Clinicopathological features of cytokeratin 5-positive pulmonary adenocarcinoma.

Cytokeratin 5 (CK5) is a marker for pulmonary squamous cell carcinoma; however, CK5 is sometimes present in pulmonary adenocarcinoma (ADC), and there is insufficient information regarding the clinicopathological features of CK5-positive ADC. We aimed to explore the clinicopathological characteristics of CK5-positive ADC using immunohistochemistry. We prepared the following two cohorts: a resected cohort containing 220 resected tumours for primarily studying the detailed morphological characteristics, and a tissue microarray (TMA) cohort containing 337 samples for investigating the associations of CK5 expression with other protein expressions, genetic and prognostic findings. CK5-positive ADC was defined to have ≥ 10% tumour cells and presence of CK5-positive tumour cells in the resected and TMA cohorts, respectively. CK5-positive ADCs were identified in 91 (16.3%) patients in the combined cohort. CK5-positive ADCs had male predominance (P = 0.012), smoking history (P = 0.001), higher stage (P < 0.001), histological high-grade components (P < 0.001), vascular invasion (P < 0.001), mucinous differentiation (P < 0.001), spread through airspaces (P < 0.001), EGFR wild-type (P < 0.001), KRAS mutations (P < 0.001), ALK rearrangement (P < 0.001) and ROS1 rearrangement (P = 0.002). In the resected cohort, more than half the CK5-positive ADCs (19 cases, 65.5%) showed mucinous differentiation; the remaining cases harboured high-grade components. In the TMA cohort, CK5-positive ADCs correlated with TTF-1 negativity (P = 0.002) and MUC5B, MUC5AC and HNF4alpha positivity (P < 0.001, 0.048, < 0.001). Further, CK5-positive ADCs had significantly lower disease-free and overall survival rates than CK5-negative ADCs (P < 0.001 for each). Additionally, multivariate analysis revealed that CK5 expression was an independent poor prognostic factor. CK5-positive ADCs showed aggressive clinical behaviour, with high-grade morphology and mucinous differentiation.

Internal anomalies in thalidomide embryopathy: results of imaging screening by CT and MRI.

AIM: To examine the prevalence and detailed radiological findings of internal anomalies in thalidomide embryopathy (TE). MATERIALS AND METHODS: Whole-body image screening for internal anomalies using unenhanced whole-body computed tomography (CT) and head magnetic resonance imaging (MRI) was performed in 22 patients (13 women and nine men; mean age, 49 years; range, 47-51 years) with TE. RESULTS: Among the 22 patients with TE, internal anomalies were detected in 19 (86.4%): anomalies of the auditory organ in 10 (45.5%), anomalies of the vascular system in six (27.3%), agenesis of the gallbladder in six (27.3%), hypoplasia or aplasia of the 7th or 8th cranial nerves in five (22.7%), block vertebrae in five (22.7%), fusion of the left lobe and quadrate lobe of the liver in three (9.1%), and others in five (22.7%), respectively. CONCLUSION: In addition to limb defects or hypoplasia, various internal anomalies can be detected at a high incidence in TE using CT and MRI. Understanding these characteristic radiological findings may help radiologists detect a wide range of radiological findings of internal anomalies associated with TE.

Dielectric spectroscopy of T-shaped blue-phase-III liquid crystal.

Dielectric relaxation spectra of a liquid crystalline (LC) material showing blue-phase-III (BPIII) for a considerably large temperature regime consisting of T-shaped molecules are investigated. A low frequency relaxation mode is observed in the isotropic phase (I) as well as in BPIII of the investigating material which is attributed to the short axis rotation of the T-shaped molecules. The outcome of the temperature and dc bias field variation of dielectric strength (Δε) and relaxation frequency (ν(c)) in the vicinity of the I-BPIII transition is also discussed. The temperature dependence of ν(c) in BPIII with a minor deviation from Arrhenius activities in the fluctuation-dominated nonlinear region (FDNLR) is found to follow the unusual thermal behavior of the activation energy (E(A)). The growth of pretransitional fluctuations is found to be nonlinear in the vicinity of the I-BPIII transition. A moderate growth of transition fluctuation commences from the value of the exponent α(eff)=0.38/°C, which is obtained by an exponential variation of ν(c) with respect to temperature in BPIII. Observed dynamic phenomenon in the vicinity of the I-BPIII transition regions is explained on the basis of the Landau-de Gennes and Maier-Saupe Theories.

Pediatric liver transplantation using reduced and hyper-reduced left lateral segment grafts: a 10-year single-center experience.

Few studies have examined the long-term outcomes and prognostic factors associated with pediatric living living-donor liver transplantation (LDLT) using reduced and hyper-reduced left lateral segment grafts. We conducted a retrospective, single-center assessment of the outcomes of this procedure, as well as clinical factors that influenced graft and patient survival. Between September 2000 and December 2009, 49 patients (median age: 7 months, weight: 5.45 kg) underwent LDLT using reduced (partial left lateral segment; n = 5, monosegment; n = 26), or hyper-reduced (reduced monosegment grafts; n = 18) left lateral segment grafts. In all cases, the estimated graft-to-recipient body weight ratio of the left lateral segment was more than 4%, as assessed by preoperative computed tomography volumetry, and therefore further reduction was required. A hepatic artery thrombosis occurred in two patients (4.1%). Portal venous complications occurred in eight patients (16.3%). The overall patient survival rate at 1, 3 and 10 years after LDLT were 83.7%, 81.4% and 78.9%, respectively. Multivariate analysis revealed that recipient age of less than 2 months and warm ischemic time of more than 40 min affected patient survival. Pediatric LDLT using reduced and hyper-reduced left lateral segment grafts appears to be a feasible option with acceptable graft survival and vascular complication rates.

The challenge of acute rejection in intestinal transplantation.

Early diagnosis and treatment of acute cellular rejection (ACR) after intestinal transplantation (ITx) is challenging. We report the outcome of three patients: two presented mild ACR improved with steroids. One presented steroid-resistant severe rejection, improved after rabbit anti-thymocyte globulin (r-ATG), but unfortunately died for encephalitis caused by opportunistic infections.

Effect of maintenance therapy with low-dose peginterferon for recurrent hepatitis C after living donor liver transplantation.

Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n =17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were -0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.

Lower limit of the graft-to-recipient weight ratio can be safely reduced to 0.6% in adult-to-adult living donor liver transplantation in combination with portal pressure control.

INTRODUCTION: The goal of this study was to examine whether the lower limit of the graft-to-recipient weight ratio (GRWR) can be safely reduced to make better use of a left-lobe graft in adult-to-adult living donor liver transplantation (LDLT) in combination with portal pressure control. PATIENTS AND METHODS: Beginning in December 2007, our institution actively selected left-lobe grafts for use in liver transplantation seeking to minimize the risks to healthy donors. We gradually decreased the lower limit of the GRWR to preferentially select a left-lobe over a right-lobe graft: from ≥0.7% beginning in December 2007 to ≥0.6% beginning in April 2009. A portal pressure control program, targeting final portal pressures below 15 mm Hg, was also introduced to overcome small-for-size graft problems. The ratio of left-lobe grafts among all adult-to-adult LDLT grafts and the donor complication rate (defined as Clavien grade ≥ III, excluding wound infection) were compared between two time periods: June 1999 to November 2007 (period 1, n = 541) and December 2007 to February 2010 (period 2, n = 119). Overall survival rates were also compared between those recipients of a GRWR < 0.8% and those with a GRWR ≥ 0.8% in 198 recipients who underwent LDLT at our institution between April 2006 and February 2010. RESULTS: Left-lobe grafts use increased from period 1 (65/541 recipients; 12.0%) to period 2 (50/119 recipients; 42.0%; P < .001). The donor complication rate tended to decrease from 13.8% in period 1 to 9.3% in period 2 (P = .115). The overall survival rate in 52 recipients with a GRWR < 0.8% did not differ from that in 146 recipients with a GRWR ≥ 0.8%. CONCLUSIONS: The lower limit of the GRWR can be safely reduced to 0.6% in adult-to-adult LDLT in combination with portal pressure control.

Supradiaphragmatic approach for Budd-Chiari syndrome with transjugular intrahepatic portosystemic shunt stent in combination with inferior vena cava reconstruction during living donor liver transplantation: a case report.

Treatment of Budd-Chiari syndrome consists of medical management, surgical shunt, transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation. Liver transplantation is indicated only when other treatments have failed. A 36-year-old Japanese man underwent living-donor liver transplantation after radiologic intervention procedures. Because of the position of the TIPS stent and the damaged vascular lesion of Budd-Chiari syndrome, a supradiaphragmatic approach was employed to achieve a safe total hepatectomy. Moreover, after resection of damaged portion of the inferior vena cava (IVC), an artificial vascular graft was utilized to fill the IVC gap. The postoperative course was uneventful; no serious complications were experienced within 2 years after liver transplantation. This supradiaphragmatic IVC approach and IVC reconstruction technique emphasized the option of surgical techniques to decrease the operative risk during liver transplantation for Budd-Chiari syndrome.

Graft loss and poor outcomes after living-donor liver transplantation owing to arterioportal shunts caused by liver needle biopsies.

BACKGROUND: Arterioportal shunts (APS) are well-known critical complications after liver transplantation (OLT). The aims of this study were to assess the frequency and causes of APS after OLT and to analyze APS patients with poor outcomes. PATIENTS: We evaluated 1415 OLT recipients retrospectively investigating APS cases. RESULTS: APS were detected in at least 9 patients (0.6%). All patients with APS had a history of posttransplant invasive procedures; percutaneous transhepatic cholangio drainage (n = 6) or needle biopsy (LNB; n = 3). Two patients with poor outcomes showed proximal APS caused by LNBs. The other 7 patients with distal APSs, showed stable conditions. Imaging findings in the 2 proximal APS patients revealed drastic changes in graft hemodynamics. Although they finally underwent re-OLT, their outcomes were poor, owing to fatal complications associated with advanced collaterals. CONCLUSION: We concluded that even careful LNBs can cause APS at unexpected points. Earlier, more aggressive treatments are required, especially for proximal APS patients.

Biliary anastomosis and biliary complications following living donor liver transplantation.

Biliary complications are one of the most important problems in liver transplantation. Regardless of various improvements of surgical technique, liver transplantation is associated with significant biliary problems. In this article, we have described a biliary anastomosis method with a continuous suture (CS) technique in the posterior wall and interrupted suture (IS) technique for the anterior wall. We performed this biliary reconstruction in 28 adult patients between September 2003 and August 2007. Prior to that time our procedure was a CS anastomosis for both the anterior and posterior walls. A 5-Fr catheter is inserted into the biliary system. The current biliary complication was 3 cases (13.0%) of stenosis at the anastomosis, which is lower than that for a CS anastomosis. This anastomosis reduced biliary complications and is simple.

Preemptive living donor liver transplantation in glycogen storage disease Ia: case report.

UNLABELLED: Even with substantial progress in the management of patients with glycogen storage disease type Ia (GSD-Ia), hepatic and renal complications may still develop during long-term follow-up. Herein, we report a case of preemptive living donor liver transplantation in a patient with GSD-Ia. PATIENT: The patient was a 5-year-old boy in whom GSD-Ia was diagnosed at age 10 months. Clinical symptoms included frequent hypoglycemic episodes, hyperlipidemia, hyperuricemia, and growth retardation, which were poorly controlled using conventional treatments. At age 5 years, frequent massive nasal bleeds developed, which led to severe anemia. The patient was brought to our institute for living donor liver transplantation (LDLT). Because GSD-Ia usually responds to dietary and medical treatments, we had a long discussion to determine whether preemptive LDLT was indicated. Transplantation was performed using the left lateral liver segment from the patients mother. The weight of his native liver was almost 2 kg. After reperfusion of the graft, the blood glucose concentration rapidly increased, and regular glucose was administered throughout the operation. The posttransplantation course was uneventful. The patient had no episodes of hypoglycemia with a regular diet. Total cholesterol, triglyceride, and uric acid concentrations also reverted to normal without medication. The patient had a few episodes of nasal bleeding after transplantation, which stopped spontaneously. He was discharged from our hospital with normal liver function. CONCLUSION: Patients with GSD-Ia should be considered for preemptive LDLT to improve their quality of life when clinical symptoms do not respond to appropriate treatment.

The excellent results of spousal kidney transplantation: experience in a Japanese single center.

In coping with the shortage of deceased kidney donors, living donor kidney transplantation is mainly performed in Japan. We started our living unrelated spousal kidney transplantation program in 1989. In this analysis, we compared the results of 64 spousal transplantations performed between September 1989 and May 2007 with those of living related and deceased donor grafts. Despite the older age of the recipients and the lower HLA matching, the graft survival rates of spousal transplants were as good as those from living related donors and better than those from deceased donors, (P < .01). The graft survival rate of spousal kidney transplantation is improving with advances in immunosuppression, so spouses are considered important donors in Japan, which lacks deceased donors.

Kidney transplantation for patients on long-term hemodialysis.

Patients surviving more than 10 years on hemodialysis (HD) are at risk of developing serious morbidity from unrelated conditions and from the many complications of long-term dialysis, such as cardiovascular disease, cerebrovascular disease, malignant tumors ectopic vascular calcification, diabetes mellitus, and disuse atrophy of the bladder. Long-term dialysis affects transplant patient outcomes and long-term graft survival. We analyzed 436 patients who underwent kidney transplantations between January 1987 and December 2007 to determine the impact of long-term dialysis on kidney transplant outcomes. The 39 patients who had been treated pretransplantation with dialysis for more than 10 years had an average length of dialysis treatment of 15.8 years (range, 10.0-32.5 years); they were denoted as the long-term hemodialysis group. The remaining 397 recipients showed an average of 3.7 years period of end-stage renal disease (ESRD) (range, 0-9.8, years; short-term hemodialysis group). There were significant differences in patient survival rates between the 2 groups: 93.2% vs 98.6%, at 1 year; 79.3% vs 95.4% at 5 years; and 58.4% vs 93.1% at 10 years (P = .0034). Also, graft survival was significantly different between the 2 groups: 89.2% vs 95.8% at 1 year; 60.4% vs 88.5% at 5 years; and 33.4% vs 80.4% at 10 years (P = .0026). Our results suggest that dialysis treatment for more than 10 years produces negative effects on post-transplantation patient and graft survival.

Estrogen-receptor-alpha-positive extramammary Paget's disease treated with hormonal therapy.

The patient was an 80-year-old man with scrotal and penile extramammary Paget's disease and prostate cancer. Both diseases were in advanced stages. Tumor cells of extramammary Paget's disease strongly expressed estrogen receptor alpha. The patient was concurrently treated with two kinds of hormonal therapy: the anti-estrogen tamoxifen (20 mg/day orally) for extramammary Paget's disease and the anti-androgen bicalutamide (80 mg/day orally) for prostate cancer. The toxicity of the therapy was mild. All of the metastatic lesions remained stable for 2 months after initiation of dual hormonal therapy. During a follow-up period of 22 months, performance status was well maintained for 17 months. Hormonal therapy may be an alternative for selected cases of advanced extramammary Paget's disease.

Liver transplantation from an identical twin without immunosuppression, with early recurrence of hepatitis C.

Hepatitis C virus reinfection after liver transplantation is universal and more severe than in nontransplant patients. Rejection episodes and immunosuppressive agents are considered risk factors for deterioration of recurrent hepatitis C. We report 2 cases of living donor liver transplantation for patients with hepatitis C-related cirrhosis who received right-lobe grafts from an identical twin. Thanks to genetic identity, no immunosuppressive drugs were administered during or after transplantation without rejection. Hepatitis C virus RNA kinetics showed a rapid increase following transplantation and liver biopsies 1 month after transplantation showed acute lobular hepatitis in both cases. Antiviral therapy using interferon alpha and ribavirin was started immediately, and both cases showed virological and histological response. In conclusion, avoidance of immunosuppression did not delay hepatitis C recurrence following transplantation, while early antiviral therapy without risk of rejection or immunosuppression led to successful viral eradication.

New protocol of immunosuppression for liver transplantation across ABO barrier: the use of Rituximab, hepatic arterial infusion, and preservation of spleen.

INTRODUCTION: An ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) is a challenge. Until 2000 systemic multidrug immunosuppression and splenectomy was the gold standard with poor results. Application of local administration with prostagrandin E1 (PGE1) and steroids via a portal vein (PV) catheter dramatically improved the survival from 20% to 60% but PV thrombus became a problem (35%). To solve it, an hepatic arterial (HA) catheter was used instead of a PV catheter and splenectomy was omitted. Although the PV thrombus problem was resolved, the ABO antibody titers significantly increased, and two cases of uncontrollable humoral rejection (HR) were experienced. In this study, Rituximab was introduced instead of splenectomy to decrease the antibody. We report the efficacy of prophylaxis with Rituximab for ABO-I LDLT. METHODS: Eight patients received. Rituximab at 2 to 14 days before LDLT. During the operation, the spleen was preserved. Methylpredonisolone and PGE1 were administered via an HA catheter for 2 to 3 weeks after LDLT in addition to an immunosuppressive regimen consisting of tacrolimus and steroids. Antibody titers were measured serially. RESULT: There was no clinical HR. Two patients died of complications unrelated to HR. The antibody titer decreased compared to patients without splenectomy/rituximab. B cells (CD19) were depleted from peripheral blood for up to 3 months. Cytomegalovirus infections were decreased compared to patients with splenectomy (P = .085). CONCLUSION: Rituximab prophylaxis and HA infusion therapy prevented clinical HR, which may provide a breakthrough to overcome the ABO blood-type barrier in liver transplantation.

The roles of CD25+CD4+ regulatory T cells in operational tolerance after living donor liver transplantation.

UNLABELLED: Recent evidence suggests that CD4+CD25+ regulatory T cells (Tregs) affect immune responses, including those to alloantigens in organ transplants. We have followed a group of liver allograft recipients with good liver graft function who have been weaned off immunosuppression (IS). The purpose of this study was to determine whether Tregs contributed functionally to the mechanisms of graft acceptance. MATERIAL AND METHODS: The functional assay used peripheral blood obtained from LTx recipients free of immunosuppression. The Whole population of CD4+ T cells and the CD4+ T cells depleted of CD4+CD25 high cells were tested for proliferation against donor versus third party stimulators. Moreover to determine the antigen-specificity of the Tregs, serially diluted numbering of CD4+CD25+ T cells were co-cultured with CD4+CD25- T cells. The proliferation responses were examined toward donor versus third party stimulators. RESULT: CD4+ T cells from all LTx recipients off immunosuppression showed hyporesponsiveness to the donor but not to third party stimulators. However, even after depletion of the CD4+CD25 high population, the cells continued to be hyporesponsive toward the donor. In four out of five cases, the suppression exhibited by CD4+CD25+ T cells was more specific for the donor. DISCUSSION: These findings suggest that donor alloantigen specific regulation by Tregs is one of multiple mechanisms that may contribute to the maintenance of liver graft survival in the absence of immunosuppression.

Proinflammatory and antiinflammatory cytokine production during ischemia-reperfusion injury in a case of identical twin living donor liver transplantation using no immunosuppression.

BACKGROUND: Bolus steroids are usually administered prior to graft reperfusion in an attempt to provide protection against ischemia reperfusion injury (IRI). However, the anti-IRI properties of steroids have not been established. Living donor liver transplantation (LDLT) between identical twins provides a unique opportunity to study the natural production of cytokines during transplantation without the confounding influences of the alloimmune response or of immunosuppression in particular steroids. METHODS: A 38-year-old male with hepatitis C virus-related cirrhosis and multiple hepatocellular carcinomas received a hepatic right lobe graft from his identical twin. No immunosuppression was administered, not even intraoperative bolus steroids. IRI was assessed by serum transaminases as well as by proinflammatory interleukin (IL) IL-1beta, tumor necrosis factor (TNF)-alpha, IL-8 cytokines and for potent regenerative/anti-inflammatory (IL-6, IL-10) mediators. RESULTS: Despite no administration of steroids, low peak levels of serum transaminases were observed. Serum IL-6 and IL-10 dramatically and rapidly increased during liver transplantation, namely, 160 and 20 times higher than baseline, respectively. In contrast, IL-1beta and TNF-alpha remained low during and after transplantation and an increase in IL-8 was less obvious. CONCLUSION: Syngeneic LDLT without intraoperative bolus steroids is feasible, yielding no penalty in terms of IRI. A predominance of protective cytokines was observed in the absence of steroids. Thus, the concept that intraoperative administration of steroids is necessary to protect liver transplants from IRI must be revisited.