Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs

BACKGROUND: Porcine pancreas is a potential source of material for islet xenotransplantation. However, the difficulty in isolating islets, because of their fragility and the variability of isolation outcome in donor age and breed, represents a major obstacle to porcine islet xenotransplantation. In this study, we compared the islet isolation yield of specific pathogen-free (SPF) Chicago Medical School (CMS) miniature pigs with that of another miniature pig breed and market pigs from a local slaughterhouse. METHODS: Nine adult CMS miniature (ACM) pigs (>12 months), six young CMS miniature (YCM) pigs (6-7 months), four adult Prestige World Genetics (PWG) miniature (APM) pigs (>12 months), and 13 adult market (AM) pigs from a local slaughterhouse were used for islet isolation. RESULTS: The islet yield per gram of pancreas from ACM pigs (9589 +/- 2823 IEQ/g) was significantly higher than that from APM pigs (1752 +/- 874 IEQ/g, P < 0.05), AM pigs (1931 +/- 947 IEQ/g, P < 0.05), or YCM pigs (3460 +/- 1985 IEQ/g, P < 0.05). Isolated islets from ACM pigs were significantly larger than those from AM pigs or YCM pigs. The in vitro and in vivo function of isolated islets showed no difference among experimental groups. The pancreases of ACM pigs contained higher mean islet volume density percentages and larger size of islets than those of AM or APM pigs. CONCLUSIONS: We isolated extremely high yields of well-functioning islets from ACM pigs bred under SPF conditions. SPF CMS miniature pigs should be one of the best porcine islet donors for clinical porcine islet xenotransplantation.     

Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts.

Osteogenesis is synergistically enhanced by the combined effect of complimentary factors. This study showed that Nell-1 and BMP-2 synergistically enhanced osteogenic differentiation of myoblasts and phosphorylated the JNK MAPK pathway. The findings are important because of the osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of coordinated BMP-2 and Nell-1 delivery. INTRODUCTION: BMPs play an important role in the migration and proliferation of mesenchymal cells and have a unique ability to alter the differentiation of mesenchymal cells toward chondrogenic and osteogenic lineages. Signaling upstream of Cbfa1/Runx2, BMPs effects are not limited to cells of the osteoblast lineage. Thus, additional osteoblast-specific factors that could synergize with BMP-2 would be advantageous for bone regeneration procedures. NELL-1 (NEL-like molecule-1; NEL [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a novel growth factor believed to preferentially target cells committed to the osteochondral lineage. MATERIALS AND METHODS: C2C12 myoblasts were transduced with AdLacZ, AdNell-1, AdBMP-2, or AdNell-1+AdBMP-2 overexpression viruses. Effects were studied by cell morphology, alkaline phosphatase activity, osteopontin production, and MAPK signaling. Additionally, in a nude mouse model, viruses were injected into leg muscles, and new bone formation was examined after 2 and 8 wk. RESULTS: C2C12 myoblasts co-transduced with AdNell-1+AdBMP-2 showed a synergistic effect on osteogenic differentiation as detected by alkaline phosphatase activity and osteopontin production. Nell-1 stimulation on AdNell-1 + AdBMP-2 preconditioned C2C12 cells revealed significant activation of the non-BMP-2 associated c-Jun N-terminal kinase (JNK) MAPK signaling pathway, but not the p38 or extracellular signal-regulated kinase (ERK1/2) MAPK pathways. Importantly Nell-1 alone did not induce osteogenic differentiation of myoblasts. In a nude mouse model, injection of AdNell-1 alone stimulated no bone formation within muscle; however, injection of AdNell-1+AdBMP-2 stimulated a synergistic increase in bone formation compared with AdBMP-2 alone. CONCLUSIONS: These findings are important because of the confirmed osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of enhanced BMP-2 action with coordinated Nell-1 delivery.     

Anterior translocaton of pulmonary artery without aortic transection in repair of tetralogy of Fallot with absent pulmonary valve.

We developed a technique of translocation of the pulmonary artery anterior to the ascending aorta without transection of the aorta in the repair of tetralogy of Fallot with absent pulmonary valve. Our technique includes detachment of the main pulmonary artery (MPA) from the pulmonary annulus, vertical division of the MPA, anterior translocation of the pulmonary artery with patch augmentation between the vertically divided MPA.     

Derivation of functional dopamine neurons from embryonic stem cells

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective degeneration of dopaminergic (DA) neurons in the substantia nigra of the midbrain. Pharmacological treatment of PD has been a prevailing strategy. However, it has some limitations because its effectiveness gradually decreases and side effects develop. As an alternative, cell transplantation therapy has been tried. Although transplantation of fetal ventral mesencephalic cells looks promising for the treatment of PD in some cases, ethical and technical problems in obtaining large numbers of human fetal brain tissues also lead to difficulty in its clinical application. Our recent studies showed that a high yield of DA neurons could be derived from embryonic stem (ES) cells and they efficiently induced behavioral recovery in a PD animal model. Here we summarize methods for generation of functional DA neurons from ES cells for application to PD models.     

Surgical completeness of robotic thyroidectomy: a prospective comparison with conventional open thyroidectomy in papillary thyroid carcinoma patients

Background

Using the da Vinci^® robotic system, surgeons can complete secure thyroidectomy without noticeable neck scarring. This study compared the surgical completeness of transaxillary robotic thyroidectomy (RT) with conventional open procedures (OT) in treating papillary thyroid carcinoma (PTC) patients.

Materials and methods

From April 2009 through February 2011, 94 PTC patients underwent total thyroidectomy with central compartment neck dissection (CCND) at Yonsei University College of Medicine. All patients received 1.1 GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBS), and diagnostic WBS (DxWBS) 1 year later. We prospectively compared patient clinicopathologic characteristics and surgical completeness between the two groups.

Results

Fifty-one patients underwent OT and 43 underwent RT. Mean age was significantly younger in the RT group. Tumor size, capsular-invasion frequency, multifocality, bilaterality, and central nodal metastasis were not different between the two groups. The number of retrieved nodes during CCND did not significantly differ between the groups. There was no significant difference between the OT and RT groups in stimulated thyroglobulin levels acquired during TxWBS and DxWBS. The RAI uptake ratios at TxWBS were significantly higher in the RT group compared with the OT group; however, follow-up DxWBS showed no difference in RAI uptake ratios. Also, the ablation success rate was similar between the two groups. There were no abnormal findings in follow-up neck ultrasonography in either group.

Conclusion

Remnant thyroid tissue ablation after transaxillary RT was successfully managed by 1.1 GBq RAI. RT showed similar surgical completeness versus conventional OT, and provides a safe and feasible surgical option for PTC patients.     

Outcome analysis of arthroscopic treatment of partial thickness rotator cuff tears

Background:

Partial thickness rotator cuff tears occupy an important position in the spectrum of rotator cuff disease. The development of a more comprehensive classification has been sought to address both the tear location and extent, which may influence clinical results. The purpose of this study is to classify partial thickness rotator cuff tears according to the arthroscopic findings and to evaluate the clinical outcomes after arthroscopic repair of partial thickness tears.

Materials and Methods:

One hundred and two patients had arthroscopic treatment of partial thickness rotator cuff tears. The inclusion criterion for the study was a partially torn supraspinatus tendon involving articular or bursal side, verified by direct arthroscopic visualization. Outcome analysis was exclusively applied to patients who underwent transtendon repair, using the shoulder index of American Shoulder and Elbow Society and the University of California Los Angeles (UCLA) rating system.

Results:

Partial thickness rotator cuff tears were divided into five groups according to arthroscopic findings. There was significant improvement after surgery in all parameters of clinical evaluation in the tears that warranted repair. Arthroscopic repair in situ (transtendon technique) may be the preferred option in unstable partial thickness tear.

Conclusion:

The proposed classification system may assist decision making in the treatment of partial thickness rotator cuff tears.     

Potential of Oncostatin M to accelerate diabetic wound healing

Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti‐inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full‐thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left‐side wounds (n = 10) and phosphate‐buffered saline was applied on the two right‐side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM‐treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P < 0·05). The results of this study indicate that topical application of OSM may have the potential to accelerate healing of diabetic wounds.     

Size discrepancy between endoscopic size and pathologic size is not negligible in endoscopic resection for early gastric cancer

Background

Accurate tumor size measurement is critical for selecting proper candidates for endoscopic resection (ER) of early gastric cancer (EGC). However, size discrepancy between endoscopic size and pathologic size often occurs during ER for EGC.

Objective

The purposes of this study were to investigate the clinicopathological characteristics related to size discrepancy and the clinical implications of size discrepancies in terms of therapeutic outcomes.

Methods

Between April 2006 and June 2013, a total of 820 patients with 826 EGCs underwent ER. Enrolled lesions were categorized into the following three groups based on size discrepancy between endoscopic size and pathologic size: well-estimated (N = 308), underestimated (N = 215), or overestimated (N = 303) lesions. The well-estimated group was defined as lesions with a ratio of endoscopic size to pathologic size from 0.7 to 1.3.

Results

The overall median size discrepancy was 5.0 mm (interquartile range 2.0–9.0). Size, location, macroscopic type, primary tumor stage, and histology differed significantly between the three groups. Larger size [odds ratio (OR) 5.07, 95 % confidence interval (CI) 3.38–7.59, p < 0.001], flat/depressed type (OR 1.71, 95 % CI 1.15–2.55, p = 0.008), and undifferentiated histology (OR 2.24, 95 % CI 1.31–3.83, p = 0.003) were independent risk factors for endoscopic size underestimation in multivariate analysis. Smaller size (OR 10.95, 95 % CI 4.64–25.87, p < 0.001) was the only independent predictor for endoscopic overestimation of size. Significantly lower complete resection and curative resection rates were detected in the underestimated group compared with the well-estimated group, while the complete resection rate in the overestimated group tended to be higher than in the well-estimated group. There was no significant difference of curative resection rate between the overestimated and the well-estimated groups.

Conclusions

Larger size, flat/depressed type, and undifferentiated histology of EGC carry a significant risk for endoscopic underestimation of lesion size, which results in the lower rates of complete and curative resections for EGC. Further studies to reduce size discrepancy are warranted.     

Transvaginal specimen extraction versus conventional minilaparotomy after laparoscopic anterior resection for colorectal cancer: mid-term results of a case-matched study

Background

Although the vagina is considered a viable route during laparoscopic surgery, a number of concerns have led to a need to demonstrate the safety of a transvaginal approach in colorectal surgery. However, the data for transvaginal access in left-sided colorectal cancer are extremely limited, and no study has compared the clinical outcomes with a conventional laparoscopic procedure.

Objective

We compared the clinical outcomes of totally laparoscopic anterior resection with transvaginal specimen extraction (TVSE) with those of the conventional laparoscopic approach with minilaparotomy (LAP) for anastomosis construction and specimen retrieval in left-sided colorectal cancer.

Methods

Fifty-eight patients underwent TVSE between October 2006 and July 2011 and were matched by age, surgery date, tumor location, and tumor stage with patients who underwent conventional LAP for left-sided colorectal cancer.

Results

Operative time was significantly longer in the TVSE group (149.3 ± 39.8 vs. 131.9 ± 41.4 min; p = 0.023). Patients in the TVSE group experienced less pain (pain score 4.9 ± 1.6 vs. 5.8 ± 1.9; p = 0.008), shorter time to passage of flatus (2.2 ± 1.1 vs. 2.7 ± 1.2 days; p = 0.026), and higher satisfaction with the cosmetic results (cosmetic score 8.0 ± 1.4 vs. 6.3 ± 1.5; p = 0.001). More endolinear staplers for rectal transection were used in the LAP group (1.2 ± 0.5 vs. 1.1 ± 0.2; p = 0.021). Overall morbidities were similar in both groups; however, three wound infections only occurred in the LAP group. After a median follow-up of 34.4 (range 11–60) months, no transvaginal access-site recurrence occurred. The 3-year disease-free survival was similar between groups (91.5 vs. 90.8 %; p = 0.746).

Conclusions

Transvaginal access after totally laparoscopic anterior resection is safe and feasible for left-sided colorectal cancer in selected patients with better short-term outcomes.