Abstract Objective Salvage liver transplantation (LT) has been proposed for patients with a small hepatocellular carcinoma (HCC) and preserved liver function. Few reports have been issued on salvage ...LT in a living-donor (LD) LT setting. Therefore, we performed this study to evaluate differences in tumor invasiveness and other risk factors on survival after salvage versus primary LDLT. Methods Between September 1996 and December 2008, 324 patients with HCC underwent LT. We excluded 138 patient from the analysis, leaving 186 HCC patients for analysis, including 17 (9.1%) who had undergone earlier resection, the salvage LDLT cohort. The other 169 patients underwent primary LDLT. Results Intrahepatic metastasis, Edmonson-Steiner histologic grade, microscopic vascular invasion, and preoperative serum alpha-fetoprotein levels significantly influenced tumor recurrence. Microscopic vascular invasion, intrahepatic metastasis, Edmonson-Steiner histologic grade, and treatment by salvage LDLT were significantly associated with poor patient survival univariate analysis. However, only microscopic vascular invasion was significant on multivariate analysis. The treatment modality (primary or salvage LDLT) was not observed to affect overall or disease-free survival significantly on multivariate analysis. Disease-free survival was significantly better in the primary than in the salvage LDLT group. Furthermore, patients in the primary LDLT group tended to show better survival. However, when stratified by the presence or absence of microscopic vascular invasion, no significant group difference was found for overall or disease-free survival among those without versus with microscopic vascular invasion. Conclusions Five-year overall survival after primary versus salvage LDLT were similar when differences in tumor pathologic features, such as microscopic vascular invasion, were taken into account. Multivariate analysis showed that the treatment itself was not a significant prognostic factor for survival.
DNA methylation regulates the expression of genes that control mechanisms of cell death. TP53 gene expression inhibits tumorigenesis, and its action is closely associated with cell death. ...5-Azacytidine (5-aza), increases the expression of the TP53 gene by inhibiting DNA methyltransferase.
Using 5-aza, we induced DNA hypomethylation in p53-null and p53-expressing cancer cell lines and investigated potential mechanisms of cancer cell death.
TP53 expression promoted cell death. Notably, methylation-specific PCR (MSP) and bisulfite sequencing revealed more methylation sites at the TP53 promoter region in p53-null cells than in p53-expressing cells.
This study suggests a novel mechanism of tumorigenesis regulated by p53 expression.
Abstract Purpose Portal vein complications (PVC) after pediatric living donor liver transplantation (LDLT) have rarely been reported. We evaluated the long-term incidence and of the risk factors for ...PVC after pediatric LDLT. Methods From April 1997 to November 2008, 96 pediatric patients underwent LDLT using left lateral segments or left lobes. We investigated recipient factors, donor factors, and operative factors through medical records. The portal vein sizes in 96 recipients ranged from 2.7 mm to 13.0 mm (median = 5.0 mm). Portal vein reconstruction was usually performed with the graft portal vein anastomosed to the bifurcation of the recipient right and left portal veins, the so-called “branch patch”. Results PVC occured in 11 patients (11.5%) including early PVC ( n = 3), late PVC ( n = 8). The disease-free survivals at 1, 5, and 10 years after LDLT were 94.7%, 88.7%, and 86.0%. Upon univariate analysis, a portal vein size < 5 mm graft-to-recipient weight ratio (GRWR) ≥ 4%, transfusion volume ≥ 270 mL were significant risk factors for PVC. Body weight < 8 kg and previous operative history tendes to be adverse for PVC. Upon multivariate analysis by Cox regression, portal vein size < 5 mm was a highly significant factor for PVC after pediatric LDLT (hazard ratio = 5.627, P = .027). Conclusion The disease-free survival at 10 years after LDLT was 86.0%. If the recipient's portal vein size < 5 mm received a large-for-size graft (GRWR ≥ 4%), it is important to observe by regular Doppler ultrasonography follow-up to detect PVC.
To prevent maternal phenylketonuria (PKU) syndrome low phenylalanine concentrations (target range, 120–360 μmol/L) during pregnancy are recommended for women with PKU. We evaluated the feasibility ...and effectiveness of current recommendations and identified factors influencing maternal metabolic control and children's outcome. Retrospective study of first successfully completed pregnancies of 85 women with PKU from 12 German centers using historical data and interviews with the women. Children's outcome was evaluated by standardized IQ tests and parental rating of child behavior. Seventy‐four percent (63/85) of women started treatment before conception, 64% (54/85) reached the phenylalanine target range before conception. Pregnancy planning resulted in earlier achievement of the phenylalanine target (18 weeks before conception planned vs. 11 weeks of gestation unplanned, p < 0.001) and lower plasma phenylalanine concentrations during pregnancy, particularly in the first trimester (0–7 weeks of gestation: 247 μmol/L planned vs. 467 μmol/L unplanned, p < 0.0001; 8–12 weeks of gestation: 235 μmol/L planned vs. 414 μmol/L unplanned, p < 0.001). Preconceptual dietary training increased the success rate of achieving the phenylalanine target before conception compared to women without training (19 weeks before conception vs. 9 weeks of gestation, p < 0.001). The majority (93%) of children had normal IQ (mean 103, median age 7.3 years); however, IQ decreased with increasing phenylalanine concentration during pregnancy. Good metabolic control during pregnancy is the prerequisite to prevent maternal PKU syndrome in the offspring. This can be achieved by timely provision of detailed information, preconceptual dietary training, and careful planning of pregnancy.
Abstract Background Urinary tract infection (UTI) may occur in the form of asymptomatic bacteruria but severe cases may cause life-threatening pyelonephritis or sepsis in immunosuppressed kidney ...transplant recipients. Vesicoureteral reflux (VUR) is one risk factor in the transplanted kidney. But controversy exists regarding the effect of VUR in terms of graft outcomes. The objective of this study was to analyze the clinical outcomes among patients with posttransplantation VUR. Patients and Methods Between April 2005 and June 2006, we examined 75 patients with functioning grafts for more than 1 year by voiding cystourethrography at 1 year for the grade of posttransplantation VUR: group A, absent (n = 28) including grade I (n = 6) and II (n = 22); group B, including grade III (n = 17) and IV (n = 2). Patient characteristics included etiology of end-stage renal disease, duration of dialysis before transplantation, serum creatinine, creatinine clearance at 1 and 12 months after transplantation, and postoperative complications. The presence/absence of UTI, acute rejection, and graft loss were compared for significance. Result Posttransplantation VUR present in 47/75 patients (61.3%) was over grade III in 19 patients. There was no difference in significant risk factors between the groups as well as between the reflux subgroups. VUR did not influence graft function with the only significant factor being acute cellular rejection. Conclusion We failed to confirm a risk of developing posttransplantation VUR. Posttransplantation VUR did not negatively affect graft function; acute cellular rejection was the only factor that influenced it. Longer follow-up needs to be performed to clarify the long-term effects of posttransplantation VUR on graft function.
Background: Although a wide variety of asthma medications have been developed and are used in clinical practice, there is limited evidence of their comparative effects on asthma exacerbations. ...Methods: We used claims data provided by the Health Insurance Review and Assessment Service. We selected subjects commencing asthma treatment between July 1,2017 and June 30,2018, with no change in drug regimen. The primary outcome was asthma exacerbation requiring systemic corticosteroids. Cox regression analysis was used to assess outcomes considering the exacerbation-free period. Results: Of the 254,951 asthma subjects, 107,694 subjects (42.2%) experienced asthma exacerbation. Inhaled corticosteroids (ICSs) (hazard ratio HR, 0.378-0.508), ICS-long-acting ^-agonist (LABAs) (HR, 0.284-0.479), long-acting muscarine antagonists (LAMAs) (HR, 0.432-0.572), leukotriene receptor antagonists (LTRAs) (HR, 0.371-0.419), and xanthines (HR, 0.326-0.482) significantly reduced the rate of first and second exacerbation of asthma (all P-values, <0.001). The clinical effectiveness of asthma medications varied according to the active ingredient (HR 0.164-0.670) and was significant for all active ingredients (all P-values, <0.001). The effectiveness of combination treatment using ICS-LABA and LTRA varied (HR, 0.159-0.670); however, all combination treatment options evaluated were effective in preventing asthma exacerbations (all P-values, <0.001). Long-term use of ICS-LABA (HR, 0.278-0.653), LTRA (HR, 0.259-0.628), and xanthines (HR, 0.351-0.783) showed consistent effectiveness (all P-values, <0.001). Conclusion: This real-world study showed that the effectiveness of asthma medications varied according to drug type, active ingredient, combination, and period of use, although effectiveness was significant in all cases studied. Keywords: asthma, medication, exacerbation, real-world data, drug, combination
The Rakhigarhi site is the location of the ruins of an ancient megacity of the Harappan civilization and had not previously been investigated thoroughly. We tried to examine the physical and ...pathological traits of human skeletons (n = 37) from the cemetery at the site. In our study, a cranial index was calculated from one male skull (dolichocranic; index value = 65.78). The mean statures estimated by long bone length were 175.8 cm (male) and 166.1 cm (female). The indices of femoral diaphyseal shape were 79.8 (males) and 90.31 (females) for the platymeric index; and 113.78 (males) and 112.74 (female) for the pilasteric index. The dental health of the subjects appeared to be good as the overall prevalence of oral pathologies (caries and antemortem tooth loss) was generally low. Periosteal reactions were found in tibias and possible evidence of osteomyelitis was also observed in a femur. Some joint parts showed signs of osteoarthritis. Although various pathologies have been identified, we could not find any specific lesions suggestive of leprosy and tuberculosis in these skeletons. Although our study has added invaluable data to the existing information pool on the health and disease status of Harappan society, more accurate conjecture on the structure of Harrappan society based on bioarchaeological evidence will need additional research based on future excavations at Rakhigarhi cemetery.
Abstract Budd-Chiari syndrome (BCS), which is characterized by hepatic venous outflow obstruction due to occlusion of the major hepatic vein and/or the inferior vena cava (IVC), is rare. ...Traditionally, a caval resection is advocated for these patients; however, such a manenver renders living donor liver transplantation (LDLT) impossible. We encountered BCS in 4/377 LDLT patients during a 5-year period (January 2003 to December 2007). This report examine the various surgical modifications in these 4 patients, who underwent to LDLT for BCS. Resection of right hepatic vein (RHV) with an adjacent fibrotic part of the IVC with direct anastomosis of the graft RHV to the IVC was performed in 2 patients. One patient underwent retrohepatic IVC excision and reconstruction with a cryopreserved autologous IVC graft. The fourth patient, with a preexisting mesoatrial shunt for BCS, underwent conversion of this to a RHV atrial shunt. Graft and patient survivals were 100%. There were few complications in either donors or recipients. LDLT for BCS can be performed safely with adequate venous drainage techniques and with anticoagulant therapy and good follow-up for early diagnosis and treatment of recurrence leading to excellent long-term results.
A 13-year-old female scimitar-horned oryx (Oryx dammah) died after progressive anorexia, weight loss, and depression. The necropsy showed that the retroperitoneum was compressed by a large ...white-to-tan uterine mass and on several sections of the mass, the uterine wall was markedly thickened because of ill-defined transmural tumor tissue. Metastatic nodules were detected in the omentum, mesentery, diaphragm, and lung. The genital tract and pulmonary and abdominal nodules exhibited highly pleomorphic sarcoma. The primary and metastatic neoplastic cells showed positive results for vimentin, desmin, and sarcomeric actin, and negative results for smooth muscle actin. Uterine metastatic rhabdomyosarcoma was diagnosed on the basis of the gross, histopathology and immunohistochemistry results.
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