Major Resections for Gall Bladder Cancer

Abstract

Extended cholecystectomy is the standard surgical procedure for gall bladder cancer (GBC), but very few patients with a preoperative diagnosis of GBC are suitable for it. Many patients with advanced GBC need more major resections. GBC patients with jaundice need CBD excision along with extended cholecystectomy and often require a major hepatectomy in the form of extended right hepatectomy (ERH). These patients require extensive invasive preoperative preparation in the form of preoperative biliary drainage and portal vein embolization. Morbidity of major hepatectomy for GBC is high and mortality is significant. Hepato-pancreatoduodenectomy (HPD) for GBC is debatable and its role is being questioned. Combined resection of adjacent organs (CRAO), e.g., colon and duodenum, is very frequently required to achieve R0 resection. Vascular, hepatic artery and portal vein, resection is not recommended for GBC.

Please also see an Invited Commentary on Major Resections for Gall Bladder Cancer by Junichi Kaneko and Kiyoshi Hasegawa (pp **–**)

Invited Commentary on Major Resections for Gall Bladder Cancer

• Junichi Kaneko &
• Kiyoshi Hasegawa 

Gall bladder cancer (GBC) is difficult to diagnose in the early stage due to the absence of specific signs or symptoms. As for advanced GBC, no appropriate treatment has been established. Prof. Kapoor has covered one of the important clinical topics of GBC in full detail. We congratulate him on his valuable review. We agree with him that the surgical indications for advanced GBC must be cautiously considered due to the poor postoperative outcomes. On the other hand, no other effective treatment choices provide better outcomes than surgery. Here we discuss our views concerning the optimal treatments for advanced GBC.

Radical cholecystectomy for T1 or T2 GBC is the standard procedure for achieving an R0 resection, but the appropriate operative procedures for T3 or T4 GBC and/or GBC with lymph node metastasis remain under debate. Goussous and colleagues reported a 90-day mortality rate of 17% according to a national cancer database of the United States (Goussous et al. 2017b), in which 59% of patients were T1 or T2 and the remaining 41% were T3 or T4. Although a 90-day mortality rate of 17% is high, we stress that treatment-related and disease-related deaths must be considered separately when evaluating the effects of each treatment choice. Because the presence of lymph node metastasis is clearly a poor prognostic factor, GBC with extensive lymph node metastasis is not a good indication for surgery. Accurately diagnosing the extent of GBC is important for deciding the optimal choice. An intraoperative step-by-step regional lymph node dissection would be helpful, as we have advocated (Kokudo et al. 2003b). On the other hand, an aggressive surgical strategy against locally advanced GBC may be justified because of the poor efficacy of nonsurgical treatments, such as chemotherapy and radiotherapy, if zero or very low postoperative mortality is achieved.

Although hepato-pancreatoduodenectomy (HPD) is a highly invasive procedure, it may be applicable for advanced GBC. Generally, GBC directly invades in two directions: the liver bed in contact with the gallbladder and lymphatic metastasis alongside the pancreas head. Pancreatoduodenectomy is required for lymphatic metastasis (Clavien et al. 2007). For example, in the distribution of positive lymph nodes in pN2 cases, the posterosuperior peripancreatic nodes (N13a) were the most prevalent metastatic sites (79% positive rate) (Kokudo et al. 2003b). In addition, HPD can achieve R0 resection for locally advanced GBC invading the right side of the hepatoduodenal ligament. Thus, HPD has a potential oncologic advantage for obtaining an R0 resection for T3 or T4 GBC (Manterola et al. 2019).

Major and extensive surgical resection, including HPD, for advanced T3 or T4 GBC remains a challenging procedure, however, because of the high-mortality rate of extensive surgical resections (13–17%) (Nimura et al. 1991; Kondo et al. 2000b). A decade after introduction of HPD for advanced T3 or T4 GBC, the Japanese Society of Hepato-Biliary-Pancreatic Surgery reported an HPD-associated in-hospital mortality rate of 8% (Aoki et al. 2018b). Although there are very few reports of major liver resection for GBC from the West, nationwide data from the United States indicate that the mortality rate of hemihepatectomy plus pancreatoduodenectomy is still relatively high—a 30-day mortality rate of 8% and an in-hospital mortality rate of 18% (Tran et al. 2015). Considering that these high mortality rates are due to the invasiveness of HPD procedures, HPD may not be a good choice, as mentioned by Prof. Kapoor.

Recently, however, we reported zero 90-day mortality in 52 HPDs for GBC (n = 13) and bile duct cancer (n = 39), suggesting that nearly zero-mortality is no longer unrealistic (Aoki et al. 2018b). The majority of GBC patients (85%) had a T classification of pT3 or T4. Among the 52 patients, 54% underwent combined resection including the portal vein (n = 2), hepatic artery (n = 1), and/or colon (n = 6). Among the 13 GBC patients, an R0 resection was achieved in 8 (62%) and an R1 resection was achieved in the remaining 5 (38%) patients. Thirty-eight percent of all the patients were UICC stage III and 54% were stage IV. In our report, the 1, 3, and 5-year overall survival rate for all 52 patients was 79%, 48%, and 45%, respectively.

Our strategy of using HPD to treat GBC has five essential elements. First, to relieve jaundice before surgery, an endoscopic approach is preferred (Aoki et al. 2018b). Second, preoperative portal vein embolization should be performed. Third, the future remnant liver volume must be precisely estimated by virtual hepatectomy using surgical planning software during pre- and post-portal vein embolization (Mise et al. 2018). Fourth, a quantitative liver-function test should be performed preoperatively using indocyanine green (ICG) dye (i.e., the rate of retention of indocyanine green determined at 15 min) (Clavien et al. 2007). Lastly, a two-stage pancreaticojejunostomy should be performed to avoid a postoperative pancreatic fistula from the anastomosis (Aoki et al. 2018b; Hasegawa et al. 2008). Certainly, although complicated preoperative preparations and procedures are required, up-to-date interventional radiology and an operating room equipped with information technology may provide the required support for confident medical specialists. HPD should only be performed with adequate preparation and in limited institutions with well-trained staff.

Further studies are required to determine the type of GBC patient that should undergo an extensive operation like HPD to obtain long-term survival. With the recent progress in chemotherapy, extensive surgery together with chemotherapy may provide satisfactory outcomes for advanced GBC patients in the near future. The development of safer surgical techniques and more effective chemotherapy is eagerly anticipated for patients with advanced GBC.