ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the ...largest single‐center experience of ABO‐incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in‐hospital mortality. The cumulative 3‐year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO‐compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody‐mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.
This article presents the clinical results of ABO‐incompatible adult living donor liver transplantation in a single institution.
Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, ...and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure.
Patients were randomized 1:1 to DHP107 (200mg/m2 orally twice daily days 1, 8, 15 every 4weeks) or i.v. paclitaxel (175mg/m2 day 1 every 3weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25.
Baseline characteristics were balanced in the 236 randomized patients (n=118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7–4.0) months for DHP107 and 2.6 (95% CI 1.8–2.8) months for paclitaxel (hazard ratio HR=0.85; 95% CI 0.64–1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR=0.93; 95% CI 0.70–1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1−11.5) months for DHP107 versus 8.9 (95% CI 7.1–12.2) months for paclitaxel (HR=1.04; 95% CI 0.76–1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%).
DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC.
NCT01839773.
Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this ...study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells.
Multicentre study.
To define the clinical characteristics of patients with tuberculosis (TB) destroyed lung due to past TB.
We reviewed patients with TB-destroyed lung between May 2005 and June 2011.
...A total of 595 patients from 21 hospitals were enrolled. The mean age was 65.63 ± 0.47 (mean ± standard error); 60.5% were male. The mean number of lobes involved was 2.59 ± 0.05. Pleural thickening was observed in 54.1% of the patients. Mean forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC, bronchodilator response and number of exacerbations per year were respectively 2.06 ± 0.03 l (61.26% ± 0.79), 1.16 ± 0.02 l (49.05% ± 0.84), 58.03% ± 0.70, 5.70% ± 0.34, and 0.40 ± 0.04. The number of lobes involved was significantly correlated with FVC and FEV(1), and with the number of exacerbations per year. Use of long-acting muscarinic antagonists or long-acting beta-2 agonists plus inhaled corticosteroids resulted in bronchodilatory effects. Multivariable regression analysis showed that age, initial FEV(1) (%) and number of exacerbations during follow-up were independent factors affecting change in FEV(1).
Decreased lung function with exacerbation, and progressive decline of FEV(1) were observed in patients with TB-destroyed lung.
Background and purpose: Dopamine dysregulation in restless legs syndrome (RLS) may be varied by the severity of RLS, which could contribute to the conflicting results from previous functional ...neuroimaging studies on the central dopaminergic neurotransmission of RLS. The aim of this study was to observe whether reduced striatal dopaminergic neurotransmission is associated with moderate to moderately severe RLS.
Methods: Thirteen elderly patients with RLS and 12 normal elderly controls were enrolled in the study. All the subjects were dopaminergic‐drug naïve and twelve patients with RLS had the severity of moderate to moderately severe degree based on the International Restless Legs Syndrome Study Group (IRLSSG) Severity Scale. We compared dopamine transporter density (DAT) availability and D2 receptor density in the striatum between patients with RLS and controls using 123I2β‐carbomethoxy‐3β‐(4‐iodophenyl)tropane single‐photon emission computed tomography (SPECT) and 123Iiodobenzamide SPECT.
Results: Dopamine transporter density of patients with RLS was increased in the caudate (P = 0.037), posterior putamen (P = 0.041), and entire striatum (P = 0.046) compared with that of normal controls. DAT density was higher in the anterior putamen of patients with RLS than controls, although statistically not significant (P = 0.079). There was no difference in the D2 receptor density between patients with RLS and normal controls in the whole striatum or any of subregions.
Conclusions: Dysregulation rather than simple upregulation or downregulation of central dopaminergic neurotransmission may underlie the pathogenesis of RLS, and decreased dopaminergic neurotransmission may cause moderate to moderately severe RLS in the elderly.
Background and purpose: The pathogenesis of rapid eye movement (REM) sleep behavior disorder (RBD) is not clear despite its frequent association with Parkinson’s disease (PD). We investigated ...whether the nigrostriatal dopaminergic system is involved in the development of idiopathic RBD.
Methods: Fourteen patients with RBD, 14 patients with PD and 12 normal controls were included in the study. The diagnosis of RBD was confirmed on polysomnography. All the participants performed single‐photon emission computed tomography imaging 3 h after injection of 123IFP‐CIT. During REM sleep of the RBD patients, each 30‐s epoch was rated as ‘tonic’ when there was at least 50% of tonically maintained chin electromyography (EMG) activity in the epoch. Phasic EMG activities were calculated as the percentage of 3‐s mini‐epoch containing phasic EMG events (leg and chin, separately).
Results: The RBD patients showed a trend of lower binding in the striatum than the normal controls (P = 0.07), and the significance was revealed in the putamen (P = 0.02). However, in 11 individual cases of the 14 RBD patients, the dopamine transporter (DAT) densities in the putamen still remained within the normal range. In the RBD patients, there was no correlation between EMG activities and DAT densities.
Conclusions: Nigrostriatal dopaminergic degeneration could be a part of the pathogenesis of RBD, but not essential for the development of RBD. The lack of correlation between RBD severity and DAT densities suggests that another pathogenic process not related to nigrostriatal dopaminergic transmission may be implicated in RBD.
Background and purpose
It is not clear which is preferred between iron supplement and a dopamine agonist in the treatment of restless legs syndrome (RLS) with iron deficiency. The efficacies of oral ...iron supplementation and pramipexole for treatment of RLS with low‐normal serum ferritin (15–50 ng/ml) were compared.
Methods
Thirty RLS patients who took either oral iron or pramipexole for 12 weeks and were followed at 2, 4, 8 and 12 weeks after treatment commencement were enrolled. Severities of RLS symptoms were assessed using the international RLS study group rating scale for severity (IRLS) at every visit. Treatment response was defined as a decrease in IRLS score of at least 50% from baseline.
Results
The 30 subjects were assigned equally to an iron or pramipexole group. At baseline, IRLS scores and serum ferritin levels were similar between these two groups. After 12 weeks, IRLS scores were lower than those at baseline in both groups (iron −9.1 ± 7.07, P < 0.001; pramipexole −8.7 ± 8.31, P = 0.001) and similar between the two groups. Changes in IRLS scores from baseline were similar between the two groups at each visit. The response rates of the groups were identical at 46.7%.
Conclusions
Pramipexole was not different from oral iron in terms of efficacy and improvement speed in RLS patients with a low‐normal serum ferritin, but response rate of either oral iron or pramipexole alone was moderate. Some proportion of RLS patients with iron deficiency might benefit from combined use of oral iron and dopamine agonists.
Abstract Portal vein thrombosis remains a challenging issue in liver transplantation. When thrombectomy is not feasible due to diffuse portosplenomesenteric thrombosis, other modalities are adapted ...such as the use of a jump graft or portal tributaries or even multivisceral transplantation. For patients with diffuse thrombosis of the splanchnic venous system, a large pericholedochal varix can be a useful vessel for providing splanchnic blood flow to the graft and for relieving portal hypertension. We report our experience of successfully treating a patient with diffuse portosplenomesenteric thrombosis using a pericholedochal varix for portal flow reconstruction during deceased donor liver transplantation and eventually preventing unnecessary multivisceral transplantation. A 56-year-old man diagnosed with liver cirrhosis due to hepatitis B underwent deceased donor liver transplantation due to refractory ascites. Preoperative imaging revealed diffuse portosplenomesenteric thrombosis with large amount of ascites. During the operation, dissection of the main portal vein was not possible due to the development of multiple large pericholedochal varices and cavernous change of the main portal vein. After outflow reconstruction, portal inflow was restored by anastomosing the graft portal vein to a large pericholedochal varix. Postoperatively, although abdominal computed tomography scan showed stenosis of portal vein anastomosis site, liver function tests improved, and Doppler sonogram revealed no flow disturbance. During follow-up, the patient repeatedly developed hydrothorax and ascites. In addition, stenosis of the portal vein anastomosis and thrombosis of the portomesenteric system still remained. The patient underwent transhepatic portal vein stent insertion. After portal vein stent insertion, hydrothorax and ascites improved and the extent of thrombosis of the portomesenteric system decreased without anticoagulation therapy. In conclusion, enlarged pericholedochal varix in patients with totally obliterated splanchnic veins can be a source of useful inflow to restore portal flow and decrease the extent of thrombosis, thereby preventing unnecessary multivisceral transplantation.
Abstract Purpose Patients with advanced liver diseases are at increased risk of cardiovascular events, resulting in a higher incidence of cardiac complications following liver transplantation (OLT). ...We assessed the clinical value of computed tomographic coronary arteriography (CTCAG) as a routine preoperative cardiac evaluation test in adult patients scheduled for living donor OLT (LDLT). Methods This single-center, prospective, observational study evaluated 247 adult patients being assessed for LDLT from April 2010 to March 2011. CTCAG was performed in patients with all-negative findings on routine cardiac workup, including thallium single photon emission computed tomography (SPECT). Results Of the 247 patients evaluated, 27 (10.9%) showed abnormal findings on CTCAG, with 18 (7.3%) showing mild to moderate involvement of one vessel; 7 (2.8%), two-vessel; and 2 (0.8%), three-vessel involvement. Coronary artery calcification was identified in patients with significant coronary artery stenosis. No adverse events occurred after CTCAG. Noticeable hypotensive episodes during LDLT surgery occurred in 5% of patients, mostly related to massive bleeding or postperfusion syndrome. During the first 3 months after LDLT, 3% of patients showed stress cardiomyopathy, but all recovered with supportive care. Conclusions The poor general medical condition of LDLT candidates and the diagnostic accuracy of CTCAG suggest that this test should be included in the routine pretransplant cardiac workup, along with thallium SPECT, for these patients.
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