Urinary Tract Infection Predictors in Patients Undergoing Retrograde IntraRenal Surgery for Renal Stones: Does the Instrument Make the Difference?

Background: Retrograde intrarenal surgery (RIRS) using flexible ureterorenoscopes is a cornerstone approach for renal stone removal, yet it carries a significant risk of postoperative urinary tract infection (UTI). With the emergence of single-use ureterorenoscopes, there is growing interest in their potential to mitigate this risk. This study aimed to compare the postoperative infection rates between single-use and multi-use ureterorenoscopes in RIRS procedures and to identify predictors of postoperative UTI. Methods: Data were collected from 112 consecutive patients who underwent RIRS for renal stones between March 2022 and September 2023. Peri-operative variables including age, gender, body mass index (BMI), stone size, stone location, type of ureterorenoscope, Hounsfield Units (HU), pre-operative hydronephrosis, laboratory analysis, and operative time were evaluated. Univariate and multivariate logistic regression analyses were performed to assess the predictors of postoperative UTI. Results: Of the cohort, 77 surgeries (68.7%) utilized multi-use ureterorenoscopes, while 35 (31.3%) utilized single-use devices. Stone diameter, number of stones, type of ureterorenoscope, and operative time were significant predictors of postoperative UTI in the univariate analysis. Multivariable logistic regression showed that operative time (OR, 1.3; 95% CI, 0.55-0.99; p = 0.03) and type of ureterorenoscope (multi-use vs. single-use) (OR, 1.14; 95% CI, 1.08-1.2; p < 0.001) were independent predictors of postoperative UTI. Conclusions: In conclusion, this study highlights that multi-use ureterorenoscopes and prolonged operative time are associated with an increased risk of postoperative UTI in RIRS procedures. Careful pre-operative evaluation and meticulous patient selection are essential to minimize the occurrence of postoperative UTIs and optimize patient outcomes in RIRS for renal stones.

Robotic Medtronic Hugo™ RAS System Is Now Reality: Introduction to a New Simulation Platform for Training Residents.

The use of robotic surgery (RS) in urology has grown exponentially in the last decade, but RS training has lagged behind. The launch of new robotic platforms has paved the way for the creation of innovative robotics training systems. The aim of our study is to test the new training system from Hugo™ RAS System-Medtronic. Between July 2020 and September 2022, a total of 44 residents from urology, gynaecology and general surgery at our institution participated in advanced robotic simulation training using the Hugo™ RAS simulator. Information about sex, age, year of residency, hours spent playing video games, laparoscopic or robotic exposure and interest in robotics (90.9% declared an interest in robotics) was collected. The training program involved three robotic exercises, and the residents performed these exercises under the guidance of a robotics tutor. The residents' performance was assessed based on five parameters: timing, range of motion, panoramic view, conflict of instruments and exercise completion. Their performance was evaluated according to an objective Hugo system form and a subjective assessment by the tutor. After completing the training, the residents completed a Likert scale questionnaire to gauge their overall satisfaction. The rate of the residents' improvement in almost all parameters of the three exercises between the first and the last attempts was statistically significant (p < 0.02), indicating significant progress in the residents' robotic surgical skills during the training. The mean overall satisfaction score ± standard deviation (SD) was 9.4 ± 1.2, signifying a high level of satisfaction among the residents with the training program. In conclusion, these findings suggest that the training program utilizing the Hugo™ RAS System is effective in enhancing robotic surgical skills among residents and holds promise for the development of standardized robotics training programs in various surgical specialties.

Video Consensus and Radical Prostatectomy: The Way to Chase the Future?

In the age of information, new platforms are consulted by patients to acquire consciousness about medical treatments. The aim of this study was to assess the level of understanding and feasibility of video consensus (VC) administration in patients scheduled for radical prostatectomy (RP), comparing it with standard informed consensus (SIC). According to the European Association of Urology Patient Information, we set up a video content for RP that was translated in Italian and implemented with information about possible perioperative and postoperative complications, days of hospitalization etc. From 2021 to 2022, all patients undergoing RP at our institution were prospectively included in this study. Patients received an SIC and after that, a VC about RP. After two consensuses were administered, patients received a preformed Likert 10 scale and STAI questionnaires. On the RP dataset, 276 patients were selected and 552 questionnaires for both SIC and VC were evaluated. Out of these, the median age was 62 years (IQR 60-65). Patients reported a higher overall satisfaction for VC (8.8/10) compared to the traditional informed consent (6.9/10). Therefore, VC may play a role in the future of surgery, improving the consciousness and satisfaction of patients and reducing preoperative anxiety.

Impact of Robotic Technologies on Prostate Cancer Patients' Choice for Radical Treatment.

Prostate cancer (PCa) surgery has a strong impact on men's social and sexual lives. For this reason, many patients ask for robotic surgery. To assess the rate of lost patients due to the lack of a robotic platform (RPl) at our center, we retrospectively selected 577 patients who underwent prostate biopsy between 2020 and 2021 who were eligible for radical prostatectomy (RP) (ISUP ≥ 2; age ≤ 70 yr). Patients eligible for surgery who decided to be operated received a phone call interview asking the reason for their choice. Overall, 230 patients (31.7%) underwent laparoscopic-assisted radical prostatectomy (LaRP) at our center, while 494 patients (68.3%) were not treated in our hospital. Finally, 347 patients were included: 87 patients (25.1%) underwent radiotherapy; 59 patients (17%) were already under another urologist's care; 113 patients (32.5%) underwent robotic surgery elsewhere; and 88 patients (25.4%) followed the suggestion of friends or relatives based on their surgical experience. Despite no surgical technique for RP having shown superiority in terms of oncological or functional outcomes, patients eligible for PCa treatment decided to be operated on elsewhere because of the lack of an RPl. Our results show how the presence of an RPl may increase the case volume of RP by 49% at our center.

Caracterización clínica epidemiológica de los pacientes con enfermedad de la Peyronie infiltrados con células mononucleares / Clinical Epidemiological Characterization of Peyronie's Disease Patients Infiltrated With Mononuclear Cells

Introducción: La enfermedad de la Peyronie resulta poco común e involucra a hombres de mediana edad. Objetivo: Caracterizar los aspectos clínicos y epidemiológicos de los pacientes con enfermedad de la Peyronie infiltrados con células mononucleares. Métodos: Se realizó un estudio observacional, analítico, longitudinal prospectivo en el Hospital General Docente "Comandante Pinares" desde junio de 2015 hasta mayo de 2018, con una muestra de 159 pacientes. Se controlaron las variables de edad, color de la piel, factores etiológicos, curvatura y desviación del pene además de síntomas y signos. Resultados: El mayor número de pacientes correspondieron a la edad de 50-59 años, de piel blanca, grados de curvatura entre 20o y 39o. Después del tratamiento 115 pacientes se encontraron con curvatura menor a 20o y desviación dorsal. Las causas más frecuentes de los microtraumas a nivel de pene resultan durante al acto sexual o en estado flácido del pene (105/159). La diabetes mellitus y la hipertensión arterial, con 59,7 y 30,8 por ciento, respectivamente resultan los factores etiológicos más frecuentes; los síntomas y signos fueron el dolor y la curvatura, 115 pacientes presentaron ausencia de dolor al hacer la comparación de la media al concluir el tratamiento, resultando significativo (p= 0,0000). Conclusiones: La enfermedad de la Peyronie resulta frecuente en pacientes de la quinta década de la vida, con color de piel blanca. La causa más frecuente son los microtraumas en la actividad sexual, la diabetes mellitus y la hipertensión arterial como antecedentes patológicos personales. Existe mejoría de la sintomatología en los pacientes infiltrados con células mononucleares(AU)

Introduction: Peyronie's disease is rare and involves middle-aged men. Objective: To characterize the clinical and epidemiological aspects of patients with Peyronie's disease infiltrated with mononuclear cells. Methods: An observational, analytical, prospective longitudinal study was carried out at the "Comandante Pinares" General Teaching Hospital from June 2015 to May 2018, with a sample of 159 patients. The variables of age, skin color, etiological factors, curvature and deviation of the penis, as well as symptoms and signs, were controlled. Results: The largest number of patients corresponded to the age of 50-59 years, white skin, degrees of curvature between 20o and 39o. After treatment, 115 patients were found to have curvature less than 20o and dorsal deviation. The most frequent cause of penile microtrauma is during sexual intercourse or in the flaccid state of the penis (105/159). Diabetes mellitus and arterial hypertension, with 59.7 and 30.8 percent, respectively, are the most frequent etiological factors; the symptoms and signs were pain and curvature, 115 patients presented absence of pain when comparing the mean at the end of the treatment, being significant (p= 0.0000). Conclusions: Peyronie's disease is frequent in patients of the fifth decade of life, with white skin color. The most frequent cause are microtraumas in sexual activity, diabetes mellitus and arterial hypertension as personal pathological antecedents. There is improvement of the symptoms in patients infiltrated with mononuclear cells(AU)

A New Approach for Impedance Tracking of Piezoelectric Vibration Energy Harvesters Based on a Zeta Converter.

Piezoelectric energy harvesters (PEHs) are a reduced, but fundamental, source of power for embedded, remote, and no-grid connected electrical systems. Some key limits, such as low power density, poor conversion efficiency, high internal impedance, and AC output, can be partially overcome by matching their internal electrical impedance to that of the applied resistance load. However, the applied resistance load can vary significantly in time, since it depends on the vibration frequency and the working temperature. Hence, a real-time tracking of the applied impedance load should be done to always harvest the maximum energy from the PEH. This paper faces the above problem by presenting an active control able to track and follow in time the optimal working point of a PEH. It exploits a non-conventional AC-DC converter, which integrates a single-stage DC-DC Zeta converter and a full-bridge active rectifier, controlled by a dedicated algorithm based on pulse-width modulation (PWM) with maximum power point tracking (MPPT). A prototype of the proposed converter, based on discrete components, was created and experimentally tested by applying a sudden variation of the resistance load, aimed to emulate a change in the excitation frequency from 30 to 70 Hz and a change in the operating temperature from 25 to 50 °C. Results showed the effectiveness of the proposed approach, which allowed to match the optimal load after 0.38 s for a ΔR of 47 kΩ and after 0.15 s for a ΔR of 18 kΩ.

Long-term Persistence of Native New York Entomopathogenic Nematode Isolates Across Crop Rotation.

Entompathogenic nematodes are found worldwide in a wide array of soil habitats with a broad host range and significant variation in foraging strategies. The primary use of entomopathogenic nematodes (EPNs) in managed plant systems has been focused on inundative releases in a biopesticide strategy. Little effort has been placed in investigating the use of natural occurring or adapted EPN strains for long-term suppression of pest outbreaks in managed systems. This study examined the potential of EPN isolates from Northern New York (NNY), inoculated at a low level (250 million IJ/ha), which are climate adapted and their persistent characteristics preserved to maintain population levels in agricultural fields (N = 82) for multiple years and across crop rotation (alfalfa:corn:alfalfa). Persistence levels for Steinernema carpocapsae (Weiser) (Rhabditida:Steinernematidae) ranged between 8 and 12% of the soil cores assayed in continuous alfalfa and 1-14% of the soil cores assayed in continuous corn rotated from EPN treated alfalfa. Steinernema feltiae (Filipjev) (Rhabditida: Steinernematidae) residual persistence level ranged between 17 and 32% in continuous alfalfa and 22-41% in continuous corn rotated from EPN treated alfalfa. Combined EPN level ranged between 27 and 43% of the soil cores in continuous alfalfa and 28-55% in continuous corn rotated from EPN-treated alfalfa. Inspection of individual fields suggested EPN populations established in prior years at the residual soil core level of 18-35% can respond positively to an increase of susceptible hosts in both alfalfa and corn, often increasing their presence to 100%.

Comportamiento de la mortalidad por cáncer en la provincia Artemisa en el año 2012 / Behavior of mortality from cáncer in Artemisa province in 2012

El cáncer constituye un serio problema de salud y una de las principales causas de muerte en todo el mundo; la Organización Mundial de Salud estimó que en el 2005 murieron por neoplasias malignas cerca de 7,6 millones de personas y se prevé que en los próximos 10 años morirán 84 millones más. En Cuba, el Ministerio de Salud Pública, y en particular la Sección Independiente para el control del cáncer despliega una ardua labor encaminada a promover acciones que permitan la reducción de la mortalidad provocada por la presencia de tumoraciones malignas. De acuerdo al análisis efectuado, se estableció como objetivo del presente trabajo, caracterizar el comportamiento de la mortalidad por cáncer en la provincia de Artemisa, en el período de enero a septiembre de 2012. Se realizó un estudio de tipo epidemiológico, descriptivo, de corte transversal, retrospectivo, se tomó el universo constituido por los pacientes reportados como fallecidos. Se logró describir el comportamiento de las variables socio-demográficas relacionadas con la mortalidad por cáncer en la provincia Artemisa en el período comprendido entre enero y septiembre de 2012, a partir de la utilización de diferentes herramientas de análisis estadístico(AU)

Cancer is a serious health problem and one of the main causes of death worldwide. The World Health Organization estimated that in 2005 around 7.6 million people died of malignant neoplasias and it is foreseen that in the next ten years, 84 million people more will die. The Ministry of Public Health of Cuba and particularly the Independent Section for the cancer control carries out a strong work aimed at promoting actions that allow the reduction of mortality from malignant tumors. According to the analysis, the objective of this paper was to characterize the behavior of mortality from cancer in Artemisa province in the period of January to September 2012. A retrospective, cross-sectional, descriptive and epidemiological study was conducted in which the universe of study was the dead patients. A description of the behavior of the socio-demographic variables related to the mortality from Cancer in Artemisa province from January to September 2012 was made, on the basis of different statistical analysis tools(AU)

Comportamiento de la mortalidad por cáncer en la provincia Artemisa en el año 2012 / Behavior of mortality from cáncer in Artemisa province in 2012

El cáncer constituye un serio problema de salud y una de las principales causas de muerte en todo el mundo; la Organización Mundial de Salud estimó que en el 2005 murieron por neoplasias malignas cerca de 7,6 millones de personas y se prevé que en los próximos 10 años morirán 84 millones más. En Cuba, el Ministerio de Salud Pública, y en particular la Sección Independiente para el control del cáncer despliega una ardua labor encaminada a promover acciones que permitan la reducción de la mortalidad provocada por la presencia de tumoraciones malignas. De acuerdo al análisis efectuado, se estableció como objetivo del presente trabajo, caracterizar el comportamiento de la mortalidad por cáncer en la provincia de Artemisa, en el período de enero a septiembre de 2012. Se realizó un estudio de tipo epidemiológico, descriptivo, de corte transversal, retrospectivo, se tomó el universo constituido por los pacientes reportados como fallecidos. Se logró describir el comportamiento de las variables socio-demográficas relacionadas con la mortalidad por cáncer en la provincia Artemisa en el período comprendido entre enero y septiembre de 2012, a partir de la utilización de diferentes herramientas de análisis estadístico.

Cancer is a serious health problem and one of the main causes of death worldwide. The World Health Organization estimated that in 2005 around 7.6 million people died of malignant neoplasias and it is foreseen that in the next ten years, 84 million people more will die. The Ministry of Public Health of Cuba and particularly the Independent Section for the cancer control carries out a strong work aimed at promoting actions that allow the reduction of mortality from malignant tumors. According to the analysis, the objective of this paper was to characterize the behavior of mortality from cancer in Artemisa province in the period of January to September 2012. A retrospective, cross-sectional, descriptive and epidemiological study was conducted in which the universe of study was the dead patients. A description of the behavior of the socio-demographic variables related to the mortality from Cancer in Artemisa province from January to September 2012 was made, on the basis of different statistical analysis tools.

Is primary surgery for locally advanced/metastatic breast cancer a better choice than chemotherapic treatment?

INTRODUCTION: A part of the literature supports the undoubtful advantage of neoadjuvant chemotherapy on the overall survival and for the possibility of surgical conservative treatment in locally advanced tumours after downstaging. Other authors report that primitive tumour's surgical removal at first, improves survival in cases with locally advanced /metastatic disease. The advantages were improvement of patient's health status, removal of a reservoir of neoplastic cell neoangiogenic cytokines and growth factors,and cytoreduction. MATERIALS AND METHODS: Aim of this study is to evaluate the effectiveness on the survival of a primary surgical treatment of the locally advanced tumours comparing two homogeneous groups. In the first group (GROUP 1) 40 patients were enrolled with stage III A, III B,IV tumours and were treated with primary surgery. The second group (GROUP 2) was made up of 40 patients with similar stage treated with neoadjuvant chemotherapy. The surgical treatment had the intention to remove the entire primary tumour. RESULTS: After a median follow up of 48,2 months,22,5 % of GROUP 1 died and 30 % of GROUP 2. The average survival of patients in GROUP 1 was 27,1 months while in GROUP 2 there was an average survival of 16,8 months. CONCLUSION: In conclusion surgical treatment plays a key role in the treatment of advanced/metastatic disease and is an independent factor associated with survival.

In vitro antimicrobial profile of Ureaplasma urealyticum from genital tract of childbearing-aged women in Northern and Southern Italy.

Ureaplasma urealyticum is an opportunistic pathogen during pregnancy and in newborns. Other clinical problems related to U. urealyticum infections are: no susceptibility to cell wall-active drugs, limits of antibiotic treatment in pregnancy, and spread of antimicrobial resistance. In addition, the results of antimicrobial susceptibility against U. urealyticum from various countries are few and controversial. The antimicrobial susceptibility of U. urealyticum, isolated from cervical swabs and collected from outpatient childbearing-aged women in Italy from 2009 to 2012, was performed against fluoroquinolones, macrolides, streptogramin and tetracyclines, using an available biochemical commercial kit and a specific solid culture medium, to improve the therapeutic management of these pathogenic agents. Ureaplasma urealyticum was detected in 49.4% of samples, but significant bacterial load was revealed in 29.8%. In vitro tetracyclines showed the best activity against U. urealyticum, followed by streptogramin, macrolides, and fluoroquinolones.

Cat scratch disease presenting as breast cancer: a report of an unusual case.

Benign lymphoreticulosis (cat scratch disease, CSD) may have a clinical course that varies from the most common lymphadenitis localized in the site of inoculation, preceded by the typical "primary lesion," to a context of severe systemic involvement. Among these uncommon clinical aspects, there is mammarian granulomatous lymphadenitis which may appear as a mastitis or a solitary intraparenchymal mass, giving the impression of a breast tumor. In these cases, intensive clinical, instrumental, and laboratory investigations are necessary to exclude malignancy. Because of its rarity, in equivocal cases, it is reasonable to use surgical excision for accurate histological examination. We report a case of CSD of the breast in a 59-year-old woman, analyzing the clinical, histopathological, and instrumental appearance and also performing a literature review.

In vitro resistance to macrolides and clindamycin by Group B Streptococcus isolated from pregnant and nonpregnant women.

BACKGROUND: Despite the introduction of screening bases intrapartum prophylaxis, Streptococcus agalactiae is still an important etiological agent of perinatal infections. The increasing rate of resistance and the differences in resistance pattern among countries suggest that a program of surveillance at the institutional level is important in determining optimal prophylaxis. In contrast, knowledge on GBS epidemiology in Italy is limited, and no data are available in the Southern region of the country. We sought to determine the occurrence of resistance to macrolides and clindamycin of GBS isolates in pregnant and nonpregnant women. METHODS: Between 2005 and 2008, 1346 vaginal and 810 rectovaginal swabs were obtained from pregnant and not-pregnant women. RESULTS: The occurrence of macrolides and clindamycin resistance was 16.5% in 2005 increasing up to 69.9% in 2008. A high percentage of isolates was resistant to tetracycline through all the study period with no statistically significant annual. CONCLUSIONS: In our cohort, an increase of in vitro resistance of GBS to macrolides and clindamycin is clearly evident. The discordance with reports from different countries emphasize the crucial role of microbiological methods in setting possible therapeutic strategies.

Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study.

PURPOSE: Single-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696). PATIENTS AND METHODS: Patients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) > or = 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m(2) weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m(2) added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral alpha .05, 355 events were needed and 400 patients planned. RESULTS: Four hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS > or = 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity. CONCLUSION: The addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.

Adjuvant therapy in colon cancer.

Colon cancer is the second leading cause of cancer death worldwide. Approximately three quarters of patients are diagnosed with disease limited to the bowel wall or surrounding lymph nodes. Over the past decade, significant progress has been made in the treatment of localized colon cancer. The use of adjuvant chemotherapy has improved prognosis in stage III disease, but much work remains to be done in optimizing adjuvant treatment. The FOLFOX4 regimen is now considered standard treatment for stage III disease. Combinations of irinotecan and 5-fluorouracil (5-FU) have not proven to be more effective than 5-FU/folinic acid. In stage II, the value of post-operative treatment remains controversial, but the identification of histopathological and molecular prognostic factors would allow selection of patients who can benefit from adjuvant treatment. The inclusion of molecular targeted agents in combination regimens with cytotoxins, which have already proven effective in advanced disease, is the main field of development in the most recent protocols of adjuvant therapy.

Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study.

BACKGROUND: The addition of cyclo-oxygenase-2 (COX-2) inhibitors and prolonged constant infusion (PCI) of gemcitabine to treatment for advanced non-small-cell lung cancer (NSCLC) might improve treatment efficacy. We aimed to assess whether the addition of rofecoxib or PCI gemcitabine could improve overall survival compared with first-line treatment with cisplatin plus gemcitabine given by standard infusion. METHODS: Patients with stage IV or IIIb (with supraclavicular nodes or pleural effusion) NSCLC who were under 70 years of age and who had performance status 0 or 1 were eligible for this multicentre, prospective, open-label, randomised phase III trial with 2 x 2 factorial design. Patients were randomly assigned to one of four treatment groups: group A, gemcitabine 1200 mg/m(2) in a 30-min intravenous infusion on days 1 and 8 and intravenous cisplatin 80 mg/m(2) on day 1, every 21 days for six cycles; group B, the same treatments as group A plus oral rofecoxib 50 mg/day until disease progression; group C, intravenous PCI gemcitabine 1200 mg/m(2) in a 120-min infusion on days 1 and 8 and intravenous cisplatin 80 mg/m(2) on day 1, every 21 days for six cycles; group D, the same drugs as group C plus oral rofecoxib 50 mg/day until disease progression. The primary endpoint was overall survival; secondary endpoints were progression-free survival, response rate, quality of life, and toxicity. Analyses were intention-to-treat. This trial is registered on the clinical trials site of the US National Institutes of Health website http://clinicaltrials.gov/ct/show/NCT00385606. FINDINGS: Between Jan 30, 2003, and May 3, 2005, 400 patients were enrolled. Median age was 60 years (range 29-71). PCI gemcitabine did not improve overall survival (median 47 weeks [95% CI 40-55] vs 44 [36-52], with standard gemcitabine infusion, hazard ratio (HR) of death 0.93 [0.74-1.17], p=0.41), progression-free survival, nor any other secondary endpoint. Vomiting and fatigue were significantly worse with PCI gemcitabine. The two rofecoxib groups were closed early (on Oct 1, 2004) due to withdrawal of the drug because of safety issues. With intention-to-treat statistical analyses limited to 240 patients (ie, those randomised before July 1, 2004) who had at least 3 months of treatment, rofecoxib did not prolong overall survival (median 44 weeks [CI 36-55] vs 44 [40-54] without rofecoxib, and HR of death 1.00 [0.75-1.34], p=0.85), or progression-free survival, but did improve response rate (41%vs 26%, p=0.02), global quality of life, physical, emotional and role functioning, fatigue, and sleeping. Rofecoxib significantly increased the incidence of diarrhoea and decreased constipation, fatigue, fever, weight loss, and pain, and analgesic consumption. Severe cardiac ischaemia was more frequent with rofecoxib than without; however, the difference was not statistically significant in the primary analysis (p=0.06) and became significant when patients who were randomised between July 1, 2004, and Sept 30, 2004, were included in the analysis (p=0.03). INTERPRETATION: Neither PCI gemcitabine nor rofecoxib prolonged survival in the patients in this study. Rofecoxib improved response rate and several quality-of-life items, including pain-related items and global quality of life. Further studies with less cardiotoxic COX-2 inhibitors are needed in NSCLC.

Phase I-II parallel study of docetaxel on a bimonthly schedule in refractory metastatic breast carcinoma.

BACKGROUND: The 3-week schedule with docetaxel (DTC) 75-100 mg/2 is associated with severe neutropenia, gastro-intestinal side-effects and fluid retention in a significant proportion of patients, which may be of concern in more elderly or poor performance status patients. A phase I-II trial was carried out to test the feasibility and the activity of a new bimonthly schedule of DCT. PATIENTS AND METHODS: The trial included a phase I study which aimed at the identification of dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of DCT on a bimonthly schedule. The first group of three patients received DCT 40 mg/m2, and in absence of DLT, DCT dosage was escalated by 10 mg/m2/cycle until DLT was reached. In the phase II study, patients were randomized to receive: (a) standard 3-weekly DCT at the dose of 75 mg/m2 (calibration arm); or (b) bimonthly schedule with DCT at the dose recommended in the phase I study. All patients were pretreated with chemotherapy, mostly anthracycline-based regimens, for advanced/metastatic disease. Analysis of response rates, toxicity, and dose-intensity were the main aims of the study. RESULTS: The DLT was represented by severe myelosuppression which was recorded in all patients treated at 70 mg/m2 dose level. Therefore, the MTD was 60 mg/m2 on a bimonthly schedule. However, the dose recommended for the phase II trial was 50 mg/m2, because no difference in delivered dose-intesity was seen between the 50 and 60 mg/m2 dose levels, and the latter dosage was still associated with grade 3 neutropenia in most patients. The parallel phase II study showed that the bimonthly schedule of DCT (50 mg/m2) allows to deliver the same dose-intensity of DCT 75 mg/m2 every 3 weeks. Grade 3-4 side-effects were rather infrequent in patients treated with the bimonthly schedule. Overall response rate (ORR) was 41 and 44% for the DCT 50 mg/m2 bimonthly and the DCT 75 mg/m2 every 3 weeks, respectively. CONCLUSIONS: Data achieved in the phase I part of the study showed that DCT 50 mg/m2 every 15 days is the recommended dose for phase II studies, while results achieved in the phase II trial suggest that DCT 50 mg/m2 in a bimonthly schedule is active as second-line chemotherapy for MBC being able to induce an ORR in the range reported for DCT 75-100 mg/m2 every 3 weeks. The bimonthly schedule is, however, associated with relatively low toxicity. This characteristic may render the bimonthly schedule particularly attractive for future phase II trials of DCT in combination with other antineoplastic agents.

Pegylated liposomal doxorubicin with vinorelbine in metastatic breast carcinoma. A phase I-II clinical investigation.

A multicenter phase I-II trial was carried out with the aim of identifying the dose-limiting toxicity and the maximum tolerated dose of vinorelbine (VNR) in combination with pegylated liposomal doxorubicin at a dose of 20 mg/m(2) every 15 days in patients with metastatic breast carcinoma. In the phase I part of the trial, VNR was given at a dose of 20 mg/m(2) every 15 days to a group of 3 patients. In absence of unacceptable toxicity, VNR was escalated to 25, 30, and 35 mg/m(2) for subsequent groups of 3 patients, until the dose-limiting toxicity was reached. No case of palmar-plantar erythrodysesthesia was recorded in these patients. Grade 4 neutropenia, grade 3 thrombocytopenia, and grade 3 mucositis were the dose-limiting toxicities recorded in patients treated with VNR 35 mg/m(2). These side effects caused a substantial decrease in programmed dose intensity. Therefore 30 mg/m(2) was considered the maximum tolerated dose of VNR in combination with pegylated liposomal doxorubicin 20 mg/m(2), both given every 15 days. These dosages were employed for the treatment of further 18 patients included in phase II of the study. The overall response rate, calculated according to an intention to treat analysis, was 63% (95% CI: 44-80%), with 2 patients achieving a complete response. The median time to progression was 7.0 months or more (range 2-14 months). Median duration of objective responses was 8.4 months or more. The duration of the 2 complete responses was 9 and 14 months, respectively. Median duration of survival was 16.0 months or more (range from 4.0 to >or=24.0). Toxicity was generally mild and easily manageable. Neutropenia and mucositis were the most frequently recorded side effects. A case of palmar-plantar erythrodysesthesia was recorded in phase II of the study. In conclusion, the maximum tolerated dose of VNR in association with pegylated liposomal doxorubicin is 30 mg/m(2) on a bimonthly schedule. Moreover, the combination of VNR and pegylated liposomal doxorubicin is active against metastatic breast carcinoma and is associated with a good toxicity profile. Further studies with this combination regimen are warranted.

Vinorelbine and cisplatin for the treatment of recurrent and/or metastatic carcinoma of the uterine cervix.

BACKGROUND: To test the clinical activity and toxicity profile of the combination regimen of vinorelbine and cisplatin in a series of patients with carcinoma of the cervix uteri with de novo metastatic disease or recurrent disease after previous therapy. The main aims of the study included analysis of objective response rates, toxicity, and time to progression. PATIENTS AND METHODS: Forty-two eligible patients were enrolled into the trial and treated with cisplatin 80 mg/m(2) on day 1 and vinorelbine 25 mg/m(2) on day 1 and 8. This regimen was repeated every 21 days upon resolution of toxicity for 3 cycles before response assessment. Enrolled patients had a median age of 53 years, a median ECOG performance status of 1, and mostly a squamous cell histology (86%). Sixteen patients (38%) were treatment-naive since first diagnosed with widespread metastatic disease, 7% had only previous surgery, 31% radiotherapy, and 24% both radiation and surgical therapy. In previously radiated patients, 21% of patients had disease only within the radiation fields, 21% only outside the radiation fields, and 12% both inside and outside the radiotherapy portals. RESULTS: All patients were evaluable for response analysis. A complete response was achieved in 5 patients (12%), and a partial response in 15 cases (36%) for an overall response rate of 48% (95% CL 22-52%). Patients with recurrent disease within the previous radiation field (including those also with disease outside the radiation fields) showed a 28% overall response rate with no complete response, while patients with disease previously untreated with radiotherapy or with tumour deposits only outside of ratiation portals yielded a 57% overall response rate with a 18% complete response rate. Only 1 out of 8 patients with performance status 2 showed a major response (12%). Median time to progression was 5.6 months (range 2.0-14 months). The median overall survival of the whole series was 9.1 months. Hematological toxicity was the most frequent side-effect. Grade 3 vomiting was recorded in 9 patients (21%), and mild mucositis in 14% of patients. Grade 3 neutropenia was observed in 21% of patients, while grade 4 in 12% of cases with neutropenic fever was seen in 4 cases. Sixteen patients (38%) complained of grade 1-2 constipation, while grade 1-2 peripheral neuropathy was seen in 8 patients (19%). CONCLUSIONS: The results achieved in this trial suggest that the combination regimen of vinorelbine and cisplatin may be safely given to patients with metastatic and/or recurrent carcinoma of the uterine cervix. This regimen is active at least in terms of objective response rates. Although satisfactory results are still lacking, these results suggest that the vinorelbine-cisplatin regimen is worthy of further studies and may represent the basis for the development of new active regimens.