Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Muscularity Defined by the Combination of Muscle Quantity and Quality is Closely Related to Both Liver Hypertrophy and Postoperative Outcomes Following Portal Vein Embolization in Cancer Patients.

BACKGROUND: Portal vein embolization (PVE) is a common procedure for preventing hepatic insufficiency after major hepatectomy. While evaluating the body composition of surgical patients is common, the impact of muscularity defined by both muscle quantity and quality on liver hypertrophy after PVE and associated outcomes after major hepatectomy in patients with hepatobiliary cancer remain unclear. METHODS: This retrospective review included 126 patients who had undergone hepatobiliary cancer resection after PVE. Muscularity was measured on preoperative computed tomography images by combining the skeletal mass index and intramuscular adipose content. Various factors including the degree of hypertrophy (DH) of the future liver remnant and post-hepatectomy outcomes were compared according to muscularity. RESULTS: DH did not differ by malignancy type. Patients with high muscularity had better DH after PVE (P = 0.028), and low muscularity was an independent predictor for poor liver hypertrophy after PVE [odds ratio (OR), 3.418; 95% confidence interval (CI), 1.129-10.352; P = 0.030]. In subgroup analyses in which patients were stratified into groups based on primary hepatobiliary tumors and metastases, low muscularity was associated with higher incidence of post-hepatectomy liver failure (PHLF) ≥ grade B (P = 0.018) and was identified as an independent predictor for high-grade PHLF (OR 3.931; 95% CI 1.113-13.885; P = 0.034) among the primary tumor group. In contrast, muscularity did not affect surgical outcomes in patients with metastases. CONCLUSIONS: Low muscularity leads to poor liver hypertrophy after PVE and is also a predictor of PHLF, particularly in primary hepatobiliary cancer.

Factors associated with early postoperative exercise tolerance after living-donor liver transplantation.

BACKGROUND: Physical dysfunction, including exercise intolerance, is a major factor for delayed societal reintegration for patients who underwent living-donor liver transplantation (LDLT). However, what may contribute to early postoperative physical function is not well known. The purpose of this study is to elucidate the perioperative factors affecting early posttransplant exercise intolerance. METHODS: 103 consecutive patients who underwent LDLT were enrolled, and 68 patients were retrospectively analyzed. We examined the relationship between postoperative exercise tolerance evaluated by a 6-minute walking distance (6MWD) at discharge after surgery and demographic data, surgical information, preoperative physical function, clinical course, and the postoperative decline in physical function with univariate and multivariate analyses. RESULTS: Almost all patients were discharged within 3 months after surgery. The postoperative 6MWD was 408 ± 94 m (68 [61-84]% of the predicted value), and patients who had a low %6MWD at discharge had significantly lower preoperative physical function than patients who had a high %6MWD at discharge (grip strength: 29.8 ± 8.9 kgf vs. 23.0 ± 8.8 kgf, P < .01, knee extensor strength: 138.9 ± 59.4 Nm vs. 95.2 ± 42.1 Nm, P < .01). Multivariate analysis revealed that preoperative knee extensor strength (standardized ß = 0.35, P < .01) and first postoperative walking day (standardized ß = -0.22, P = .04) were independently associated with the postoperative %6MWD. CONCLUSION: These results suggest that maintaining preoperative muscle strength and allowing for early postoperative mobilization might help to enhance the recovery of physical function and facilitate the patient's social reintegration after LDLT.

Intraoperative High Fraction of Inspiratory Oxygen is Independently Associated with Worse Outcome After Living-Donor Liver Transplantation: A Retrospective Study.

BACKGROUND: Ischemia and reperfusion injury is an important factor that determines graft function after liver transplantation, and oxygen plays a crucial role in this process. However, the relationship between the intraoperative high fraction of inspiratory oxygen (FiO2) and living-donor-liver-transplantation (LDLT) outcome remains unclear. PATIENTS AND METHODS: A total of 199 primary adult-to-adult LDLT cases in Kyoto University Hospital between January 2010 and December 2017 were enrolled in this study. The intraoperative FiO2 was averaged using the total amount of intraoperative oxygen and air and defined as the calculated FiO2 (cFiO2). The cutoff value of cFiO2 was set at 0.5. RESULTS: Between the cFiO2 <0.5 (n = 156) and ≥0.5 group (n = 43), preoperative recipients' background, donor factors, and intraoperative parameters were almost comparable. Postoperatively, the cFiO2 ≥0.5 group showed a higher early allograft dysfunction (EAD) rate (P = 0.049) and worse overall graft survival (P = 0.036) than the cFiO2 <0.5 group. Although the cFiO2 ≥0.5 was not an independent risk factor for EAD in multivariable analysis (OR 2.038, 95%CI 0.992-4.186, P = 0.053), it was an independent risk factor for overall graft survival after LDLT (HR 1.897, 95%CI 1.007-3.432, P = 0.048). CONCLUSION: The results of this study suggest that intraoperative high FiO2 may be associated with worse graft survival after LDLT. Avoiding higher intraoperative FiO2 may be beneficial for LDLT recipients.

Implementation of advance care planning decision aids for patients undergoing high-risk surgery: a field-testing study.

BACKGROUND: Patients undergoing high-risk surgery are at a risk of sudden deterioration of their health. This study aimed to examine the feasibility of the development of two patient decision aids (PtDAs) to assist patients undergoing high-risk surgeries in informed decision-making about their medical care in a crisis. METHODS: This field testing implemented two PtDAs that met the international criteria developed by the researchers for patients before surgery. Study participants were patients scheduled to be admitted to the intensive care unit after surgery at one acute care hospital in Japan and their families. The study used a mixed-methods approach. The primary outcome was patients' decision satisfaction evaluated by the SURE test. Secondary outcomes were the perception of the need to discuss advance care planning (ACP) before surgery and mental health status. The families were also surveyed on their confidence in proxy decision-making (NRS: 0-10, quantitative data). In addition, interviews were conducted after discharge to assess the acceptability of PtDAs. Data were collected before (preoperative outpatients, baseline: T0) and after providing PtDAs (in the hospital: T1) and following discharge (T2, T3). RESULTS: Nine patients were enrolled, of whom seven agreed to participate (including their families). The SURE test scores (mean ± SD) were 2.1 ± 1.2 (T0), 3.4 ± 0.8 (T2), and 3.9 ± 0.4 (T3). The need to discuss ACP before surgery was 8.7 ± 1.3 (T1) and 9.1 ± 0.9 (T2). The degree of confidence in family surrogate decision-making was 6.1 ± 2.5 (T0), 7.7 ± 1.4 (T1), and 8.1 ± 1.5 (T2). The patients reported that using PtDAs provided an opportunity to share their thoughts with their families and inspired them to start mapping their life plans. Additionally, patients wanted to share and discuss their decision-making process with medical professionals after the surgery. CONCLUSIONS: PtDAs supporting ACP in patients undergoing high-risk surgery were developed, evaluated, and accepted. However, they did not involve any discussion of patients' ACP treatment wishes with their families. Medical providers should be coached to provide adequate support to patients. In the future, larger studies evaluating the effectiveness of PtDAs are necessary.

Corticosteroid-associated osteonecrosis of the femoral head after orthotopic liver transplantation and the outcomes of subsequent total hip arthroplasty.

BACKGROUND: Corticosteroids are essential for immunosuppression after orthotopic liver transplantation (OLT), but also have many side effects. Osteonecrosis of the femoral head (ONFH) is one of the most serious complications requiring prostheses. However, few studies have investigated ONFH after OLT. The purpose of this study is to survey the incidence of corticosteroid-induced ONFH after OLT and the outcomes of total hip arthroplasty (THA). METHODS: Between January 2001 and December 2010, a series of 926 patients underwent OLT at our Hospital. A retrospective analysis was performed on a total of 738 patients who survived at least 2 years after OLT. The incidence of symptomatic ONFH, the interval from OLT to the initial diagnosis of ONFH, and the cumulative dose of corticosteroids were analyzed. The side effects related to OLT, such as other osteonecrosis lesions, osteoporotic fractures, and infection, were monitored. For patients who underwent THA, radiological findings and Japanese Orthopaedic Association (JOA) scores were evaluated. RESULTS: ONFH occurred in 10 patients (13 hips) (6 men [7 hips], 4 women [6 hips]), with an incidence of 1.36%. The average age at OLT was 51.4 years (range, 31-61 years). The average interval from OLT to ONFH was 86.7 months (range, 22-155 months). The average cumulative dose of corticosteroids was 7274 mg (range, 1342-29,514 mg). Twenty patients suffered from side effects related to OLT. Seven patients (8 hips) underwent THA. No adverse events including infection arose during the perioperative process. One hip dislocated, and one femoral stem displayed a radiolucent line. The average JOA score improved from 45.4 (range, 25-76) preoperatively to 86.9 (range, 73-99) at final follow-up. No patients required revision surgery. CONCLUSIONS: The incidence of symptomatic ONFH after OLT was 1.36%. Once the graft function becomes stable, THA can be a safe and effective treatment option for patients with ONFH after OLT.

Surgery for Recurrent Hepatocellular Carcinoma: Achieving Long-term Survival.

OBJECTIVE: To evaluate the long-term outcomes of surgery for recurrent hepatocellular carcinoma (HCC). BACKGROUND: HCC recurs with high incidence after liver resection. Little is known about long-term outcomes of patients undergoing surgery for recurrent HCC. METHODS: Among 989 patients who underwent R0/R1 liver resection for HCC between 1995 and 2014, 676 patients who exhibited recurrence were included. Repeat surgery was performed in 128 patients (RS group), and not in the remaining 548 patients (NS group). Prognostic value after repeat surgery was evaluated by comparing survival after recurrence (SAR) between the RS and NS groups. Subgroup analyses according to the 3 recurrence patterns [intrahepatic recurrence (IHR), extrahepatic recurrence (EHR), and intra plus extrahepatic recurrence (IHR + EHR)] were performed. RESULTS: Seventy-three of 430 patients (17.0%) with IHR, 17 of 57 patients (29.8%) with EHR, and 38 of 189 patients (20.1%) with IH + EHR underwent repeat surgery. Compared with the NS group, the RS group had better liver function and their time to recurrence was significantly longer (16.5 vs 11.4 months; P < 0.001). In the overall and 3 recurrence patterns, the 5-year SAR rate was better in the RS group compared with the NS group (RS vs NS group; overall, 53.0% vs 25.7%; IHR, 73.8% vs 37.2%; EHR, 30.0% vs 0%; IHR + EHR, 34.1% vs 10.6%; all P < 0.001, respectively). On multivariate analysis, repeat surgery was identified as an independent factor for better SAR (P < 0.001). CONCLUSION: Surgery for recurrent HCC may yield long-term survival for not only IHR but also for EHR in selected patients.

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients.

Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha-fetoprotein, Model for End-Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest-risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest-risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2-14.2] vs. 70.6% [48.3-92.9] and PDC:4.6% [0.1%-9.8%] vs. 47.1% [22.6-71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C-index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index = 0.71) and OS (C-index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.

Identifying Patients Who May Benefit from Liver Resection Compared to Living Donor Liver Transplantation for Hepatocellular Carcinoma Using 18F-FDG PET.

BACKGROUND: This study aimed to assess an oncologic setting where patients with hepatocellular carcinoma (HCC) could benefit from liver resection (LR) compared to living donor liver transplantation (LDLT) using 18F-fluorodeoxyglucose (FDG) positron emission tomography. METHODS: The consecutive data of patients with HCC who underwent 18F-FDG PET before LR (LR group, n = 314) and LDLT (LDLT group, n = 65) between 2003 and 2015 were retrospectively analyzed. Tumor 18F-FDG avidity was quantified as the tumor to liver standardized uptake value ratio (TLR, cut-off value was defined at 2). Multivariate analysis was performed to assess significant preoperative tumor factors in the LR group. Survival outcomes between the two groups were stratified by these factors. RESULTS: The 5-year overall survival (OS: 56.9% vs. 73.8%, LR vs. LDLT, p < 0.001) and recurrence-free survival rate (RFS: 27.4% vs. 70.7%, p < 0.001) were significantly better in the LDLT group compared to the LR group. In the LR study, multivariate analysis identified TLR and tumor multiplicity as significant preoperative tumor factors for OS. In patients with solitary and TLR < 2 HCC, the 5-year OS rate was not significantly different between the LR and LDLT groups (70.3% vs. 71.8%, p = 0.352); meanwhile, RFS rate was better in the LDLT group (34.3% vs. 71.8%, p = 0.001). CONCLUSIONS: LDLT is associated with better long-term outcomes than LR in patients with HCC; however, selected patients with solitary and TLR < 2 HCC may benefit from LR.

The combination of a male donor's high muscle mass and quality is an independent protective factor for graft loss after living donor liver transplantation.

We evaluated the hypothesis that grafts from donors with high muscle mass and quality may have a better outcome after living-donor-liver-transplantation (LDLT) than those from usual donors. A total of 376 primary adult-to-adult LDLT cases were enrolled in this study. Donor skeletal muscle mass index (SMI) and intramuscular adipose tissue content (IMAC) were used as markers of muscle mass and quality. In male donor cases (n = 198), those with higher SMI and lower IMAC than age-adjusted values were defined as the "high muscularity donors" (n = 38) and the others were defined as the "control" (n = 160). The high muscularity donor showed better 1-year (97% vs 82%, P = .020) and overall graft survival rate (88% vs 67%, P = .024) than the control group after LDLT. Contrastingly, the influence of the muscularity was not observed in female donor cases. Multivariable analysis including donor age confirmed that a high muscularity donor was an independent protective factor for overall graft survival after LDLT (hazard ratio, 0.337; 95% CI: 0.101-0.838; P = .017). Our study first confirmed that high muscle mass and quality of a male donor is a protective factor of allograft loss after LDLT, independently from donor age.

Long-term impact and clinical significance of living donor liver transplantation with respect to donor liver restoration and spleen size: A prospective study.

This study aimed to evaluate postoperative long-term liver restoration and splenic enlargement and their clinical significance in living donor liver transplantation. One hundred and sixteen donors who had donated livers more than 5 years previously accepted the invitation to participate in this study. The liver restoration rate and the splenic enlargement rate were calculated as the rate with respect to the original volume. The mean liver restoration rate was 0.99 ± 0.12 and older age was associated with a higher incidence for liver restoration rate <0.95 (P = .005), whereas type of donor operation was not. The donors with liver restoration rate <0.95 showed lower serum albumin levels than those with liver restoration rate ≥0.95. The mean splenic enlargement rate was 1.10 ± 0.16. Right lobe donors demonstrated higher splenic enlargement rate (1.14 ± 0.18) than left lobe/lateral segment donors (1.06 ± 0.13). In the donors with splenic enlargement rate ≥1.10, platelet count was not fully restored to the preoperative level. In conclusion, older age increases the risk for incomplete postoperative liver restoration, which may be associated with a decrease in albumin more than 5 years after donation. Right lobe donation poses a risk of splenic enlargement, which is associated with incomplete restoration of platelet count.

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.

Proposed Definition for Oligometastatic Recurrence in Biliary Tract Cancer Based on Results of Locoregional Treatment: A Propensity-Score-Stratified Analysis.

BACKGROUND: Oligometastatic recurrence involves relapsed tumors for which locoregional treatment (LT) may yield a survival benefit. However, there are no clear criteria for selecting patients for LT or determining the effects of LT in recurrent biliary tract cancer (BTC). The aim of this retrospective study is to assess the effects of LT on survival outcomes and to identify potential criteria for selecting LT in recurrent BTC. PATIENTS AND METHODS: In the present work, 232 consecutive patients with recurrent BTC who initially underwent curative surgery between 1996 and 2015 were evaluated. The primary outcome was length of survival after recurrence (SAR). Propensity score stratification with various tumor-related factors was used to identify patients who would likely benefit from LT. RESULTS: Among the cohort, 60 (25.9%) patients underwent LT, whereas 172 (74.1%) patients did not. The multivariate Cox model identified carbohydrate antigen 19-9 levels of > 50 U/mL, multiorgan recurrence, tumor number > 3, tumor size > 30 mm, and early recurrence (≤ 1 year) as independent predictors of poor SAR (P < 0.001 for each factor). In the propensity-score-stratified analysis, LT was associated with survival benefits for patients representing single-organ recurrence with at most three tumors and late-onset recurrence (> 1 year) (median SAR: 48.6 vs. 14.2 months, n = 33 vs. n = 34, hazard ratio: 0.10, 95% confidence interval: 0.04-0.20, P < 0.001). CONCLUSIONS: Patients with recurrent BTC may benefit from LT if they have single-organ recurrence with at most three tumors and late-onset recurrence. We propose that these patients may have clinically relevant "oligometastatic recurrence" of BTC.

Pretransplantation splenomegaly frequently persists after liver transplantation and can manifest as hypersplenism and graft fibrosis - a retrospective study.

The risk factors and clinical impact of post-transplantation splenomegaly (SM) are poorly understood. We investigated the predictors and impacts of post-transplantation SM in 415 LT patients at Kyoto University Hospital from April 2006 to December 2015. First, the predictors and clinical consequences of SM three years post-transplantation were analyzed among spleen-preserved recipients. Second, the clinical data of surviving recipients three years post-transplantation were compared between splenectomized and spleen-preserved recipients. There was no difference in indication for liver transplantation between these two groups. Third, survival outcomes were compared between splenectomized and spleen-preserved recipients. SM was determined as a SV/body surface area (BSA) higher than 152 ml/m2 . In the first analysis, preoperative SM occurred in 79.9% recipients and SM persisted three years post-transplantation in 72.6% recipients among them. Preoperative SV/BSA was the only independent predictor of three year post-transplantation SM, which was associated with lower platelet (PLT), white blood cell (WBC) counts and significant graft fibrosis (21.4% vs. 2.8%). In the second analysis, spleen-preservation was related to lower PLT, WBC counts and a higher proportion of significant graft fibrosis (26.7% vs. 7.1%) three years post-transplantation. In the third analysis, spleen-preserved recipients showed worse survival than splenectomized recipients. In conclusion, preoperative SM frequently persists more than three years post-transplantation and is associated with subclinical hypersplenism, graft fibrosis, graft loss, and even death.

Use of Nakanuma staging and cytokeratin 7 staining for diagnosing recurrent primary biliary cholangitis after living-donor liver transplantation.

AIM: Diagnosis of primary biliary cholangitis (PBC), which recurs in approximately 30% of liver transplant recipients, is histology-based, but no staging system has been established for recurrent PBC (rPBC). We used the Nakanuma staging system and cytokeratin 7 (CK7) staining to examine post-transplant liver biopsy specimens retrospectively and to evaluate histological features of rPBC. METHODS: From 107 patients who underwent living donor liver transplantation for PBC, 60 recipients with 214 liver biopsies after 1-year post transplant were enrolled. Fibrosis, bile duct loss (BL), cholangitis activity, hepatitis activity, and CK7-positive hepatocytes were scored. Nakanuma staging was based on fibrosis and BL scores. We examined the correlation of scores and clinicolaboratory data among rPBC patients. We also evaluated whether chronological change of stage was correlated with liver-related failure. RESULTS: Of 214 biopsies, 52 were protocol biopsy; 162 were episodic. Higher BL, cholangitis activity, and hepatitis activity scores were associated with rPBC diagnosis. At median follow up of 10.0 years (range 1.4-18.7 years), 29 (48%) patients were diagnosed with rPBC at 4.6 years (range 1.3-14.5 years). Liver-related failure occurred in five rPBC cases; three from rPBC, and two from chronic rejection. At rPBC diagnosis, higher BL and CK7 scores were more frequent in patients who developed liver-related failure than in other patients (P = 0.04, P < 0.01, respectively). In failure patients, the Nakanuma stage increased over time, and reached up to stage 4, whereas the Scheuer stage did not reach above stage 3. CONCLUSIONS: Nakanuma staging is associated with rPBC and disease progression. Scores for BL and CK7 might be early markers for progressive rPBC.

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.

Recent evolution of living donor liver transplantation at Kyoto University: How to achieve a one-year overall survival rate of 99%?

Previously, living donor liver transplantation was considered as a "high-risk, high-return" medical treatment due to the relatively high short-term mortality. It is our task to change "high-risk, high-return" into a "low-risk, high-return" situation. In this review article, the recent evolutions in living donor liver transplantation for both donors and recipients at Kyoto University such as portal vein pressure modulation, hybrid donor operation, and perioperative management considering sarcopenia, focusing on improvement of short-term outcomes are described. Under a paradigm of "marketing and innovation", various innovations and efforts have been made over the last decade aiming at improving the short-term outcomes of both donors and recipients. By doing so, excellent short-term results after living donor liver transplantation have been achieved, along with a potentially epoch-making discoveries.

Structure and surgical dissection layers of the bare area of the liver.

BACKGROUND: The bare area was reportedly formed by direct adhesion between the liver and diaphragm, meaning that the bare area lacked serosal components. This study aimed to analyze the structure of the bare area by an integrated study of surgical and laparoscopic images and pathological studies and describe surgical procedures focusing on the multilayered structure. METHODS: Several surgical specimens of hepatectomy were analyzed histologically to evaluate the macroscopic structure of the bare area. Laparoscopic images and cadaver anatomy of the bare area were also examined. RESULTS: The multilayered structure of the bare area comprised the liver, sub-serosal connective tissue, liver serosa, parietal peritoneum, retroperitoneal connective tissue, epimysium of the diaphragm, and diaphragm, in order from the liver to the diaphragm. The liver serosa and the parietal peritoneum fused with each other. This multilayered structure of the bare area is observed almost constantly. There are two layers in the dissection of the bare area in surgical procedures, an outer layer of the fused peritoneum (near the diaphragm) and an inner layer of the fused peritoneum (near the liver). Laparoscopic images enabled us to recognize the multilayered structure of the bare area. CONCLUSIONS: Histopathological findings showed the bare area to be a multilayered structure. In cases where tumors are located underneath the bare area, it could be important to dissect the bare area, with careful attention to its multilayered structure. Surgical dissection of the bare area in the outer layer of the fused peritoneum could allow a sufficient safety margin.

Impact of imbalanced graft-to-spleen volume ratio on outcomes following living donor liver transplantation in an era when simultaneous splenectomy is not typically indicated.

The impact of an imbalanced graft-to-spleen volume ratio (GSVR) on posttransplant outcomes other than postreperfusion portal hypertension remains unknown. The importance of GSVR might vary according to whether simultaneous splenectomy (SPX) is performed. This retrospective study divided 349 living donor liver transplantation (LDLT) recipients from 2006 to 2017 into 2 groups: low GSVR (≤0.70 g/mL) and normal GSVR (>0.70 g/mL). The cutoff value of GSVR was set based on the first quartile of the distributed data. Graft survival and associations with various clinical factors were investigated between the groups according to whether SPX was performed. Low GSVR did not affect outcomes when SPX was performed. In contrast, it was associated with an increased incidence of early graft loss (EGL) and poor graft survival by presenting posttransplant thrombocytopenia, cholestasis, coagulopathy, and massive ascites when the spleen was preserved. Among patients with a preserved spleen, the multivariable analysis results revealed that older donor age and low GSVR were independent risk factors for graft loss. In conclusion, low GSVR was an independent predictor of graft loss after LDLT when the spleen was preserved. Preserved spleen with extremely low GSVR may be related to persistent hypersplenism, impaired graft function, and consequent EGL.

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.