Xenotransplantation of human mesenchymal stem cells for repair of osteochondral defects in rabbits using osteochondral biphasic composite constructs

Purpose

The aim of this work is to investigate the feasibility of non-autologous transplantation of human mesenchymal stem cells (hMSCs) with or without differentiation for the regeneration of osteochondral defects in rabbits using a biphasic composite construct composed of platelet-rich fibrin glue (PR-FG) and hydroxyapatite.

Methods

After isolation and culture, hMSCs were seeded on biphasic composite constructs (hydroxyapatite + PR-FG) and transplanted into osteochondral defects of adult New Zealand white rabbits. Treatment of individual defects was applied by random assignment to one of five groups: (1) control, defects untreated; (2) hydroxyapatite, defects filled with hydroxyapatite only; (3) hydroxyapatite + PR-FG, defects filled with a composite of hydroxyapatite and PR-FG; (4) hydroxyapatite + PR-FG + undifferentiated hMSCs; and (5) hydroxyapatite + PR-FG + differentiated hMSCs. Rabbits were killed at 4 or 8 weeks post-surgery, at which time osteochondral repair was macroscopically and histologically evaluated and scored using the modified International Cartilage Repair Society scoring system.

Results

The group in which defects were seeded with differentiated hMSCs (group 5) showed superior healing of osteochondral defects based on macroscopic and histological observations compared to other groups. Specifically, 8 weeks after implantation, defects were filled with more hyaline-like cartilage and were better integrated with the surrounding native cartilage. The histological scores were significantly better than those of other groups (16.3 at 8 weeks, p < 0.01).

Conclusion

Xenogeneic transplantation of differentiated hMSCs using a biphasic composite construct effectively repaired osteochondral defect in a rabbit model. Differentiated hMSCs showed superior healing of chondral lesion to undifferentiated hMSCs.     

Sagittal and coronal plane location of the popliteal artery in the open-wedge high tibial osteotomy

Purpose

The objectives of this study were (1) to evaluate the sagittal and coronal plane location of the popliteal artery during the advancement of open-wedge high tibial osteotomy and (2) to confirm the effect of osteoarthritis if it changes the relationship between the popliteal artery and posterior cortex.

Methods

Two hundred consecutive patients were enrolled, and we divided patients into two subgroups according to age and cartilage status in the radiologic report of magnetic resonance imaging (group I: 100 non-arthritic knees; group II: 100 arthritic knees). For prediction of the location of the popliteal artery during the operation, sagittal and coronal plane location along the osteotomy plane was evaluated.

Results

The distance between the posterior cortex of the osteotomy and popliteal artery was 13–14 mm on the sagittal plane, and the popliteal artery was located at an approximately 35 ± 5.5 mm portion from the starting point of the osteotomy on the coronal plane. The distance at the starting point of osteotomy was larger than at the end portion and prominent area. In comparison between groups I and II, group II showed a larger distance on the sagittal planes [osteotomy–vascular: 13.6 vs 14.4 (p = 0.01), fibula–vascular: 4.88 vs 6.5 (p < 0.01), and prominence–vascular: 4.3 vs 5.3 (p < 0.01)] compared to the group I.

Conclusions

Special caution and some protection should be given until the approximately 35 mm portion from the starting point of the posteromedial cortex with consideration for the approximity on the sagittal plane. In comparison between the non-arthritic and arthritic knee, differences were observed on the sagittal plane. However, the value was minimal, and the clinical relevance was questionable.

Level of evidence

Case series, Level IV.     

IL-10 promoter gene polymorphism associated with the occurrence of chronic GVHD and its clinical course during systemic immunosuppressive treatment for chronic GVHD after allogeneic peripheral blood stem cell transplantation

BACKGROUND: The current study attempted to evaluate the association between IL-10 promoter gene polymorphism and transplant outcomes including the occurrence of chronic graft-versus-host disease (GVHD) and its clinical course during systemic immunosuppressive treatment (IST) among 60 recipients of cytokine-mobilized peripheral blood stem cell (PBSC) from HLA-matched sibling donors. METHODS: We analyzed 3 single-nucleotide polymorphisms in proximal region of IL-10 promoter gene (-1082/-819/-592). RESULTS: In the current study, only two haplotypes (1082*A/819*T/592*A [ATA] and 1082*A/819*C/592*C [ACC]) were found. An increased occurrence of chronic GVHD was noted dependent on the IL-10 haplotypes (43% vs. 68% vs. 96% in ACC/ACC vs. ATA/ACC vs. ATA/ATA haplotype, P=0.003). In a logistic regression based on multinomial model, ATA/ATA homozygote had 7-fold increasing risk of the development of chronic GVHD compared with ACC/ACC homozygote. The incidence of chronic GVHD at 1 year was 46%+/-20%, 64%+/-10%, and 82%+/-5% in ACC/ACC, ATA/ACC and ATA/ATA group, respectively (P=0.0266). Plus, the duration of systemic IST was significantly shorter in recipients without ATA-haplotype comparing with those with ATA haplotype (339 days vs. 1,146 days, P=0.0091). CONCLUSION: IL-10 promoter gene polymorphism was found to be apparently associated with chronic GVHD after allogeneic peripheral blood stem cell transplantation from HLA-matched sibling donors.     

Clinicopathologic analysis of early ampullary cancers with a focus on the feasibility of ampullectomy

OBJECTIVE: The purpose of this study was to evaluate whether ampullectomy can substitute for pancreatoduodenectomy (PD) in early ampullary cancer by clinicopathologic study. SUMMARY BACKGROUND DATA: Although ampullectomy has been attempted in early ampullary cancer (pTis, pT1), the indication and extent of resection have not been established. METHODS: Of 201 patients who had undergone PD for ampullary cancer between 1986 and 2002, 67 patients with a histologic diagnosis of pTis (n = 5) or pT1 (n = 62) cancer were analyzed retrospectively. Pathologic PD specimens were reviewed to analyze the cancer spread pattern, and medical records were reviewed for clinical outcomes. RESULTS: The 5-year survival rate of the 66 patients with early ampullary cancer (excluding one mortality) was 83.7%. Recurrence was confirmed in 12 patients (18.2%) and all died because of the recurrence. Pathologic review showed that 22 patients (32.8%) had at least one risk factor for failure after ampullectomy: lymph node metastasis (n = 6, 9.0%), perineural invasion (n = 1), or mucosal tumor infiltration along the CBD or P-duct (n = 15, 22.4%). Mean lengths of invasion into the CBD or the P-duct beyond the sphincter of Oddi were 7.7 mm (range, 1-25 mm) or 6.3 mm (range, 2-18 mm), respectively. Moreover, these risk factors were not correlated with tumor size, histologic grade, or the gross morphology of the primary tumor, although pTis cancer or pT1 cancer sized 1.0 cm or less was found to be least associated with risk factors. CONCLUSIONS: Ampullectomy for early ampullary cancer should not be considered an alternative operation to PD because of the high possibility of recurrence. PD should be preferably performed for adequate radical resection, even in early ampullary cancer, and ampullectomy should be reserved for those who have pTis or pT1 cancer sized 1.0 cm or less with high operative risk.     

Lumbar Lordosis of Spinal Stenosis Patients during Intraoperative Prone Positioning

Background

To evaluate the effect of spondylolisthesis on lumbar lordosis on the OSI (Jackson; Orthopaedic Systems Inc.) frame. Restoration of lumbar lordosis is important for maintaining sagittal balance. Physiologic lumbar lordosis has to be gained by intraoperative prone positioning with a hip extension and posterior instrumentation technique. There are some debates about changing lumbar lordosis on the OSI frame after an intraoperative prone position. We evaluated the effect of spondylolisthesis on lumbar lordosis after an intraoperative prone position.

Methods

Sixty-seven patients, who underwent spinal fusion at the Department of Orthopaedic Surgery of Gwangmyeong Sungae Hospital between May 2007 and February 2012, were included in this study. The study compared lumbar lordosis on preoperative upright, intraoperative prone and postoperative upright lateral X-rays between the simple stenosis (SS) group and spondylolisthesis group. The average age of patients was 67.86 years old. The average preoperative lordosis was 43.5° (± 14.9°), average intraoperative lordosis was 48.8° (± 13.2°), average postoperative lordosis was 46.5° (± 16.1°) and the average change on the frame was 5.3° (± 10.6°).

Results

Among all patients, 24 patients were diagnosed with simple spinal stenosis, 43 patients with spondylolisthesis (29 degenerative spondylolisthesis and 14 isthmic spondylolisthesis). Between the SS group and spondylolisthesis group, preoperative lordosis, intraoperative lordosis and postoperative lordosis were significantly larger in the spondylolisthesis group. The ratio of patients with increased lordosis on the OSI frame compared to preoperative lordosis was significantly higher in the spondylolisthesis group. The risk of increased lordosis on frame was significantly higher in the spondylolisthesis group (odds ratio, 3.325; 95% confidence interval, 1.101 to 10.039; p = 0.033).

Conclusions

Intraoperative lumbar lordosis on the OSI frame with a prone position was larger in the SS patients than the spondylolisthesis patients, which also produced a larger postoperative lordosis angle after posterior spinal fusion surgery. An increase in lumbar lordosis on the OSI frame should be considered during posterior spinal fusion surgery, especially in spondylolisthesis patients.     

100 multivisceral transplants at a single center

OBJECTIVE: The objective of this study was to summarize the evolution of multivisceral transplantation over a decade of experience and evaluate its current status. SUMMARY BACKGROUND DATA: Multivisceral transplantation can be valuable for the treatment of patients with massive abdominal catastrophes. Its major limitations have been technical and rejection of the intestinal graft. METHODS: This study consisted of an outcome analysis of 98 consecutive patients who received multivisceral transplantation at our institution. This represents the largest single center experience to date. RESULTS: The most common diseases in our population before transplant were intestinal gastroschisis and intestinal dysmotility syndromes in children, and mesenteric thrombosis and trauma in adults. Kaplan Meier estimated patient and graft survivals for all cases were 65% and 63% at 1 year, 49% and 47% at 3 years, and 49% and 47% at 5 years. Factors that adversely influenced patient survival included transplant before 1998 (P = 0.01), being hospitalized at the time of transplant (P = 0.05), and being a child who received Campath-1H induction (P = 0.03). Among 37 patients who had none of these 3 factors (15 adults and 22 children), estimated 1- and 3-year survivals were 89% and 71%, respectively. Patients transplanted since 2001 had significantly less moderate and severe rejections (31.6% vs 67.6%, P = 0.0005) with almost half of these patients never developing rejection. CONCLUSIONS: Multivisceral transplantation is now an effective treatment of patients with complex abdominal pathology. The incidences of serious acute rejection and patient survival have improved in the most recent experience. Our results show that the multivisceral graft seems to facilitate engraftment of transplanted organs and raises the possibility that there is a degree of immunologic protection afforded by this procedure.     

Effects of obesity on lower urinary tract symptoms in Korean BPH patients

We analyzed the effects of obesity on lower urinary tract symptoms （LUTSs） in Korean benign prostatic hyperplasia （BPH） patients. This is a multicenter, cross-sectional, prospective study conducted in four centers in Korea. A total of 602 men with LUTSs secondary to BPH were included. BPH/LUTSs cases were men aged ≥ 40 years with intemational prostate symptom scores （IPSS） ≥ 8 points. Height, weight and waist circumference were measured. Among the 602 patients, 156 patients had a waist circumference above 90 cm, representing central obesity, and 215 patients had a body mass index above 25 kg m2. Waist circumference was positively correlated with prostate volume （P = 0.034）. Men with waist circumference 〉 90 cm experienced a 1.36-fold increased risk of severe LUTSs （95% CI 0.82-2.41） compared with men with waist circumference ≤ 90 cm. Prostate volume was positively correlated with urgency and nocturia in men with central obesity. In this population of Korean men diagnosed with BPH, central obesity rather than overall obesity seems to be the more important predictor of LUTSs correlated with BPH.     

Effect of radiofrequency radiation exposure on mouse skin tumorigenesis initiated by 7,12-dimethybenz[α]anthracene

Purpose: Although radiofrequency (RF) radiation is not considered mutagenic, it has been suggested as a promoter of tumorigenesis. To study if RF radiation has a tumor promoting effect, we exposed mice with skin tumorigenesis initiated by 7,12-dimethybenz[α]anthracene (DMBA) to RF radiation.

Materials and methods: Eighty male ICR mice were subjected to a single DMBA application (100 μg/100 μl acetone/mouse) on shaved dorsal skin at the age of 7 weeks. After one week, the mice were randomized into four equal groups of 20 mice each: i.e., sham-, 849 MHz-, 1,763 MHz-exposed, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated groups. The RF exposure was conducted at a whole body average specific absorption rate (SAR) of 0.4 W/Kg, for 2 cycles of 45 min exposure with a 15 min interval each day, 5 days a week for 19 weeks. The TPA-treated group served as a positive control for skin tumorigenesis and were administered TPA (4 μg/100 μl acetone/mouse) twice weekly without RF exposure.

Results: All mice were examined weekly at a macroscopic level. No skin tumors were observed in any groups except in the TPA-treated positive control group. TPA is known tumor promoter in DMBA-induced skin carcinogenesis and tumor incidence in the TPA treated group was 95%. At week 20 after DMBA initiation, skin tissues were analyzed immunohistochemically using anti-proliferating cell nuclear antigen (PCNA) antibody. No differences were observed by pathological examination or by PCNA staining between the sham- and the RF-exposed groups. The expression of cyclin D1 and c-fos were detected only in the tumorous skin tissues of the TPA-treated group.

Conclusion: No evidence was found that RF radiation serves as a tumor promoter for skin tumors. Our data suggests that 849 MHz and 1,763 MHz RF radiations, similar to those emitted from mobile phones, do not have any promoting effect on skin tumor development in DMBA-initiated mice.