Impact of thoracic shape on the surgical outcomes of laparoscopic-assisted living donor hepatectomy.

Background: Although laparoscopic-assisted donor hepatectomy (LADH) has become the definitive procedure for harvesting living donor livers, its surgical outcomes in association with donor body shape have not been elucidated. Methods: The impact of donor factors, including thoracic shape, on LADH outcomes was retrospectively investigated. Thoracic anthropometric data were examined in all LADHs with a left/right graft between 2013 and 2022. Results: The study included 210 LADHs, consisting of 106 left- and 104 right-lobe donors with similar blood loss and similar operation time. Males have greater thoracic depth and greater thoracic width compared with females, respectively. Thoracic depth was associated with graft weight (p < 0.001), blood loss (p < 0.001), and operation time (p < 0.001). On multivariate analyses, blood loss >500 mL and operation time >8 h were associated with graft weight in the left-lobe donors, and blood loss >500 mL was associated with thoracic depth in the right-lobe donors. Conclusion: The greater thoracic depth is associated with massive blood loss in right-lobe donors. Anthropometric parameters might be helpful for estimating LADH outcomes.

Dual Lumen Microcatheter in Percutaneous Biliary Drainage for Postoperative Bile Leakage: A Case Report.

Percutaneous biliary intervention is widely accepted as an effective and safe treatment for various types of bile duct diseases. We present the case of a 44-year-old woman who developed bile leakage after a living-donor liver transplantation for locally advanced cholangiocarcinoma. A percutaneous drainage tube was placed in the segment 8 bile duct via the blind end of the jejunum. However, the bile leakage was unchanged. Bile leakage from the right posterior hepatic duct was suspected. Using a dual lumen microcatheter, a percutaneous drainage tube was placed in the segment 7 bile duct via the blind end of the jejunum, which reduced the bile leakage. These results suggest that a dual lumen microcatheter is a valuable tool for navigating the biliary tree during difficult percutaneous biliary interventions.

Effects of Adding Congested Segment IV to the Left Lateral Graft on Short-term Outcomes in Pediatric Living-donor Liver-transplant Recipients.

Background: In some pediatric patients undergoing living-donor liver transplantation, segment IV without the middle hepatic vein can be added to a left lateral segment graft to obtain larger graft volume. Because no clear consensus on this technique exists, this study investigated the effects of congested areas on postoperative outcomes in pediatric patients with biliary atresia undergoing living-donor liver transplantation. Methods: We retrospectively reviewed data of recipients with biliary atresia aged ≤15 y who had undergone living-donor liver transplantation at Kyoto University Hospital between 2006 and 2021 and with graft-to-recipient weight ratios (GRWR) of ≤2%. Based on the percentage of congested area in the graft, patients were classified into the noncongestion (n = 40; ≤10%) and congestion (n = 13; >10%) groups. To compare the differences between groups with similar nooncongestive GRWRs and investigate the effect of adding congested areas, patients in the noncongestion group with GRWRs of ≤1.5% were categorized into the small noncongestion group (n = 24). Results: GRWRs and backgrounds were similar between the noncongestion and congestion groups; however, patients in the congestion group demonstrated significantly longer prothrombin times, higher ascites volumes, and longer hospitalization. Further, compared with the small noncongestion group, the congestion group had significantly greater GRWR and similar noncongestive GRWR; however, the congestion group had significantly longer prothrombin time recovery (P = 0.020, postoperative d 14), higher volume of ascites (P < 0.05, consistently), and longer hospitalization (P = 0.045), requiring significantly higher albumin and gamma-globulin transfusion volumes than the small noncongestion group (P = 0.027 and P = 0.0083, respectively). Reoperation for wound dehiscence was significantly more frequent in the congestion group (P = 0.048). Conclusions: In pediatric liver-transplant recipients, adding a congested segment IV to the left lateral segment to obtain larger graft volume may negatively impact short-term postoperative outcomes.

Impact of very early introduction of everolimus on liver regeneration after partial liver transplantation in rats.

BACKGROUND/PURPOSE: This experimental study in rats aimed to investigate the impact of very early introduction (within 3 h) of everolimus (EVR) + reduced-tacrolimus (TAC) after partial liver transplantation (LT) on liver regeneration, rejection, and survival. METHODS: Based on appropriate dose of EVR + reduced-TAC in 70% hepatectomy (Experiment 1), allogeneic 30% partial LT (Experiment 2) and whole LT (Experiment 3) were performed. RESULTS: After partial LT in EVR + reduced-TAC therapy, restoration of liver graft weight (to that of the whole liver) was delayed compared with standard dose TAC monotherapy (standard-TAC) on day 3 (59.3% vs. 72.9%; p < .001) and 14 (88.1% vs. 95.5%; p = .01). Survival was 75%, which was not as high as the value of 100% observed for standard-TAC, because neither infection nor rejection could be prevented. By contrast, survival after whole LT was 100% as neither infection nor rejection occurred. CONCLUSIONS: The very early introduction of EVR + reduced-TAC after partial LT delayed liver regeneration, and made it difficult to manage the dose required to suppress both infection and rejection. On the other hand, EVR + reduced-TAC could be introduced safely very early after whole LT.

Stepwise Approach for Acquisition of Microsurgical Skills through Rat Orthotopic Liver Transplantation Experiments.

Although rat liver transplantation (LT) is useful in training surgeons to perform microsurgery, mastering these surgical techniques remains difficult. Systematized training protocols that enable learning of the proper skills in a short period of time are needed. The present study describes an efficient five-step rat LT training protocol for surgeons designed to be mastered within 3 months through continuous training. The first step was to review all procedures by watching full videos of rat LT and to watch actual LT operations performed by a skilled surgeon, enabling recognition of the anatomy of rat abdominal organs. The second step was to perform ten donor operations, including ex vivo graft preparation, to learn the atraumatic and delicate techniques. The third step was to perform ten LTs, with the goal of achieving an anhepatic time <20 min and surviving until the next day. The fourth step was to perform ten additional LTs, with the goal of achieving 7 days of survival. The fifth step was to perform 5-10 more LTs, with the goal of achieving 7 days of survival in five consecutive LT operations. Systematizing the training was found to increase its efficiency. Furthermore, determining the specific number of operations in advance is useful to maintain motivation for training. Mastering efficient rat LT will not only enhance the success of preclinical research but will enable young surgeons to better perform vascular anastomoses under a microscope in humans.

Dissecting aneurysm of the proper hepatic artery after laparoscopic hepatectomy possibly related to the Pringle maneuver: A case report.

In hepatectomy, the Pringle maneuver is commonly used, but its association with iatrogenic injury is not yet well understood. This report presents a case of dissecting aneurysm of the proper hepatic artery (PHA) possibly associated with the Pringle maneuver during laparoscopic hepatectomy, that was successfully treated by transcatheter arterial embolization (TAE). The patient was a woman in her 70s, and repeat hepatectomy for liver metastasis of rectal neuroendocrine neoplasm was planned. She underwent hand-assisted laparoscopic hepatectomy with the Pringle maneuver. On postoperative day (POD) 7, enhanced computed tomography showed a dissecting aneurysm of the PHA. TAE of the PHA to prevent hemorrhage was performed on POD 9 with no complications. Even after TAE, intrahepatic arterial flow was provided by the peribiliary arteries. This case suggests the possibility that the Pringle maneuver can cause a dissecting aneurysm of the hepatic artery.

Micro- and macro-borderless surgery using a newly developed high-resolution (4K) three-dimensional video system.

OBJECTIVE: Microsurgery using conventional optical microscopes or surgical loupes features a limited field of view and imposes a serious strain on surgeons especially during long surgeries. Here we advocate the micro- and macro-borderless surgery (MMBS) using a novel high-resolution (4K) three-dimensional (3D) video system. This study aimed to confirm the applicability of this concept in several surgical procedures. METHODS: We evaluated the possible use and efficacy of MMBS in the following experiments in porcine subjects. Experiment 1 (non-inferiority test) consisted of dissection and anastomosis of carotid artery, portal vein, proper hepatic artery, and pancreatoduodenectomy with surgical loupe versus MMBS. Experiment 2 (feasibility test) consisted of intra-abdominal and intra-thoracic smaller arteries anastomosed by MMBS as a pre-clinical setting. Experiment 3 (challenge on new surgery) consisted of orthotopic liver transplantation of the graft from a donor after circulatory death maintained by machine perfusion. Circulation of the cardiac sheet with a vascular bed in experiment 2 and liver graft during preservation in experiment 3 was evaluated with indocyanine green fluorescence imaging equipped with this system. RESULTS: Every procedure was completed by MMBS. The operator and assistants could share the same field of view in heads-up status. The focal depth was deep enough not to be disturbed by pulsing blood vessels or respiratory movement. The tissue circulation could be evaluated using fluorescence imaging of this system. CONCLUSIONS: MMBS using the novel system is applicable to various surgeries and valuable for both fine surgical procedures and high-level surgical education.

Novel mouse model for cholestasis-induced liver fibrosis resolution by cholecystojejunostomy.

BACKGROUND AND AIM: Studies on the resolution of liver fibrosis are becoming more important in this era of etiologic eradication. In contrast to the extensive research on the recovery of liver fibrosis induced by hepatotoxic injuries, regression of cholestatic liver fibrosis has been insufficiently examined owing to the limited availability of animal models. METHODS: We examined our novel recanalization mice model of biliary obstruction, involving anastomosis between the gallbladder and jejunum (G-J anastomosis) by invagination. Transgenic mice expressing green fluorescent protein (GFP) under the collagen 1(α)1 promoter underwent G-J anastomosis 14 days after bile duct ligation (BDL) and were sacrificed 14 days later. RESULTS: Transaminase and total bilirubin levels decreased to almost normal values on day 14 after G-J anastomosis. G-J anastomosis resulted in dramatic reversal of liver fibrosis induced by BDL. Activated portal fibroblasts (PFs) double-positive for GFP and Thy-1 on immunofluorescence in the liver of BDL-injured mice became less noticeable following G-J anastomosis. Messenger RNA expression of markers for activated PFs in the liver was downregulated after anastomosis. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were induced by BDL. After anastomosis, expressions of MMP-3, 8 as well as hepatocyte growth factor were further upregulated, whereas those of TIMP-1 and TIMP-3 were markedly downregulated. CONCLUSIONS: Our established G-J anastomosis model is associated with fibrosis resolution and reduced PF activation through reopening of bile duct obstruction and will be valuable for studying the recovery process of cholestatic liver fibrosis.

Orthotopic Kidney Auto-Transplantation in a Porcine Model Using 24 Hours Organ Preservation And Continuous Telemetry.

In the present era of organ transplantation with critical organ shortage, various strategies are employed to expand the pool of available allografts for kidney transplantation (KT). Even though, the use of allografts from extended criteria donors (ECD) could partially ease the shortage of organ donors, ECD organs carry a potentially higher risk for inferior outcomes and postoperative complications. Dynamic organ preservation techniques, modulation of ischemia-reperfusion and preservation injury, and allograft therapies are in the spotlight of scientific interest in an effort to improve allograft utilization and patient outcomes in KT. Preclinical animal experiments are playing an essential role in translational research, especially in the medical device and drug development. The major advantage of the porcine orthotopic auto-transplantation model over ex vivo or small animal studies lies within the surgical-anatomical and physiological similarities to the clinical setting. This allows the investigation of new therapeutic methods and techniques and ensures a facilitated clinical translation of the findings. This protocol provides a comprehensive and problem-oriented description of the porcine orthotopic kidney auto-transplantation model, using a preservation time of 24 hours and telemetry monitoring. The combination of sophisticated surgical techniques with highly standardized and state-of-the-art methods of anesthesia, animal housing, perioperative follow up, and monitoring ensure the reproducibility and success of this model.

[A Case of Advanced Gastric Cancer Treated Effectively with Combination Chemotherapy of Paclitaxel plus Ramucirumab].

A 74-year-old man was referred to our hospital because of a gastric tumor. A Borrmann type 2 gastric tumor was found on upper gastrointestinal endoscopy, but tissue biopsy indicated only necrotic tissue and the preoperative diagnosis was difficult. Contrast CT and FDG-PET revealed lymphadenopathy at multiple sites accompanied by high accumulation of FDG in the perigastric lymph nodes, left upper collarbicular fossa, bilateral hilar ganglia, and longitudinal cauda. Because the tumor was strongly suspected to be gastric cancer or malignant lymphoma, distal gastrectomy was performed. The tumor was finally diagnosed as a poorly differentiated adenocarcinoma with multiple lymph node metastasis. S-1 plus cisplatin therapy was administered as first-line chemotherapy, and paclitaxel(PTX)plus ramucirumab(RAM)therapy was administered as secondline chemotherapy. PTX plus RAM therapy was effective, and the patient achieved complete remission(CR), as observed on imaging. However, because adverse events such as numbness in the periphery of the limbs were noted, PTX plus RAM therapy was discontinued per the patient's request. Currently, 13 months since the interruption of treatment, the CR has been maintained, as determined on imaging.

Auxiliary xenotransplantation as an in vivo bioreactor-Development of a transplantable liver graft from a tiny partial liver.

BACKGROUND: We established a completely novel method of auxiliary xenogeneic partial liver transplantation and examined whether liver grafts procured from Syrian hamsters regenerated in nude rats, which were used as in vivo bioreactors. METHODS: The hamsters and the rats were all males (n = 10). Partial liver grafts from hamsters were transplanted into nude rats in an auxiliary manner. We evaluated liver graft injury, rejection, and regeneration during 7 days after auxiliary xenogeneic partial liver transplantation. RESULTS: All rats survived until sacrifice on post-operative day (POD) 1, 3, and 7. HE-staining showed normal at POD1, mild periportal edema, and slight bile duct and venous endothelial inflammation at POD3, and moderate acute cellular rejection at POD7 without parenchymal necrosis. The liver regeneration rates at POD3 and 7 were 1.54 ± 0.23 and 2.54 ± 0.43, respectively. The Ki-67 labeling index was also elevated at POD3 (27.5 ± 4.1%). Serum HGF and VEGF were elevated at POD1 and 3. ATP levels of liver grafts recovered at POD7. CONCLUSIONS: These results revealed that with appropriate immunosuppressive therapy, partial liver graft regeneration occurred in a xenogeneic animal, which suggests liver grafts regenerated in xenogeneic environments, such as an in vivo bioreactor, have potential to be transplantable liver grafts for humans.

Impact of Graft Quality and Fluid Overload on Postoperative Massive Ascites After Living Donor Liver Transplantation.

After living donor liver transplantation, we encounter cases with massive ascites, which is difficult to manage. We analyzed the risk factors for massive ascites after living donor liver transplantation. The subjects were 100 adult recipients who underwent living donor liver transplantation at Kyoto University Hospital from 2013 to 2017. We retrospectively assessed patient, graft, operative factors, and percent fluid overload, which were defined as [(weight on the day - preoperative weight)/preoperative weight] × 100%. We defined the massive ascites group as having a14-day average ascites ≥ 2500 mL and the mild ascites group as having a 14-day average ascites < 2500 mL. Forty-seven patients were included in the massive group, and 53 patients were included in the mild group. There was no difference in short- and long-term survival. In multivariate analysis, the presence of preoperative ascites (P = .0008), 14-day average percent fluid overload ≥ 14.5% (P = .0095), graft-to-recipient weight ratio < 0.86 (P = .0253), and donors' age ≥ 47 years (P = .0466) were identified as independent risk factors for massive ascites after living donor liver transplantation. A liver graft with a small graft-to-recipient weight ratio or from an elderly donor, which may indicate poor graft quality, presence of preoperative ascites, and postoperative fluid overload were associated with massive ascites after living donor liver transplantation.

Sclerosing encapsulating peritonitis after living-donor liver transplantation: A case series, Kyoto experience.

Sclerosing encapsulating peritonitis (SEP), or abdominal cocoon is a rare cause of intestinal obstruction, and still etiology remains unknown. We report a series of 4 patients with abdominal cocoon, and all the 4 patients had previously undergone living-donor liver transplantation (LDLT). There was no evidence of SEP before and during LDLT. At the time of diagnosis of SEP, 3 out of 4 patients had ascites. First and fourth patients had multiple episodes or attacks of cholangitis, which were managed by percutaneous transhepatic biliary drainage and hepaticojejunostomy, respectively. All 4 patients presented with intestinal obstruction and 3 of them underwent a successful operation. The fourth patient died due to liver failure and complications of the SEP. The first 3 patients are doing well without SEP recurrence. Our experience suggest that the prognosis of SEP is poor in patients with poor graft liver functions after LDLT.

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats.

Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD.