Clinical implication of surgical resection for recurrent biliary tract cancer: Does it work or not?

Abstract Although recent advances in imaging diagnosis, surgical techniques, and perioperative management can result in increased resectability and improved surgical outcomes, most resected patients still develop cancer recurrence. If patients develop cancer recurrence, their prognosis is very ominous. However, there have been some recent reports to show promising outcomes by aggressive surgical strategy in selected patients who developed cancer recurrence. Because there are various surgical procedures being selected at initial surgery in patients with biliary tract cancers, recurrent patterns after resection are very variable in each patient. However, surgical procedures might usually be very complicated and difficult if re‐surgical resection is considered in patients with recurrent biliary tract cancer, Therefore, surgical re‐resection could bring about high surgical morbidity and mortality rates in most previously reported series. Although re‐surgical resection might offer a chance of favorable outcome in selected patients with biliary tract cancers, these aggressive surgical approaches should be carried out in strictly selected patients by expert surgeons at high‐volume centers.

Therefore, the hilar type of ICC might be involved in perihilar could be defined as proximal bile ducts until the first-order biliary radicle at the hilar region. Reconstruction of the IVC is repaired by ringed Goretex for segmental resection, and auto-vein patch graft for partial resection. Retrohepatic IVC reconstruction after combined IVC resection below the confluence of the hepatic veins might not always be requisite as reported by Yoshidome et al. 16 They reviewed 36 cases undergoing resection of the IVC concomitant with resection of malignancies. Among them, 10 patients underwent circumferential resection of the IVC. Most of the patients who did not undergo replacement of the IVC showed no sign of swelling of the lower limbs, but one patient showed persistent leg edema with oliguria. This patient had poor development of collateral circulation and mild obstruction of the IVC before surgery. They concluded that caval replacement after circumferential resection of the IVC may be necessary in patients who have preoperative development of collateral circulation or who have oliguria or unstable hemodynamics during surgery.
Whether surgical lymphadenectomy for ICC plays a beneficial role for survival in surgical resection is not clearly shown. Although patients with lymph nodal involvement had worse prognosis than those without lymph nodal involvement after surgical resection, surgical resection with lymphadenectomy in the patients with lymph nodal involvement was shown to be beneficial on the prognosis as compared with the prognosis of the unresectable patients. 11 Therefore, lymph nodal involvement in patients with ICC might not be considered a good indication, but it might not be a contraindication to surgical resection. In the eighth edition of the AJCC staging system, 17 regional lymph node N category is defined according to the hepatic location of ICC. For right-liver ICC, regional lymph nodes include the hilar (common bile duct, hepatic arteries, portal vein, and cystic duct), periduodenal and peripancreatic lymph nodes. For left-liver ICC, regional lymph nodes include infra-phrenic, hilar and gastrohepatic lymph nodes. For ICC, spread to the celiac and/ or periaortic and caval lymph nodes is distant metastasis (M1). In the seventh edition, gastrohepatic lymph nodes in left-liver ICC is newly emerged as regional lymph nodes. This newly emerging definition was proposed according to the study of Tsuji et al. 18 After surgical resection of ICC, high rates of recurrence of between 46% and 65% are reported. 19 There are several prognostic factors reported for predicting survival after surgical resection: lymph node involvement, surgical margin, bile duct infiltration, intrahepatic metastasis, and CA19-9. According to the study of Endo et al., the liver is the most common site of recurrence (63%). 20 Other recurrent sites are intraperitoneal dissemination, commonly lymph nodes.
Intrahepatic solitary recurrence without any other distant metastases might be a possible indication to repeat hepatectomy when future remnant liver volume after repeat hepatectomy is sufficient for a patient to withstand surgery. Some studies reported achieving a beneficial prognosis after repeat hepatectomy for solitary intrahepatic recurrence after initial hepatectomy for ICC. 21 Surgical re-resections have been reported in a small study series (Table 1). In these studies, recurrent site of ICC in most patients who underwent surgical reresection for the recurrent lesion was intrahepatic. 13

| EXTRAHEPATIC BILE DUCT CANCER
Complete surgical resection, R0 resection of extrahepatic bile duct cancer is the most effective and only potentially curative treatment.
With the advent of improved imaging diagnosis, and skilled surgical technique, surgical curative resection is more frequently applied and the surgical resection rate has increased gradually. However, the prognosis after surgical resection for bile duct cancer still remains unsatisfactory. Reported survival rates range from 24% to 40%. [34][35][36] Recurrent biliary tract cancer usually manifests as local failure, liver metastasis, lymph nodes metastasis and peritoneal metastasis.
Locoregional failure is the most common pattern of disease recurrence after margin-negative resection. Liver metastasis is one of the common major causes of treatment failure in bile duct cancer, especially in the case of distal bile duct cancer and ampullary cancer. 37 However, surgical results of hepatectomy for liver metastasis have not been fully justified. Kurosaki et al. 38 reported 13 patients with bile duct cancer 7 and ampullary cancer 6 who underwent hepatectomy for hepatic recurrence after initial pancreaticoduodenectomy.
In their series, four of the 13 cases survived more than 5 years. All four long-term survivors underwent margin-negative hepatectomy for a solitary metastasis and were given postoperative adjuvant chemotherapy. They concluded that hepatectomy for a solitary metastasis is the treatment of choice even after pancreaticoduodenectomy, but indication for hepatectomy for multiple metastases is still limited. In patients with extrahepatic bile duct cancer occupying the middle portion of the extrahepatic bile duct who underwent bile duct resection at initial surgery, pancreaticoduodenectomy or hepatectomy was carried out for recurrence of bile duct cancer in a small series including a case report. Takahashi et al. 27 46 also revealed risk factors influencing recurrence, and patterns of recurrence after radical resection in 166 patients for gallbladder carcinoma. In their series, regional lymph nodes and the liver were found to be the most common site for recurrence after curative resection. Lymph node metastases were identified as an independent predictor of tumor recurrence by multivariate analysis. Furthermore, in their retrospective study, 46 it was shown that there was no significantly different disease-free survival rate between the no-adjuvant therapy group and the adjuvant therapy group. As to hepatic metastases from gallbladder cancer, Ohtsuka et al. 48 showed by pathological study that the most important route in the development of hepatic metastasis from gallbladder cancer is along the portal tract after direct hepatic parenchymal invasion. Shirai et al. 49 also reported that extent of microscopic angiolymphatic portal tract invasion correlates with gross depth of direct invasion of the liver. Therefore, the concept of "regional hepatic metastases" 50,51 might be considered to exist in the case of gallbladder cancer directly invading the liver parenchyma through the gallbladder bed. Surgical resection for this type of hepatic recurrence pattern after initial surgical resection for gallbladder cancer may be implicative for obtaining some beneficial effect on the prognosis. However, as yet, there is no promising evidence on the results of hepatectomy for hepatic metastases from gallbladder cancer. Very few reports are shown in the literature at the present time (Table 3).
T A B L E 2 Surgical re-resection for recurrence of extrahepatic bile duct cancer after initial resection