Renal cell carcinoma: incidental detection and pathological staging

In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p < 0.05; Chi-square test). The disease free survival was significantly better for those with incidental detection (86% c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.     

Distribution of ran-domised controlled trials of drugs for post-operative nausea and vomiting

Purpose: Randomised controlled trials (RCTs) guide therapeutic decisions. But which RCTs are done; which omitted; and which should be done? This study illustrates a method to explore these questions applied to drugs for post-operative nausea and vomiting (PONV). Methods: Review artides listed 18 drugs for PONV. All RCTs of these drugs for PONV were sought. The first drug mentioned in an RCT was counted and tabulated against others in all the arms of the RCT (against itself in a dose-ranging RCT). Additional drugs mentioned in these RCTs were added to the study, for a total of 40 drugs. Results: Drugs involved in the most RCTs were: ondansetron 131 RCTs; propofol 118; droperidol 74; metoclopramide 67; granisetron 52; scopolamine 22; tropisetron 16. Drugs involved in the fewest RCTs: two drugs with 2 RCTs; twelve drugs with one; three with none. Probability that this distribution occurred by chance:P<0.00001; that the distribution of dose-ranging RCTs occurred by chance:P<0.001. Regression of RCT numbers on cost: R=0.86,P<0.0001; on year of drug introduction: R=0.14. Of 1600 possible comparisons of drugs for PONV, (including dose-ranging) 97.8% have never been published. Conclusion: Although some antiemetic drugs for PONV have been studied in large numbers of RCTs, many have not been adequately evaluated. Finding relevant RCTs and tabulating their comparison arms is useful for directing future research, and is applicable to any symptom or disorder.     

Clinics in diagnostic imaging (50). Leiomyosarcoma of bladder

A 39-year-old man presented with intermittent painless macroscopic haematuria. He was subsequently diagnosed to have a high grade leiomyosarcoma of the bladder. He underwent total cystoprostatectomy and radiotherapy but died of metastatic disease five months after the initial diagnosis. Aspects of the imaging and diagnostic pathway of painless haematuria are discussed. The management of leiomyosarcomas in the urinary system is highlighted.     

Clinics in diagnostic imaging (46). Renal cell carcinoma in acquired cystic kidney disease

Acquired cystic disease of the kidney and renal cell carcinoma are associated with chronic renal failure. In recent years, there has been increased incidental detection of renal tumours through the liberal use of ultrasonography (US) and computed tomography (CT). A 40-year-old man suffering from chronic renal failure and who was being treated with haemodialysis for six years, was found to have a complex cystic lesion on US and CT. Nephrectomy was performed and the lesion was confirmed to be renal cell carcinoma associated with acquired cystic kidney disease. The current role of imaging in the management of affected patients are discussed.     

Ambulatory labor epidural analgesia: bupivacaine versus ropivacaine

Dilute concentrations of bupivacaine combined with fentanyl have recently been used to initiate labor epidural analgesia in an attempt to balance adequate analgesia and minimal maternal motor blockade. Similar concentrations of ropivacaine have not been evaluated. This prospective, randomized, double-blinded study was designed to compare the efficacy of 20 mL of either 0.08% bupivacaine plus 2 microg/mL fentanyl or 0.08% ropivacaine plus 2 microg/mL fentanyl to initiate ambulatory labor epidural analgesia. Forty nulliparous women in early ( 0 but < 20 at 20 min. The time (mean +/- SD) to visual analog scale score = 0 was BF (n = 18): 12.0 +/- 4.5 min and RF (n = 19): 12.4 +/- 4.0 min (P > 0.05). Spontaneous micturition was observed in 65% (13 of 20) BF compared with 100% (20 of 20) RF (P < 0.01), and ambulation was demonstrated in 75% (15 of 20) BF compared with 100% (20 of 20) RF (P < 0.03). The incidence of forceps delivery was 35% (7 of 20) BF compared with 10% (2 of 20) RF (P < 0.04). The results of this study indicate that dilute ropivacaine combined with fentanyl effectively initiates epidural analgesia while concurrently preserving maternal ability to void and ambulate. Implications: As compared with a similar dilute concentration of bupivacaine, 20 mL of dilute (0.08%) ropivacaine combined with fentanyl (2 microg/mL) effectively initiates epidural analgesia in nulliparous women in early, established labor while preserving their ability to micturate and ambulate. Of importance, it appears that a true ambulatory epidural analgesic for women in labor is now possible.     

Combination bcl-2 antisense and radiation therapy for nasopharyngeal cancer.

PURPOSE: A wide variety of tumors depend on the dysregulation of Bcl-2 family proteins for survival. The resulting apoptotic block can often provide a mechanism for resistance to anticancer treatments, such as chemotherapy and radiation. This current study evaluates the efficacy of combining systemically delivered Bcl-2 phosphorothioate antisense (Bcl-2 ASO) and radiation for nasopharyngeal cancer therapy. RESULTS: Antisense uptake was unaffected by 0, 3, or 6 Gy radiation. Radiation decreased the fraction of viable C666-1 cells to 60%, with a further decrease to 40% in combination with Bcl-2 ASO. Despite a modest in vitro effect, Bcl-2 ASO alone caused the regression of established xenograft tumors in mice, extending survival by 15 days in a C666-1 and by 6 days in a C15 model. The survival times for mice treated with both Bcl-2 ASO and radiation increased by 52 days in C666-1 and by 20 days in C15 tumors. This combination resulted in a more-than-additive effect in C666-1 tumors. Less impressive gains observed in C15 tumors might be attributable to higher expression of antiapoptotic Bcl-2 family proteins and limited drug distribution in the tumor. Retreatment of C666-1 tumors with the Bcl-2 ASO-radiation combination, however, was effective, resulting in mice surviving for >80 days relative to untreated controls. CONCLUSIONS: Our results show that the Bcl-2 ASO and radiation combination is a highly potent therapy for nasopharyngeal cancer. Further examination of combination therapy with radiation and other Bcl-2 family-targeted anticancer agents in both preclinical and clinical settings is definitely warranted.     

Bone marrow genotoxicity of 2,5‐dimethylfuran,a green biofuel candidate

2,5‐Dimethylfuran (DMF) is being considered as a potential green transportation biofuel, but there is limited information about its toxicity and safety. We examined DMF toxicity in the bone marrow using a murine in vitro erythropoietic micronucleus assay and found that exposure to DMF (0.1 mM, 1 hr) induced an increase in micronuclei frequency compared with controls. These data suggest that DMF may be genotoxic to hematopoietic cells and that more thorough toxicological studies on DMF should be conducted to ensure public and occupational safety before it is considered a viable biofuel and produced in mass quantities. As well as specific data on DMF, our study further validates an in vitro cell culture system that captures the essential features of the in vivo mammalian micronucleus genotoxicity assay, enabling increased throughput and controlled studies on hematopoietic DNA damage response, while reducing animal sacrifice. In vitro assays, such as the in vitro micronucleus assay, will be essential as international chemical policy is increasingly utilizing green chemistry principles that require more toxicological testing. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.     

Additional benefit of combined therapy with melatonin and apoptotic adipose‐derived mesenchymal stem cell against sepsis‐induced kidney injury

This study tested whether combined therapy with melatonin and apoptotic adipose‐derived mesenchymal stem cells (A‐ADMSCs) offered additional benefit in ameliorating sepsis‐induced acute kidney injury. Adult male Sprague–Dawley rats (n = 65) were randomized equally into five groups: Sham controls (SC), sepsis induced by cecal‐ligation and puncture (CLP), CLP‐melatonin, CLP‐A‐ADMSC, and CLP‐melatonin‐A‐ADMSC. Circulating TNF‐α level at post‐CLP 6 hr was highest in CLP and lowest in SC groups, higher in CLP‐melatonin than in CLP‐A‐ADMSC and CLP‐melatonin‐A‐ADMSC groups (all P < 0.001). Immune reactivity as reflected in the number of splenic helper‐, cytoxic‐, and regulatory‐T cells at post‐CLP 72 hr exhibited the same pattern as that of circulating TNF‐α among all groups (P < 0.001). The histological scoring of kidney injury and the number of F4/80+ and CD14+ cells in kidney were highest in CLP and lowest in SC groups, higher in CLP‐melatonin than in CLP‐A‐ADMSC and CLP‐melatonin‐A‐ADMSC groups, and higher in CLP‐A‐ADMSC than in CLP‐melatonin‐A‐ADMSC groups (all P < 0.001). Changes in protein expressions of inflammatory (RANTES, TNF‐1α, NF‐κB, MMP‐9, MIP‐1, IL‐1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF‐β) markers, reactive‐oxygen‐species (NOX‐1, NOX‐2), and oxidative stress displayed a pattern identical to that of kidney injury score among the five groups (all P < 0.001). Expressions of antioxidants (GR+, GPx+, HO‐1, NQO‐1+) were lowest in SC group and highest in CLP‐melatonin‐A‐ADMSC group, lower in CLP than in CLP‐melatonin and CLP‐A‐ADMSC groups, and lower in CLP‐melatonin‐ than in CLP‐A‐ADMSC‐tretaed animals (all P < 0.001). In conclusion, combined treatment with melatonin and A‐ADMSC was superior to A‐ADMSC alone in protecting the kidneys from sepsis‐induced injury.