Progression into sepsis: an individualized process varying by the interaction of comorbidities with the underlying infection.

BACKGROUND: Development of sepsis is a process with significant variation among individuals. The precise elements of this variation need to be defined. This study was designed to define the way in which comorbidities contribute to sepsis development. METHODS: Three thousand five hundred nine patients with acute pyelonephritis (AP), community-acquired pneumonia (CAP), intraabdominal infections (IAI) or primary bacteremia (BSI) and at least two signs of the systemic inflammatory response syndrome were analyzed. The study primary endpoint was to define how comorbidities as expressed in the Charlson's comorbidity index (CCI) and the underlying type of infection contribute to development of organ dysfunction. The precise comorbidities that mediate sepsis development and risk for death among 18 comorbidities recorded were the secondary study endpoints. RESULTS: CCI more than 2 had an odds ratio of 5.67 for sepsis progression in patients with IAI between significantly higher than AP and BSI. Forward logistic regression analysis indicated seven comorbidities that determine transition into sepsis in patients with AP, four comorbidities in CAP, six comorbidities in IAI and one in BSI. The odds ratio both for progression to sepsis and death with one comorbidity or with two and more comorbidities was greater than in the absence of comorbidities. CONCLUSIONS: The study described how different kinds of infection vary in the degree to which they lead to sepsis. The number of comorbidities that enhances the risk of sepsis and death varies depending on the underlying infections.

Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment?

Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells.

Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result.

INTRODUCTION: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a posi¬tive second biopsy in males considered for re-biopsy. MATERIAL AND METHODS: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testos¬terone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. RESULTS: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). CONCLUSION: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.

Immunomodulatory intervention with interferon-γ in Escherichia coli pyelonephritis.

PURPOSE: We investigated the efficacy of recombinant human interferon-γ in experimental pyelonephritis due to Escherichia coli. MATERIALS AND METHODS: Pyelonephritis was induced by intrapelvic inoculation of bacteria after ureteral ligation in 38 rabbits assigned to 1 of 3 groups, including group 1-16 controls, group 2-14 rabbits treated with intravenous recombinant human interferon-γ and group 3-8 rabbits treated with intravenous recombinant human interferon-γ plus amikacin. Bacterial counts, cytokines and malondialdehyde were measured in blood. Peripheral blood mononuclear cells were isolated to measure TNFα transcripts, cytokine stimulation and apoptosis. Survival was recorded, and the tissue bacterial load and myeloperoxidase activity were measured after sacrifice. RESULTS: The mortality rate in groups 1, 2 and 3 was 66.7%, 25% and 12.5%, respectively. The circulating bacterial count and tissue bacterial load were less in group 2 than in group 1. Circulating malondialdehyde negatively correlated with the bacterial load of the spleen. Although the number of TNFα transcripts in circulating peripheral blood mononuclear cells did not differ, peripheral blood mononuclear cells isolated from group 2 at 48 hours produced much greater concentrations of tumor necrosis factor-α after stimulation with Pam3Cys. In parallel, the apoptosis rate of circulating monocytes was increased in group 2 at 48 hours. Lung myeloperoxidase activity at 24 hours, serving as indirect evidence of neutrophil infiltration, was decreased in group 2. CONCLUSIONS: Recombinant human interferon-γ administration prolonged survival in rabbits with experimental E. coli urosepsis. Its action was probably related to increased bacterial phagocytosis after modulation of oxidant status and reversal of monocyte immunoparalysis.

Evaluating the Impact of Benign Prostatic Hyperplasia Surgical Treatments on Sexual Health.

Benign prostatic hyperplasia (BPH), a prevalent condition in older men, is often managed through various surgical interventions. This narrative review aims to explore the impact of these surgical treatments on sexual function, a critical aspect of patient quality of life often overlooked in BPH management. The methodology encompassed a thorough review of contemporary surgical techniques for BPH, including prostate resection, enucleation, vaporization, and minimally invasive therapies such as UroLift, Rezum, and Aquablation. Additionally, the focus was on patient-centered outcomes, with a special emphasis on sexual health following surgery. Findings reveal that, while surgical interventions effectively alleviate BPH symptoms, they often have significant repercussions in sexual function, including erectile and ejaculatory dysfunction. However, emerging techniques demonstrate potential in preserving sexual function, underscoring the need for patient-centric treatment approaches. The study highlights the complex interplay between BPH surgery and sexual health, with minimally invasive treatments showing promise in balancing symptom relief and sexual function preservation. In conclusion, the study advocates for an integrated, interdisciplinary approach to BPH treatment, emphasizing the importance of considering sexual health in therapeutic decision-making. This narrative review suggests a paradigm shift towards minimally invasive techniques could optimize patient outcomes, marrying symptom relief with quality-of-life considerations. The need for further research in this domain is evident, particularly in understanding long-term sexual health outcomes following different surgical interventions for BPH.

Advanced Paternal Age in Focus: Unraveling Its Influence on Assisted Reproductive Technology Outcomes.

As global demographics shift toward increasing paternal age, the realm of assisted reproductive technologies (ARTs), particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), faces new challenges and opportunities. This study provides a comprehensive exploration of the implications of advanced paternal age on ART outcomes. Background research highlights the social, cultural, and economic factors driving men toward later fatherhood, with a focus on the impact of delayed paternity on reproductive outcomes. Methods involve a thorough review of existing literature, centering on changes in testicular function, semen quality, and genetic and epigenetic shifts associated with advancing age. Study results point to intricate associations between the father's age and ART outcomes, with older age being linked to diminished semen quality, potential genetic risks, and varied impacts on embryo quality, implantation rates, and birth outcomes. The conclusions drawn from the current study suggest that while advanced paternal age presents certain risks and challenges, understanding and mitigating these through strategies such as sperm cryopreservation, lifestyle modifications, and preimplantation genetic testing can optimize ART outcomes. Future research directions are identified to further comprehend the epigenetic mechanisms and long-term effects of the older father on offspring health. This study underscores the need for a comprehensive approach in navigating the intricacies of delayed fatherhood within the context of ART, aiming for the best possible outcomes for couples and their children.

Diagnostic Challenges and Management of Acquired Hemophilia A Presenting as Gross Hematuria: A Case Report.

Acquired hemophilia A (AHA) is a rare autoimmune disorder marked by autoantibodies against coagulation factor VIII, leading to bleeding complications. This case report explores a unique presentation of AHA, initially manifested as gross hematuria, a symptom often encountered in healthcare settings with a broad range of differential diagnoses. The background of this study highlights the rarity of AHA and its diverse clinical presentations. The case involves a 62-year-old man with no history of bleeding disorders, presenting with gross hematuria and later developing severe anemia and ecchymoses. Methods employed in the evaluation included urological assessments such as cystoscopy and computed tomography, alongside hematological investigations, which later revealed a prolonged activated partial thromboplastin time (aPTT) and a critically low factor VIII level, indicative of AHA. Results showed a lack of early recognition of coagulation abnormalities, underscoring the need for comprehensive initial assessments in cases of unexplained hematuria. The patient's management at a specialized Hemophilia Center involved inhibitor eradication therapy and management of acute bleeding episodes, resulting in significant clinical improvement. The conclusions drawn from this case emphasize the importance of considering rare conditions like AHA in the differential diagnosis of hematuria and the necessity for a broad diagnostic approach. It advocates for heightened awareness and early coagulation studies in unexplained cases of hematuria to prevent delayed diagnoses and improve patient outcomes. This case contributes to the understanding of AHA's clinical variability and the critical nature of early and comprehensive diagnostic approaches in hematuria evaluation.

Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor.

INTRODUCTION: Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed. METHODS: A prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden. RESULTS: Serum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥ 17 and suPAR ≥ 12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II <17 and suPAR <12 ng/ml with mortality 5.5%; ii) APACHE II < 17 and suPAR ≥ 12 ng/ml with mortality 17.4%; iii) APACHE II ≥ 17 and suPAR <12 ng/ml with mortality 37.4%; and iv) APACHE II ≥ 17 and suPAR ≥ 12 ng/ml with mortality 51.7%. This prediction rule was confirmed by the Swedish cohort. CONCLUSIONS: A novel prediction rule with four levels of risk in sepsis based on APACHE II score and serum suPAR is proposed. Prognostication by this rule is confirmed by an independent cohort.

The use of intravesical hyaluronic acid in the management of symptomatic premenopausal women with pseudomembranous trigonitis: Are symptoms related to cystoscopy and pathological findings?

OBJECTIVES: To determine the effectiveness and safety of intravesical hyaluronic acid (HA) in symptomatic women with trigonitis and to correlate the severity of symptoms with the endoscopic and histological findings. METHODS: Thirty-seven patients (aged 20-46 years) were enrolled. All patients had cystoscopy and biopsy of the bladder trigone followed by intravesical instillations of sodium HA once weekly for 10 weeks and then once monthly for the next 10 months. Clinical response was evaluated by Pain and Urgency/Frequency (PUF) Symptom Scale, visual analog scale (VAS) for pain and urgency and functional bladder capacity. A repeat cystoscopy and biopsy were performed at the end of the treatment. Symptoms and cystoscopy and pathological findings were compared before and after treatment. RESULTS: The average initial score for pain was reduced from 5.5 to 2.8 (P < 0.001) at 10 weeks and further to 2.4 (P < 0.001) at 12 months and the score for urgency from 6.9 to 3.8 (P < 0.001) and further to 3.3 (P < 0.001). The average PUF score initially decreased from 20.5 to 12.1 (P < 0.001) and then further to 10.1 (P = 0.21). The mean functional bladder capacity increased from 125 to 204 mL (P < 0.001). No association was found between baseline PUF score and cystoscopy findings (P = 0.87). The PUF score was not changed significantly between patients with improved cystoscopy and those with stable findings (P = 0.74). No significant changes were reported between initial and final biopsies. CONCLUSIONS: Intravesical HA appeared to be effective and well tolerated, although a clear relationship between symptoms and trigonitis was not confirmed.

TREM-1 expression on neutrophils and monocytes of septic patients: relation to the underlying infection and the implicated pathogen.

BACKGROUND: Current knowledge on the exact ligand causing expression of TREM-1 on neutrophils and monocytes is limited. The present study aimed at the role of underlying infection and of the causative pathogen in the expression of TREM-1 in sepsis. METHODS: Peripheral venous blood was sampled from 125 patients with sepsis and 88 with severe sepsis/septic shock. The causative pathogen was isolated in 91 patients. Patients were suffering from acute pyelonephritis, community-acquired pneumonia (CAP), intra-abdominal infections (IAIs), primary bacteremia and ventilator-associated pneumonia or hospital-acquired pneumonia (VAP/HAP). Blood monocytes and neutrophils were isolated. Flow cytometry was used to estimate the TREM-1 expression from septic patients. RESULTS: Within patients bearing intrabdominal infections, expression of TREM-1 was significantly lower on neutrophils and on monocytes at severe sepsis/shock than at sepsis. That was also the case for severe sepsis/shock developed in the field of VAP/HAP. Among patients who suffered infections by Gram-negative community-acquired pathogens or among patients who suffered polymicrobial infections, expression of TREM-1 on monocytes was significantly lower at the stage of severe sepsis/shock than at the stage of sepsis. CONCLUSIONS: Decrease of the expression of TREM-1 on the membrane of monocytes and neutrophils upon transition from sepsis to severe sepsis/septic shock depends on the underlying type of infection and the causative pathogen.

Tamsulosin versus transurethral resection of the prostate: effect on nocturia as a result of benign prostatic hyperplasia.

Our objective was to compare the effect of tamsulosin versus transurethral resection of the prostate (TURP) for the management of nocturia in previously untreated men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and no other predisposing factors for nocturia. The study group included 66 patients (mean age 68.9 years, range 52-81) randomized to receive either tamsulosin 0.4 mg per os daily (n = 33) or TURP (n = 33). Nocturia was assessed at baseline, after 3 months and after 1 year, by the number of nocturnal awakenings and hours of undisturbed sleep (HUS) obtained from a 72-h Frequency Volume Chart (FVC). Furthermore, the International Prostate Symptom Score (IPSS), the International Consultation on Incontinence Questionnaire Nocturia (ICIQ-N) and the International Consultation on Incontinence Questionnaire Nocturia Quality of Life (ICIQ-NQoL) were recorded. At baseline, there were no statistically significant differences between the two groups. ICIQNQoL and ICIQ-N scores correlated with the number of awakenings and HUS, respectively. Both tamsulosin and TURP improved all examined parameters during the follow up. TURP was associated with a statistically significant improvement in the number of nocturnal awakenings and in the IPSS, ICIQ-N and ICIQ-NQol scores in comparison with tamsulosin. HUS increased in both groups, but without any statistically significant difference. In conclusion, TURP is superior in comparison with tamsulosin for the management of BPH-related nocturia.

The role of the cell adhesion molecules (integrins/cadherins) in prostate cancer.

During prostate carcinogenesis the cellular adhesion molecules, i.e.; integrins and cadherins mediate aberrant interactions between glandular epithelial cells and the extracellular matrix. Several integrin α subunits are downregulated, while ß subunits are up-regulated. The expression of several cadherins and catenins has specific prognostic value. There is an association between the expression of the E-cadherin/catenin complex and high grade prostate cancer. Clinical trials evaluating the efficacy of integrin antagonists are ongoing with promising results. In this article we update the role of integrins and cadherins in prostate carcinogenesis and evaluate the therapeutic potential of their manipulation.

Computed Tomography-Guided Percutaneous Microwave Ablation for Renal Cell Carcinoma: Impact of Tumor Size on the Progression Survival Rates.

The aim of the present study was to evaluate the safety and efficacy of computed tomography (CT)-guided percutaneous microwave ablation (MWA) of renal cell carcinoma (RCC) along with identifying prognostic factors affecting the progression survival rate. Institutional database retrospective research identified 69 patients with a biopsy proven solitary T1a (82.6%) or TIb (17.4%) RCC who have underwent percutaneous CT-guided MWA. Kaplan-Meier survival estimates for events were graphed and Cox regression analysis was conducted. Mean patient age was 70.4 ± 11.5 years. Mean size of the lesions was 3 ± 1.3 cm. Mean follow up time was 35.6 months (SD = 21.1). The mean progression free survival time from last ablation was 84.2 months. For T1a tumors, the cumulative progression free survival rate for 1, 6, 12 and 36 months were 100% (SE = 0%), 91.2% (SE = 3.7%), 91.2% (SE = 3.7%) and 87.5% (SE = 4.4%); the recurrence free survival rate for T1a RCC was 94.9%. For T1b tumors, the cumulative progression free survival rate for 1, 6, 12 and 36 months were 100% (SE = 0%), 63.6% (SE = 14.5%), 63.6% (SE = 14.5%) and 63.6% (SE = 14.5%). Grade 1 complications were recorded in 5 (7.2%) patients. Significantly greater hazard for progression was found in cases with a tumor size > 4 cm (HR = 9.09, p = 0.048). No statistically important difference regarding tumor progression was recorded between T1a tumors with a diameter ≤3 cm and >3 cm. In summary, the results of the present study show that CT guided percutaneous MWA is an effective technique for treatment of T1a renal cell carcinomas, irrespective of tumor size. T1b tumors were associated with higher progression rates.

Referral for "Neoadjuvant Chemotherapy" for Muscle-Invasive Bladder Cancer to a Multidisciplinary Board: Patterns, Management and Outcomes.

BACKGROUND: Utilization of neoadjuvant chemotherapy for the treatment of muscle invasive bladder cancer in everyday practice differs from that of clinical trials. We describe the patterns of referral for "neoadjuvant chemotherapy", treatment and outcomes in a multidisciplinary tumor board. METHODS: This was an observational study. Patients referred for neoadjuvant chemotherapy received 4 cycles of dose-dense gemcitabine/cisplatin and were then assessed for definitive local therapy. Patients had a minimum follow-up of 2 years. Primary objective was a 3-year disease-free survival rate. RESULTS: Forty-six patients (clinical stages II: 28, IIIA: 9, IIIB: 4, IVA: 3, missing: 2) were included. Following chemotherapy, 30 underwent radical cystectomy, 8 radiotherapy and 8 no further therapy. Pathological downstaging was observed in 14 (46.6%) of the 30 patients who underwent radical cystectomy; clinical TNM staging was correlated with disease-free survival in the whole population, while clinical and pathological stages, as well as pathological downstaging, were correlated with disease-free survival in patients undergoing radical cystectomy. Three-year disease-free survival rates for the whole cohort and for patients undergoing radical cystectomy were 67.3% (95% confidence interval [CI]: 51-79.2) and 65.2 (95% CI: 44.9-79.6), respectively. CONCLUSION: Real-world muscle invasive bladder cancer patients who receive neoadjuvant chemotherapy are characterized by more advanced diseases and less frequent radical surgery than those included in clinical trials. Nevertheless, outcomes were comparable and, therefore, offering patients with stage II-IVA muscle invasive bladder cancer neoadjuvant chemotherapy after assessment by multidisciplinary tumor boards should be strongly encouraged.

The novel prostate cancer antigen 3 (PCA3) biomarker.

PCA3 is a prostate specific, nonprotein coding RNA that is significantly over expressed in prostate cancer, without any correlation to prostatic volume and/or other prostatic diseases (e.g. prostatitis). It can now easily be measured in urine with a novel transcription-mediated amplification based test. Quantification of PCA3 mRNA levels can predict the outcome of prostatic biopsies with a higher specificity rate in comparison to PSA. Several studies have demonstrated that PCA3 can be used as a prognostic marker of prostate cancer, especially in conjunction with other predictive markers. Novel PCA3-based nomograms have already been introduced into clinical practice. PCA3 test may be of valuable help in several PSA quandary situations such as negative prostatic biopsies, concomitant prostatic diseases, and active surveillance. Results from relevant clinical studies, comparative with PSA, are warranted in order to confirm the perspective of PCA3 to substitute PSA.

Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study.

Erectile dysfunction (ED) affects more than 30 million men; endothelial dysfunction plays a significant role in EDs pathogenesis. The aim of this study was to administer mesenchymal stem cells (MSC) derived from adipose tissue and platelet lysate (PL) into patients with erectile dysfunction. This pilot study enrolled eight patients with diagnosed ED. Patients enrolled were suffering from organic ED due to diabetes melitus, hypertension, hypercholesterolaemia, and Peyronie disease. The patients were distributed in 2 groups. Patients in group A received adipose derived mesenchymal stem cells (ADMSC) resuspended in PL while patients in group B received only PL. ADMSCs were isolated from patients' adipose tissue and expanded. In addition, blood sampling was obtained from the patients in order to isolate platelet lysate. After the application of the above treatments, patients were evaluated with an International Index of Erectile Function (IIEF-5) questionnaire, penile triplex, and reported morning erections. After MSCs and PL administration, patients presented improved erectile function after 1 and 3 months of follow-up. A statistically significant difference was observed in the IIEF-5 score before and after administration of both treatments after the first month (p < 0.05) and the third month (p < 0.05). No statistically significant difference was observed in the IIEF-5 score between group A and B patients. All patients were characterized by improved penile triplex and increased morning erections. No severe adverse reactions were observed in any patient except a minor pain at the site of injection, which was in the limits of tolerability. The results of this study indicated the satisfactory use of MSCs and PL in ED. MSCs in combination with PL or PL alone seems to be very promising, especially without having the negative effects of the current therapeutic treatment.

The impact of multidrug resistance on the pathogenicity of Escherichia coli: an experimental study.

Based on the controversial findings of clinical studies regarding the influence of multidrug resistance on mortality, 10 susceptible and 10 multidrug-resistant (MDR) and extended-spectrum beta-lactamase-producing isolates of Escherichia coli were applied to stimulate monocytes isolated from healthy donors. Immune mediators were estimated in supernatants. Four susceptible isolates (Group A) and four MDR isolates (Group B) were used to initiate acute pyelonephritis in 48 rabbits following inoculation of the pathogen into the right renal pelvis. Survival was recorded and blood monocytes were isolated and incubated to estimate the ex vivo release of tumour necrosis factor-alpha (TNFalpha). Release of TNFalpha, interleukin (IL)-6 and IL-8 was higher after 2 h and 4 h of stimulation by MDR isolates compared with susceptible isolates. The opposite occurred for the release of IL-12. Death occurred in 22 rabbits in Group A (91.7%) compared with 12 in Group B (50.0%) (P=0.003). Monocytes isolated at 24 h from Group A rabbits released significantly higher TNFalpha than monocytes from Group B. Tissue bacterial load after animal death was significantly higher in the kidneys of Group A rabbits. It is concluded that susceptible and MDR E. coli stimulate monocytes resulting in a different pattern of release of pro-inflammatory cytokines, which is accompanied by prolonged survival following experimental sepsis by MDR isolates.

Upper urinary tract transitional cell carcinoma. A 10-year experience.

OBJECTIVE: To present our 10-year experience with patients surgically treated for upper urinary tract transitional cell carcinoma. PATIENTS AND METHODS: We reviewed the medical records of 264 patients (218 males and 46 females), aged 37-93 years (mean, 69.5), treated surgically for upper tract transitional cell carcinoma during the period January 1996 to December 2005. RESULTS: During the mean follow-up of 58 months (range, 12-120), local relapse was diagnosed in 14% of the patients. The mean time to recurrence was 13 months (range, 1-102). The overall mortality was 14%, and the mean survival was 109 months. Survival was significantly influenced by the following parameters: male gender (P = 0.0151), age over 80 years (P = 0.0012), location in both the pelviocaliceal system and the ureter (P = 0.051), a two incision operation (P = 0.0075), grade III (P = 0.0314), stage T3 and T4 (P < 0.0001). CONCLUSIONS: Tumor stage was identified as the most important determinant in predicting recurrence and survival. Other predictors of survival included male gender, age over 80 years, location in the pelviocaliceal system and the ureter, a two incision operation, and high grade.

Biweekly carboplatin/gemcitabine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: report of efficacy, quality of life and geriatric assessment.

OBJECTIVE: We evaluated safety and efficacy of first-line gemcitabine/carboplatin in unfit-for-cisplatin patients with advanced urothelial carcinoma and the effect on the quality of life and functional status of elderly patients (aged >70). METHODS: Unfit patients had ECOG performance status (PS) > or =2, creatinine clearance <50 ml/min or comorbidities precluding cisplatin administration. Carboplatin at area under the curve of 2.5 and gemcitabine 1,250 mg/m(2) were administered biweekly. Elderly patients were stratified into group 1 (no activities of daily living (ADL) or instrumental ADL dependency and no comorbidities), group 2 (instrumental ADL dependency or 1-2 comorbidities) and group 3 (ADL dependency or > or =2 comorbidities). RESULTS: Thirty-four patients were enrolled: 68% had PS 2-3, 69% a creatinine clearance <50 ml/min and 65% had 1 or more comorbidities. There were 3 cases of grade 3 toxicity (9%). Response rate was 24% [95% confidence interval (CI) 11-41]. Median follow-up was 8 months, median progression-free survival 4.4 months (95% CI 1.03-7.75) and median overall survival 9.8 months (95% CI 4.7-14.9). Patients in geriatric assessment groups 1 and 2 had a significantly longer median progression-free survival compared to group 3 [6.9 months (95% CI 1.3-12.4) vs. 1.9 months (95% CI 0.5-3.2); p = 0.005]. CONCLUSION: First-line gemcitabine/carboplatin combination is active in unfit-for-cisplatin patients with advanced urothelial carcinoma. Pretreatment quality of life and geriatric assessment may be useful in selecting patients likely to benefit from this treatment.

Oleuropein: a novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa.

Oleuropein, a novel immunomodulator derived from olive tree, was assessed in vitro and in experimental sepsis by Pseudomonas aeruginosa. After addition in monocyte and neutrophil cultures, malondialdehyde, TNF-alpha, IL-6, and bacterial counts were estimated in supernatants. Acute pyelonephritis was induced in 70 rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy was administered in four groups postchallenge by one multidrug-resistant isolate (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups postchallenge by one susceptible isolate (E, controls; F, oleuropein; G, amikacin). Survival was recorded; bacterial growth in blood and organs was counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF-alpha in serum were estimated. TNF-alpha and IL-6 of cell supernatants were not increased compared with controls when triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants. Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in groups B and D compared with A and in groups F and G compared with E. Total antioxidant status decreased steadily over time in groups A, C, D, and G, but not in groups B and F. TNF-alpha of groups B, C, and D was lower than A at 48 h. Tissue bacteria decreased in group F compared with E. Oleuropein prolonged survival in experimental sepsis probably by promoting phagocytosis or inhibiting biosynthesis of proinflammatory cytokines.