Gallbladder carcinoma incidentally encountered during ... - Springer Link

Clin Transl Oncol (2011) 13:25-33 DOI 10.1007/s12094-011-0613-1

E D U C AT I O N A L S E R I E S

Ye l l o w S e r i e s *

ADVANCES IN CLINICAL MANAGEMENT AND THERAPY OF CANCER

Gallbladder carcinoma incidentally encountered during laparoscopic cholecystectomy: how to deal with it Ketao Jin · Huanrong Lan · Tieming Zhu · Kuifeng He · Lisong Teng

Received: 26 July 2010 / Accepted: 26 September 2010

Abstract Gallbladder cancer (GBC), characterised by rapid progression and a poor prognosis with a high mortality rate, is a complex disease to treat. Incidental gallbladder carcinoma (IGBC) is defined as carcinoma of the gallbladder suspected for the first time during cholecystectomy or accidentally found on histological examination of the gallbladder. With the increasingly widespread acceptance of laparoscopic cholecystectomy (LC) and difficulties in diagnosing GBC preoperatively, the number of cases of IGBC during and after LC has increased. However, management of IGBC is a difficult issue in the absence of established guidelines. Problems associated with IGBC related to LC are the decisions of whether, when and how to perform additional surgery. Controversy remains regarding the effectiveness of additional resection in different stages of GBC.

*Supported by an unrestricted educational grant from MSD Oncology K. Jin · K. He · L. Teng (쾷) Department of Surgical Oncology First Affiliated Hospital, College of Medicine Zhejiang University 79 Qingchun Road Hangzhou, Zhejiang 310003, China e-mail: [email protected] K. Jin · T. Zhu Department of Surgery Zhuji Hospital, Wenzhou Medical College Zhuji, Zhejiang, China H. Lan Department of Gynecology and Obstetrics Zhuji Hospital, Wenzhou Medical College Zhuji, Zhejiang, China

This review gives an overview of IGBC related to LC, and further discusses the preoperative, intraoperative and postoperative diagnosis and management of IGBC during LC. Keywords Cholecystectomy · Gallbladder carcinoma · Incidental gallbladder carcinoma · Laparoscopic cholecystectomy

Introduction With the advantages of decreased postoperative pain, earlier oral intake, shorter hospital stay, early resumption of normal activity and improved cosmesis, laparoscopic cholecystectomy (LC) has become routine, supplanting the traditional surgical procedure in general surgery for the treatment of benign gallbladder diseases all over the world [1, 2]. Gallbladder cancer (GBC) is the fifth most common cancer involving the gastrointestinal tract, but it is the most common malignant tumour of the biliary tract worldwide [3–9]. GBC is a rare cancer, with an incidence of 3 per 100,000 [8, 10] and a very aggressive disease, with reported 5-year survival of 3–13% [11, 12] and median survival of 3–11 months [11, 12]. Life expectancy of GBC varies greatly with clinical stage at time of detection [13]. More than 75% of all GBC are not resectable at time of diagnosis [11, 12, 14]. Because no specific symptoms are produced during the early stage, GBC is often only discovered during surgery or diagnosed at an advanced stage of the disease. The small group of patients with prolonged survival rates are those patients with tumours in early stages who were diagnosed by chance after a cholecystectomy or LC for cholecystolithiasis [15, 16].

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Incidental gallbladder carcinoma (IGBC) is defined as carcinoma of the gallbladder suspected for the first time during cholecystectomy or accidentally found on histological examination of the gallbladder. Over two-thirds of all GBC are unknown prior to surgery [17]. Patients with IGBC have a better prognosis than patients with GBC already known preoperatively [17, 18]. However, 15–30% of patients with GBC show no preoperative or intraoperative evidence of malignancy and IGBC is discovered in 0.3–2% of all cholecystectomies performed for benign conditions during or after cholecystectomy [4, 16, 18–21]. LC can now be safely performed for cholecystolithiasis because of the technical improvements and advances in instrumentation. With the wide range of LC procedures being carried out and difficulties in diagnosing GBC preoperatively, the number of IGBC found during or after LC is increasing. It has been reported that IGBC is encountered in 0.2–2.9% of patients undergoing LC [21–32]. However, management of IGBC is a difficult problem in the absence of established guidelines. Problems associated with IGBC related to LC are the decisions of whether, when and how to perform additional surgery. Controversy remains regarding the effectiveness of additional resection in different stages of GBC. In this review, we made an overview of IGBC related to LC, and further discussed the preoperative, intraoperative and postoperative diagnosis and management of IGBC during LC.

Overview of IGBC related to LC IGBC is identified when GBC is found in histopathology analyses after removal of gallbladder tissue for symptomatic benign gallbladder disease [33]. GBC is suspected preoperatively for only 30% of all patients [8, 10]. The remaining 70% of all GBC cases are discovered incidentally by the pathologist. Because of the increased use of LC and difficulties in diagnosing GBC preoperatively, IGBC discovered during and after LC has become more frequent. LC has become a standard procedure for the treatment of benign gallbladder diseases but perhaps a contraindication in preoperatively diagnosed GBC. In a large series of carcinoma of the gallbladder evaluated by laparoscopy, surgical removal was thought to be appropriate in only 1 of 98 cases [34]. It is also important to exclude advanced cases of GBC from treatment with LC preoperatively, although preoperative diagnosis of GBC is generally difficult, particularly in patients with inflammation and cholelithiasis. Cases of obvious advanced GBC diagnosed before surgery should not be treated with LC. The treatment of IGBC has been in dispute because of tearing of the gallbladder wall and bile spillage, which can increase the incidence of peritoneal dissemination and port-site recurrence after LC [31, 35–38]. However, many authors report that laparoscopic surgery may not worsen the prognosis of patients with IGBC [21, 39–42], although

Clin Transl Oncol (2011) 13:25-33

there are some opinions to the contrary [37, 43]. Analysis of survival after LC for IGBC has been carried out by several authors. Cucinotta et al. [41] reported that the tumour stage is the most important prognostic factor. Wakai et al. [38] reported that gallbladder perforation during LC is associated with peritoneal dissemination and port-site recurrence and worsens patient survival. Furthermore, peritoneal dissemination and port-site recurrence develop after LC for IGBC [35–37], and bile spillage and damage to the gallbladder wall during LC are known to significantly influence the prognosis of patients with IGBC [10, 40]. The survival rate of patients with IGBC after LC is reported to be comparable to that of patients with IGBC after open cholecystectomy (OC) [31]. The 5-year survival rate after LC for IGBC was 92% in patients with T1 cancer and 59% in patients with T2 cancer [39].

Preoperative, intraoperative and postoperative diagnosis of suspected GBC The preoperative diagnosis of the extent of GBC is important in determining the management plan. Vague symptoms such as cute cholecystitis, pain and fever do not help to differentiate the disease as GBC. Before surgery, the tumour should be adequately staged with preoperative imaging. A variety of preoperative imaging modalities, including ultrasonography (USG), computed tomography (CT) scan, magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS), diagnostic laparoscopy (DL), laparoscopic ultrasonography (LUS), magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP) [44, 45] and percutaneous transhepatic cholangiography (PTC) [46] have been used to assess patients with GBC. USG is a useful initial modality for investigating patients with jaundice or abdominal pain. Preoperative USG evaluation can more readily detect polypoid mucosal lesions of the gallbladder than flat lesions [47], and those greater than 1 cm in diameter have been shown to be associated with malignancy [47–49]. When lesions of this type are detected preoperatively, the suspicion of malignancy must be high. Under USG, GBC manifests as focal or diffuse wall thickening, or as a mass replacing the gallbladder. USG may detect advanced disease in up to 70% of cases, but the sensitivity of USG in detecting early-stage GBC is variable [47, 50–52]. USG has been reported to be relatively nonspecific and insensitive as a means of providing a diagnosis of early-stage GBC preoperatively [53]. CT scan and MRI with MRCP or ERCP provide additional information for tumour staging and resectability such as distant metastases, hepatic invasion, bile duct invasion, lymph node metastasis and vascular invasion [54–60]. A CT scan is commonly used to demonstrate the primary lesion and local spread of GBC. The overall accuracy of CT scan for staging GBC was reported as 71–93% [54–57].


However, it has not consistently been accurate in clearly identifying GBC [43, 51, 61] and is limited for detecting vascular and biliary invasion. Several studies describe the usefulness of MRI in the evaluation of GBC. The sensitivity and specificity of MRI have been reported as 80–100% for bile duct invasion, 87–100% for vascular invasion, 67–100% for hepatic invasion and 56–92% for lymph node metastasis, respectively [58–60]. MRCP is useful in diagnosing the extension of invasion [62]. The sensitivity of MRCP in differentiating between benign and malignant bile duct strictures is 70–96% and that in identifying the site of obstruction is 94–99% [63–65]. Therefore, MRCP is a recommendable procedure. EUS is an excellent procedure for depicting a protruded lesion in the gallbladder and is an accurate modality for imaging gallbladder structures because of the close proximity of the duodenum to the gallbladder and extrahepatic biliary tree. EUS is considered superior to transabdominal USG for imaging the biliary system. EUS can differentiate the double-layered structure of the gallbladder wall and provide higher resolution for imaging small polypoid lesions. Because EUS allows detailed visualisation of the layers of the gallbladder wall, there has been interest in using EUS for preoperative staging of GBC. Its sensitivity in differentiating benign gallbladder disease from GBC is reported to be excellent, ranging from 92% to 97% [66, 67]. It is reported that EUS is also useful for the diagnosis of the depth of mural invasion, the rate of accurate diagnosis being 100% for invasion limited to the mucosa and muscularis propria, and 75% for invasion limited to the subserosa and invasion of the serosal surface or more [68]. There is also a report that in a case of pedunculated lesions, EUS showed that all of these lesions were cancers with invasion limited to the mucosa [69]. Furthermore, EUS criteria for T staging of GBC was proposed by Fujita et al. [70] and the accuracy of these EUS T-staging criteria were confirmed by Sadamoto et al. [69]. DL and LUS are beneficial in the staging of pancreatic and upper gastrointestinal malignancies, but their roles in GBC have not been well established. The potential benefits of identifying occult unresectable disease or major vascular invasion with DL or LUS include less pain and morbidity, decreased hospital stay and overall cost, and earlier initiation of non-surgical therapy. Laparoscopic staging was reported to avoid further surgery in 36–56% patients with hepatobiliary malignancy [71–74]. The results of a prospective intention-to-treat study of patients with early-stage GBC indicated that preoperative CT alone is inadequate. Subsequent EUS evaluation of patients with T1 or T2 disease based on CT criteria revealed invasive disease in 6 of 36 patients (16.7%). LUS identified invasive lesions missed by EUS and thus expertise in LUS appears critical to operative planning. By the combination of CT, EUS and LUS, about one-third of patients were determined to have benign disease; these patients clearly benefited from the planned LC [75]. While most GBCs are first realised after cholecystectomy for presumed benign biliary conditions, some are dis-

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covered during an operative endeavour. Early-stage GBC, appearing as ulcerations or small plaques, may be subtle on gross examination of the opened specimen. The wall of the gallbladder may be firm and thickened, making it difficult to grossly differentiate an early GBC from changes secondary to cholecystitis [76]. More advanced lesions appear as firm masses that infiltrate through the full thickness of the gallbladder wall. Laparoscopy limits the role of palpation in assessing tissues for the presence of malignancy [52], further emphasising the importance of intraoperative examination of the removed gallbladder. Although it was proposed that all cholecystectomy specimens should be opened in the operating room by the operating surgeon and the mucosa of the gallbladder should be carefully examined [77–79], it would be more reasonable if an experienced pathologist could do this macroscopic examination during the operation. Accurate diagnosis of cancer during LC and radical surgery is essential to improve the patients’ prognosis. In gallbladders that are full of gallstones, mucosal changes are impossible to detect using USG, and the diagnosis of small carcinomas remains unreliable using either USG or CT. Moreover, the flat type of GBC is difficult to detect macroscopically, and sclerotic mucosa and thickening of one part of the gallbladder wall has been detected in almost all patients with cholecystolithiasis or chronic cholecystitis, which can confound the diagnosis [76]. For cases in which malignancy is highly suspicious, an intraoperative frozen section is recommended to be performed during LC [30, 76]. Frozen section diagnosis is indispensable as a means of minimising early postoperative recurrence or metastasis. Aoki et al. reported that frozen section during LC was performed in 990 patients with gallstones, and 983 cases were diagnosed as benign and 7 cases as malignant [76]. The accuracy of diagnosing the depth of invasion by frozen section examination was reported to be 70–86% [80, 81]. Once a tumour invades the subserosal layer of the gallbladder (T2 stage), as confirmed by intraoperative frozen section, conversion to the open method during laparoscopic surgery or a second operation for radical surgery is warranted to improve long-term outcome [38]. Another easy, rapid and high-quality diagnosis method, imprint cytology, was also recommended for intraoperative detection of GBC [82, 83]. One more problem may arise when GBC is not readily recognised at the time of LC. GBC at early stages or masked by acute or chronic inflammation could be overlooked during LC, and the diagnosis would then be made only after microscopic examination of paraffin-embedded tissue. The intraoperative frozen tissue diagnosis is fairly reliable in determining whether lesions are malignant or benign, but the frozen tissue diagnosis and the final pathological diagnosis are sometimes not identical [81]. Definitive staging of GBC is dependent on pathological examination of the entire fixed specimen postoperatively. Figure 1 illustrated a proposed strategy for preoperative, intraoperative and postoperative diagnosis and management of LC for patients with suspected GBC.

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Suspected GBC USG, CT, MRI, EUS

DL, LUS

Without liver invasion

Open radical cholecystectomy and lymphadenectomy

With liver invasion

Benign

Malignant

Finish of surgery

LLA

Intraoperative

Gross examination of the opened specimen and intraoperative frozen section diagnosis

LC

Preoperative

With liver invasion

Without liver invasion

or Conversion of laparoscopic to open cholecystectomy and lymphadenectomy

H&E staining

No further resection

Malignant

Postoperative

Benign

Resection

Fig. 1 A proposed strategy for preoperative, intraoperative and postoperative diagnosis, and management of LC for patients with suspected GBC

Management of IGBC during LC Management of GBC based on T stage Surgical resection is the only potentially curative therapy for GBC. Although many authors have reported improved survival rates for patients with GBC after radical surgery [84, 85], the optimal surgical approach may vary according to the disease stage at the time of diagnosis. The therapeutic approach of GBC according to stage is supported by most authors [86–88]. Tis and T1 GBC are usually diagnosed after cholecystectomy. There is a consensus that simple cholecystectomy is an adequate treatment for Tis and T1a GBC. Excellent 5-year survival (up to 100%) has been reported for T1a disease [33, 89]. Nevertheless, there is controversy in the management of T1b GBC. Some authors reported long-term survival after simple cholecystectomy and did not recommend radical resection for T1b GBC [20, 90, 91]. Wakai et al. reported a retro-

spective study of 25 patients with T1b GBC, 13 of whom underwent simple cholecystectomy and 12 radical resection with regional lymph node dissection [90]. Both overt metastases and micrometastases were absent in all lymph nodes examined. The overall 10-year survival was 87% with comparable results after simple cholecystectomy and radical resection (10-year survival 100% vs. 75%). A few studies also reported 5-year survival of 95–100% for T1b GBC after simple cholecystectomy [20, 91]. However, some authors have even advocated more extensive surgery than simple cholecystectomy for T1b GBC due to the problem of locoregional recurrences or lymph node metastasis after simple cholecystectomy [8, 24, 27, 31, 32, 38, 92–97]. Treatment failure with locoregional recurrence was commonly reported after simple cholecystectomy for T1b GBC and the 5-year survival was reported as 37.5– 68% [41, 92, 94, 96, 98–100]. In the cohort study carried out by Otero et al., consecutive patients with T1b GBC (n=26) were treated with simple cholecystectomy [92].


After a mean of 6 years’ follow-up, nine patients with T1b GBC died of recurrence, indicating that some patients with T1b GBC were under-treated. Otero et al. [92] reported that a simple cholecystectomy in cases of T1b GBC yields a 5-year survival rate of 20–100% and concluded that the simple cholecystectomy is not sufficient for T1b GBC. More authors recommended a radical cholecystectomy in a T1b situation [8, 93] and these authors reported a survival benefit of 60–100% for T1b GBC managed with extended resection [93]. As a consequence, some authors advocate aggressive surgery (extended cholecystectomy, wedge resection of gallbladder bed or segment IVb and V resection of liver, N1 lymph node dissection) for T1b GBC. There is no controversy in the management of T2 GBC with radical resection. The reported 5-year survival for patients with T2 GBC treated with simple cholecystectomy and radical resection was 10–61% and 54–100%, respectively [24, 38, 41, 89, 91, 92, 94, 96, 98–107]. Radical resection with liver resection (wedge resection of gallbladder bed or segment IVb and V of liver) and regional lymph node dissection are necessary [91, 102, 108]. Many reports have suggested extended resection with regional lymph node dissection for T2 GBC [91, 109–111] and for more advanced carcinomas [110]. Some reports have also suggested that extended operations combining hepatic resection with a local lymph node dissection can improve longterm survival [112, 113]. The treatment of a locally advanced GBC (T3 and T4) is a challenging problem. The long-term benefit of aggressive surgery for advanced GBC is unclear as the survival benefit may be offset by the surgical morbidity and mortality [114, 115]. The role for surgery in patients with advanced GBC remains controversial, but most surgeons believe that an aggressive surgical approach improves survival for these patients [3, 116, 117]. Surgical resection for advanced GBC is recommended only if a potentially curative R0 resection is technically possible. The 5-year survival of radical surgery for advanced GBC varies from 0% to 32% [89, 95, 99, 111, 118–122]. Some surgeons attempted to combine hepatectomy with pancreaticoduodenectomy for the treatment of locally advanced GBC to increase the chance of R0 resection. Several Japanese surgical groups have demonstrated the feasibility of this combined procedure with acceptable morbidity and mortality and an apparent improvement in patients’ survival for advanced GBC [123–126]. The reported 5-year survival varied from 29% to 87% and the reported surgical morbidity and mortality varied from 40% to 57.1% and 0% to 6%, respectively [123–126]. However, in the five patients reported by Doty et al., four patients died of recurrent tumour at an interval of 11–23 months and the fifth patient was alive and free of clinical disease at 42 months after operation [127]. Therefore, this aggressive approach for advanced GBC remains controversial and the decision for surgery should be based on a balance between the risk of surgery and the outcome [128].

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OC for GBC Although most cholecystectomies for gallbladder diseases are carried out laparoscopically nowadays, LC is absolutely contraindicated when GBC is known or suspected preoperatively. Patients with a preoperative suspicion of GBC should undergo open exploration and cholecystectomy after proper preoperative assessment. If GBC is suspected preoperatively, OC must be performed to enable a complete evaluation of the disease extent and to allow a radical resection if necessary. The type of operation ranges from simple cholecystectomy to combined partial hepatectomy (wedge resection, segment IVb and V resection, right hepatectomy or extended right hepatectomy) and regional lymph node dissection. The extent of resection is at least partly dependent on the extent of the tumour [116]. The extent of hepatectomy depends on the T stage, the anatomical location and the size of the tumour. Any adherent organs should be resected en bloc with the tumour. The initial sites of liver spread are located mostly in segments IVb and V. In patients with hepatic hilar invasion, extended right hepatectomy with or without bile duct resection, or portal vein resection is necessary for resection with a curative intent. Lymph node involvement is an important prognostic factor in patients with GBC. There are significant differences in survival between nodal negative disease and nodal positive disease (5-year survival, 58–77% vs. 0–45%) [119, 129–133]. The extent of lymph node dissection remains controversial. N1 and N2 regional lymph node dissection is indicated for T2–T4 disease. The role of para-aortic lymph node dissection in advanced GBC is not known. Kondo et al. showed that the routine use of regional and para-aortic lymph node dissection provided no survival benefit for patients with para-aortic disease; and the postoperative survival for patients with positive para-aortic lymph nodes without distant metastases was as poor as those patients with distant metastases [110].

LC for IGBC LC has been a treatment of choice for benign diseases of the gallbladder [134, 135]. At present, the gallbladder is removed laparoscopically in more than 75% of cases [24]. With the wide use of LC, the likelihood of IGBC during or after LC has increased [17]. GBC is found incidentally in 0.2–2.9% of patients during or after LC [21–32]. However, some authors suggest that this tumour has a significantly better chance for cure if it is diagnosed as an incidental finding during or after LC [29, 31], mainly because IGBC tends to be in the early stages, most of the cases belonging to T1 or T2 stage [23, 91]. LC alone for treating patients with T2 GBC is not enough because a considerable proportion of the patients with T2 GBC have a possibility of positive lymph node metastasis [133]. Many authors have already reported lymph node dissection as a recommended surgical procedure to

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IGBC during LC

Removal of the suspected GBC in a retrieval bag and waiting for intraoperative frozen section diagnosis or postoperative pathological examination

Tis and T1 a GBC

LC is sufficient

T1b, T2 and more advanced GBC

Conversion to open or more liver bed resection and lymphadenectomy

Excision of all port-sites, segments IVb and V of liver and complete portal lymphadenectomy

Fig. 2 A proposed treatment modality for patients with IGBC during LC

improve the survival of patients with GBC [110, 132]. Laparoscopic lymphadenectomy (LLA) is now widely applied for treating colon cancer and gastric cancer. The efficacy of LLA for these two malignant neoplasms has been reported to be adequate in terms of the oncologic aspects [136]. The LLA requires more experience than open lymphadenectomy because this operative procedure is technically demanding. Therefore, it might be reasonable and safer to convert to open lymphadenectomy when frozen section confirms GBC unless the surgeon has significant experience and expertise in advanced laparoscopic dissection. If GBC is incidentally discovered during LC, open conversion is generally recommended. To improve the prognosis, when GBC is detected postoperatively in patients who have undergone simple LC under the suspicion of benign disease, a second operation for radical re-resection is recommended for those patients with T2 GBC or more advanced carcinomas by many investigators [24, 35, 39, 40, 78, 91, 102, 108, 137]. Furthermore, the analysis of Goetze and Paolucci [137] shows a substantial and statistically significant survival benefit for re-resection of T1b GBC, so this approach must be highly recommended. Figure 2 illustrates a proposed treatment modality for patients with IGBC during LC. If a second operation is indicated, the status of the cystic duct margin from the cholecystectomy specimen should be identified by the surgeon performing the surgical procedure or by a pathologist if possible, usually using an intraoperative frozen section. If the cystic duct margin from the cholecystectomy specimen was negative for malignant cells, the biliary tree would be spared and a lymphadenectomy in conjunction with a IVb and V gallbladder bed liver resection would be performed. If the cystic duct margin from the cholecystectomy specimen was positive, then the cystic duct should be identified intraoperatively. If this operational approach is successful, the cystic duct can usually be resampled. If the cystic duct stump is posi-

tive, or is not identified, then the common duct is usually resected with the portal nodes and liver bed to optimise surgical margins. Though removing the bile duct may improve lymph node clearance, we are not in favour of routine radical bile duct resection and feel that it should be used to obtain a negative margin when the cystic duct stump is positive.

Peritoneal dissemination and port-site recurrence Many reports have indicated the risk of peritoneal dissemination and port-site recurrence with laparoscopic surgery for malignancy [10, 26, 138–140]. The incidence of peritoneal dissemination and port-site recurrence of IGBC ranges from 10 to 29% [22, 23, 39, 43, 78, 138, 141–145]. The reasons for tumour peritoneal dissemination and port-site recurrence after LC for IGBC are gallbladder manipulation with forceps, perforation, extraction without a bag [10] and CO2 pneumoperitoneum [146]. Gallbladder perforation during LC was associated with a high incidence of port-site recurrence (40%) [22]. According to the data of Z’graggen et al., the incidence of port-site recurrence increased from 9% in patients without intraoperative perforation to 40% in those with perforation [22]. Therefore, most authors advocate excision of the port-site during the radical re-resection. A preoperative diagnosis for GBC may be made in as few as 10% of cases [147]. Hence, peritoneal dissemination and port-site recurrence following LC for IGBC will be a problem of some magnitude in the years to come. The risk of peritoneal dissemination and port-site recurrence encouraged the development of retrieval systems to prevent these complications [148]. An appropriate retrieval system during laparoscopy is important for preventing wound contamination. Though it is not feasible to implement a general policy of extracting the gallbladder in a retrieval bag to avoid occasional dissemination because the


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incidence of IGBC is too low [40], routine use of retrieval bags must be recommended for several reasons: (1) it is not always possible to foresee problems with retraction of the gallbladder; (2) it may often be too late to use a bag if the gallbladder ruptures before or during the extraction through a small incision; and (3) the use of a bag is easy to handle. Indeed, the use of a protective retrieval bag is considered ideal during extraction of the GBC, but this precaution does not always exclude an intraperitoneal dissemination event [149–151]. Also, because peritoneal dissemination and port-site recurrence appear early after the second operation [35–37], many authors recommend excision of the port-site at the time of the second operation [39, 43, 78]. Moreover, several reports emphasise the conclusion that excision of the port-site after recurrence may prolong survival [34, 39, 43].

early GBC difficult. With the increase of cholecystectomies due to the wide acceptance of LC, the IGBC during LC is more frequent. The preoperative, intraoperative and postoperative diagnosis of GBC is very important in determining the following management plan. Increased awareness of the presence of GBC and the understanding of appropriate management are extremely important for improved outcome. In patients with Tis or T1a GBC, LC is sufficient. In T1b, T2 and more advanced GBC, a conversion to open reoperation with liver bed resection and lymphadenectomy is indicated. At re-operation of IGBC following LC, it is recommended to excise all port-sites, segment IVb and V of liver and complete portal lymphadenectomy. Additionally, use of a retrieval bag is recommended in cases of LC when GBC is suspected, to minimise the risk of peritoneal dissemination and port-site recurrence.

Conclusions

Acknowledgements This project was supported by the State Key Basic Research and Development Program of China (973 Program, Grant 2009CB521704) and National High-tech Research & Development Program of China (863 Program Grant 2006AA02A245).

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