Hepatectomy for hepatocellular carcinoma after perioperative management of portal hypertension.

BACKGROUND: Indications for hepatectomy in patients with hepatocellular carcinoma (HCC) who have portal hypertension (PH) have been controversial. Some studies have concluded that PH is a contraindication to hepatectomy, whereas others have suggested that perioperative prophylactic management (PPM) can help overcome complications after hepatectomy associated with PH. The objective of this retrospective study was to assess the short- and long-term outcomes after hepatectomy for HCC in patients with PH, with or without PPM. METHODS: Records were reviewed of consecutive patients who underwent hepatectomy for HCC, with or without PPM of PH, in a single institution from 1994 to 2015. Patients were divided into three groups: those who received PPM for PH (PPM group), patients who had PH but did not receive PPM (no-PPM group) and those without PH (no-PH group). RESULTS: A total of 1259 patients were enrolled, including 123 in the PPM group, 181 in the no-PPM group and 955 in the no-PH group. Three- and 5-year overall survival rates were 74·3 and 53·1 per cent respectively in the PPM group, 69·2 and 54·9 per cent in the no-PPM group, and 78·1 and 64·2 per cent in the no-PH group (P = 0·520 for PPM versus no PPM, P = 0·027 for PPM versus no PH, and P < 0·001 for no PPM versus no PH). Postoperative morbidity and mortality rates were 26·0 and 0·8 per cent respectively in the PPM group, 29·8 and 1·1 per cent in the no-PPM group, and 20·3 and 0 per cent in the no-PH group. CONCLUSION: The present study has demonstrated acceptable outcomes among patients with HCC who received appropriate management for PH in an Asian population. Enhancement of the safety of hepatic resection through use of PPM may provide a rationale for expansion of indications for hepatectomy in patients with PH.

Thermo-, photo-, and mechano-responsive liquid crystal networks enable tunable photonic crystals.

Tunable photonic crystals exhibiting optical properties that respond reversibly to external stimuli have been developed using liquid crystal networks (LCNs) and liquid crystal elastomers (LCEs). These tunable photonic crystals possess an inverse opal structure and are photo-responsive, but circumvent the usual requirement to contain dye molecules in the structure that often limit their applicability and cause optical degradation. Herein, we report tunable photonic crystal films that reversibly tune the reflection peak wavelength under thermo-, photo- and mechano-stimuli, through bilayering a stimuli-responsive LCN including azobenzene units with a colourless inverse opal film composed of non-responsive, flexible durable polymers. By mechanically deforming the azobenzene containing LCN via various stimuli, the reflection peak wavelength from the bilayered film assembly could be shifted on demand. We confirm that the reflection peak shift occurs due to the deformation of the stimuli-responsive layer propagating towards and into the inverse opal layer to change its shape in response, and this shift behaviour is repeatable without optical degradation.

Outflow Reconstruction Using Cryopreserved Homologous Venous Grafts in Living Donor Liver Transplantation.

OBJECTIVES: The techniques and outcomes of outflow reconstruction in living donor liver transplantation (LDLT) using cryopreserved homologous veins at the University of Tokyo Hospital are presented. METHODS: We performed 540 LDLTs from January 1996 to March 2015. Graft types included right liver graft (n = 262), left liver graft (n = 196), left lateral sector graft (n = 53), and posterior sector graft (n = 28). We routinely use cryopreserved homologous vein grafts for the hepatic vein reconstructions to secure the large outflow of the graft. In addition to the presentation of our techniques, the cases with symptomatic outflow obstruction and the treatments were also investigated. RESULTS: The 1-, 3-, and 5-year graft survival rates were 90.6%, 86.1%, and 83.5%, respectively. The incidence of severe complications (Clavien-Dindo grade IIIb and more) was 38%. The overall incidence of outflow obstruction requiring invasive treatment was 1.9% (10/540), including 3 left liver grafts (1.5%, 3/196) and 7 right liver grafts (2.7%, 7/262). Regarding the patency of the reconstructed veins, the left hepatic vein, middle hepatic vein, and right hepatic vein achieved nearly 100% patency. On the contrary, venous tributaries such as V5, V8, and inferior right hepatic vein were frequently occluded in the postoperative course. CONCLUSIONS: Outflow reconstruction is a key for the successful LDLT. Cryopreserved homologous vein graft is useful for the promising hepatic vein reconstruction.

Living Liver Donor Selection and Resection at the University of Tokyo Hospital.

OBJECTIVES: Donor selection and operative procedures for adult-to-adult living donor liver transplantation at the University of Tokyo are presented. METHODS: Donor selection criteria are as follows: age between 20 and 65 years, within 3 degrees of consanguinity, without coercion, free from any major comorbidities, body mass index (BMI) < 30, and ABO blood type identical or compatible. Liver biopsy is indicated for BMI > 25 kg/m(2) or any liver function abnormality, and those with macroscopic steatosis >10% are rejected. Thereafter, an indocyanine green retention test and dynamic computed tomography are evaluated. Graft type is determined based on computed tomography volumetry. An estimated graft volume of 40% to recipient standard liver volume ratio is the lower limit. For donor safety, the left liver is the first choice, provided that it satisfies the lower limit. Otherwise, right liver harvesting is indicated, providing that the estimated remnant liver volume is >30% of the donor's total liver volume. A posterior sector graft is a possible option. RESULTS: Between 1996 and 2014, 462 donor hepatectomies were performed, with 257 right livers, 179 left livers, and 26 posterior sectors. There was no mortality, and the incidence of morbidity grades I, II, IIIa, and IIIb was 16%, 5%, 5%, and 3%, respectively, without a difference between right and left liver grafts. The left liver was used without impairing recipient outcome. Two aborted hepatectomies (0.4%) and 3 near-miss events (0.6%) were encountered. CONCLUSIONS: Maximal effort should be applied to donor selection and operation for donor safety.

Use of a Right Lateral Sector Graft in Living Donor Liver Transplantation Is Feasible, but Special Caution Is Needed With Respect to Liver Anatomy.

Right lateral sector (RLS) grafting has been introduced to enlarge the potential donor pool for living donor liver transplantation (LDLT); however, evidence of its feasibility is limited. Data from 437 LDLTs carried out between 2000 and 2013 were analyzed retrospectively. LDLTs using a right liver graft (n = 251) were compared with those using a RLS graft (RLSG; n = 28). No donor mortality occurred, and the major complication rates were similar between the two groups. Postoperative liver function preservation was better in the RLSG donors. Concerning the recipients, the mortality and overall survival rates were similar between the two groups. The complication rate for the recipients was higher when more than two arterial or biliary anastomoses were necessary. A systematic literature search identified four reports on LDLT using RLSGs. Among 66 LDLTs, including the present series, there were no cases of donor death, and the rates of major and minor complications in the donors were 6% and 29%, respectively. The major complication and overall mortality rates in the recipients were 29% and 6%, respectively. LDLT using an RLSG is feasible, with an acceptable survival rate among the recipients.

Adult right living-donor liver transplantation with special reference to reconstruction of the middle hepatic vein.

Two hundred fifty-three consecutive living-donor liver transplant recipients with a right liver graft (RLG) were divided into three groups: an extended right liver graft (ERLG) group (n = 47) in which the middle hepatic vein (MHV) trunk was included in the graft, a modified right liver graft (MRLG) group (n = 114) in which the MHV tributaries were reconstructed with cryopreserved homologous veins and a simple RLG group (n = 92) in which the MHV tributaries were sacrificed. The volume of the anterior sector was significantly impaired in the RLG group compared to the other two groups, whereas the volume of the posterior sector was significantly improved in the RLG group, indicating that the impaired anterior sector regeneration by MHV deprivation was compensated by the posterior sector regeneration. The regeneration rate of the anterior sector was highest in the ERLG group (92%), moderate in the MRLG group (71%) and lowest in the RLG group (52%). The whole graft regeneration rate of the ERLG group was significantly higher than that of the other two groups. Poor regeneration, however, was not correlated with delayed functional recovery or long-term outcome. Short-term, the patency of reconstructed MHV tributaries was over 90%, but occlusion occurred frequently over the long-term, especially in V5.

A single-center experience of the use of interleukin-2 receptor antagonists for various situations in liver transplant recipients.

BACKGROUND: Interleukin-2 receptor antagonists (IL2Ra) are used mainly for (1) induction as an adjunct to conventional immunosuppression, (2) induction to facilitate calcineurin inhibitor (CNI) or steroid minimization, and (3) induction to facilitate steroid avoidance in hepatitis C virus (HCV)-positive recipients. The aim of this study was to present our strategy for IL2Ra rescue therapy and its outcome. METHODS: A total of 20 patients were treated with IL2Ra at our institute for the following indications: (1) rescue for acute rejection (n = 13), (2) CNI sparing in cases of CNI toxicity (n = 5), and (3) induction for complicated cases (n = 2). RESULTS: Rescue therapy for steroid-resistant rejection and rejection in HCV-positive recipients was successful in 11 cases, but 2 grafts were lost due to uncontrollable rejection. CNI cessation was successfully achieved with IL2Ra treatment in 3 cases with thrombotic microangiopathy and 2 cases of encephalopathy, with complete cure of these life-threatening complications of CNI. Induction with IL2Ra was successful in 2 complicated cases, 1 for CNI sparing due to renal failure and the other for adjunct immunosuppression in a case of positive lymphocytotoxic crossmatch. The overall patient/graft survival and the rate of infectious complications were comparable between those with and without IL2Ra treatment. CONCLUSIONS: IL2Ra could be safely and effectively used after liver transplantation in various situations.

Thrombotic microangiopathy after living-donor liver transplantation.

Thrombotic microangiopathy (TMA) is an infrequent but severe life-threatening disorder in solid organ transplant recipients. Few studies of TMA in living donor liver transplant (LDLT) recipients, however, have been reported. We investigated the clinical characteristics and prognostic factors of TMA after LDLT. Among 393 adult LDLT recipients, 30 patients (7.6%) were identified to have TMA. The 1-, 3- and 5-year survival rates of these patients were lower (60.6%, 52.5% and 47.7%, respectively) than those of patients without TMA (93.0%, 89.0% and 87.3%, respectively). Multivariate analysis confirmed that reduced administration of fresh frozen plasma and sensitization against HLA are closely related with TMA (odds ratio [OR]: 2.6 and 16.1, respectively). However, a review of the cases revealed that individual responses to treatment varied considerably and the main etiologies were difficult to determine. A comparison of the clinical factors suggested that late onset (>30 days), poor response to treatment and delayed diagnosis and/or treatment are associated with a poor outcome. Because the prevention of TMA in LDLT patients is difficult, early diagnosis and initiation of intensive therapies may be crucial to improve the prognosis.

Impact of live donor age (>or=50) on liver transplantation.

BACKGROUND: The question of whether donor age negatively impacts recipient outcome in adult-to-adult living donor liver transplantation (LDLT) is rarely discussed. The aim of this study was to evaluate the impact of older donor age (50 years or older) on recipient outcomes in adult-to-adult LDLT. METHODS: LDLT data were retrospectively evaluated from our 299 LDLT cases in 297 recipients, which were divided into 2 groups: a younger group (group Y, donor age<50, n=237) and an older group (Group O, donor age>or=50, n=62). Clinical parameters of both recipients and donors were comparable between groups. RESULTS: There was no difference between the groups in patient survival or postoperative complications of either donors or recipients. In recipients, graft regeneration was significantly impaired in Group O. Graft function, including protein synthesis and cholestasis, was comparable between the 2 groups. CONCLUSION: Although the regeneration capacity of aged grafts was impaired, the function of grafts from older donors was comparable to that of those from younger donors. There was no difference in the clinical outcomes between the groups.

Preemptive treatment of fungal infection based on plasma (1 --> 3)beta-D-glucan levels after liver transplantation.

BACKGROUND: Invasive fungal infection remains a major challenge in liver transplantation and the mortality rate is high. Early diagnosis and treatment are required for better results. PATIENTS: We prospectively measured plasma (1 --> 3)beta-D-glucan (BDG) levels in 180 living donor liver transplant recipients for 1 year after surgery. Fungal infection was defined as proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group. Preemptive treatment (intravenous fluconazole and trimethoprim-sulfamethoxazole) was started when the BDG level was greater than 40 pg/ml. RESULTS: Twenty-four patients (13%) were diagnosed with invasive fungal infection. The responsible pathogens included Candida spp. in 14 cases, Aspergillus fumigatus in 5, Cryptococcus neoformans in 3, and Pneumocystis jiroveci in 2. Preemptive treatment was performed in 22% of patients (n = 40). Renal impairment and mild gastrointestinal intolerance due to the drugs were observed in 28% (11/40) of patients during treatment. Among them 14 patients were diagnosed with fungal infection including seven candidiasis, five aspergillosis, and two Pneumocystis jiroveci pneumonia. The sensitivity and specificity of BDG for overall fungal infection was 58% and 83%, respectively, with a positive predictive value of 35% and a negative predictive value of 93%, and a positive likelihood ratio of 3.41 and a negative likelihood ratio of 1.98. The overall mortality for fungal infection in our series was 0.6%. CONCLUSION: Although the sensitivity and positive predictive value were low, the low mortality rate after fungal infection and the mild side effects of the preemptive treatment might justify our therapeutic strategy. Based on the effectiveness, this strategy warrants further investigation.

Phosphorylation and interaction of the movement and coat proteins of brome mosaic virus in infected barley protoplasts.

The 3a movement protein (B3a) of brome mosaic virus (BMV) plays essential roles in the cell-to-cell movement of BMV. B3a is known to bind nucleic acids, to transport RNA to neighbouring cells, and to form tubular structures. Here, we tested the assumption that phosphorylation may be a mechanism that regulates B3a functions and showed that not only B3a but also the coat protein, BCP, was phosphorylated in BMV-infected barley protoplasts. Both BCP and B3a were detected in a complex immunoprecipitated from BMV-infected protoplasts with anti-B3a antiserum, implying an interaction between BCP and B3a.

Rapid and high-resolution detection of IgH gene rearrangements using PCR and melting curve analysis.

The analytical methods of Southern blot hybridization (SBH) and the polymerase chain reaction (PCR) for complementarity determining region-3 (CDR3) are fundamental for detecting IgH gene rearrangement. However, there are problems stemming from the characteristics of both methods; especially, the long turn around time (TAT) because of the complex process in the SBH, and the low analytical sensitivity for amplicons in the PCR. Thus, to improve the PCR procedure, we investigated the application of detecting the clonal amplicons based on the different melting Temperature (T(m)) in internal melting domains corresponding to the CDR3 hypervariable region. Our new protocol is based on the combination of a LightCycler Technology with high-speed amplification, and Idaho-Technology with rapid and high-resolution melting curve analysis (MCA), designated PCR-MCA. This method can provide the results within 3 h with an analytical sensitivity of 10(-3). The diagnostic sensitivity and specificity relative to the results documented with the SBH analysis were 89.2% and 100%, respectively. This indicates that the new protocol of PCR-MCA is acceptable for clinical testing; especially, PCR-MCA is relevant in terms of the rapid and sensitive detection of IgH clonality within amplicons.

Successful treatment of disseminated Nocardia farcinica infection in a living-donor liver transplantation recipient.

Nocardiosis is a serious infection with high mortality. We report a case of subcutaneous and neural lesions due to Nocardia farcinica infection after living-donor liver transplantation. The neural lesion was cured with antibiotics without drainage.

Impact of celiac axis stenosis on living donor hepatectomy.

BACKGROUND: Celiac axis stenosis was once cited as a reason for exclusion from living donor liver transplantation. Donor hepatectomy, however, leaves the pancreaticoduodenal artery arcade untouched, and theoretically, celiac axis stenosis has no impact on otherwise possible donors. METHODS: Among 350 consecutive adult living donors of liver transplantation at Tokyo University Hospital, we experienced 11 (3%) donors with celiac axis stenosis or occlusion due to the median arcuate ligament. RESULTS: Harvesting of the right liver was the most common procedure (n = 8), followed by harvesting of segments II and III (n = 2), and left liver (n = 1). The postoperative course was uneventful in all of the donors. CONCLUSIONS: Our results indicate that donor hepatectomy can be safely performed in the presence of significant celiac artery stenosis.

Hemophagocytic syndrome after adult-to-adult living donor liver transplantation.

Hemophagocytic syndrome is a fatal complication after liver transplantation that is rarely reported. Among 260 adult patients who underwent living donor liver transplantation at our hospital, three cases (1%) were complicated with hemophagocytic syndrome. Intensive investigation revealed Aspergillus, cytomegalovirus, and hepatitis C virus as the most likely causative organisms in each patient. Despite the immediate initiation of anti-infectious treatment and supportive care, all patients died. When pancytopenia with possible underlying infectious disease is observed in liver transplant recipients, hemophagocytic syndrome should be suspected and bone marrow biopsy considered. The prognosis of hemophagocytic syndrome remains poor and further investigations are required to establish effective therapeutic options.

Renal impairment after living donor liver transplantation.

BACKGROUND: There are few reports of postoperative renal impairment after living donor liver transplantation (LDLT). METHODS: We reviewed 246 LDLT recipients to examine the effects of postoperative renal impairment on the results of LDLT. RESULTS: The incidence of renal impairment and the requirements for postoperative renal replacement therapy were 29% and 9%, respectively. Intraoperative blood loss (P<.0001) and preoperative serum creatinine (P=.0002) were significant independent risk factors for the development of early renal dysfunction. Patients who required renal replacement therapy had a lower survival rate (P=.01). CONCLUSIONS: We identified the risk factors for postoperative renal impairment, providing useful metrics to establish a treatment strategy for high risk liver transplant patients.

Clinical outcomes of uterine sarcomas: results from 14 years worth of experience in the Kinki district in Japan (1990-2003).

To review clinical outcomes and therapeutic varieties, we were invited to submit data from the patients who were treated for uterine sarcomas in Japan from 1990 to 2003. Uterine sarcomas were defined as leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and carcinosarcoma (CS). Of a total of 97 patients, 36 (37.1%) were diagnosed with LMS of the uterine corpus, 15 (15.5%) with ESS, 46 (47.4%) with CS. Median age at diagnosis was 59 (21-85) years. Clinical stages based on FIGO were 41 (42.3%) with stage I disease, 6 (6.2%) with staged II, 34 (35.1%) with stage III, and 16 (16.5%) with stage IV. The median follow-up period for all patients was 13 (1-108) months and median disease-free period was 9 (0-96) months. The 1-year survival rate and disease-free survival (DFS) rate were calculated in patients with all sarcomas (overall survival [OAS], 61.3%; DFS, 46.6%). Statistical analysis showed that younger age (less than 50 years), early stage (stages I and II), and surgical procedure (extended hysterectomy [EH] and radical hysterectomy [RH]) were associated with significantly better OAS. Histologic types did not affect the survival period. In conclusion, aggressive surgery including EH or RH at the time of initial operation offers the possibility of prolonged survival.

Proviral status of HTLV-1 integrated into the host genomic DNA of adult T-cell leukemia cells.

Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and leukemic cells always carry the proviral genome monoclonally integrated into their host genomes at the same sequence site, designated as the monoclonal integration. Using Southern blot hybridization (SBH) and sequenced tagged site polymerase chain reaction assays, we examined the proviral status in 558 clinical specimens from 350 patients who are suspected to have ATL. A total of 321 specimens (57.5%) from 241 patients showed positive results for the monoclonal integration according to SBH, using EcoR1 and Pst1. The 241 patients consisted of 136 patients (56.4%) with the complete provirus (C-type), 62 patients (25.7%) with a defective provirus (D-type), and 43 patients (17.8%) with multibands (M-type). The incidence of the D- and M-types were in the order of smoldering, chronic, and acute subtypes of ATL, suggesting that such an aberrant proviral status is generated on the way to multistep carcinogenesis and is subsequently clinically important for the malignant behavior of the disease. Moreover, our data showed that the partial deletion of the proviral genome is initiated first at the site of the gag region and spreads into the sites of the pol and env regions, whereas the long terminal repeats and pX regions are almost always conserved. These results suggest that analysis of the proviral status provides useful diagnostic and virologic-oncological information about ATL and HTLV-1 pathology, especially the important role of pX gene in tumorigenesis.

Relation between the middle hepatic vein drainage area volume and alanine aminotransferease after left liver harvesting.

Complete outflow is impossible to maintain on both sides in donors undergoing hemiliver graft harvesting, because the middle hepatic vein (MHV) can be preserved on only one side. The area in which outflow veins are disrupted becomes congested and does not sufficiently regenerate. The relation between changes in alanine aminotransferase (ALT) and the congestive area volume of the congestive area is unknown. The 64 subjects presented herein were living donors who provided the left liver with the caudate lobe and MHV trunk. The midpoint between the tributaries of the MHV and the right hepatic vein was determined preoperatively using computed tomography. The midpoint between the tributaries of the MHV and right hepatic vein and the borderline between the right and left liver were used to predict the MHV drainage area volume. ALT was measured in donors on postoperative days 1, 3, 5, 7, 10, and 14. The patients were divided into three groups according to the ratio of calculated MHV drainage area volume in the remnant right liver: less than 15% (n = 21, group A); greater than 15% and less than 20% (n = 18, group B); greater than 20% (n = 25, group C). There were significant differences in the ALT levels between groups (P = .004). MHV drainage area volume, calculated using the present method, was associated with high ALT levels after left liver harvesting with the MHV. The present study suggests that persistently high ALT levels are associated with the volume of the interrupted MHV drainage area.

Cryptococcosis after living donor liver transplantation: report of three cases.

Cryptococcosis is the third most common invasive fungal infection in solid organ transplantation, which usually occurs more than 6 months after the primary operation. In our series of 180 consecutive adult living-donor liver transplantation recipients, three (1.5%) had cryptococcosis and one of these patients died. The serum cryptococcal antigen examination was positive in all three patients who suffered from cryptococcosis. The serum cryptococcal antigen test might contribute to the early detection and treatment of cryptococcosis.