J Hepatobiliary Pancreat Surg (2001) 8:525–529
Open versus laparoscopic cholecystectomy for gallbladder carcinoma Owe Lundberg and Anders Kristoffersson Department of Surgery, University Hospital of Northern Sweden, S-901 85, Umeå, Sweden
Abstract Laparoscopic surgery has replaced conventional open cholecystectomy for benign gallbladder disease. A major concern is how to handle gallbladder cancer in the laparoscopic era, since there are numerous case reports of port site metastases from gallbladder cancer after laparoscopic cholecystectomy. There are also many experimental studies favoring the opinion that the laparoscopic technique implies a higher risk of spreading malignant disease. This opinion has gained wide acceptance despite little previous clinical effort to determine the risk of tumor dissemination and the lack of comparisons between open and laparoscopic surgery. This report is a short summary of our own studies and present knowledge with special respect to the clinical aspects of the development and incidence of abdominal wall metastases. Among 270 patients with verified gallbladder carcinoma in whom 210 had open surgery and 60 a laparoscopic cholecystectomy, 12 patients (6.5%) in the open cholecystectomy group and 9 (15%) in the laparoscopic group developed incisional metastases. Although the sparse clinical documentation does not unavoidably mean that laparoscopic cholecystectomy has an increased risk of disseminating tumor cells, we recommend open surgery in cases of known or suspected gallbladder carcinoma. Key words Gallbladder Laparoscopy
cancer
·
Cholecystectomy
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has not been extensively debated in benign gallbladder disease but has become more controversial in malignancies. The occurrence of port site metastases in particular has raised substantial concern.1–3 The discussion of laparoscopic cancer surgery in general and port site metastases in particular has mainly been focused on cancer surgery on the large bowel.4 In colorectal surgery there are several reports on wound metastases after open surgery indicating an incidence of approximately 1%.5,6 This figure has consequently been generally accepted in laparoscopic colorectal surgery and regarded as a baseline for laparoscopic surgery in malignant disease.7 Some studies reported an incidence of port site metastases of 1% or less after laparoscopic colorectal cancer surgery.7,8 This indicates that it is possible to perform laparoscopic colorectal surgery for malignant disease with an acceptable number of incisional metastases, at least in expert hands. The scientific documentation on gallbladder cancer and laparoscopic surgery has been sparse and it appears inappropriate to advocate laparoscopic surgery in gallbladder carcinoma based on the results from studies on colorectal cancer.
Gallbladder cancer and cholecystectomy Introduction During the past decade laparoscopic cholecystectomy has replaced the conventional open technique, and today about 90% of all cholecystectomies are done laparoscopically. The use of the laparoscopic technique
Offprint requests to: O. Lundberg Received: January 9, 2001 / Accepted: August 1, 2001
Gallbladder cancer is the sixth most common gastrointestinal malignancy and the ninth most lethal neoplasm of the gastrointestinal tract.9 The 5-year survival rate has been reported to be 5%–13% after curative surgery.10 The standard procedure has been open cholecystectomy with or without extended resection (hepatic/common bile duct resection and/or lymphatic clearance). Although a rare disease, unsuspected gallbladder cancer is reported in 1%–2% of all cholecystectomies.11,12 The finding of port site recurrences after laparoscopic cholecystectomy in these preoperatively unsuspected malignancies has raised the question of
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O. Lundberg and A. Kristoffersson: Open vs laparoscopic cholecystectomy for gallbladder carcinoma
whether the laparoscopic technique implies an increased risk of spreading malignant disease.13 Among more than 100 case reports on port site metastases in general, the majority are reported from gallbladder cancer after laparoscopic cholecystectomy.14 Despite the lack of knowledge of the true incidence of port site recurrences, their mere existence is the main reason why the use of laparoscopic procedures in malignancies is still highly controversial. Scattered reports exist of attempts to determine the incidence of port site metastases from gallbladder cancer after laparoscopic cholecystectomy. Z’graggen et al.15 and Paolucci et al.16 in two large series including 10 925 and 117 840 laparoscopic cholecystectomies during which 37 and 409 gallbladder cancers were retrieved, reported an incidence of 14% and 17% port site metastases, respectively. In Japan, Suzuki and coworkers reviewed 3566 laparoscopic cholecystectomies and found 30 gallbladder carcinomas and 3 patients (10%) with port site metastases.17 Yamaguchi et al., in a report from a smaller series, noted an incidence of port site metastases of 12.5%.18 Ricardo et al. in 1997 reported from a tertiary referral center on 79 patients with gallbladder cancer, of whom 63 had undergone cholecystectomy.19 Twentyone had a laparoscopic operation, 16 a converted procedure, and 26 an open cholecystectomy independent of the surgical procedure, an incidence of wound or port site metastases of 30% was registered. In Ricardo et al.’s study 89% of the patients had advanced cancer (T3/T4). We have recently published the first study in an unselected patient population with wound recurrence from gallbladder cancer after open cholecystetomy.20 The incidence of port site metastases from gallbladder cancer after laparoscopic cholecystectomy had previously been investigated in the same population.21 In this paper, we summarize the findings from those two stud-
ies and although a direct retrospective comparison was impossible to design, data on incisional metastases in a large group of patients with open and laparoscopic cholecystectomy are presented below.
Patients and methods Personal data from all patients with histopathologically verified adenocarcinoma or carcinoma in situ of the gallbladder at the 8 university and 24 country hospitals, comprising 5.5 million inhabitants in Sweden in 1991–1994, were obtained from the Swedish Oncologic Centres. These centers register all patients with confirmed malignancies by clinical and histopathologic diagnoses. The National Board of Health and Welfare records all operations performed in Sweden with a surgical classification code, and data were collected from their files. To identify those patients who underwent cholecystectomy we matched all patients with surgical classification codes for cholecystectomy (open, laparoscopic, or converted) against all patients with verified gallbladder carcinoma. Of 447 patients with gallbladder cancer, 270 had a cholecystectomy (210 open and 60 laparoscopic) (Fig. 1). The first study focused on port site metastases after laparoscopic cholecystectomy21 and a written questionnaire was sent to the participating hospitals. The questionnaire requested information on the number of laparoscopic cholecystectomies performed during the study period and the number of port site metastases encountered. To verify that all laparoscopic cholecystectomies were correctly registered, i.e., were actually performed as laparoscopic surgery, we double-checked with the Swedish Registry of Laparoscopic Cholecystectomy. The second study concerned wound recurrences from gallbladder cancer after open cholecystectomy20 in
Fig. 1. Surgical procedures in 447 patients with histopathologically verified adenocarcinoma or carcinoma in situ of the gallbladder
O. Lundberg and A. Kristoffersson: Open vs laparoscopic cholecystectomy for gallbladder carcinoma
the same population of patients. The clinical records of all patients with gallbladder carcinoma who underwent open cholecystectomy were scrutinized and the pathologic reports reexamined and classified according to the TNM system. Additional information was also collected from local hospitals as well as from outside hospital records.
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Of the 215 patients with gallbladder cancer who underwent open cholecystectomy, 6 were excluded due to other malignant diagnoses (pancreas, duodenal, and bile duct carcinoma) and files on 18 patients were not obtained. Of the remaining 186 patients, 110 (59%) had a T3 or T4 lesion and 72 (39%) a Tis, T1, or T2 lesion. In 4 patients tumor stage was not stated. The mean follow-up was 53 months. The mean survival time from cholecystectomy until death for the entire open cholecystectomy group was 6 months. At follow-up 26 patients (14%) were alive with no signs of metastatic disease. Twelve (6.5%) patients who had undergone open cholecystectomy and with verified gallbladder carcinoma developed wound metastases. The mean time for developing wound recurrence was 5.5 months. Individual data on patients with wound metastases are shown in Table 2.
Results Replies were obtained from 94% (30/32) of the clinics. A total of 11 976 laparoscopic cholecystectomies were performed during 1991–1994. Sixty patients had gallbladder cancer and 9 (15%) developed port site metastases. Clinical data on the patients with port site metastases are depicted in Table 1.
Table 1. Demographic, clinical, and survival data in 9 patients with port site metastases from gallbladder cancer after laparoscopic cholecystectomy Patient no. 1 2 3 4 5 6 7 8 9
Sex/age
Indication for surgery
Tumor stage (TNM)
Interval to recurrence (months)
Verification/resection of metastases
Survival (months)
M/66 F/58 F/66 F/71 M/50 F/73 M/70 F/70 F/72
Cholelithiasis Cholelithiasis Cholelithiasis Cholelithiasis Gallbladder polyp Cholelithiasis Cholelithiasis Cholelithiasis Cholecystitis
T3 T3 T3 T3 Tis T3 — — T2
3 6 18 3 28 12 6 — 41
Histology resection Histology resection Histology resection Histology resection Histology resection Histology resection Histology biopsy Clinical examination Histology resection
5 18 22 6 Alive (54 months) 18 16 Lost to follow-up Alive (46 months)
Table 2. Demographic, clinical, and survival data in 12 patients with wound metastases from gallbladder carcinoma after open cholecystectomy Patient no.
Sex/age
1
F/81
2
F/79
3 4
M/65 F/58
5 6 7
F/66 F/66 M/77
8 9 10 11 12
F/73 F/60 F/90 F/71 M/69
Indication for surgery Suspected malignancy Jaundice Cholelithiasis Suspected malignancy Cholelithiasis Cholelithiasis Suspected malignancy Acute cholecystitis Cholelithiasis Cholelithiasis Jaundice Acute cholecystitis
Tumor stage (TNM)
Interval to recurrence (months)
Verification of metastases
Survival (months)
Cholecystectomy
T4
22
Clinical exam
25
Cholecystectomy
T3
2
Clinical exam
3
Cholecystectomy Cholecystectomy
T1 T3
7 6
Histology Cytology
65 9
Extended resection Extended resection Cholecystectomy
T2 T3 T3
4 8 5
Histology Histology Histology
18 15 7
Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy
T2 T3 T3 T3 T3
17 3 5 6 2
Histology Histology Histology Histology Histology
28 6 30 11 5
Surgical procedure
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O. Lundberg and A. Kristoffersson: Open vs laparoscopic cholecystectomy for gallbladder carcinoma
Discussion The findings from our studies appear to indicate that the risk of incisional metastases is higher after laparoscopic cholecystectomy. Except for Ricardo et al.’s study, this is in accordance with other reports.15–18 For obvious reasons, it will not be possible to perform prospective, randomized studies enabling us to conclude which method should be preferred. The observation that laparoscopic surgery may be associated with an increased risk of spreading malignant cells has gained even more acceptance after numerous experimental studies.22–24 Several animal studies have also indicated that insufflation of the abdominal cavity, especially with carbon dioxide, may increase the risk of peritoneal implantation of cancer cells.25–27 Even if the sparse documentation regarding the incidence of wound metastases after open cholecystectomy indicates a minor risk compared to that after laparoscopic surgery, it is significantly higher than that seen after open colorectal surgery.5,6 An obvious bias in the retrospective design of our study on open cholecystectomy is that some wound metastases may never have been detected. This was also shown in the study of Reilly et al., in which the majority of wound metastases after open colorectal surgery were incidentally identified at reoperation.5 One of the major differences between gallbladder and colorectal cancer surgery is that in the latter the tumors are known preoperatively and thereby handled using oncologic principles. This is in contrast to gallbladder cancer, which has been thought to be seldom known preoperatively.28 However, our study on open cholecystectomies showed that the indication for surgery was “suspicion of malignancy” in 40% of the cases and “jaundice” or “acute cholecystitis” in another 44%. Only 15% of the 186 patients who were found to have gallbladder cancer had the indication “symptomatic gallstones.” This indicates that we more often than previously assumed should suspect a diagnosis of gallbladder cancer preoperatively in the cholecystectomy situation. In our opinion, the high incidence of incisional metastases in open as well as in laparoscopic cholecystectomy further confirms the aggressiveness of gallbladder carcinoma. An interesting observation in our study on open cholecystectomy was that the mean time for developing wound recurrence was equal to the mean survival of the entire open cholecystectomy group. This could indicate that many of the patients who had an open cholecystectomy may not have lived long enough to develop any obvious recurrent disease in the surgical wound. Even if the difference in incidence of incisional metastases between open and laparoscopic cholecystectomy is small, we recommend open surgery in cases of
gallbladder carcinoma. The latest reports of port site recurrence show that probably the single most important factor for the development of port site metastases is surgical technique.29–31 In laparoscopic cholecystectomy the gallbladder (⫽ the tumor) in handled with traumatic forceps, a maneuver regarded as disastrous in all oncologic surgery. There is also a higher risk of perforating the gallbladder in laparoscopic cholecystectomy, which gives early cancer the opportunity to disseminate and thereby transform a curative operation into a palliative one. Three patients with port site metastases who had in situ gallbladder cancers have been reported, and all their gallbladders were perforated intraoperatively.13,21,32 Intraoperative perforation also appears to be more frequent in patients with wound metastases after open cholecystectomy (9/12 in our series). We therefore believe that in laparoscopic surgery, the unavoidable direct handling of the malignant gallbladder is unfavorable and that pneumoperitoneum may be involved in the spread of tumor cells. However, the significance of pneumoperitoneum is still unclear and in the clinical setting it may even be overestimated. The majority of port site metastases are probably signs of disseminated disease, although the presence of longterm survivors after resection of the metastases could suggest that in some cases they represent an isolated recurrence.15,21,33 With present knowledge, we advocate conventional open surgery in cases of known or suspected gallbladder cancer, especially since laparoscopic cholecystectomy has become a widespread procedure, often performed by surgeons with minor experience in advanced laparoscopic and particularly oncologic surgery. Accordingly, when signs of malignancy are found during laparoscopic cholecystectomy, the operation should be converted into an open surgical procedure.
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