Tomoki Ebata

Hepatectomy with portal vein resection for hilar cholangiocarcinoma: audit of 52 consecutive cases.

Objective: To better determine the role of portal vein resection and its effect on survival, as well as to appreciate the impact of portal vein invasion on prognosis in hilar cholangiocarcinoma. Summary Background Data: Hepatectomy with portal vein resection is sometimes performed for locally advanced hilar cholangiocarcinoma. However, the significance of microscopic invasion of the portal vein has not been determined. Methods: Medical records of 160 patients with hilar cholangiocarcinoma who underwent macroscopically curative hepatectomy with (n = 52) or without portal vein resection (n = 108) were reviewed. Invasion of the portal vein was assessed histologically on the surgical specimen, and results were correlated with clinicopathologic features and survival. Results: Surgical mortality, including all hospital deaths, was similar in patients who did and did not undergo portal vein resection (9.6% vs. 9.3%), but the primary tumor was more advanced in patients who underwent portal vein resection. Histologically, no invasion was found in 16 (30.8%) of resected portal veins. However, dense fibrosis adjacent to the portal vein was common, and the mean distance between the leading edge of cancer cells and the adventitia of the portal vein was 437 ± 431 &mgr;m. The prognosis was worse in patients with than without portal vein resection (5-year survival, 9.9% vs. 36.8%; P < 0.0001). The presence or absence of microscopic invasion of the resected portal vein did not influence survival (16.6 months in patients with microscopic invasion vs. 19.4 months in those without; P = 0.1506). Multivariate analysis identified histologic differentiation, lymph node metastasis, and macroscopic portal vein invasion as independent prognostic factors. Conclusions: Microscopic invasion of the portal vein may be misdiagnosed clinically in patients with hilar cholangiocarcinoma. However, the distance between tumor and adventitia is so narrow that curative resection without portal vein resection is unlikely to be possible. Gross portal vein invasion has a negative impact on survival, and hepatectomy with portal vein resection can offer long-term survival in some patients with advanced hilar cholangiocarcinoma.

Perioperative Synbiotic Treatment to Prevent Postoperative Infectious Complications in Biliary Cancer Surgery A Randomized Controlled Trial

Summary Background Data:Use of synbiotics has been reported to benefit human health, but clinical value in surgical patients remains unclear. Objective:To investigate the effect of perioperative oral administration of synbiotics upon intestinal barrier function, immune responses, systemic inflammatory responses, microflora, and surgical outcome in patients undergoing high-risk hepatobiliary resection. Methods:Patients with biliary cancer involving the hepatic hilus (n = 101) were randomized before hepatectomy, into a group receiving postoperative enteral feeding with synbiotics (group A); or another receiving preoperative plus postoperative synbiotics (group B). Lactulose-mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, natural killer (NK) cell activity, interleukin-6 (IL-6), fecal microflora, and fecal organic acid concentrations were determined before and after hepatectomy. Postoperative infectious complications were recorded. Results:Of 101 patients, 81 completed the trial. Preoperative and postoperative changes in L/M ratio and DAO activity were similar between groups. Preoperatively in group B, NK activity, and lymphocyte counts increased, while IL-6 decreased significantly (P < 0.05). Postoperative serum IL-6, white blood cell counts, and C-reactive protein in group B were significantly lower than in group A (P < 0.05). During the preoperative period, numbers of Bifidobacterium colonies cultured from and total organic acid concentrations measured in feces increased significantly in group B (P < 0.05). Postoperative concentrations of total organic acids and acetic acid in feces were significantly higher in group B than in group A (P < 0.05). Incidence of postoperative infectious complications was 30.0% (12 of 40) in group A and 12.1% (5 of 41) in group B (P < 0.05). Conclusions:Preoperative oral administration of synbiotics can enhance immune responses, attenuate systemic postoperative inflammatory responses, and improve intestinal microbial environment. These beneficial effects likely reduce postoperative infectious complications after hepatobiliary resection for biliary tract cancer.

“Anatomic” Right Hepatic Trisectionectomy (Extended Right Hepatectomy) With Caudate Lobectomy for Hilar Cholangiocarcinoma

Background:The techniques of right hepatic trisectionectomy are now standardized in patients with hepatocellular or metastatic carcinoma, but not in those with hilar cholangiocarcinoma. Methods:Under preoperative diagnosis of hilar cholangiocarcinoma, 8 patients underwent “anatomic” right hepatic trisectionectomy with en bloc resection of the caudate lobe and the extrahepatic bile duct, in which the bile ducts of the left lateral section were divided at the left side of the umbilical fissure following complete dissection of the umbilical plate. Results:Liver resection was successfully performed, and all patients were discharged from the hospital in good condition, giving a mortality of 0%. All patients were histologically diagnosed as having cholangiocarcinoma. The proximal resection margins were cancer-negative in 7 patients and cancer-positive in 1 patient. Four patients with multiple lymph node metastases died of cancer recurrence within 3 years after hepatectomy. One patient died of liver failure without recurrence 42 months after hepatectomy. The remaining 3 patients without lymph node metastasis are now alive after more than 5 years. Conclusions:Anatomic right hepatic trisectionectomy with caudate lobectomy can produce a longer proximal resection margin and can offer a better chance of long-term survival in some selected patients with advanced hilar cholangiocarcinoma.

Hepatopancreatoduodenectomy for cholangiocarcinoma: a single-center review of 85 consecutive patients.

Objective:To outline our experience with hepatopancreatoduodenectomy (HPD) as a treatment for cholangiocarcinoma and to appraise the clinical significance of this challenging procedure. Background:Cholangiocarcinomas often exhibit an extensive ductal spread invading from the hepatic hilus to the lower bile duct, and such tumors can be completely resected only by HPD. Early experiences with HPD were associated with high mortality and morbidity, leading to an underestimation of the survival benefit of HPD. Methods:We retrospectively reviewed the medical records of 85 patients with cholangiocarcinoma who underwent HPD from 1992 to 2011. Major hepatectomy was performed in 79 patients (92.9%), and combined vascular resection was performed in 26 patients (30.6%). Results:The operating time was 762 ± 141 minutes, and blood loss was 2696 ± 1970 mL. Liver failure was the most common abdominal complication (n = 64), followed by pancreatic fistula (n = 60), wound sepsis (n = 33), intra-abdominal abscess (n = 22), refractory ascites (n = 17), bacteremia (n = 16), bile leakage (n = 13), and delayed gastric emptying (n = 12). Re-laparotomy was necessary in 9 cases (11.1%). Overall, 19 patients (22.4%) exhibited Clavien grade 0 to II complications, 58 (68.2%) exhibited grade III, 6 (7.1%) exhibited grade IV, and 2 (2.4%) exhibited grade V (mortality). The overall survival rate for the 85 patients was 79.7% after 1 year, 48.5% after 3 years, 37.4% after 5 years, and 32.1% after 10 years; 9 (10.5%) patients survived for more than 5 years. The rate of survival for the 53 patients with pM0 disease who underwent R0 resection was the most favorable, with 5- and 10-year survival rates of 54.3% and 46.6%, respectively. Conclusions:HPD is technically demanding and is associated with high morbidity. However, this surgery can be performed with low mortality and offers a better probability of long-term survival in selected patients. As hepatobiliary surgeons, we should consider HPD to be a standard procedure for laterally advanced cholangiocarcinomas that are otherwise unresectable.

The concept of perihilar cholangiocarcinoma is valid

The term perihilar cholangiocarcinoma has been used for all tumours involving or requiring resection of the hepatic confluence. However, it does not distinguish between intrahepatic and extrahepatic hilar tumours, and has no clinicopathological basis. This retrospective study examined whether the concept of perihilar cholangiocarcinoma is valid clinically.

Portal Vein Embolization before Extended Hepatectomy for Biliary Cancer: Current Technique and Review of 494 Consecutive Embolizations

Backgrounds: Portal vein embolization (PVE) has been widely applied before extended hepatectomy; however, its clinical utility for patients with biliary cancer has not been fully addressed. Methods: Between 1991 and 2010, 494 patients with cholangiocarcinoma (n = 353) or gallbladder cancer (n = 141) underwent PVE before extended hepatectomy. PVE was performed by a transhepatic ipsilateral approach using fibrin glue or absolute ethanol with steel coils. Surgical outcomes of this cohort were retrospectively reviewed. Results: PVE-related complications requiring interventions were found in 3 (0.6%) of the 494 patients; no patient died of these complications. Among the 494 patients, 122 (24.7%) did not undergo subsequent hepatectomy. The unresectability rate was significantly higher in patients with gallbladder cancer than in those with cholangiocarcinoma [43.2% (61/141) and 17.3% (61/353), respectively, p < 0.001]. The remaining 372 patients underwent hepatectomy, and 24 (6.5%) died of postoperative complications [13 of 80 (16.3%) with gallbladder cancer vs. 11 of 292 (3.8%) with cholangiocarcinoma, p < 0.05]. The overall survival for patients with cholangiocarcinoma was significantly better than that for patients with gallbladder cancer, where the 5-year survival rate was 39 and 23%, respectively (p < 0.001). Thirty-six patients with cholangiocarcinoma and 10 patients with gallbladder cancer survived more than 5 years after extended surgery. Conclusion: PVE can be performed safely in patients with cholestatic liver, and it has a potential benefit for patients with advanced biliary cancer who are to undergo extended, difficult hepatectomy.

Proposal to modify the International Union Against Cancer staging system for perihilar cholangiocarcinomas

The International Union Against Cancer (UICC) staging system for perihilar cholangiocarcinoma changed in 2009. The aim of this study was to validate and optimize the UICC system for these tumours.

Immunohistochemically Demonstrated Lymph Node Micrometastasis and Prognosis in Patients With Gallbladder Carcinoma

Objective:To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2–4 tumors). Summary Background Data:The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma. Methods:A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival. Results:Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors. Conclusions:Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.

Pancreatic and duodenal invasion in distal bile duct cancer: paradox in the tumor classification of the American Joint Committee on Cancer.

BackgroundDistal bile duct cancer often invades the pancreas and/or duodenum. Invasion of the pancreas is defined as a T3 and that of the duodenum as a T4 tumor in the T classification of the American Joint Committee on Cancer (AJCC). The aim of this study was to assess whether this T classification is rational from the viewpoint of prognostic power.MethodNinety-five patients with distal bile duct cancer were retrospectively analyzed according to the current T classification of the AJCC.ResultsThe main determinant of pT3 (n = 32) and pT4 (n = 30) was pancreatic and duodenal invasion, respectively, and the survival rates for patients with pT3 and pT4 are similar (p = 0.595). Duodenal invasion was present in 39% of the patients with pancreatic invasion, whereas pancreatic invasion was observed in 86% of those with duodenal invasion. The survival for patients with pancreatic invasion was not significantly different (p = 0.283) whether or not there was concomitant duodenal invasion (n = 19 and n = 37, respectively). Multivariate analysis identified venous invasion, distant metastasis, histologic grade, and pancreatic invasion as independent prognostic factors.ConclusionAlthough duodenal invasion usually occurs after pancreatic invasion, it is not a significant prognostic factor while pancreatic invasion is. The current T classification should be revised since it expresses tumor extension but does not reflect a survival in distal bile duct cancer.

Clinicopathologic Comparison of Siewert Type II and III Adenocarcinomas of the Gastroesophageal Junction

BackgroundSince Misumi et al. and Siewert proposed a new classification for carcinoma of the gastroesophageal junction (GEJ), few surgical studies using these criteria have been reported from Eastern countries. Siewert type II adenocarcinomas are managed using general rules for either gastric or esophageal cancer. We set out to determine whether type II adenocarcinoma is a distinct clinical entity requiring a more specific treatment plan.MethodsAmong 125 Japanese patients who underwent resection of adenocarcinoma of the GEJ (type I, 2; type II, 44; type III, 79), 101 who underwent R0 resections (type II, 40; type III, 61) were analyzed to evaluate surgical results and compare clinicopathologic factors.ResultsBarrett’s epithelium was recognized in two patients with type II adenocarcinoma. Type II differed significantly from type III in higher prevalence of Borrmann macroscopic type 2, more frequent lymph node metastasis (58% vs. 34%), higher metastatic rate to lower mediastinal lymph nodes (13%), increased risk of hepatic recurrence, and lower 5-year survival after R0 resection (67.4% vs. 87.1%).ConclusionsClinicopathologic differences were evident between type II and III adenocarcinomas. Siewert type II adenocarcinoma differs sufficiently to be considered a clinical entity distinct and independent from type III.