ERS: A simple scoring system to predict early recurrence after surgical resection for hepatocellular carcinoma.

BACKGROUND: Surgical resection (SR) is a potentially curative treatment of hepatocellular carcinoma (HCC) hampered by high rates of recurrence. New drugs are tested in the adjuvant setting, but standardised risk stratification tools of HCC recurrence are lacking. OBJECTIVES: To develop and validate a simple scoring system to predict 2-year recurrence after SR for HCC. METHODS: 2359 treatment-naïve patients who underwent SR for HCC in 17 centres in Europe and Asia between 2004 and 2017 were divided into a development (DS; n = 1558) and validation set (VS; n = 801) by random sampling of participating centres. The Early Recurrence Score (ERS) was generated using variables associated with 2-year recurrence in the DS and validated in the VS. RESULTS: Variables associated with 2-year recurrence in the DS were (with associated points) alpha-fetoprotein (<10 ng/mL:0; 10-100: 2; >100: 3), size of largest nodule (≥40 mm: 1), multifocality (yes: 2), satellite nodules (yes: 2), vascular invasion (yes: 1) and surgical margin (positive R1: 2). The sum of points provided a score ranging from 0 to 11, allowing stratification into four levels of 2-year recurrence risk (Wolbers' C-indices 66.8% DS and 68.4% VS), with excellent calibration according to risk categories. Wolber's and Harrell's C-indices apparent values were systematically higher for ERS when compared to Early Recurrence After Surgery for Liver tumour post-operative model to predict time to early recurrence or recurrence-free survival. CONCLUSIONS: ERS is a user-friendly staging system identifying four levels of early recurrence risk after SR and a robust tool to design personalised surveillance strategies and adjuvant therapy trials.

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.

Laparoscopic liver resection versus percutaneous radiofrequency ablation for small hepatocellular carcinoma.

BACKGROUND: Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) play central roles to treat early-stage hepatocellular carcinoma (HCC, ≤3 cm, 1-3 nodules, and no macrovascular involvement), although data are lacking regarding whether LLR or RFA is preferable. This study aimed to compare outcomes of both treatments for small HCCs. METHODS: Treatment outcomes of small HCCs were compared between all the minor LLRs performed between 2005 and 2016 and RFAs performed between 2011 and 2016 at Kyoto University. RESULTS: A total of 85 and 136 patients underwent LLR and RFA, respectively. Patients that underwent LLR had higher incidence of blood transfusions, complications, and longer hospital stay. Overall and disease-specific survival rates were similar between LLR and RFA; however, recurrence-free (49.2% vs. 22.1% at 3-year) and local recurrence-free survival rates (94.9% vs. 63.6% at 3-year) were higher after LLR. Multivariate analyses identified that multiple nodules and 65-year-old and above are predictors of disease-specific survival, and that RFA is a predictor of recurrence and local recurrence. CONCLUSION: RFA is less invasive, although both LLR and RFA are safe and effective. LLR provides better local control with superior recurrence-free and local-recurrence free survival. These results help optimize treatment selection based on patient-specific factors.

Etiology of Liver Steatosis Influences the Severity of Ischemia/Reperfusion Injury and Survival After Liver Transplantation in Rats.

Liver steatosis is a leading cause of graft disposal in liver transplantation, though the degree of steatosis is often the single factor determining acceptability of the graft. We investigated how the cause of liver steatosis affects graft function in rat orthotopic liver transplantation (OLT). OLT was performed using 2 types of steatotic liver grafts: the fasting and hyperalimentation (FHA) model and the methionine- and choline-deficient diet models. The FHA and 4-week feeding of a methionine- and choline-deficient diet (MCDD4wk) groups showed similar liver triglyceride levels without signs of steatohepatitis. Therefore, the 2 groups were compared in the following experiment. With 6-hour cold storage, the 7-day survival rate after OLT was far worse in the FHA than in the MCDD4wk group (0% versus 100%, P = 0.002). With 1-hour cold storage, the FHA group showed higher aspartate aminotransferase and alanine aminotransferase levels and histological injury scores in zones 1 and 2 at 24 hours after reperfusion than the normal liver and MCDD4wk groups. Intrahepatic microcirculation and tissue adenosine triphosphate levels were significantly lower in the FHA group after reperfusion. Hepatocyte necrosis, sinusoidal endothelial cell injury, and abnormal swelling of the mitochondria were also found in the FHA group after reperfusion. Tissue malondialdehyde levels were higher in the MCDD4wk group before and after reperfusion. However, the grafts up-regulated several antioxidant enzymes soon after reperfusion. Even though the degree of steatosis was equivalent, the 2 liver steatosis models possessed quite unique basal characteristics and showed completely different responses against ischemia/reperfusion injury and survival after transplantation. Our results demonstrate that the degree of fat accumulation is not a single determinant for the usability of steatotic liver grafts.

Impact of the preoperative bone mineral density on the outcomes after resection of pancreatic cancer.

PURPOSE: The aim of this study is to evaluate the correlation between bone mineral density (BMD) and other body composition markers, as well as, the impact of preoperative BMD on the surgical outcomes after resection of pancreatic cancer. METHODS: This retrospective study included 275 patients who underwent surgical resection of pancreatic cancer in our institute between 2003 and 2016. Patients were divided according to BMD into low and normal groups and their postoperative outcomes were compared. Risk factors for mortality and tumor recurrence were also evaluated. RESULTS: Patients with low BMD were older (P < 0.001), had a higher intramuscular adipose tissue content (P = 0.011) and higher visceral fat area (P = 0.003). The incidence of postoperative pancreatic fistula (POPF) (grade ≥ B) was higher in the low BMD group. No significant difference was observed between the two groups regarding overall survival and recurrence-free survival and low BMD was not a risk factor for mortality or tumor recurrence after resection of pancreatic cancer. CONCLUSION: A low preoperative BMD was not found to be a risk factor for mortality or tumor recurrence after resection of pancreatic cancer; however, it was associated with a higher incidence of clinically relevant POPF.

Impact of Sarcopenic Obesity on Outcomes in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

OBJECTIVE: To evaluate preoperative body composition, including skeletal muscle and visceral adipose tissue, and to clarify the impact on outcomes after hepatectomy for hepatocellular carcinoma (HCC). BACKGROUND: Recent studies have indicated that sarcopenia is associated with morbidity and mortality in various pathologies, including cancer, and that obesity or visceral adiposity represents a significant risk factor for several cancers. However, the impact of sarcopenic obesity on outcomes after hepatectomy for HCC has not been fully investigated. METHODS: We retrospectively analyzed 465 patients who underwent primary hepatectomy for HCC between April 2005 and March 2015. Skeletal muscle mass and visceral adipose tissue were evaluated by preoperative computed tomography to define sarcopenia and obesity. Patients were classified into 1 of 4 body composition groups according to the presence or absence of sarcopenia and obesity. RESULTS: Body composition was classified as nonsarcopenic nonobesity in 184 patients (39%), nonsarcopenic obesity in 219 (47%), sarcopenic nonobesity in 31 (7%), and sarcopenic obesity in 31 (7%). Compared with patients with nonsarcopenic nonobesity, patients with sarcopenic obesity displayed worse median survival (84.7 vs. 39.1 mo, P = 0.002) and worse median recurrence-free survival (21.4 vs. 8.4 mo, P = 0.003). Multivariate analysis identified sarcopenic obesity as a significant risk factor for death (hazard ratio [HR] = 2.504, P = 0.005) and HCC recurrence (HR = 2.031, P = 0.006) after hepatectomy for HCC. CONCLUSION: Preoperative sarcopenic obesity was an independent risk factor for death and HCC recurrence after hepatectomy for HCC.

Laparoscopic Parenchymal-Sparing Hepatectomy for Multiple Colorectal Liver Metastases Improves Outcomes and Salvageability: A Propensity Score-Matched Analysis.

BACKGROUND: Parenchymal-sparing hepatectomy (PSH) is regarded as the standard of care for colorectal liver metastases (CRLMs) in open surgery. However, the surgical and oncological benefits of laparoscopic PSH compared with laparoscopic major hepatectomy (MH) have not been fully documented. METHODS: A total of 269 patients who underwent initial laparoscopic liver resections with curative intent for CRLMs between 2004 and 2017 were enrolled. Preoperative patient characteristics and tumor burden were adjusted with propensity score matching, and laparoscopic PSH was compared with laparoscopic MH after matching. RESULTS: PSH was performed in 148 patients, while MH was performed in 121 patients. After propensity score matching, 82 PSH and 82 MH patients showed similar preoperative characteristics. PSH was associated with lower rates of major postoperative complications compared with MH (6.1 vs. 15.9%; p = 0.046). Recurrence-free survival (RFS) and liver-specific RFS rates were comparable between both groups (p = 0.595 and 0.683). Repeat hepatectomy for liver recurrence was more frequently performed in the PSH group (63.9 vs. 36.4%; p = 0.022), and the PSH group also showed a trend toward a higher overall survival (OS) rate (5-year OS 79.4 vs. 64.3%; p = 0.067). Multivariate analyses revealed that initial MH was one of the risk factors to preclude repeat hepatectomy after liver recurrence (hazard ratio 2.39, p = 0.047). CONCLUSIONS: Laparoscopic PSH provided surgical and oncological benefits for CRLMs, with less complications, similar recurrence rates, and increased salvageability through repeat hepatectomy, compared with laparoscopic MH. PSH should be the standard approach, even in laparoscopic procedures.

Laparoscopic Left Lateral Sectionectomy Using the Extrahepatic Glissonean Approach: A Secure Option for Achieving a Negative Margin for Lesions with Ductal Extension.

INTRODUCTION: In patients with liver lesions with ductal extension, the corresponding Glissonean pedicle should be divided at its origin to achieve a negative ductal margin; however, during laparoscopic hepatectomy, it is difficult to precisely transect the liver and divide the Glissonean pedicle as planned. METHODS: We present a video of a laparoscopic left lateral sectionectomy using the extrahepatic Glissonean approach for a lesion with ductal extension. RESULTS: A 76-year-old woman presented with a cystic neoplasm in the liver segment 3 bile duct (B3). The preoperative workup suggested biliary extension of the lesion towards the origin of B3. A decision was made to perform laparoscopic left lateral sectionectomy with division of the segment 3 Glissonean pedicle (G3) at its origin, and, additionally, left hepatectomy if the B3 ductal margin turned out to be positive. During the procedure, prior to parenchymal transection, the Arantius' ligament was dissected, and G2 and G3 were extrahepatically taped. The ischemic border was visualized by clamping the isolated pedicle, and was also clearly demonstrated by indocyanine green fluorescence. After transecting the liver towards the tape, G3 was divided at its origin, and the frozen section of the ductal margin was negative for tumors. CONCLUSION: The extrahepatic Glissonean approach can help to obtain a maximal ductal margin for liver lesions with possible biliary extension, although the technique potentially poses the risk of bleeding and/or biliary injury, and requires expertise in hepatobiliary surgery. Further studies with larger sample sizes are warranted to validate the feasibility and efficacy of this strategy.

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.

Etiologies, risk factors, and outcomes of bacterial cholangitis after living donor liver transplantation.

The interpretation of bacterial cholangitis after liver transplantation (LT) remains vague, because the presence of bacteria in bile, namely bacteriobilia, does not necessarily indicate an active infection. We investigated the association between post-LT bacterial cholangitis and a variety of short- and long-term outcomes. Two-hundred-seventy-four primary adult-to-adult living donor LT recipients from 2008 to 2016 were divided into three groups according the presence or absence of bacteriobilia and clinical symptoms: (1) no bacteriobilia (N group), (2) asymptomatic bacteriobilia (B group), and (3) cholangitis (C group). The number of patients was by group: N, 161; B, 64; and C, 49. Donor age ≥ 45 years (p = 0.012), choledochojejunostomy (p < 0.001), and post-LT portal hypertension (p = 0.023) were independent risk factors for developing cholangitis. Survival analysis revealed that the C group had significantly worse short- and long-term graft survival. The C group was associated with an increased incidence of early graft loss (EGL) (p < 0.001). While the frequency of readmission for recurrent cholangitis was significantly higher in both the B and C groups (p < 0.001), late graft loss (LGL) due to chronic cholangitis was only commonly observed in the C group (p = 0.002). Post-LT cholangitis could result in not only EGL but also chronic cholangitis and associated LGL.

Recurrence patterns after laparoscopic resection of colorectal liver metastases.

BACKGROUND: The major issue after liver resection for colorectal liver metastases (CRLM) is the high incidence of recurrence. Unlike open liver resection (OLR), recurrence following laparoscopic liver resection (LLR) is not well documented. The aim of this study was to analyze recurrence patterns and treatment following LLR for CRLM. STUDY DESIGN: All patients who underwent LLR for CRLM from 2000 to 2016 were reviewed. Patients who presented with recurrence were compared to those who did not. Recurrence-free survival (RFS), overall survival (OS), and risk of recurrence and survival prognostic factors were analyzed. RESULTS: Overall, 273 patients were included, of which 157 (57.5%) were treated for one liver metastasis (LM). Median follow-up was 41 (12-187) months and associated extrahepatic disease was present in 27% of patients (mainly pulmonary, 65%). After a median of 16 (3-151) months, 197 (72%) patients presented with recurrence. Recurrences were early (< 6 months) in 22.8% of cases, occured in a single site in 66% and were intrahepatic, extrahepatic, or both in 44, 30, and 26%, respectively. Recurrences were treated with surgery or chemotherapy only in 45 and 47%, respectively. 3-, 5-, and 10-year OS was 82, 71, and 43%, respectively. Independent risk factors for recurrence were node-positive primary tumor, extrahepatic disease before hepatectomy, and R1 resection. CONCLUSION: LLR for CRLM does not seem to be associated with distinctive recurrence patterns. LLR for CRLM yielded satisfying RFS and OS and should therefore be considered whenever possible.

Impact of Visceral Adiposity as Well as Sarcopenic Factors on Outcomes in Patients Undergoing Liver Resection for Colorectal Liver Metastases.

OBJECTIVES: We have reported preoperative low skeletal muscularity as an independent risk factor for poor outcomes after liver transplantation, resection of hepatocellular carcinoma, pancreatic cancer and extrahepatic biliary malignancies. However, the impacts of visceral adiposity and muscularity on outcomes after liver resection for colorectal liver metastases (CLM) have not been fully investigated. METHODS: We retrospectively analyzed 124 patients undergoing primary liver resection for CLM between 2005 and 2014. Using preoperative computed tomography at the third lumbar vertebra level, skeletal muscle and abdominal adipose tissue were evaluated by skeletal muscle index (SMI), intramuscular adipose tissue content (IMAC) and visceral-to-subcutaneous adipose tissue area ratio (VSR), respectively. Impacts of preoperative SMI, IMAC and VSR on outcomes after liver resection for CLM were investigated. RESULTS: Low SMI and high VSR were not significantly associated with poor overall or recurrence-free survivals (P = 0.324 and P = 0.106, P = 0.964 and P = 0.738, respectively). Overall survival rate tended to be lower in patients with high IMAC than in patients with normal IMAC (P = 0.054). Recurrence-free survival rate did not differ significantly between high and normal IMAC (P = 0.721). Multivariate analysis showed that low SMI, high IMAC and high VSR were not significant risk factors for death or recurrence after liver resection for CLM. CONCLUSION: Neither preoperative visceral adiposity nor low muscularity were poor prognostic factors in patients undergoing liver resection for CLM.

Impact of Enteral Nutrition with an Immunomodulating Diet Enriched with Hydrolyzed Whey Peptide on Infection After Liver Transplantation.

BACKGROUND: Infection is a leading cause of death after liver transplantation (LT). Therefore, prevention of infection is crucial for improving outcomes after LT. We examined the impact of early enteral nutrition with an immunomodulating diet (IMD) enriched with hydrolyzed whey peptide (HWP) formulation on infection after living donor LT (LDLT), focusing on sarcopenia. METHODS: This study enrolled 279 consecutive patients who underwent primary LDLT at our institute between January 2008 and April 2015. Early enteral nutrition with the IMD enriched with HWP formulation and a conventional elemental diet were started within the first 24 h after surgery for 164 (IMD-HWP) and 115 (conventional) patients. Sequential changes in nutritional parameters, and the incidences of acute cellular rejection (ACR) and bacteremia were compared between the IMD-HWP and control groups. The comparison was made between those members of each group that did or did not exhibit sarcopenia. Risk factors for post-transplant bacteremia were also assessed. RESULTS: Postoperative nutritional parameters and the incidence of ACR were comparable between the groups, except for the prealbumin level. The incidence of bacteremia was significantly lower in the IMD-HWP group, and among patients without sarcopenia in the IMD-HWP group compared with the conventional group (24.4 vs. 41.7%; P = 0.002 and 20.8 vs. 39.0%; P = 0.040, respectively). Independent risk factor for bacteremia comprised bleeding ≥10,000 mL (P = 0.025). In contrast, enteral nutrition without HWP formulation was not significantly associated with bacteremia. However, enteral nutrition without HWP formulation (P = 0.080), MELD scores (P = 0.097), and ABO incompatibility (P = 0.088) showed a trend toward increased incidence of bacteremia, although they did not reach statistical significance in the multivariate analysis. CONCLUSION: Postoperative immunonutrition with an IMD enriched with HWP formulation was closely involved with post-transplant bacteremia.

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.

Visceral Adiposity and Sarcopenic Visceral Obesity are Associated with Poor Prognosis After Resection of Pancreatic Cancer.

BACKGROUND: Visceral fat accumulation and muscle depletion have been identified as poor prognostic factors for various cancers. However, the significance of visceral adiposity and sarcopenic visceral obesity on outcomes after resection of pancreatic cancer remains unclear. METHODS: A retrospective analysis of 301 patients who underwent resection for localized pancreatic cancer between 2004 and 2015 was performed. The extent of visceral adiposity [visceral to subcutaneous adipose tissue area ratio (VSR)] and visceral obesity [visceral fat area (VFA)] were measured on preoperative computed tomography images, together with skeletal muscle index (SMI) and muscle attenuation (MA). The impacts of these body composition parameters on outcomes after pancreatic resection were investigated. RESULTS: The overall survival (OS) and recurrence-free survival (RFS) rates in patients with high VSR were significantly lower than those in patients with low VSR (P = 0.001, P = 0.007, respectively). There were no differences in OS and RFS between high VFA and low VFA group; however, when analyzed together with sarcopenic factors, OS and RFS rates of the patients with sarcopenic visceral obesity were significantly lower compared with those of the others. Multivariate analyses revealed that high VSR was an independent risk factor for mortality (hazard ratio (HR) 1.58, P = 0.009) and recurrence (HR 1.41, P = 0.026) together with low SMI, low MA, high CA19-9, microvascular invasion, and nodal metastasis. CONCLUSIONS: Visceral adiposity and sarcopenic visceral obesity, as well as low muscle mass and quality, were closely associated with mortality and recurrence after resection of pancreatic cancer.

Impact of Skeletal Muscle Mass, Muscle Quality, and Visceral Adiposity on Outcomes Following Resection of Intrahepatic Cholangiocarcinoma.

BACKGROUND: Decrease in skeletal muscle mass and function, known as sarcopenia, is associated with poor prognosis. Visceral fat accumulation also is related to mortality. This study investigated the impact of preoperative skeletal muscle mass, muscle quality, and visceral adiposity on outcomes in patients undergoing resection of intrahepatic cholangiocarcinoma (ICC). METHODS: A retrospective analysis was performed of 109 patients undergoing resections of ICC between January 2004 and April 2015. Skeletal muscle mass [skeletal muscle index (SMI)], skeletal muscle quality [muscle attenuation (MA)], and visceral adiposity [visceral to subcutaneous adipose tissue area ratio (VSR)] were measured on preoperative computed tomography images. The impacts of these parameters on outcomes after ICC resections were analyzed. RESULTS: The overall survival rates were significantly lower in patients with low SMI (P = 0.002), low MA (P = 0.032), and high VSR (P = 0.026) compared with patients with high SMI, high MA, and low VSR, respectively. With multivariate analyses, in patients with stage I-III, low SMI (hazard ratio (HR) 3.29, P = 0.003) and low MA (HR 2.86, P = 0.010) were revealed as independent significant risk factors for mortality. In patients with stage IV, none of these parameters was identified as risk factors, with only the absence of adjuvant chemotherapy identified as an independent risk factor for mortality (HR 5.92, P = 0.001). CONCLUSIONS: Although stage was the most important factor, low skeletal muscle mass and quality were closely related to mortality after resection of ICC in patients with stage I-III.

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.

Muscle Steatosis is an Independent Predictor of Postoperative Complications in Patients with Hepatocellular Carcinoma.

BACKGROUND: Skeletal muscle depletion, referred to as sarcopenia, has been shown to be an independent predictor of lower disease-free and overall survivals in various kinds of diseases. The quality of skeletal muscle has recently attracted much attention as a new parameter of sarcopenia, but its impact on surgical complications is still unknown. METHODS: A retrospective analysis of 492 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) in our institution between April 2005 and December 2014 was performed. The quality of skeletal muscle was evaluated by intramuscular adipose tissue content (IMAC) using preoperative CT imaging at the umbilical level. The impact of sarcopenia on postoperative complications and the predictors of surgical complications after hepatectomy for HCC were analyzed. RESULTS: Patients with high IMAC were older and had higher body mass index, higher indocyanine green retention test at 15 min, and more operative blood loss. Among 492 patients, 108 (22 %) patients had major postoperative complications (Clavien grade ≥ III), and infectious complications were found in 74 (15 %) patients. Twelve (2 %) patients died from postoperative complications. On multivariate analysis, preoperative high IMAC was an independent risk factor for increased major postoperative complications [odds ratio (OR) 1.580; P = 0.049] and infectious complications (OR 1.903; P = 0.021). CONCLUSIONS: Preoperative muscle steatosis evaluated with IMAC was closely correlated with increased postoperative complications, especially infectious complications. The preoperative nutritional intervention and rehabilitation might lead to the improvement of postoperative outcomes after hepatectomy for HCC.

Impact of quality as well as quantity of skeletal muscle on outcomes after liver transplantation.

Intramuscular fat accumulation has come to be associated with loss of muscle strength and function, one of the components of sarcopenia. However, the impact of preoperative quality of skeletal muscle on outcomes after living donor liver transplantation (LDLT) is unclear. The present study evaluated the intramuscular adipose tissue content (IMAC) and psoas muscle mass index (PMI) in 200 adult patients undergoing LDLT at our institution between January 2008 and October 2013. Correlations of IMAC with other factors, overall survival rates in patients classified according to IMAC or PMI, and risk factors for poor survival after LDLT were analyzed. IMAC was significantly correlated with age (r = 0.229, P = 0.03) and PMI (r = -0.236, P = 0.02) in males and with age (r = 0.349, P < 0.001) and branched-chain amino acid (BCAA)-to-tyrosine ratio (r = -0.250, P = 0.01) in females. The overall survival rates in patients with high IMAC or low PMI were significantly lower than those for patients with normal IMAC or PMI (P < 0.001, P < 0.001, respectively). Multivariate analysis showed that high IMAC [odds ratio (OR) = 3.898, 95% confidence interval (CI) = 2.025-7.757, P < 0.001] and low PMI (OR = 3.635, 95% CI = 1.896-7.174, P < 0.001) were independent risk factors for death after LDLT. In conclusion, high IMAC and low PMI were closely involved with posttransplant mortality. Preoperative quality and quantity of skeletal muscle could be incorporated into new selection criteria for LDLT. Perioperative nutritional therapy and rehabilitation could be important for good outcomes after LDLT.

Left-sided major hepatectomy with en bloc resection of the hepatoduodenal ligament utilizing a liver-transection first approach: A video vignette.

TECHNIQUE: Hepatoduodenal ligamentectomy (HL) is a challenging surgery for advanced perihilar cholangiocarcinoma extensively invading the hepatoduodenal ligament1-3. A liver-transection first approach in HL is a no-touch technique wherein liver transection is performed first, and the affected liver and hepatoduodenal ligament are removed en bloc. This approach allows for the early assessment of resectability and feasibility of vascular reconstruction4. RESULTS: This video shows a 57-year-old man with advanced intrahepatic cholangiocarcinoma in the left hepatic lobe, which had directly invaded the perihilar region and the hepatoduodenal ligament via lymph node metastasis. The lymph node was extensively invasive into both the proper hepatic artery and portal vein. The case was initially deemed unresectable, but after three months of chemotherapy, conversion surgery was considered feasible. The common hepatic artery and gastroduodenal artery and then the common bile duct and main trunk of portal vein were secured at the pancreatic superior border. Hepatic dissection was performed along the Cantlie line. The right Glissonean pedicle was secured, including the right hepatic duct, right hepatic artery and right portal vein, and the operation was deemed feasible. The portal vein was dissected and reconstructed using the right external iliac vein. The left and caudate lobe with the middle hepatic vein and hepatoduodenal ligament were resected en bloc. Subsequentially, the common hepatic artery and right hepatic artery were reconstructed using the jejunal artery. CONCLUSION: The liver-transection first approach allowed us to determine the resectability of en bloc resection of the hepatoduodenal ligament at an early stage of surgery.