Anesthetic management of MIDCAB in a patient with Wolff-Parkinson-White syndrome

We experienced the anesthetic management of a minimally invasive direct coronary artery bypass (MIDCAB) in a patient with Wolff-Parkinson-White (WPW) syndrome. A 55-year-old male had chest pain on effort and was diagnosed as having stenosis of the left coronary artery (#6). He was scheduled to undergo MIDCAB. Anesthesia was induced with midazolam 5 mg, fentanyl 300 micrograms, and vecuronium 10 mg and maintained with air-oxygen, propofol, and fentanyl (27 micrograms.kg-1). Diltiazem was continuously infused at a rate of 0.5-1.5 micrograms.kg-1.min-1 throughout the surgery. The hemodynamic parameters were maintained stable and paroxysmal supraventricular tachycardia was not observed during the procedure. We conclude that the administration of propofol and a medium dose of fentanyl is useful for the anesthetic management of MIDCAB in patients with WPW syndrome and that intraoperative administration of diltiazem might be needed to avoid paroxysmal supraventricular tachycardia.     

AdIκBα转染通过诱导凋亡逆转人非小细胞肺癌对泰素的耐药性

目的研究携带抑制性核因子κBα(IκBα)的腺病毒(AdIκBα)联合化疗对人非小细胞肺癌细胞株H460及H460荷瘤小鼠的作用。方法(1)检测50%抑制浓度(IC50)以确定化疗单用或联合AdIκBα对H460细胞增殖的影响,同时采用Annexin-V/PI染色法和caspase3活性测定来检测治疗引起的细胞凋亡情况;(2)观察泰素单用及联合不同浓度AdIκBα转染对H460荷瘤小鼠的作用,同时通过免疫组化染色观察核因子κB(NFκB)与p53及NFκB与血管内皮生长因子(VEGF)之间的关系。结果(1)联合AdIκBα3moi转染明显降低了泰素对H460的IC50,与激活caspase3途径而诱导了更多的细胞凋亡有关;在低剂量化疗组,联合治疗的疗效更加明显。(2)体内联合治疗明显抑制了H460荷瘤小鼠的肿瘤生长;免疫组化染色证实泰素治疗诱导了H460移植瘤细胞的NFκB表达增加,AdIκBα转染则消除了其表达,同时伴有轻度增加的VEGF表达,而p53表达不受影响。结论IκBα可通过阻滞NFκB表达和诱导凋亡而增加化疗疗效,同时减弱了VEGF表达,但与p53状态无关。推测联合治疗可减少化疗药的剂量,从而增加临床应用的耐受性。     

Effect of amount of water in dispersed phase on drug release characteristics of dextran microspheres prepared by emulsion-solvent evaporation process

Microspheres containing theophylline (TH) were prepared from a hydrophobic dextran derivative by emulsion solvent evaporation method. The objective of this study was to evaluate the effects of poor solvent in dispersed phase on the particle properties and drug release characteristics of the microspheres. Mixtures of acetone and water were used as the dispersed phase and liquid paraffin as the continuous phase. The amount of water (poor solvent for polymer) was varied from 0.5 to 2 ml in 15 ml of dispersed phase. Drug release from the microspheres was examined using JPXIV 1st Fluid (pH 1.2) containing 0.02% Tween 20, and their structure was analyzed by scanning electron microscopy (SEM). The drug release behaviors were greatly affected by the amount of water. The percentage released until 8 h were 89% and 23% for 0.5 and 2.0 ml of water, respectively. The release mechanism shifted from Fickian diffusion to zero-order transport as the amount of water increased. According to SEM observations, TH was uniformly distributed over the entire microsphere prepared using 0.5 ml of water, and existed in the center of the microsphere, having a core-shell structure, when prepared using 2 ml of water. The amount of poor solvent in the dispersed phase was found to be a crucial factor determining the internal structure of microspheres and drug release characteristics.     

Formulation Optimization of Paclitaxel Carried by PEGylated Emulsions Based on Artificial Neural Network

PURPOSE: To develop paclitaxel carried by injectable PEGylated emulsions, an artificial neural network (ANN) was used to optimize the formulation--which has a small particle size, high entrapment efficiency, and good stability--and to investigate the role of each ingredient in the emulsion. METHODS: Paclitaxel emulsions were prepared by a modified ethanol injection method. A computer optimization technique based on a spherical experimental design for three-level, three factors [soybean oil (X1), PEG-DSPE (X2) and polysorbate 80 (X3)] were used to optimize the formulation. The entrapment efficiency of paclitaxel (Y1) was quantified by HPLC; the particle size of the emulsions (Y2) was measured by dynamic laser light scattering and the stability of paclitaxel emulsions was monitored by the changes in drug concentration (Y3) and particle size (Y4) after storage at 4 degrees C. RESULTS: The entrapment efficiency, particle size and stability of paclitaxel emulsions were influenced by PEG-DSPE, polysorbate 80, and soybean oil. Paclitaxel emulsions of small size (262 nm), high entrapment efficiency (96.7%), and good stability were obtained by the optimization. CONCLUSIONS: A novel formulation for paclitaxel emulsions was optimized with ANN and prepared. The contribution indices of each component suggested that PEG-DSPE mainly contributes to the entrapment efficiency and particle size of paclitaxel emulsions, while polysorbate 80 contributes to stability.     

Sustained release of highly water-soluble drugs with micelle forming ability from polyionic matrix tablets

The aim of present study was to evaluate the application of a hydrophilic matrix tablet capable of polyion complex (PIC-tablet) to a controlled-release device for highly water-soluble drugs. The PIC-tablet was prepared from a mixture of dextran sulfate and [2-(diethylamino)ethyl] dextran chloride, and diltiazem hydrochloride was used as a model drug. Release tests revealed that the drug release was sustained even in 50% drug loading and was influenced by ionic strength but not by pH in medium. The drug release mechanism was thus investigated from the viewpoint of drug micelle forming property. The micelle forming ability of diltiazem was examined by the conductivity method, and was found to be influenced by ionic strength but not by pH value in accordance with the release tests. The results suggested that the drug's micelle interacted with the polyionic matrix. Further studies were conducted using metoprolol tartrate and thiamine hydrochloride as cationic drugs and sodium cloxacillin and sodium salicylic acid as anionic ones. The release profiles of the micelle-forming drugs metoprolol tartrate and sodium cloxacillin were also suppressed in spite of different solubility or opposite ionic charge from diltiazem hydrochloride. These findings demonstrated that the PIC-tablet is a promising device for oral controlled release delivery of water-soluble drugs with good micelle-forming ability.     

A multicenter phase II study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer: Kyushu thoracic oncology group trial

Purpose: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). Patients and methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m²) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: Seventy-four patients (45 men) with a median age of 62 years (range 40–74) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4–47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observeded in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. Conclusions: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis.     

TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

ObjectivePrecursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.MethodsWe analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.Results TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.ConclusionThe sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.     

Endoscopic Treatment of Superficial Gastric Cancer: Present Status and Future

Although the mortality rates of gastric cancer (GC) are gradually declining, gastric cancer is still the fourth leading cause of cancer-related death worldwide. This may be due to the high rate of patients who are diagnosed with GC at advanced stages. However, in countries such as Japan with endoscopic screening systems, more than half of GCs are discovered at an early stage, enabling endoscopic resection (ER). Especially after the introduction of endoscopic submucosal dissection (ESD) in Japan around 2000, a high en bloc resection rate allowing pathological assessment of margin and depth has become possible. While ER is a diagnostic method of treatment and may not always be curative, it is widely accepted as standard treatment because it is less invasive than surgery and can provide an accurate diagnosis for deciding whether additional surgery is necessary. The curability of ER is currently assessed by the completeness of primary tumor removal and the possibility of lymph node metastasis. This review introduces methods, indications, and curability criteria for ER of EGC. Despite recent advances, several problems remain unsolved. This review will also outline the latest evidence concerning future issues.     

Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.     

Predicting Individual Survival After Hepatectomy for Hepatocellular Carcinoma: a Novel Nomogram from the “HCC East &amp; West Study Group”

Introductions

Different staging systems have been devised for patients undergoing resection for hepatocellular carcinoma (HCC) with disparate results. The aim of this study was to create a new nomogram to predict individual survival after hepatectomy for HCC.

Methods

Based on the “Hepatocellular Carcinoma: Eastern & Western Experiences Network,” data from 2046 patients who underwent HCC resections at ten centers were reviewed. Patient survival was analyzed with Cox-regression analysis to construct a unique nomogram and contour plots to predict survival.

Results

The nomograms built on the multivariate analyses, which showed that the independent predictors were tumor size, tumor number, vascular invasion, cirrhosis, preoperative bilirubin value, and esophageal varices, showed good calibration and discriminatory abilities with C-index value of 0.62 (95 % CI, 0.59–0.69) and 0.61 (95 % CI, 0.56–0.64) for overall and disease-free survival, respectively. The 5-year survival contour plots showed that the presence of vascular invasion was associated with decreased survival, regardless of the tumor number or size. Cirrhosis and varices were equally associated with decreased survival, according to the tumor number or size.

Conclusions

These nomograms accurately predict individual prognosis after HCC resection and support an expansion of the selection criteria for resection. They offer useful guidance to clinicians for individual survival prediction.