No abstract

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.

From 1977 to 1997, surgical resection was possible in 142 (80%) of 177 patients with hilar cholangiocarcinoma after relieving jaundice by single or multiple percutaneous transhepatic biliary drainage followed by percutaneous transhepatic cholangioscopy and/or percutaneous trans-hepatic portal vein embolization. Curative resection was possible in 108 (61%) of the 142 patients, and 100 of these patients underwent various types of hepatectomy with caudate lobectomy for a 30-day operative mortality rate of 6% and 9% hospital mortality. Combined portal vein resection was carried out in 43 cases including 41 hepatectomies and 2 bile duct resections. Hepatopancreatoduodenectomy was performed in 16 patients. Cancer recurrence was observed in 58 of the 108 patients undergoing curative resection. The 3-, 5-, and 10-year survival rates for 100 patients undergoing curative hepatectomy and 8 with curative bile duct resection were 43%, 26%, and 19%; and 31%, 16%, and 0%, respectively; those for 40 patients with positive lymph node metastasis, 84 with perineural invasion, and 43 with combined portal vein resection were 27%, 14%, and 7%; 34%, 21%, and 13%; and 18%, 6%, and 0%, respectively. These survival rates are significantly better than those for 35 patients with unresectable cancer. Curative resection after aggressive preoperative management is recommended as a reasonable surgical approach to hilar cholangiocarcinoma.

Purpose: The carcinoembryonic antigen glypican-3 (GPC3) is an ideal target of anticancer immunotherapy against hepatocellular carcinoma (HCC). In this nonrandomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3 peptide vaccination in patients with advanced HCC.Experimental Design: Thirty-three patients with advanced HCC underwent GPC3 peptide vaccination (intradermal injections on days 1, 15, and 29 with dose escalation). The primary endpoint was the safety of GPC3 peptide vaccination. The secondary endpoints were immune response, as measured by IFN-g ELISPOT assay, and the clinical outcomes tumor response, time to tumor progression, and overall survival (OS).Results: GPC3 vaccination was well-tolerated. One patient showed a partial response, and 19 patients showed stable disease 2 months after initiation of treatment. Four of the 19 patients with stable disease had tumor necrosis or regression that did not meet the criteria for a partial response. Levels of the tumor markers a-fetoprotein and/or des-g-carboxy prothrombin temporarily decreased in nine patients. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 30 patients. Furthermore, GPC3-specific CTL frequency after vaccination correlated with OS. OS was significantly longer in patients with high GPC3-specific CTL frequencies (N ¼ 15) than in those with low frequencies (N ¼ 18; P ¼ 0.033).Conclusions: GPC3-derived peptide vaccination was well-tolerated, and measurable immune responses and antitumor efficacy were noted. This is the first study to show that peptide-specific CTL frequency can be a predictive marker of OS in patients with HCC receiving peptide vaccination.

ObjectiveTo assess the status of the regional and paraaortic lymph nodes in hilar cholangiocarcinoma and to clarify the efficacy of systematic extended lymphadenectomy. Summary Background DataThere have been no studies in which regional and paraaortic lymphadenectomies for hilar cholangiocarcinoma have been routinely performed. Therefore, the metastasis rates to the regional and paraaortic nodes, the mode of lymphatic spread, and the effect of extended lymph node dissection on survival remain unknown. MethodsThis study involved 110 patients who underwent surgical resection for hilar cholangiocarcinoma with lymph node dissection including both the regional and paraaortic nodes. A total of 2,652 nodes retrieved from the surgical specimens were examined microscopically.

The survival probability in patients with resected bile duct cancer was not significantly different between the gemcitabine adjuvant chemotherapy group and the observation group. Registration number: UMIN 000000820 (http://www.umin.ac.jp/).

Regional and para-aortic lymphadenectomy provides no survival benefit for patients with para-aortic disease, which has an influence on poor prognosis equivalent to that of distant metastasis. It has the potential to bring survival benefit only in selected patients with metastasis limited to the regional nodes. A sampling biopsy of the para-aortic nodes before starting radical surgery is recommended because they are involved more frequently than expected.

Changes in lobar volume of the liver and in total hepatic function were studied in 19 patients with biliary tract cancer who underwent right portal vein embolization as preoperative management for extensive liver resection. Computed tomography (CT) was performed to estimate liver volume before and approximately 11 days after embolization. An indocyanine green (ICG) test was performed before and 11 to 13 days after embolization. The calculated volume of the right lobe decreased from 761 +/- 181 cm3 to 625 +/- 110 cm3 11 days after embolization (P < .0001), whereas the volume of the left lobe increased from 420 +/- 94 cm3 to 555 +/- 110 cm3 (P < .0001). Thus, portal embolization produced a gain in left lobe volume of 136 +/- 62 cm3 and an almost equivalent loss in right lobe volume. The hypertrophy ratio of the left lobe, expressed as percentage of postembolization volume of the left lobe to preembolization size, of the 5 patients with diabetes mellitus (DM) was lower than that of the 14 patients without diabetes (116.7 +/- 6.3% vs. 140.4 +/- 18.4%; P < .005). The ICG disappearance rate in 16 patients improved from 0.163 +/- 0.034 to 0.177 +/- 0.027 (P < .05). The improvement was especially evident in 9 of 14 post-jaundice patients, although the rate decreased slightly in 2 patients without jaundice. We conclude that right portal vein embolization can produce a compensatory hypertrophy of the left lobe within 11 days without seriously affecting hepatic function. In diabetic patients, however, a longer interval between embolization and operation may be needed to achieve sufficient hypertrophy of the left lobe.