Hepatic resection for colorectal liver metastases: prospective study.

OBJECTIVE: To assess the operative and long-term survival outcomes of hepatic resection for colorectal liver metastases during an 11-year period in a tertiary referral centre in Hong Kong. DESIGN: Prospective study. SETTING: University teaching hospital, Hong Kong. SUBJECTS AND METHODS: Between January 1989 and December 1999, 72 patients underwent hepatic resection for colorectal liver metastases. Clinical, pathological, and outcome data were prospectively collected and analysed. Factors affecting long-term survival were also evaluated. RESULTS: Twenty-five (34.7%) patients were found to have synchronous hepatic metastasis at the time of colorectal resection. Fifty-two (72.2%) patients underwent major hepatic resection. The operative morbidity and hospital mortality rates were 19% and 4%, respectively. The 5-year survival rate after hepatectomy was 31.9%. The median disease-free survival and median overall cumulative survival were 18.5 months and 30.8 months, respectively. On multivariate analysis, a high preoperative serum carcinoembryonic antigen level (>200 ng/mL) and tumour involvement of the resection margin at histology were the two independent risk factors that adversely affected survival outcome. CONCLUSION: Hepatic resection for colorectal liver metastases can be performed safely, with minimal operative mortality and acceptable morbidity, and results in satisfactory survival. High preoperative serum carcinoembryonic antigen level and histological involvement of resection margin by cancer adversely affect the survival outcome.published_or_final_versio

Potential enhancement of post-stroke angiogenic response by targeting the oligomeric aggregation of p53 protein

Tumor suppressor gene p53 and its aggregate have been found to be involved in many angiogenesis-related pathways. We explored the possible p53 aggregation formation mechanisms commonly occur after ischemic stroke, such as hypoxia and the presence of reactive oxygen species (ROS). The angiogenic pathways involving p53 mainly occur in nucleus or cytoplasm, with one exception that occurs in mitochondria. Considering the high mitochondrial density in brain and endothelial cells, we proposed that the cyclophilin D (CypD)-dependent vascular endothelial cell (VECs) necrosis pathway occurring in the mitochondria is one of the major factors that affects angiogenesis. Hence, targeting p53 aggregation, a key intermediate in the pathway, could be an alternative therapeutic target for post-stroke management

Hospitalized poisonings after renal transplantation in the United States

BACKGROUND: The national incidence of and risk factors for hospitalized poisonings in renal transplant recipients has not been reported. METHODS: Historical cohort study of 39,628 renal transplant recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998. Associations with time to hospitalizations for a primary diagnosis of poisonings (ICD-9 codes 960.x-989.x) within three years after renal transplant were assessed by Cox Regression. RESULTS: The incidence of hospitalized poisonings was 2.3 patients per 1000 person years. The most frequent causes of poisonings were immunosuppressive agents (25.3%), analgesics/antipyretics (14.1%), psychotropic agents (10.0%), and insulin/antidiabetic agents (7.1%). In Cox Regression analysis, low body mass index (BMI, <21.6 vs. >28.3 kg/m(2), adjusted hazard ratio (AHR), 3.02, 95% CI, 1.45–6.28, and allograft rejection, AHR 1.83, 95% CI, 1.15–2.89, were the only factors independently associated with hospitalized poisonings. Hospitalized poisonings were independently associated with increased mortality (AHR, 1.54, 95% CI 1.22–1.92, p = 0.002). CONCLUSIONS: Hospitalized poisonings were associated with increased mortality after renal transplantation. However, almost all reported poisonings in renal transplant recipients were due to the use of prescribed medications. Allograft rejection and low BMI were the only independent risk factors for poisonings identified in this population

Ten-year experience with liver transplantation at Queen Mary Hospital: retrospective study.

OBJECTIVE: To report the experience with liver transplantation at the Queen Mary Hospital from 1991 to 2000. DESIGN: Retrospective study. SETTING: Liver transplant centre of a University teaching hospital, Hong Kong. PATIENTS: One hundred and forty-eight patients (127 adults and 21 children) who underwent a total of 155 liver transplants using 75 cadaver grafts (full-size, 67; reduced-size, 5; split, 3) and 80 living donor grafts (left lateral segment, 15; left lobe, 6; right lobe, 59) from October 1991 to December 2000 were reviewed. MAIN OUTCOME MEASURES: Graft and patient survival rate. RESULTS: The most common disease indications for liver transplantation were chronic hepatitis B-related liver disease (n=74) in adults and biliary atresia (n=14) in children. Eighteen patients had hepatocellular carcinoma. Forty-eight (31%) liver transplants (three ABO-incompatible) were performed in high-urgency situations for patients requiring intensive care. The proportion of living donor liver transplants was 47.7% in adults and 73.9% in children. The overall 1-year and 5-year patient survival rates were 82% and 77%, respectively. The survival of high-risk recipients, such as those with fulminant hepatic failure (80%), chronic hepatitis B (81%), or hepatocellular carcinoma (94%), was not inferior to that of other patients. CONCLUSION: Over the last decade, the promotion of (cadaver) organ donation through public education coupled with innovative techniques in living donor liver transplantation have enabled a liver transplantation programme to be established in Hong Kong with gratifying results.published_or_final_versio

The Berkeley Sample of Stripped-Envelope Supernovae

We present the complete sample of stripped-envelope supernova (SN) spectra observed by the Lick Observatory Supernova Search (LOSS) collaboration over the last three decades: 888 spectra of 302 SNe, 652 published here for the first time, with 384 spectra (of 92 SNe) having photometrically-determined phases. After correcting for redshift and Milky Way dust reddening and reevaluating the spectroscopic classifications for each SN, we construct mean spectra of the three major spectral subtypes (Types IIb, Ib, and Ic) binned by phase. We compare measures of line strengths and widths made from this sample to the results of previous efforts, confirming that O I {\lambda}7774 absorption is stronger and found at higher velocity in Type Ic SNe than in Types Ib or IIb SNe in the first 30 days after peak brightness, though the widths of nebular emission lines are consistent across subtypes. We also highlight newly available observations for a few rare subpopulations of interest.Comment: 13 pages; 14 figures; 3 tables. Accepted for publication in MNRA

Men in Macau SAR have higher prevalence in metabolic syndrome and among related metabolic components: a cross-sectional Macau Health Survey

Abstract Background: Macau has recently experienced expansive socioeconomic growth, leading to lifestyle changes that could have contributed to the development of certain diseases. Little information exists on the prevalence of metabolic syndrome (MetS) and associated risk factors. This information is important, since the management of MetS is tightly connected with prevention of cardiovascular diseases in the population. Methods: This study is based on the cross-sectional Macau Health Survey 2006. Information on anthropometry, physical measurements, socio-demographics, laboratory tests and life-style habits was collected by trained health professionals from a random sub-population sample, aged 18-44 (32.6 ± 8.3). Body Mass Index (BMI) cut-offs were based on WHO criteria for Asian population. The prevalence of MetS, as defined by the International Diabetes Federation was calculated and the associated lifestyle factors were analysed. Results: Among Macau&apos;s adults (n = 1592), the age-adjusted prevalence of MetS was over two times higher in men (10.5%) than in woman (3.7%), (p &lt;0.01). 15.8% were overweight (BMI ≥23 &lt; 25) and 18.8% were obese (BMI ≥25). Man had significantly higher risk profile in almost all components of MetS (p &lt;0.001), except the waist circumference and HDL. BMI, age and education were significantly related to MetS in both genders (p &lt;0.001). Conclusions: We found significant gender differences in MetS among the 18 -44 year old population of Macau, which should be addressed separately in the gender-specific preventive strategies

Sirt7 protects against vascular calcification via modulation of reactive oxygen species and senescence of vascular smooth muscle cells

Vascular calcification is frequently seen in patients with chronic kidney disease (CKD), and significantly increases cardiovascular mortality and morbidity. Sirt7, a NAD+-dependent histone deacetylases, plays a crucial role in cardiovascular disease. However, the role of Sirt7 in vascular calcification remains largely unknown. Using in vitro and in vivo models of vascular calcification, this study showed that Sirt7 expression was significantly reduced in calcified arteries from mice administered with high dose of vitamin D3 (vD3). We found that knockdown or inhibition of Sirt7 promoted vascular smooth muscle cell (VSMC), aortic ring and vascular calcification in mice, whereas overexpression of Sirt7 had opposite effects. Intriguingly, this protective effect of Sirt7 on vascular calcification is dependent on its deacetylase activity. Unexpectedly, Sirt7 did not alter the osteogenic transition of VSMCs. However, our RNA-seq and subsequent studies demonstrated that knockdown of Sirt7 in VSMCs resulted in increased intracellular reactive oxygen species (ROS) accumulation, and induced an Nrf-2 mediated oxidative stress response. Treatment with the ROS inhibitor N-acetylcysteine (NAC) significantly attenuated the inhibitory effect of Sirt7 on VSMC calcification. Furthermore, we found that knockdown of Sirt7 delayed cell cycle progression and accelerated cellular senescence of VSMCs. Taken together, our results indicate that Sirt7 regulates vascular calcification at least in part through modulation of ROS and cellular senescence of VSMCs. Sirt7 may be a potential therapeutic target for vascular calcification.</p

Risk Factors for Nonsynchronous Second Primary Malignancy and Related Death in Patients with Differentiated Thyroid Carcinoma

BACKGROUND: Differentiated thyroid cancer (DTC) survivors are at increased risk of developing nonsynchronous second primary malignancy (NSPM). This study aims to examine possible risk factors leading to occurrence of NSPM as well as risk factors leading to NSPM-related death in patients with DTC. METHODS: Of the 1,106 patients with DTC managed at our institution, 92 (8.3%) patients developed NSPM and 40 (3.6%) patients died of NSPM. All causes of death were confirmed by medical record, autopsy report or death certificate. Clinicopathological variables were compared between those without NSPM and with NSPM as well as between those who died of NSPM and did not die of NSPM. Significant variables on univariate analysis were entered into a Cox proportional hazards model. RESULTS: The median latency period from diagnosis of DTC to NSPM was 142.7 (range 16.8-511.0) months. For occurrence of NSPM, age at DTC diagnosis >/=50 years old [relative risk (RR) = 2.35], cumulative radioactive iodine (RAI) activity 3.0-8.9 GBq (RR = 2.38), and external local radiotherapy (ERT) (RR = 1.95) were significant risk factors. For NSPM-related death, age at DTC diagnosis >/=50 years old (RR = 3.32) and nonbreast cancer (RR = 5.76) were significant risk factors. CONCLUSIONS: NSPM accounted for 18.7% of all deaths in DTC, but mortality was high (43.5%). Age at DTC diagnosis >/=50 years old, cumulative RAI activity 3.0-8.9 GBq, and ERT were significant risk factors for occurrence of NSPM, whereas age at DTC diagnosis >/=50 years old and the diagnosis of nonbreast cancer were significant risk factors for NSPM-related death.published_or_final_versionSpringer Open Choice, 21 Feb 201

Nuclear-Targeted Deleted in Liver Cancer 1 (DLC1) Is Less Efficient in Exerting Its Tumor Suppressive Activity Both In Vitro and In Vivo

BACKGROUND: Deleted in liver cancer 1 (DLC1) serves as an important RhoGTPase activating protein (RhoGAP) protein that terminates active RhoA signaling in human cancers. Increasing evidence has demonstrated that the tumor suppressive activity of DLC1 depends not only on RhoGAP activity, but also relies on proper focal adhesion localization through its interaction with tensin family proteins. Recently, there are reports showing that DLC1 can also be found in the nucleus; however, the existence and the relative tumor suppressive activity of nuclear DLC1 have never been clearly addressed. METHODOLOGY AND PRINCIPAL FINDINGS: We herein provide new evidence that DLC1 protein, which predominantly associated with focal adhesions and localized in cytosol, dynamically shuttled between cytoplasm and nucleus. Treatment of cells with nuclear export blocker, Leptomycin B (LMB), retained DLC1 in the nucleus. To understand the nuclear entry of DLC1, we identified amino acids 600-700 of DLC1 as a novel region that is important for its nuclear localization. The tumor suppressive activity of nuclear DLC1 was directly assessed by employing a nuclear localization signal (NLS) fusion variant of DLC1 (NLS-DLC1) with preferential nuclear localization. In SMMC-7721 HCC cells, expression of NLS-DLC1 failed to suppress colony formation and actin stress fiber formation in vitro. The abrogated tumor suppressive activity of nuclear DLC1 was demonstrated for the first time in vivo by subcutaneously injecting p53(-/-) RasV12 hepatoblasts with stable NLS-DLC1 expression in nude mice. The injected hepatoblasts with NLS-DLC1 expression effectively formed tumors when compared with the non-nuclear targeted DLC1. CONCLUSIONS/SIGNIFICANCE: Our study identified a novel region responsible for the nuclear entry of DLC1 and demonstrated the functional difference of DLC1 in different cellular compartments both in vitro and in vivo