A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma

Background and purpose

To evaluate the therapeutic benefits by adding chemotherapy (+C) and/or accelerated-fractionation (AF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma.

Materials and methods

From 1999 to 2004, 189 eligible patients were randomized to one of four treatment groups (CF/CF + C/AF/AF + C). The number of fractions/week was 5 for the CF groups and 6 for the AF groups. Patients in the +C groups were given concurrent cisplatin plus adjuvant cisplatin and fluorouracil.

Results

The AF + C group achieved significantly higher failure-free rate (88% at 5-year) than the CF group (63%; p = 0.013), the AF group (56%; p = 0.001) and the CF + C group (65%; p = 0.027). As compared with CF alone, the increase in late toxicity was statistically insignificant (36% vs. 20%; p = 0.25). Deaths due to cancer progression decreased (7% vs. 33%; p = 0.011) but deaths due to incidental causes increased (9% vs. 2%; p = 0.62). Improvement in overall survival reached borderline significance (85% vs. 66%; p = 0.058).

Conclusions

Concurrent-adjuvant chemotherapy combined with AF significantly reduced failure and cancer-specific deaths. Although the increase in major late toxicity and incidental deaths were statistically insignificant, a subtle increase in non-cancer deaths narrowed the overall survival gain.     

Reversal of P-glycoprotein-mediated multidrug resistance in human hepatoma cells by hedyotiscone A, a compound isolated from Hedyotis corymbosa

Multidrug resistance is a major problem in hepatocellular carcinoma. Hedyotiscone A, a compound isolated from Chinese herbal medicine Hedyotis corymbosa (HC, family Rubiaceae), was used as the chemical marker to distinguish between HC and an anticancer herb Hedyotis diffusa (HD) in our previous study. The present study aimed to investigate whether HA exhibited antiproliferative activities in multidrug-resistant hepatocellular carcinoma cells R-HepG2 and the parental cells HepG2 using MTT assay and [(3)H]-thymidine incorporation assay. Our results showed that HA could significantly inhibit cell proliferation in R-HepG2 and HepG2 (IC(50)?=?43.7 and 56.3 μg/mL, respectively), but not in normal human liver cells WRL-68 (IC(50) > 100 μg/mL) cells, suggesting its selective cytotoxic effects. Besides, HA induced apoptosis in R-HepG2 cells, as confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant increase of cleaved caspases-3, -7 and -9 in HA-treated R-HepG2 cells. The activities and protein expression of P-glycoprotein as well as mRNA expression of MDR1 were also decreased in HA-treated R-HepG2 cells. Our study demonstrated for the first time the antiproliferative activities of hedyotiscone A in multidrug-resistant R-HepG2 cells. The findings revealed the potential of this compound in treating multidrug-resistant tumor.     

Self-assembling peptide-based nanoparticles enhance cellular delivery of the hydrophobic anticancer drug ellipticine through caveolae-dependent endocytosis

A special class of self-assembling peptide (EAK16-II) has been found to stabilize the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this study, the mechanism of such peptide-EPT complexes to enhance cellular delivery and anticancer activity was evaluated. Results revealed that EAK16-II can form nanoparticles with EPT, having an average size of ～100 nm. This nanoformulation had cytotoxicity to human lung carcinoma A549 cells that was comparable to EPT dissolved in dimethyl sulfoxide. It enhanced EPT uptake drastically when compared to the microformulation. Such enhanced uptake was significantly reduced by inhibitors specifically for the caveolae-dependent pathway. We also found both protonated and neutral forms of EPT present in the cells. Interestingly, both were found in the cytoplasm, co-localized with LysoTracker, whereas only protonated EPT was seen in the nucleus. The promising therapeutic efficacy, specific delivery pathway, and intracellular distribution pattern discovered in this work may help further develop EPT as a nanoformulation for clinical applications. FROM THE CLINICAL EDITOR: A special class of self-assembling peptide (EAK16-II) has been found to stabilize ellipticine in aqueous solution. The authors demonstrate therapeutic efficacy, describe specific delivery pathways, and effective intracellular distribution pattern, which will aid the development of this technology for future clinical applications.     

Risk factors and mortality of nosocomial infections of methicillin-resistant Staphylococcus aureus in an intensive care unit

Purpose

Methicillin-resistant Staphylococcus aureus (MRSA) infections are an increasing worldwide problem. We determined risk factors and predictors of mortality of MRSA nosocomial infections (NIs).

Materials and Methods

A prospective cohort study was performed in an adult mixed medical and surgical intensive care unit from 2003 to 2007. Stratified analyses and generalized linear modeling were used to assess risk factors and predictors of infection and mortality.

Results

A total of 184 infections (3.6% of all infections) were due to S aureus, and 97.8% of these were methicillin resistant. The most common infection sites were respiratory tract (35.6%) and bloodstream (30.6%). Stratified analyses of length of stay (LOS) before onset of MRSA NI and death indicated that MRSA infection (odds ratio [OR], 38.49; 95% confidence interval [CI], 25.53-58.09) and mortality (OR, 4.72; 95% CI, 1.92-11.99) were more likely for LOS more than 15 days than for LOS less than 7 days. After controlling for potentially confounding factors by use of generalized linear modeling analysis, we identified the following as independent risk factors: LOS before onset of MRSA infection (OR, 1.03; 95% CI, 0.01-1.04), serum creatinine (OR, 5.87; 95% CI, 1.37-9.21) level, use of mechanical ventilator (OR, 6.71; 95% CI, 1.58-8.5), and central venous catheter (OR, 1.13; 95% CI, 1.05-1.31).

Conclusions

Methicillin resistance is very common with S aureus infection. In our intensive care unit, use of invasive devices/procedures and LOS were the most important risk factors for infection.     

MR diffusion imaging in ischemic stroke

Diffusion-weighted MRI provides image contrast that is dependent on the molecular motion of water. Diffusion-weighted imaging is the most reliable method for early detection of cerebral ischemia, for the definition of infarct core, and for the differentiation of acute ischemia from other disease processes that mimic stroke. Diffusion tensor imaging and diffusion kurtosis imaging may offer additional diagnostic information on the microstructural status of tissue. This review discusses the development and applications of diffusion-weighted imaging, diffusion tensor imaging, and diffusion kurtosis imaging in acute and chronic ischemia.     

Traumatic pancreatic fistula with sinistral portal hypertension: Surgical management

Combined ductal and vascular injuries are awesome complications of pancreatic injury. We report on a 29-year-old male unrestrained driver who sustained a blunt abdominal injury from the steering wheel in a high velocity head-on car collision. He developed a pancreatic fistula, portosplenic venous thrombosis and sinistral portal hypertension as a result of complete duct disruption at the pancreatic neck. We describe a safe surgical strategy of spleen-preserving distal pancreatectomy after failed medical and endoscopic management.     

Dual-Energy X-ray Absorptiometry With Serum Ferritin Predicts Liver Iron Concentration and Changes in Concentration Better Than Ferritin Alone

Accurate assessment of liver iron concentration (LIC) is critical for optimal monitoring of iron toxicity in multitransfused patients. Serum ferritin is the most widely used although its association to LIC is only modest. We studied if a liver-specific measure using dual-energy X-ray absorptiometry (DXA) systems could improve LIC estimates over ferritin alone in Thalassemia (Thal) patients. Thirty-seven patients with Thal (19.2 ± 9.0 yr, 20 male) were studied and 10 had multiple visits. Height, weight, ferritin, whole-body DXA, and hepatic superconducting quantum interference device (SQUID) were measured within 5 wk. DXA hepatic density was measured using right rib, whole liver, and multiple subliver regions. The best agreement to SQUID LIC was found using a combination of ferritin, weight, DXA subliver region 3 bone mineral content (BMC), and right rib BMC. DXA with ferritin improved the ferritin alone correlation from R² = 0.35 to R² = 0.62. Serial LIC changes using DXA were associated with serial SQUID changes (r = 0.73, p = 0.02). Changes in ferritin alone were not significant (p = 0.06). We conclude that the addition of whole-body DXA measures and body weight substantially increased the accuracy of LIC and change in LIC estimates over the use of ferritin alone and could be useful when magnetic resonance imaging or SQUID is not available.