Renal vein dilation predicts poor outcome in patients with refractory cirrhotic ascites

Aim

Renal venous hypertension is known to be associated with worsening of renal function in patients with decompensated heart failure. Intra‐abdominal hypertension including cirrhotic ascites also leads to renal venous hypertension. We aimed to clarify the effect of renal venous hypertension on cirrhotic ascites.

Methods

Two hepatologists measured the left renal vein diameter in 142 consecutive patients with refractory cirrhotic ascites using non‐contrast computed tomography. The renal vein diameter was measured at the renal vein main trunk and upstream of the confluence of collateral veins.

Results

The inter‐observer agreements were high for the measurements of the left renal vein (r = 0.918, P < 0.001). The median overall survival for patients with renal vein diameter ≥11 mm was less than that for patients with renal vein diameter <11 mm (P < 0.001; 2.5 vs. 32.0 months). One‐year survival rates were 15.3% versus 66.4%. Multivariate analysis revealed renal vein diameter ≥11 mm (hazard ratio, 2.94; P < 0.001; 95% confidence interval, 1.67–5.20) and a high Model for End‐stage Liver Disease score combined with serum sodium level (MELD‐Na) (hazard ratio, 3.39; P < 0.001; 95% confidence interval, 2.00–5.74) were significant independent predictors of mortality.

Conclusions

Renal vein dilation is a risk factor of mortality in patients with refractory cirrhotic ascites, independent of the MELD‐Na score.     

Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer

The purpose of this study was to develop a new type of gene vector, polyamidoamine (PAMAM) dendriplex pharmaceutically modified, based on electrostatic interactions, by various anionic polymers. The γ-polyglutamic acid (γ-PGA)/PAMAM dendriplex and the α-PGA/PAMAM dendriplex formed a stable complex, although α-polyaspartic acid and heparin released pDNA from the complex. The addition of anionic polymer decreased the ζ-potential, although it did not greatly affect the size of the complex. As a result of an in vitro gene expression study of mouse melanoma cells, we found that the γ-PGA/PAMAM dendriplex showed high gene expression comparable to the PAMAM dendriplex, although the α-PGA/PAMAM dendriplex showed lower gene expression. Tail vein injection of the γ-PGA/PAMAM dendriplex into mice also led to high gene expression in the spleen and lung. The γ-PGA/PAMAM dendriplex showed no cytotoxicity and no agglutination, although severe cytotoxicity and agglutination were observed in the PAMAM dendriplex. Thus, we discovered that complexes of pDNA, PAMAM dendrimers, and γ-PGA showed higher gene expression in vitro and in vivo, and markedly lower toxicity. This complex is valuable and is expected to be a safe and effective gene vector.     

Protective effect of geranylgeranylacetone against loxoprofen sodium-induced small intestinal lesions in rats

We studied the effect of the selective serotonin reuptake inhibitor (SSRI) paroxetine on the immobility time in the forced swimming test using different strains of mice (ICR, ddY, C57BL/6, BALB/c and DBA/2). There was a difference between strains in the response to paroxetine (although it induced anti-immobility effects in all strains of mice used). The mouse strain most sensitive to paroxetine was DBA/2; the ICR strain showed the lowest sensitivity. We previously demonstrated variations in the responses to another SSRI, fluvoxamine, in different strains of mice, which was in agreement with the present findings. In DBA/2 and ICR mice, the anti-immobility effects of paroxetine were significantly antagonized by the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). The noradrenergic α(1)-adrenoceptor antagonist prazosin significantly reduced the anti-immobility effects elicited by a high dose (5mg/kg) of paroxetine in DBA/2 and ICR mice. However, prazosin did not affect the anti-immobility effects of a lower dose of paroxetine (1mg/kg) in DBA/2 mice. This suggests that the anti-immobility effects of a higher dose of paroxetine in mice are associated with serotonergic and noradrenergic neurons. Prazosin did not the affect anti-immobility effects of fluvoxamine. These results suggest that there are differences between mice strains in the antidepressant-like effects of paroxetine (which are similar to those elicited by fluvoxamine). Moreover, involvement of the noradrenergic system was partly related to the anti-immobility effects of paroxetine (which are different to those elicited by fluvoxamine).     

Effect of viscous additives on the absorption and hepatic disposition of 5-fluorouracil (5-FU) after application to liver surface in rats

Objectives The aim was to study the effect of viscous additives on the absorption and hepatic disposition of 5‐fluorouracil (5‐FU) after application to the liver surface in rats. Methods 5‐FU solution with or without viscous additives was applied to the rat liver surface with a cylindrical diffusion cell. Then, blood and the remaining solution in the diffusion cell were collected at selected times, followed by excision of the liver. The excised liver was divided into three sites and assayed for 5‐FU content. Key findings The absorption rate of 5‐FU from the liver surface was decreased in the presence of carboxymethylcellulose sodium (CMC‐Na) and polyvinyl alcohol (PVA) as compared with the control. The k_a values of PVA 15% and CMC‐Na 1% were reduced to about 80 and 67% of the control. The maximum plasma concentration of 5‐FU was decreased by incorporation of viscous additives. The 5‐FU concentration at the diffusion cell attachment site of the liver (site 1) plateaued at 180 min in the absence of viscous additives. On the other hand, the concentration of 5‐FU at site 1 increased in a time‐dependent manner until 360 min in the presence of viscous additives. Conclusion Viscous additives might be useful for retaining drugs at their application site and controlling the rate of absorption from the liver surface.     

Cervical non-squamous carcinoma: an effective combination chemotherapy of taxane, anthracycline and platinum for advanced or recurrent cases

Objective

An effective salvage chemotherapy for advanced and recurrent non-squamous carcinoma of the uterine cervix has not yet been established. The aim of the present study was to analyze the safety and efficacy of a combination chemotherapy for this disease using taxane, anthracycline, and platinum.

Study design

This was a retrospective analysis of advanced and recurrent non-squamous cervical cancers treated at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases during a 10 year study period from 2000 to 2009. Single agent chemotherapies and combination chemotherapies for advanced and recurrent cervical cancer cases of non-squamous histology which were reported in the English literature were also reviewed.

Results

Salvage chemotherapy, using taxane, anthracycline and platinum, was performed for 5 advanced and 14 recurrent cases. Prior to the salvage chemotherapy, 15 (79%) of the 19 patients had already received either radiation or chemotherapy. A complete or partial tumor response was achieved in 8 (42%) of the 19 cases. The response rate for recurrent disease in a previously irradiated field was 40%. The median progression-free survival (PFS) and overall survival (OS) were 8 months (1–108) and 13 months (5–108), respectively. Grade 4 and febrile grade 3 neutropenia was observed in 6 cases (32%), but there was no case in which salvage chemotherapy had to be cancelled due to toxicity. According to previous reports, the cumulative response rate of combination chemotherapy (35%) was significantly higher than that of single agent chemotherapy (17%) (p < 0.001). OS tended to be longer in the combination chemotherapy cases (8.7 months to 18 months) than that of single agent chemotherapy cases (7.3+ months to 9.1+ months).

Conclusion

Combination chemotherapy of taxane, anthracycline, and platinum was found to have a survival benefit for advanced and recurrent cervical cancer patients of non-squamous carcinoma histology, with a tolerable toxicity.     

Discordance of motion artifacts on magnetic resonance imaging in Creutzfeldt-Jakob disease: comparison of diffusion-weighted and conventional imaging sequences

Purpose Motion artifact is problematic in the diagnosis of Creutzfeldt-Jakob disease (CJD) because of dementia. The purpose was to compare the occurrence of this artifact between a diffusion-weighted (DW) magnetic resonance (MR) imaging sequence and conventional sequences. Materials and methods Ten MR examinations comprising T2-weighted, T1-weighted, DW, and fluid-attenuated inversion recovery imaging in seven CJD patients were retrospectively evaluated. The occurrence of motion artifacts on each sequence were assessed, and the examination was classified into four groups as follows: group A, motion artifact not revealed on DW imaging but revealed on one or more other sequences; group B, revealed on DW imaging and one or more other sequences; group C, not revealed on any sequences; and group D, revealed on DW imaging but not on any other sequences. Results The 10 MR examinations were classified as eight group A (80%), one B (10%), one C (10%), and zero D (0%). Conclusion Motion artifacts are likely to occur in any conventional imaging sequences in CJD, but the fast-imaging ability of DW imaging can reduce this artifact. The combination of an absence of motion artifact on DW imaging and the presence on conventional sequences may be one of the frequent findings of CJD.     

Adrenal masses: the value of additional fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in differentiating between benign and malignant lesions

Objective  To investigate whether integrated fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) can differentiate benign from adrenal malignant lesions on the basis of maximum standardized uptake value (SUV_max), tumor/liver (T/L) SUV_max ratio, and CT attenuation value (Hounsfield Units; HU) of unenhanced CT obtained from FDG-PET/CT data. Methods  We studied 30 patients with 35 adrenal lesions (16 adrenal benign lesions, size 16 ± 5 mm, in 15 patients; and 19 adrenal malignant lesions, 24 ± 12 mm, in 15 patients) who had confirmed primary malignancies (lung cancer in 23 patients, lymphoma in 2, esophageal cancer in 2, hypopharyngeal cancer in 1, prostate cancer in 1, and 1 patient in whom lesions were detected at cancer screening). All patients underwent PET/CT at 1 h post FDG injection. Diagnosis of adrenal malignant lesions was based on interval growth or reduction after chemotherapy. An adrenal mass that remained unchanged for over 1 year was the standard used to diagnose adrenal benign lesions. Values of FDG uptake and CT attenuation were measured by placing volumetric regions of interest over PET/CT images. Adrenal uptake of SUV_max ≥ 2.5 was considered to indicate a malignant lesion; SUV_max < 2.5 was considered to indicate a benign lesion. In further analysis, 1.8 was employed as the threshold for the T/L SUV_max ratio. Unenhanced CT obtained from PET/CT data was considered positive for adrenal malignant lesions based on a CT attenuation value ≥ 10 HU; lesions with a value < 10 HU were considered adrenal benign lesions. Mann–Whitney’s U test was used for statistical analyses. Results  SUV_max in adrenal malignant lesions (7.4 ± 3.5) was higher than that in adrenal benign lesions (2.1 ± 0.5, p < 0.05). The CT attenuation value of adrenal malignant lesions (27.6 ± 11.9 HU) was higher than that of adrenal benign lesions (10.1 ± 12.3 HU, p < 0.05). In differentiating between adrenal benign and malignant lesions, a CT threshold of 10 HU corresponded to a sensitivity of 57%, specificity of 94%, accuracy of 74%, positive predictive value of 92% and negative predictive value of 65%. An SUV_max cut-off value of 2.5 corresponded to a sensitivity of 89%, specificity of 94%, accuracy of 91%, positive predictive value of 94% and negative predictive value of 88%. The T/L SUV_max ratio was 1.0 ± 0.2 for adrenal benign lesions and 4.5 ± 3.0 for adrenal malignant lesions. And T/L SUV_max ratio cut-off value of 1.8 corresponded to a sensitivity of 85%, specificity of 100%, accuracy of 91%, positive predictive value of 100% and negative predictive value of 83%. Conclusions  FDG-PET/CT with additional SUV_max analysis improves the diagnostic accuracy of adrenal lesions in cancer patients.     

Evaluation of Immune-enhancing Effects of Ibuprofen in an Immunodeficiency Model

Three children and one adult with chronic mucocutaneous candidosis with documented deficient cellular immunity to Candida antigen were evaluated as a model to study the specific cellular immune-enhancing potential of the prostaglandin synthetase inhibitor ibuprofen. Oral ibuprofen failed to have any consistent effect during sequential 4-week on and off cycles on the following parameters: delayed hypersensitivity skin testing; lymphocyte transformation to Candida antigen; T-cell subsets as determined by monoclonal antibody techniques; production of human immune interferon in response to staphylococcal enterotoxin A (SEA). Two patients showed a trend toward enhanced lymphocyte transformation to PHA while taking ibuprofen. In two patients who were studied 8-10 weeks after discontinuation of oral ketoconazole therapy, clinical recurrence of CMC was not prevented by oral ibuprofen therapy.