Enhanced recovery after surgery (ERAS) might be a standard care in radical prostatectomy: a systematic review and meta-analysis.

BACKGROUND: Several enhanced recovery after surgery (ERAS) protocols for radical prostatectomy (RP) have been reported in recent years. Nonetheless, there is no sufficient evidence to support the implementation of ERAS as a standard of care modality. METHODS: A search was done in the PubMed, Embase, Clinical Trials.gov, Cochrane Library, CNKI Library databases and reference lists to identify relevant studies from inception until May 2019 to be included in the study. A systematic review of five randomized controlled trials (RCTs), one prospective cohort study and four retrospective studies covering 3,803 patients, comparing ERAS with conventional care was performed. Outcomes of interest for the study were intraoperative outcomes (operation time and blood loss), postoperative outcomes (hospital stay, catheter stay, first defecation and first anal exhaust) and postoperative complications. Random events meta-analyses were performed. Sensitivity analysis was also performed to determine whether the results of the meta-analysis were robust. RESULTS: Notably, ERAS group had significantly shorter hospital stay [overall standardized mean difference (SMD) =-1.65, 95% confidence interval (CI): -2.53, -0.76, P<0.001], shorter time to first defecation (overall SMD =-1.56, 95% CI: -2.71, -0.42, P=0.008), shorter time to first anal exhaust (overall SMD =-1.23, 95% CI: -1.97, -0.50, P=0.001) and lower incidence of nausea [overall risk ratio (RR) =0.62, 95% CI: 0.40, 0.94, P=0.024] compared to the conventional group. There was no statistical difference in intraoperative outcomes, catheter stay and other postoperative complications between the two groups (P>0.05). CONCLUSIONS: The data presented so far consistently show that ERAS may be utilized as a standard of care in RP treatment.

Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer.

Ovarian cancer is the most lethal gynecologic malignancy and the fifth most lethal cancer type overall in women. Ovarian cancer often presents genome instability, with almost half of the ovarian cancers harbor defects in one or more of the six DNA repair pathways, most of them in homologous recombination (HR). Targeting DNA repair genes has becoming a unique strategy to combat HR-deficient cancers in recent years. The multi-functional enzyme Poly ADP ribose polymerase (PARP) plays an impart role in DNA damage repair and genome stability. PARP inhibitors inhibit DNA repair pathways and cause apoptosis of cancer cells, especially in homologous recombination (HR)-deficient cells. PARP inhibitors (PARPi) have drawn increasing amount of attention due to their remarkable efficacy and low toxicity in treating HR-deficient ovarian cancers (i.e. BRCA1/2 mutated). To date, three PARP inhibitor drugs have been approved for treating ovarian cancer by FDA in United States, namely Olaparib, Rucaparib, and Niraparib. In this review, we summarized the current research progress of PARPi from basic science to clinical studies. We discussed the mechanism of action of PARP inhibitors and the exciting results from the clinical studies of the FDA-approved PARP inhibitors. We also highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics.

Penetration profile and human cadaver skin distribution of finasteride from vesicular nanocarriers.

The skin accumulation of therapeutic agents affects the efficiency of topical drug delivery. In this study, in vitro distribution of finasteride of ethosomes and liposomes in human cadaver skin after percutaneous delivery were investigated. Experiments were performed using modified Franz diffusion cells. Finasteride ethosomes, liposomes or hydroethanolic solutions were used as donor medium. Drug distribution at different skin layers and depths were studied by hotplate separation and frozen horizontal slicing technique. The result showed that the accumulation of finasteride in skin ranged from 9.7-24.3 µg/cm2 at 12 or 24 hours. The ethosomes demonstrated better enhancing ability to deliver finasteride into the dermis layer than liposomes did. The finasteride concentration in the dermis layer from ethosomes was more than sevenfold higher than from liposomes. The finasteride accumulation in ethosomes group showed a distinctive reversed distribution profile. This distinctive reversed distribution profile is meaningful for exerting a favorable pharmacological effect for finasteride. The drug distribution profile in skin layers showed no significant difference between 12 and 24 hours application (p > 0.05). The study demonstrated that finasteride can be accumulated at target site more effectively and maintained at higher level through the application of novel ethosomal carriers.

A validated RP-HPLC method to investigate finasteride in human skin after in vitro topically applying vesicular nanocarrier.

The pharmacotherapeutic efficiency of topical drug delivery systems is mainly dominated by the skin distribution of therapeutic agents. In this work, a sensitive, rapid and fully-validated reversed-phase high performance liquid chromatography (RP-HPLC) method was developed to determine finasteride in human cadaver skin after different vesicular formulations were applied. Drug in different depth of skin layers were measured with an EclipseXDB-C18 column. The mobile phase consisted of 75% (v/v) methanol containing 0.2% phosphoric acid buffered to pH 3.0 with triethylamine under isocratic conditions. The system was operated at 40°C and the mobile phase flow rate was set at 1 mL/min. The standard-calibration curve was linear within range of 5 to 200 ng/ml with correlation coefficient 0.9996. The intra-assay precision was less than 3.9% while the inter-assay precision was less than 7.1% with the bias range of -8.6 to 4.1%. This method was found to be specific, accurate, and sensitive and was successfully used to determine the accumulation of finasteride after in-vitro percutaneous delivery by liposomal or ethosomal drug delivery nanocarriers.

Thrombocytopenia associated with 5-aminosalicylate prodrug, olsalazine: is the devil still there?

CASE DESCRIPTION: We present a case of a 63-year-old Chinese female who developed severe thrombocytopenia after receiving olsalazine 1.5 g daily for 3 months, and eventually culminated in hospital admission. According to a Medline search, this is the first case report of olsalazine-associated thrombocytopenia in Asia. CONCLUSION: Olsalazine, similar to other 5-aminosalicylates, can also cause thrombocytopenia. Clinicians should be aware of this potential adverse drug reaction. Future studies should focus on the trigger mechanism and possible cross-reaction between olsalazine and other aminosalicylates.

In vitro percutaneous permeation and skin accumulation of finasteride using vesicular ethosomal carriers.

In order to develop a novel transdermal drug delivery system that facilitates the skin permeation of finasteride encapsulated in novel lipid-based vesicular carriers (ethosomes)finasteride ethosomes were constructed and the morphological characteristics were studied by transmission electron microscopy. The particle size, zeta potential and the entrapment capacity of ethosome were also determined. In contrast to liposomes ethosomes were of more condensed vesicular structure and they were found to be oppositely charged. Ethosomes were found to be more efficient delivery carriers with high encapsulation capacities. In vitro percutaneous permeation experiments demonstrated that the permeation of finasteride through human cadaver skin was significantly increased when ethosomes were used. The finasteride transdermal fluxes from ethosomes containing formulation (1.34 +/- 0.11 microg/cm(2)/h) were 7.4, 3.2 and 2.6 times higher than that of finasteride from aqueous solution, conventional liposomes and hydroethanolic solution respectively (P < 0.01).Furthermore, ethosomes produced a significant (P < 0.01) finasteride accumulation in the skin, especially in deeper layers, for instance in dermis it reached to 18.2 +/- 1.8 microg/cm(2). In contrast, the accumulation of finasteride in the dermis was only 2.8 +/- 1.3 microg/cm(2) with liposome formulation. The study demonstrated that ethosomes are promising vesicular carriers for enhancing percutaneous absorption of finasteride.