Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Use of carcass weight to classify Manchego sucking lambs and its relation to carcass and meat quality

Eighty-seven Manchego sucking lambs raised exclusively on maternal milk were slaughtered. The carcasses were weighed immediately after dressing and classified according to hot carcass weight (HCW) low HCW (<5.5 kg), medium HCW (5.5 to 6.5 kg) and high HCW (≥ 6.5 kg). The effects of this classification system on carcass and meat quality were studied. Carcass conformation improved as carcass weight increased; carcasses became more compact. Carcass fatness increased (P<0.001) as carcasses became heavier. With regard to the joints, leg (P<0.001) and shoulder (P<0.05) proportions decreased as carcass weight increased, whereas loin-rib (P<0.001) and flank (P<0.001) proportions increased. The proportion of fat in the leg clearly increased in the heavier carcasses (P<0.001), while that of bone decreased (P<0.001) and that of muscle was not affected. pH at 24 h in the m. longissimus dorsi and m. semitendinosus decreased as carcass weight increased. The only meat colour parameter affected by carcass weight was the yellowness index; lighter-weight carcasses displayed lower index (P<0.05). Cooking losses were unaffected as carcass weight increased, whereas with regard to tenderness, the shear force value tended to be higher in the low carcass weight group. No differences between carcass weight groups were found in the sensory analysis. Fatty acid composition did not show any significant effect due to carcass weight except in stearic fatty acid (C180); C180 proportion decreased (P<0.01) as carcasses became heavier. Carcass weight affected carcass quality (all carcass quality parameters studied were higher in the heavier carcasses), whereas meat quality varied little as a result the small variation between carcass weights in sucking lambs

Live weight effect on the prediction of tissue composition in suckling lamb carcasses using the European Union scale

Forty-eight Manchega breed suckling lambs were slaughtered at 10, 12 and 14 kg live weight. Carcass degree of fatness was assessed by three assessors on carcass colour photographs, using the European Union scale for light lambs (EU) subdivided into 0.25-point intervals. Left half-carcasses were jointed and dissected into lean, fat and bone. Muscle percentage, bone percentage and whole fat percentage (obtained by addition of every fat depot subcutaneous fat, intermuscular fat, inguinal fat and kidney knob and channel fat) were determined. Ten kilograms group showed a higher number of variates significantly correlated to assessors' fatness scoring than 12 and 14 kg groups; no statistically significant regression was seen in 14 kg group. Results suggest that, as live weight increases, the utility of this method to predict carcass and joints tissue composition in suckling lamb carcasses decreases. EU scale associated with weight variates can really improve prediction of carcass composition. It would be interesting to extend this study in order to determine a similar effect on the prediction of heavier groups of carcasses. © 2005 Elsevier B.V. All rights reserved

Body composition in relation to slaughter weight and gender in suckling lambs

Body composition was evaluated in 49 males and females suckling lambs of the Manchego breed slaughtered at 10, 12 and 14 kg. Lambs slaughtered at 14 kg had a greater proportion of loin-rib than those slaughtered at 10 kg. Male lambs exhibited a larger forequarter (neck, anterior rib and shoulder) while females had larger loin-rib. Slaughter weight affected the distribution of fat, and proportion of fat in loin-rib increased with slaughter weight. Males at 10 kg had more muscle in shoulder and neck than females. Significant slaughter weight × gender interaction was observed for total fat proportion in leg, loin-rib, anterior rib and flank. These proportions increased with slaughter weight in male lambs while in female lambs remained constant. The carcass composition of the suckling lamb showed significant correlations with muscle, fat and bone of the individual cuts, mainly leg and loin-rib. As expected, the proportion of muscle in the carcass was highly correlated with muscle in loin-rib, leg and shoulder. In conclusion, carcass composition may be predicted from the composition of leg and loin-rib. © 2005 Elsevier B.V. All rights reserved

Use of concentrate or pasture for fattening lambs and its effect on carcass and meat quality

Two production systems, pasture and sheepfold based on lambs fed concentrates ad libitum was evaluated for carcass and meat quality of lambs slaughtered at body weights of 24 and 28 kg. There was no effect of production system on growth rate of lambs. In sheepfold, commercial carcass dressing values of slaughter lambs were heavier than in those raised at pasture with more dorsal fat thickness (1.6 mm vs. 1.1 mm), kidney knob and channel fat (1.6% vs. 1.2%) and a greater percentage of leg fat (8.5% vs. 6.6%). Lambs at heavier weights had more fat. Meat quality, pH, water-holding capacity and collagen content parameters were not affected by the production systems. The color of the longissimus dorsi muscle was somewhat darker in lambs fattened at pasture, but no color differences were seen in the rectus abdominis muscle. In both subcutaneous and intramuscular fat of the two cuts studied (leg and loin), sheepfold lambs presented a lower percentage of stearic acid (C180) and a higher proportion of palmitic (C160) and linoleic (C182) acids, and thus a lower percentage of SFA and a higher one of TUFA, while a better (n - 6)/(n - 3) ratio was observed in lambs raised at pasture. Lambs at heavier weights displayed a lower percentage of PUFA and PUFA/SFA ratio in the intramuscular fat of the longissimus dorsi muscle and higher levels of oleic (C181) and palmitic (C160) fatty acids and a lower one of myristic acid (C140) in both depots. © 2002 Elsevier Science B.V. All rights reserved

Carcass and meat quality of light lambs using principal component analysis

Eighty-six male light lambs of Manchego breed were used in this study. Principal component (PC) analysis was performed to study the relationship between carcass quality variables (n=22) and between meat quality measures (n=21). The carcass quality was assessed using objective and subjective measurements of conformation and fatness besides the joints proportion and tissues proportion of the leg. The measurements used to evaluate meat quality were pH in longissimus dorsi and semitendinosus muscles, the colour, moisture, water holding capacity, cooking losses, texture and sensorial analysis on longissimus dorsi. The five first PCs explained about 77% of the total variability for carcass measures whereas for meat quality the 74% of the total variability was explained for the eight first PCs. All the carcass measurements showed similar weight to define the first PC, whereas the muscle and bone proportion as well as musclebone ratio of the leg were useful to define the second PC. The meat quality measures that were more effective to define the first PC were the meat colour measurements, whereas the sensorial variables defined the second PC. The projection of the carcass quality data in the first two PCs allowed to distinguish clearly between heavier carcasses (higher than 6.5 kg) and lighter carcasses (lower than 5.5 kg). The carcasses with a weight higher than 6.5 kg were on the left side of the figure, where the variables of conformation and fatness lie. The group of medium carcass weight were placed between the two previous groups. The projection of the meat quality data in the first two PCs did not differ between hot carcass weights, although there was a trend, the lighter carcasses lay on the left side of the graph, which implies small differences between meat quality in this range of carcass weight. © 2004 Elsevier Ltd. All rights reserved