Esophageal magnetic compression anastomosis in dogs.

BACKGROUND: Magnetic compression anastomosis (MCA) is a novel suture-free reconstruction of the digestive tract. It has been used in gastrointestinal anastomosis, jejunal anastomosis, cholangioenteric anastomosis and so on. The traditional operative outcomes of congenital esophageal atresia and benign esophageal stricture are poor, and there are too many complications postoperatively. AIM: To test MCA technology to reconstruct the esophagus in dogs, prior to studying the feasibility and safety of MCA in humans. METHODS: Thirty-six dogs were randomized into either the study or control group (n = 18 per group). The dogs in the study group were subjected to end-to-end esophageal anastomosis with the magnetic compression device, while those in the control group underwent hand-sewn anastomosis with 4-0 absorbable multifilament Vicryl. We used interrupted single-layer inverting sutures. The anastomosis time, gross appearance, weight and pathology of the anastomosis were evaluated at one month, three months and six months postoperatively. RESULTS: The anastomosis time of the MCA group was shorter than that of the hand-sewn group (7.5 ± 1.0 min vs 12.5 ± 1.8 min, P < 0.01). In the MCA group, X-ray examination was performed every day to locate the magnetic device in the esophagus before the magnetic device fell off from the esophagus. In the hand-sewn group, dogs did not undergo X-ray examination. One month after the surgeries, the mean weight of the dogs in the hand-sewn group had decreased more than that of the dogs in the MCA group (11.63 ± 0.71 kg vs 12.73 ± 0.80 kg, P < 0.05). At 3 mo and 6 mo after the operation, the dogs' weights were similar between the two groups (13.75 ± 0.84 kg vs 14.03 ± 0.82 kg, 14.93 ± 0.80 kg vs 15.44 ± 0.47 kg). The number of inflammatory cells in MCA group was lower than that in hand-sewn group on 1 mo after operation. CONCLUSION: MCA is an effective and safe method for esophageal reconstruction. The anastomosis time of the MCA group was less than that of the hand-sewn group. This study shows that MCA technology may be applied to human esophageal reconstruction, provided these favorable results are confirmed by more publications.

Nutlin-3-Induced Sensitization of Non-Small Cell Lung Cancer Stem Cells to Axitinib-Induced Apoptosis Through Repression of Akt1/Wnt Signaling.

The aim of this study was to investigate the potential biological activities of nutlin-3 in the regulation of growth and proliferation of non-small cell lung cancer (NSCLC) stem cells (CSCs), which may help in sensitizing to axitinib-induced apoptosis. Nutlin-3 induction of p53 expression was used to test its role in controlling the cell division pattern and apoptosis of NSCLC cells. A549 cells and H460 cells were pretreated with nutlin-3 and then treated with either an Akt1 activator or shRNA-GSK3ß, to investigate the potential role of p53 sensitization in the biological effects of axitinib. We also determined the expression levels of GSK3ß and p-Akt1 in patients with NSCLC and determined their potential association with survival data using Kaplan-Meier plots and CBIOTAL. Increased p53 expression stimulated the induction of apoptosis by axitinib and promoted asymmetric cell division (ACD) of NSCLC CSCs. The repression of Akt phosphorylation induced by nutlin-3 promoted the ACD of lung CSCs, decreasing the proportion of the stem cell population. In addition to the induction of apoptosis by axitinib through inhibition of Wnt signaling, nutlin-3 treatment further enhanced axitinib-induced apoptosis by inhibiting Akt1/GSK3ß/Wnt signaling. The low expression of GSK3ß and increased expression of p-Akt in patients with NSCLC were closely associated with the development of NSCLC. TP53 stimulates the induction of apoptosis in NSCLC by axitinib and the ACD of lung CSCs through its regulatory effects on the p53/Akt/GSK3ß pathways.

Sutureless anastomoses using magnetic rings in canine liver transplantation model.

BACKGROUND: In the first posttransplant month, the most frequent complications are due to technical problems related to complex vascular and bile duct reconstructions during the operation. Moreover, despite great improvements in suturing technique and materials, severe organ ischemia-reperfusion caused by time-consuming hand suturing is still an important factor in graft survival. During the operation, severe hypotension, hypoxic acidosis, hyperkalemia, and renal dysfunction may occur during the anhepatic phase due to the prolonged venous clamping time required for hand suturing. Therefore, hand suturing is a handicap in the development of further advancements in liver transplantation. In this study, we aimed to test a new "mechanical installation method" for rapid vascular reconstruction. METHODS: The magnetic pinning-ring device was developed consisting of paired magnetic rings coated with titanium oxide and embedded in a polypropylene shell. The rings were equipped with alternately spaced holes and titanium pins. Forty adult mongrel dogs were randomly divided into groups: A (n = 16), all vascular and bile duct reconstruction by magnetic ring without venous bypass; B (n = 16), all vascular and bile duct reconstruction by hand suturing with venous bypass; C (n = 8), sham transplantation group, transection of all vessels and common bile duct followed by anastomosis with the magnetic rings without liver transplantation. From groups A and B, dogs were randomly selected as donors (n = 8) or recipients (n = 8) of liver transplantations. We recorded operation time, vascular and bile duct anastomosis time, anhepatic time, administration of supplemental fluids during operation, and survival; blood samples were collected for the detection of liver damage (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and tumor necrosis factor α level. Patency was confirmed using ultrasound scans at various time points as late as 24 wk after surgery. Angiography was used to evaluate the anastomoses formed with magnetic rings. In group C, gross observation, histologic staining, and scanning electron microscopy were used to evaluate the vessels and bile ducts 12 wk postoperatively. RESULTS: In group A, the total operation time, inferior vena cava, and portal vein anastomosis times were significantly shortened, and the anhepatic phase was reduced to about one-fifth that of group B, which was a significant difference between the two groups (P < 0.01). The mean total operative time was 2.54 ± 0.45 h. In order to maintain adequate blood pressure, the mean fluid volume infused was 800.56 ± 60.56 mL in the recipients of group A, which was lower than that in group B (2241.67 ± 390.78 mL, P < 0.01). Use of a pressor agent in group A was unnecessary. After operation, five of eight animals in group A survived more than 7 d after operation. The main cause of death was acute rejection. Only three of eight animals in group B survived more than 1 wk after operation due to chronic anastomotic bleeding, kidney failure, heart failure, and gastrointestinal bleeding. There was a statistically significant difference (P < 0.01) between the short-term survival rate in the two groups (75.0% versus 37.5%). The ALT (1544.46 ± 286.27) U/L and AST (1710.74 ± 252.27) U/L levels after operation in the animals with hand suturing were significantly higher than those in the sutureless group (ALT = 1116.41 ± 210.55 U/L; AST = 1176.95 ± 248.25) U/L after reperfusion (P < 0.01). The serum tumor necrosis factor α levels (45.56 ± 10.78) ng/L in group B were significantly higher than those of group A (26.64 ± 10.84) ng/L after reperfusion (P < 0.01). Re-endothelialization was confirmed in all vessels in group C, with neither formation of aneurysms nor thickening of the vascular wall noted after 12 wk. The bile duct anastomoses also healed well. CONCLUSIONS: The magnetic pinning-ring device offers a simple, fast, reliable, and efficacious technique for nonsuturing vascular and bile duct anastomoses. Use of this device shortens operation time, maintains a high patency rate, and improves the healing of tissue. Application of the magnetic ring anastomosis technique can effectively reduce the complications caused by hand suturing, and can reduce the extent of ischemia-reperfusion injury, leading to smoother operations and improved prognosis.

A new veno-venous bypass type for ex-vivo liver resection in dogs.

Ex-vivo liver resection is a procedure in which the liver is completely removed, perfused and after bench surgery, the liver is autotransplanted to the original site. Ex-vivo liver resection is an important treatment for unresectable liver tumors. This surgical procedure requires long operation time, during which blood flow must be carefully maintained to avoid venous congestion. An effective veno-venous bypass (VVB) may meet this requirement. The present study was to test our new designed VVB device which comprised one heparinized polyvinylchloride tube and three magnetic rings. The efficacy of this device was tested in five dogs. A VVB was established in 6-10 minutes. There was no leakage during the procedure. Hemodynamics was stable at anhepatic phase, which indicated that the bypass was successful. This newly-developed VVB device maintained circulation stability during ex-vivo liver resection in our dog model and thus, this VVB device significantly shortened the operation time.

Nonsuture anastomosis of arteries and veins using the magnetic pinned-ring device: a histologic and scanning electron microscopic study.

BACKGROUND: The goal of this study was to evaluate the performance of the magnetic pinned-ring device for nonsuture vascular anastomosis. METHODS: The magnetic pinned-ring device consists of paired magnetic rings that are coated with titanium nitride and embedded in a polypropylene shell; the rings are equipped with alternately spaced holes and titanium pins. The vascular anastomosis procedure using the novel magnetic pinned-ring device was performed on 14 mongrel dogs, and the traditional hand-sewing technique was used on 14 additional dogs. In situ end-to-end anastomoses were performed in the femoral artery and the inferior vena cava. Patency was confirmed through ultrasonographic scans at different time points as late as 24 weeks after surgery. Gross observation, histological staining, and scanning electron microscopy were used to evaluate the results at 24 weeks postoperatively. RESULTS: The time required to perform the vascular anastomosis was significantly shorter for the magnetic device than for hand sewing. A continuity of re-endothelialization was confirmed in all anastomotic stomas after 24 weeks, and neither formation of aneurysms nor thickening of the vascular wall was noted. The re-endothelialization was smooth at the anastomotic site of the magnetic device, whereas hand sewing resulted in rough and uneven re-endothelialization and the presence of visible sutures. Moreover, the endothelial cells were regularly arranged at the anastomotic site of the magnetic device, whereas different-sized and irregularly aligned endothelial cells were present at the hand-sewn anastomotic site. Use of the magnetic device was associated with significantly decreased deposition of fibrotic collagen and depressed infiltration of inflammatory cells compared with use of the hand-sewing technique. CONCLUSIONS: The magnetic pinned-ring device offers a simple, fast, reliable, and efficacious technique for nonsuture vascular anastomosis. Use of this device shortens operation time, maintains a high patency rate, and improves the healing of vascular tissue.