Multidisciplinary management of locally advanced and metastatic cutaneous squamous cell carcinoma.

Non-melanoma skin cancers are the most prevalent form of cancer, with cutaneous squamous cell carcinoma (cscc) being the 2nd most common type. Patients presenting with high-risk lesions associated with locally advanced or metastatic cscc face high rates of recurrence and mortality. Accurate staging and risk stratification for patients can be challenging because no system is universally accepted, and no Canadian guidelines currently exist. Patients with advanced cscc are often deemed ineligible for either or both of curative surgery and radiation therapy (rt) and, until recently, were limited to off-label systemic cisplatin-fluorouracil or cetuximab therapy, which offers modest clinical benefits and potentially severe toxicity. A new systemic therapy, cemiplimab, has been approved for the treatment of locally advanced and metastatic cscc. In the present review, we provide recommendations for patient classification and staging based on current guidelines, direction for determining patient eligibility for surgery and rt, and an overview of the available systemic treatment options for advanced cscc and of the benefits of a multidisciplinary approach to patient management.

Five-year outcomes of the First Distal Uninstrumented Vertebra after posterior fusion for Adolescent Idiopathic Scoliosis Lenke 1 or 2.

BACKGROUND: Tilt of the First Distal Uninstrumented Vertebra (FDUV) reflects changes in the main curve and compensatory lumbar curve after posterior fusion to treat thoracic Adolescent Idiopathic Scoliosis (AIS). HYPOTHESIS: FDUV tilt 5 years or more post-fusion depends chiefly on reduction of the main curve and on other factors such as selection of the last instrumented vertebra. MATERIAL AND METHOD: A multicenter retrospective cohort of 182 patients with Lenke 1 or 2 AIS treated with posterior instrumentation and followed up for a mean of 8 years and a minimum of 5 years was studied. The patients were divided into two groups based on whether tilt of the upper endplate of the FDUV was ≤5° or >5°at last follow-up. Variables associated with tilt were identified by multiple logistic regression. RESULTS: Six variables were significantly associated with FDUVtilt: percentage of correction at last follow-up, correction loss, lumbar modifier B, number of instrumented vertebrae, inclusion within the instrumentation of the distal neutral vertebra, and inclusion within the instrumentation of the lowest vertebra intersected by the central sacral vertical line. DISCUSSION AND CONCLUSION: The main variables associated with FDUVtilt ≤5° were a final correction percentage ≥60% and absence of correction loss between the postoperative period and last follow-up. Given the stable reduction provided by contemporary instrumentations, we recommend selective thoracic fusion of Lenke 1 or 2 AIS with lumbar modifiers A, B, and C. The lowest instrumented vertebra should be either the neutral vertebra or the vertebra intersected by the central sacral vertical line if it is distal to the neutral vertebra. LEVEL OF EVIDENCE IV: Retrospective multicenter study.

Evolution and complications after surgery for spine deformation in patients with Parkinson's disease.

INTRODUCTION: Surgical treatment of spinal deformity is high risk in patients suffering from Parkinson's disease (PD). Several series have already reported a high rate of complications. However, none of these studies included more than 40 patients and none of the risk factors of complications were described. The aim of this study was to describe the rate and risk factors of revision surgery as well as the clinical outcome at the last visit in a large multicenter study of PD patients operated for spinal deformities. METHODS: A multicenter retrospective study included arthrodesis for spinal deformity in patients with PD. Clinical and surgical data including revision surgeries were collected. Assessment of functional outcomes at last follow-up was classified in 3 grades and spinal balance was assessed on anteroposterior and lateral plain X-rays of the entire spine. RESULTS: Forty-eight patients were included. Median age was 67 years old (range 41-80). Median follow-up was 27 months. The rate of surgical revision was 42%. Eighty per cent of revisions were performed for chronic mechanical complication. Global results were considered to be good in 17 patients (35%), doubtful in 17 patients (35%) and a failure in 14 patients (30%), for the whole series. CONCLUSIONS: The results of surgery for spinal deformities in patients with Parkinson disease vary with a high rate of complications and revisions. Nevertheless, these results should be seen in relation to the natural progression of these spinal deformities once spinal imbalance has developed. The association between preoperative clinical balance and final outcome suggests that early surgery can probably play a role in treatment. LEVEL OF EVIDENCE: Level IV (e.g. case series).

Reproducibility of clinical events adjudications in a trial of venous thromboembolism prevention.

Essentials The reproducibility of Clinical Events Committee (CEC) adjudications is almost unexplored. A random selection of events from a venous thromboembolism trial was blindly re-adjudicated. 'Unexplained sudden deaths' (possible fatal embolism) explained most discordant adjudications. A precise definition for CEC adjudication of this type of events is needed and proposed. SUMMARY: Background When clinical trials use clinical endpoints, establishing independent Clinical Events Committees (CECs) is recommended to homogenize the interpretation of investigators' data. However, the reproducibility of CEC adjudications is almost unexplored. Objectives To assess the reproducibility of CEC adjudications in a trial of venous thromboembolism (VTE) prevention. Methods The PREVENU trial, a multicenter trial of VTE prevention, included 15 351 hospitalized medical patients. The primary endpoint was the composite of symptomatic VTE, major bleeding or unexplained sudden death (interpreted as possible fatal pulmonary embolism [PE]) at 3 months. The CEC comprised a chairman and four pairs of adjudicators. Of 2970 adjudicated clinical events, a random selection of 179 events (121 deaths, 40 bleeding events, and 18 VTE events) was blindly resubmitted to the CEC. Kappa values and their 95% confidence intervals (CIs) were calculated to measure adjudication agreement. Results Overall, 18 of 179 (10.1%, 95% CI 6.5-15.3%) adjudications proved discordant. Agreement for the PREVENU composite primary endpoint was good (kappa = 0.73, 95% CI 0.61-0.85). When analyzed separately, agreements were very good for non-fatal VTE events (1, 95% CI not applicable), moderate for all (fatal and non-fatal) VTE events (0.58, 95% CI 0.34-0.82), good for fatal and non-fatal major bleeding events (0.71, 95% CI 0.55-0.88), and moderate for all fatal events (0.60, 95% CI 0.40-0.81). Unexplained sudden death interpreted as possible fatal PE was responsible for nine of 18 (50%) discordant adjudications. Conclusion The reproducibility of CEC adjudications was good or very good for non-fatal VTE and bleeding events, but insufficient for VTE-related deaths, for which more precise and widely accepted definitions are needed.

Hurdles and delays in access to anti-cancer drugs in Europe.

Demographic changes in the world population will cause a significant increase in the number of new cases of cancer. To handle this challenge, societies will need to adapt how they approach cancer prevention and treatment, with changes to the development and uptake of innovative anticancer drugs playing an important role. However, there are obstacles to implementing innovative drugs in clinical practice. Prior to being incorporated into daily practice, the drug must obtain regulatory and reimbursement approval, succeed in changing the prescription habits of physicians, and ultimately gain the compliance of individual patients. Developing an anticancer drug and bringing it into clinical practice is, therefore, a lengthy and complex process involving multiple partners in several areas. To optimize patient treatment and increase the likelihood of implementing health innovation, it is essential to have an overview of the full process. This review aims to describe the process and discuss the hurdles arising at each step.

Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Prevalence of CTEPH after pulmonary embolism.

Chronic thromboembolic pulmonary hypertension (CTEPH) has been estimated to occur in 0.1-0.5% of patients who survive a pulmonary embolism (PE), but more recent prospective studies suggest that its incidence may be much higher. The absence of initial haemodynamic evaluation at the time of PE should explain this discrepancy. We performed a prospective multicentre study including patients with PE in order to assess the prevalence and to describe risk factors of CTEPH. Follow-up every year included an evaluation of dyspnea and echocardiography using a predefined algorithm. In case of suspected CTEPH, the diagnosis was confirmed using right heart catheterisation (RHC). Signs of CTEPH were searched on the multidetector computed tomography (CT) and echocardiography performed at the time of PE. Of the 146 patients analysed, eight patients (5.4%) had suspected CTEPH during a median follow-up of 26 months. CTEPH was confirmed using RHC in seven cases (4.8%; 95%CI, 2.3 - 9.6) and ruled-out in one. Patients with CTEPH were older, had more frequently previous venous thromboembolic events and more proximal PE than those without CTEPH. At the time of PE diagnosis, patients with CTEPH had a higher systolic pulmonary artery pressure and at least two signs of CTEPH on the initial CT. After acute PE, the prevalence of CTEPH appears high. However, initial echocardiography and CT data at the time of the index PE suggest that a majority of patients with CTEPH had previously unknown pulmonary hypertension, indicating that a first clinical presentation of CTEPH may mimic acute PE.

Discrepancies in cancer incidence and mortality and its relationship to health expenditure in the 27 European Union member states.

BACKGROUND: The European Union (EU) is a confederation of 27 member states, the institutions of which work according to negotiated decisions. The EU has implemented similar legislation and a common market, and has adopted the same currency in most of its member states. Although financing health systems is a responsibility of the national governments, the EU has enacted the Charter of Fundamental Rights to standardize public health policies. However, for historical reasons, health policy and health expenditure is not uniform across the 27 EU member states (EU-27). MATERIAL AND METHODS: We hypothesized that increased health expenditure would be associated with better cancer outcome and that this would be most apparent in breast cancer, because of the availability of effective screening methods and treatments. Using publically available data from the World Health Organization, the International Monetary Fund, and the World Bank, we assessed associations between cancer indicators and wealth and health indicators. To do so, we constructed scatter plots and used the Spearman's rank correlation coefficient. RESULTS: A marked difference in wealth and health expenditure indicators was observed between Eastern and Western European countries, with Western European being the higher. Higher wealth and higher health expenditures were associated both with increased cancer incidence and decreased cancer mortality. In breast cancer, the association with incidence was stronger. We created mortality/incidence ratios and observed that the more spent on health, the fewer the deaths after a cancer diagnosis. CONCLUSION: Despite the initiatives to standardize public health policies of the EU-27, health expenditure continues to be higher in Western European countries and this is associated with better cancer outcome in these countries.

Endovenous laser ablation of great saphenous vein and perforator veins improves venous stasis ulcer healing.

BACKGROUND: We sought to compare the outcomes of endovenous laser ablation (EVLA) of the great saphenous vein (GSV) to EVLA of the GSV and calf incompetent perforator veins (IPVs) in management of venous stasis ulcers (VSUs). METHODS: A retrospective review of patients with active VSUs (clinical, etiology, anatomy, and pathophysiology [CEAP] classification C6) that received EVLA of the GSV or combined EVLA of the GSV and IPV between May 2005 and May 2010 was completed. Primary outcomes measured include ulcer healing and a change in the venous clinical severity score (VCSS). Secondary end points included complications, ulcer recurrence rate, and time to ulcer healing. RESULTS: Ninety-five patients (108 limbs) met inclusion criteria with active VSU (CEAP classification C6) before ablation. The average age was 58 years, with a male predominance (61%). Seventy-eight patients (91 limbs) were treated with EVLA of the GSV alone. Subgroup analysis revealed that 46 of 91 limbs (35 patients) had GSV reflux only (group 1) and 45 of 91 limbs (43 patients) had underlying IPV (group 2). Seventeen patients (17 limbs) underwent combined EVLA of the GSV and IPV (group 3). VSU healing (CEAP classification C5) occurred in 21 of 46 limbs (46%) in group 1, 15 of 45 limbs (33%) in group 2, and 12 of 17 limbs (71%) in group 3. A comparison of ulcer healing between groups 1 and 2 and between groups 1 and 3 revealed no significant difference (Fisher's exact test; P = 0.285 and P = 0.095, respectively). However, there was a significant difference in ulcer healing between groups 2 and 3 (P = 0.011). Group 1 ulcers healed in an average of 14.8 weeks, group 2 ulcers in 11.2 weeks, and group 3 in 13.2 weeks (analysis of variance; P = 0.918). Postoperative complications occurred in 7 limbs (15%) in group 1, 5 limbs (11%) in group 2, and 3 (18%) limbs in group 3. Recurrence of VSU occurred in 2 limbs (4%) in group 1, 5 limbs in group 2 (11%), and in no limbs in group 3 (Fisher's exact test; P = 0.676). Mean follow-up was 16.9 weeks for group 1, 19.2 weeks for group 2, and 14.0 weeks for group 3 (P = 0.69). CONCLUSIONS: Ulcer healing was accomplished to a significantly greater degree using EVLA of the GSV and IPV compared to GSV ablation alone for the treatment of active VSU in patients with combined reflux. This study suggests that limbs with VSU disease should be routinely examined for both superficial axial and perforator venous reflux and, when appropriate, combined ablation of the GSV and IPV should be considered in management of this disease.

The association between resting and mild-to-moderate exercise pulmonary artery pressure.

The mean pulmonary artery pressure (P(pa)) achieved on mild-to-moderate exercise is age related and its haemodynamic correlates remain to be documented in patients free of pulmonary hypertension (PH). Our retrospective study involved patients free of PH investigated in our centre for possible pulmonary vascular disease between January 1, 2007 and October 31, 2009 who underwent right heart catheterisation at rest and during supine exercise up to 60 W. The 38 out of 99 patients aged <50 yrs were included and a P(pa) of 30 mmHg was considered the upper limit of normal on exercise. The 24 subjects who developed P(pa)>30 mmHg on exercise had higher resting P(pa) (19±3 versus 15±4 mmHg) and indexed pulmonary vascular resistance (PVRi; 3.4±1.5 versus 2.2±1.1 WU·m(2); p<0.05) than the remaining 14 subjects. Resting P(pa) >15 mmHg predicted exercise P(pa) >30 mmHg with 88% sensitivity and 57% specificity. The eight patients with resting P(pa) 22-24 mmHg all had exercise P(pa) >30 mmHg. In subjects aged <50 yrs investigated for possible pulmonary vascular disease and free of PH, patients with mild-to-moderate exercise P(pa) >30 mmHg had higher resting PVRi and higher resting P(pa), although there was no resting P(pa) threshold value that could predict normal response on mild-to-moderate exercise. The clinical relevance of such findings deserves further long-term follow-up studies.

[Pulmonary complications in adult sickle cell disease]. / Complications pulmonaires des syndromes drépanocytaires majeurs chez l'adulte.

Sickle cell disease is an autosomal genetic condition which represents the most frequent genetic disease in Île-de-France and Caribbean islands. The main clinical manifestations can be divided into infectious disease, hemolytic anemia and vaso-occlusive events. Pulmonary complications represent 20 to 30% of mortality due to sickle cell and can be divided into acute and chronic events. Acute chest syndrome (ACS) is an acute lung injury often preceded by a vaso-occlusive crisis and triggered by different factors including: hypoventilation, pulmonary infectious disease and vascular occlusions. These occlusions can be secondary to fat embolism, thrombosis or sickling. Treatment is mainly supportive combining oxygen supplementation adequate hydration analgesia and sedation. Exchange transfusion may be indicated in severe forms of ACS, characterized by a right ventricular dysfunction and acute respiratory failure. Pulmonary hypertension is the most serious chronic complication. Its frequency is estimated at 6% in adult patients and is more often described in patients with venous ulcers and higher levels of chronic hemolysis. Prognosis is poor with 12.5% of patients dying in the first two years following diagnosis irrespective of the actual pulmonary artery pressure level. There are currently limited data on the effects of any treatment modality. Other respiratory complications such as sleep disorders and nocturnal hypoxemia, infiltrative lung disease and exertional dyspnea are described and should be considered.

Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. We studied 674 consecutive adult patients who were prospectively enrolled in the French PAH registry (121 incident and 553 prevalent cases). Two survival analyses were performed. First, the cohort of 674 patients was followed for 3 yrs after study entry and survival rates described. Then, we focused on the subset with incident idiopathic, familial and anorexigen-associated PAH (n = 56) combined with prevalent patients who were diagnosed <3 yrs prior to study entry (n = 134). In the cohort of 674 patients, 1-, 2-, and 3-yr survival rates were 87% (95% CI 84-90), 76% (95% CI 73-80), and 67% (95% CI 63-71), respectively. In prevalent idiopathic, familial and anorexigen-associated PAH, 1-, 2-, and 3-yr survival rates were higher than in incident patients (p = 0.037). In the combined cohort of patients with idiopathic, familial and anorexigen-associated PAH, multivariable analysis showed that survival could be estimated by means of a novel risk-prediction equation using patient sex, 6-min walk distance, and cardiac output at diagnosis. This study highlights survivor bias in prevalent cohorts of PAH patients. Survival of idiopathic, familial and anorexigen-associated PAH can be characterised by means of a novel risk-prediction equation using patients' characteristics at diagnosis.