Inactivation of axon guidance molecule netrin-1 in human colorectal cancer by an epigenetic mechanism.

Netrin-1, the protein product of the NTN1 gene, is an axon guidance molecule implicated in regulation of cell survival and tumorigenesis. Expression of the netrin-1 receptors deleted in colorectal cancer (DCC) and uncoordinated 5 homolog (UNC5H) is frequently silenced in colorectal cancer (CRC) by either loss of heterozygosity or epigenetic mechanisms. However, netrin-1 expression and regulation in CRC are mostly unknown. Here, we report that NTN1 expression is significantly reduced in most CRC tissues compared to the adjacent normal intestinal mucosa, and that NTN1 DNA methylation is significantly higher in CRCs (24.6%) than in the adjacent normal intestinal mucosa (4.0%). In 6 CRC cell lines, NTN1 expression is low. Treatment with 5-Aza-2'-deoxycytidine increased expression of NTN1 in CRC cell lines, indicating that DNA methylation represses NTN1 transcription in CRCs. NTN1 DNA hypermethylation was significantly associated with advanced CRC disease. Median netrin-1 serum levels were significantly decreased in CRC patients (330.1 pg/mL) compared with normal individuals (438.6 pg/mL). Our results suggest that netrin-1 is a candidate biomarker for CRC.

A Review of 7 Cases of Laparoscopic Cholecystectomy for Pediatric Cholecystolithiasis.

Pediatric cholecystolithiasis is a relatively rare disease, but it is recently increasing in Japan. Laparoscopic cholecystectomy (LC) is a standard procedure for cholecystolithiasis not only in adults but also in children, and we are aggressively introducing single-incision laparoscopic cholecystectomy (SILC) at our hospital. We reviewed the patient characteristics, operation procedures and outcomes of 7 children (15 years old and under) with cholecystolithiasis who underwent LC in our hospital between August 1995 and December 2015. The 7 patients included 5 males and 2 females, with a mean age of 8 years 6 months. Underlying diseases were found in 5 patients (cerebral palsy in 2 patients, pancreaticobiliary maljunction with common bile duct stones in 1, acute lymphocytic leukemia in 1, hereditary stomatocytosis in 1), and none were found in the other 2. LC (3 conventional LC and 2 SILC) was performed in 5 of the patients. Laparoscopic choledocholithotomy was performed in 1 patient and laparoscopic splenectomy (LS) was performed in 1 patient at the same time. The mean operative time in all the cases of LC was 108 (70-140) minutes (conventional LC 113 (70-140) min, SILC 100 (90-100) min). Intraoperative cholangiography was performed in 4 cases and omitted in 3 cases. The only postoperative complication was a wound infection in 1 patient. The umbilical skin incision length in the SILC was 2.0 cm. We conclude that LC can be safely performed for children with cholecsytolithiasis, and that SILC is feasible and advantageous in terms of its improved cosmesis.