A standardized method of X-ray CT for sagittal splitting osteotomy of the mandibular ramus

A useful standardized method of X-ray computed tomography (CT) was proposed for the preoperative examination of sagittal splitting osteotomy of the mandibular ramus. In our assessment conducted for cases of mandibular prognathism operated on by a modified technique, the most informative CT image of the mandibular ramus was provided by the scans between the upper and lower dentitions in the open mouth position at which the scan-plane angulation was given as parallel to the dentition in each jaw. These sections enabled preoperative assessment on the mesio-lateral thickness of the marrow space and the positional relationship between the ramal cortices and the mandibular canal together with other geography of the ramal bone structure. Using these CT images, the plane of sagittal osteotomy is predictable. A technique for obtaining standardized CT slice is proposed in this report.     

Endoscopic radial artery harvesting: patient satisfaction and complications

Endoscopic radial artery harvesting was recently introduced to reduce the morbidity associated with conventional open harvesting and improve cosmetic outcomes. From January 2004 through December 2006, 25 radial arteries were harvested endoscopically from 25 patients using the VasoView endoscopic system. Bilateral radial arteries were harvested from 6 patients by both the endoscopic and open techniques, and postoperative patient satisfaction was assessed using a visual analogue scale. Mean harvesting time was 61.9 +/- 16.0 min (range, 44-105 min), and mean harvested conduit length was 16.8 +/- 2.0 cm (range, 15-19 cm). Objective dorsal thenar numbness remained in 2 patients (8%); none complained of forearm numbness. All patients expressed marked satisfaction with the endoscopic technique and the small incision. Patient satisfaction was significantly higher with the endoscopic technique than with the open technique (visual analogue scale of 9 vs 5). Postoperative angiography revealed occlusion of a graft that had been anastomosed to a small diagonal branch. The overall graft patency was 96.6%. Endoscopic radial artery harvesting can be performed safely with infrequent complications. This method results in excellent patient satisfaction, particularly regarding the cosmetic outcome.     

Fungal metabolite, epoxyquinol B, crosslinks proteins by epoxy-thiol conjugation

Epoxyquinol B (EPQB) is a fungal metabolite, containing two alpha,beta-epoxy ketones. We previously showed that EPQB inhibited the signal transduction involved in angiogenesis through the binding to cysteine residues of receptor kinases. However, the inhibitory mechanism was undefined. In this report, we found that one EPQB molecule is covalently bound to two L-cysteine molecules through two epoxide residues on EPQB. Furthermore, EPQB crosslinked binding proteins through the cysteine residues. These results suggest that EPQB inhibits receptor kinases by crosslinking with other protein or by intramolecular crosslinking.     

Clinical and genetic features of Charcot‐Marie‐Tooth disease 2F and hereditary motor neuropathy 2B in Japan

Mutations in small heat shock protein beta‐1 (HspB1) have been linked to Charcot‐Marie‐Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole‐exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1‐related disorders.     

Clinical significance of the mutational landscape and fragmentation of circulating tumor DNA in renal cell carcinoma

Reliable biomarkers for renal cell carcinoma (RCC) have yet to be determined. Circulating tumor DNA (ctDNA) is an emerging resource to detect and monitor molecular characteristics of various tumors. The present study aims to clarify the clinical utility of ctDNA for RCC. Fifty‐three patients histologically diagnosed with clear cell RCC were enrolled. Targeted sequencing was carried out using plasma cell‐free DNA (cfDNA) and tumor DNA. We applied droplet digital PCR (ddPCR) to validate detected mutations. cfDNA fragment size was also evaluated using a microfluidics‐based platform and sequencing. Proportion of cfDNA fragments was defined as the ratio of small (50‐166 bp) to large (167‐250 bp) cfDNA fragments. Association of mutant allele frequency of ctDNA with clinical course was analyzed. Prognostic potential was evaluated using log‐rank test. A total of 38 mutations across 16 (30%) patients were identified from cfDNA, including mutations in TP53 (n = 6) and VHL (n = 5), and median mutant allele frequency of ctDNA was 10%. We designed specific ddPCR probes for 11 mutations and detected the same mutations in both cfDNA and tumor DNA. Positive ctDNA was significantly associated with a higher proportion of cfDNA fragments (P = .033), indicating RCC patients with ctDNA had shorter fragment sizes of cfDNA. Interestingly, the changes of mutant allele frequency in ctDNA concurrently correlated with clinical course. Positive ctDNA and fragmentation of cfDNA were significantly associated with poor cancer‐specific survival (P < .001, P = .011). In conclusion, our study shows the clinical utility of ctDNA status and cfDNA fragment size as biomarkers for prognosis and disease monitoring in RCC.