T Cell CEACAM1-TIM-3 Crosstalk Alleviates Liver Transplant Injury in Mice and Humans.

BACKGROUND & AIMS: Carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) acts through homophilic and heterophilic interactions with T cell immunoglobulin domain and mucin domain-containing protein 3 (TIM-3), which regulates innate immune activation in orthotopic liver transplantation (OLT). We investigated whether cluster of differentiation (CD) 4+ T cell-dependent CC1-TIM-3 crosstalk may affect OLT outcomes in mice and humans. METHODS: Wild-type (WT) and CC1-deficient (CC1 knock-out [KO]) mouse livers were transplanted into WT, CC1KO, or T-cell TIM-3 transgenic (TIM-3Tg)/CC1KO double-mutant recipients. CD4+ T cells were adoptively transferred into T/B cell-deficient recombination activating gene 2 protein (Rag2) KO recipients, followed by OLT. The perioperative liver-associated CC1 increase was analyzed in 50 OLT patients. RESULTS: OLT injury in WT livers deteriorated in CC1KO compared with CC1-proficient (WT) recipients. The frequency of TIM-3+CD4+ T cells was higher in WT than CC1KO hosts. Reconstitution of Rag2KO mice with CC1KO-T cells increased nuclear factor (NF)-κB phosphorylation and OLT damage compared with recipients repopulated with WT T cells. T-cell TIM-3 enhancement in CC1KO recipients (WT â†’ TIM3Tg/CC1KO) suppressed NF-κB phosphorylation in Kupffer cells and mitigated OLT injury. However, TIM-3-mediated protection was lost by pharmacologic TIM-3 blockade or an absence of CC1 in the donor liver (CC1KO â†’ TIM-3Tg/CC1KO). The perioperative CC1 increase in human OLT reduced hepatocellular injury, early allograft dysfunction, and the cumulative rejection rate. CONCLUSIONS: This translational study identifies T cell-specific CC1 signaling as a therapeutic means to alleviate OLT injury by promoting T cell-intrinsic TIM-3, which in turn interacts with liver-associated CC1 to suppress NF-κB in Kupffer cells. By suppressing peritransplant liver damage, promoting T-cell homeostasis, and improving OLT outcomes, recipient CC1 signaling serves as a novel cytoprotective sentinel.

Is Palliative Gastrojejunostomy for Malignant Gastric Outlet Obstruction an Optimal Choice for Very Elderly Patients? A Report from a Long-Lived Country.

BACKGROUND: Gastrojejunostomy (GJ) is a surgical option for malignant gastric outlet obstruction (mGOO). Confronting an aging society, the demand to treat elderly cancer patients with unresectable malignancies is increasing; however, the benefit of GJ to the very elderly (≥ 80 years of age) has never been investigated. METHODS: This multicenter, retrospective review included 108 patients who had undergone GJ for mGOO from two medical centers in Japan, one of the most long-lived countries. Patients were divided into two groups, with 80 years of age as the cut-off. Various factors, including surgical complications and patient survival, were compared. RESULTS: GJ in the very elderly (aged ≥ 80 years) was associated with a higher incidence of surgical complications (p = 0.049), such as delayed gastric emptying (DGE; p < 0.001), aspiration pneumonia (p = 0.029), and consequent mortality (p = 0.016). Age ≥80 years was also identified as an independent predictor of DGE (odds ratio 6.444, p = 0.005) and survival after GJ (hazard ratio 7.767, p = 0.016). In particular, the median survival time after GJ in the population aged ≥80 years with gastric cancer was only < 2 months. About the surgical procedure, antiperistaltic anastomosis with partial stomach partitioning (PSP) yielded the lowest occurrence rate of DGE (3.4%) and aspiration pneumonia (1.7%). CONCLUSIONS: GJ does not seem to be the optimal choice for very elderly patients, particularly those with gastric cancer. If performed, antiperistaltic anastomosis with PSP should be employed to reduce the surgical complications.

Surgeons' involvement in COVID-19 treatment: a practice by a regional core hospital in Japan to avoid physician burnout.

BACKGROUND: To prevent task accumulation on certain divisions, our institution developed a unique system of allocating inpatient treatment of COVID-19 patients to doctors who were not specialized in respiratory infections. The objective of this study was to investigate whether surgeons can be involved in the COVID-19 inpatient treatment without negatively affecting patient outcome, and how such involvement can affect the wellbeing of surgeons. METHODS: There were 300 patients diagnosed with COVID-19 and hospitalized from January to June 2021, and 160 of them were treated by the redeployed doctors. They were divided into 3 groups based on the affiliation of the treating doctor. Patient characteristics and outcomes were compared between the groups. In addition, the impact of COVID-19 duty on participating surgeons was investigated from multiple perspectives, and a postduty survey was conducted. RESULTS: There were 43 patients assigned to the Department of Surgery. There were no differences in the backgrounds and outcomes of patients compared with other groups. The surgeon's overtime hours were significantly longer during the duty period, despite no change in the number of operations and the complication rate. The questionnaire revealed that there was a certain amount of mental and physical burden from the COVID-19 duty. CONCLUSION: Surgeons can take part in inpatient COVID-19 treatment without affecting patient outcome. However, as such duty could negatively affect the surgeons' physical and mental wellbeing, further effort is needed to maintain the balance of fulfilling individual and institutional needs.

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.

Occult bacteremia in living donor liver transplantation: a prospective observational study of recipients and donors.

PURPOSE: To investigate the incidence and clinical impact of occult bacteremia in liver transplantation (LT). METHODS: This prospective observational study involved a fixed-point observation for up to 2 weeks after living donor LT in 20 recipients, with 20 donors as comparison subjects. Bacteria in the blood samples were detected using the ribosomal RNA-targeted reverse-transcription quantitative polymerase chain reaction method. To identify the causality with the gut microbiota (GM), fecal samples were collected and analyzed simultaneously. RESULTS: Occult bacteremia was identified in four recipients (20%) and three donors (15%) before the operation, and in seven recipients (35%) and five donors (25%) after the operation. Clostridium leptum subgroup, Prevotella, Colinesella, Enterobacteriaceae, and Streptococcus were the main pathogens responsible. Although it did not negatively affect the donor post-hepatectomy outcomes, the recipients with occult bacteremia had a higher rate of infectious complications post-LT. The GM analyses showed fewer post-LT predominant obligate anaerobes in both the recipients and donors with occult bacteremia. CONCLUSIONS: Occult bacteremia is a common condition that occurs in both donors and recipients. While occult bacteremia generally remains subclinical in the healthy population, there is potential risk of the development of an apparent post-LT infection in recipients who are highly immunosuppressed.

Association Between Constipation and a Reduction in Lower Limb Muscle Strength in Preoperative Patients with Thoracic Spinal Tumors.

Objective To investigate the clinical symptoms experienced by patients with thoracic spinal tumors and verify the associated symptoms that are predictive of a decline in muscle strength in the lower limbs. Methods A single-center, retrospective cross-sectional study was conducted on in-patients diagnosed with epidural thoracic spinal tumors between January 2011 and May 2021. The study involved a review of electronic medical records and radiographs and the collection of clinical data. The differences in clinical manifestations between patients with constipation and those without constipation were analyzed. Binary logistic regression analyses were performed to identify risk factors associated with a decline in muscle strength in the lower limbs.Results A total of 227 patients were enrolled, including 131 patients with constipation and 96 without constipation. The constipation group had a significantly higher proportion of patients who experienced difficulty walking or paralysis compared to those without constipation prior to surgery (83.2% vs. 17.7%, χ2 = 99.035,P < 0.001). Constipation (OR = 9.522, 95%CI: 4.150-21.849, P < 0.001) and urinary retention (OR = 14.490, 95%CI: 4.543-46.213, P < 0.001) were independent risk factors for muscle strength decline in the lower limbs. Conclusions The study observed that patients with thoracic spinal tumors who experienced constipation symptoms had a higher incidence of lower limb weakness. Moreover, the analysis revealed that constipation and urinary retention were independent risk factors associated with a preoperative decline in muscle strength of lower limbs.

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.

Dysbiosis and Depletion of Fecal Organic Acids Correlate With the Severity of Rejection After Rat Liver Transplantation.

The impact of T cell-mediated rejection (TCMR) after liver transplantation (LT) on the alterations in the gut microbiota (GM) and associated intestinal environment represented by fecal organic acids (OAs) require further elucidation. A rat allogeneic LT model was prepared without immunosuppressants or antibiotics, and a syngeneic model was used as a control. Qualitative and quantitative analyses of fecal samples at fixed time points were performed. Correlation analyses were also performed between liver function and GMs and OA levels. In the allogeneic TCMR group, the number of predominant obligate anaerobes decreased as liver function declined. Clostridioides difficile, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus were significantly increased. Regarding fecal OA concentration, short-chain fatty acid (SCFA) concentrations were depleted as liver function declined. In contrast, in the syngeneic group, GM and OAs exhibited only slight, transient, and reversible disturbances. In addition, alanine aminotransferase and total bilirubin were positively correlated with the number of Enterobacteriaceae and Enterococcus, and negatively correlated with the fecal concentration of SCFAs. The allogeneic TCMR model demonstrated distinct dysbiosis and depletion of fecal OAs as TCMR progressed after LT. The degree of graft injury was closely related to the number of specific bacterial strains and the concentrations of fecal SCFAs.

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.

Donor-dominant one-way matching of human leukocyte antigen-A/B/DR alleles predicts graft-versus-host disease following living donor liver transplantation.

AIM: Graft-versus-host disease (GVHD) following liver transplantation is rare but fatal. Therefore, it is important to identify possible risk factors before transplantation. Although it has been suggested that donor-dominant one-way human leukocyte antigen (HLA) matching of three loci (HLA-A/B/DR) is associated with the occurrence of GVHD, the precise significance of HLA matching including HLA-C/DQ/DP remains unclear. METHODS: We retrospectively analyzed the impact of donor-dominant one-way HLA matching at six HLA loci at the allele level on GVHD using clinical registry data from 1759 cases who underwent living donor liver transplantation between June 1990 and June 2019. We extracted cases with donor-dominant one-way HLA matching at the antigen level and reconfirmed them at the allele level using preserved DNA samples. RESULTS: Three of four cases (75%) who developed GVHD showed donor-dominant one-way HLA matching at three HLA-A/B/DR loci. These cases also showed donor-dominant one-way HLA matching at HLA-C/DQ/DP. Three of six cases (50%) with donor-dominant one-way HLA matching at three loci of HLA-A/B/DR developed GVHD. Notably, none of the cases with donor-dominant one-way HLA matching at one or two HLA-A/B/DR loci developed GVHD, irrespective of matching status at HLA-C/DQ/DP. The HLA matching status at the antigen level was revised in 22 of 56 cases, following reconfirmation at the allele level. CONCLUSIONS: Pairing of donors and recipients with donor-dominant one-way HLA matching at three HLA-A/B/DR loci should be avoided to prevent GVHD. No impact of HLA-C/DQ/DP on GVHD was identified. For liver transplantation, HLA genotypes should be determined at the allele level.

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.

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.

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.

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 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.

Older Donor Age Is a Risk Factor for Negative Outcomes After Adult Living Donor Liver Transplantation Using Small-for-Size Grafts.

Adult-to-adult living donor liver transplantation (ALDLT) using small-for-size grafts (SFSGs), ie, a graft with a graft-to-recipient weight ratio (GRWR) <0.8%, has been a challenge that should be carefully dealt with, and risk factors in this category are unclear. Therefore, we aimed to examine the risk factors and outcomes of ALDLT using SFSGs over a 13-year period in 121 patients who had undergone their first ALDLT using SFSGs. Small-for-size syndrome (SFSS), early graft loss, and 1-year mortality were encountered in 21.6%, 14.9%, and 18.4% of patients, respectively. By multivariate analysis, older donor age (≥45 years) was an independent risk factor for SFSS (odds ratio [OR], 4.46; P = 0.004), early graft loss (OR, 4.11; P = 0.02), and 1-year mortality (OR, 3.76; P = 0.02). Child-Pugh C class recipients were associated with a higher risk of SFSS development (P = 0.013; OR, 7.44). Despite no significant difference between GRWR categories in the multivariate outcome analysis of the whole population, in the survival analysis of the 2 donor age groups, GRWR <0.6% was associated with significantly lower 1-year survival than the other GRWR categories in the younger donor group. Moreover, in the high final portal venous pressure (PVP) group (>15 mm Hg), younger ABO-compatible donors showed 100% 1-year survival with a significant difference from the group of other donors. Older donor age was an independent risk factor for SFSS, early graft loss, and 1-year mortality after ALDLT using SFSGs. GRWR should not be <0.6%, and PVP modulation is indicated when grafts from older or ABO-incompatible donors are used.

Risk-benefit point of the Model for End-stage Liver Disease score in patients waiting for deceased-donor liver transplantation: A single-center experience.

AIM: To clarify the risk-benefit point of the Model for End-stage Liver Disease (MELD) score in patients waiting for deceased-donor liver transplantation (DDLT). METHODS: The present study retrospectively investigated 213 patients registered on the waiting list at Kyoto University (Kyoto, Japan) between 2005 and 2016. Patients were stratified by MELD score (6-9/10-14/15-20/21-30/31-40) and classified into two groups: the DDLT group (30 patients) and the waiting group (183 patients). Their post-registration mortality risk and long-term survival were compared. RESULTS: For all MELD categories, the mortality risk was lower in the DDLT group than in the waiting group. The hazard ratio of post-registration mortality decreased in the DDLT group compared to the waiting group as the MELD score increased (0.36/0.12/0.06/0.042/0.004). Survival was significantly better among patients in the DDLT group with a MELD score of 15 or more than among patients in the waiting group. CONCLUSION: For all MELD categories, DDLT reduced the mortality risk of patients on the waiting list.

Outcomes of endoscopic and microscopic transsphenoidal surgery on non-functioning pituitary adenomas: a systematic review and meta-analysis.

Both microscopic and endoscopic transsphenoidal surgery are effective approaches for nonfunctioning pituitary adenomas. The issue on the comparison of their efficacy and safety remains inconsistent. A thorough search of the literatures (PubMed, EMBASE, MEDLINE) were performed up to March 2017. Studies reporting outcomes of microscopic or endoscopic transsphenoidal surgery on nonfunctioning pituitary adenomas were included. A meta-analysis was performed focusing on the early stage and long term outcomes. The final search yielded 19 eligible studies enrolling 3847 patients, 389 of them underwent microscopic approach and 3458 of them with endoscopic approach. As to the early stage outcomes, the rate of gross tumor resection was significantly higher in the endoscopic group than that in microscopic group (73% versus 60%, P < 0.001). Meanwhile, endoscopic approach showed priority over microscopy on postoperative hypopituitarism (63% versus 65%, P < 0.001) and CSF leakage (3% versus 7%, P < 0.001). For the long term outcomes, the rate of visual improvement was significant higher in the endoscopic group than that in microscopic group (77% versus 50%, P < 0.001). However, there was no significant difference between the groups regarding the rate of permanent diabetic insipidus and meningitis. The endoscopic approach may be associated with higher rate of gross tumor movement and lower risk of postoperatively complications for treating nonfunctioning pituitary adenoma, when compared with microscopic approach. However, the confidence was shorted due to limited high quality evidence (largely randomized and controlled studies).

Is Portal Venous Pressure Modulation Still Indicated for All Recipients in Living Donor Liver Transplantation?

There is a consensus that portal venous pressure (PVP) modulation prevents portal hypertension (PHT) and consequent complications after adult-to-adult living donor liver transplantation (ALDLT). However, PVP-modulation strategies need to be updated based on the most recent findings. We examined our 10-year experience of PVP modulation and reevaluated whether it was necessary for all recipients or for selected recipients in ALDLT. In this retrospective study, 319 patients who underwent ALDLT from 2007 to 2016 were divided into 3 groups according to the necessity and results of PVP modulation: not indicated (n = 189), indicated and succeeded (n = 92), and indicated but failed (n = 38). Graft survival and associations with various clinical factors were investigated. PVP modulation was performed mainly by splenectomy to lower final PVP to ≤15 mm Hg. Successful PVP modulation improved prognosis to be equivalent to that of patients who did not need modulation, whereas failed modulation was associated with increased incidence of small-for-size syndrome (SFSS; P = 0.003) and early graft loss (EGL; P = 0.006). Among patients with failed modulation, donor age ≥ 45 years (hazard ratio [HR], 3.67; P = 0.02) and ABO incompatibility (HR, 3.90; P = 0.01) were independent risk factors for graft loss. Survival analysis showed that PVP > 15 mm Hg was related to poor prognosis in grafts from either ABO-incompatible or older donor age ≥ 45 years (P < 0.001), but it did not negatively affect grafts from ABO-compatible/identical and young donor age < 45 years (P = 0.27). In conclusion, intentional PVP modulation is not necessarily required in all recipients. Although grafts from both ABO-compatible/identical and young donors can tolerate PHT, lowering PVP to ≤15 mm Hg is a key to preventing SFSS and consequent EGL with grafts from either ABO-incompatible or older donors.