Sucutinirane-diterpene derivatives induce apoptosis via oxidative stress in HL-60 cells

Previously, we reported the isolation of cassane-type diterpenes, sucutiniranes A–F, from the seeds of Bowdichia nitida. In this study, a series of sucutinirane derivatives was prepared, and their in vitro toxicity in the HL-60 cell line was evaluated. Then the action mechanism of a representative compound that induces cell death was investigated. Whereas C-6 or C-7 diol esters and ether decreased the activity against the HL-60 cell line, furan-oxidized derivatives 12 and 13 showed improvement or retention of the activity compared with those of the natural products sucutinirane A (11), E (1), and F (2). Treatment with sucutinirane derivative 13 elevated caspase 3/7 activity and also decreased expression of Bcl-2 family proteins, Mcl-1, and Bid. Derivative 13 generated reactive oxygen species in HL-60 cells, whose apoptotic effects were attenuated by the addition of an antioxidant, N-acetyl-l-cysteine. These results suggest that cassane butenolide 13 induces apoptosis in HL-60 via its oxidative effects.     

Clinical significance of definite muscle layer in TUR specimen for evaluating progression rate in T1G3 bladder cancer: multicenter retrospective study by the Sapporo Medical University Urologic Oncology Consortium (SUOC)

Purpose

To evaluate the clinical impact on progression and recurrence according to presence and absence of a muscle layer, we conducted a retrospective, multicenter study.

Methods

We retrospectively reviewed 247 patients who received transurethral resection (TUR) of bladder tumors and were pathologically diagnosed as having T1G3 bladder cancer from 1990 to 2009. We ruled out 8 patients who received immediate cystectomy and analyzed the remaining 239 T1G3 patients. Patients who had invasion to the prostatic urethra and patients who underwent a second TUR were not included.

Results

TUR specimens from 194 patients were confirmed to have a definite muscle layer and those from 45 did not. The median follow-up period was 53 months, ranging from 3 to 181 months. The progression-free survival rates at 5 years after TUR were 91.1 % for patients who had a muscle layer in their specimen and 77.3 % for those who did not (p = 0.005, log-rank test). Multivariate analysis indicated that the absence of a muscle layer was a risk factor for progression (p = 0.006, Cox proportional hazards analysis).

Conclusions

Patients without a muscle layer in the specimen had high risk for progression. The initial TUR must have a muscle layer in the specimen. Variations of progression rates in previous studies might be due to different proportions of patients who had a muscle layer in TUR specimens.     

20-Year Analysis of Kidney Transplantation: A Single Center in Japan

Background

Patient and graft survival after successful kidney transplantation (KT) have improved despite an increase in the number of challenging cases. Various factors have evolved during the long history of kidney transplantation.

Methods

Between 1988 and 2012, a total of 292 living donor and 56 deceased donor KTs were performed at Niigata University Hospital. Long-term patient and graft survival and changes in background during a 20-year period in a single center were retrospectively analyzed.

Results

Excellent patient survival rates of 95.1% at 20 years for living donor KT and 96.2% at 15 years for deceased donor KT were observed. Graft survival rates at 1, 5, 10, 15, and 20 years were 96.8%, 95.4%, 83.1%, 61.8%, and 56.2% in living donor KT, respectively. In contrast, graft survival rates at 1, 5, 10, and 15 years in deceased donor KT were 89.0%, 80.3%, 77.3%, and 33.8%, respectively. These survival rates have dramatically improved since 2002 (91.7% for living and 80.9% for deceased donor KT at 10 years post-transplantation). The number of elderly recipients (older than 60 years) and the percentage of grafts donated from spouses have increased. The rejection rate decreased and the cytomegalovirus antigenemia–positive rate increased during the 20-year period assessed. The percentage of pre-emptive KTs progressively increased, with graft survival in this group tending to be better than non-preemptive KTs. The causes of graft loss were chronic allograft dysfunction (54.7%), acute rejection (11.1%), and malignancies (9.4%). After living donor KT, the principal predictors of graft loss were if the recipient was younger than 30 years, if the donor was older than 50 years, and if the rejection episodes occurred after living donor KT. In contrast, the only risk factor in the case of deceased donor KT occurred after transplantation from donors who were older than 50 years.

Conclusions

A summary of the long-term outcome of KT over 20 years in a single center has been reported. Along with the changes in patient backgrounds, immunosuppressive drugs, and our knowledge of transplantation, patient and graft survival outcomes have also changed. Investigation into such outcomes during a different transplantation era is required to fully appreciate advances in KT.     

Safety and Efficacy of Once-Daily Modified-Release Tacrolimus in Kidney Transplant Recipients: Interim Analysis of Multicenter Postmarketing Surveillance in Japan

Introduction

Modified-release formulation of tacrolimus (TAC-MR) has been developed with the intent of improving patient adherence and quality of life. A number of studies have indicated that the efficacy and safety of once-daily TAC-MR were comparable with those of the original formulation, twice-daily TAC. However, its dosage, trough level, safety, and efficacy in the multicenter clinical experience of Japanese kidney transplant recipients have not been reported.

Methods

This post-marketing surveillance designed as an open-label, prospective, noncomparative, noninterventional observational study was performed. The 256 patients were enrolled for de novo transplantation, and the 106 patients were enrolled for conversion to TAC-MR from 52 medical institutions in Japan. The follow-up period in de novo transplantation was 5 years, but here we report the results of the 24-week interim analysis. The observation period in conversion was 24 weeks.

Results

Regarding de novo transplantation, the median daily TAC-MR dose was 0.150 mg/kg/d at the initial administration and the median TAC trough level was 12.1 ng/mL at 3 days. The common adverse drug reactions were infections, renal disorders, and glucose tolerance disorders at incidence rates of 23.6%, 6.8%, and 5.6%, respectively. Both patient and graft survival rates at 24 weeks were 98.2% and the rejection rate was 16.1%. Regarding conversion to TAC-MR, the median conventional TAC dose before conversion was 3.2 mg/d, and the median TAC-MR dose at the converted day was 3.2 mg/d. The median TAC trough level was 5.4 ng/mL before conversion, and it was 5.2 ng/mL after conversion. The most common adverse drug reactions were infections at an incidence rate of 4.9%. There was 1 graft loss and death, and there was 1 episode of rejection.

Conclusion

This interim analysis shows that a TAC-MR–based immunosuppressive regimen is safe and effective as used in Japanese clinical practice.     

Skip pedicle screw fixation combined with Ponte osteotomy for adolescent idiopathic scoliosis

Purpose

This study aimed to determine whether Ponte osteotomy combined with skip pedicle screw fixation (SPSF) can improve the correction rate and restore thoracic kyphosis for patients with adolescent idiopathic scoliosis.

Methods

Surgical time, blood loss, preoperative Cobb angle of the main thoracic curve, flexibility, Cobb angle at 1 year after surgery, thoracic curve correction rate, and Cincinnati correction index (CCI) were determined for both the Ponte (n = 17) and non-Ponte (control; n = 21) groups. Furthermore, kyphotic angles at T5–T12 before and 1 year after the surgery were measured.

Results

The following measurements were obtained for the Ponte and control groups, respectively: surgical time, 236 ± 13 and 187 ± 9 min; blood loss, 1,141 ± 150 and 745 ± 120 g; preoperative Cobb angle of the main thoracic curve, 52.5° ± 10.4° and 51.5° ± 9.2°; flexibility, 31.7 ± 13.2 and 45.1 ± 12.3 % (p = 0.003); thoracic curve correction rate, 62.0 ± 2.5 and 63.6 ± 2.5 %; CCI, 2.2 ± 0.2 and 1.5 ± 0.1 (p = 0.003); preoperative kyphotic angle at T5–T12, 11.3° ± 11.2° and 13.0° ± 9.0°; and kyphotic angle at T5–T12 at 1 year after the surgery, 21.8° ± 1.7° and 24.2° ± 1.9°.

Conclusion

Ponte osteotomy was combined with SPSF in case of rigid curve. CCI was significantly greater in the Ponte group. Postoperative thoracic kyphotic angles were identical in both groups.     

Screw perforation features in 129 consecutive patients performed computer-guided cervical pedicle screw insertion

Study design

A cross-sectional study of the data retrospectively collected by chart review.

Objectives

This study aimed to clarify screw perforation features in 129 consecutive patients treated with computer-assisted cervical pedicle screw (CPS) insertion and to determine important considerations for computer-assisted CPS insertion.

Summary of background data

CPS fixation has been criticized for the potential risk of serious injury to neurovascular structures. To avoid such serious risks, computed tomography (CT)-based navigation has been used during CPS insertion, but screw perforation can occur even with the use of a navigation system.

Methods

The records of 129 consecutive patients who underwent cervical (C2–C7) pedicle screw insertion using a CT-based navigation system from September 1997 to August 2013 were reviewed. Postoperative CT images were used to evaluate the accuracy of screw placement. The screw insertion status was classified as grade 1 (no perforation), indicating that the screw was accurately inserted in pedicle; grade 2 (minor perforation), indicating perforation of less than 50 % of the screw diameter; and grade 3 (major perforation), indicating perforation of 50 % or more of the screw diameter. We analyzed the direction and rate of screw perforation according to the vertebral level.

Results

The rate of grade 3 pedicle screw perforations was 6.7 % (39/579), whereas the combined rate of grades 2 and 3 perforations was 20.0 % (116/579). No clinically significant complications, such as vertebral artery injury, spinal cord injury, or nerve root injury, were caused by the screw perforations. Of the screws showing grade 3 perforation, 30.8 % screws were medially perforated and 69.2 % screws were laterally perforated. Of the screws showing grades 2 and 3 perforation, 21.6 % screws were medially perforated and 78.4 % screws were laterally perforated. Furthermore, we evaluated screw perforation rates according to the vertebral level. Grade 3 pedicle screw perforation occurred in 6.1 % of C2 screws; 7.5 % of C3 screws; 13.0 % of C4 screws; 6.5 % of C5 screws; 3.2 % of C6 screws; and 4.0 % of C7 screws. Grades 2 and 3 pedicle screw perforations occurred in 12.1 % of C2 screws, 22.6 % of C3 screws, 31.5 % of C4 screws, 22.2 % of C5 screws, 14.4 % of C6 screws, and 12.1 % of C7 screws. C3–5 screw perforation rate was significantly higher than C6–7 (p = 0.0024).

Conclusions

Careful insertion of pedicle screws is necessary, especially at C3 to C5, even when using a CT-based navigation system. Pedicle screws tend to be laterally perforated.     

Intraoperative thrombectomy for occluded carotid arteries in patients with acute aortic dissection: report of two cases

The present study describes two cases in which intraoperative thrombectomy was performed for occluded or severely stenosed carotid arteries in patients with acute aortic dissection complicated by cerebral malperfusion. A Fogarty catheter was inserted into the true lumen of the occluded branch under hypothermic circulatory arrest, and thrombi within the false lumen were removed. The arch vessels were patent on subsequent computed tomographic imaging, and no neurological complications were found postoperatively. In these cases, the choice of appropriate management strategies took into consideration the brain ischemic time and the presence or absence of cerebral infarction. This technique represents a useful option for the management of this clinical scenario.