Anticancer Effect of Statins in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

The anticancer effect of statins is drawing attention. However, it is unclear whether statin use reduces the risk of hepatocellular carcinoma (HCC) recurrence in patients who undergo liver transplantation (LT) for HCC. Consecutive patients who underwent LT for HCC between 1995 and 2019 were enrolled. The effects of statins on HCC recurrence and mortality were compared between statin user and statin nonuser groups. We performed the analyses in a variety of ways, including inverse probability treatment weighting (IPTW) methods to balance any confounders and the landmark method to avoid immortal time bias. A total of 430 patients were enrolled, among whom 323 (75.1%) were statin nonusers and 107 (24.9%) were statin users. During a median of 64.9 months (IQR, 26.1-122.6 months) of follow-up, 79 patients (18.4%) had HCC recurrence and 111 (25.8%) died. Among those who died, 53 (47.7%) were identified as HCC-related mortalities. Statin use was a predictor of HCC recurrence (adjusted hazard ratio [HR], 0.3; 95% confidence interval [CI], 0.1-0.6; P = 0.002), all-cause mortality (adjusted HR, 0.3; 95% CI, 0.2-0.5; P < 0.001), and HCC-related mortality (adjusted HR, 0.4; 95% CI, 0.2-0.9; P = 0.03). The effects of statin use on clinical outcomes were also identified through IPTW analysis. There was a dose-dependent relationship between statin use and HCC recurrence. The anticancer effect of statins on HCC recurrence was consistently significant across multivariable-stratified and sensitivity analyses. Statin use significantly reduced the risk of HCC recurrence and improved the survival of patients who underwent LT for HCC.

Comparative long-term outcomes for pancreatic volume change, nutritional status, and incidence of new-onset diabetes between pancreatogastrostomy and pancreatojejunostomy after pancreaticoduodenectomy.

BACKGROUND: The difference in volume change in a pancreatic remnant according to the type of pancreaticoenterostomy after pancreaticoduodenectomy (PD) for long-term follow-up is unknown. Also, there are few studies that evaluate the difference in general nutritional status and pancreatic endocrine function, including new-onset diabetes mellitus (NODM) depending on the type of pancreaticoenterostomy. This study aimed to compare serial pancreatic volume changes in pancreatic remnants between pancreatogastrostomy (PG) and pancreatojejunostomy (PJ) after PD and to evaluate the difference in general nutritional status and incidence of NODM between PG and PJ. METHODS: This study enrolled 115 patients who had survived for more than 3 years after PD. They were divided into the PG group and the PJ group. Their clinicopathologic factors were collected and analyzed. We calculated serial pancreas volume and pancreatic duct size precisely from preoperative stage to 5 years after surgery by image-processing software specifically designed for navigation and visualization of multimodality and multidimensional images. Consecutive changes of albumin and body mass index (BMI) as related to general nutritional status were compared between the PG and PJ groups. To evaluate the incidence and risk factors of NODM following PD, subgroup analysis was performed in 88 patients who did not have diabetes preoperatively. RESULTS: Most patient demographics were not significantly different between the PG group (n=45) and PJ group (n=70). There was no significant difference in volume reduction between the groups from postoperative 1 month to 5 years (PG group -18.21±14.66 mL versus PJ group -14.43±13.05 mL, P=0.209). But there was a significant difference in increased pancreatic duct size between the groups from postoperative 1 month to 5 years (PG group 1.66±2.20 mm versus PJ group 0.54±1.54 mm, P=0.007). There was no significant difference in the increase of total serum albumin between the groups for 5 years after surgery (PG group 0.51±0.47 g/dL, 14.3% versus PJ group 0.42±0.60 g/dL, 11.3%, P=0.437). There was also no significant difference in BMI decrease between the groups (PG group -1.13±3.12, -4.9% versus PJ group -1.97±2.01, -8.7%, P=0.206). On the whole, NODM was diagnosed in 19 patients out of the 88 patients (21.6%) who did not have DM preoperatively. The incidence of NODM was not significantly different between the groups (PG group 21.6% versus PJ group 21.5%, P=0.995). In addition, pancreaticoenterostomy was not an independent risk factor for NODM by logistic regression analysis (odds ratio, 0.997, 95% CI: 0.356-0.2.788, P=0.995). No other risk factors for NODM were found. CONCLUSIONS: PG and PJ following PD induced similar pancreatic volume reduction during long-term follow-up. There was no difference in general nutritional status or incidence of NODM between the groups after PD.

Diminished food-related motivation in adult rats treated with methamphetamine during adolescence.

Drug use among adolescents continues to be an area of concern because of the possibility of long-lasting physical and mental changes. The aim of this study was to determine whether methamphetamine exposure during adolescence results in long-lasting neurobehavioral alterations in adulthood. Sprague-Dawley rats were injected with methamphetamine (4 mg/kg/day) during postnatal days 28-37. Once rats reached postnatal days 150, they were placed in standard operant chambers, where they were trained to respond to a lever for sucrose pellets, the experimental reinforcement. Methamphetamine exposure during adolescence did not result in a noteworthy impairment in the development of the correct lever touch response in the autoshaped learning test with 4 seconds delayed reinforcement. These rats were also tested for the motivation to obtain sucrose pellets under a progressive ratio schedule of the reinforcement on postnatal days 170. Decreased lever-pressing response was noted in male rats exposed to methamphetamine during adolescence, but not in female rats. These results indicate that methamphetamine exposure during adolescence results in a decrease in the motivation for a natural reinforcer later in adulthood, particularly in male rats. From our data, we suggest that male brains are less capable of facilitating recovery than female brains after methamphetamine-induced perturbation of brain function during the adolescent period.

Impact of the Reconstruction Material on the Patency of Middle Hepatic Vein in Living Donor Liver Transplantation Using the Right Liver.

BACKGROUND: A right liver graft with middle hepatic vein (MHV) reconstruction is the standard graft for adult-to-adult living donor liver transplantation (LDLT). The patency of reconstructed MHV affects the recovery and regeneration of graft. The aim of the study is to evaluate the patency rate of reconstructed MHV according to the reconstruction material in LDLT using the right liver. METHODS: The data was collected retrospectively on 521 patients who underwent LDLT with right liver graft form August 2003 to December 2012 at the Seoul St. Mary's Hospital in Seoul. Two serial comparisons were performed. At first, patients were divided into 2 groups: biologic graft group (n = 252) and synthetic graft group (n = 177). Second, patients were divided into 6 groups: No MHV reconstruction (n = 92); MHV was reconstructed by greater saphenous vein (GSV) (n = 20); recipient's portal vein (PV) (n = 219); cryopreserved iliac artery (CIA) (n = 2); cryopreserved iliac vein (CIV) (n = 11); polytetrafluoroethylene (PTFE) graft (n = 105); and polyethylene terephthalate (PETE) graft (n = 72). We compared the patency of reconstructed MHV among these groups by computed tomography angiography at 7 days, 20 days, 90 days, and 1 year. RESULTS: At the first comparison, the patency rate of the biologic graft group on the seventh postoperative day was 61.9%, and the synthetic graft group was 72.4% (P = .029). At postoperative 1 year, the patency rate of the biologic graft group was 42.9%, and the synthetic graft group was 24.1% (P = .001). At the second comparison, the MHV patency of GSV, PV, CIA, CIV, PTFE, and PETE was 65.0%, 62.5%, 50%, 63.6%, 75%, 72% on the seventh postoperative days (P = .318); 60%, 57.1%, 50%, 54.5%, 69%, 55.6% on the 20th postoperative days (P = .444); 40%, 48.8%, 50%, 27.3%, 47%, 34.1% on the 90th postoperative days (P = .294); and 30%, 45.2%, 50%, 27.3%, 27%, 26.4% at 1 postoperative year (P = .008). CONCLUSION: Although there was no statistical difference in comparison of each material, there were significant differences in MHV patency rates between the biologic and the synthetic group. Therefore, the synthetic graft could be considered in living donor liver transplantation with MHV reconstruction.

Impact of Enterococcal Bacteremia in Liver Transplant Recipients.

BACKGROUND: Enterococcus species are a common cause of bacteremia in liver transplant recipients. Vancomycin-resistant enterococci (VRE) have become an important cause of nosocomial infection. In this study, we analyzed the incidence, antibiotic resistance, and outcomes of enterococcal bacteremia in living donor liver transplant recipients and the risk factors for VRE. PATIENTS AND METHODS: This single-center, retrospective review included 536 patients who underwent liver transplant between January 2008 and December 2017. RESULTS: Among 536 patients, 42 (7.8%) experienced a total of 58 enterococcal bacteremic episodes (37 Enterococcus faecium, 17 Enterococcus faecalis, 2 Enterococcus casseliflavus, 1 Enterococcus. avium, and 1 Enterococcus raffinosus). Most cases of enterococcal bacteremia (46/58, 79.3%) occurred within 6 months after transplant; among the 26 cases of VRE bacteremia, 50% occurred within 1 month after transplant. E. faecium isolates had the highest rate of vancomycin resistance (25/37, 67.5%), whereas all E. faecalis isolates were susceptible to vancomycin. According to multivariate analysis, post-transplant dialysis (odds ratio, 3.95; 95% CI, 1.51-10.34; P = .005) and length of post-transplant hospital stay (odds ratio, 1.03; 95% CI, 1.009-1.04; P = .004) were significantly associated with VRE bacteremia. One-year mortality was 31% (13/42) among recipients with enterococcal bacteremia, 5.0% (20/384) among nonbacteremic patients, and 11.1% (10/90) among patients with nonenterococcal bacteremia (P < .001). CONCLUSION: In this study, enterococcal bacteremia showed high incidence in liver transplant recipients, especially with vancomycin resistance, occurred in early period after transplant, and was associated with increased mortality. High rates of resistance to vancomycin warrant further efforts to manage enterococcal infection in liver transplant recipients at our center.

Invasive fungal infection in liver transplant recipients in a prophylactic era: A multicenter retrospective cohort study in Korea.

The epidemiology of invasive fungal infections (IFIs) after liver transplantation (LT) is continuing to evolve in the current era of antifungal prophylactic therapy. This multicenter retrospective cohort study aimed to evaluate the epidemiology, risk factors, and outcomes of IFIs among LT recipients in the current era.We analyzed a total of 482 LT recipients aged 18 years and older who were admitted to 3 tertiary hospitals in Korea between January 2009 and February 2012.Twenty-four episodes of IFIs occurred in 23 patients (4.77%; 23/482). Of these episodes, 20 were proven cases and 4 were probable cases according to EORTC/MSG criteria. Among these cases, IFI developed within 30 days of transplantation in 47.8% of recipients, from 31 to 180 days in 34.8% of recipients, and from 181 to 365 days in 17.4% of recipients. The most common isolates were Candida species (n = 12, 52.2%; Candida albicans, 6 cases; Candida tropicalis, 1 case; Candida glabrata, 1 case; Candida parapsilosis, 1 case; and unspecified Candida species, 1 case) and Aspergillus species (n = 7, 30.4%). The mortality in patients with IFIs was significantly higher than that in patients without IFIs (47.83% [11/23] vs 7.18% [33/459], P < .001). The incidence of late-onset IFIs is increasing in the antifungal prophylactic era, and fluconazole-resistant non-albicans Candida species have not yet emerged in Korea.

Laparoscopic end-to-end biliary reconstruction with T-tube for transected bile duct injury during laparoscopic cholecystectomy.

PURPOSE: This report describes the laparoscopic end-to-end biliary reconstruction with T-tube for transected bile duct injury (BDI) during laparoscopic cholecystectomy. METHODS: We performed a retrospective descriptive analysis for all patients with a transected BDI at a single institution. We collected and analyzed data for injury site and type, reconstruction methods, conversion rate, previous intervention, and outcomes. RESULTS: Between January 2014 and December 2017, 2,901 patients underwent laparoscopic cholecystectomy at a single institution. Among them, 8 patients experienced a transected BDI during laparoscopic cholecystectomy, so the surgeon performed laparoscopic end-to-end biliary reconstruction with T-tube. Our patient series consisted of 6 women (75%) and 2 men (25%) with a mean age of 48.3 years (median, 49 years; range, 29-77 years). Two cases were converted to open surgery. The most common injured site was the common bile duct (5 of 8, 62.5%). The most common injury type, using Bismuth's classification system, was type I (3 of 8, 37.5%). The mean operating time was 136.8 minutes (median, 135.0 minutes; range, 0-180.0 minutes). The mean hospital stay was 7.0 days (median, 4.5 days, range: 3.0-21.0 days). The mean follow-up was 36.4 months (median, 34.0 months; range, 16.0-63.0 months). We observed one postoperative complication during the follow-up period. The patient had an anastomosis site leakage and was cured after reoperation. CONCLUSION: Laparoscopic end-to-end biliary reconstruction with T-tube for transected BDI during laparoscopic cholecystectomy seems to be safe and feasible in selected patients. However, long-term follow-up to identify complications from bile duct stricture remains important.

Assessment of mGluR5 KO mice under conditions of low stress using a rodent touchscreen apparatus reveals impaired behavioural flexibility driven by perseverative responses.

Genetic and pharmacological manipulations targeting metabotropic glutamate receptor 5 (mGluR5) affect performance in behavioural paradigms that depend on cognitive flexibility. Many of these studies involved exposing mice to highly stressful conditions including electric foot shocks or water immersion and forced swimming. Because mGluR5 is also implicated in resilience and stress responses, however, apparent impairments in inhibitory learning may have been an artifact of manipulation-induced changes in affective state. To address this, we present here a characterization of cognitive flexibility in mGluR5 knockout (KO) mice conducted with a rodent touchscreen cognitive assessment apparatus in which the animals experience significantly less stress.Our results indicate a significant reversal learning impairment relative to wild-type (WT) controls in the two-choice Visual Discrimination-Reversal (VDR) paradigm. Upon further analysis, we found that this deficit is primarily driven by a prolonged period of perseveration in the early phase of reversal. We also observed a similar perseveration phenotype in the KO mice in the Extinction (EXT) paradigm. In addition, mGluR5 KO mice show higher breakpoints in the touchscreen Progressive Ratio (PR) and altered decision making in the Effort-related Choice (ERC) tasks. Interestingly, this impairment in PR is an additional manifestation of an increased propensity to perseverate on the emission of relatively simplistic behavioural outputs.Together, these findings suggest that under conditions of low stress, mGluR5 KO mice exhibit a pronounced perseverative phenotype that blunts cognitive flexibility.

Heme oxygenase-1 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration.

Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 µg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition.

Fraxinellone inhibits inflammatory cell infiltration during acute pancreatitis by suppressing inflammasome activation.

Inflammasomes promote the production of pro-inflammatory cytokines, such as interleukin (IL)-1ß and IL-18, which are the representative mediators of inflammation. Abnormal activation of inflammasomes leads to the development of inflammatory diseases such as acute pancreatitis (AP). In this study, we demonstrate the inhibitory effects of a new natural compound fraxinellone on inflammasome formation and examine the role of inflammasomes in a mouse model of AP. AP was induced with hourly intraperitoneal injections of supramaximal concentrations of the stable cholecystokinin analogue cerulein (50 µg/kg) for 6 h. Mice were sacrificed 6 h after the final cerulein injection. Blood and pancreas samples were obtained for further experiments. Intraperitoneal injection of fraxinellone significantly inhibited the pancreatic activation of multiple inflammasome molecules such as NACHT, LRR and PYD domains-containing protein 3 (NLRP3), PY-CARD, caspase-1, IL-18, and IL-1ß during AP. In addition, fraxinellone treatment inhibited pancreatic injury, elevation in serum amylase and lipase activities, and infiltration of inflammatory cells such as neutrophils and macrophages but had no effect on pancreatic edema. To investigate whether inflammasome activation leads to the infiltration of inflammatory cells, we used parthenolide, a well-known natural inhibitor, and IL-1 receptor antagonist mice. The inhibition of inflammasome activation by pharmacological/or genetic modification restricted the infiltration of inflammatory cells, but not edema, consistent with the results observed with fraxinellone. Taken together, our study highlights fraxinellone as a natural inhibitor of inflammasomes and that inflammasome inhibition may lead to the suppression of inflammatory cells during AP.

Dual-Incision Laparoscopic Spleen-Preserving Distal Pancreatectomy: Merits Compared to the Conventional Method.

BACKGROUND: Herein, we assess the safety and feasibility of dual-incision laparoscopic spleen-preserving distal pancreatectomy (DILSPDP) through lateral approach with reduced trocars for benign and low-grade malignancy in pancreas tail. We compare DILSPDP with surgical outcomes of conventional laparoscopic spleen-preserving distal pancreatectomy (LSPDP). METHODS: Patients with benign pancreas tail mass that had been scheduled for LSPDP were selected to undergo DILSPDP. These patients had spleen-preserving distal pancreatectomy with the dissection in lateral-to-medial fashion using a multichannel trocar in the right lateral decubitus position of patient. We compared the demographics and operative outcomes of DILSPDP with those of conventional LSPDP which was performed with dissection in medial-to-lateral fashion using four or five trocars in supine position. RESULTS: Twenty two cases of DILSPDP and 26 cases of conventional LSPDP were reviewed. There was no difference in terms of demographic features including diagnosis or tumor size, although the location of the tumor was fundamentally different between the two groups. Significantly shorter operative times and reduced blood loss were observed in DILSPDP group (p = 0.004 and 0.011, respectively) and the preservation of splenic vessels was more successful with DILSPDP than conventional surgery (95.5% vs. 65.4%, p = 0.013). CONCLUSIONS: DILSPDP appears to be a feasible method of spleen-preserving distal pancreatectomy for benign or low-malignancy of pancreas tail and is accompanied by advantages in terms of splenic vessel preservation and reduced parietal trauma.

Clinical outcome of 1,000 consecutive cases of liver transplantation: a single center experience.

PURPOSE: The aim of this study was to analyze survival outcomes in 1,000 consecutive liver transplantations (LTs) performed at a single institution from 1993 to April 2017. METHODS: The study population was divided into 2 groups based on donor type: deceased donor LT (DDLT; n = 181, 18.1%) and living donor LT (LDLT; n = 819; 81.9%), and into 3 periods based on the number of cases (first 300 cases, middle 300 cases, last 400 cases). RESULTS: Infection was the most common cause of death, accounting for 34.8% (95 of 273). Mortality due to hepatocellular carcinoma recurrence occurred most frequently between 1 and 5 years after transplantation. Mortality rate by graft rejection was highest between 5 and 10 years after transplantation. And mortality by de novo malignancy occurred most frequently after 10 years after transplantation. The patient survival rates for the entire population at 5 and 10 years were 74.7%, and 68.6%, respectively. There was no difference in survival rate between the LDLT and DDLT groups (P = 0.188). Cause of disease, disease severity, case period, and retransplantation had a significant association with patient survival (P = 0.002, P = 0.031, P = 0.003, and P = 0.024, respectively). CONCLUSION: Surgical techniques and perioperative management for transplant patients have improved and undergone standardization. Controlling perioperative infection and managing patients with HCC as LT candidates will result in better outcomes.

Clinical Course of Hepatic Artery Thrombosis After Living Donor Liver Transplantation Using the Right Lobe.

Hepatic artery thrombosis (HAT) can result in biliary tree necrosis and graft loss, necessitating retransplantation. The most effective treatment approach is still controversial. This study was performed to review the outcomes of HAT after living donor liver transplantation (LDLT) and to clarify the feasibility of different strategies. From May 1996 to August 2017, LDLT using the right lobe was performed in 827 adult patients in our center. Our technique of hepatic artery (HA) reconstruction is end-to-end anastomosis under a microscope (10×). Diagnosis of HAT was performed using Doppler sonography and computed tomography (CT) angiography. HAT was initially treated with surgical or endovascular procedure, and retransplantation was considered according to the graft condition. Among the 827 cases of LDLT using the right lobe, HAT occurred in 16 (1.9%) cases within 1 month after transplantation. Within the first week, 7 of these HAT cases (43.8%) occurred (early HAT), while the remaining 9 cases (56.2%) occurred between the first week and 1 month (late HAT). The incidence of graft failure was high in early HAT (42.9%), and the frequency of biliary complications was high in late HAT (77.8%). The success rate of HA recanalization was 62.5% (10/16): 100% (5/5) after reoperation and 45.5% (5/11) after the endovascular procedure. Of the patients in whom treatment failed in late HAT (n = 5), 4 underwent neovascularization during observation. A total of 5 patients underwent graft failure, and 3 of these patients underwent repeat liver transplantation (LT). Mortality occurred in 3 patients, including 1 in the surgical group and 2 in the endovascular group. In conclusion, early diagnosis and aggressive treatment of HAT are necessary to avoid graft failure, and the choice of treatment depends on various factors. Although further studies are required, early HAT requires preparation for graft failure, while late HAT requires treatment for biliary complications.

Outcome of donor biliary complications following living donor liver transplantation.

Background/Aims: Biliary complications are the most common donor complication following living donor liver transplantation (LDLT). The aim of this study is to investigate the long-term outcomes of biliary complications in right lobe adult-to-adult LDLT donors, and to evaluate the efficacy of endoscopic treatment of these donors. METHODS: The medical charts of right lobe donors who developed biliary complications between June 2000 and January 2008 were retrospectively reviewed. RESULTS: Of 337 right lobe donors, 49 developed biliary complications, including 36 diagnosed with biliary leakage and 13 with biliary stricture. Multivariate analysis showed that biliary leakage was associated with the number of right lobe bile duct orifices. Sixteen donors, five with leakage and 11 with strictures, underwent endoscopic retrograde cholangiography (ERC). ERC was clinically successful in treating eight of the 11 strictures, one by balloon dilatation and seven by endobiliary stenting. Of the remained three, two were treated by rescue percutaneous biliary drainage and one by conservative care. Of the five patients with leakage, four were successfully treated using endobiliary stents and one with conservative care. In overall, total 35 improved with conservative treatment. All inserted stents were successfully retrieved after a median 264 days (range, 142 to 502) and there were no recurrences of stricture or leakages during a median follow-up of 10.6 years (range, 8 to 15.2). Conclusions: All donors with biliary complications were successfully treated non-surgically, with most improving after endoscopic placement of endobiliary stents and none showing recurrence on long term follow-up.

Serial Monitoring of Immune Markers Being Represented Regulatory T Cell/T Helper 17 Cell Ratio: Indicating Tolerance for Tapering Immunosuppression after Liver Transplantation.

Recipients of liver transplantation (LT) require long-term immunosuppressive drug treatment, but lifelong immunosuppressive treatment has severe side effects. It is known that some LT recipients develop immune tolerance, and although the development of such operational tolerance should allow a decrease in the burden of immunosuppressive drug treatment, the factors that indicate operational tolerance are not clear. This study aimed to monitor immunological markers over time in LT recipients to identify those markers indicating the development of operational tolerance. We performed a prospective pilot study measuring immune markers, including the ratio of regulatory T (Treg) and T helper (Th) 17 cells in peripheral blood in the 14 most immunologically stable patients among 70 clinically stable LT recipients. The doses of immunosuppressive drugs given to these 14 LT recipients were tapered over time and they were monitored for immunological markers related to the development of immune tolerance. As the doses of immunosuppressive drugs were reduced, the Treg/Th17, Th1/Th17, and CD8/Th17 ratio in tolerant recipients was significantly increased compared with that of nontolerant recipients. These results suggest that monitoring of changes in the immune makers, including Treg/Th17 ratio during tapering of immunosuppression may allow prediction of the development of tolerance.

Clinical advantages of single port laparoscopic hepatectomy.

AIM: To evaluate the clinical advantages of single-port laparoscopic hepatectomy (SPLH) compare to multi-port laparoscopic hepatectomy (MPLH). METHODS: We retrospectively reviewed the medical records of 246 patients who underwent laparoscopic liver resection between January 2008 and December 2015 at our hospital. We divided the surgical technique into two groups; SPLH and MPLH. We performed laparoscopic liver resection for both benign and malignant disease. Major hepatectomy such as right and left hepatectomy was also done with sufficient disease-free margin. The operative time, the volume of blood loss, transfusion rate, and the conversion rate to MPLH or open surgery was evaluated. The post-operative parameters included the meal start date after operation, the number of postoperative days spent in the hospital, and surgical complications was also evaluated. RESULTS: Of the 246 patients, 155 patients underwent SPLH and 91 patients underwent MPLH. Conversion rate was 22.6% in SPLH and 19.8% in MPLH (P = 0.358). We performed major hepatectomy, which was defined as resection of more than 2 sections, in 13.5% of patients in the SPLH group and in 13.3% of patients in the MPLH group (P = 0.962). Mean operative time was 136.9 ± 89.2 min in the SPLH group and 231.2 ± 149.7 min in the MPLH group (P < 0.001). The amount of blood loss was 385.1 ± 409.3 mL in the SPLH group and 559.9 ± 624.9 mL in the MPLH group (P = 0.016). The safety resection margin did not show a significant difference (0.84 ± 0.84 cm in SPLH vs 1.04 ± 1.22 cm in MPLH, P = 0.704). Enteral feeding was started earlier in the SPLH group (1.06 ± 0.27 d after operation) than in the MPLH group (1.63 ± 1.27 d) (P < 0.001). The mean hospital stay after operation was non-significantly shorter in the SPLH group than in the MPLH group (7.82 ± 2.79 d vs 7.97 ± 3.69 d, P = 0.744). The complication rate was not significantly different (P = 0.397) and there was no major perioperative complication or mortality case in both groups. CONCLUSION: Single-port laparoscopic liver surgery seems to be a feasible approach for various kinds of liver diseases.

Comparison of the long-term efficacy and safety of generic tacrolimus, Tacrobell, with Prograf in liver transplant recipients.

INTRODUCTION: The purpose of this study was to compare the safety and efficacy of generic tacrolimus (Tacrobell [TCB]) and a reference tacrolimus (Prograf [PGF]) in liver transplant recipients. PATIENTS AND METHODS: We retrospectively analyzed 167 patients who used TCB or PGF between January 2009 and March 2016 for >1 year (TCB group, n=86; PGF group, n=81). To assess the efficacy and safety of TCB, we evaluated the relationship between drug dose and trough level, survival, rejection, infection, kidney function, and side effects. RESULTS: There was no difference in the preoperative demographics between the two groups. Moreover, there was no difference in the drug dose and trough level between the groups at 1 week after surgery. Coefficient of variation (CV) values were obtained at the drug trough level for each patient and no differences in CV values were identified within 1 year (p=0.587) and up to 5 years (p=0.824) in both groups. Rehospitalization (p=0.1) and total rejection (p=0.915) did not differ between the two groups, but the rejection severity, recorded as the rejection activity index value, was worse in the PGF group (p=0.039). No difference was found in the infection rate (p=0.818), and with regard to nephrotoxicity, there was no difference in the rate of patients with chronic kidney disease stage 3 and above during the follow-up period. No differences were found between the two groups in terms of drug side effects and adverse events. CONCLUSION: The generic tacrolimus, TCB, is a comparable alternative to the original tacrolimus, PGF, as a main immunosuppressive drug for liver transplantation.

Prognostic Prediction Models for Resection of Large Hepatocellular Carcinoma: A Korean Multicenter Study.

BACKGROUND: We developed a prognostic prediction model (PPM) using 4 factors for hepatic resection (HR) of large hepatic cellular carcinoma (HCC). Multiplication of α-fetoprotein (AFP), des-γ-carboxy prothrombin, and tumor volume (TV) (ADV score) is a surrogate marker for post-resection prognosis. This study intended to validate the predictive power of 4-factor PPM and to develop new ADV score-based PPM. METHODS: A total of 526 patients who underwent HR for solitary HCC ≥ 8 cm were selected from 9 Korean institutions between 2008 and 2014. RESULTS: Median tumor diameter and TV were 11.0 cm and 398 mL, respectively. Tumor recurrence and patient survival rates were 53.0 and 78.4% at 1 year and 70.2 and 49.3% at 5 years, respectively. Independent risk factors for both tumor recurrence and patient survival included AFP ≥ 100 ng/mL, hypermetabolic FDG-positron emission tomography (PET), microvascular invasion and satellite nodules, which comprised 4 factors of the PPM. Five subgroups based on the number of involved risk factors exhibited significant differences in tumor recurrence and patient survival. ADV score cutoff was set at 7log (ADV7log) after cluster prognostic analysis. Patient grouping according to combination of ADV7log and FDG-PET findings (ADV7log-PET) exhibited significant differences in tumor recurrence and patient survival, comparable to those of the 4-factor PPM. CONCLUSIONS: Two PPMs using 4 risk factors and ADV7log-PET could reliably predict the risk of early HCC recurrence and long-term survival outcomes in patients who underwent HR for large HCC. We believe that these PPMs can guide surgical treatment for large HCCs from preoperative HR planning to post-resection follow-up.

Deep gray matter iron measurement in patients with liver cirrhosis using quantitative susceptibility mapping: Relationship with pallidal T1 hyperintensity.

BACKGROUND: The liver is a central organ for the metabolism of iron and manganese and the places where those metals are commonly deposited overlap in the brain. PURPOSE/HYPOTHESIS: To elucidate the relationship between pallidal T1 hyperintensity and iron deposition in the deep gray matter of liver cirrhosis patients using quantitative susceptibility mapping (QSM). STUDY TYPE: Retrospective case-control study SUBJECTS: In all, 38 consecutive liver cirrhosis patients who received brain magnetic resonance imaging (MRI) as pretransplant evaluation. FIELD STRENGTH/SEQUENCE: QSM was reconstructed from 3D multi- or single-echo phase images at 3T. T1 -weighted images were used for the assessment of pallidal hyperintensity and pallidal index (PI). ASSESSMENT: Patients were divided into two groups according to the presence of pallidal hyperintensity by consensus of two radiologists. Susceptibility values were acquired for five deep gray matter structures. STATISTICAL TEST: QSM measures were compared between two groups using the t-test. We also calculated Pearson correlations between QSM measures and PI. RESULTS: In all, 26 patients showed pallidal hyperintensity (T1 h group) and 12 did not (T1 n group). The susceptibility of the globus pallidus (GP) in the T1 h group (120.6 ± 38.1 ppb) was significantly lower than that in the T1 n group (150.0 ± 35.2, P = 0.030). The susceptibility of the dentate nucleus (DN) in the T1 h group (88.1 ± 31.0) was significantly lower than that in the T1 n group (125.6 ± 30.6, P = 0.001). Negative correlation between the susceptibility of GP (r = -0.37, P = 0.022) and the PI, and between DN (r = -0.43, P < 0.001) and the PI was found. DATA CONCLUSION: Liver cirrhosis patients with pallidal T1 hyperintensity had lower susceptibility values in the GP and DN than those without it. This suggests a possible interaction between iron and manganese in the brains of liver cirrhosis patients. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1342-1349.