Patrice Forget

Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery

BACKGROUND An association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and better outcome after mastectomy and lung surgery for cancer has been recently suggested. In a retrospective analysis, we investigated the association between intraoperative NSAIDs use in conservative breast cancer surgery and breast cancer disease-free survival (DFS). Similarly, we also evaluated the association between breast cancer DFS and preoperative neutrophil:lymphocyte ratio (NLR). METHODS A retrospective analysis of a single-centre cohort was performed in breast cancer patients (n=720) with uni- and multivariate analyses, using a Cox regression model. RESULTS In conservative breast cancer surgery, the intraoperative use of NSAIDs (ketorolac or diclofenac) was associated with an improved DFS {hazard ratio (HR)=0.57 [95% confidence interval (CI): 0.37-0.89], P=0.01} and an improved overall survival (OS) [HR=0.35 (95% CI: 0.17-0.70), P=0.03]. In these patients, an NLR >3.3 (identified by a receiver-operating characteristic curve) was associated with a shorter DFS [HR=1.99 (95% CI: 1.16-3.41), P=0.01] and OS [HR=2.35 (95% CI: 1.02-5.43), P=0.046]. CONCLUSIONS Intraoperative NSAIDs and higher preoperative NLR are associated with improved outcome in conservative breast cancer surgery. Prospective, randomized trials to evaluate if these associations are causal are warranted.

The neutrophil-to-lymphocyte ratio: a narrative review

Cellular-mediated inflammatory response, lymphocytes, neutrophils, and monocytes are increasingly being recognised as having an important role in tumorigenesis and carcinogenesis. In this context, studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) can be used as an independent prognostic factor in a variety of cancers. Particularly in breast cancer, several studies have shown that a high NLR is associated with shorter survival. Because the NLR can be easily determined from the full blood count, it could potentially provide a simple and inexpensive test cancer prognosis. This review addresses the possibilities and limitations of using the NLR as a clinical tool for risk stratification helpful for individual treatment of breast cancer patients. The potential underlying phenomena and some perspectives are discussed.

What is the place of clonidine in anesthesia? Systematic review and meta-analyses of randomized controlled trials

STUDY OBJECTIVE A place for clonidine has been suggested for many indications in perioperative medicine. The aim of this systematic review and these meta-analyses is to systematically, and quantitatively, evaluate these potential indications of clonidine. DESIGN, SETTING, PATIENTS AND INTERVENTIONS We selected and analyzed (qualitatively and, when possible, quantitatively) the available literature published on PubMed/Medline and on the Cochrane database. Inclusion criteria included: human randomized controlled trials involving adults who received perioperative systemic (oral, intramuscular, transdermal and intravenous) clonidine for every type of surgery. MEASUREMENTS AND MAIN RESULTS We identified 775 trials and thereafter excluded 718 and analyzed 57 trials concerning, in total, 14,790 patients of whom 7408 received clonidine and 6836 received placebo. Most important results shows that, in qualitative and quantitative analyses, clonidine vs placebo reduces analgesics consumption in, respectively, (159 vs 154 patients: 24%, 95%CI[16%-32%]; p<0.001), reduces nausea and vomiting (risk ratio, in 180 vs 181 patients: 0.35, 95%CI[0.25-0.51]; p<0.001), improves hemodynamic stability (reduction of HR: 14.9bpm, 95%CI[10.4-19.5]; p<0.001; reduction of the MAP: 12.5mmHg, 95%CI[7.14-17.86]; p<0.001); 1min after tracheal intubation, in 67 vs 68 patients), prevents postoperative shivering (risk ratio, in 140 vs 140 patients: 0.17, 95%CI[0.10-0.29]; p<0.001). On the other hand, clonidine does not have any influence on renal and cardiac outcomes (adverse events rates, in 5873 vs 5533 patients: 0.00, 95%CI[-0.10-0.11]; p=0.96) and does not prolong awakening time. CONCLUSIONS In conclusion, these systematic review and meta-analyses of 57 trials confirm that clonidine improves pain control, reduces PONV, improves hemodynamic and sympathetic stability, with no adverse consequences on renal function or awakening time, but does not influence cardiac outcome in the general population, after non-cardiac surgery. Nevertheless, given the high heterogeneity between the studies, this does not exclude different results in patient subgroups or specific procedures.

In vivo optical spectroscopy monitoring in a new model of muscular compartment syndrome

BACKGROUND Muscular compartment syndrome (MCS) is a rare but serious postoperative complication. In vivo optical spectroscopy (INVOS) monitors continuously and non-invasively regional oxygen saturation (rSO(2)), and could predict the development of MCS. METHODS In 10 healthy volunteers, we inflated a tourniquet to the mean arterial pressure to produce slight venous congestion and arterial hypoperfusion. Comparisons were made between the relative reduction in rSO(2) with baseline (deltaINVOS) and the time to observe motor nerve block (with non-invasive electromyography). Neurological symptoms, pain, and invasive intracompartmental pressure (ICP) were assessed. RESULTS In the eight volunteers completing the protocol, we observed a profound motor nerve conduction block, immediately reversible. Baseline values were: [mean (sd)] INVOS: 73.3 (8.9)% and ICP: 16.9 (8.6) mm Hg. At the time of the block, values were: INVOS: 46.4 (10.9)%, deltaINVOS: 28.7 (10.6)%, and ICP: 70.0 (5.5) mm Hg. The time to reach the block was 33.0 (10.9) min, and to a deltaINVOS>10%: 27.4 (10.4) min. Receiver-operating characteristic curves demonstrated a similar accuracy of ICP and INVOS to predict the occurrence of the block. Twenty minutes with a deltaINVOS>10% or ICP>30 mm Hg were associated with a sensitivity and a specificity of 95% and 70%; or 91% and 65%, respectively. CONCLUSIONS We have developed a model of acute immediately reversible MCS. Monitoring using the INVOS technology is as accurate as measurement of ICP, and could be a useful tool to prevent development of intraoperative MCS.

Potential Benefit of Intra-operative Administration of Ketorolac on Breast Cancer Recurrence According to the Patient’s Body Mass Index

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently used in some countries as analgesics in primary cancer surgery. Retrospective studies suggest that NSAIDs could reduce breast cancer recurrences. Because NSAIDs also act on biological mechanisms present in patients with increased adiposity, we aimed at assessing whether the intra-operative administration of ketorolac or diclofenac would be associated with a reduction of recurrence in patients with elevated body mass index (BMI). Methods We considered two institutional retrospective series of 827 and 1007 patients evaluating the administration of ketorolac (n = 529 with, n = 298 without) or diclofenac (n = 787 with, n = 220 without). The BMI subgroups were defined as less than 25 kg/m2 (lean) and 25 or more kg/m2 (overweight and obese). Cumulative incidence estimation of distant metastases as well as Fine-Gray and Dixon-Simon models was used. These analyses were adjusted for clinico-pathological variables. All statistical tests were two-sided. Results The administration of ketorolac was statistically significantly associated with decreased incidence of distant recurrences (adjusted hazard ratio [aHR]= 0.59, 95% confidence interval [CI] = 0.37 to 0.96, P = .03). In particular, the association was evident in the high-body mass index (BMI) group of patients (aHR = 0.55, 95% CI = 0.31 to 0.96, P = .04). The administration of diclofenac was not statistically significantly associated with decreased incidence of distant recurrences, either in the global population or in the BMI subgroups. Conclusions These results show that the intra-operative administration of ketorolac, but not diclofenac, is statistically significantly associated with a reduction of distant recurrences in patients with increased BMI. Altogether, this study points to a potentially important repositioning of ketorolac in the intra-operative treatment of patients with elevated BMI that, if prospectively validated, might be as impactful as and cheaper than adjuvant systemic anticancer therapies.

Long Term Consequences of Acute Inflammation in Cancer Surgery

Perioperative inflammation assessment can be used to screen and stratify the perioperative status of the cancer patient. Biomarkers such as the neutrophil-to-lymphocyte ratio help clinicians and researchers develop and apply new screening and monitoring strategies. To control the perioperative inflammatory reaction, and to promote early resolution, pharmacological interventions such as NSAIDs are proposed as promising. One of their applications is the prevention of the early peak of recurrence, seen in the first few years after surgery. Additionally, to progress toward the development of new options a combined role of database analyses and incorporation of biomarkers is proposed.