Current Status of Robot-Assisted Partial Nephrectomy

The incidence of incidentally diagnosed small renal masses is rising. Although open partial nephrectomy (OPN) remains the reference standard for clinically localized renal lesions, growing experience with minimally invasive PN has demonstrated equivalent oncologic efficacy and improved short-term perioperative outcomes compared to open techniques. Compared to the technically demanding laparoscopic PN (LPN), robotic PN (RPN) overcomes a number of the technical hurdles of LPN with a shorter learning curve, and now has emerged as an attractive minimally invasive treatment option for amenable tumors. Although experience with RPN has been limited to date, early series have demonstrated short-term oncologic outcomes comparable to OPN and equivalent perioperative outcomes to LPN (all ≤ level III evidence). Although prospective evidence would be ideal, clinical trial comparisons with LPN and OPN will be fraught with accrual challenges and are not expected in the near future. This review summarizes the advantages and indications for a robotic approach, operative principles and emerging technologies, early functional and oncologic outcomes, and expected future advances of RPN for localized renal tumors.     

Longitudinal changes in social functioning in mildly disabled patients with relapsing–remitting multiple sclerosis receiving subcutaneous interferon β-1a: results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study (II)

Purpose

To report longitudinal changes in and explore the influence of cognition on social functioning in mildly disabled patients with relapsing?Cremitting multiple sclerosis (RRMS).

Methods

Italian patients (18?C50?years) with RRMS and Expanded Disability Status Scale (EDSS) score ??4.0 were assigned to interferon ??-1a, 44 or 22???g subcutaneously three times weekly, and underwent annual assessments for social functioning (Environmental Status Scale [ESS]) over 3?years.

Results

Baseline total ESS score did not differ between patients with and without cognitive impairment (P?=?0.505). Total ESS score remained low (<2.0) and stable over 3?years in the whole study population, but worsened slightly when assessed by assigned treatment or treatment and baseline cognitive status (both P?=?0.004), driven mostly by changes in the ??transportation?? and ??financial/economic status?? subscales. The strongest independent predictor of worsening ESS score was baseline EDSS score. Test?Cretest analyses confirmed that total ESS score and most subscales changed little over 3?years.

Conclusion

ESS scores remained low and changed minimally over 3?years, reflecting the mild physical disability and good cognitive performance in this patient population. Determining the influence of cognitive function and treatment on longitudinal changes in social functioning requires further studies.     

Risk stratification and prognosis of patients with known or suspected coronary artery disease by use of supine bicycle exercise stress echocardiography.

BACKGROUND: The aim of this study was to assess the long-term predictive values of supine bicycle exercise stress echocardiography (ESE), and the ESE additional role compared to other traditional clinical and rest echocardiographic variables, in 607 patients with low, intermediate and high pretest risk of cardiac events. METHODS: Clinical status and long-term outcome were assessed for a mean period of 46 months (range 12-60 months). ESE was performed for the diagnosis of suspected coronary artery disease (CAD) in 267 patients (43.9%), and for risk stratification of known CAD in 340 patients (56.1%). At baseline, the mean value of wall motion score index (WMSI) was 1.22 +/- 0.36, and the mean left ventricular ejection fraction was 58.5 +/- 10.9%. RESULTS: ESE was positive for ischemia in 210 patients (34.9%), while ECG was suggestive for ischemia in 157 patients (25.8%). During the test only 97 patients (15.9%) experienced angina. At peak effort, the mean WMSI was 1.38 +/- 0.46. A low workload was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 82 hard events (36.9%), 48 deaths (21.6%) and 34 acute non-fatal myocardial infarction (15.3%). At stepwise multivariate model, cigarette smoking (p < 0.01), peak WMSI (p < 0.001), ESE positive for ischemia (p < 0.001) and low workload (p < 0.01) were the only independent predictors of cardiac death, while positive ESE, peak WMSI, angina during the test and hypercholesterolemia were the only independent determinants of hard cardiac events. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 83.7% in patients with positive ESE (log rank 13.6; p < 0.00001). CONCLUSIONS: ESE yields prognostic information in known or suspected CAD, especially in patients with intermediate pretest risk level. The combined evaluation of clinical variables and other ESE variables, such as peak WMSI and exercise capacity, may further select patients at greatest risk of cardiac death in the overall population.     

Thyroid sarcoidosis as a unique localization.

Sarcoidosis is a systemic disorder characterized by granulomatous lesions, principally affecting the lungs. There are numerous reports in the literature of an associated involvement of the thyroid, much more frequently in hypothyroid than in hyperthyroid subjects. The present case report refers to a woman presenting with thyroid nodules and normal biochemical levels and thyroid function parameters, while histology revealed sarcoid-type lesions. Subsequent investigations and a long follow-up showed no evidence of involvement of other sites, including the lungs. Consequently, after a long period of normal health associated with the negative results of the examinations, a diagnosis of sarcoidosis limited to the thyroid was proposed, which was cured by thyroidectomy.     

CCM2 gene polymorphisms in Italian sporadic patients with cerebral cavernous malformation: a case-control study

Cerebral cavernous malformations (CCMs) are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1 (Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Among our group of CCM Italian patients, we selected a cohort of sporadic cases negative for mutations in CCM genes. In this cohort, five variants in CCM2 gene were detected, which proved to be the known polymorphisms in intronic regions (IVS2-36A>G and IVS8 +119 C>T) and in coding sequence (c.157 G>A in exon 2, c.358 G>A in exon 4 and c.915 G>A in exon 8). Therefore, we undertook a case-control study to investigate the possible association of these polymorphisms with sporadic CCMs. The five polymorphisms were identified in 91 CCM sporadic patients and in 100 healthy controls by direct sequencing methods using lymphocyte DNA. Polymorphisms IVS2-36A>G and c.915 G>A showed statistically significant differences in frequencies between patients and controls [(χ2, 6.583; P<0.037); (χ2, 14.205; P<0.001)]. The prevalence of the wild-type genotype was significantly lower in the CCM group than in the control sample. Patients with the A/G and G/G genotypes (IVS2-36A>G) had a significant increase for CCM risk (OR, 3.08; 95% CI, 1.5-5.9 and OR, 4.3; 95% CI, 1.4-22.6) and the same was observed for the polymorphism c.915 G> A (genotype G/A OR, 6.1; 95% CI, 3.0-12.6 and genotype A/A OR, 2.79). In addition, the polymorphisms c.358 G>A in exon 4 (χ2, 15.977; P<0.04) and c.915 G>A in exon 8 (χ2, 18.109; P<0.02) were significantly associated with different types of symptoms. Haplotype analysis, performed only on polymorphisms c.358 G>A (p.Val120Ile), c.915 G>A (p.Thr305 Thr) and IVS2-36A>G, shows that haplotype GAG (+--) significantly increased among CCM sporadic patients compared to the control group. Significant differences between patients and controls were observed only for IVS2-36A>G and c.915 G>A polymorphisms indicating their possible association with sporadic CCMs and an increased risk of CCM. On the other hand, polymorphisms c.358 G>A and c.915 G>A were associated with a more benign course of the disease. These data were confirmed by the haplotype GAG (+--) frequencies.     

Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient''s prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.Key words: Colorectal carcinoma, Preoperative carcinoembryonic antigen, Disease-free survival, Independent prognostic factorIn the world today, more than 1 million cases of patients with colorectal neoplasia are identified each year. Forty percent of these will have a poor prognosis for which targeted therapeutic strategies could most likely be more effective.^1–3 For this reason, finding prognostic factors that are early, reliable, and related to the extent of the tumor is of the utmost importance. Among these, the most that are considered even to this day are T and N parameters.^1,2,4,5 Less relied upon, however, is the M parameter, which is often understaged due to inadequate pretreatment diagnostic methods.⁶ However, these parameters, which are available to us only after surgery, do not represent the gold standard. In fact, the prognosis of patients with the same staging is often various and that the need to continually implement ever-changing variables in an already excessively fragmented staging is still present.^2,4,7–9Recently, in light of these needs, great attention has been paid to the study of molecular and genetic markers. At present, these markers still have not found a regular application due to the complexity of their determination, the difficulty of standardization and, last but not least, the low cost-benefit ratio.^1,3,4,9,10With this in mind, in our opinion, the carcinoembryonic antigen (CEA) maintains its position, as for over 30 years it has continued to be the most widely used marker¹¹ and whose validity, with regard to colorectal follow-up, has been sanctioned by leading organizations such as the American Society of Clinical Oncology (ASCO)¹² and the European Group on Tumor Markers.¹³ Moreover, as Herrera¹⁴ and Wanebo¹⁵ had already reported by the end of the ‘70s, the preoperative determination of the CEA (p-CEA) seems to be related both to the staging of colorectal neoplasia and to the patient''s prognosis. However, to date, none of this has been conclusively demonstrated and is still a matter of intense debate both in prestigious scientific journals^{4,7,11,16–21} as well as in different guidelines.²²The American Society of Clinical Oncology itself, if on the one hand suggests using the determination of the CEA in the preoperative staging thus justifying a worse prognosis when increased,¹² on the other, does not validate using the p-CEA in the determination of an adjuvant or neo-adjuvant therapeutic strategy.²³Regarding this issue, we believe it still pertinent to evaluate whether in a sample of patients radically treated for colorectal carcinoma, the determination of the p-CEA may have a prognostic value and constitute an independent risk factor in relation to disease-free survival (DFS).     

Use of systemic therapy and factors affecting survival for patients undergoing cytoreductive nephrectomy

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To present a multi‐institutional experience evaluating the use of systemic therapy in patients undergoing cytoreductive nephrectomy (CN), as prospective randomized trials showed a survival benefit for CN in patients with metastatic renal cell carcinoma treated with immunotherapy, and these data have been extrapolated to support CN in the era of targeted therapy, but the likelihood that patients with metastatic kidney cancer who undergo CN will receive systemic treatment afterward remains poorly defined.

PATIENTS AND METHODS

In all, 141 patients who underwent CN between 1990 and 2008 were identified from our Institutional Kidney Cancer Registries. Kaplan‐Meier analyses and Cox regression models were used to assess the effect of clinicopathological and perioperative variables on patients’ subsequent receipt of systemic therapy, and survival after CN.

RESULTS

Overall, 98 of the 141 patients (69.5%) received postoperative systemic treatment, at a median (range) of 2.5 (0.1–61.5) months after CN. In this group, 52 (53%) patients received immunotherapy, 34 (35%) targeted agents, and 12 (12%) other regimens. By contrast, 43 patients (31%) did not receive systemic therapy, because of rapid disease progression (13, 30%), decision for surveillance by medical oncology (nine, 21%), patient refusal (10, 23%), perioperative death (eight, 19%), and unknown reasons in three (7%). The median (range) survival after CN was 16.7 (0–120) months. The risk of death after surgery correlated with the number of metastatic sites (P = 0.012) and symptoms (P = 0.001) at presentation, poor performance status (P = 0.001), high tumour grade (P = 0.006), and presence of sarcomatoid features (P < 0.024).

CONCLUSION

Nearly a third of patients undergoing CN did not receive systemic treatment. While some were electively observed or declined therapy, others did not receive treatment due to rapidly progressive disease. Further investigation is warranted to identify those patients at highest risk of rapid postoperative disease progression who might benefit instead from an initial approach to treatment with systemic therapy.     

Relation of C-reactive protein to oxidative stress and to endothelial activation in essential hypertension

BACKGROUND: C-reactive protein (CRP) predicts cardiovascular outcome. Oxidative stress is considered to be involved in endothelial alteration. We hypothesized that in essential hypertension (EH), oxidative stress, as measured by 8-iso-prostaglandin-F(2alpha) (8-iso-PGF(2alpha)), should be associated with increased CRP and endothelial activation, as evaluated by soluble intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) plasma levels. METHODS: In 83 subjects with mild EH and in 50 healthy control subjects we measured, in basal conditions, plasma levels of hs-CRP, 8-iso-PGF(2alpha), ICAM-1 and VCAM-1, and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Subjects with EH had higher levels of 8-iso-PGF(2alpha) (P < .0001), CRP (P < .001), ICAM-1 and VCAM-1 (P < .001), and TNF-alpha (P < .001) than did control subjects. We divided successively EH according to CRP values (<1, 1-3, >3 mg/L), and we observed increasing and significantly different levels of the endothelial parameters and of TNF-alpha along with increasing CRP. Linear analysis of correlation pointed out significant correlation of CRP with 8-iso-PGF(2alpha) (r = 0.730, P < .001), ICAM-1 and VCAM-1 (r = 0.642 and 0.468, P < .001 respectively), and TNF-alpha (r = 0.609, P < .001). Multiple regression analysis using CRP as a dependent variable confirmed the relationship of CRP with systolic blood pressure (beta 0.216, P = 0.039) and with 8-iso-PGF(2alpha) (beta 0.602, P = .0001). CONCLUSIONS: Our data demonstrate that in EH, inflammatory molecules such as CRP and TNF-alpha are increased and related to both oxidative stress and endothelial activation.