Usefulness of docetaxel as first‐line chemotherapy for metastatic extramammary Paget's disease

In invasive extramammary Paget's disease (EMPD), distant metastases may develop and the condition may become fatal; however, no standardized treatment has been established. Although based on only a few cases, several chemotherapy regimens were reported to be promising. We conducted a multicenter, retrospective study to evaluate the efficacy of docetaxel for metastatic EMPD. We retrospectively collected data on 18 metastatic EMPD patients treated using docetaxel from 1998 to 2012 in 12 institutes in Japan. The following clinical data were collected: tumor response, time to progression, overall survival and adverse effects. Of those, three patients treated combined with S‐1, one patient treated with weekly schedule and one patient treated combined with radiotherapy were excluded from the further analysis. All 13 patients received monthly docetaxel as the first‐line treatment. The average number of treatment cycles was 9.1. Among the 12 patients with a confirmed response, seven (58%) showed a partial response, three (25%) stable disease and two (17%) progressive disease. The disease control rate (partial response + stable disease) was as high as 83%. The time to progression and median overall survival were 7.1 and 16.6 months, respectively. The 1‐year overall survival rate determined by the Kaplan–Meier method was 75.0%. All adverse effects were manageable and no treatment‐related deaths were observed. The high disease control rate and overall survival shown by this study suggest that first‐line use of docetaxel may be a promising treatment for metastatic EMPD. A prospective clinical trial is required to confirm our results.     

Impact of infection control measures on the related costs and the amount of broad-spectrum antimicrobial agents used in a hospital: A time-series analysis

Health care–associated infections (HAIs) worsen patient prognoses and increase medical costs. Antimicrobial stewardship (AMS), which involves appropriate use of antimicrobial agents and antiseptics, may be beneficial for addressing the issue of HAIs. In hospitals, an infection control team (ICT) plays an important role on the appropriate use of antimicrobial agents and antiseptics based on AMS. We aimed to conduct a time-series analysis of the efficacies of infection control measures in terms of related costs, amount of broad-spectrum antimicrobial agents used (carbapenems and quinolones), and methicillin-resistant Staphylococcus aureus (MRSA) detection rates. This retrospective cross-sectional study included in-hospital patients treated at a single institute between January 2012 and December 2015. The intervention start point (initiation of infection control measures) was January 2014. All survey items were subjected to segmented regression analysis using an autoregressive integrated moving average (ARIMA) model. Differences between pre-intervention and postintervention levels and their trends were assessed, using a statistical significance cutoff of P < .05. The infection control costs demonstrated a significantly increasing trend, despite significant decreases in the amount of carbapenems used. Accordingly, the implementation of infection control measures was associated with increased costs, whereas carbapenem use decreased immediately after intervention. Postintervention levels, trends of quinolone use, or MRSA detection rates did not reveal significant changes. Although implementation of infection control measures induced gradual increases in related costs, these measures led to immediate reductions in carbapenem use. Our study findings will support the establishment of more effective and economical infection control measures.     

Polymers containing stable free radicals, 4. Preparation of 2,4-diphenyl-6-(3-maleoyliminophenyl)-3,4-dihydro-s-tetrazin-1(2H)-yl and its anionic polymerization

2,4-Diphenyl-6-(3-maleoyliminophenyl)-3,4-dihydro-s-tetrazin-1(2H)-yl ( 6 ) was synthesized and anionically polymerized with a catalytic amount of sodium 1,4-dihydro-1,4-naphthalenediide, with a conversion up to 96%. The polymer was a dark green powder with a content of radical groups of about 58% (based on unit mol), and its relative molecular mass was about 4 800, corresponding to 12 monomeric units.     

MEMBRANOUS GLOMERULONEPHRITIS ASSOCIATED WITH ACTIVE LIVER CIRRHOSIS BOTH INVOLVED BY HBs ANTIGEN

This is a case report of a 35-year-old female who showed a relatively short clinical course of severe liver cirrhosis and proteinuria. On light microscopical studies of autopsy material, besides active postnecrotic type liver cirrhosis, typical membranous glomerulonephritis was found. Immunofluorescent study disclosed not only clustered HBsAg (hepatitis type B surface antigen) in occasional hepatic cells but also beaded granular type deposition of HBsAg, IgG, IgM, IgA and complement G_s along renal glomerular basement membrane (GBM). Electron microscopical study disclosed multiple particulated material in occasional inclusion bodies of hepatic cells and in subepithelial and subendothelial dense deposits along the GBM. Enzymatic immunoelectron microscopical study confirmed these particles especially along the GBM being HBsAg themselves. It was concluded that HBsAg-Ab (antibody) complex was the pathogenetic factor responsible for the glomerular change of this particular case. Although HBsAg and Ab were examined to be negative in serum throughout the patient's clinical course, the possibility of the presence of circulating HBsAg-Ab complex in serum was discussed.     

Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

Purpose

This multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.

Methods

Thirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.

Results

The RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).

Conclusion

The current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

     

Adenovirus-mediated transfer of wild-type p53 gene results in apoptosis or growth arrest in human cultured gastric carcinoma cells.

We examined the susceptibility of six human gastric carcinoma cell lines to infection with recombinant p53 adenovirus vector (AxCA-p53). AxCA-p53 infection at a muliplicity of infection (MOI) of 50 resulted in apoptotic cell death (MKN-1 cells), growth arrest (MKN-45, MKN-74 and KATO-III cells), or non-effectiveness (TMK-1 and OCUM-2M cells). Western blot analysis revealed increasing expression levels of p21/WAF1 protein after infection with AxCA-p53 in all the cell lines. After infection with AxCA-p53, the expression levels of bax or bcl-XL protein changed in MKN-1, but not in the other cell lines. These results suggest that the apoptotic pathway (dependence on the expressions of bcl-2 family proteins) dominates the growth arrest pathway (dependence on the expressions of p21/WAF1 protein) after infection with AxCA-p53. Thus, the bcl-2 family might play a crucial role in p53-mediated growth arrest and apoptosis in human gastric carcinoma cells.