Role of caudate lobectomy in type III A and III B hilar cholangiocarcinoma: a 15-year experience in a tertiary institution.

BACKGROUND: Concomitant liver resection for type III hilar cholangiocarcinoma could improve the R0 resection rate and long-term outcome. In the present study, we examine the specific role of caudate lobectomy in liver resection for type III(A) and III(B) hilar cholangiocarcinoma and the prognostic factors for survival in this group of patients. METHODS: We reviewed all patients with type III(A) and III(B) hilar cholangiocarcinoma who underwent liver resection in Samsung Medical Center from January 1995 to July 2010. Patients were divided into those with and without caudate lobectomy (CL). The log rank test and Cox regression analysis were employed to investigate for prognostic factors of survival. RESULTS: There were 127 patients in this cohort, 57 without CL (44.9%) and 70 with CL (55.1%). The demographics and symptoms of presentation were comparable. The median preoperative bilirubin level was significantly higher in the group undergoing CL (p = 0.017). Patients with CL had a significantly better overall survival (OS) (CL: 64.0 months vs without CL: 34.6 months) (p = 0.010) and disease-free survival (DFS) (CL: 40.5 months vs without CL: 27.0 months) (p = 0.031). Multivariate analysis showed that presence of symptoms (p = 0.025) and positive lymph node (LN) metastasis (p < 0.001) were negative prognostic factors for OS. Furthermore, multivariate analysis for DFS found that caudate lobectomy (p = 0.016) and positive LN metastasis (p = 0.001) were positive and negative prognostic factors, respectively. CONCLUSIONS: Caudate lobectomy contributed to improvement of DFS and OS in type III hilar cholangiocarcinoma. Other prognostic factors include positive LN metastasis and presence of symptoms.

Clinical outcomes of salvage chemoradiotherapy for locally recurrent biliary tract cancer.

PURPOSE: The purpose of this study was to investigate the clinical outcomes and prognostic factors of concurrent chemoradiotherapy (CCRT) for locally recurrent biliary tract cancer (BTC) after curative surgical resection. METHODS: We performed a retrospective cohort study of patients with locally recurrent BTC treated with CCRT between October 2004 and December 2013. The study included and analyzed 42 patients with a history of curative-intent surgical resection of confirmed adenocarcinoma originating from the biliary tract. RESULTS: The median time to recurrence after surgery was 16.1 months (range, 4.5-77.8 months). Median follow-up after CCRT was 26.9 months (range, 5.2-81.9) with no grade 3 or higher gastrointestinal toxicities. Analysis of the first site of failure showed local progression (LP) developed in 20 patients (47.6%); among these, 16 (38.1%) had isolated LP. The median values were 15.8 months (range, 1.7-81.7) for LP-free survival (LPFS), 10.6 months (range, 1.7 - 81.7) for progression-free survival (PFS) and 41.2 months (range, 5.2-81.9) for overall survival (OS). Multivariate analysis showed that the level of pre-CCRT carbohydrate antigen (CA) 19-9 and the chemotherapy regimen were significant prognostic factors for LPFS and PFS; pT stage was the only significant prognostic factor for OS. CONCLUSIONS: CCRT for locally recurrent BTC showed promising outcomes as a salvage modality, but LP was still frequent. The pre-CCRT CA 19-9 level and the chemotherapy regimen were prognostic factors for LPFS and PFS.

HIPK2 modification code for cell death and survival.

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine protein kinase that participates in the regulation of diverse cellular activities as a transcriptional cofactor and signal transducer. HIPK2 senses various signaling cues that in turn phosphorylate downstream substrates to coordinate developmental processes, cell cycle regulation, cell proliferation, differentiation, and the DNA damage response. HIPK2 functions are affected by its catalytic activity, stability, and subcellular localization, which in turn are dynamically regulated by diverse post-translational modifications such as polyubiquitination, SUMOylation, phosphorylation, and acetylation. HIPK2 is not modified with small molecules and/or peptides individually or independently, but in a combinatorial manner that is referred to as the "HIPK2 modification code." HIPK2 integrates various signaling cues and senses different doses of DNA damage and ROS stimuli, which are reflected by unique patterns of HIPK2 modification. Hence, the HIPK2 modification code differentially contributes to cellular homeostasis and determination of cell fate depending on cellular context.