 0.03) (Table 2). Port-site excision did not improve overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively), compared to patients without PSE (78%, 55%, 33% at 1, 3, and 5 years, respectively, P = 0.37) (Fig. 3). Among the patients undergoing R0 resection, PSE did not improve survival (79%, 60%, 24% vs. 82%, 63%, 35% respectively, P = 0.29) (Fig. 4). Diseasefree survival was not modified by the performance of PSE. In the PSE group, 19 (35%) patients had a recurrence, seven of which were peritoneal carcinomatosis, comparable to the 37 (39%) patients with recurrence in the group without PSE, nine of which were peritoneal carcinomatosis.
Discussion In the 2009 AFC report on gallbladder carcinoma, 5-year survival was 27% irrespective of treatment modalities [23]. Incidental gallbladder carcinoma discovered on the specimen after cholecystectomy for benign disease represents a privileged situation for which re-operation with curative intent should be proposed [24] in that long-term survival is better than when cancer is suspected preoperatively [23]. ‘‘Radical cholecystectomy’’ consists of hepatic resection centered on the gallbladder bed associated with regional lymphadenectomy without routine resection of the main bile duct.
Figure 4. Overall survival of 51 patients with port-site excision (green curve) and 83 patients without port-site excision (blue curve) having undergone R0 resection (Kaplan-Meier) (P = 0.29).
1 year 3 years 5 years Port-site excision (n = 51) Overall survival (%) Patients at risk (n) No port-site excision (n = 83) Overall survival (%) Patients at risk (n)
79 23
60 10
24 3
82 50
63 25
35 9
The peritoneal tropism associated with gallbladder carcinoma seems to be aggravated by the laparoscopic route, the most common approach for cholecystectomy today. Several mechanisms have been suggested to explain the increased incidence: intraoperative perforation [15,16,24,25], CO2 pneumoperitoneum, repeated passages of instruments through the trocars, increased abdominal pressure, tumoral manipulation and the relative diminution of cellular immunity induced by pneumoperitoneum [24]. However, in spite of these suggested mechanisms, routine PSE remains controversial. In our series, of 218 patients with incidental gallbladder carcinoma, 68% underwent re-resection with curative intent, compared to 37% of the 435 patients in the series originating from MSKCC. Conversely, 70% of patients undergoing resection had PSE in the North American series compared with only 36% in our population. In our study, the incidence of port-site involvement in patients with IGBC was 2%, corresponding to the lower limit of the range reported in the literature (from 2 to 29%) [15,18,21]. The median interval to onset of port-site metastases ranged from four to 10 months after laparoscopic cholecystectomy [15,16,20,26,27] and involved all portsites indifferently [21]. The incidence was 19% in the MSKCC series [21]. However, among the 13 patients with histologically proven port-site metastasis, seven had macroscopically incomplete resections (R2) because of concomitant peritoneal carcinomatosis, found in 86% of cases. Port-site involvement seems to be a factor of poor prognosis. In the MSKCC series, of the six patients with R0 resection of their involved port-site, only one was still alive at 3
Is port-site resection necessary in the surgical management of gallbladder cancer?
Figure 5. awl.
283
Intraoperative view of the technique of port-site excision. The cylindrical resection is guided by the insertion of a Redon drain
years. In this series, disease-free survival was considerably reduced in patients with port-site involvement. Conversely, overall survival was unchanged, probably because of the small number of patients. ‘‘Poor’’ prognosis seems related to several factors. First, these are advanced-stage tumors: port-site involvement was never observed for T1b tumors in these two series. Likewise, lymph node involvement was present in 100% and 92% of patients in both of these series, respectively. Lastly, port-site involvement seems to be associated with concomitant peritoneal carcinomatosis (six of 13 patients in the MSKCC series). In the MSKCC series, all patients with port-site involvement had tumor recurrence, most often peritoneal, irrespective of the tumor margin status. In our series, the only patient with histologically proven port-site involvement, having undergone en bloc resection of a carcinomatosis nodule, died of peritoneal recurrence 15 months after initial cholecystectomy. We therefore confirmed the results of the MSKCC series, showing that port-site excision does not improve overall survival, disease-free survival or the delay between initial cholecystectomy and recurrence (irrespective of margin status). Of note, among the NPSE patients, between 2 and 29% had microscopic involvement. In our series, PSE was more likely to be performed in association with major hepatectomies and adjacent organ resections. Even if the R0 margin rate was significantly higher, survival did not differ between the two groups. Similar results were observed in the R0 resection subgroup. From a technical point of view, PSE is difficult and often incorrectly performed. One possible explanation for the absence of difference between the two groups might be that a PSE centered only on the skin scar may leave tumor behind
if the trocar had been inserted in an oblique direction. To this end, we propose insertion of a thin drain trocar joining the two scars (skin and peritoneal) to guide the PSE (Fig. 5). Lastly, 8% of our patients presented with a specific complication of PSE, i.e. incisional hernia. This rate is comparable with that observed in the MSKCC series (nine patients of 69) and should be taken into consideration in the therapeutic strategy. Our multicenter study was retrospective, and therefore contained several biases including a measurement bias (small sample, low percentage of patients undergoing PSE). However, the low incidence of port-site involvement makes it improbable if not impossible to perform a therapeutic trial on the subject. In conclusion, we confirmed that PSE need not be routinely performed during secondary resection with curative intent for IGBC discovered after cholecystectomy. We would rather propose a frozen section examination of the peritoneum surrounding the peritoneal trocar orifices for all gallbladder carcinoma greater or equal to T2.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
References [1] Varshney S, Buttirini G, Gupta R, et al. Incidental carcinoma of the gallbladder. Eur J Surg Oncol 2002;28:4—10.
284 [2] Wullstein C, Woeste G, Barkhausen S, Gross E, Hopt UT, et al. Do complications related to laparoscopic cholecystectomy influence the prognosis of gallbladder cancer? Surg Endosc 2002;16:828—32. [3] Benoist S, Panis Y, Fagniez PL, et al. Long-term results after curative resection for carcinoma of the gallbladder. Am J Surg 1998;175:118—22. [4] Cubertafond P, Gainant A, Cuchiaro G, et al. Surgical treatment of 724 carcinomas of the gallbladder. Results of the French Surgical Association survey. Ann Surg 1994;219:275—80. [5] Regimbeau JM, Fuks D, Le Treut YP, et al. Surgery for hilar cholangiocarcinoma: a multi-institutional update on practice and outcome by the AFC-HC study group. J Gastrointest Surg 2011;15:480—8. [6] Box JC, Edge SB. Laparoscopic cholecystectomy and unsuspected gallbladder carcinoma. Semin Surg Oncol 1999;16:327—31. [7] Pawlik TM, Gleisner AL, Vigano L, et al. Incidence of finding residual disease for incidental gallbladder carcinoma: implications for re-resection. J Gastrointest Surg 2007;11:1478—86. [8] Goetze TO, Paolucci V. Adequate extent in radical re-resection of incidental gallbladder carcinoma: analysis of the German Registry. Surg Endosc 2010;24:2156—64. [9] Romano F, Franciosi C, Caprotti R, et al. Laparoscopic cholecystectomy and unsuspected gallbladder cancer. Eur J Surg Oncol 2001;27:225—8. [10] Suzuki K, Kimura T, Ogawa H. Long-term prognostic of gallbladdder cancer diagnosed after laparosopic cholecystectomy. Surg Endosc 2000;14:712—6. [11] Goetze TO, Paolucci V. Benefits of reoperation of T2 and more advanced incidental gallbladder carcinoma: analysis of the German Registry. Ann Surg 2008;247:104—8. [12] Goetze TO, Paolucci V. Immediate re-resection of T1 incidental gallbladder carcinomas: a survival analysis of the German Registry. Surg Endosc 2008;22:2462—5. [13] Hu JB, Sun XN, Xu J, He C. Port site and distant metastases of gallbladder cancer after laparoscopic cholecystectomy diagnosed by positron emission tomography. World J Gastroenterol 2008;14:6428—31. [14] Giuliante F, Ardito F, Vellone M, Clemente G, Nuzzo G. Port-sites excision for gallbladder cancer incidentally found
D. Fuks et al.
[15]
[16]
[17]
[18]
[19]
[20] [21]
[22] [23]
[24] [25]
[26]
[27]
after laparoscopic cholecystectomy. Am J Surg 2006;191: 114—6. Lundberg O, Kristoffersson A. Port site metastases from gallbladdercancer after laparoscopic cholecystectomy. Results of a Swedish survey and review of published reports. Eur J Surg 1999;165:215—22. Z’Graggen K, Birrer S, Maurer CA, Wehrli H, Klaiber C, Baer HU. Incidence of port site recurrence after laparoscopic cholecystectomy for preoperatively unsuspected gallbladder carcinoma. Surgery 1998;124:831—8. Weiland ST, Mahvi DM, Niederhuber JE, Heisey DM, Chicks DS, Rikkers LF. Should suspected early gallbladder cancer be treated laparoscopically? J Gastrointest Surg 2002;6:50—6. Zhang WJ, Xu GF, Zou XP, et al. Incidental gallbladder carcinoma diagnosed during or after laparoscopic cholecystectomy. World J Surg 2009;33:2651—6. Fong Y, Brennan MF, Turnbull A, Colt DG, Blumgart LH. Gallbladder cancer discovered during laparoscopic surgery. Potential for iatrogenic tumor dissemination. Arch Surg 1993;128:1054—6. Ricardo AE, Feig BW, Ellis LM, et al. Gallbladder cancer and trocar site recurrences. Am J Surg 1997;174:619—22. Maker AV, Butte JM, Oxenberg J, et al. Is port site resection necessary in the surgical management of gallbladder cancer? Ann Surg Oncol 2012;19:409—17. http://www.snfge.asso.fr/01-Bibliotheque/0G-Thesauruscancerologie/publication5/sommaire-thesaurus.asp Regimbeau JM, Pruvot FR, Farges O, editors. Chirurgie des cholangiocarcinomes intrahépatiques, hilaires et vésiculaires. France: Arnette Wolker Kluver; 2009. Chiche L, Metairie S. Fortuitous discovery of gallbladder cancer. J Chir (Paris) 2001;138:336—41. Wibbenmeyer LA, Wade TP, Chen RC, Meyer RC, Turgeon RP, Andrus CH. Laparoscopic cholecystectomy can disseminate in situ carcinoma of the gallbladder. J Am Coll Surg 1995;181:504—10. Paolucci V, Schaeff B, Schneider M, Gutt C. Tumor seeding following laparoscopy: international survey. World J Surg 1999;23:989—95. Paolucci V. Port site recurrences after laparoscopic cholecystectomy. J Hepatobiliary Pancreat Surg 2001;8:535—43.