Stauffer's syndrome: A comprehensive review and proposed updated diagnostic criteria.

BACKGROUND: Stauffer's syndrome corresponds to a set of clinical and analytical changes of paraneoplastic nature firstly recognized more than 50 years ago, in association to renal cell carcinoma. A definitive review including universal diagnostic criteria and updated knowledge since the original description is lacking. BASIC PROCEDURES: The authors conducted a comprehensive bibliographical review and propose updated diagnostic criteria to standardize diagnosis for clinical practice purposes and avoid misclassification. MAIN FINDINGS: Although having been described in association with renal cell carcinoma, the syndrome has been reported in correlation with other malignancies-either solid or hematological tumors. Additionally, a variant syndrome presenting with jaundice has also been characterized, but appears to have a similar clinical course to that of the classical Stauffer's syndrome. Although often described as rare, it may be more frequent than previously recognized. Stauffer's syndrome etiopathogenesis is still poorly understood, but immune mechanisms seem to play a role underscored by the malignancies to which the syndrome is associated, several of which having immunotherapy drugs approved for their treatment. PRINCIPAL CONCLUSIONS: A set of diagnostic criteria should be used to simplify, broaden and standardized diagnosis, under the entity characterized by reversible paraneoplastic intrahepatic cholestasis. Clinicians should be aware of the syndrome, namely consider further investigation if a plausible cause for unexplained intrahepatic cholestasis in an otherwise healthy patient is not found. Even though no universal approach is available, investigation should be considered regarding metastatic disease after resection of a primary tumor which has revealed persistence or recurrence of symptoms.

Dithiothreitol-based protein equalization technology to unravel biomarkers for bladder cancer.

This study aimed to assess the benefits of dithiothreitol (DTT)-based sample treatment for protein equalization to assess potential biomarkers for bladder cancer. The proteome of plasma samples of patients with bladder carcinoma, patients with lower urinary tract symptoms (LUTS) and healthy volunteers, was equalized with dithiothreitol (DTT) and compared. The equalized proteomes were interrogated using two-dimensional gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry. Six proteins, namely serum albumin, gelsolin, fibrinogen gamma chain, Ig alpha-1 chain C region, Ig alpha-2 chain C region and haptoglobin, were found dysregulated in at least 70% of bladder cancer patients when compared with a pool of healthy individuals. One protein, serum albumin, was found overexpressed in 70% of the patients when the equalized proteome of the healthy pool was compared with the equalized proteome of the LUTS patients. The pathways modified by the proteins differentially expressed were analyzed using Cytoscape. The method here presented is fast, cheap, of easy application and it matches the analytical minimalism rules as outlined by Halls. Orthogonal validation was done using western-blot. Overall, DTT-based protein equalization is a promising methodology in bladder cancer research.

Androgen deprivation therapy in castrate-resistant prostate cancer: how important is GnRH agonist backbone therapy?

BACKGROUND: A growing number of treatment options exist to treat metastatic castrate-resistant prostate cancer (mCRPC), and with these newer options, many questions about optimising treatment remain unanswered. One recommendation that may potentially be overlooked by practitioners is that androgen deprivation therapy (ADT) should be maintained when CRPC develops and when treatment with any of the newer agents is initiated. AIM: However, to emphasise this recommendation, it is valuable to interrogate the evidence for maintaining ADT in different clinical situations. OUTCOME: This statement, reflecting the views of the authors, provides a discussion of this evidence and the rationale behind the recommendation that ADT should be continued in CRPC.

Is intermittent androgen-deprivation therapy beneficial for patients with advanced prostate cancer?

Use of intermittent androgen-deprivation therapy (IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side-effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first-line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high-risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short- and long-term side-effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side-effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT-related side-effects, and, to a degree, their impact on patient health-related quality of life (HRQL). Further comparative study is required, particularly in relation to HRQL and long-term complications associated with ADT.

Intermittent hormonal therapy for prostate cancer.

PURPOSE OF REVIEW: Intermittent hormonal therapy (IHT) for prostate cancer aims to minimize treatment-related side-effects, to improve overall quality of life, to reduce the cost of care, and possibly to delay progression to castration-resistant prostate cancer. RECENT FINDINGS: With preclinical evidence suggesting a potential benefit for IHT in terms of time to androgen independence, with phase II and phase III studies producing optimistic results, and with the potential for reductions in cost and complications, IHT has become a popular modality of therapy around the globe. SUMMARY: In the near future intermittent therapy will have place in the treatment strategy in the management of prostate cancer, particularly on men with locally advanced disease.

Sequential intravesical chemoimmunotherapy with mitomycin C and bacillus Calmette-Guérin and with bacillus Calmette-Guérin alone in patients with carcinoma in situ of the urinary bladder: results of an EORTC genito-urinary group randomized phase 2 trial (30993).

BACKGROUND: Bacillus Calmette-Guérin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS). OBJECTIVE: Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non-muscle-invasive bladder cancer patients with CIS. DESIGN, SETTING, AND PARTICIPANTS: In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR. INTERVENTION: Patients received six weekly instillations of MMC followed by six weekly instillations of BCG or six weekly instillations of BCG, 3 wk rest, and three further weekly instillations of BCG. Complete responders received three weekly maintenance instillations at 6, 12, 18, 24, 30, and 36 mo in accordance with the initial randomization. MEASUREMENTS: End points were complete response (CR) rate at the first control cystoscopy 16-18 wk after start of treatment, disease-free interval, overall survival, and side effects. RESULTS AND LIMITATIONS: Ninety-six patients were randomized, 48 to each treatment group. Ten patients were ineligible, and three did not start treatment. In all randomized patients, CR rates on MMC plus BCG and BCG alone were 70.8% and 66.7%, respectively. In 83 eligible patients who started treatment, CR rates were 75.6% and 73.8%, respectively. Based on a median follow-up of 4.7 yr, 25 patients (52.1%) on MMC plus BCG and 22 patients (45.8%) on BCG alone were disease free. Twelve patients stopped treatment due to toxicity: three during induction (two MMC plus BCG, one BCG) and nine during maintenance (three MMC plus BCG, six BCG). CONCLUSIONS: In the treatment of patients with CIS, sequential chemoimmunotherapy with MMC plus BCG had acceptable toxicity. CR and disease-free rates were similar to those on BCG alone and to previous publications on sequential chemoimmunotherapy. TRIAL REGISTRATION: This study was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC-30993). http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=68869&version=HealthProfessional&protocolsearchid=7920643.

[Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study]. / Comparaison d'un produit de phytothérapie (Permixon) et d'un alpha-bloquant (tamsulosine) dans le traitement de l'hypertrophie bénigne de la prostate: étude internationale randomisée d'une durée de 12 mois.

OBJECTIVE: While the lipidosterolic extract (LSESr) of Serenoa repens--Permixon--has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin. METHODS: Eight hundred and eleven men with symptomatic BPH (international prostdate symptom score, I-PSS > or = 10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4 mg per day (N = 354) or Permixon 320 mg per day (N = 350). I-PSS, QoL and maximum urinary flow rate (Qmax) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol (PP) population of 542 patients (tamsulosin: N = 273; Permixon: N = 269). RESULTS: At 12 months, I-PSS decreased by 4.4 in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Qmax was similar in both treatment groups (1.8 ml/s Permixon, 1.9 ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group. CONCLUSION: This study demonstrated that Permiwon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.

Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study.

OBJECTIVE: While the lipido-sterolic extract of Serenoa repens (LSESr)-Permixon((R))-has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin. METHODS: Eight hundred and eleven men with symptomatic BPH (I-PSS> or =10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4mg/day (N=354) or Permixon 320mg/day (N=350). I-PSS, QoL and Q(max) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol population of 542 patients (tamsulosin: N=273; Permixon: N=269). RESULTS: At 12 months, I-PSS decreased by 4.4in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Q(max) was similar in both treatment groups (1.8ml/s Permixon, 1.9ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group. CONCLUSION: This study demonstrates that Permixon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.