Persistent status of metabolic syndrome and risk of cholangiocarcinoma: A Korean nationwide population-based cohort study.

OBJECTIVE: It is unknown whether persistent metabolic syndrome (MetS) is associated with an increased risk of cholangiocarcinoma (CCA). Therefore, we investigated the risk of CCA according to changes in MetS status. RESEARCH DESIGN AND METHODS: This nationwide cohort study included 8,581,407 adults who underwent anthropometric measurements and laboratory tests in two consecutive national health screenings during 2009-2012 and observed the subjects until 2017. Individuals with cancer, or follow-up duration <1 year were excluded (n = 377,915). Subjects were classified into the MetS-free, MetS-developed, MetS-improved, and MetS-persistent groups. The outcome was the incidence of CCA, identified using the claims database. Multivariable Cox proportional hazards regression models were used. RESULTS: Among the 8,203,492 subjects (mean age 48.9 ± 12.8 years; 56.7% male), 7506 CCA patients were newly identified during a median follow-up of 5.1 years. The probability of CCA was consistently higher in the MetS-persistent group than in the MetS-free group (P < 0.001). MetS-persistent status was significantly associated with an increased risk of CCA compared with the MetS-free status (unadjusted hazard ratio [HR] 2.8, 95% confidence interval [CI] 2.66-2.95), even after adjusting for multiple covariates (adjusted HR 1.07, 95% CI 1.01-1.13). Improved or newly developed MetS was not associated with CCA risk in the fully adjusted model (aHR 1.02, 95% CI 0.94-1.10 and aHR 0.99, 95% CI 0.92-1.06, respectively). CONCLUSIONS: MetS was associated with an increased risk of CCA if it persisted for ≥2 years. Our finding suggests that MetS may be a potentially modifiable risk factor for CCA.

Regorafenib in previously treated advanced hepatocellular carcinoma: Impact of prior immunotherapy and adverse events.

BACKGROUND & AIMS: Regorafenib demonstrated a clinical benefit for patients with unresectable hepatocellular carcinoma (uHCC) in the phase III RESORCE trial. Considering the heterogeneity of uHCC and discrepancies in its characteristics between prospective trials and daily practice, real-life evidence is necessary. METHODS: This multicentre, retrospective analysis was performed by the Korean Cancer Study Group. In total, 440 patients who received regorafenib between January 2017 and November 2019 were identified in nine tertiary referral hospitals in Korea. RESULTS: All patients received prior sorafenib, and the median time-to-progression (TTP) on sorafenib was 3.9 months (range, 0.2-71.6). Regorafenib was used as the second, third and fourth to seventh lines of therapy in 305 (69.3%), 115 (26.1%) and 20 (4.5%) patients respectively. According to the RECIST v1.1, the overall response rate was 7.7% (n = 34), and the median progression-free survival (PFS) and overall survival (OS) were 3.2 (95% CI, 2.8-3.5) and 12.1 (95% CI, 9.7-14.5) months respectively. Immune checkpoint inhibitors (ICIs) were given in 115 patients (26.1%) prior to regorafenib. There were no differences in PFS and OS with regorafenib according to the prior use of ICIs (PFS, P = .61; OS, P = .63). The occurrence of hand-foot skin reaction (HFSR) was associated with a better OS (P < .001). CONCLUSIONS: The real-life clinical outcomes of regorafenib for patients who progressed on prior systemic therapy including ICIs were consistent with the phase III trial results. HFSR was significantly associated with better OS with regorafenib.

Identification of natural pneumococcal isolates expressing serotype 6D by genetic, biochemical and serological characterization.

The recently discovered pneumococcal serotype 6C was created when the original wciN gene in the 6A capsule gene locus was naturally replaced with a new gene. Since the capsule gene loci of 6A and 6B serotypes may differ by only one base pair in the wciP gene, it was speculated that a new serotype '6D' would be possible if the new wciN gene were inserted into the 6B capsule gene locus. Although pneumococci expressing serotype 6D could be produced in the laboratory, initial searches for natural pneumococcal isolates expressing serotype 6D were unsuccessful. However, we now report the discovery of two naturally occurring pneumococcal isolates from Korea that have the serological, genetic and biochemical features predicted for serotype 6D.