What is the impact of cardiovascular and renal complications on the benefit/risk ratio of the NSAIDs?

Long-term studies of NSAIDs have demonstrated cardiovascular toxicity which poses a general problem of the benefit risk between the relief of the patient's symptoms and the risk of digestive and cardiovascular toxicity. The digestive complications and the risk factors associated with the ingestion of NSAIDs have been defined by numerous studies but the prevention of this digestive toxicity can be attempted. The benefit-risk ratio caused by the digestive and cardiovascular toxicities of the NSAIDs and COX-2 inhibitors must be evaluated for each individual before starting a treatment. For a treatment of short duration in patients with a low risk of digestive and cardiovascular complications, the risk of digestive toxicity must be taken into consideration first and the COX-2 inhibitors are favoured. For a treatment of long duration the risk must be evaluated with the greatest care. In the case of cardiovascular risk factors, the cardiovascular risk must be evaluated and the treatment must be prescribed at the lowest dose for the shortest duration. In patients with very high risk of digestive and cardiovascular complications, since the digestive and cardiovascular extra-mortality associated with the ingestion of NSAIDs or COX-2 inhibitors is high, it is advised to abandon this type of long-term treatment.     

Aprotinin in cardiac surgery patients: is the risk worth the benefit?

Background: Aprotinin is the only Food and Drug Administration-approved agent to reduce haemorrhage related to cardiac surgery and its safety and efficacy has been extensively studied. Our study sought to compare the efficacy, early and late mortality and major morbidity associated with aprotinin compared with e-aminocaproic acid (EACA) in cardiac surgery operations. Methods: Between January 2002 and December 2006, 2101 patients underwent coronary artery bypass grafting (CABG), valve surgery or CABG and valve surgery in our institution with the use of aprotinin (1898 patients) or EACA (203 patients). Logistic regression and propensity score analysis were used to adjust for imbalances in the patients’ preoperative characteristics. The propensity score-adjusted sample included 570 patients who received aprotinin and 114 who received EACA (1–5 matching). Results: Operative mortality was higher in the aprotinin group in univariate (aprotinin 4.3% vs EACA 1%, p = 0.023) but not propensity score-adjusted multivariate analysis (4% vs 0.9%, p = 0.16). In propensity score-adjusted analysis, aprotinin was also associated with a lower rate of blood transfusion (38.8% vs 50%, p = 0.04), a lower rate of haemorrhage-related re-exploration (3.7% vs 7.9%, p = 0.04) and a higher risk of in-hospital cardiac arrest (3.7% vs 0%, p = 0.03) and a marginally but not statistically significantly higher risk of acute renal failure (6.8% vs 2.6%, p = 0.09). In Cox proportional hazards regression analysis, the risk of late death was higher in the aprotinin compared to EACA group (hazard ratio = 4.33, 95% confidence interval (CI) = 1.60–11.67, p = 0.004). Conclusion: Aprotinin decreases the rate of postoperative blood transfusion and haemorrhage-related re-exploration, but increases the risk of in-hospital cardiac arrest and late mortality after cardiac surgery when compared to EACA. Cumulative evidence suggests that the risk associated with aprotinin may not be worth the haemostatic benefit.     

When is aftercare useful in renal cell cancer?

Diagnosis of tumor recurrence and of therapy-related side effects as well as psychological support are the main goals of a surveillance program of cancer patients. While the latter may represent a time-consuming effort, most diagnostic procedures are expensive. Whether we can efficiently detect tumor recurrence in renal cell carcinoma depends on various parameters of the recurrent disease (e.g., frequency, localization, or therapeutic options). Available data lend support to "lean" follow-up strategies in patients with renal cell carcinoma.     

How to evaluate the cardiovascular and renal risk at the individual level?

The cardiovascular impact of the non-steroidal anti-inflammatory drugs and the higher cardiovas-cular mortality during treatment of inflammatory rheumatism impose a rigorous evaluation of the cardiovascular risk of rheumatic patients. Large epidemiological studies have identified risk factors for cardiovascular diseases such as the age, male gender, family history (infarct, stroke), tobacco consumption, systolic arterial pressure, renal insufficiency, hypercholesterolemia, diabetes mellitis, sedentariness, obesity and "electric" ventricular hypertrophy. Some equations make it possible to evaluate the absolute cardiovascular risk at the individual level, which corresponds to the onset risk of a stroke in the 10 years to come in a subject according to the number and importance of each of his risk factors. It has been demonstrated that the correction of one or more risk factors reduce the overall cardiovascular risk, justifying the strategies for evaluating this risk to define therapeutic intervention thresholds. The impact of a long-term anti-inflammatory treatment or an inflammatory disease such as rheu-matoid arthritis has not been the subject of specific epidemiological study allowing these elements to be included in an equation of the estimation of the cardiovascular risk. However, the introduction of an anti-inflammatory treatment, likely to increase the cardiovascular risk of a patient, certainly justifies an evaluation of the absolute cardiovascular risk.     

Obesity and the kidney: Why is the kidney at risk?

Two recent studies may help to account for the increase in risk of renal injury associated with obesity. One study pointed to a role for renin-system activation. In the other study, the pattern of renal hemodynamics was compatible with a renin mechanism.     

Does renal tumor biopsies for small renal carcinoma increase the risk of upstaging on final surgery pathology report and the risk of recurrence?

BackgroundRenal tumor biopsies (RTB) have been proposed as a means to diminish overtreatment of small renal masses. A potential concern of RTB is tumor seeding along the biopsy tract leading to worse clinical outcomes.ObjectivesTo evaluate whether RTB was associated with greater upstaging to pT3a compared to patients without a biopsy and to determine if pathologic upstaging affects the risk of recurrence.Design, setting and participantsThe Canadian Kidney Cancer information system was used to identify patients who underwent radical or partial nephrectomy for malignant renal tumors ≤ 4cm (cT1a) between January 1, 2011 and July 2, 2019.InterventionRTB prior to nephrectomy or nephrectomy without biopsy.Outcomes measurements and statistical analysisUpstaging to pT3a and cancer recurrence were compared between subjects that had a RTB compared to those who did not. A multivariable analysis was used to evaluate factors associated with disease upstaging and recurrence.Results and limitationsThe cohort consisted of 1993 cT1a patients, followed for a median of 17.5 months. Of these patients, 502 (25%) had a preoperative RTB. There was no difference in the proportion with tumor upstaging to pT3a between patients that had RTB compared to those who did not (7.2% vs. 6.3%; P = 0.5). On multivariable analysis, RTB was not associated with pathological upstaging (Odds Ratio 0.90; 95% Confidence Interval 0.61–1.34) or recurrence (Odds Ratio 1.04; 95% Confidence Interval 0.57–1.89). The main limitation is that the study is underpowered to detect small differences between groups.ConclusionsIn this large, multi-institution cohort, RTB was not associated with increased risk of tumor upstaging or recurrence. Hence, tumor tract seeding, although possible, should not be a clinical deterrent to using RTBs as a means of personalizing renal masses management and diminishing overtreatment.Patient summaryRecent evidence suggests that tumor seeding following RTB may be more common than initially perceived. Our results have demonstrated that RTB was not associated with an increased risk of tumor upstaging or disease recurrence.     

Is the renal risk of adults determined in utero?

Renal (and cardiovascular) risks are to a considerable extent determined in utero. The results of the prospective study of Verburg et al., sequentially measuring the growth of fetuses and the volume of their kidneys in a large population-based sample, identify some determinants of impaired growth of fetal kidneys.     

Tolerance: is it worth the risk?

BACKGROUND: The success of orthotopic liver transplantation (OLT) has been limited by the adverse effects of immunosuppression. The purpose of this study was to determine the safety and feasibility of withdrawing immunosuppression in OLT recipients to achieve tolerance. METHODS: Eighteen adult OLT recipients in our steroid-free protocol without rejection were selected for this protocol. All patients chosen for this trial were on tacrolimus monotherapy with normal liver function tests (LFTs). Tacrolimus was weaned as long as LFTs remained stable. Weaning was halted for elevations of liver enzymes and tacrolimus was increased to the last dosage at which the patients had normal LFTs. Rejection was treated by increasing tacrolimus to levels of 10-15 ng/ml. Mycophenolate mofetil (MMF) or sirolimus was added if there was severe rejection by biopsy. Steroids were used if there was no improvement. RESULTS: One patient has been weaned off immunosuppression. Three additional patients were weaned completely off but had tacrolimus resumed because of mild elevations in LFTs. Eleven of 18 (61%) patients had rejection. Two patients required steroid therapy and one required rabbit antithymocyte globulin in addition to MMF and steroids. One of the patients with rejection developed diabetes and one patient had renal failure, which subsequently resolved. One patient died following a stroke. CONCLUSIONS: Clinical tolerance can be achieved in a minority of patients, even when being maintained on minimum immunosuppression. The potential benefit of achieving tolerance must be weighed against the risks of rejection therapy in patients doing well on low-dose immunosuppression.     

Adjuvant therapy in renal cell carcinoma: is it the right strategy to inhibit VEGF?

Despite several clinical trials have assessed different agents in the adjuvant setting, renal cell carcinoma (RCC) still remains a disease orphan of an effective adjuvant treatment. In fact, systemic therapies targeting angiogenesis that have been observed to be effective in metastatic setting failed to show an improvement in terms of clinical outcomes when used ad adjuvant treatments. In this study, we performed a meta-analysis of 5 randomized clinical trials to assess the impact of tyrosine kinase inhibitors (TKIs) targeting angiogenesis after surgery: ASSURE, S-TRAC, PROTECT, ATLAS, SORCE. Among the 6,531 patients assessed, we confirmed the lack of efficacy of adjuvant treatments in terms of disease-free survival (DFS) (pooled-HR 0.93, 95% CI, 0.84–1.02, P=0.16) and overall survival (OS) (pooled-HR 0.98, 95% CI, 0.88–1.09, P=0.54). To the best of our knowledge, we still ignore why some treatments active in the metastatic setting do not show similar efficacy as adjuvant treatment. Exploring possible reasons of this apparently conflicting results is important as it may offer new insights that should be evaluated in next generation adjuvant trials. Immune checkpoint inhibitors (ICIs) have reported significant results—as monotherapy or in combinations with other anticancer agents—in metastatic setting, and the results of trials evaluating these agents in the adjuvant setting are awaited.     

Alpha-linolenic acid and the risk of prostate cancer. What is the evidence?

PURPOSE: Several studies have examined the association between polyunsaturated fatty acids and prostate cancer risk. We evaluated the evidence on the association between the essential polyunsaturated fatty acid, known as alpha-linolenic acid, and the risk of prostate cancer in humans. MATERIALS AND METHODS: We comprehensively reviewed published studies on the association between alpha-linolenic acid and the risk of prostate cancer using MEDLINE. RESULTS: A number of studies have shown a positive association between dietary, plasma or red blood cell levels of alpha-linolenic acid and prostate cancer. Other studies have demonstrated either no association or a negative association. The limitations of these studies include the assumption that dietary or plasma alpha-linolenic acid levels are positively associated with prostate tissue alpha-linolenic acid levels, and measurement errors of dietary, plasma and red blood cell alpha-linolenic acid levels. CONCLUSIONS: More research is needed in this area before it can be concluded that there is an association between alpha-linolenic acid and prostate cancer.