Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

PATIENT’S COMPLIANCE TO BCG. DO WE ADEQUATELY CONSIDER IT?

Introduction: Several studies and meta-analysis demonstrated that BCG is the best treatment for conservative management of high-risk NMI-BC with a net benefit in terms of both recurrence-free and progression-free survival (1, 2). Maintenance lasting minimum one year is recommended. In spite of the effectiveness, the amount of patients who complete the manteinance schedule does not exceed 50% (3). The reasons of BCG maintenance interruption remain still unclear. The aim of our study was to investigate the causes of low adherence to 1-year full dose maintenance BCG in a large series. Patients and Methods: The clinical files of consecutive patients affected by T1 HG NMI-BC and undergoing adjuvant BCG for one year, between 2000 and 2012, were reviewed. Main exclusion criteria were presence of Tis, previous T1 HG, number of tumors more than 3 and diameter greater than 3 cm, genitourinary tract infections or other disease potentially impacting tolerability and compliance to BCG. One-year BCG maintenance was scheduled according to the South West Oncology Group (SWOG) including 3 weekly instillations at 3, 6 and 12 months starting 21-40 days after TUR. No dose reduction was considered. Both local and systemic side effects and any reason of treatment suspension were recorded. BCG tollerability was classified in four grades: 0. no need of postponement, 1. one-week postponement, 2. two-week postponement, 3. one single instillation omitted, 4. definitive stop. Results: The files of 545 consecutive patients with HG NMI-BC, selected for conservative management at two tertiary referral centers were reviewed. Out of them, 411 patients (75.4%) satisfied the inclusion criteria. The induction cycle was completed and suspended by 380 (92.5%) and 31 (7.5%) patients respectively. Suspension was due to toxicity in 20 (4.8%) and to no toxicity-related reasons in 11 (2.6%) patients. Maintenance was initiated by 308 (74.9%) patients while 72 (17.5%) never started. Particularly, 32 (8.4%) patients refused it due to personal choice and/or practical limitation, 22 (5.8%) were withdrawn by the urologist before the first planned 3- week cycle due to persistent haematuria or early recurrence and 18 more patients (4.7%) never started and were lost at followup. Out of the 308 patients starting the 1-year maintenance, 215 (52.3%) patients completed it, while 93 (30.2%) did not. The manteinance regimen was interrupted by 9 patients (9.7%) due to recurrence, while 14 (15.1%) experienced grade 3 toxicity and 55 (59.1%) refused it in absence of grade 2-3 toxicity or other evident causes. Grade-I toxicity and/or mild side effects, not responsible for maintenance treatment modification, were recorded in 193 (62.7%) patients. Discussion and Conclusion: The European Association of Urology (EAU) and the National Comprehensive Cancer Network (NCCN) recommend one year BCG maintenance as the elective intravesical adjuvant regimen in intermediate- and high-risk NMI-BC, conservatively treated. The scientific urologic community does not consider BCGrelated toxicity as the major limiting factor. In the present study patient’s compliance during the induction cycle reached 92%. However during the interval between the induction course and the first maintenance instillation, 50 patients (13%) became reluctant to treatment while 22 (6%) were excluded after cystoscopy for suspicious bladder lesion. Toxicity (moderate to severe) was responsible for the interruption of BCG maintenance only in a low number of patients. The high rate of patients who abandoned the treatment could be attributable to the persistency of mild symptoms causing consistent discomfort that justified the reluctance to carry on the therapy. Moreover the inadequate counseling in everyday clinical practice when compared to multi-institutional trials should be taken into account. A structured periodical counseling and a timely recognition and treatment of symptoms, might significantly ameliorate the acceptance of BCG maintenance. Acknowledgements: We wish to thank the GSTU Foundation for administrative support. 1 Sylvester RJ et al: Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 168: 1964-1970, 2002. ANTICANCER RESEARCH 34: 2593-2686 (2014) 2618 2 Malmstrom PU et al: An individual patient data metaanalysis of the long-term outcome of randomised studies comparing intravesical mitomycin c versus bacillus Calmette-Guerin for non–muscle-invasive bladder cancer. Eur Urol 56: 247-256, 2009. 3 Oddens J et al: Final results of an EORTC-GU of EORTC genito-urinary cancers group randomized study of maintenance bacillus comparing intravesical instillations of Calmette-Guerin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol 63: 462-472, 2013

FIBRONECTIN (FN) AND UROTHELIAL DAMAGE SECONDARY TO ADJUVANT INTRAVESICAL THERAPY

Introduction and Objectives: Intravesical chemotherapy has been proven effective in preventing recurrence of low-risk non-muscle invasive bladder cancer (NMIBC). BCG is recognised as the best conservative treatment for intermediate and high risk NMIBC. Maintenance for at least one year is required to ameliorate the efficacy of adjuvant therapy. Discomfort and toxicity often cause interruption of adjuvant therapy, BCG particularly. Almost 50% of the patients undergoing BCG does not complete one year. A biomarker of urothelium damage would be helpful for timely detection of toxicity in order to ameliorate patient’s tolerance and compliance. The aim of the present study was to evaluate the gene expression of Fibronectin (FN) in bladder washing in relation with local toxicity due to adjuvant intravesical therapy. Patients and Methods: Out of 26 asymptomatic patients undergoing intravesical prophylaxis with mitomycin (40 mg/40 ml), epirubicin (80 mg/50 ml) or BCG Connaught (81 mg/50 ml) and 10 volunteers as control group, 62 samples of bladder washing were collected before, during and after therapy. The samples were analyzed by isolation of cellular RNA using a miRNeasy Mini Kit (Qiagen®). FN gene expression was analyzed by RT-PCR. The ΔΔCt method after normalization with endogenous reference 18s rRNA was adopted. An average Ct value for each RNA was obtained for triplicate reactions. Local toxicity was classified into 3 grades: 0-1. mild (no medical therapy); 2. moderate (medical therapy); 3. severe (instillation postponed for 1-2 weeks or intravesical solution of hyaluronic acid and chondroitin sulphate administered). Results: FN gene expression, compared to controls, was increased 1.1 fold after TUR and before intravesical therapy. During therapy it remained unchanged (1.0 fold). However it was increased 1.1 fold in absence of local toxicity, but to a median value of 3.6 fold in presence of severe toxicity. Particularly, the mean values, compared to controls, were 2.4 (range: 0.3-6.1), 1.1 (range: 0.1-2.3), 9.3 (range: 0.2-45.2), before therapy, in absence and in presence of local toxicity, respectively. Of interest, patients receiving intravesical hyaluronic acid and chondroitin sulphate solution showed a median FN gene expression of 0.2 fold (range 0.1- 0.7), decreasing from 3 to 0.6 and from 4 to 0.2 fold in two patients contemporary with symptomatic relief. Discussion: Few studies have correlated the gene expression of FN to bladder urothelial damage, in interstitial cystitis (1). FN plays an important role on BCG activity (2). A marker of topical toxicity would be helpful to improve the tolerance and to reduce the drop-out rates of intravesical therapy. The measurement in bladder washing is a simple and direct evaluation of urothelial FN gene activity. This method avoids all the bias due to the evaluation of FN protein expression in urine. The overexpression of FN gene indicates the presence of urothelial damage and activation of repairing processes. Normal and downexpression indicate the absence or healing of urothelial damage. Preliminarily, our study shows a significant correlation between FN gene expression on bladder washing and local toxicity. Furthermore, FN seems to be reduced by the intravesical administration of intravesical hyaluronic acid and chondroitin sulphate solution. Conclusion: FN gene expression in bladder washing emerges as a simple and promising marker of urothelial damage. Further and larger studies should be justified. Acknowledgements: We wish to thank IBSA for unrestricted grant and the GSTU Foundation for administrative support. 1 Blalock EM et al: Gene expression analysis of urine sediment: evaluation for potential noninvasive markers of interstitial cystitis/bladder pain syndrome. J Urol 187: 725, 2012. 2 Eissa S et al: Diagnostic value of fibronectin and mutant p53 in the urine of patients with bladder cancer: impact on clinicopathological features and disease recurrence 27: 1286, 2010

Fibronectin (FN), epidermal growth factor-receptor (EGF-R) and heparin-binding epidermal growth factor-like (HB-EGF) urinary expressions and topical toxicity of adjuvant intravesical therapy for non muscle invasive bladder cancer (NMI-BC)

NMI bladder cancer, EGF-R, intravesical therapy. fibronecti

Azione antalgica di Hydrogel nell'orbitopatia basedowiana

La terapia dell'orbitopatia,nella fase acuta,si basa oltre che sulla correzione della turba endocrinologica,sulla protezione della cornea e sull'uso dei corticosteroidi ad alto dosaggio o di farmaci immunosoppressori o, in alternativa,sulla radioterapia orbitaria.Per attenuare la sintomatologia dolorosa,frequente nella fase acuta e che può inficiare la qualità della vita,data la componente flogistica,abbiamo voluto valutare gli effetti di una terapia antalgica mediante appliocazione sulla superficie palpebrale di un gel chirurgico criogenico decongestinante ( a contenuto di estratto di ananas più acido betaglicirretico),ad oggi utilizzato con risultati soddisfacenti in soggetti sottoposti a trattamenti chirurgici degli annessi oculari.Sono stati studiati in doppio cieco 50 soggetti ( 16 uomini e 34 donne, range età 35-46,5 anni) con orbitopatia basedowiana ( OB) di grado 3,in fase dinamica,secondo la classificazione dell'American Thyroid Association.Tutti i pazienti,egualmente distribuiti in due gruppi,erano in terapia tireostatica con MMI.Nessun effetto collaterale è stato riscontrato.All'esame clinico-strumentale-oftalmologico (visus,motilità oculare,fundus,esoftalmometria e tonometria) non si sono apprezzate variazioni significative pre e post trattamento in nessuno dei due gruppi.2 soggetti del gruppo placebo hanno riferito un miglioramento complessivo della sintomatologia, mentre nel gruppo trattato 24 soggetti hanno riferito un sensibile miglioramento come da questionario validato.Nel nostro studio la terapia con Hydrogel si è rivelata una valida strategia antalgica da associare ai farmaci ad azione sistemica

Prognostic Stratification of Patients With ST-Segment-Elevation Myocardial Infarction (PROSPECT): A Cardiac Magnetic Resonance Study.

Cardiac magnetic resonance (CMR) is a robust tool to evaluate left ventricular ejection fraction (LVEF), myocardial salvage index, microvascular obstruction, and myocardial hemorrhage in patients with ST-segment-elevation myocardial infarction. We evaluated the additional prognostic benefit of a CMR score over standard prognostic stratification with global registry of acute coronary events (GRACE) score and transthoracic echocardiography LVEF measurement. Two hundred nine consecutive patients with ST-segment-elevation myocardial infarction (age, 61.4±11.4 years; 162 men) underwent transthoracic echocardiography and CMR after succesful primary percutaneous coronary intervention. Major adverse cardiac events (MACE) were assessed at a mean follow-up of 2.5±1.2 years. MACE occurred in 24 (12%) patients who at baseline showed higher GRACE risk score (P<0.01), lower LVEF with both transthoracic echocardiography and CMR, lower myocardial salvage index, and higher per-patient myocardial hemorrhage and microvascular obstruction prevalence and amount as compared with patients without MACE (P<0.01). The best cut-off values of transthoracic echocardiography-LVEF, CMR-LVEF, myocardial salvage index, and microvascular obstruction to predict MACE were 46.7%, 37.5%, 0.4, and 2.6% of left ventricular mass, respectively. Accordingly, a weighted CMR score, including the following 4 variables (CMR-LVEF, myocardial salvage index, microvascular obstruction, and myocardial hemorrhage), with a maximum of 17 points was calculated and included in the multivariable analysis showing that only CMR score (hazard ratio, 1.867 per SD increase [1.311-2.658]; P<0.001) was independently associated with MACE with the highest net reclassification improvement as compared to GRACE score and transthoracic echocardiography-LVEF measurement. CMR score provides incremental prognostic stratification as compared with GRACE score and transthoracic echocardiography-LVEF and may impact the management of patients with ST-segment-elevation myocardial infarction