Advanced/metastatic bladder cancer: current status and future directions.

In 2015 bladder cancer was the fourth most frequent malignancy and the eighth cause of death for cancer. At diagnosis, about 30% of bladder cancer (BC) patients present a muscle-invasive bladder cancer (MIBC) and 5% a metastatic bladder carcinoma (MBC). For fit MBC patients, combination chemotherapy (CC) is the standard of care for first-line treatment. CC includes both the treatment with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) either the classical or the dose-dense MVAC regimen, and the doublet therapy with cisplatin and gemcitabine (CG). Median progression free survival (PFS) was 7 months and median overall survival (OS) was 15 months. The present review provides an update on the management of MBC, with focus on target therapies, immune checkpoint inhibition, looking for prognostic and predictive factors.

Penile cancer: prognostic and predictive factors in clinical decision-making.

Penile cancer (PC) is a typical tumor of non-industrialized countries. The incidence is 20-30 times higher in Africa and South America, considering the elevated prevalence of sexually transmitted diseases. Histologically, PC includes squamous cell carcinoma (SCPC), the most frequent, and nonsquamous carcinoma (NSCPC). Early diagnosis is the goal, whereas later diagnosis relates to poor functional outcomes and worse prognosis. The 5-year survival rate is 85% for patients with histologically regional negative lymph nodes, compared to 29%-40% for those with histologically regional positive lymph nodes. To date no new drugs are approved, and there are few new data about molecular mechanisms underlying tumorigenesis. The SCPC remains a rare tumor and the current therapeutic algorithm is based principally on retrospective analysis and less on prospective trials. In this review article, biomarkers of prognosis and efficacy of current treatments are summarized with a focus on those that have the potential to affect treatment decision-making in SCPC.

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

[Cardiac involvement in rheumatoid arthritis]. / Il coinvolgimento cardiaco nell'artrite reumatoide.

Rheumatoid arthritis (RA) is a systemic disease of unknown etiology characterized by a chronic inflammatory process mainly leading to destruction of synovial membrane of small and major diarthrodial joints. The prevalence of RA within the general adult population is about 1% and female subjects in fertile age result mostly involved. It's an invalidating disease, associated with changes in life quality and a reduced life expectancy. Moreover, we can observe an increased mortality rate in this population early after the onset of the disease. The mortality excess can be partially due to infective, gastrointestinal, renal or pulmonary complications and malignancy (mainly lung cancer and non-Hodgkin lymphoma). Among extra-articular complications, cardiovascular (CV) involvement represents one of the leading causes of morbidity and mortality. Every cardiac structure can be affected by different pathogenic pathways: heart valves, conduction system, myocardium, endocardium, pericardium and coronary arteries. Consequently, different clinical manifestations can be detected, including: pericarditis, myocarditis, myocardial fibrosis, arrhythmias, alterations of conduction system, coronaropathies and ischemic cardiopathy, valvular disease, pulmonary hypertension and heart failure. Considering that early cardiac involvement negatively affects the prognosis, it is mandatory to identify high CV risk RA patients to better define long-term management of this population.

Association between myocardial right ventricular relaxation time and pulmonary arterial pressure in chronic obstructive lung disease: analysis by pulsed Doppler tissue imaging.

This study assessed right ventricular function in chronic obstructive lung disease and pulmonary hypertension by Doppler tissue imaging. Doppler echocardiography of the right ventricle and Doppler tissue imaging of the tricuspid annulus were performed in 63 subjects: 20 healthy controls, 20 with lung disease, and 23 with both lung disease and pulmonary hypertension. Two-dimensional tricuspid systolic plane excursion was lower in patients with pulmonary hypertension than in the other 2 groups. Doppler tricuspid inflow measurements distinguished patients in both of the diseased groups from the control subjects, but they did not differentiate patients with pulmonary hypertension from those without it. The ratio of peak E-wave to peak A-wave velocities derived by Doppler tissue imaging was significantly lower and the myocardial acceleration time longer in both groups of lung disease than in the control group. Only myocardial relaxation time distinguished the 3 groups (all P <.01); a gradual increase in time occurred, with the shortest time seen in controls, a longer time in patients with chronic obstructive lung disease without pulmonary hypertension, and the longest time in patients with lung disease and pulmonary hypertension. In the overall population including subjects with at least minimal tricuspid regurgitation, myocardial relaxation time was positively related to pulmonary systolic pressure. In conclusion, Doppler tissue imaging distinguishes subsets of patients affected by lung disease with or without pulmonary hypertension and identifies patients with different levels of pulmonary artery systolic pressure.

[Cephalic zoster with involvement of the 5th, 7th, 8th, 9th and 10th cranial nerves]. / Zoster cefalico con interessamento del 5, 7, 8, 9 e 10 nervo cranico.

A case of cephalic zoster with involvement of the 5th, 7th, 8th, 9th and 10th left cranial nerves is described. The anatomopathological findings are surveyed. These show that lesions are often found in several areas of the nervous system. The pathogenesis of these forms is examined, with particular reference to the mechanism of involvement of several cranial nerves. It is felt that this is primarily due to reactivation of the virus in several ganglia.

Impact of myocardial diastolic dysfunction on coronary flow reserve in hypertensive patients with left ventricular hypertrophy.

BACKGROUND: The aim of the study was to assess the possible association, in hypertensive patients, between left ventricular myocardial diastolic dysfunction and coronary flow reserve (CFR) in relation to the presence of left ventricular hypertrophy (LVH). METHODS: Twenty-eight untreated hypertensives (22 males, 6 females, mean age 53.1 years), free of coronary artery disease, were enrolled in the study. Standard Doppler echocardiography, color Doppler tissue imaging of the posterior septum during dobutamine stress and second harmonic Doppler of the distal left anterior descending coronary vessel, at baseline and after maximal hyperemia induced by dipyridamole, were performed. CFR was estimated as the ratio between hyperemic and baseline diastolic velocities. Hypertensives were divided into two groups according to the left ventricular mass index: 15 without LVH (left ventricular mass index < 51 g/m2.7) and 13 with LVH (left ventricular mass index > 51 g/m2.7). The two groups were comparable for sex prevalence, age, body mass index, baseline heart rate and blood pressure. RESULTS: Color Doppler tissue imaging did not show any significant difference of both the baseline and high-dobutamine septal systolic peak velocities between the two groups. The ratio between myocardial early and atrial peak velocities (Em/Am ratio) was lower in patients with LVH, either at baseline (p < 0.01) or at high-dose dobutamine (p < 0.0001). Also, CFR was lower in the presence of LVH (p < 0.01). After adjusting for age, body mass index, left ventricular mass index, diastolic blood pressure and high-dose dobutamine heart rate by a multiple linear regression analysis, the high-dose dobutamine Em/Am ratio was an independent contributor of CFR in the overall hypertensive population (beta = 0.65, p < 0.0001) (cumulative r2 = 0.38, p < 0.0001). CONCLUSIONS: The combined use of second harmonic Doppler and color Doppler tissue imaging identifies, in arterial hypertension, an association between myocardial diastolic properties and CFR, independent of the presence of LVH. In hypertensive patients free of coronary artery stenosis, left ventricular myocardial diastolic dysfunction may be a determinant in the impairment of the coronary microvessel vasodilation capacity or a marker of silent ischemia involving the microvascular circulation.

Right ventricular myocardial diastolic dysfunction in different kinds of cardiac hypertrophy: analysis by pulsed Doppler tissue imaging.

BACKGROUND: Right ventricular (RV) chamber involvement has been demonstrated in hypertrophic cardiomyopathy (HCM) as well as in hypertensive left ventricular hypertrophy (LVH) but little is known about RV myocardial dysfunction occurring in these two pathologies. The aim of this study was to compare Doppler tissue imaging (DTI) of the right ventricle in HCM and LVH in relation to DTI of the left ventricle and Doppler standard of the RV and left ventricular (LV) inflow. METHODS: Thirty controls, 20 hypertensives with LVH, and 23 patients with HCM involving the interventricular septum underwent Doppler echocardiography and pulsed DTI of the LV lateral mitral annulus and the RV lateral tricuspid annulus. RESULTS: Patients with HCM had a higher blood pressure, septal thickness and LV mass in comparison with the other two groups. The RV wall thickness did not differ between HCM and LVH. The fractional shortening, but not the tricuspid annular plane excursion, was higher in HCM. After adjusting for the mean blood pressure, the Doppler-derived global LV and RV diastolic functions were more impaired in HCM than in LVH. Also the majority of DTI LV and RV diastolic measurements were altered more in HCM. At the RV tricuspid annulus, myocardial diastolic indexes were impaired in HCM and LVH in comparison with controls but the deceleration and relaxation times distinguished also HCM and LVH, being much longer in HCM (p < 0.0001). In the overall population, the RV myocardial relaxation time was positively related to the septal wall thickness and the RV wall thickness, even after adjusting for age, heart rate, diastolic blood pressure, fractional shortening and DTI mitral relaxation time. CONCLUSIONS: The impairment of RV myocardial relaxation is much more evident in HCM than in LVH, its degree being independently associated with the extent of both the septal and RV wall thickness. Pulsed DTI may be useful to distinguish the extent of RV myocardial dysfunction in different types of cardiac hypertrophy.

Long-term prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease.

BACKGROUND: Pharmacological stress echocardiography (PSE) is increasingly used for cardiac risk stratification. Our study was undertaken to assess the long-term prognostic significance of PSE in patients with known or suspected coronary artery disease. METHODS: We studied 622 consecutive patients who underwent PSE with either dobutamine or dipyridamole. Outcome was finally assessed in 448 patients for a mean period of 32.9 months. Death and hard events (death and myocardial infarction) were considered as endpoints. RESULTS: PSE was positive for ischemia in 192 patients (42.9%). During the follow-up, 53 hard events occurred, including 28 deaths and 25 acute non-fatal myocardial infarctions. With multivariate analysis, peak ejection fraction < 40% appeared to be the strongest predictor of cardiac-related deaths and of hard endpoints (chi2 28.4 and 32.0, respectively). Peak wall motion score index revealed a strong predictive value of the same events (chi2 8.6 and 16.3, respectively). An ischemic pattern at PSE predicted a 2.4 higher cardiac mortality rate over a 5-year follow-up (9.4 vs 3.9%, p < 0.01; log rank 5.68), while patients with a peak ejection fraction < 40% had a cardiac-related mortality 4 times higher (16.3 vs 4.1%, p < 0.00001; log rank 21.16). Hard events occurred in 6.7% of patients with a negative test vs 18.8% of patients with a positive test (p < 0.001; log rank 15.8), while hard event rate was 8.4% in patients with a peak ejection fraction > 40% vs 27.5% in patients with a peak ejection fraction < 40% (p < 0.00001; log rank 38.64). CONCLUSIONS: The ischemic response to PSE showed a sustained prognostic value for cardiac events, especially in patients considered at either intermediate or high risk on the basis of recognized clinical risk factors. However, only the evaluation of both descriptors of global left ventricular performance and of the extension of induced ischemia may better help to select patients at higher risk of cardiac death.

[Food ileus caused by a phytobezoar of the small intestine]. / L'ileo alimentare da fitobezoario del tenue.

One case of small bowel obstruction due to phytobezoar is reported. The various aetiological factors are discussed. The clinical features are not typical and small bowel obstruction can be initially recurrent until a complete intestinal occlusion. The diagnosis is not easy, and is nearly always made during urgent laparotomy. Surgical treatment consists of phytobezoar removal by enterotomy. The recognition of high-risk patients and their education to prevent phytobezoar are emphasized.

[Intrathoracic goiters]. / I gozzi endotoracici.

Reference is made to the nosographical classification of intrathoracic goitre and the difficulties associated with its diagnosis. Particular attention is devoted to the correct surgical technique required. Surgery is mandatory in mediastinal cases on account of the slow and gradual progression of the swelling and exacerbation of the symptoms, and also because complications may supervene (cancer, intraparenchymal haemorrhage, etc.). The approach routes are discussed, along with the conditions requiring resort to a complementary route--usually median sternotomy--in addition to cervicotomy.

[Heterotopic pancreas in a gastric site]. / Il pancreas eterotopico a sede gastrica.

The authors describe two cases of heterotopic pancreas tissue involving the stomach. After some general comments on the frequency and anatomopathological aspects of this disease, they discuss the clinical features and modern technics for the diagnosis of heterotopic pancreas tissue, with special emphasis on gastroscopic detection and execution of aimed biopsy specimen collection. Last, they discuss the indications for surgical treatment of the disease.

Effects of long-term disease-modifying antirheumatic drugs on endothelial function in patients with early rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long-term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty-five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS-28), 2D-echo derived coronary flow reserve (CFR), common carotid intima-media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS-28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P < 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P < 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.

Transthoracic echo-Doppler assessment of coronary microvascular function late after Kawasaki disease.

The goal of this study was to demonstrate that Doppler transthoracic echocardiography (TTE) may represent a valuable tool for the noninvasive demonstration of coronary microvascular dysfunction in children with previous Kawasaki disease (KD) by the measurement of coronary flow reserve (CFR) during cold pressor test (CPT). Twenty-five children with previous KD (mean follow-up, 4.6 +/- 2.6 years) were included in the study-16 with no evidence of coronary artery lesions (CALs(-)) by TTE and 9 with coronary aneurysms (CALs(+)). Seventeen age-matched healthy subjects were also recruited. Diastolic peak velocity was measured by pulsed Doppler both at rest (DPV(Rest)) and during CPT (DPV(CPT)) in the anterior descending artery. CFR was calculated as DPV(CPT)/DPV(Rest). KD patients demonstrated significantly higher values of DPV(Rest) (0.21 +/- 0.05 vs 0.13 +/- 0.01 cm/sec, p < 0.0001) and DPV(CPT) (0.33 +/- 0.07 vs 0.27 +/- 0.03 cm/sec, p < 0.005). CFR was reduced in KD compared to control subjects (1.5 +/- 0.4 vs 2.1 +/- 0.2, p < 0.0001). CFR was decreased in a similar manner in both CALs(+) patients (1.4 +/- 0.4, p = 0.002 vs controls) and CALs(-) patients (1.6 +/- 0.4, p < 0.0001 vs controls). Doppler TTE at rest and during CPT may represent a valuable modality for CFR evaluation in children with a history of KD. CFR is significantly reduced in KD patients independently of the presence of CALs.

[Multiple organ resection in advanced gastric carcinoma: experience of 7 years]. / Resezioni multiorgano nel carcinoma gastrico avanzato setti anni di esperienza.

In this work we report our experience on multiorgan resections (MOR) for local advanced gastric cancer. From 1998 to 2004 in our Department 79 patient underwent total or partial resection of stomach associated with removal of various other organs. The results we report come from the evaluation of perioperative mortality and morbidity rates and further analysis of median survival time and quality of residual life. In conclusion, we affirm the utility of major surgery in advanced gastric cancer only in conditions that guarantee an acceptable rate of major complications.

Right ventricular diastolic dysfunction in arterial systemic hypertension: analysis by pulsed tissue Doppler.

AIMS: This study analyses right ventricular longitudinal function in arterial systemic hypertension by pulsed tissue Doppler. METHODS AND RESULTS: Thirty normotensives and 30 hypertensives, free of cardiac drugs, underwent standard Doppler echocardiography and pulsed tissue Doppler of right ventricular lateral tricuspid annulus and left ventricular lateral mitral annulus. By tissue Doppler, systolic and diastolic measurements were obtained. Hypertensives had higher left ventricular mass and impaired Doppler diastolic indexes, without changes of global systolic function. Tissue Doppler showed reduction of right ventricular E/A ratio and prolongation of relaxation time in comparison with controls (both P<0.00001). In the overall population, the length of tissue Doppler derived right ventricular relaxation time was positively related to right ventricular anterior wall thickness while right ventricular E/A ratio was positively related to E/A ratio of left ventricular mitral annulus (both P<0.00001). These relations remained significant even after adjusting for clinical and echocardiographic confounders by separate multivariate models. CONCLUSIONS: Arterial systemic hypertension is associated to right ventricular longitudinal diastolic dysfunction. This dysfunction involves the prolongation of active relaxation, which is independently associated with the degree of right ventricular hypertrophy and the impairment of passive wall properties, which is mainly due to ventricular interaction occurring under left ventricular pressure overload conditions.

Involvement of right ventricle in left ventricular hypertrophic cardiomyopathy: analysis by pulsed Doppler tissue imaging.

AIMS: This study uses pulsed Doppler tissue imaging to analyse right ventricular myocardial function and its interaction with left ventricle in hypertrophic cardiomyopathy involving ventricular septum. METHODS AND RESULTS: Thirty-four patients with septal hypertrophic cardiomyopathy and 30 normal subjects, comparable for sex, age, body mass index and heart rate, underwent complete standard Doppler echocardiography and pulsed Doppler tissue imaging of both posterior septum and right ventricular free wall, calculating myocardial velocities and both systolic and diastolic time intervals. Except for peak velocity A, the other Doppler tricuspid inflow measurements were significantly impaired in hypertrophic cardiomyopathy, without changes of tricuspid annular systolic excursion. Right ventricular Doppler tissue imaging showed longer right ventricular myocardial relaxation time in hypertrophic cardiomyopathy than in controls (P<0.00001), without a significant difference from other myocardial diastolic and systolic measurements. In the overall population, Doppler measurements of right and left ventricular inflow were not significantly associated, while (with the exception of myocardial deceleration time) all the other myocardial systolic and diastolic measurements derived by tissue imaging were directly related to the homologous septal myocardial indexes. In addition, a significant inverse relation was found between septal wall thickness and myocardial relaxation index (right-left myocardial relaxation time/right ventricular relaxation time x 100). CONCLUSIONS: This study shows the usefulness of pulsed Doppler tissue imaging to detect impairment of right ventricular myocardial function and to provide evidence about ventricular interaction in forms of hypertrophic cardiomyopathy which involve interventricular septum.