Is laparoscopic cholecystectomy hazardous for gallbladder cancer? Kenji Suzuki, MD, Taizo Kimura, MD, and Hiroshi Ogawa, MD, Hamamatsu, Japan
Background. There have been several case reports of unexpected gallbladder cancer diagnosed after laparoscopic cholecystectomy (LC) being associated with fatal recurrence of cancer in the abdominal wall. Therefore there is a risk that LC might worsen the prognosis of gallbladder cancer. The objective of this study was to examine the frequency of recurrence of cancer in the abdominal wall and the prognosis of patients with unexpected gallbladder cancer diagnosed after LC. Methods. A clinicopathologic study was performed on 30 patients with postoperatively diagnosed gallbladder cancer among 3566 patients undergoing LC at 19 institutions. The cumulative survival rate was compared with that reported for gallbladder cancer diagnosed after open cholecystectomy. Results. Recurrence of cancer in the abdominal wall occurred in three patients, and two of them died. The 3-year survival rate was 100% for early gallbladder cancer and 70% for advanced tumors. These results were comparable to the 3-year survival rates for gallbladder cancer diagnosed after open cholecystectomy. Conclusions. The incidence of recurrence of cancer in the abdominal wall was increased, but the medium-term prognosis was not worsened by laparoscopy. It does not appear necessary to exclude patients with cholecystitis or gallbladder wall hypertrophy from undergoing laparoscopic procedures on the grounds that they might have gallbladder cancer. (Surgery 1998;123:311-4.) From the First Department of Surgery, Hamamatsu University School of Medicine, and the Department of Pathology, Seirei Mikatabara General Hospital, Hamamatsu, Japan
LAPAROSCOPIC CHOLECYSTECTOMY (LC) IS WIDELY used to treat cholelithiasis and cholecystitis.1 Therefore LC is sometimes inadvertently performed in patients with gallbladder cancer for whom it is generally contraindicated.2 It has been reported that the frequency of unexpected gallbladder cancer is about 1% among patients undergoing LC.3 There have also been several reports of recurrence at the laparoscopic port sites.4-6 Accordingly, concern has been expressed that LC might adversely affect the prognosis of gallbladder cancer.3,7,8 The objectives of this study were to clarify (1) the frequency of recurrence of cancer in the abdominal wall and (2) the prognosis of gallbladder cancer diagnosed after LC. MATERIAL AND METHODS The medical records, imaging data, operative records, and pathologic findings were reviewed in 30 patients with unexpected gallbladder cancer among 3566 patients undergoing LC at 19 instituAccepted for publication Aug. 5, 1997. Reprint requests: Kenji Suzuki, MD, First Department of Surgery, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu, 431-31 Japan. Copyright © 1998 by Mosby, Inc. 0039-6060/98/$5.00 + 0 11/56/85938
tions in Shizuoka prefecture from February 1992 to July 1996. Follow-up data were obtained on January 31, 1997, for all patients from their outpatient clinical records and by contact with their treating physicians. In 16 patients, 5 mm serial sections of the entire gallbladder were prepared, and in the other patients sections of the main tumor were obtained. One pathologist reexamined the hematoxylineosin–stained specimens. Tumor stage was classified according to the pathologic tumor (pT) system.9 It is based on the extent of local invasion as follows: pTis, carcinoma in situ; pT1, tumor invading the mucosa or muscle layer (pT1a, tumor invading the mucosa and pT1b, tumor invading the muscle layer); pT2, tumor invading the perimuscular connective tissue with no extension beyond the serosa or into the liver; pT3, tumor invading beyond the serosa or into adjacent organs (extending 2 cm or less into liver), and pT4, tumor extending more than 2 cm into the liver or two or more adjacent organs (stomach, duodenum, colon, pancreas, omentum, and extrahepatic bile ducts). The median follow-up time was 29 months, ranging from 7 to 59 months. The cumulative survival rate was calculated according to the KaplanMeier method. Statistical analysis was performed SURGERY 311
312 Suzuki, Kimura, Ogawa
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Fig. 1. Survival curves by pT category in 30 patients with unexpected gallbladder cancer after laparoscopic cholecystectomy.
Table I. Preoperative examinations of unexpected gallbladder cancer (n = 30) No. of cases Ultrasonography Cholangiography ERC IVC PTC PTCC CT Plain Enhanced EUS Angiography
30 30 22 9 1 2 24 24 19 5 0
% 100 100 73 30 3 7 80 80 63 17
ERC, Endoscopic retrograde cholangiography; IVC, intravenous cholangiography; PTC, percutaneous transhepatic cholangiography; PTCC, percutaneous transhepatic cholecystography; EUS, endoscopic ultrasonography.
with the chi-squared test (Fisher’s exact method) for categoric information, with significance being set at the p < 0.05 level. Calculations were performed with the StatView 4.5 program (Abacus Concepts, Inc., Berkeley, Calif.) and a Macintosh computer (Apple Computer Inc., Cupertino, Calif.). RESULTS The 30 patients with unexpected gallbladder cancer included eight men and 22 women aged 39 to 86 years (mean age, 69.9 years). For preoperative evaluation almost all patients underwent ultrasonography, computed tomography (CT), and cholangiography. (In Japan preoperative ultrasonography and cholangiography are performed routinely for patients with cholelithiasis, cholecystitis, and gallbladder polyps. Even CT was done routinely at most of the institutions.) Endoscopic ultrasonography was performed in only five patients, and angiography was not done (Table I). The preoperative diagnosis was cholelithiasis in 12 patients, cholecystitis in nine patients, and gall-
bladder polyp in nine patients. In three of nine patients with polypoid lesions, the possibility of early gallbladder cancer was raised on the basis of the size of the polyps (13, 15, and 17 mm, respectively). However, there was no clear evidence of cancer, so they underwent LC. In only one patient was malignancy confirmed directly by laparoscopic cholecystoscopy.10 However, no evidence of malignancy or metastasis was noted during LC in the other patients. Bile spillage occurred in 15 (50%) of 30 patients. The cause was gallbladder perforation during dissection of the gallbladder bed or by the grasping forceps in 11 patients, slippage of clips in two patients, injury during extraction of the gallbladder from the abdomen in one patient, and laparoscopic cholecystoscopy in one patient. There was no correlation between bile spillage and tumor stage (p = 0.15). LC was converted to open cholecystectomy in four patients, including three in whom laparoscopic procedures proved difficult and one who had a diagnosis of cancer on laparoscopic cholecystoscopy. Histologic examination revealed a carcinoid tumor in one patient and adenocarcinoma in all other patients. The lesion was well-differentiated adenocarcinoma in 25 patients, moderately differentiated adenocarcinoma in two patients, and poorly differentiated adenocarcinoma in two patients. The tumor stage was pTis in one patient, pT1a in 13, pT1b in five, pT2 in 10, and pT3 in one patient. No patient had pT4 disease. Lymphatic invasion was found in five patients, venous invasion in seven patients, and perineural infiltration in three patients. All of these patients had pT2 or pT3 tumors, whereas in patients with pTis and pT1 disease results were negative for such invasion. A significant correlation was found between disease stage and lymphatic invasion (p < 0.01), venous invasion (p < 0.01), or perineural infiltration (p < 0.01). Invasion of the cut end of the cystic duct was found in one patient with pT2 disease, and metastasis to the cystic lymph nodes was seen in another patient with pT2 disease. After a diagnosis of gallbladder cancer was made, additional operations were performed in eight patients. Eight patients with pT2 or pT3 disease who were in fair or good condition were recommended to undergo further operations, and six of them agreed. One patient underwent regional lymphadenectomy and excision of the liver bed. Four patients underwent regional lymphadenectomy, excision of the liver bed, and resection of the extrahepatic bile duct. The umbilical and midabdominal ports were also widely excised in one patient. In one patient with pT3 disease only exploratory laparotomy was performed because of
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Table II. Clinicopathologic characteristics of 11 patients with pT2 or pT3 gallbladder cancer Case no.
Age (yr)
Gender
Bile spillage
pT
Reexcision
1 2 3 4 5 6 7 8 9 10 11
73 77 78 77 83 68 70 71 61 78 65
M M M M F F F F F F F
+ + – + – + + + – – +
2 2 2 2 2 2 2 2 2 2 3
L, B, port – – L – L, B – L, B L, B – Laparotomy
Residual tumor +
– – + – +
Status (mo)
Follow-up (mo)
Died of fall Died of cerebral infarction No evidence of disease Port site recurrence (12), alive No evidence of disease Local recurrence (18), alive Port site recurrence (3), died of disease No evidence of disease No evidence of disease No evidence of disease Port site recurrence (2), died of disease
11 2 16 16 21 29 14 37 38 42 11
M, Male; L, liver bed excision; B, extrahepatic bile duct resection; port, abdominal wall resection including port site; F, female.
peritoneal dissemination. Additional operations were generally not proposed for patients with early cancer. However, in one patient diagnosis was made on the initial pathology report of pT1a tumor invasion of the muscle layer near the liver bed, so the liver bed was excised. In one patient with pT1b disease a carcinoid tumor was diagnosed, so the regional lymph nodes were dissected. Cancer was found at reoperation in two patients with pT2 disease; it was near the cut end of the cystic duct (lymphatic involvement) in one patient and around the common bile duct (perineural infiltration) in the other patient. There was no microscopic implantation in the resected tissue from around the port sites. There were no operative deaths and all of the patients could be followed up. Recurrence of cancer in the abdominal wall was found in three (10%) of the 30 patients, including two with pT2 disease and one with pT3 disease. Local recurrence was suspected in another patient with pT2 disease by CT. There was no significant relation between recurrence in the abdominal wall and histologic grade (p = 0.15), lymphatic invasion (p = 0.17), venous invasion (p = 0.27), or perineural infiltration (p = 0.13). All 19 patients with pTis or pT1 tumors were alive with no evidence of disease 7 to 59 months after LC. Two patients with pT2 disease died of other causes (cerebral infarction and fall). Two patients with abdominal wall recurrence (one pT2 and one pT3) died of the cancer (Table II). The 3-year survival rate was 100% for patients with pTis and pT1 disease, falling to 70% for patients with pT2 disease (Fig. 1). DISCUSSION Among 3566 patients who underwent LC, the incidence of unexpected gallbladder cancer was 0.85%, which was comparable to that in other reports.3,11 Preoperative diagnosis of gallbladder cancer is generally difficult, particularly in patients
with cholelithiasis.12 Retrospective analysis of the imaging data from the 30 patients in this study confirmed that identification and diagnosis of the lesions was difficult in all patients. The mode of spread of gallbladder cancer includes local invasion, regional lymph node involvement, and distant metastasis (lung and liver). Detailed figures have not been reported, but the incidence of abdominal wall recurrence generally appears to be low.13 However, there have been many reports of port site recurrence after LC.3-8 We detected abdominal wall recurrence in three patients (10%). It had been reported that factors such as perforation of the gallbladder during LC,14,15 loss of the peritoneal barrier at the trocar site,6 pneumoperitoneum,16 o r CO 2 17 may be responsible for the high rate of recurrence at the port site. In this study the incidence of bile spillage during LC for unexpected gallbladder cancer was as high as 50%. In the literature it was reported as 10% to 40% for cholelithiasis and cholecystitis.14 Although data on the incidence of bile spillage among all 3566 patients were not available, spillage occurred in 29 (26.3%) of 110 patients who were operated on at our institution in 1993.15 Thus bile spillage may be more likely to occur in patients with gallbladder cancer than in those with cholelithiasis and cholecystitis. Does an increase of abdominal wall recurrence influence the prognosis of unexpected gallbladder cancer diagnosed after LC? To answer this question, it is necessary to make a comparison with the prognosis of gallbladder cancer diagnosed after open cholecystectomy. According to the literature,18,19 the 3-year survival rate was 100% for pT1 disease, 60% to 70% for pT2 disease overall, and 90% to 100% for patients with pT2 disease undergoing reexcision. In this study the 3-year survival rate after LC was not significantly different from that reported after open cholecystectomy.
314 Suzuki, Kimura, Ogawa
When LC was performed in patients with gallbladder cancer, the incidence of recurrence of cancer in the abdominal wall increased, but it did not appear that the medium-term prognosis was affected. This may be because recurrence in the abdominal wall at the trocar site is a form of peritoneal dissemination (i.e., patients with such recurrence would have peritoneal dissemination even if they underwent open cholecystectomy and thus would die anyway, leading to no difference in the prognosis). It is difficult to reach a decision on how to treat gallbladder cancer diagnosed after LC. Good results have been reported after simple open cholecystectomy in patients with pT1 disease.18-21 Reexcision after open cholecystectomy is considered to be required if invasion of the perimuscular connective tissue (pT2) is confirmed or involvement of the surgical margin or cystic duct is observed.17 Taking this into consideration, the following measures are proposed for patients with gallbladder cancer diagnosed after LC. Additional treatment should be decided on the basis of a detailed pathologic examination of the entire resected gallbladder to determine the depth of invasion and the adequacy of the surgical margin. For patients with pTis or pT1 disease, observation is adequate. In patients with pT2 or pT3 disease the bile duct, liver bed, and regional lymph nodes (no. 1a and 1b nodes) should generally be resected. Abdominal wall resection, including the trocar sites, should also be performed to detect tumor cell implantation. In conclusion, this study suggested that it was not necessary to exclude patients from undergoing LC when gallbladder cancer cannot be ruled out (i.e., when there is cholecystitis or thickening of the gallbladder wall). However, the recurrence rate and long-term prognosis remain uncertain. It will therefore be necessary to investigate a larger group of patients with gallbladder cancer diagnosed after LC and to undertake a longer follow-up study. We thank the following 18 institutions for their assistance in compiling this series: Enshu General Hospital, Fuji City Hospital, Fujieda Municipal General Hospital, Fujinomiya City General Hospital, Haibara General Hospital, Heisei Memorial Hospital, Izu Teishin Hospital, Juntendo University Izunagaoka Hospital, Kawamura Hospital, Kikugawa General Hospital, Kosai General Hospital, Shimada Municipal Hospital, Shimizu Kosei Hospital, Shizuoka General Hospital, Seirei Numazu General Hospital, Seirei Hamamatsu General Hospital, Seirei Mikatabara General Hospital, and Yaizu Municipal General Hospital.
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13. 14.
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19. 20.
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