Machine perfusion preservation with hemoglobin based oxygen vesicles alleviate ultrastructural damages in porcine liver donated after cardiac death.

Midthermic machine perfusion (MMP) of post-circulatory arrest donor liver grafts has the advantage of preserving the functional ultrastructure of hepatocytes in donor grafts. It was reported that oxygenation during MMP reduces portal venous resistance and increases bile production. The MMP with hemoglobin-based oxygen vesicles (HbV) keeps the lower aspartate aminotransferase level (an indicator of liver injury) and maintains the functional ultrastructure of mitochondria in the hepatocytes. To evaluated differences of ultrastructural damages in donor livers between the MMP with and without HbV, porcine liver grafts after 60 min of warm ischemia were perfused at 22°C for 4 h with or without HbV, and a part of liver grafts were analyzed by transmission electron microscopy (TEM) and osmium-maceration scanning electron microscopy (OM-SEM). The remaining grafts were perfused with autologous blood at 38°C for 2 h in an isolated liver reperfusion model (IRM) that mimics the inside of the body after transplantation, and then analyzed by TEM and OM-SEM. Hepatocytes after MMP had small round mitochondria with rod-shaped cristae and reticulovesicular rough endoplasmic reticulum (rER) in both HbV(+) and HbV(-) livers. After IRM of HbV(+) livers, the well-developed lamellar rER was often found in hepatocytes. Liver sinusoidal endothelial cells (LSECs) after MMP contained some large vacuolar structures containing amorphous garbage in the cytoplasm, and their size along with appearance frequency were smaller and lower, respectively, in HbV(+) livers than HbV(-). Oxygenation during the MMP by using HbV suppressed the ultrastructural damages in donor livers, in particular for the LSECs. RESEARCH HIGHLIGHTS: Liver sinusoidal endothelial cells after midthermic machine perfusion had large vacuolar organelles with amorphous garbage. Oxygenation during the perfusion made them less and smaller, ultrastructurally supporting its utility.

Beneficial Effects of Combined Use of Extracorporeal Membrane Oxygenation and Hypothermic Machine Perfusion in Porcine Donors after Cardiac Death for Liver Transplantation.

Grafts from donors after cardiac death (DCD) have greatly contributed to expanding the donor organ pool. This study aimed to determine the benefits of subnormothermic extracorporeal membrane oxygenation (ECMO) and hypothermic machine perfusion (HMP) in a porcine model of DCD liver. Female domestic crossbred Large Yorkshire and Landrace pigs weighing approximately 20 kg were used. The abdominal aorta and inferior vena cava were cannulated and connected to an ECMO circuit for in situ perfusion of the abdominal organs at 22 °C for 60 min, 45 min after cardiac death. The pigs were divided into the cold storage (CS) group (n = 3), where liver grafts were preserved at 4 °C, and the HMP group (n = 3), where liver grafts were preserved by HMP at 8-10 °C. After 4 h of preservation, liver function was evaluated using an isolated liver reperfusion model for 2 h. Although the difference was insignificant, the liver effluent enzyme levels in the HMP group were lower than those in the CS group. Furthermore, morphological findings showed fewer injured hepatocytes in the HMP group than in the CS group. The combined use of in situ subnormothermic ECMO and HMP was beneficial for the functional improvement of DCD liver grafts.

Preservation Efficacy of a Quercetin and Sucrose Solution for Warm Ischemically Damaged Porcine Liver Grafts.

BACKGROUND: The University of Wisconsin (UW) solution is the gold standard for preserving the liver, kidneys, and pancreas. For renal preservation, the addition of the flavonoid, quercetin (QE), to the preservation solution reduces damage to renal tubular cells, and the addition of sucrose (Suc) is also beneficial for preservation. The aim of this study was to investigate the protective effects of QE and Suc on porcine livers in terms of warm and cold injury and to evaluate whether their use improves ischemia-reperfusion (I/R) injury after simple cold storage (CS). METHODS: We tested porcine livers procured after 30 minutes of warm ischemia followed by preservation for 6 hours under the following 2 conditions: group 1, preserved with the CS/UW solution (n = 4); group 2, preserved with the CS/UW solution containing Que 33.1 µM and Suc 0.1 M (n = 6). All livers were evaluated using an ex vivo isolated liver reperfusion model with saline-diluted autologous blood. RESULTS: Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels in group 2 were significantly lower at 30 minutes of reperfusion than in group 1. Furthermore, histologic evaluation by hematoxylin and eosin staining showed significantly fewer morphologic changes in group 2 than in group 1, as indicated by the total Suzuki score. Group 2 also had significantly better scores for sinusoidal congestion and hepatocyte cytoplasmic vacuolization. CONCLUSION: Adding Que and Suc to the UW solution can effectively prevent cold injury in livers donated after circulatory death.

Combined Use of Subnormothermic Extracorporeal Support and Hypothermic Oxygenated Machine Perfusion for Liver Graft After Cardiac Death in Pigs.

BACKGROUND: The use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. This study aims to determine the benefits of extracorporeal membrane oxygenation (ECMO) and hypothermic oxygenated machine perfusion (HOPE) in a large animal model of DCD liver. METHODS: After cardiac arrest, the abdominal aorta and the inferior vena cava were cannulated and connected to an ECMO circuit. Porcine livers were perfused in situ with ECMO at 22°C for 60 minutes after 45 minutes of cardiac death. Then, the livers were perfused for 4 hours by cold storage (CS) or HOPE. In group 1, non-in situ ECMO and grafts were preserved by HOPE. In group 2, in situ ECMO and grafts were preserved by HOPE. In group 3, in situ ECMO and grafts were preserved by CS. After preservation, all grafts were evaluated using an isolated reperfusion model (IRM) with autologous blood for 2 hours. RESULTS: During HOPE, aspartate aminotransferase (AST) levels and hepatic arterial pressure in group 2 tended to be lower than in group 1. Hematoxylin-eosin staining findings after HOPE showed more massive sinusoidal congestion and hepatocyte cytoplasmic vacuolization in group 1 than in group 2. The AST and LDH levels in group 2 at the start-up of IRM tended to be lower than in group 1. CONCLUSIONS: The combined use of in situ subnormothermic ECMO and HOPE is essential for the functional recovery of DCD liver grafts.

First Multicenter Clinical Trial on Machine Perfusion Preservation for Marginal Donor Kidney Transplantation in Japan.

BACKGROUND: Machine perfusion has not been widely used because of its low demand in Japan; however, we believe its advantages may increase the number of organ transplants. METHODS: Here, we report the first clinical trial of machine perfusion for kidney transplantation in Japan. We used the CMP-X08 perfusion device (Chuo-Seiko Co, Ltd, Asahikawa, Hokkaido, Japan) to preserve the donated organs. The flow rate, perfusion pressure, renal resistance, and temperature were monitored during continuous hypothermic perfusion. RESULTS: From August 2020 to the present, 13 cases of perfusion-preserved kidney transplantation have been performed. Of these, ten and 3 cases were performed using organs donated after brain death (DBD) and cardiac death (DCD), respectively. The average age of the recipients was 55.9 ± 7.3 (45-66) years. The average dialysis period was 14.8 ± 8.4 (0-26) years. The donor's final creatinine level before organ retrieval was 1.58 ± 1.0 (0.46-3.07) mg/dL. The warm ischemic times of the 3 DCD donors were 3, 12, and 18 minutes. The average total ischemic time was 12.0 ± 3.7 (7.17-19.88) hours. The average MP time was 140 (60-240) minutes. A total of 7 cases had delayed graft function. The best creatinine level during hospitalization was 1.17 ± 0.43 (0.71-1.85) mg/dL. There were no primary non-functional cases, and perfusion preservation was safely performed in all cases. CONCLUSIONS: Therefore, we present this report as the first clinical trial on machine perfusion for kidney transplantation from marginal donors with DBD and DCD in Japan.

Applicability of the histidine-tryptophan-ketoglutarate solution as a machine perfusion solution for marginal liver grafts.

BACKGROUND AND AIM: There are very few reports comparing the use of the University of Wisconsin solution and histidine-tryptophan-ketoglutarate solution as machine perfusion solutions for marginal liver grafts. We aimed to clarify whether the use of the histidine-tryptophan-ketoglutarate solution in hypothermic machine perfusion improves the split-liver graft function in a large animal model. METHODS: Porcine split-liver grafts were created by 75% liver resection. Hypothermic machine perfusion experimental groups were divided as follows: Group 1, perfusate, University of Wisconsin gluconate solution (UW group; n = 5), and Group 2, perfusate, histidine-tryptophan-ketoglutarate solution (HTK group; n = 4). After 4 h of preservation, the liver function was evaluated using an isolated liver reperfusion model for 2 h. RESULTS: In the HTK group, the portal vein and hepatic artery resistance during hypothermic machine perfusion and the portal vein resistance during isolated liver reperfusion were lower than those in the UW group. In addition, the total Suzuki score for hepatic ischemia-reperfusion injury in the HTK group was significantly better than that in the UW group. The number of anti-ETS-related genes staining-positive sinusoid epithelial cell nuclei in the HTK group was higher than that in the UW group (not significant). CONCLUSIONS: The histidine-tryptophan-ketoglutarate solution can be perfused with lower vascular resistance than the University of Wisconsin solution, reducing shear stress and preventing sinusoid epithelial cell injury in marginal grafts used as split-liver grafts.

The experience of 100 cases of 8K/two-dimensional laparoscopic colorectal surgery - The evaluation of 8K/two-dimensional laparoscopy and how to use it.

Background: The resolution of 8K ultra-high-definition imaging technology (7680 × 4320 pixels) is 16-fold higher than the current high-definition technology (1920 × 1080 pixels). 8K/two-dimensional (2D) laparoscopy was clinically available in 2014, but few reports concerning its application have been published. The aim of this study was to evaluate the appropriate methods of usage and problems learned from clinical use of 8K/2D laparoscopy. Subjects and Methods: The patients were 100 colorectal surgery patients who underwent 8K/2D laparoscopy at Asahikawa Medical University Hospital between November 2018 and March 2021. We evaluated the effectiveness, operating conditions, methods and issues of 8K/2D laparoscopy. Results: The median age was 68.5 years. The primary disease was malignancy of the left side of the colon and rectum in 92 patients. The right-sided colectomy was performed in five cases, total proctocolectomy of ulcerative colitis was performed in 3 cases. The proper application of 8K/2D laparoscopy can be achieved by adhering to certain tips, such as darkening the operation room and keeping an appropriate distance from the monitor. Regarding intraoperative complications caused by the 8K/2D laparoscope, skin burns due to heat from the tip of the laparoscope were observed in one patient. There were no cases of complications due to the 8K/2D laparoscopy. Conclusion: 8K/2D laparoscopy can be used safely in colorectal surgery. There are still some tips for proper use, such as keeping an appropriate distance to the monitor and darkening the room. However, 8K/2D laparoscopy can provide delicate images and can be used without any operational problems.

Lymphoepithelioma-like cholangiocarcinoma not associated with Epstein-Barr virus or hepatitis virus: case report and literature review of 100 reported cases.

Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a type of lymphoepithelioma-like carcinoma (LELC) and a rare variant of primary liver tumor. Although it is uncommon and only 100 cases have been reported thus far, the number of reports has increased in recent years. LEL-CC reportedly occurs more frequently in Asian women; Epstein-Barr virus (EBV) and hepatitis viruses are both strongly associated with tumor development. Here, we describe a 76-year-old woman who exhibited LEL-CC not associated with EBV or hepatitis virus. She was referred to our department with a 3.0-cm × 2.8-cm tumor in the left lobe of the liver. Based on computed tomography and magnetic resonance imaging findings, the tumor was preoperatively diagnosed as hepatocellular carcinoma. Thus, we performed extended left hepatectomy with caudal lobectomy. Histopathological examinations revealed columnar tumor cells with atypical nuclei that proliferated in a cord-like or glandular tubular pattern with dense lymphocytic infiltration. Immunohistochemical analysis showed negative HepPar-1 and arginase findings, indicating non-hepatocyte origin; however, the biliary-type cytokeratins CK7 and CK19 were detected. Based on these findings, the tumor was identified as LEL-CC. EBV-encoded RNA in situ hybridization findings were negative; the patient's clinical characteristics were not suggestive of hepatitis virus infection. In conclusion, we suggest that clinicians consider LEL-CC as a differential diagnosis for liver tumors in Asian women, including patients without EBV or hepatitis virus.

Ultrastructural changes in porcine liver sinusoidal endothelial cells of machine perfused liver donated after cardiac death.

BACKGROUND: The machine perfusion (MP) preservation including hypothermic MP (HMP) and midthermic MP (MMP) has been considered as a promising strategy to preserve the functions of liver donated after cardiac death. The importance of understanding liver sinusoidal endothelial cells (LSEC) damage in regulating liver injury during MP has been emphasized. However, the ultrastructural changes in the LSEC and sinusoids around them after MP are unclear. AIM: To investigate the ultrastructural changes in the LSEC and sinusoids around them after MP. METHODS: Porcine liver grafts undergo a warm ischemia time of 60 minutes perfused for 4 h with modified University of Wisconsin gluconate solution. Group A grafts were preserved with HMP at 8 °C constantly for 4 h. Group B grafts were preserved with a rewarming solution at 22 °C by MMP for 4 h. Then the ultrastructural changes in the LSEC and sinusoids in Group A and B were comparatively analyzed by using osmium-maceration scanning electron microscopy with complementary transmission electron microscopy methods. RESULTS: An analysis of the LSEC after warm ischemia revealed that mitochondria with condensed-shaped cristae, abnormal vesicles, reduction of ribosomes and the endoplasmic reticulum (ER) surround the mitochondria appeared. The MP subsequent after warm ischemia alleviate the abnormal vesicles and reduction of ribosomes in LSEC, which indicated the reduction of the ER damage. However, MMP could restore the tubular mitochondrial cristae, while after HMP the condensed and narrow mitochondrial cristae remained. In addition, the volume of the sinusoidal space in the liver grafts after MMP were restored, which indicated a lower risk of pressure injury than HMP. CONCLUSION: MMP alleviates the ER damage of LSEC by warm ischemia, additionally restore the metabolism of LSEC via the normalization of mitochondria and prevent the share stress damage of liver grafts.

Oxygenated Hypothermic Machine Perfusion of Kidney Transplantation from Donors After Cardiac Death Due to Long-Term Low Blood Pressure and Hypoxia: The First Case Report of a Clinical Trial Using a New Japanese Perfusion System.

BACKGROUND: Machine perfusion of marginal kidney grafts obtained from donors after cardiac death (DCD) has become a standard therapy worldwide. However, the use of grafts from DCD due to long-term low blood pressure is associated with a high incidence of primary graft nonfunction. Furthermore, the importance of oxygenation in machine perfusion remains unclear. We report the first case of a clinical trial of a kidney transplant obtained from a DCD using a Japanese oxygenated hypothermic perfusion system (CMX-08W, Chuo Seiko Co Ltd, Asahikawa, Japan). PATIENTS AND METHODS: The donor was a 61-year-old man with amyotrophic lateral sclerosis. His SpO2 decreased to 80% to 90%, his blood pressure remained consistently low for 4 hours and 30 minutes, and he suffered a cardiac arrest. Subsequently, we carried him to the operating room. The warm ischemic time was 12 minutes, and the cold ischemic time was 418 minutes. The recipient was a 58-year-old man who had been undergoing hemodialysis for 26 years. He was diagnosed with nephrosclerosis and multiple renal cysts. Oxygenated hypothermic machine perfusion was used on the kidney transplant obtained from the DCD. RESULTS: The recipient gradually recovered and was withdrawn from hemodialysis therapy 14 days post transplantation. His renal function improved, and he was discharged on postoperative day 36. Currently, his renal function remains good (phosphocreatine, 1.7). CONCLUSIONS: Oxygenated machine perfusion is used to preserve organs and determine if an organ is suitable for transplantation. This may provide the possibility of perfusion preservation and expand the criteria for cardiac arrest-associated renal transplantation.

Beneficial effects of end-ischemic oxygenated machine perfusion preservation for split-liver transplantation in recovering graft function and reducing ischemia-reperfusion injury.

This study examined the efficacy of end-ischemic hypothermic oxygenated machine perfusion preservation (HOPE) using an originally developed machine perfusion system for split-liver transplantation. Porcine split-liver grafts were created via 75% liver resection after 10 min of warm ischemia. In Group 1, grafts were preserved by simple cold storage (CS) for 8 h (CS group; n = 4). In Group 2, grafts were preserved by simple CS for 6 h and end-ischemic HOPE for 2 h (HOPE group; n = 5). All grafts were evaluated using an isolated ex vivo reperfusion model with autologous blood for 2 h. Biochemical markers (aspartate aminotransferase and lactate dehydrogenase levels) were significantly better immediately after reperfusion in the HOPE group than in the CS group. Furthermore, the HOPE group had a better histological score. The levels of inflammatory cytokines (tumor necrosis factor-α, interferon-γ, interleukin-1ß, and interleukin-10) were significantly lower after reperfusion in the HOPE group. Therefore, we concluded that end-ischemic HOPE for split-liver transplantation can aid in recovering the graft function and reducing ischemia-reperfusion injury. HOPE, using our originally developed machine perfusion system, is safe and can improve graft function while attenuating liver injury due to preservation.

Severe liver injury with traumatic cardiac arrest successfully treated by damage control surgery and transcatheter arterial embolization in the hybrid operating room: a case report.

BACKGROUND: The damage control approach is known to reduce the mortality rate in severely injured patients and has now become a common practice. Transcatheter arterial embolization (TAE) has been shown to be useful with combining with damage control laparotomy in identifying and controlling active arterial hemorrhage. Hybrid operating room (OR) allows both damaged control surgery and TAE in the same location in minimal time. We report a case of a patient with three cardiac arrests who was saved by early intervention using damage control surgery (DCS) with interventional radiology (IVR) in the hybrid OR. CASE PRESENTATION: A 46-year-old woman was injured in a collision with a tree while snowboarding. She was eventually transported to hybrid operating room in our hospital with the diagnosis of significant liver laceration and hemorrhagic shock. Damage control surgery was performed with perihepatic packing (PHP) and TAE was conducted to stop active bleeding from right hepatic artery. She experienced 3 times of cardiopulmonary arrest, which was successfully resuscitated on each occasion. Although she had total of 3 times of laparotomy but tolerated well. She was discharged on day 82 of hospitalization and showed no neurological sequelae. CONCLUSION: Saving the life of a patient with severe trauma requires a multidisciplinary approach with cooperation and early information sharing among trauma team members. Sharing treatment strategy with the trauma team and early intervention using DCS with IVR in the hybrid operating room could save the patient's life.

A comparison of laparoscopic procedures performed by novice medical students using 8K ultra-high-definition/two-dimensional and 2K high-definition/three-dimensional monitors.

PURPOSE: 8K Ultra-high-definition (UHD) imaging has been developed in accordance with the progression of imaging technologies. We evaluated laparoscopic procedures performed by novice medical students using 2K/two-dimensional (2D), 2K/three-dimensional (3D) and 8K/2D monitors, with a particular focus on depth perception. METHODS: Nine medical students were enrolled. They performed two tasks using 2K/2D, 2K/3D and 8K/2D monitors. In Task 1, they were asked to grasp three metal rods with forceps using each hand. In Task 2, they were asked to grasp a metal rod with forceps held in the right hand, pass the metal rod through a metal ring and transfer it to their left hand. RESULTS: In Task 1, when performed with the dominant hand, the procedures performed using 2K/3D took a significantly shorter time than those performed using 8K/2D (P = 0.04). However, there was no significant difference among the three groups in the time required for procedures performed by the non-dominant hand. In Task 2, the procedure time with 2K/2D was significantly longer than that with 2K/3D or 8K/2D (P = 0.02). CONCLUSION: 2K/3D showed superior utility to 8K/2D for performing forceps procedures using the dominant hand. However, when the movement of both hands was coordinated ("bi-hand coordination"), the laparoscopic procedures were performed almost as deftly with 8K/2D and 2K/3D.

A Novel Preservation Solution Containing Quercetin and Sucrose for Porcine Kidney Transplantation.

In organ transplantation, the University of Wisconsin (UW) solution has been the gold standard for organ preservation. Quercetin (Que) has numerous antioxidant and anti-inflammatory activities, and sucrose (Suc) may be effective for cold storage (CS). This study aimed to investigate the in vitro protective effect of Que and Suc on cold injury to the kidney and to determine whether Que + Suc could improve ischemia-reperfusion injury during CS and hypothermic oxygenated perfusion (HOPE) in autologous transplantation models. METHODS: BHK-21 cells were stored at 4°C for 3 days in UW solution for CS/machine perfusion (CS/MP-UW) with Que (33.1 µM, 3.3 µM, 0.33 µM) and Suc (0.1 M). In a porcine model of renal autologous transplantation, left kidney grafts were preserved under 3 conditions: group 1, CS preservation for 24 hours; group 2, CS preservation for 22 hours and HOPE with CS/MP-UW solution for 2 hours; and group 3, identical preservation as group 2, with Que and Suc added to the solution. Animals were euthanized on day 7 after autologous transplantation. RESULTS: After 3 days of CS preservation, the CS/MP-UW solution with Que (33.1 µM, 3.3 µM) and Suc showed significant cell protection against cold injury. In the porcine model of renal autologous transplantation, the last blood Cre level and the blood lipid hydroperoxide on posttransplantation day 2 were significantly different between group 1 and group 3. Moreover, the total endothelial, glomerular, tubular, interstitial (EGTI) histology score in the kidney tissue was also significantly different. Regarding the change in renal resistance in HOPE, the decrease observed in group 3 was significantly larger than that in group 2. CONCLUSIONS: Our results suggest that the addition of Que and Suc to a UW solution can improve kidney preservation and could potentially enhance the outcome of kidney transplantation.

The ultrastructural characteristics of bile canaliculus in porcine liver donated after cardiac death and machine perfusion preservation.

The effects of each type of machine perfusion preservation (MP) of liver grafts donated after cardiac death on the bile canaliculi of hepatocytes remain unclear. We analyzed the intracellular three-dimensional ultrastructure of the bile canaliculi and hepatocyte endomembrane systems in porcine liver grafts after warm ischemia followed by successive MP with modified University of Wisconsin gluconate solution. Transmission and osmium-maceration scanning electron microscopy revealed that lumen volume of the bile canaliculi decreased after warm ischemia. In liver grafts preserved by hypothermic MP condition, bile canaliculi tended to recover in terms of lumen volume, while their microvilli regressed. In contrast, midthermic MP condition preserved the functional form of the microvilli of the bile canaliculi. Machine perfusion preservation potentially restored the bile canaliculus lumen and alleviated the cessation of cellular endocrine processes due to warm ischemia. In addition, midthermic MP condition prevented the retraction of the microvilli of bile canaliculi, suggesting further mitigation of the damage of the bile canaliculi.

Applicability of Hypothermic Oxygenate Machine Perfusion Preservation for Split-Liver Transplantation in a Porcine Model: An Experimental Study.

BACKGROUND Split-liver transplantation can be useful in situations of limited donor resources. However, novel preservation methods are required to help the recipient recover from severe ischemic reperfusion injury incurred due to receiving a relatively small liver graft. MATERIAL AND METHODS Our experiment was performed using porcine livers without warm ischemia time, assuming a brain-dead organ. We made porcine split-liver grafts by 75% liver resection at the back table and divided the specimens into 4 groups. Group 1 was preserved with simple cold storage after splitting (CS; n=3), Group 2 was preserved with hypothermic perfusion preservation (HMP) after splitting (SBP; n=3), Group 3 was preserved with HMP after splitting under perfusion preservation (SDP; n=4), and Group 4 had the whole liver perfused as control grafts (Whole Liver; n=3). To assess potential methods of preservation and their effects, all grafts were evaluated by an ex vivo isolated liver reperfusion model using diluted autologous blood. RESULTS Portal vein pressure resistances during reperfusion were low in Group3 (SDP). Hepatic artery pressure resistances during reperfusion were markedly higher in Group 1(CS) than in the other groups. The levels of AST and LDH were high and increased at 2 h after reperfusion in Group 1 (CS). The histological findings show that the liver cell structure was irregular in Group 1 (CS) but remained regular in Groups 2 (SBP) and 3 (SDP). Histological Suzuki scores were also significantly better in Groups 2 (SBP) and 3 (SDP) compared with Group 1 (CS). CONCLUSIONS Splitting the liver under machine perfusion preservation may help restore the function and reduce ischemia-reperfusion injury.

Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment: A case report.

BACKGROUND: Lenvatinib has been shown to be noninferior to sorafenib regarding prognosis and recurrence rate in patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic chemotherapy. In patients treated with lenvatinib, 40% of cases achieved sufficient tumor reduction to make potential surgery possible. However, the outcomes of such surgery are unknown. We report a successful case of hepatic resection for recurrent HCC after lenvatinib treatment. CASE SUMMARY: A 69-year-old man underwent right anterior sectionectomy for HCC in segment 8 of the liver. Ten months later, he was found to have an intrahepatic HCC recurrence that grew rapidly to 10 cm in diameter with sternal bone metastases. After confirming partial response to lenvatinib administration for 2 mo, a second hepatectomy was performed. Pathological examination showed that 80% of the tumor was necrotic. The patient did not develop any adverse effects under lenvatinib treatment. He was discharged at 25 d after surgery. Radiation therapy for bone metastases continued to be given under lenvatinib, and the patient has remained alive for 1 year after the second hepatectomy. CONCLUSION: The prognosis of patients with recurrent HCC may be improved by liver resection combined with prior lenvatinib therapy.

Impact of Machine Perfusion on Sinusoid Microcirculation of Liver Graft Donated After Cardiac Death.

BACKGROUND: The present study examined the impact of oxygenated machine perfusion on preservation of liver grafts donated after cardiac death by measuring sinusoidal endothelial injury and microcirculatory disturbances. MATERIALS AND METHODS: Fifteen porcine livers were retrieved 60 min after warm ischemia and allocated into three groups as follows: (1) CS group: static cold storage, (2) HMP group: oxygenated hypothermic perfusion preservation, (3) SNMP group: oxygenated subnormothermic perfusion preservation. The liver grafts donated after cardiac death were preserved for 4 h in different treatment conditions mentioned previously, then subject to ex vivo reperfusion for 2 h using diluted allogeneic blood. The hemodynamic parameters, liver function tests, tissue adenosine triphosphate (ATP) levels, and immunohistochemical findings were investigated. RESULTS: The number of sinusoidal epithelial cells and trabecular structures were maintained after 4 h of preservation in the CS, HMP, and SNMP group. Liver tissue ATP levels after 4 h of preservation in the HMP and SNMP groups were significantly higher compared with that in the CS group. The sinusoidal epithelial cells were significantly exfoliated to a more severe extent in the CS group than in the HMP and SNMP groups. Intrasinusoidal platelet aggregation occurred more frequently in the CS group than in the HMP and SNMP groups. CONCLUSIONS: The results indicated that oxygenated machine perfusion preservation was important to prevent the depletion of tissue ATP and maintain sinusoidal homeostasis regardless of the perfusate temperature. Our findings suggest oxygenated machine perfusion preservation as an effective alternative to static cold storage.

Initial perfusate purification during subnormothermic machine perfusion for porcine liver donated after cardiac death.

Improvement of machine perfusion (MP) technologies is required to enhance organ quality for donor after cardiac death (DCD) grafts. Installing a dialyzer or a filter into the perfusion circuit to maintain the perfusate condition has some advantages. However, the consequences of purification perfusate during subnormothermic machine perfusion (SNMP) remain unexplained. In this study, the effects of initial purification perfusate with simple method of replacing the first 0.5-L perfusate during SNMP were investigated to consider installation effect of the filter or the dialyzer. Porcine liver grafts, which have 60-min warm ischemia time, were procured to imitate the DCD graft condition. Purified SNMP (PSNMP) results were compared with simple cold storage and conventional SNMP. In PSNMP, initial perfusate of 0.5 L was removed to substitute for purification. After preservation process, the preserved grafts were reperfused with diluted autologous blood for 2 h under normothermic machine perfusion condition to evaluate the liver function using an isolated reperfusion model. The vascular pressures, enzyme release rates and the metabolic indexes during reperfusion were analyzed. The pressures in the hepatic artery after reperfusion 60 min were significantly lower in PSNMP group compared with cold storage (CS) and SNMP groups. In addition, lactate dehydrogenase and alkaline phosphatase were significantly lower after PSNMP than after the CS or SNMP. Also, the metabolic indexes of hyaluronic acid and lactate were significantly decreased by purifying the perfusate in MP preservation than in CS or SNMP. The effectiveness of initial purification perfusate during SNMP was investigated.

Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model.

The recent clinical application of perfusion technology for the machine preservation of donation after cardiac death (DCD) grafts has some advantages. Oxygenation has been proposed for the preservation of DCD liver grafts. The aim of this study is to clarify whether the use of HbV-containing preservation solution during the subnormothermic machine perfusion (SNMP) of the liver graft improves the graft function of DCD porcine livers in an ex vivo reperfusion model. Pig livers were excised after 60 minutes of warm ischemic time and were preserved under one of three preservation conditions for 4 hours. The preservation conditions were as follows: 4°C cold storage (CS group; N = 5), Hypothermic machine preservation (HMP) with UW gluconate solution (HMP group; N = 5), SNMP (21°C) with UW gluconate solution (SNMP group; N = 5), SNMP (21°C) with HbVs (Hb; 1.8 mg/dl) perfusate (SNMP+HbV group; N = 5). Autologous blood perfusion was performed for 2 hours in an isolated liver reperfusion model (IRM). The oxygen consumption of the SNMP and SNMP+HbV group was higher than the HMP groups (p < 0.05). During the reperfusion, the AST level in the SNMP+HbV group was lower than that in the CS, HMP and SNMP groups. The changes in pH after reperfusion was significantly lower in SNMP+HbV group than CS and HMP groups. The ultrastructural findings indicated that the mitochondria of the SNMP+HbV group was well maintained in comparison to the CS, HMP and SNMP groups. The SNMP+HbVs preservation solution protected against metabolic acidosis and preserved the liver function after reperfusion injury in the DCD liver.