Alessandro Uzzau

Intrarenal Hemodynamics in Primary Aldosteronism before and after Treatment

CONTEXT Elevated urinary albumin excretion has been reported in primary aldosteronism and might partially reflect reversible abnormalities initiated by glomerular hyperfiltration. OBJECTIVE The aim of the study was to examine the outcome of renal function and intrarenal Doppler velocimetric indices in primary aldosteronism. DESIGN We conducted a prospective study of patients with primary aldosteronism who were reevaluated 1 yr after either adrenalectomy or treatment with spironolactone. SETTING The study was conducted at a university referral center. PATIENTS Fifty-four patients with tumoral or idiopathic aldosteronism were followed after either surgical (n = 24) or medical (n = 30) treatment. Patients with primary aldosteronism were compared with 100 patients with primary hypertension and comparable severity and duration of disease. MAIN OUTCOME MEASURES Changes in renal function and intrarenal echo-Doppler indices were measured. RESULTS Patients with primary aldosteronism had greater creatinine clearance and urinary albumin excretion than patients with primary hypertension. Patients with primary aldosteronism and creatinine clearance above the median (105 ml/min per 1.73 m(2)) had significantly lower resistance and pulsatility index than patients with creatinine clearance below the median, independent of disease subtype. After 1 yr, creatinine clearance and albuminuria declined, and resistance and pulsatility index increased to the same extent in patients with primary aldosteronism treated with either adrenalectomy or spironolactone. Changes in glomerular filtration and albuminuria were inversely related with baseline values of the resistance index. In primary hypertension, echo-Doppler velocimetric indices did not change during follow-up. CONCLUSIONS In primary aldosteronism, sonographic evidence of decreased intrarenal vascular resistance is associated with glomerular hyperfiltration. Both adrenalectomy and spironolactone revert the intrarenal hemodynamic pattern and decrease urinary protein losses.

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (LT) is usually reserved for Child B and C patients with single or multiple nodules. The aim of this study was to compare HR and LT for HCC within the Milan criteria on an intention‐to‐treat basis. Forty‐eight patients were treated by LT and 38 by HR. The median time on the waiting list for transplantation was 118 days. The estimated overall survival was significantly higher (P = 0.005) in the LT group than in the HR one. The estimated freedom from recurrence was also significantly higher (P < 0.0001) for LT patients than for HR ones. Indeed, the probability of HCC recurrence after resection was higher than after transplantation achieving 31% and 76% for HR and 2% and 2% for LT at 3 and 5 years after surgery. Multivariate analysis confirmed that transplantation was superior to resection in terms of patient’s survival and risk of HCC recurrence. We conclude that LT is superior to HR for small HCC in cirrhotic patients assuming that LT should be performed within 6–10 months after listing to reduce the dropouts for reasons of tumor progression.

Relationship of Plasma Renin With a Prothrombotic State in Hypertension: Relevance for Organ Damage

BACKGROUND Components of the renin-angiotensin-aldosterone system (RAAS) and a prothrombotic state are predictors of cardiovascular events in hypertensive patients. A relationship between the RAAS and the coagulation/fibrinolytic systems has been demonstrated, but its clinical relevance in hypertension is unclear. We investigated the relationships of the RAAS and the hemostatic system with hypertensive organ damage. METHODS Plasma components of the RAAS and parameters that directly assess the activation of coagulation and fibrinolysis were measured in 247 essential hypertensive patients in whom the extent of organ damage had been characterized at the cardiac, renal, and vascular level. RESULTS Positive association with increasing plasma renin activity (PRA) was demonstrated for plasma fibrinogen, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) levels. PRA was directly correlated with plasma aldosterone, fibrinogen, d-dimer, and PAI-1. The relationship of PRA with fibrinogen and PAI-1 remained significant after correction for age, gender, duration of hypertension, and smoking status. Plasma aldosterone levels were directly correlated with fibrinogen, D-dimer, and PAI-1, whereas plasma angiotensin-converting enzyme was not related with any of the coagulation parameters. Elevated PRA, aldosterone, fibrinogen, D-dimer, prothrombin fragment 1+2, and PAI-1 levels were associated with clinical and/or instrumental evidence of hypertension-related cardiac and renal damage. Both fibrinogen and PAI-1 were independent predictors of the presence of organ damage and their inclusion in a multivariate model eliminated PRA and aldosterone as independent predictors. CONCLUSIONS A strong and independent association exists between renin, aldosterone, and markers of a prothrombotic state in essential hypertension. This relationship might contribute to the development of hypertensive organ damage.

Mineralocorticoid antagonists treatment versus surgery in primary aldosteronism.

Recent evidence indicates a greater frequency of primary aldosteronism (PA) among patients with hypertension than the previously accepted prevalence. PA was once considered a relatively benign form of hypertension associated with low incidence of organ complications. Recent views, however, suggest that long-term exposure to increased aldosterone levels might result in cardiovascular, renal, and metabolic sequelae that occur independently of the blood pressure level. Cross-sectional comparisons with patients with essential hypertension have demonstrated that patients with PA are at higher risk of cardiovascular events, have more frequent left ventricular hypertrophy and diastolic dysfunction, have greater urinary albumin losses as a marker of a hemodynamic intrarenal adaptation, and are insulin resistant. Some of these findings have been corroborated by the results of short-term, follow-up studies where it was shown that unilateral adrenalectomy or treatment with mineralocorticoid receptor (MR) antagonists are effective in correcting hypertension and hypokalemia. Normalization of blood pressure and correction of hypokalemia, however, are not the only goals in managing PA and effective prevention of organ complications is mandatory in these patients. The relative efficacy of adrenalectomy and MR antagonists, in the long-term, on the cardiovascular, renal, and metabolic outcomes still needs evaluation, being the aldosterone-induced tissue damage the main factor that could justify the cost of increasing efforts in screening of disease and differentiation of subtypes. In this narrative review, we summarize the results obtained with either surgical or medical treatment of PA and outline the findings of long-term, prospective studies on the effects of treatment on cardiovascular and renal outcomes and on insulin sensitivity.

Surgical Treatment and Survival in Patients with Liver Metastases from Neuroendocrine Tumors: A Meta-Analysis of Observational Studies

Introduction. The role of hepatic resection in patients with liver metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is still poorly defined. Therefore, we examined the results obtained with surgical resection and other locoregional or systemic therapies by reviewing the recent literature on this topic. We performed the meta-analysis for comparing surgical resection of hepatic metastases with other treatments. Materials and Methods. In this systematic review and meta-analysis of observational studies, the literature search was undertaken between 1990 and 2012 looking for studies evaluating the different survivals between patients treated with surgical resection of hepatic metastases and with other surgical or nonsurgical therapies. The studies were evaluated for quality, publication bias, and heterogeneity. Pooled hazard ratio (HR) estimates and 95% confidence intervals (CI.95) were calculated using fixed-effects model. Results. We selected six studies in the review, five of which were suitable for meta-analysis. We found a significant longer survival in patients treated with hepatic resection than embolisation HR 0.34 (CI.95 0.21–0.55) or all other nonsurgical treatments HR 0.45 (CI.95 0.34–0.60). Only one study compared surgical resection with liver transplantation and meta-analysis was not feasible. Conclusions. Our meta-analysis provides evidence supporting the hypothesis that hepatic resection increases overall survival in patients with liver metastases from GEP-NETs. Further randomized clinical trials are needed to confirm these findings and it would be desirable to identify new markers to properly select patients for surgical treatment.

LIVER RESECTION FOR HEPATOCELLULAR CARCINOMA: A MULTIVARIATE ANALYSIS OF FACTORS ASSOCIATED WITH IMPROVED PROGNOSIS. THE ROLE OF CLINICAL, PATHOLOGICAL AND SURGICAL RELATED FACTORS

Aims and background Hepatocellular carcinoma (Hcc) is the third most common cause of cancer death. The aim of this study is to examine the factors associated with improved prognosis in Hcc after liver resection. Patients and methods From September 1989 to March 2005, 134 consecutive patients had liver resection for Hcc on cirrhosis at our department. We performed 54 major liver resections and 80 limited resections. All patients enrolled in the study were followed-up three times during the first year after resection and twice the next years. Results In-hospital mortality rate was 7.4%, about 50% of these cases were Child-Pugh B patients. Morbidity rate was 47.7%, caused by the rising of ascites, temporary liver impairment function, biliary fistula, hepatic abscess, hemoperitoneum and pleural effusion. Overall survival resulted to be influenced by etiology (P = 0.03), underlying liver disease, in particular Child A vs BC (P = 0.04), Endmondson-Steiner grading (P = 0.01), the absence of a capsule (P = 0.004), the presence of more than one lesion (P = 0.02), lesions size over 5 cm (P = 0.04), Pringle maneuver length over than 20 minutes (P = 0.03), an amount of resected liver volume lesser than 50% of total liver volume (P = 0. 03), and the relapse of Hcc (P = 0.01). Conclusions The treatment of hepatocellular carcinoma should be both the most radical to obtain the best outcome and to reduce the recurrences rate, and the most suitable according to the patients condition, lesions characteristics and underlying liver disease: because of the large number of factors affecting the outcome of Hcc, unfortunately, we are still far from an agreement upon a group of criteria useful to select the best candidates for liver resection.

Mineralocorticoid Receptor Antagonists and Clinical Outcomes in Primary Aldosteronism: As Good as Surgery?

Primary aldosteronism (PA) is detected with increasing frequency in hypertensive patients and is associated with excess cardiovascular, renal, and metabolic complications. For these reasons, appropriate choices for treatment of this endocrine condition are mandatory. Adrenalectomy is safely performed in PA patients when adrenal venous sampling (AVS) demonstrates lateralized aldosterone secretion. AVS, however, is a complex procedure and even among worldwide referral centers there are substantial discrepancies for interpretation of results. Also, in the majority of PA patients with lateralized aldosterone secretion, hypertension may persist after adrenalectomy requiring use of additional antihypertensive agents. Treatment with mineralocorticoid receptor antagonists (MRAs) is currently recommended for PA patients with bilateral adrenal disease, but these agents effectively decrease blood pressure also in patients with unilateral disease, although concern remains for possible sex-related side effects. Prospective studies indicate that MRAs have therapeutic values comparable to surgery in the long-term, inasmuch as they effectively correct metabolic abnormalities and subclinical organ damage and reduce the risk of cardiovascular events and renal disease progression. This article overviews the clinical outcomes obtained in patients with PA with use of MRAs.

Minimally invasive esophagectomy: a comparative study of transhiatal laparoscopic approach versus laparoscopic right transthoracic esophagectomy.

Background The development of minimally invasive surgery gave birth to an interest in a mini-invasive approach to esophageal cancer; however, it is still considered to be one of the most complex gastrointestinal surgical operations, and many questions still remain unanswered, regarding the oncologic results of a mini-invasive approach in long-term follow-ups. Here, the authors report on the short-term and long-term results of a series of laparoscopic esophagectomies. Patients and Methods From January 2002 to March 2006, 22 nonrandomized patients were recruited to undergo an esophagectomy for neoplastic disease. The esophagectomy and esophagogastroplasty were carried out using the laparoscopic transhiatal technique in 9 patients; whereas, a combined laparoscopic and right-transthoracic incision was performed in the other 13 patients. Results The mean follow-up was 21±3.23 months (mean±SD); range, 2 to 46 months. The overall survival rate resulted 84.0% at 12 months, 61.3% at 24 months, and 51.0% at 36 months. The proportions of cumulative survival showed significant differences when the following variables were considered: site of neoplasm (lower esophagus), American Society of Anesthesiologists 2, chronic obstructive pulmonary disease, type of surgical procedure, and inclusion in neoadjuvant protocol and staging. Recurrence rates were 3 (25%) in the radio-chemotherapy–treated group, and 5 (50%) in the primary surgery group (P=n.s.). Conclusions The two-year survival rates (61.3%) recorded in our series are comparable with those reported in other series of both laparoscopic and open surgeries. The logical conclusion was that a less invasive procedure did not imply a less curative one.

Schwannoma of the sympathetic cervical chain presenting as a lateral cervical mass.

We discuss about the diagnosis and treatment of Schwannoma arising from the sympathetic cervical chain on the basis of a case report on a patient whose previously diagnosis was paraganglioma.

Distant Metastases from Cervical Esophagus Cancer

Cancer of the cervical esophagus has a poor prognosis in relation to stage. Correct staging is thus essential in order to establish the prognosis and the treatment program. Distant metastases can involve the lymph nodes (mediastinal and celiac lymph nodes) or they can be extranodal visceral types. Correct lymph node staging can be performed with esophageal endoscopic ultrasonography, computed tomography (CT) scan and, currently, with positron emission tomography (PET) and minimally invasive surgery. For hematogenous metastases, CT scan and PET are mainly used, as well as minimally invasive surgery, with the eventual aid of intraoperative ultrasonography.