Microsatellite Instability Is Insufficiently Used as a Biomarker for Lynch Syndrome Testing in Clinical Practice.

Purpose: The pan-cancer presence of microsatellite instability (MSI)-positive tumors demonstrates its clinical utility as an agnostic biomarker for identifying immunotherapy-eligible patients. Additionally, MSI is a hallmark of Lynch syndrome (LS), the most prevalent cancer susceptibility syndrome among patients with colorectal and endometrial cancer. Therefore, MSI-high results should inform germline genetic testing for cancer-predisposing genes.

The Impact of Enhanced Recovery after Surgery Protocol Implementation on Postoperative Pain Management in the Era of Opioid Crisis: The Postchemotherapy Open RPLND Experience.

Aim: Enhanced Recovery After Surgery (ERAS) protocols have been proven to optimize postoperative outcomes; however, misuse of opioid analgesics can still hinder postoperative recovery due to related side effects and potential complications.

Introduction: To determine if the implementation of ERAS protocol in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) patients could help with reducing postoperative pain and opioid use.

Methods: A case-control study of consecutive testicular cancer patients with indications for PCRLPND, who were offered Conventional Post-operative Management (CPM) or ERAS protocol.

Explorative investigation of the anti-glycative effect of a rapeseed by-product extract.

The formation of advanced glycation end-products (AGEs) in biological systems is increased during hyperglycaemia due to higher levels of circulating glucose and carbonyl reactive species. AGEs are causative factors of common chronic diseases. Since synthetic AGE-inhibitors exert unwanted side effects and polyphenols act as potent antiglycative agents, vegetables (fruits, seeds and related by-products) are good candidates when searching for natural inhibitors.

Sexual dysfunction in testicular cancer patients subjected to post-chemotherapy retroperitoneal lymph node dissection: a focus beyond ejaculation disorders.

Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) represents an integral part of multidisciplinary treatment of advanced germ cell cancer; however, it is associated with a high complications rate. The present study aimed to describe sexual disorders in 53 patients with testicular cancer who underwent full bilateral, non-nerve-sparing PC-RPLND in our institution, focusing beyond ejaculatory dysfunction. The International Index for Erectile Function (IIEF) questionnaire was used as diagnostic tool of male sexual functioning pre-operatively and three months after RPLND, while post-operatively patients were asked to describe and evaluate changes in selected sexual parameters.

Simple and reliable HPLC method for the monitoring of methotrexate in osteosarcoma patients.

Methotrexate (MTX) is a dihydrofolate reductase inhibitor that is used for the treatment of tumors and autoimmune diseases. Several automated binding assays are used in clinical practice and numerous chromatographic methods have been developed toward higher specificity and sensitivity. In the present study, phenyl cartridges were used for the solid-phase extraction (SPE) of MTX from human serum samples; subsequently, extracts were analyzed by reversed-phase high-performance liquid chromatography.

Revisiting bleomycin from pathophysiology to safe clinical use.

Bleomycin is a key component of curative chemotherapy regimens employed in the treatment of curable cancers, such as Hodgkin lymphoma (HL) and testicular germ-cell tumours (GCT), yet its use may cause bleomycin-induced lung injury (BILI), which is associated with significant morbidity and a mortality rate of 1-3%. Diagnosis of BILI is one of exclusion and physicians involved in the care of HL and GCT patients should be alerted. Pharmacogenomic studies could contribute towards the identification of molecular predictors of bleomycin toxicity on the aim to optimize individual use of bleomycin.

Expression of neutral endopeptidase, endothelin-1, and nuclear factor kappa B in prostate cancer: interrelations and associations with prostate-specific antigen recurrence after radical prostatectomy.

Objective. To study the impact of the neutral endopeptidase (NEP)/neuropeptides (NPs) axis and nuclear factor kappa B (NFκB) as predictors of prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Patients and Methods.

Basic Concepts in Metastatic Cardiac Disease.

The involvement of the heart in metastatic cancer is a rare clinical diagnosis, as it may be asymptomatic or symptoms, when present, may be attributed to other causes. Issues regarding incidence, intracardiac location, clinical presentation, diagnosis and treatment of metastatic cardiac tumors will be discussed here.

Bortezomib reverses the proliferative and antiapoptotic effect of neuropeptides on prostate cancer cells.

Objectives: Neuropeptides are important signal initiators in advanced prostate cancer, partially acting through activation of nuclear factor kappa B. Central to nuclear factor kappa B regulation is the ubiquitin-proteasome system, pharmacological inhibition of which has been proposed as an anticancer strategy. We investigated the putative role of the proteasome inhibitor bortezomib in neuropeptides signaling effects on prostate cancer cells.

CD10 is inversely associated with nuclear factor-kappa B and predicts biochemical recurrence after radical prostatectomy.

Introduction: The cell surface endopeptidase CD10 (neutral endopeptidase) and nuclear factor-κB (NF-κB) have been independently associated with prostate cancer (PC) progression. We investigated the correlations between these two factors and their prognostic relevance in terms of biochemical (prostate-specific antigen, PSA) relapse after radical prostatectomy (RP) for localized PC.

Patients And Methods: The immunohistochemical expression of CD10 and NF-κB in samples from 70 patients who underwent RP for localized PC was correlated with the preoperative PSA level, Gleason score, pathological stage and time to PSA failure.

Lack of prognostic significance of p16 and p27 after radical prostatectomy in hormone-naïve prostate cancer.

Background: Loss of normal cell cycle control is an early event in the evolution of cancer. The expression of cyclin-dependent kinase (CDK) inhibitors p16 and p27 has been previously associated with progression of prostate cancer (PC). 70 patients diagnosed with early stage PCwere treated with radical prostatectomy (RP) at our institution and their tumor specimens were immunohistochemically evaluated for expression of p16 and p27.

Comparative study of spatial localization of HER-2 and CEP17 signals and of HER-2/CEP17 ratios, in "thin" and "thick" tissue sections.

One presumed drawback of performing fluorescence in situ hybridization on routine tissue sections for HER-2 status evaluation in breast carcinomas is nuclear truncation. Therefore, HER-2/CEP 17 ratios were compared in routine (4 μm) vs. thicker (15 μm) tissue sections.

p53 and cyclooxygenase-2 expression are directly associated with cyclin D1 expression in radical prostatectomy specimens of patients with hormone-naïve prostate cancer.

Prostate cancer (PCa) is a potentially curable disease when diagnosed in early stages and subsequently treated with radical prostatectomy (RP). However, a significant proportion of patients tend to relapse early, with the emergence of biochemical failure (BF) as an established precursor of progression to metastatic disease. Several candidate molecular markers have been studied in an effort to enhance the accuracy of existing predictive tools regarding the risk of BF after RP.

Inverse baseline expression pattern of the NEP/neuropeptides and NFκB/proteasome pathways in androgen-dependent and androgen-independent prostate cancer cells.

Background: Castration-resistance in prostate cancer (PC) is a critical event hallmarking a switch to a more aggressive phenotype. Neuroendocrine differentiation and upregulation of NFκB transcriptional activity are two mechanisms that have been independently linked to this process.

Methods: We investigated these two pathways together using in vitro models of androgen-dependent (AD) and androgen-independent (AI) PC.

Nonbacterial thrombotic (marantic) endocarditis in a patient with colorectal cancer.

Background: Marantic endocarditis, presently termed nonbacterial thrombotic endocarditis (NBTE), is an infrequent post-mortem diagnosis in the adult population but a not so rare event in the course of neoplastic conditions.

Case Report: We describe the case of a 74-year-old woman with advanced sigmoid adenocarcinoma, who developed aseptic vegetations in the right atrium of the heart. Systemic anticoagulation therapy was started, and upon clinical improvement systemic chemotherapy was added, resulting in partial response to antineoplastic therapy along with improvement of her cardiopulmonary status.

The ubiquitin-proteasome system in cancer, a major player in DNA repair. Part 1: post-translational regulation.

DNA repair is a fundamental cellular function, indispensable for cell survival, especially in conditions of exposure to environmental or pharmacological effectors of DNA damage. The regulation of this function requires a flexible machinery to orchestrate the reversal of harmful DNA lesions by making use of existing proteins as well as inducible gene products. The accumulation of evidence for the involvement of ubiquitin-proteasome system (UPS) in DNA repair pathways, that is reviewed here, has expanded its role from a cellular waste disposal basket to a multi-dimensional regulatory system.

The ubiquitin-proteasome system in cancer, a major player in DNA repair. Part 2: transcriptional regulation.

DNA repair is an indispensable part of a cell's defence system against the devastating effects of DNA-damaging conditions. The regulation of this function is a really demanding situation, particularly when the stressing factors persist for a long time. In such cases, the depletion of existing DNA repair proteins has to be compensated by the induction of the analogous gene products.

Prospective assessment of systemic therapy followed by surgical removal of metastases in selected patients with renal cell carcinoma.

Objective: To prospectively establish objective selection criteria for metastasectomy in patients with metastatic renal cell carcinoma (mRCC).

Patients And Methods: Between 1991 and 1999, 38 patients with mRCC with responsive or stable disease after initial systemic therapy, and with potentially resectable disease, were enrolled. Patients had a metastasectomy with curative intent and received consolidative adjuvant systemic therapy.

Prognostic significance of fascin expression in advanced poorly differentiated serous ovarian cancer.

Background: High expression of the actin-bundling protein fascin correlates well with histological grade and clinical stage of ovarian carcinoma. This study addresses fascin expression in advanced poorly differentiated serous ovarian cancer with respect to progression free interval (PFI) and overall survival.

Patients And Methods: Fascin and Ki-67 expression were analysed in paraffin blocks tissue sections of 56 stage III, poorly differentiated (G3) serous adenocarcinoma patients by immunohistochemistry.

Employing the treatment-free interval of intermittent androgen ablation to screen candidate prostate cancer therapies.

Background: Because neither continuous nor intermittent hormonal therapy is curative, we designed a clinical model to screen new drugs for additive or synergistic effects with hormonal therapy and used IM862, a naturally occurring dipeptide with antiangiogenic and immunomodulatory properties, to test it.

Methods: Patients with prostate cancer who had rising PSA levels after radical prostatectomy and/or radiation therapy were given combined androgen ablation for 3 months. After 2 months' treatment, patients were randomly assigned in a double-blind fashion to receive intranasal IM862 or placebo daily.

CT quantification of effects of thalidomide in patients with metastatic renal cell carcinoma.

Objective: Our objective was to use functional CT to evaluate the effects of thalidomide in patients with metastatic renal cell carcinoma.

Subjects And Methods: Patients with proven metastatic renal cell carcinoma were examined prospectively with functional CT. Functional CT studies (cine mode, 4 x 5 mm) were performed through the tumor after i.

Phase II study of capecitabine single-agent therapy in patients with metastatic renal cell carcinoma.

Fluoropyrimidines are known to have modest activity in the treatment of metastatic renal cell carcinoma (RCC). Capecitabine is an orally administered prodrug that is converted to fluorouracil and is of potential use in the treatment of this disease. We conducted a Phase II clinical trial of capecitabine administered as a single agent to patients with metastatic RCC.

Thalidomide/estramustine/paclitaxel in metastatic androgen-independent prostate cancer.

Background: This is a phase I/II trial of thalidomide with estramustine and paclitaxel in men with androgen-independent prostate cancer (AIPC) who underwent previous chemotherapy.

Patients And Methods: Men with progressive AIPC were treated with oral thalidomide (200 mg, 400 mg, or 600 mg daily), intravenous paclitaxel (100 mg/m2 over 3 hours on days 3 and 10), and oral estramustine (140 mg 3 times daily on days 1-5 and days 8-12) every 21 days.

Results: Phase I: first cycle dose-limiting toxicity occurred in 0 of 3 patients at 200 mg thalidomide daily, 0 of 3 at 400 mg daily, and 1 of 3 at 600 mg daily (the designated maximum tolerated dose).