Myelin Basic Protein as a Novel Genetic Risk Factor in Rheumatoid Arthritis—A Genome-Wide Study Combined with Immunological Analyses

Rheumatoid arthritis (RA) is a major cause of adult chronic inflammatory arthritis and a typical complex trait. Although several genetic determinants have been identified, they account for only a part of the genetic susceptibility. We conducted a genome-wide association study of RA in Japanese using 225,079 SNPs genotyped in 990 cases and 1,236 controls from two independent collections (658 cases and 934 controls in collection1; 332 cases and 302 controls in collection2), followed by replication studies in two additional collections (874 cases and 855 controls in collection3; 1,264 cases and 948 controls in collection4). SNPs showing p<0.005 in the first two collections and p<10−4 by meta-analysis were further genotyped in the latter two collections. A novel risk variant, rs2000811, in intron2 of the myelin basic protein (MBP) at chromosome 18q23 showed strong association with RA (p = 2.7×10−8, OR 1.23, 95% CI: 1.14–1.32). The transcription of MBP was significantly elevated with the risk allele compared to the alternative allele (p<0.001). We also established by immunohistochemistry that MBP was expressed in the synovial lining layer of RA patients, the main target of inflammation in the disease. Circulating autoantibody against MBP derived from human brain was quantified by ELISA between patients with RA, other connective tissue diseases and healthy controls. As a result, the titer of anti-MBP antibody was markedly higher in plasma of RA patients compared to healthy controls (p<0.001) and patients with other connective tissue disorders (p<0.001). ELISA experiment using citrullinated recombinant MBP revealed that a large fraction of anti-MBP antibody in RA patients recognized citrullinated MBP. This is the first report of a genetic study in RA implicating MBP as a potential autoantigen and its involvement in pathogenesis of the disease

Pure Laparoscopic Hepatectomy Combined with a Pure Laparoscopic Pringle Maneuver in Patients with Severe Cirrhosis

Laparoscopic hepatectomy is a standard surgical procedure. However, it is difficult to perform in patients with severe cirrhosis because of fibrosis and a high risk of hemorrhage. We report our recent experience in five cases of pure laparoscopic hepatectomy combined with a pure laparoscopic Pringle maneuver in patients with severe cirrhosis. From 2012 to 2014, we performed pure laparoscopic partial hepatectomy in five patients with severe liver cirrhosis (indocyanine green retention rate at 15&#x2009;min [ICG R15] >30% and fibrosis stage f4). A pure laparoscopic Pringle maneuver was employed in all patients. We investigated operative time, blood loss, duration of hospitalization and the days when discharge was possible, and compared these findings with those of patients with a normal liver (ICG R15 <10%, f0) who underwent pure laparoscopic partial hepatectomy during the same period (n = 7). As a result, operative time, blood loss, duration of hospitalization and the days when discharge was possible were similar in patients with cirrhosis undergoing pure laparoscopic hepatectomy combined with a pure laparoscopic Pringle maneuver to those in patients with a normal liver undergoing pure laparoscopic partial hepatectomy. In conclusion, pure laparoscopic hepatectomy combined with a pure laparoscopic Pringle maneuver appears to be safe in patients with severe cirrhosis

Prostatic Stromal Tumor of Uncertain Malignant Potential Which Was Difficult to Diagnose

Here, we report a case of stromal tumor of uncertain malignant potential (STUMP) that was difficult to diagnose. A 53-year-old male was found to have a hard nodule on digital rectal examination; magnetic resonance imaging revealed a large nodule on the left side of the prostate, indicating prostate cancer. However, pathological diagnosis of the biopsy specimen was benign prostatic hyperplasia. Although a papillary tumor in the prostatic urethra was also seen on urethrocystoscopy, the tumor specimen obtained from transurethral resection was not malignant. The tumor in the prostatic urethra recurred only 3 months after transurethral resection, and pathological findings revealed benign hyperplasia not only in the stromal tissue but also in the epithelium; therefore, the prostate tumor was suspected to be STUMP. It took many prostate pathologists a long time to reach the final diagnosis of STUMP. STUMP is a rare benign tumor, difficult to diagnose, and sometimes transforms into stromal sarcoma. Thus, we should consider radical resection in such cases