Crocetin preconditioning attenuates ischemia reperfusion-induced hepatic injury by disrupting Keap1/Nrf2 interaction and activating Nrf2/HO-1 pathway.

BACKGROUND: Ischemia reperfusion (I/R) injury is a frequent occurrence during liver transplantation surgery, resulting from the temporary cessation of blood flow and subsequent restoration of blood flow. Serious I/R injury is a significant factor causing transplant failure. Hepatic I/R process is characterized by excessive inflammation, oxidation, and apoptosis. Crocetin (Crt) is a natural compound exhibiting beneficial roles in various I/R-induced organ damages. However, Crt's potential role in hepatic I/R remains unexplored. OBJECTIVE AND METHODS: In order to reveal the impact of Crt on hepatic I/R and the associated signaling pathway, we utilized a syngeneic orthotopic liver transplantation rat model to induce hepatic I/R injury. RESULTS: Pretreatment with Crt significantly mitigated hepatic I/R injury. This was evident by decreased activities of serum ALT, AST and LDH, indicating improved liver function. Crt treatment also alleviated oxidative stress, as demonstrated by decreased serum MDA content and elevated serum SOD and GSH-Px activities. Furthermore, Crt suppressed inflammatory responses by downregulating both the serum and liver IL-1ß, IL-6 and TNF-α while upregulating IL-10 expression. Additionally, Crt reduced apoptosis by decreasing pro-apoptotic Bax, cleaved caspase-3 and cleaved caspase-9, while increasing anti-apoptotic Bcl2 expression. Notably, these protective effects of Crt were dose-dependent. Moreover, our data indicates that Crt plays protective functions during hepatic I/R via disrupting Keap1/Nrf2 interaction and activating Nrf2/HO-1 signaling. This was further supported by observations of alleviated hepatic histopathological changes in I/R rats treated with Crt. CONCLUSIONS: Crt shows potential as a therapeutic agent for preventing hepatic I/R injury during clinical liver transplantation.

Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis: An initial cohort study.

BACKGROUND: Some cases of laparoscopic-assisted liver transplantation (LA-LT) with utilization of reduced-size grafts has been reported. We here introduced successful utilization of LA-LT with whole liver grafts and magnetic portal vein anastomosis. METHODS: Eight patients with liver cirrhosis were included for LA-LT using donor organs after cardiac death. The surgical procedures included purely laparoscopic explant hepatectomy and whole-liver graft implantation via the midline incision. After explant removal, the whole-liver graft was then placed in situ, and a side-to-side cavo-caval anastomosis with 4-5 cm oval opening was performed. The magnetic rings were everted on the donor and recipient portal vein, respectively, and the instant attachment of the two magnets at the donor and recipient portal vein allowed fast blood reperfusion, followed by continuous suturing on the surface of the magnets. RESULTS: The median operation time was 495 (range 420-630). The median time of explant hepatectomy and IVC anastomosis was 239 (range 150-300) min and 14.5 (range 10-19) min, respectively. Of note, the median anhepatic time was 25 (range 20-35) min. All the patients were discharged home with no major complications after more than six months follow-up. CONCLUSION: LA-LT with full-size graft is feasible and utilization of magnetic anastomosis would further simplify the procedure.

Liver transplantation using magnetic anastomosis in pigs.

Magnetic anastomosis substantially shortens the duration of vascular anastomosis. We aimed to apply magnetic anastomosis technology (MAT) to donor liver implantations in pig orthotopic liver transplantation (OLT). Twenty healthy adult pigs were randomly divided into donors and recipients, and major vascular anastomosis was performed using MAT during OLT. Recipient liver and kidney function was measured pre-surgery and 12, 24 and 72 h post-surgery. Vascular anastomoses examinations were performed using ultrasound or angiography weekly post-surgery, and pathological examinations of vascular anastomoses were performed during autopsy after animal euthanasia. All recipients survived 24 h after surgery, which is considered as successful transplantation. Anhepatic duration was only 13 min, and no anastomotic obstruction or stenosis, magnetic displacement and anastomotic angulation, or distortion was found upon postoperative examinations of major liver vasculature. Aspartate aminotransferase, alanine aminotransferase, and total bilirubin serum levels increased considerably postoperatively. The follow-up period for this study was 1 year, and the median survival time of all recipients was 115 d (interquartile range = 11-180 d). The main causes of death were liver failure, immune rejection, infection, and arterial anastomotic bleeding. Moreover, vascular anastomoses healed well with a survival time of more than two weeks. We developed a novel magnetic device to create a fast and safe technique to perform major vascular anastomoses in pig liver transplantations. Additionally, the liver graft implantation using MAT considerably shortened the recipient warm ischemia time, which will reduce the extent of ischemia-reperfusion injury. We conclude that MAT is an effective method for donor liver fast implantation in OLT in pigs.

[Research Progress of Magnetically Anchored Abdominal Video System].

Magnetic anchoring technology provides a new development opportunity for current minimally invasive surgery. The magnetic anchoring abdominal video system based on this technology can effectively improve the operability and minimally invasiveness of single-port laparoscopic surgery. The development history of magnetically anchored abdominal video system was reviewed, and the design features and deficiencies of various types of magnetically anchored video devices were compared and analyzed. The evolution characteristics of the magnetic anchored video system are explained from minimally invasive and intelligent perspectives, and the challenges and opportunities of magnetic anchored video system are summarized and prospected.

Adhesive anastomosis for organ transplantation.

The recent development of tough tissue adhesives has stimulated intense interests among material scientists and medical doctors. However, these adhesives have seldom been tested in clinically demanding surgeries. Here we demonstrate adhesive anastomosis in organ transplantation. Anastomosis is commonly conducted by dense sutures and takes a long time, during which all the vessels are occluded. Prolonged occlusion may damage organs and even cause death. We formulate a tough, biocompatible, bioabsorbable adhesive that can sustain tissue tension and pressurized flow. We expose the endothelial surface of vessels onto a gasket, press two endothelial surfaces to the adhesive using a pair of magnetic rings, and reopen the bloodstream immediately. The time for adhesive anastomosis is shortened compared to the time for sutured anastomosis. We have achieved adhesive anastomosis of a great vein in transplanting the liver of a pig. After the surgery, the adhesive is absorbed, the vein heals, and the pig lives for over one month.

Magnetic-assisted laparoscopic liver transplantation in swine.

BACKGROUND: Although laparoscopic technology has achieved rapid development in the surgical field, it has not been applied to liver transplantation, primarily because of difficulties associated with laparoscopic vascular anastomosis. In this study, we introduced a new magnetic-assisted vascular anastomosis technique and explored its application in laparoscopic liver transplantation in pigs. METHODS: Two sets of magnetic vascular anastomosis rings (MVARs) with different diameters were developed. One set was used for anastomosis of the suprahepatic vena cava (SHVC) and the other set was used for anastomosis of the infrahepatic vena cava (IHVC) and portal vein (PV). Six laparoscopic orthotopic liver transplantations were performed in pigs. Donor liver was obtained via open surgery. Hepatectomy was performed in the recipients through laparoscopic surgery. Anastomosis of the SHVC was performed using hand-assisted magnetic anastomosis, and the anastomosis of the IHVC and PV was performed by magnetic anastomosis with or without hand assistance. RESULTS: Liver transplants were successfully performed in five of the six cases. Postoperative ultrasonographic examination showed that the portal inflow was smooth. However, PV bending and blood flow obstruction occurred in one case because the MVARs were attached to each other. The durations of loading of MVAR in the laparoscope group and manual assistance group for IHVC and PV were 13 ± 5 vs. 5 ± 1 min (P < 0.01) and 10 ± 2 vs. 4 ± 1 min (P < 0.05), respectively. The durations of MVAR anastomosis in the laparoscope group and manual assistance group for IHVC and PV were 5 ± 1 vs. 1 ± 1 min (P < 0.01), and 5 ± 1 vs. 1 ± 1 min (P < 0.01), respectively. The anhepatic phase was 43 ± 4 min in the laparoscope group and 23 ± 2 min in the manual assistance group (P < 0.01). CONCLUSIONS: Our study showed that magnetic-assisted laparoscopic liver transplantation can be successfully carried out in pigs.

Author Correction: End-to-end vascular anastomosis using a novel magnetic compression device in rabbits: a preliminary study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

End-to-end vascular anastomosis using a novel magnetic compression device in rabbits: a preliminary study.

Magnetic compression anastomosis (MCA) has been appreciated as an innovative alternative to manual suturing in vascular reconstruction. However, magnetic devices have limitations in their applications. The present study aimed to introduce a newly developed magnetic device for end-to-end vascular anastomosis. Twenty male New Zealand rabbits were randomly assigned to receive end-to-end postcaval vein anastomosis using either a newly designed MCA device (Group MCA) or continuous-interrupted suturing (Group CIS). The anastomotic patency was evaluated by Doppler or venography immediately, 1 week, and 12 weeks after surgery. Anastomotic quality was evaluated gross and microscopic histological study 12 weeks after surgery. The procedure was successfully performed and all animals survived until sacrifice. The duration of surgery and anastomosis time in Group MCA were significantly shorter compared to Group CIS (all p < 0.001), and the incidence of anastomotic patency and postoperative morbidity were comparable between the two groups (all p > 0.05). Hematoxylin-eosin staining showed that anastomotic intima from Group MCA was much smoother with more regularly arranged endothelial cells than from compared to the Group CIS. A novel MCA device was successfully applied in rabbit vascular anastomosis. We demonstrated the reliability and effectiveness of this newly developed MCA in this study.

Magnetic compression anastomosis for the treatment of benign biliary strictures: a clinical study from China.

BACKGROUND: Magnetic compression anastomosis (MCA) is a revolutionary minimally invasive method to perform choledochocholedochostomy in patients with benign biliary stricture (BBS). We conducted MCA for the treatment of severe BBS that could not be treated by conventional methods. PATIENTS AND METHODS: Patients with BBSs that could not be treated using conventional treatments were included. All patients underwent percutaneous transhepatic biliary drainage (PTBD) before MCA, and underwent cholangiography via simultaneous PTBD and endoscopic retrograde cholangiopancreatography (ERCP). The MCA device consisted of a parent and a daughter magnet. The daughter magnet was delivered via the PTBD route to the proximal end of the obstruction, and the parent magnet was delivered via ERCP to the distal end of the obstruction. After recanalization, the MCA device was removed, and biliary stenting (or PTBD) was performed for at least 6 months. RESULTS: Of the 9 patients (age 49 ± 12.9 years), 6 had undergone orthotopic liver transplantation. MCA was successful in all 9 patients. The stricture length was 3 ± 1.7 mm, and recanalization occurred after 16.3 ± 13.2 days. Multiple plastic stents (4 patients), fully covered self-expandable metallic stents (4 patients), or PTBD (1 patient) was used after recanalization. Two mild adverse events occurred (cholangitis, 1 patient; biliary bleeding, 1 patient), but were resolved with conservative treatment. Stents were retrieved after > 6 months, and no stenosis occurred during 2-66 months of stent-free follow-up. CONCLUSION: The MCA technique is a revolutionary method for choledochocholedochostomy in patients with severe BBS unresponsive to conventional procedures.

Characterization of the PM2.5 concentration in surgical smoke in different tissues during hemihepatectomy and protective measures.

The characteristics of the PM2.5 concentration in surgical smoke produced by operating on different human tissues during hemihepatectomy were explored to provide a reference for protective measures. Our results showed that the highest concentration of PM2.5 produced by the electrosurgical knife was the liver tissue, followed by muscle, adipose, and vascular tissue. When the single-layer disposable medical mask, double-layer disposable medical mask, and surgical particulate respirator were used to cover the sampling port of the detector, the PM2.5 concentration for all tissue types could be reduced by approximately 40%, 55% and 75%, respectively. In the liver, the average concentration of PM2.5 produced by the ultrasonic scalpel was approximately twice that produced by the electrosurgical knife, suggesting that the air pollution around the chief surgeon caused by the ultrasonic scalpel is more serious than that caused by the electrosurgical knife. Much more protective work should be given for the liver-related surgery.

Magnetic Anastomosis Rings to Create Portacaval Shunt in a Canine Model of Portal Hypertension.

PURPOSE: This study evaluated a novel magnetic compression technique (magnamosis) for creating a portacaval shunt in a canine model of portal hypertension, relative to traditional manual suture. METHODS: Portal hypertension was induced in 18 dogs by partial ligation of the portal vein (baseline). Six weeks later, extrahepatic portacaval shunt implantation was performed with either magnetic anastomosis rings, or traditional manual suture (n = 9, each). The two groups were compared for operative time, portal vein pressure, and serum biochemical indices. Twenty-four weeks post-implantation, the established anastomoses were evaluated by color Doppler imaging, venography, and gross and microscopic histological examinations. RESULTS: Anastomotic leakage did not occur in either group. The operative time to complete the anastomosis for magnamosis (4.12 ± 1.04 min) was significantly less than that needed for manual suture (24.47 ± 4.89 min, P < 0.01). The portal vein pressure in the magnamosis group was more stable than that in the manual suture group. The blood ammonia level at the end of the 24-week post-implantation observation period was significantly lower in the magnamosis group than in the manual suture group. Gross and microscopic histological examinations revealed that better smoothness and continuity of the vascular intima had been achieved via magnamosis than with manual suture. CONCLUSION: Magnamosis was superior to manual suture for the creation of a portacaval shunt in this canine model of portal hypertension.

Magnetic Anastomosis for Biliojejunostomy: First Prospective Clinical Trial.

BACKGROUND: Magnetic compression anastomosis (magnamosis, MCA) has been verified safe and effective by us and others in animal bilioenteric anastomosis (BEA). The objective of the present study was to introduce clinical application of magnetic compression bilioenteric anastomosis (MC-BEA) with a unique device in series of patients. METHODS: Patients with obstructive jaundice with an indication of BEA were prospectively enrolled from 2012 to 2015. After dissection of bile ducts, the mother ring and drainage tube were placed in the proximal bile duct and the purse-string suture was tightened over the drainage tube. The drainage tube was introduced into the jejunal lumen at the anastomotic site and used to guide the daughter ring to assemble with the mother ring. All the patients were routinely followed up for magnets discharge or any complications associated. RESULTS: Forty-one patients were included. Thirty-four (82.9%) patients had a malignant primary disease, while seven (17.1%) had benign disease. The median time for MC-BEA was 10.5 min (interquartile range [IQR] 8.3-13.0 min). No perioperative morbidity or mortality associated with MC-BEA was observed. The median time for a patent bilioenteric anastomosis formation was 19.0 days (IQR 14.5-23.0 days), and the magnets were discharged with a median postoperative duration of 35.0 days (IQR 28.0-43.0 days). With a median follow-up of 547.5 days (range 223-1042 days), no patients had biliary fistula, while two (4.9%) developed anastomotic stricture at 4 months and 14 months after surgery, and underwent reoperation for reconstruction of BEA. CONCLUSIONS: MCA is a safe, effective, and time-saving modality for biliojejunostomy.

An application research on a novel internal grasper platform and magnetic anchoring guide system (MAGS) in laparoscopic surgery.

BACKGROUND: Laparoendoscopic single-site surgery and natural orifice transluminal endoscopic surgery attempt to reduce transabdominal port sites. These require all instruments to pass through a single access point, leading to instruments collide or work at unfamiliar angles. Thus, we designed an internal grasper under magnetic anchoring guide system (MAGS) platform and investigated its utility and operability. METHODS: We measured the configuration for magnetic force decay over distance using a standardized, ex vivo laboratory testing apparatus. An electronic balance was used to measure the force of the gallbladder pull in ten patients with gallbladder stones. One pig (11 mm abdominal wall thickness) underwent a compressed trial of MAGS platform. The device was left in place for 20 min before tissue sections were harvested, and histologic assessment was performed. The utility and operability were investigated in four pigs (38-280 kg weight). RESULTS: The magnetic attraction force decayed exponentially over distance; the force of pulling gallbladder was 7.46 ± 0.54 N. This pairing of components allowed for coupling to a theoretical distance of 10 mm. No gross tissue damage was observed. H-E stain showed no necrosis in all specimens. One failed due to wall thickness of 45 mm. Others showed the critical view, triangulation of instruments was obtained, and instrument collision or "sword fighting" was reduced. CONCLUSIONS: The MAGS platform overcomes limitations such as collisions and lack of triangulation, reduces transabdominal port sites, and is easy to operate. However, our internal grasper requires the abdominal wall thickness below 10 mm.

Fast magnetic reconstruction of the portal vein with allogeneic blood vessels in canines.

BACKGROUND: The resection and reconstruction of large vessels, including the portal vein, are frequently needed in tumor resection. Warm ischemia before reconstruction might have deleterious effects on the function of some vital organs and therefore, how to reconstruct the vessels quickly after resection is extremely important. The present study was to introduce a new type of magnetic compression anastomosis (MCA) device to establish a quick non-suture anastomosis of the portal vein after resection in canines. METHODS: The new MCA device consists of a pair of titanium alloy and neodymium-ferrum-boron magnet (Ti-NdFeB) composite rings. The NdFeB magnetic ring as a core of the device was hermetically sealed inside the biomedical titanium alloy case. Twelve canines were divided into two groups: a MCA group in which the end-to-end anastomoses was made with a new device after resection in the portal vein and a traditional manual suture (TMS) group consisted of 6 canines. The anastomosis time, anastomotic patency and quality were investigated at week 24 postoperatively. RESULTS: The portal vein was reconstructed successfully in all of the animals and they all survived. The duration of portal vein anastomosis was significantly shorter in the MCA group than in the TMS group (8.16+/-1.25 vs 36.24+/-2.17 min, P<0.05). Portography and ultrasound showed that the blood flow was normal without angiostenosis or thrombosis in all of the canines. Hematoxylin-eosin staining and electron microscope scanning showed in contrast to the TMS group, MCA anastomotic intimal was much smoother with more regularly arranged endothelial cells at week 24 postoperatively. CONCLUSIONS: The Ti-NdFeB composite MCA device was applicable in reconstruction of large vessels after resection. This device was easy to use and the anastomosis was functionally better than the traditional sutured anastomosis.

Healing of stoma after magnetic biliary-enteric anastomosis in canine peritonitis models.

OBJECTIVE: To assese the healing of stoma after magnetic anastomosis for the reconstruction of biliary-enteric continuity under severe inflammation. METHODS: Acute bile duct injury was constructed as a bile peritonitis model in mongrel dogs (n=32). Magnetic anastomosis (group A, n=16) and traditional suture anastomosis (group B, n=16) were performed to reconstruct the biliary-enteric continuity in one stage. Half of the dogs in each group were euthanized on the 30th postoperative day, and the other half on the 90th postoperative day to harvest the stoma region. The healing conditions of the stoma after the 2 anastomotic approaches were observed with naked eyes, under light microscope and scanning electron microscope. RESULTS: The stoma leakage rate (50% versus 0% on the 30th postoperative day, 37.5% versus 12.5% on the 90th postoperative day, both P<0.05) and stenosis degree (13.9%±0.3% versus 7.1%±0.3% on the 30th postoperative day, 17.2%±0.4% versus 9.4%±0.4% on the 90th postoperative day, both P<0.01) were significantly higher in group B than in group A. Compared with traditional manual anastomoses, the histological analysis under light and electron microscope showed a more continuous stoma with more regular epithelium proliferation and collagen arrangement, less inflammation in group A. CONCLUSIONS: Magnetic anastomosis stent ensures better healing of the stoma even under the circumstance of severe inflammation.

[The development of the system of blood flow block by using magnetic compression abdominal large vascular].

A new system of blood flow block for control of bleeding in abdominal operation is composed of an abdominal magnetic blocking unit, an abdominal external electromagnet unit and other non-magnetic operation instrument. The abdominal external electromagnetic unit is placed in advance in the operation bed. The abdominal magnetic blocking unit can be placed directly on the ventral of the large vessels when need to blocking the abdominal large vessels during the operation. According to the non-contact suction characteristics of magnetic materials, the two magnetic units will attract each other and compression the vessels. Using this system for vascular occlusion does not need clear exposure and without separating vessel. There is the advantage of rapid, accurate and reliable for the system.

[Systematic review of gastrointestinal injury caused by magnetic foreign body ingestions in children and adolescence].

OBJECTIVE: To study the diagnosis and treatment of gastrointestinal injury caused by magnetic foreign body ingestions in children. METHODS: A literature search was performed to identify all the studies related to gastrointestinal tract injury caused by ingesting magnetic foreign body using databases including Google, Medline, ISI Web of Knowledge, Ovid, Wanfang data, VIP, CNKI, degree dissertation, meeting abstracts, and request for document delivery. Language was limited to English, Chinese, Japanese, and Korean. Parameters studies were age at diagnosis, gender, country, regional distribution, number of magnetic foreign bodies, source of magnetic foreign bodies, clinical features, diagnosis, and method for foreign body removal. RESULTS: A total of 98 cases of magnet ingestion were identified from 17 countries and regions. There were 94 patients under the age of 18, with most children younger than 5 years old(62.2%,61/98). The age at peak incidence was 3 years old (16.3%, 16/98). Magnetic foreign bodies ingested included toys(74.5%), medical apparatus(8.2%), accessories(4.1%), and others(6.2%). The number of bodies ranged from 2 to 100. Eleven (11.2%) patients were complicated with allotriophagia or autism. Delay diagnosis and treatment existed in all the patients to varying extents, of whom one died from severe infection. Exploratory laparotomy showed a wide range of bowel damage from the esophagus to the colon, including perforation and intestinal fistula. Intestinal damage was the most common injury (51.0%), followed by intestine-colon fistula (15.3%). All the patients required bowel resection with anastomosis or fistula repair except for 2 children who were managed by endoscopic removal of the foreign bodies. CONCLUSION: Ingesting more than one magnet will lead to severe gastrointestinal injury. Early diagnosis and surgical intervention are important. More precautious measures should be taken for children aged younger than 5 years old.