To evaluate a laparoscopic approach to gallbladder lesions including polyps, wall-thickening lesions, and suspected T1 and T2 gallbladder cancer (GBC).

We performed 50 cases of laparoscopic whole-layer cholecystectomy (LCWL) and 13 cases of laparoscopic gallbladder bed resection (LCGB) for those gallbladder lesions from April 2010 to November 2016. We analyzed the short-term and long-term results of our laparoscopic approach.

The median operation time was 108 min for LCWL and 211 min for LCGB. The median blood loss was minimal for LCWL and 28 ml for LCGB. No severe morbidity occurred in either procedure. Nine patients who underwent LCWL and 7 who underwent LCGB were postoperatively diagnosed with GBC. One of these patients had undergone LCGB for pathologically diagnosed T2 GBC after LCWL. All of the final surgical margins were negative. Three of these 15 patients underwent additional open surgery. The mean follow-up period was 26 mo, and only one patient developed recurrence.

LCWL and LCGB are safe and useful procedures that allow complete resection of highly suspected or early-stage cancer and achieve good short-term and long-term results.

Laparoscopic cholecystectomy (LC) is a basic approach for benign diseases such as cholecystolithiasis. However, laparoscopic surgery for gallbladder carcinoma (GBC) has not been widely employed. This is because of the highly malignant potential of GBC, higher rates of port-site recurrence (PSR) and peritoneal dissemination caused by intraoperative perforation of the gallbladder in LC than in open cholecystectomy, and the technical difficulties involved in the laparoscopic performance of standard GBC procedures[1]. Meanwhile, many benign lesions are difficult to differentiate from GBC, including polyps and wall thickening lesions such as chronic cholecystitis and adenomyomatosis[2-12]. Such lesions are sometimes diagnosed as GBC postoperatively by pathological examination. Achieving the correct preoperative diagnosis and stage of GBC is very difficult[13]. Tumor exposure as well as intraoperative gallbladder perforation can increase the risk of cancer relapse; therefore, the above-mentioned lesions, which are associated with suspected GBC, should be carefully managed. We use a laparoscopic approach depending on the type of gallbladder lesion, including suspected T1 and T2 GBC, in our institution. In this study, we evaluated the short-term and long-term outcomes of our strategy.

The patients’ perioperative characteristics, including their clinicopathological and surgical data, are summarized in Table 1. There were no conversions from either LCWL or LCGB to open surgery. The median operation time was 108 (61-221) min for LCWL and 211 (111-269) min for LCGB. The median blood loss was minimal (> 0-150) mL for LCWL and 28 (> 0-150) mL for LCGB. Intraoperative perforation was seen in only one patient (2.0%) who underwent LCWL. There were no instances of severe postoperative complications (Clavien-Dindo grade ≥ 3) and no mortality in either procedure. The length of the postoperative hospital stay was 3 (1-6) d for LCWL and 6 (4-11) d for LCGB. The data of the patients pathologically diagnosed with GBC are shown in Table 2. Among patients who underwent LCWL, nine were postoperatively diagnosed with GBC. The depth of invasion was pT1a in four patients, pT2 in four patients, and pT3 in one patient. Only the one patient with pT3 invasion had lymph node metastases. Two patients with pT2 GBC and one patient with pT3 GBC underwent additional resection. We performed open S4a and S5 segmentectomy with extrahepatic bile duct resection (EBR) and regional lymphadenectomy in one patient with pT2 and one patient with pT3 GBC. One patient (Case No. 9) with pT2 GBC underwent LCGB with D2 lymphadenectomy without EBR as additional resection. The other two patients with pT2 GBC did not undergo additional resection because of their old age. On the other hand, among the patients who underwent LCGB, seven were diagnosed with GBC. One of them was the above-mentioned patient (Case No. 9) who had previously undergone LCWL. The depth of invasion in patients who underwent LCGB was pT1a in two patients and pT2 in five patients. Two of the five patients with pT2 GBC had lymph node metastases. We performed LCGB with D2 lymphadenectomy for three patients with pT2 GBC, including the above-mentioned patient (Case No. 9). One patient with pT2 GBC underwent additional open lymphadenectomy with EBR. In both LCWL and LCGB, all of the final surgical margins were pathologically negative. The mean follow-up period after the operation for GBC was 26 mo, and only one patient (6.7%) who had undergone LCGB with D2 lymphadenectomy for pT2 GBC with multiple lymph node metastases (Case No. 7) developed recurrence 9 mo after the operation and died 14 mo postoperatively. One patient (Case No. 3) died 2 mo after LCWL and 1 mo after the additional resection because of another disease that was not associated with the surgical procedure or the GBC. No port site recurrence or peritoneal dissemination was found. The postoperative RFS rate in patients who underwent the laparoscopic approach is shown in Figure 4.

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Figure 4 Relapse-free survival rate after laparoscopic surgery for pathologically diagnosed T1a and T2 gallbladder carcinoma.

LC is a common procedure for treatment of benign disease. Several studies on laparoscopic radical resection for GBC have also been reported[15-18]. However, the performance of laparoscopic surgery for GBC has not become widespread. The reasons for this are associated with the highly malignant potential of GBC and technical difficulties in performing regional lymphadenectomy and gallbladder bed resection.

The dissection during conventional LC on the liver side is performed along the inner layer of the subserosal layer. When the depth of invasion of the GBC extends to the subserosal layer, residual GBC may exist after conventional LC. Even a mucosal carcinoma in the Rokitansky-Aschoff sinus may result in a positive surgical margin. Moreover, LC for GBC has serious problems with respect to PSR and peritoneal dissemination because of the bile leakage caused by intraoperative perforation. The incidence of PSR after LC for GBC has been reported to range from 11% to 16%[19-22]. Ouchi et al[23] reported that gallbladder perforation occurred in 20% of patients with GBC who underwent LC. Wakai et al[19] reported that gallbladder injury occurred in 25% of patients, of whom PSR or local recurrence developed in 43% who underwent LC among 28 patients with GBC. Both research groups found that patients with gallbladder perforation had a significantly poorer prognosis than did those without perforation. Lee et al[24] described that the incidence of PSR and peritoneal dissemination in patients who underwent LC was higher than that in patients who underwent open cholecystectomy. As just described, laparoscopic surgery for GBC is associated with several difficulties. However, laparoscopic surgery has been widely employed for other various malignancies, and it provides patients with a minimally invasive treatment and early recovery from the surgery. If we can overcome the defects of laparoscopic surgery for GBC, such patients will benefit from this procedure.

GBC is sometimes encountered incidentally. Accurate preoperative diagnosis of GBC and its depth of invasion is difficult. In particular, some lesions, such as chronic cholecystitis (the prime example is xanthogranulomatous cholecystitis) and adenomyomatosis, are important differential diagnoses of GBC that may be difficult to confirm[3-7]. Several studies have reported that polypoid lesions are highly suspected to be GBC when they are larger than 10 mm, solitary, sessile, or rapidly growing[8-12]. Yeh et al[2] reported that polypoid gallbladder lesions larger than 15 mm are more strongly suspected to be malignancies. The above-mentioned lesions should be more carefully treated to avoid causing bile spillage and tumor exposure.

We now use the laparoscopic approach on the types of gallbladder lesions shown in Figure 1. The present study has shown that the risk of gallbladder perforation in both LCWL and LCGB was much lower (2.0% and 0.0%, respectively) than that in conventional LC because the dissection layer is more outside than usual. The entire subserosal layer is removed by LCWL; thus, T1 or T2 GBC can be completely resected in theory. However, suspected GBC is now indicated for LCGB so that a safety margin from the tumor is secured. Proper indications for LCWL and LCGB help to avoid tumor exposure and achieve complete resection of GBC. Intraoperative pathological examination is not always performed because of our institutional system. The specimen is macroscopically evaluated immediately after its extraction to confirm the existence of GBC and negative surgical margins. Further investigation by pathological examination is performed postoperatively. We believe that it is most important to achieve complete resection of the tumor and an accurate diagnosis, including staging, without increasing the risk of recurrence in the first-stage operation. Therefore, we take extreme care to avoid tumor exposure and bile spillage during the first-stage operation; if necessary, we plan an additional second-stage surgery.

When the diagnosis of GBC is made by intraoperative or postoperative pathological examination, an additional resection including regional lymphadenectomy should be considered depending on the depth of GBC invasion. In patients diagnosed with T1a carcinoma, an additional resection is not necessary if the surgical margin of the cystic duct stump is negative. However, an additional extended radical resection including regional lymphadenectomy is recommended in patients with T1b or more advanced GBC because vascular and perineural invasion and positive lymph node metastasis are observed at high rates[25-29]. Such an additional resection was previously performed by open surgery. However, now it can be carried out laparoscopically because of technical improvements. The laparoscopic magnified view allows for more accurate identification of the dissection plane and performance of finer procedures than in open surgery. These are great advantages of laparoscopic surgery, and can lead to reduced bleeding volume and accurate lymph node dissection.

The necessity of routine EBR is controversial[25,30-33]. There is currently no obvious evidence that recommends the routine EBR[1]. We usually perform regional lymphadenectomy without EBR when ductal involvement is not present. The advantages of EBR are facilitation of regional lymphadenectomy, removal of the possible presence of microscopic periductal involvement, and avoidance of postoperative ischemic biliary stenosis. The laparoscopic magnified view allows for sufficient lymph node dissection around the common bile duct and preservation of pericholedochal small vessels to prevent biliary ischemia. However, the lymphatic infiltration around the bile duct is a main pathway for tumor spread[25,34]. Therefore, when positive lymph node metastasis or advanced microscopic neurovascular invasion is detected, we now perform thorough regional lymphadenectomy with EBR by laparotomy, not by laparoscopic surgery.

Several studies have revealed that the long-term survival of patients with T1 or T2 GBC treated by laparoscopic radical cholecystectomy was comparable with that of patients treated by open surgery[17,18]. In the present study, our laparoscopic approach achieved good short-term outcomes and provided acceptable long-term outcomes although there was a limitation that the follow-up period was comparatively short. Until now, there have been no reports on effective laparoscopic approaches to the lesions suspected of GBC as well as definite GBC. Our laparoscopic approach to suspected T1 and T2 GBC is feasible and valid. It is necessary to accumulate the experience of the laparoscopic surgery for GBC and to compare the long-term results with open surgery.

Our laparoscopic approach to suspected T1 and T2 GBC is a safe and useful procedure that overcomes the risk of recurrence caused by conventional LC.