Revisiting the safety of living liver donors by reassessing 441 donor hepatectomies: is a larger hepatectomy complication-prone?

Donor safety is of paramount importance in performing living donor liver transplantation (LDLT). We retrospectively reviewed donor medical records to confirm whether larger donor hepatectomy is absolutely complication-prone. A total of 441 living donor hepatectomies were performed between October 1996 and July 2012 in our institute, which were divided into three eras (Era I, October 1996 to March 2004; Era II, April 2004 to March 2008; Era III, April 2008 to July 2012) and the incidences of postoperative complications were compared among the three types of hepatectomy-right hepatectomy (RH), left hepatectomy (LH) and left lateral segmentectomy (LLS). Although severe complications (Clavien's grade 3 or more) frequently occurred in RH in Eras I and II (15.4% and 10.7%, respectively), the incidence in Era III decreased to the comparable level observed in LH and LLS (5.4% in RH, 2.3% in LH and 5.3% in LLS). The incidence of postoperative complications did not relate to the type of hepatectomy selected in the latest era. Since most complications after hepatectomy were considered preventable, step-by-step meticulous surgical procedures are a prerequisite for further assuring donor safety irrespective of the type of hepatectomy selected.

Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis.

BACKGROUND: Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT). METHODS: Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed. RESULTS: Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively. CONCLUSIONS: Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis.

Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia.

The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult-to-adult LDLT grafts without anatomical, immunological or hepatitis-related issues were included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH-20) was used to characterize PGD. DFH-20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH-20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PT-INR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH-20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH-20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality.

The impact of IL28B genetic variants on recurrent hepatitis C in liver transplantation: significant lessons from a dual graft case.

IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients.

Prognostic significance of inflammatory biomarkers in hepatocellular carcinoma following hepatic resection.

Background: Cancer-related inflammation has been correlated with cancer prognosis. This study evaluated inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), programmed death ligand (PD-L) 1 expression, and tumour microenvironment in relation to prognosis and clinicopathological features of patients with hepatocellular carcinoma (HCC) undergoing curative hepatic resection. Methods: Patients who had liver resection for HCC in 2000-2011 were analysed. Univariable and multivariable analyses were conducted for overall (OS) and recurrence-free (RFS) survival. Immunohistochemical analyses of PD-L1, CD8 and CD68 expression were performed. HCC cell lines were evaluated for PD-L1 expression. A subgroup analysis was conducted to determine patient features, survival and the tumour microenvironment. Results were validated in a cohort of patients with HCC treated surgically in 2012-2016. Results: Some 281 patients who underwent hepatic resection for HCC were included. Multivariable analysis showed that low LMR was an independent prognostic factor of OS (hazard ratio (HR) 1·59, 95 per cent c.i. 1·00 to 2·41; P = 0·045) and RFS (HR 1·47, 1·05 to 2·04; P = 0·022) after resection. Low preoperative LMR values were correlated with higher α-fetoprotein values (P < 0·001), larger tumour size (P < 0·001), and high rates of poor differentiation (P = 0·035) and liver cirrhosis (P = 0·008). LMR was significantly lower in PD-L1-positive patients than in those with PD-L1 negativity (P < 0·001). Results were confirmed in the validation cohort. PD-L1 expression was upregulated in HCC cell lines treated with interferon-γ and co-cultured with THP-1 monocyte cells. Conclusion: LMR is an independent predictor of survival after hepatic resection in patients with HCC. Modulation of the immune checkpoint pathway in the tumour microenvironment is associated with a low LMR.

Real-Time Ultrasound-Guided Thrombectomy for Extensive Portal Vein Thrombosis in Living Donor Liver Transplantation.

Thrombectomy is a routine or common practice for treating organized portal vein thrombosis (PVT) during liver transplantation. However, this procedure is often performed in a blinded fashion and can result in insufficient thrombectomy or devastating consequences such as injury to the retropancreatic portal vein where prompt repair is very difficult. To overcome these drawbacks for blind thrombectomy, we herein describe a new technique that makes complex thrombectomy safe and easy under direct ultrasound vision. This procedure is readily available and highly reproducible and can be used as the standard procedure for treating extensive PVT.

Frontal cerebral blood flow change associated with infant-directed speech.

OBJECTIVE: To examine the auditory perception of maternal utterances by neonates using near-infrared spectroscopy (NIRS). METHODS: Twenty full-term, healthy neonates were included in this study. The neonates were tested in their cribs while they slept in a silent room. First, two probe holders were placed on the left and right sides of the forehead over the eyebrows using double-sided adhesive tape. The neonates were then exposed to auditory stimuli in the form of infant-directed speech (IDS) or adult-directed speech (ADS), sampled from each of the mothers, through an external auditory speaker. RESULTS: A 2 (stimulus: IDS and ADS) x 2 (recording site: channel 1 (right side) and channel 2 (left side)) analysis of variance for these relative oxygenated haemoglobin values showed that IDS (Mean = 0.25) increased brain function significantly (F = 3.51) more than ADS (Mean = -0.26). CONCLUSIONS: IDS significantly increased brain function compared with ADS. These results suggest that the emotional tone of maternal utterances could have a role in activating the brains of neonates to attend to the utterances, even while sleeping.

Successful Recombinant Thrombomodulin Treatment for Thrombotic Microangiopathy After Liver Transplantation: A Case Report.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but severe complication after liver transplantation. In contrast to other thrombotic microangiopathies, treatment for TA-TMA has yet to be clarified. A 52-year-old male patient with liver cirrhosis due to hepatitis C underwent split liver transplantation from a deceased donor. His clinical course was without complication until 4 days after transplantation, when he experienced impaired consciousness, hemolytic anemia with fragmented erythrocytes, and marked thrombocytopenia. TA-TMA was diagnosed, and recombinant thrombomodulin was administered for 4 days. The patient's clinical symptoms and laboratory data rapidly improved. He has been followed up for 6 months and has not shown any complications. The pathogenesis of TA-TMA is endothelial damage in the vasculature. Recombinant thrombomodulin, an endothelial cell-protecting agent, is a promising new therapeutic choice for TA-TMA after liver transplantation.

The comparative and developmental study of auditory information processing in autistic adults.

The present study examined brain functions related to information processing in autistic subjects, using auditory evoked potentials (AEP) and missing stimulus potentials (MSP). In order to study the development of autism, autistic adults served as subjects. Normal adults and children also served as control groups. Both normal and autistic adults showed normal patterns and lateralities with respect to AEP for music stimuli, but normal children did not show such matured patterns and lateralities. On the other hand, with respect to MSP, autistic adults showed matured patterns with a specific laterality. These results suggest that autistic subjects might develop some cognitive functions.

[A case of jejunal vein thrombosis due to medroxyprogesterone acetate].

The patient was a 68-year-old woman with advanced breast cancer which had been treated by modified radical mastectomy two years and nine months earlier. After the surgery, tamoxifen citrate (TAM) was orally administered in addition to various types of chemotherapy. Because the patient complained of nausea and weight loss, medroxyprogesterone acetate (MPA) was orally administered instead of TAM. The patient complained of intense abdominal pain on the 35th day of administration. Laparotomy was then performed for her acute abdominal problem. Because necrosis from bleeding due to jejunal vein thrombosis was observed in the jejunum for about 15 cm, resection of the jejunum was carried out. Histological observation demonstrated thrombosis in the vein, and cellular infiltration around the thrombosis. The postoperative prognosis has been favorable and the postoperative course is now being monitored at our clinic (2 months after surgery). The patient has no complications such as diabetes mellitus or hypercholesterolemia. The thrombosis observed in the jejunal vein, which is a rare site for it on the 35th day of MPA administration was induced by MPA. Due attention must be paid to the formation of thrombosis when using MPA.

[A case of colonic cancer with multiple liver metastases effectively treated by intra-arterial chemotherapy].

A 36-year-old female underwent sigmoidectomy and insertion of an intra-hepatic arterial catheter for advanced sigmoid cancer with multiple liver metastases. After the operation, intra-hepatic arterial infusion of the chemotherapeutic agents that showed sensitivity in the histoculture drug response assay (HDRA) to the liver metastasis was done for one year. The metastatic liver lesions other than those in the lateral segment which were fed by an accessory artery decreased remarkably. Therefore, we performed lateral segmentectomy. The patient has been doing well without recurrence for 18 months after the first operation. Intra-hepatic arterial infusion chemotherapy for liver metastasis from colorectal cancer can produce an excellent result with the use of sensitive chemotherapeutic agents.

[Interrelationship between the facial expression and familiarity: analysis using spatial filtering and inverted presentation].

We investigated interrelationship between the facial expression and familiarity using spatial filtering and inverted presentation. The stimuli were facial images (smiling and neutral faces) band-pass filtered in the spatial domain. If the filtering is carried out at low spatial frequencies, the images convey more global features than the local ones, whereas the local features are emphasized in the images filtered at high frequencies. The task of subjects was to judge the expression (Experiment 1) or familiarity (Experiment 2) of such images, which were presented in the upright or inverted orientation. The following results were obtained. 1) Spatial frequency components in the middle range (12.4 and 24.8 cycles/face-width) were important in recognizing both expression and familiarity, 2) there was close relationship between the facial expression and familiarity, and 3) smiling faces were harder to recognize when they are shown in the inverted orientation. These results suggest that there are the common and different recognition processes between facial expression and familiarity.

[Object-specific priming in apparent motion display].

The perceptual process of an object with multiple features mainly consists of two stages. At first, features are encoded independently at the modular level (feature level). Secondly, they are recombined to build a temporal representation of the object (conjunctive level). Using the apparent motion technique in which stimuli were defined by color and shape, we examined the levels at which the object-specific priming takes place. Although the discrimination of the second stimulus was facilitated when it shared the features with the first stimulus, the priming effects were different according to the number of stimulus items of the first frame. When the first frame contained one stimulus item, the priming benefits were obtained at the both conjunctive and the feature levels. However, the benefit was found only at the feature level when the item number was increased to eight (one of them disappeared in the following frames as the apparent motion stimulus). The roles of modular analysis and attention integration were discussed in terms of the economical validity of feature preservation in object perception.

Application of postoperative Model for End-Stage Liver Disease scoring system for evaluating liver graft function after living donor liver transplantation.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score has been validated to predict the mortality rate of patients with various chronic liver diseases on the waiting list for liver transplantation (LT). The aim of this study was to assess the value of the postoperative MELD scoring system as an early postoperative predictor of outcome in patients undergoing living donor LT (LDLT). METHODS: A retrospective analysis of 217 adult-to-adult LDLT patients was performed. The values of the MELD score on various postoperative days (PODs) as predictors of graft loss within 6 months after LDLT were examined by calculating the areas under the receiver operating characteristic (AUROC) curves. The 6-months graft survival rates were compared between patients with (n = 22) and without (n = 195) graft loss. Univariate and multivariate analyses were performed to identify the factors associated with mortality. RESULTS: The MELD score on POD2 was a predictor of graft loss, with an AUROC c-statistic of 0.779, a specificity of 79.5%, and a sensitivity of 68.2% at optimal cutoff, whereas the preoperative MELD score c-statistic was 0.605 with 44.6% sensitivity. Multivariate analyses for postoperative mortality revealed MELD-POD2 ≥19 (odds ratio, 5.601; 95% confidence interval [CI], 1.395-4.508; P = .0009) as an independent predictor of short-term graft loss following LDLT, in addition to preoperative hospitalization status. Later MELD POD scores were also predictive of graft loss. CONCLUSIONS: The early postoperative MELD scoring system is feasible as an index for prediction of postoperative mortality following LDLT.

rs8099917 and viral genotyping as indications for living donor liver transplantation for hepatitis C: a case report.

INTRODUCTION: Appropriate antiviral treatment is essential for living donor liver transplantation (LDLT) to be effective for treating hepatitis C. However, it has never been reported that pre-LDLT genetic analyses of both host and virus, with prediction of the outcome of post-LDLT antiviral treatment, indicated LDLT for a borderline case. CASE REPORT: We have reported the case of a 68-year-old woman with liver cirrhosis caused by genotype 1b hepatitis C, a history of ruptured esophageal varices, and adequately controlled minor ascites. Her liver function was classified as Child-Pugh grade B. The donor was a 42-year-old woman with an estimated left lobe graft volume (GV) of 33.8% based on the standard liver volume of the recipient. Molecular analyses used to confirm the indication of LDLT for this combination revealed the following: The rs8099917 genotype was T/T in the donor and recipient, the HCV core protein was double wild type, there were no mutations in the interferon sensitivity-determining region, and 8 mutations were found in the interferon/ribavirin resistance-determining region. LDLT was performed because very high sensitivity to interferon treatment was predicted. DISCUSSION: Six months after LDLT and uneventful post-LDLT courses, pegylated interferon-α2a and ribavirin were administered under immunosuppression with cyclosporine and mycophenolate mofetil. This regimen was continued for 48 weeks, resulting in a viral response at 10 weeks and a sustained viral response, as predicted. CONCLUSIONS: We have reported the usefulness of molecular analyses of host and viral factors for indicating LDLT to treat hepatitis C in a borderline case.

Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma.

We have proposed risk factors for tumor recurrence, such as tumor nodule ≥ 5 cm and des-gamma-carboxy prothrombin ≥ 300 mAU/mL after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors for HCC recurrence and mortality within our criteria. We enrolled 152 adult recipients who had undergone LDLT for end-stage liver disease with HCC who met our criteria. The recurrence-free survival rates after LDLT were calculated. Risk factors for tumor recurrence were identified. On univariate analysis, factors affecting recurrence-free survival were pretransplant treatment for HCC, neutrophil-to-lumphocyte ratio (NLR) >4, alpha-fetoprotein ≥ 400 ng/mL, ≥ 5 nodules, and bilobar tumor distribution. Multivariate analysis identified that NLR >4 and ≥ 5 nodules were independent risk factors for tumor recurrence after LDLT (P = .003 and P = .002, respectively). Two-step selection criteria enable selection of patients who have high-risk of tumor recurrence.

Developmental change in cognitive organization underlying stroop tasks of Japanese orthographies.

Cognitive processes underlying Stroop interference tasks of two Japanese orthographies, hiragana (a phonetic orthography) and kanji (a logographic orthography) were studied from the developmental point of view. Four age groups (first, second, third graders, and university students) were employed as subjects. Significant interference was yielded both in the hiragana and in the kanji version. Performance time on interference task decreased with age. For elementary school children, the error frequency on the interference task was higher than that on the task of naming patch colors or on the task of reading words printed in black ink, but the error frequencies did not differ among tasks for university students. In the interference task more word reading errors were yielded in the kanji version than in the hiragana version during and after third grade. The findings suggested that (1) the recognition system of hiragana and of kanji becomes qualitatively different during and after third grade, (2) the integrative system, which organizes cognitive processes underlying Stroop task, develops with age, and (3) efficiency of the organization increases with age.