Gemcitabine-based versus fluoropyrimidine-based chemotherapy with or without platinum in unresectable biliary tract cancer: a retrospective study

<p>Abstract</p> <p>Background</p> <p>There is no standard palliative chemotherapy regimen in biliary tract cancers (BTC). Fluoropyrimidine or gemcitabine, with or without platinum, are most frequently used. We conducted this study to clarify the efficacy of palliative chemotherapy in BTC.</p> <p>Methods</p> <p>Patients with unresectable BTC treated with palliative chemotherapy between Oct 2001 and Aug 2006 at Seoul National University Hospital were reviewed retrospectively. Histologically confirmed cases of intrahepatic cholangiocarcinoma, gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater carcinoma were enrolled. We analyzed the efficacy of regimens: gemcitabine (G) <it>versus </it>fluoropyrimidine (F) and with or without platinum (P).</p> <p>Results</p> <p>A total of 243 patients were enrolled. 159 patients (65%) were male and the median age of the patients was 60 years (range 26–81). Intrahepatic cholangiocarcinoma, gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater carcinoma were 92, 72, 58, and 21 cases, respectively. The median progression free survival (PFS) was 4.3 months (95% CI, 3.7–4.9) and median overall survival (OS) was 8.7 months (95% CI, 7.4–10.0). Ninety-nine patients received G-based chemotherapy (94 GP, 5 G alone), and 144 patients received F-based chemotherapy (83 FP, 61 F alone). The response rate (RR), disease control rate (DCR), PFS and OS of G-based chemotherapy <it>versus </it>F-based chemotherapy were 16.7% <it>vs</it>. 19.5% (P = 0.591), 52.8% <it>vs</it>. 58.9% (P = 0.372), 4.0 months <it>vs</it>. 4.3 months (P = 0.816), and 7.8 months <it>vs</it>. 9.1 months (P = 0.848), respectively. Sixty-six patients received F or G without P, and 177 patients received F or G with P. The RR, DCR, PFS and OS of chemotherapy without P <it>versus </it>chemotherapy including P were 12.7% <it>vs</it>. 20.6% (P = 0.169), 46.0% <it>vs</it>. 60.6% (P = 0.049), 3.3 months <it>vs</it>. 4.4 months (P = 0.887), and 10.6 months <it>vs</it>. 8.1 months (P = 0.257), respectively.</p> <p>Conclusion</p> <p>In unresectable BTC, F-based and G-based chemotherapy showed similar efficacy in terms of RR, DCR, PFS and OS. The benefit of adding P to F or G was not significant except for DCR. Further prospective studies which define the efficacy of various chemotherapeutic regimens in BTC are warranted.</p

Effects of Antioxidant, Anti-Collagenase, Anti-Elastase, Anti-Tyrosinase of The Extract and Fraction From Turbinaria decurrens Bory.

Brown macroalgae (BM) which contain fucoxanthin exhibited high antioxidant activity. This study was performed to examine antioxidant, anti-collagenase, anti-elastase, anti-tyrosinase activities, and effect on cell viability of Human Dermal Fibroblast adult (HDFa) of BM, Turbinaria decurrens Bory. T. decurrens dried powder were macerated by ethanol to obtain extract (ETD) and was fractination by column chromatography to obtain fraction (FTD). Fucoxanthin content was determined using HPLC. The antioxidant activities, anti-collagenase, anti-elastase, and tyrosinase inhibitory assay were performed. The effect of ETD and fucoxanthin standard on cell viability were conducted on HDFa cell-induced by hydrogen peroxide (H2O2). The HPLC analysis showed that ETD and FTD contain fucoxanthin of 284.9±3.3µg/g and of 653.4±30.6µg/g dry-weight, respectively. The antioxidant assay showed that ETD and FTD produced high antioxidant activity by ferric reducing antioxidant power (FRAP) and b-carotene bleaching (BCB) methods that were comparable to fucoxanthin. ETD exhibited significantly higher tyrosinase inhibitory than kojic acid (p&lt;0.01), while FTD had a comparable effect to kojic acid. The result also revealed that ETD and FTD produced anti-elastase and anti-collagenase (matrix metalloproteinase-1 (MMP-1). Fucoxanthin and ETD were able to maintain cell viability on HDFa cell-induced H2O2. This study suggests that T. decurrens may be effective to prevent skin aging and wrinkle formation, possibly through the antioxidant activity and maintain cell viability of fibroblast.

Entanglement-assisted codeword stabilized quantum codes

Entangled qubit can increase the capacity of quantum error correcting codes based on stabilizer codes. In addition, by using entanglement quantum stabilizer codes can be construct from classical linear codes that do not satisfy the dual-containing constraint. We show that it is possible to construct both additive and non-additive quantum codes using the codeword stabilized quantum code framework. Nonadditive codes may offer improved performance over the more common sta- bilizer codes. Like other entanglement-assisted codes, the encoding procedure acts only the qubits on Alice's side, and only these qubits are assumed to pass through the channel. However, errors the codeword stabilized quantum code framework gives rise to effective Z errors on Bob side. We use this scheme to construct new entanglement-assisted non-additive quantum codes, in particular, ((5,16,2;1)) and ((7,4,5;4)) codes

CDKN2A/p16INK4a expression is associated with vascular progeria in chronic kidney disease

Patients with chronic kidney disease (CKD) display a progeric vascular phenotype linked to apoptosis, cellular senescence and osteogenic transformation. This has proven intractable to modelling appropriately in model organisms. We have therefore investigated this directly in man, using for the first time validated cellular biomarkers of ageing (CDKN2A/p16INK4a, SA-β-Gal) in arterial biopsies from 61 CKD patients undergoing living donor renal transplantation. We demonstrate that in the uremic milieu, increased arterial expression of CDKN2A/p16INK4a associated with vascular progeria in CKD, independently of chronological age. The arterial expression of CDKN2A/p16INK4a was significantly higher in patients with coronary calcification (p=0.01) and associated cardiovascular disease (CVD) (p=0.004). The correlation between CDKN2A/p16INK4a and media calcification was statistically significant (p=0.0003) after correction for chronological age. We further employed correlate expression of matrix Gla protein (MGP) and runt-related transcription factor 2 (RUNX2) as additional pathognomonic markers. Higher expression of CDKN2A/p16INK4a, RUNX2 and MGP were observed in arteries with severe media calcification. The number of p16INK4a and SA-β-Gal positive cells was higher in biopsies with severe media calcification. A strong inverse correlation was observed between CDKN2A/p16INK4a expression and carboxylated osteocalcin levels. Thus, impaired vitamin K mediated carboxylation may contribute to premature vascular senescence

Intrahepatic cholangiocarcinoma: review and update

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that could develop at any level from the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar and distal on the basis of its anatomical location. Of note, these three CCA subtypes have common features but also important inter-tumor and intra-tumor differences that can affect the pathogenesis and outcome. A unique feature of iCCA is that it recognizes as origin tissues, the hepatic parenchyma or large intrahepatic and extrahepatic bile ducts, which are furnished by two distinct stem cell niches, the canals of Hering and the peribiliary glands, respectively. The complexity of iCCA pathogenesis highlights the need of a multidisciplinary, translational and systemic approach to this malignancy. This review will focus on the advances of iCCA epidemiology, histo-morphology, risk factors, molecular pathogenesis, revealing the existence of multiple subsets of iCCA

Subarachnoid Hemorrhage Misdiagnosed as an Acute ST Elevation Myocardial Infarction

Without significant coronary artery stenosis, ischemic electrocardiographic change including ST segment elevation, segmental wall motion abnormality and elevated serum cardiac-specific markers (creatine kinase-MB, Troponin-T) may develop after central nervous system injuries such as subarachnoid, intracranial or subdural hemorrhage. Misdiagnosing these patients as acute myocardial infarction may result in catastrophic outcomes. By reporting a case of a 55-year old female with subarachnoid hemorrhage mimicking acute ST elevation myocardial infarction, we hope to underline that careful attention of neurologic abnormality is critical in making better prognosis

Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI

BACKGROUND: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. RESULTS: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001). CONCLUSIONS: Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE-FLAIR ClinicalTrials.gov number, NCT02053038 .)info:eu-repo/semantics/publishedVersio

Genetically engineering encapsulin protein cage nanoparticle as a SCC-7 cell targeting optical nanoprobe

Background - Protein cage nanoparticles are promising nanoplatform candidates for efficient delivery systems of diagnostics and/or therapeutics because of their uniform size and structure as well as high biocompatibility and biodegradability. Encapsulin protein cage nanoparticle is used to develop a cell-specific targeting optical nanoprobe. Results - FcBPs are genetically inserted and successfully displayed on the surface of encapsulin to form FcBP-encapsulin. Selectively binding of FcBP-encapsulin to SCC-7 is visualized with fluorescent microscopy. Conclusions - Encapsulin protein cage nanoparticle is robust enough to maintain their structure at high temperature and easily acquires multifunctions on demand through the combination of genetic and chemical modifications.ope