The Role of Liver-directed Surgery in Patients with Hepatic Metastasis from a Gynecologic Primary Carcinoma

Background  

The management of patients with liver metastasis from a gynecologic carcinoma remains controversial, as there is currently little data available. We sought to determine the safety and efficacy of liver-directed surgery for hepatic metastasis from gynecologic primaries.     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

Enhancement of erythrocyte superoxide dismutase activity: effects on cellular oxidant defense

To delineate further the role of superoxide dismutase (SOD) in red blood cell (RBC) oxidant defense, normal human erythrocytes were osmotically lysed and resealed in the presence of varying concentrations of exogenous SOD. This resulted in a dose-dependent increase in SOD activity in the resealed erythrocytes while maintaining nearly normal RBC hemoglobin concentration (less than 10% decrease from the control value), cell volume, and cellular deformability. Surprisingly, a five- or ninefold increase in SOD activity yielded no additional protection against superoxide-generating drugs (phenazine methosulfate or menadione sodium bisulfite). No significant differences were observed between the control and SOD-loaded RBCs in O2-driven methemoglobin formation or generation of thiobarbituric acid-reactive substances. In contrast, RBCs with elevated SOD activity pretreated with sodium azide (to block catalase activity) or 1-chloro-2,4- dinitrobenzene (to deplete reduced glutathione, GSH) showed significantly enhanced methemoglobin generation in response to superoxide generating drugs. No differential response was noted between the control, control-resealed, and SOD-loaded RBCs to oxidants other than superoxide. Based on our results and other data, we conclude that elevated SOD activity may imbalance cellular oxidant defense, resulting in enhanced oxidation due to the accelerated generation of H2O2, the product of O2- dismutation. This effect is significantly exacerbated under conditions in which H2O2 catabolism is altered.     

Plasma P-selectin is increased in thrombotic consumptive platelet disorders

P-selectin is a 140-kD protein found in the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells that on cell activation is expressed on the cell surface and also secreted into the plasma. The secreted form of P-selectin, like plasma P-selectin, differed from platelet membrane P-selectin in that its molecular mass was approximately 3 kD lower under reducing conditions. Both the secreted and plasma forms of P-selectin contained cytoplasmic sequence as determined by Western blot analysis with an affinity-purified rabbit anti-P-selectin cytoplasmic peptide antibody. We have measured plasma P- selectin and beta-thromboglobulin (beta TG) concurrently in (1) patients with consumptive thrombotic disorders, including disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia (HIT), and thrombotic thrombocytopenic purpura (TTP)/haemolytic uremic syndrome (HUS); (2) patients with idiopathic thrombocytopenic purpura (ITP); and (3) healthy controls. Patients with DIC, HIT, and TTP/HUS, but not ITP, had significantly elevated plasma P-selectin and beta TG levels when compared with their age-matched healthy controls. The increased plasma P-selectin and beta TG in patients with thrombotic disorders were likely to be the result of in vivo platelet and endothelial cell damage or activation. We also found that avoidance of veno-occlusion and other tedious measures customarily taken during blood collection and sample preparation to prevent in vitro platelet activation did not affect plasma P-selectin assay results. In addition, plasma P-selectin levels were not influenced by the presence of renal failure or heparin administration. These results indicate that plasma P- selectin may be a useful new marker for thrombotic diseases.     

Purification of Hageman factor (factor XII) on columns of popcorn- agarose

Purification of Hageman factor (HF, factor XII) from human plasma is a tedious procedure and the product is not always in the precursor form. Hojima has described a protein derived from corn kernels that inhibits the enzymatic properties of HF. This inhibitor binds to the precursor form of HF. Rapid purification of HF was achieved by using as the major purification step adsorption of this clotting factor to popcorn inhibitor bound to agarose. The product had a specific activity of 50.0 to 67.1 coagulant units of HF per milligram protein, and the yield was 33% to 40% of the HF content of the starting plasma. The purified protein displayed a single band upon unreduced or reduced sodium dodecyl sulfate polyacrylamide gel electrophoresis and less than 0.1% was in an activated form, as measured in coagulant assays. The technique described is more rapid and reliable than methods described earlier.     

New universal precaution aspiration tray

A new tray has been designed for use during procedures involving needles and other sharp objects. The tray includes a foam adhesive pad, marked into 10 sections, into which the sharp objects can be placed point first. After the procedure, the objects can be safely withdrawn by their handles and then discarded. The tray has been used in more than 250 procedures.     

Digital beam attenuator technique for compensated chest radiography

The feasibility of producing patient-specific beam attenuators for chest radiography has been investigated using an anthropomorphic phantom and a human volunteer. A low-dose test exposure is digitized, processed, and used to print a small cerium filter, which is placed in the x-ray beam near the collimator. The final radiograph is recorded on film. The technique results in relatively uniform film exposure, so that structures in all regions of the chest are simultaneously displayed with optimal film contrast. The equalized exposure improves image quality in the normally underpenetrated regions and reduces the role of cross-scatter from the lungs. The image is analogous to optical or computer-processed unsharp masking techniques, but the processing is accomplished in the x-ray beam and results in an improved exposure distribution, giving advantages that cannot be achieved with image processing techniques alone.     

骨形态发生蛋白4转基因治疗大鼠的胫骨缺损

目的:观察基因工程技术构建人骨形态发生蛋白4复制缺陷腺病毒的成骨效果。方法:实验于2006-03/08在安徽医科大学第一附属医院实验动物中心完成。实验分组:选取普通级雄性SD大鼠30只,体质量(200±10)g,全部动物胫骨上端部分分别造成8mm×5mm长方形缺损。采用自身对照法,右侧骨缺损为实验组,左侧骨缺损为对照组。实验组植入人骨形态发生蛋白4复制缺陷腺病毒复合明胶海绵,对照组植入单纯明胶海绵。实验评估:术后分别于4,6,8周麻醉后处死10只动物,取材行X线、组织病理、免疫组织化学、透视电镜检查,观察成骨情况。结果:纳入30只大鼠,全部进入结果分析。①大鼠胫骨缺损X线、组织病理学检查结果:术后8周实验组和对照组骨缺损均得到修复,但实验组无论从成骨时间、成骨效果、新生骨量等方面都要优于对照组。其中各时间点实验组骨密度明显高于对照组,差异有显著性意义[4周:(95.91±16.33),(87.93±11.52);6周:(128.34±10.64),(102.41±9.81);8周:(138.36±10.49),(121.56±9.63);P<0.01]。各时间点实验组新生骨占骨缺损面积比明显高于对照组,差异有显著性意义[4周:(41.39±5.65)%,(26.58±5.62)%;6周:(80.35±7.25)%,(65.41±6.52)%;8周:(96.45±2.76)%,(82.22±7.30)%;P<0.01]②术后4周免疫组织化学染色结果:实验组软骨及骨痂内呈强阳性反应,而对照组骨痂内骨形态发生蛋白4表达微弱。结论:人骨形态发生蛋白4重组腺病毒具有良好的成骨活性,骨形态发生蛋白4直接转基因治疗能够加快骨缺损的修复。     

Comparable efficacy of adapalene 0.3% gel and tretinoin 0.05% cream as treatment for cutaneous photoaging

Background

Adapalene has been previously evaluated as a treatment for actinic keratosis (AK) and solar lentigines and shown to improve signs of photoaging.

Objectives

To evaluate whether adapalene 0.3% gel is non-inferior to tretinoin 0.05% cream as treatment for photoaged skin.

Materials & Methods

An investigator-blinded, parallel-group comparison study was conducted in Brazil. Subjects were randomised in a 1:1 ratio to receive, once daily, adapalene 0.3% gel or tretinoin 0.05% cream. Subjects were evaluated at Weeks 1, 4, 8, 12, 16, 20 and 24, based on clinical signs of cutaneous photoaging, histopathological and digital morphometric findings, as well as safety and tolerability.

Results

A comparison of clinical efficacy showed that both treatments did not differ significantly regarding clinical evaluation of the following criteria: global cutaneous photoaging, periorbital wrinkles, ephelides/melanosis, forehead wrinkles, and AK.

Conclusion

Adapalene 0.3% gel showed non-inferior efficacy to tretinoin 0.05% cream as treatment for photoaged skin, with a similar safety profile. Adapalene 0.3% gel may therefore be considered a safe and effective option for the treatment of mild or moderate photoaging.

     

Conditional survival in patients with pancreatic ductal adenocarcinoma resected with curative intent

BACKGROUND:

Prognosis after surgery for pancreatic ductal adenocarcinoma (PDAC) is typically reported from the date of surgery. Survival estimates, however, are dynamic and may change based on the time already survived. The authors sought to assess conditional survival among a large cohort of patients who underwent resection of PDAC.

METHODS:

Between 1970 and 2008, 1822 patients who underwent resection for PDAC with curative intent were identified. Kaplan‐Meier and Cox regression analyses were performed to validate established predictors of survival, and results were compared with 2‐year conditional survival.

RESULTS:

Actuarial survival was 18% at 5 years, with a median survival of 18 months. Multivariate analysis revealed that tumor size, lymph node ratio, and positive margins were associated with worse survival (all P < .001). Differences in actuarial versus conditional survival estimates were greater the more years already survived by the patient. The 2‐year conditional survival at 3 years—the probability of surviving to postoperative year 5 given that the patient had already survived 3 years—was 66% versus a 5‐year actuarial survival calculated from the time of surgery of 18%. Stratification of 2‐year conditional survival by lymph node ratio and margin status revealed that patients with high lymph node ratio or positive margins saw the greatest increase in 2‐year conditional survival as more time elapsed (both P ≤ .01).

CONCLUSIONS:

Differences in actuarial versus conditional survival estimates were more pronounced based on the additional years already survived by the patient. Conditional survival may be a helpful tool in counseling patients with PDAC, as it is a more accurate assessment of future survival for those patients who have already survived a certain amount of time. Cancer 2011. © 2011 American Cancer Society.