Current status of embolic agents for liver tumor embolization

Gelatin sponge and polyvinyl alcohol particles have been the most popular particulate embolic agents for transarterial chemoembolization (TACE) of liver tumors. Over the last decade, calibrated microspheres have been introduced and increasingly used in liver tumor embolization in Western countries. In addition, drug-eluting beads (DEB) have been introduced for sustained local drug release. Such long-awaited spherical embolic agents will be introduced in Japan in the near future. The advantages of these microspheres are that particles are uniform in size and shape, and easy to inject through a microcatheter. They can travel distally to vessels corresponding to the particle size; in other words, the occlusion level can be predicted according to the particle size chosen. Thus, new bland microspheres and DEB may bring a significant advancement to embolization for primary liver tumors as well as hepatic metastases from various cancers. However, at this point, the published data suggests that both conventional TACE and DEB-TACE are equally effective for treatment of unresectable hepatocellular carcinoma, when patients are carefully selected. Therefore, indication, patient selection, and embolization techniques will be essential in order to individually adapt newer embolic agents based on oncological, anatomical and technical considerations.     

Retrospective analysis of third-line and fourth-line chemotherapy for advanced non-small-cell lung cancer

BackgroundThe efficacy of third-line and further-line chemotherapy for advanced non–small-cell lung cancer (NSCLC) remains unknown.Patients and MethodsWe evaluated the clinical outcome of third- and fourth-line chemotherapy for the treatment of advanced NSCLC in consecutive patients who received first-line chemotherapy at our institute between July 2002 and June 2006. From a hospital-based registry, the following data were extracted: (a) patient characteristics, (b) type of chemotherapeutic agents, and (c) objective response and survival data.ResultsA total of 599 patients were included in this analysis. Overall, 69.3%, 38.4%, 17.7%, and 6.0% of the patients received second-, third-, fourth-, and fifth-line chemotherapy, respectively. Significant differences in age (P < .0001), performance status at the start of first-line chemotherapy (P < .0001), and histology (P = .0175) were observed between patients who received third-line chemotherapy and those who did not. Docetaxel, gefitinib, and S-1 were the most frequently used regimens for third- or fourth-line chemotherapy. Five percent of the patients had participated in phase I trials of investigational new drugs. The objective response rates and disease control rates of third- and fourth-line chemotherapy were 17.0% and 34.4% and 11.3% and 24.5%, respectively. The median survival times (95% confidence interval [CI]) from the start of first-, second-, third-, and fourth-line chemotherapy until death were 15.3 months (95% CI, 13.8-16.5 months), 12.8 months (95% CI, 10.7-14.5 months), 12.0 months (95% CI, 9.3-14.2 months), and 9.9 months (95% CI, 8.6-12.0 months), respectively.ConclusionAs many as 38% of patients with advanced NSCLC who received first-line chemotherapy could receive third-line chemotherapy. This result emphasizes the need for randomized controlled trials of third-line treatment in patients with advanced NSCLC.     

Successful Treatment of Antifungal Combination Therapy with Inhaled Liposomal Amphotericin B and Oral Voriconazole for Intractable Chronic Progressive Pulmonary Aspergillosis

We experienced a case of the successful treatment of intractable pulmonary aspergillosis with inhaled liposomal amphotericin B (L-AMB) and oral voriconazole (VRCZ). A 52-year-old man was admitted to our hospital with a fever. Chest computed tomography (CT) revealed an infiltrative shadow. Two separate sputum cultures detected Aspergillus niger. Although we treated the patient with single and combined antifungal agents, the infiltrative shadow worsened. After obtaining sufficient informed consent from the patient, we switched him to an inhaled L-AMB. The infiltrative shadow subsequently improved. The patient has remained well for one year without exacerbation. We herein report the usefulness of inhaled L-AMB and oral VRCZ.     

Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer

Purpose

The pharmacokinetic (PK)–pharmacodynamic (PD) relationship of amrubicin and its active metabolite, amrubicinol, has only been evaluated using trough levels of these agents since the full PK profiles not yet been clarified so far. This study was performed to analyze the full PK profiles of amrubicin and amrubicinol and to evaluate their toxicity–PK relationships in Japanese patients.

Methods

Amrubicin (35–40?mg/m²) was administered to 21 lung cancer patients on days 1–3 every 3–4?weeks. Fourteen blood samples were obtained per patient over the course of 3 administration days. The plasma concentrations of amrubicin and amrubicinol were quantitated by HPLC, and the relationships between PK parameters of these compounds and hematological toxicities were evaluated.

Results

The overall PK profiles of amrubicin and amrubicinol were well characterized using a 3-compartment model and a 1-compartment model with a first-order metabolic process, respectively. The major toxicities were hematological. The clearance of amrubicinol was significantly correlated with grade 4 neutropenia (P?=?0.01). The percentage decreases in the neutrophil count, hemoglobin level and platelet count were well correlated with the amrubicinol AUC.

Conclusion

The pharmacokinetic profiles of amrubicin and amrubicinol were clarified, and the subsequent PK–PD analyses indicate that the clearance of amrubicinol is the major determinant of neutropenia.     

Technical standardization of laparoscopic splenectomy harmonized with hand-assisted laparoscopic surgery for patients with liver cirrhosis and hypersplenism

Background/purpose

The aims of this study were to standardize the techniques of laparoscopic splenectomy (LS) to improve safety in liver cirrhosis patients with portal hypertension.

Methods

From 1993 to 2008, 265 cirrhotic patients underwent LS. Child-Pugh class was A in 112 patients, B in 124, and C in 29. Since January 2005, we have adopted the standardized LS including the following three points: hand-assisted laparoscopic surgery (HALS) should be performed in patients with splenomegaly (≧1,000 mL), perisplenic collateral vessels, or Child-Pugh score 9 or more; complete division and sufficient elevation of the upper pole of the spleen should be performed before the splenic hilar division; and when surgeons feel the division of the upper pole of the spleen is too difficult, conversion to HALS should be performed.

Results

There were no deaths related to LS in this study. After the standardization, conversion to open surgery significantly reduced from 11 (10.3%) of 106 to 3 (1.9%) of 159 patients (P < 0.05). The average operation time and blood loss significantly reduced from 259 to 234 min (P < 0.01) and from 506 to 171 g (P < 0.01), respectively.

Conclusions

With the technical standardization, LS becomes a feasible and safe approach in the setting of liver cirrhosis and portal hypertension.     

Changes in lung function and health status in patients with COPD treated with tiotropium or salmeterol plus fluticasone

Background and objective: The effects of tiotropium, a long‐acting anticholinergic drug, were compared with those of the combination of salmeterol, a long‐acting β₂‐agonist, and fluticasone, an inhaled corticosteroid, in patients with COPD. Methods: A 4‐month, randomized, open cross‐over study of tiotropium, 18 µg once daily, versus salmeterol, 50 µg, plus fluticasone, 200 µg, twice daily, was conducted in patients with COPD. Efficacy was assessed by spirometry and responses to the St George's Respiratory Questionnaire (SGRQ). After 4 months, patients were asked to select their subsequent therapy and indicate the reasons for their selection. Results: A total of 78 patients completed the study. There were no significant differences in the improvements in FEV₁ or SGRQ scores between the therapies. Similar numbers of patients selected tiotropium (42.3%) and salmeterol plus fluticasone (57.7%). However, those who preferred one of the therapies demonstrated greater improvements in SGRQ scores with that therapy. One subgroup of patients (30.8%) showed greater improvements in dyspnoea and FEV₁ in response to tiotropium, and the other subgroup of patients (35.9%) showed greater improvements in dyspnoea and FEV₁ in response to salmeterol plus fluticasone. Some patients (14.1%) selected salmeterol plus fluticasone because of positive effects on sputum expectoration. Conclusions: The study was unblinded and the results need to be interpreted with caution. However, tiotropium and salmeterol plus fluticasone had similar overall effects on pulmonary function and SGRQ scores in patients with COPD. Responses to the two therapies were heterogeneous, and the patients who showed greater improvements in FEV₁ or SGRQ scores with one of the therapies preferred it for their subsequent treatment.     

Lithium and dementia: a preliminary study

Recent studies have shown that lithium may block the accumulation of amyloid-beta (Abeta) peptides and to inhibit the hyperphosphorylation of tau via the inhibition of GSK-3alpha in the brain of mice. The purpose of the present study is to examine whether lithium could potentially be effective for the prevention of Alzheimer's disease. We investigated the clinical records of 1,423 outpatients at a university psychiatric outpatient clinic and classified patients according to the following criteria: (a) absence of a diagnosis of dementia, (b) age 60 years or older, and (c) lithium had been prescribed and/or was currently prescribed. We compared these patients with randomly selected age and gender matched control group who had never been prescribed lithium. Despite no significant difference in MMSE scores between the lithium group, which consisted of patients receiving lithium treatment, and the control group, those who had previously received lithium and/or were currently prescribed lithium had significantly better MMSE scores than the control patients. The findings provide partial evidence to support the contention that lithium could offer hope as a preventive treatment for Alzheimer's disease. Further prospective studies with a large number of patients are warranted to investigate this potentially important effect.