N064A (Alliance): Phase II Study of Panitumumab,Chemotherapy, and External Beam Radiation in Patients with Locally Advanced Pancreatic Adenocarcinoma

BackgroundThis North Central Cancer Treatment Group (NCCTG) N064A (Alliance) phase II trial evaluated upfront chemoradiotherapy incorporating the EGFR inhibitor panitumumab, followed by gemcitabine and panitumumab for unresectable, non-metastatic pancreatic cancer.MethodsThe treatment consisted of fluoropyrimidine and panitumumab given concurrently with radiotherapy followed by gemcitabine and panitumumab for 3 cycles followed by maintenance panitumumab. The primary endpoint was the 12-month overall survival (OS) rate and secondary endpoints included confirmed response rate (RR), OS, progression-free survival (PFS), and adverse events. Enrollment of 50 patients was planned and the study fully accrued.ResultsFifty-two patients were enrolled, but only 51 were treated and included in the analysis. The median age of patients was 65 years and 54.9% were women. Twenty-two patients received at least 1 cycle of systemic therapy following radiotherapy, but 29 patients received chemoradiotherapy only without receiving subsequent chemotherapy after completion of chemoradiotherapy. The overall RR was 5.9% (95% CI: 1.2%-16.2%). The 12-month OS rate was 50% (95% CI: 38%-67%) which fell short of the per-protocol goal for success (51.1%). The median PFS was 7.4 months (95% CI: 4.5-8.6) and the median OS was 12.1 months (95% CI 7.9-15.9). Grade 3 or higher adverse events were reported by 88%.ConclusionThe combination of panitumumab, chemotherapy, and external beam radiation therapy was associated with very high rates of grades 3-4 toxicities and survival results did not meet the trial’s goal for success. This regimen is not recommended for further study (ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT00601627","term_id":"NCT00601627"}}NCT00601627).     

Posterior corneal curvature changes after myopic laser in situ keratomileusis

OBJECTIVE: To assess the posterior corneal power and asphericity changes after myopic laser in situ keratomileusis (LASIK) and to correlate these changes with the amount of correction and the residual stromal bed thickness. DESIGN: Prospective nonrandomized (self-controlled) comparative study. PARTICIPANTS: Fifty-seven eyes of 14 women and 15 men, mean age at the time of surgery 33 +/- 9 (range, 19-53) years with a spherical equivalent (SEQ) of -1.00 to -15.50 (mean, -5.07 +/- 2.81) diopters (DI). INTERVENTION: All procedures were performed with the Keratom II Coherent-Schwind excimer laser and and the Moria Model One microkeratome (150-microm head). Subjective refractometry, Orbscan slit scanning corneal topography analysis and pachymetry were performed before and 3 months after LASIK for myopia (n=35, -1.00 to -15.50 D, mean -4.75 +/- -3.07 D) or myopic astigmatism (n=22, sphere 0.00 to -9.75 D, mean -4.75 +/- 2.36 D; cylinder -0.75 to -3.50 D, mean -1.68 +/- 0.86 D). Intended ablation depth ranged from 12 to 108 (mean, 48 +/- 22) microm. Topographic raw data were decomposed into a set of Zernike polynomials as published in detail previously, and parameters potentially indicative for detection of a "mild keratectasia" were derived. MAIN OUTCOME MEASURES: Posterior central corneal power and asphericity before and after LASIK were compared, and changes of these variables were correlated with the SEQ change (deltaSEQ)and the residual corneal bed thickness RBT). RESULTS: The mean RBT after LASIK was 280 +/- 42 microm. Overall, change of posterior power (-6.28 +/- 0.22 D/ -6.39 +/- 0.23 D, P=0.02) was statistically significant and change of asphericity (0.98 +/-0.07/1.14 +/- -.20, P<0.0001) was highly significant. In eyes with RBT < or =250 microm, the average change of posterior central power (-0.20 +/- 0.10 D vs. -0.08 +/- 0.18 D) was significantly greater than in eyes with RBT >250 microm (P=0.003). The change of posterior corneal power correlated significantly with deltaSEQ (P=0.004) and the RBT (P=0.002). CONCLUSIONS: Increased negative keratometric diopters and oblate asphericity of the posterior corneal curvature suggest that mild "keratectesia" of the cornea may be common early after LASIK. Further stuudies with longer follow-up are required to clarify whether this biomechanical deformation is progressive and whether a residual bed thickness of >250 microm can completely prevent it.     

Der Nachweis von Heparin in den basophilen Leukocyten

Ohne Zusammenfassung     

微小染色体维持蛋白5和细胞增殖核抗原在肺癌组织中的表达及其临床意义

目的:检测MCM5蛋白和PCNA在肺癌组织中的表达,探讨两者与肺癌各临床病理因素之间的关系及两者相互的联系,从而为评估肺癌的发生发展、预后及治疗提供理论依据。方法:运用免疫组织化学技术分别检测MCM5蛋白和PCNA在68例肺癌组织和20例正常组织中的表达情况,分析其与临床病理因素之间的关系及两者相互的联系。结果:MCM5表达的阳性信号位于细胞核,胞浆无着色。在正常肺组织中,MCM5的表达局限在上皮基底部的1/3至1/2的细胞,在肺癌组织中,MCM5的表达分布广泛,靠近上皮表面的细胞也可见大量表达。(1)正常肺组织和肺癌组织的MCM5的表达的差别有统计学意义(P<0.01)。(2)肺癌中MCM5表达与分化程度、淋巴结转移有显著相关性(P<0.05),与病人年龄、性别无显著相关性(P>0.05)。(3)PCNA的表达与肺癌的分化程度无显著相关性(P>0.05)。(4)在肺正常组织中,PCNA标记指数高于MCM5标记指数,两者具有显著差异性(P<0.05)。在肺癌组织中,PCNA与MCM5标记指数无显著差异性(P>0.05)。结论:(1)在肺组织中,微小染色体维持蛋白5(MCM5)是一种可靠的细胞增殖标志物。根据MCM5染色的组织结构差异和平均光密度能比较准确区分肺正常组织和癌组织。MCM5表达与肺癌的分化程度显著相关,因此MCM5表达可以提示肺癌的恶性程度,有助于临床判断病人的预后以及选择合适的治疗方法。MCM5与其他增殖标志PCNA相比是一种更好的细胞增殖标志物,是肺癌细胞的更好标志和分级指标。(2)PCNA在肺癌组织中过表达,提示PCNA的过表达与肺癌的发生发展关系密切。     

Personalisierte Medizin bei Zytokin-gerichteten Therapien

Personalized healthcare tries to predict the effectiveness and safety in individual therapeutic approaches by defining individual patient characteristics (biomarkers), while stratification uses diagnostic patterns for groups of patients for prediction of therapeutic response with less adverse reactions caused by the drugs applied. Both methods are implemented in oncology and infectiology and in the therapy of rheumatological diseases there is a need for both. Cytokine-directed therapies are important for the treatment of rheumatological diseases, especially when therapy with conventional disease-modifying antirheumatic drugs (DMARD) has failed. Despite the high potency of these drugs for inhibiting pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin 1 (IL-1) and IL-6, sufficient responses are only seen in some of the patients. Therefore, stratification and personalized medicine are ways to optimize efficacy and tolerability of biologic therapies. Some initial evidence is available for potential future strategies using molecular and genetic markers for stratified cytokine inhibition.     

Portal Hypertension: Concepts in Diagnosis and the Role of Transjugular Intrahepatic Portosystemic Shunts in the Management of Complications

Portal hypertension is responsible for many of the manifestations of chronic liver disease. Some of these complications are the direct consequences of portal hypertension, such as gastrointestinal bleeding from either ruptured gastroesophageal varices or portal hypertensive gastropathy, ascites, and portosystemic encephalopathy.In the last 15 years, new endovascular procedures such as transjugular liver biopsy with its hemodynamic evaluation have been playing an important role in the diagnosis and management of this entity. Also, in cases where complications of severe portal hypertension such as acute or refractory bleeding or ascites are present, a transjugular portosystemic shunt procedure can decompress the portal system with a success rate greater than 90% of the cases. This review article provides the basic concepts of portal hypertension and its management using endovascular approach.     

Caregiver-Care Recipient Relationship Closeness is Associated With Neuropsychiatric Symptoms in Dementia

Objective

Closer caregiver-care recipient (CG-CR) relationships are associated with better cognitive and functional abilities, activities of daily living (in persons with dementia), and lower informal care costs.

Pharmacokinetics of artesunate following oral and rectal administration in healthy Sudanese volunteers

The aims of this study were to determine the pharmacokinetic parameters of a single dose of 200 mg oral and rectal artesunate in healthy volunteers, and to suggest a rational dosage regimen for rectal administration. The study design was a randomized open cross-over study of 12 healthy volunteers; the analytical method used was a reversed phase high performance liquid chromatography with post column derivatization and subsequent ultraviolet detection. Pharmacokinetic parameters were derived from the main metabolite alpha-dihydroartemisinin data due to the rapid disappearance of artesunate from the plasma. Dihydroartemisinin following oral administration of artesunate had a significantly higher AUC(0-infinity) (P<0.05 95% confidence interval (CI) -1168.73, -667.61 ng x h/mL(-1)) and Cmax (P<0.05; 95% CI -419.73, -171.44 ng/mL(-1)), and had shorter tmax (P<0.05; 95% CI -0.97, -0.10 h) than that following rectal artesunate. There was no statistically significant difference in the elimination half-life between both routes of administration (P>0.05; 95% CI -0.14, 0.53 h). The relative bioavailability of rectal artesunate was [mean (coefficient of variation %) 54.9 (24.8%) %]. On the basis of these data an 8 hourly dosing regimen per day with rectal artesunate is proposed.     

Differential enhancement of collagen crosslink excretion in cases of osteosarcoma and chondrosarcoma

Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are markers of collagen absorption and LP is specific for collagen type I in bone. In the present study we evaluated the concentration of HP and LP in urine of patients with osteosarcoma (n=20; age range 16–49 years) and chondrosarcoma (n=15; age range 18–70 years). The values were compared with those obtained from 74 healthy controls (age range 16–83 years). The range and upper limit of normal values (HP_max and LP_max) were measured in our control group. High performance liquid chromatography (HPLC) was used to determine concentrations of HP and LP (nmol/mmol creatinine). The average urinary HP concentrations were significantly increased in patients with osteosarcoma (p=0.001) and chondrosarcoma (p<0.001), whereas HP remained within the normal range in approximately half of the patients. The average urinary LP concentrations were not increased in osteosarcoma and chondrosarcoma patients as compared with the control group. Further studies in a large group of patients are necessary to evaluate whether HP might be a valuable marker of prognosis, and if its urinary concentration can be correlated to tumour burden.