Direct insertion of an ultra‐slim upper endoscope for cholangioscopy in patients undergoing choledochoduodenostomy

Direct peroral cholangioscopy (POC) using an ultra‐slim upper endoscope is one modality of POC for intraductal endoscopic evaluation and treatment of the bile duct. Choledochoduodenostomy (CDS) is one modality of biliary bypass surgery that provides a new route to the bile duct. We carried out direct POC using an ultra‐slim upper endoscope without the use of accessories in 10 patients (four sump syndromes, three bile duct strictures and three intrahepatic duct stones) previously undergoing surgical CDS. Direct POC was successful in all patients. The use of an intraductal balloon catheter was required in one patient for advancement of the endoscope into the bile duct. Distal bile ducts with sump syndromes were cleared using baskets and water irrigation under direct POC. Cholangiocarcinoma was diagnosed in one patient with hilar bile duct stricture after cholangioscopic evaluation and a targeting forceps biopsy under direct POC. Intrahepatic duct stones were successfully extracted after intraductal fragmentation under direct POC. Oozing bleeding occurred during intraductal lithotripsy but stopped spontaneously. Direct POC using an ultra‐slim upper endoscope without the assistance of accessories can easily be carried out in patients undergoing CDS.     

Uncalcified Synovial Chondromatosis in the Pisotriquetral Joint

Synovial chondromatosis is a rare lesion in the wrist, but some cases in the distal radioulnar joint have been reported and previous case reports emphasize joint calcifications, shown on preoperative plain radiographs. We report an extremely uncommon case of synovial chondromatosis in the pisotriquetral joint, in which radiographs and magnetic resonance imaging did not demonstrate apparent calcified bodies. In our case, for the accurate diagnosis and treatment, surgical exploration of the joint and synovectomy with removal of loose bodies was performed.     

Sensitivity of the environmental costs of air pollution caused by SOx,NOx, and PM from power plants applied to the power mix configuration in South Korea

In the 6th Basic Plan for Long-Term Electricity Supply and Demand (6th BPE) for Korea, for the first time, the environmental costs of air pollution caused by oxides of sulfur (SOx), oxides of nitrogen (NOx), and particulate matters (PM) from power plants were estimated and included. However, several deficiencies in evaluating the environmental costs were found. In this study, (1) the validity of the environmental costs used in the 6th BPE was assessed, (2) a systematic approach was suggested and used to improve the environmental costs estimation, and (3) the sensitivity of the cost of generating electricity to the environmental costs by fuel type with the proposed approach was discussed. We found that the applied environmental costs used in the 6th BPE did not fully include the demographic characteristics of Korea. By applying more realistic parameter values, it was found that the newly estimated environmental cost was about 23 times higher than the cost estimated in the original 6th BPE for coal-fired power plants and about 1.5 times higher for liquefied natural gas (LNG)-fired power plants, suggesting that LNG-fired power plants are more economical if using more realistic environmental costs. Thus, it is critical to check the validity of parameter values when calculating environmental costs.     

A Phase I Trial of Trametinib in Combination with Sorafenib in Patients with Advanced Hepatocellular Cancer

Lessons Learned

• The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
• Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
• The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.

BackgroundThe RAS/RAF/MEK/ERK signaling pathway is associated with proliferation and progression of hepatocellular carcinoma (HCC). Preclinical data suggest that paradoxical activation of the MAPK pathway may be one of the resistance mechanisms of sorafenib; therefore, we evaluated trametinib plus sorafenib in HCC.MethodsThis was a phase I study with a 3+3 design in patients with treatment‐naïve advanced HCC. The primary objective was safety and tolerability. The secondary objective was clinical efficacy.ResultsA total of 17 patients were treated with three different doses of trametinib and sorafenib. Two patients experienced dose‐limiting toxicity, including grade 4 hypertension and grade 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin over 7 days. Maximum tolerated dose was trametinib 1.5 mg daily and sorafenib 200 mg twice a day. The most common grade 3/4 treatment‐related adverse events were elevated AST (37%) and hypertension (24%). Among 11 evaluable patients, 7 (63.6%) had stable disease with no objective response. The median progression‐free survival (PFS) and overall survival (OS) were 3.7 and 7.8 months, respectively. Phosphorylated‐ERK was evaluated as a pharmacodynamic marker, and sorafenib plus trametinib inhibited phosphorylated‐ERK up to 98.1% (median: 81.2%) in peripheral blood mononuclear cells.ConclusionTrametinib and sorafenib can be safely administered up to trametinib 1.5 mg daily and sorafenib 200 mg twice a day with limited anticancer activity in advanced HCC.