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Objectives: The primary aim of this study was to develop and validate radiomics models, applied to ultrasound images, capable of differentiating from other cancers high-risk endometrial cancer, as defined jointly by the European Society for Medical Oncology, European Society of Gynaecological Oncology and European Society for Radiotherapy & Oncology (ESMO-ESGO-ESTRO) in 2016. The secondary aim was to develop and validate radiomics models for differentiating low-risk endometrial cancer from other endometrial cancers.Methods: This was a multicenter, retrospective, observational study. From two participating centers, we identified consecutive patients with histologically confirmed diagnosis of endometrial cancer who had undergone preoperative ultrasound examination by an experienced examiner between 2016 and 2019. Patients recruited in Center 1 (Rome) were included as the training set and patients enrolled in Center 2 (Milan) formed the external validation set. Radiomics analysis (extraction of a high number of quantitative features from medical images) was applied to the ultrasound images. Clinical (including preoperative biopsy), ultrasound and radiomics features that were statistically significantly different in the high-risk group vs the other groups and in the low-risk group vs the other groups on univariate analysis in the training set were considered for multivariate analysis and for developing ultrasound-based machine-learning risk-prediction models. For discriminating between the high-risk group and the other groups, a random forest model from the radiomics features (radiomics model), a binary logistic regression model from clinical and ultrasound features (clinical-ultrasound model) and another binary logistic regression model from clinical, ultrasound and previously selected radiomics features (mixed model) were created. Similar models were created for discriminating between the low-risk group and the other groups. The models developed in the training set were tested in the validation set. The performance of the models in discriminating between the high-risk group and the other groups, and between the low-risk group and the other risk groups for both validation and training sets was compared.Results: The training set comprised 396 patients and the validation set 102 patients. In the validation set, for predicting high-risk endometrial cancer, the radiomics model had an area under the receiver-operating-characteristics curve (AUC) of 0.80, sensitivity of 58.7% and specificity of 85.7% (using the optimal risk cut-off of 0.41); the clinical-ultrasound model had an AUC of 0.90, sensitivity of 80.4% and specificity of 83.9% (using the optimal cut-off of 0.32); and the mixed model had an AUC of 0.88, sensitivity of 67.3% and specificity of 91.0% (using the optimal cut-off of 0.42). For the prediction of low-risk endometrial cancer, the radiomics model had an AUC of 0.71, sensitivity of 65.0% and specificity of 64.5% (using the optimal cut-off of 0.38); the clinical-ultrasound model had an AUC of 0.85, sensitivity of 70.0% and specificity of 80.6% (using the optimal cut-off of 0.46); and the mixed model had an AUC of 0.85, sensitivity of 87.5% and specificity of 72.5% (using the optimal cut-off of 0.36).Conclusions: Radiomics seems to have some ability to discriminate between low-risk endometrial cancer and other endometrial cancers and better ability to discriminate between high-risk endometrial cancer and other endometrial cancers. However, the addition of radiomics features to the clinical-ultrasound models did not result in any notable increase in performance. Other efficacy studies and further effectiveness studies are needed to validate the performance of the models. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: The aim of our systematic review was to assess the role of interventional radiotherapy (IRT, brachytherapy) in the management of primary and/or recurrent vulvar carcinoma. Evidence acquisition: A systematic research using PubMed, Scopus and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Only full-text English-language articles related to IRT for treatment of primary or recurrent VC were identified and reviewed. Conference paper, survey, letter, editorial, book chapter and review were excluded. Time restriction (1990–2018) as concerns the years of the publication was considered. Evidence synthesis: Primary disease: the median 5-year LC was 43.5% (range 19–68%); the median 5-year DFS was 44.5% (range 44–81%); the median 5-year OS was 50.5% (range 27–85%). Recurrent disease: the median 5-year DFS was 64% (range 56–72%) and the median 5-year OS was 45% (range 33%-57%). Acute ≥ grade 2 toxicity was reported in three patients (1.6%). The severe late toxicity rates (grade 3–4) ranged from 0% to 14.3% (median 7.7%). Conclusion: IRT as part of primary treatment for primary and/or recurrent vulvar cancer is associated with promising clinical outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: From a clinical point of view, Kimura's disease is typically characterized by a subcutaneous mass occurring predominantly in the head and neck region. It occurs predominantly in young men of Asian descent, with a peak incidence in the second and third decades of life. However, KD has been also reported in other ethnic groups and in children. The most frequently used local treatments are surgical excision, radiotherapy, and surgical excision followed by radiotherapy. The aim of this multicenter systematic review is to highlight the available literature evidence about the outcome of RT in this setting. MATERIALS AND METHODS: A systematic review of any relevant literature in the principal medical databases, such as PubMed, Scopus and Cochrane library, was conducted. The inclusion criteria were original articles specifically reporting about KD and RT, including both prospective and retrospective studies. RESULTS: We were able to identify 11 studies, published from 1989 to 2021, eligible for inclusion in this review. Overall, data on 124 patients were recorded and are presented in this systematic review. The median recurrence rate, considering all patients, was 11% (ranging from 0% to 41.2%). In seven out of 11 studies, the relapse rate was less than 20%. Moreover, the relapse rate was 0% in four studies. CONCLUSIONS: The results of this multicenter systematic literature review show that evidence on RT of KD is limited and derives only from retrospective studies. In this setting RT seems to be well-tolerated and able to produce very high response rates in unresected lesions and reasonable results in terms of local control both as an exclusive and adjuvant treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this paper is to provide an update about the current clinical indications of RT in this poorly explored field outside the traditional oncological setting. MATERIALS AND METHODS: We performed a literature search on the main databases, including PubMed, Scopus and Cochrane from their inception until 31st December 2020. An additional manual check of scientific meeting proceedings and books was conducted in order to identify all the potentially useful sources. Only essays published in English have been considered for the purposes of this analysis. The searched items included: "Radiotherapy or Radiation Therapy" and "Benign disorder or Benign disease". RESULTS: We provided a list of current clinical indications for benign disorders based on the latest international surveys available, including major sites: eye, bone, head and neck, skin, brain, heart and peripheral vascular system. CONCLUSIONS: Radiotherapy for benign diseases is still a feasible therapeutic strategy, which may allow to treat several invalidating conditions, especially after medical therapies have failed thus avoiding potentially invalidating major surgical procedures. A careful evaluation in selecting the indication is essential and all the choices should be thoroughly discussed with the patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This review aimed at examining efficacy of interventional radiotherapy (brachytherapy-IRT) alone or combined with external beam radiotherapy (EBRT) in stage I esophageal cancer as exclusive treatment. MATERIALS AND METHODS: A systematic research using PubMed, Scopus, and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. We analyzed only clinical study as full-text publication, reporting on patients with stage I esophageal cancer treated with IRT alone or in combination with other treatments (e.g., EBRT). Conference paper, survey, letter, editorial, book chapter, and review were excluded. Patients who underwent previous surgery were excluded. Time restriction (1990-2018) was applied for years of the publication. RESULTS: Twelve studies have been selected. The number of evaluated patients was 514; the median age was 69 years. In the IRT group, the median: local control (LC) was 77% (range 63%- 100%), disease-free survival (DFS) was 68.4% (range 49%-86.3%), the overall survival (OS) was 60% (range 31%-84%), the cancer specific survival (CSS) was 80% (range 55-100%), and grade 3-4 toxicity range was 0%-26%. CONCLUSIONS: IRT alone or combined to EBRT is an effective and safe treatment option for patients with stage I esophageal cancer. Definitive radiation therapy could be an alternative to surgery in patients with superficial cancer. [ABSTRACT FROM AUTHOR]

Objective: Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC), but ultrasound variables used to predict partial response to neoadjuvant treatment are not well defined. Our goal was to analyze prospectively the potential role of transvaginal ultrasound in early prediction of partial pathological response, assessed in terms of residual disease at histology, in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery.Methods: Between October 2010 and June 2014, we screened 108 women with histologically documented LACC Stage IB2-IVA, of whom 88 were included in the final analysis. Tumor volume, three-dimensional (3D) power Doppler indices and contrast parameters were obtained before (baseline examination) and after 2 weeks of treatment. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (microscopic and/or macroscopic residual tumor at pathological examination). Complete-response and partial-response groups were compared and receiver-operating characteristics (ROC) curves were generated for ultrasound variables that were statistically significant on univariate analysis to evaluate their diagnostic ability to predict partial pathological response.Results: There was a complete pathological response to neoadjuvant therapy in 40 (45.5%) patients and a partial response in 48 (54.5%). At baseline examination, tumor volume did not differ between the two groups. However, after 2 weeks of neoadjuvant treatment, the tumor volume was significantly greater in patients with partial response than it was in those with complete response (P = 0.019). Among the 3D vascular indices, the vascularization index (VI) was significantly lower in the partial-response compared with the complete-response group, both before and after 2 weeks of treatment (P = 0.037 and P = 0.024, respectively). At baseline examination in the contrast analysis, women with partial response had lower tumor peak enhancement (PE) as well as lower tumor wash-in rate (WiR) and longer tumor rise time (RT) compared with complete responders (P = 0.006, P = 0.003, P = 0.038, respectively). There was no difference in terms of contrast parameters after 2 weeks of treatment. ROC-curve analysis of baseline parameters showed that the best cut-offs for predicting partial pathological response were 41.5% for VI (sensitivity, 63.6%; specificity, 66.7%); 16123.5 auxiliary units for tumor PE (sensitivity, 47.9%; specificity, 84.2%); 7.8 s for tumor RT (sensitivity, 68.8%; specificity, 57.9%); and 4902 for tumor WiR (sensitivity, 77.1%; specificity, 60.5%). ROC curves of parameters after 2 weeks of treatment showed that the best cut-off for predicting partial pathological response was 18.1 cm3 for tumor volume (sensitivity, 70.8%; specificity 60.0%) and 39.5% for VI (sensitivity; 62.5%; specificity, 73.5%).Conclusions: Ultrasound and contrast parameters differ between LACC patients with complete response and those with partial response before and after 2 weeks of neoadjuvant treatment. However, neither ultrasound parameters before treatment nor those after 2 weeks of treatment had cut-off values with acceptable sensitivity and specificity for predicting partial pathological response to neoadjuvant therapy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Due to aging and resources limitation, septic patients are often admitted to medical wards (MWs). Early warning deterioration is a relevant issue in this setting. Unfortunately, a suitable prognostic score has not been identified, yet. Aim: To explore the ability of Modified Early Warning Score (MEWS) to predict the in-hospital mortality in septic patients admitted to MWs. Design: Secondary analysis of a multicentric prospective study. Methods: Consecutive septic patients with positive blood culture admitted to 31 Italian MWs were included. Baseline characteristics, clinics, isolates, rate of transfer to ICU, MEWS was collected on admission according to the study protocol. The accuracy of MEWS in predicting the in-hospital mortality was assessed with the area under the receiver-operating characteristic curves. Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratio (LR) were calculated for different MEWS cut-offs and age/comorbidities subgroups. Results: In total 526 patients were included in this analysis. Median MEWS was (range 0-11). In-hospitalmortality was 14.8% and transfer to ICU 1.3%. Mortality progressively increased according to MEWS (3% in MEWS 0 vs. 27% in MEWS >5; Chi square for trend P < 0.05). The AUC of MEWS in predicting in-hospitalmortality was 0.596 (95% CI, 0.524, 0.669). MEWS did not appear to have an adequate sensitivity, sensibility, PPV, NPV and LR both in the whole population and in the pre-specified subgroups. Conclusions: Our findings do not seemto support the use of MEWS to predict the in-hospitalmortality risk of sepsis in MWs. [ABSTRACT FROM AUTHOR]

The effect of intramuscular injections of vitamin E on growth, carcass traits, intramuscular collagen (IMC) characteristics and decorin of growing lambs was studied. A total of 24 15-day-old Ile de France suckling male lambs were divided into two groups and weekly intramuscular injections of DL-α-tocopheryl acetate (control group, 0 IU; Vitamin E treatment, 150 IU) were given until the lambs were 64 days old. Lambs were individually weighted at 15, 29, 43, 57 days of age and at slaughter (71 days old). Dry matter intake and average daily weight gain were recorded. Hot and cold carcass weights were recorded and dressing percentages were calculated after dressing and chilling (2°C to 4°C for 24 h). Carcass shrink losses were calculated as well. Longissimus muscle (LM) pH and area were measured. The pelvic limb was removed and its percentage was calculated based on cold carcass weight. IMC and decorin analyses were assessed on LM and semimembranosus muscle (SM). DL-α-tocopheryl acetate treatment reduced (P <0.05) collagen maturity and increased (P <0.05) decorin in both LM and SM muscles of growing lambs, while it did not affect IMC content. In addition, vitamin E did not influence growth, carcass weight, dressing percentage, carcass shrink losses and area of LM but decreased (P <0.05) the pelvic limb percentage. The LM pH values were higher (P <0.05) in vitamin group than in control group. Furthermore, different IMC characteristics between the muscles (P <0.01) were apparent. Multiple intramuscular injections of DL-α-tocopheryl acetate influence extracellular matrix in lambs, which could affect meat tenderness. [ABSTRACT FROM AUTHOR]

Background: Evaluated in this study were the feasibility and the efficacy of concurrent low dose fractionated radiotherapy (LD-FRT) and chemotherapy as palliative treatment for recurrent/progressive glioblastoma multiforme (GBM).Patients and Methods: Eligible patients had recurrent or progressive GBM, Karnofsky performance status ≥ 70, prior surgery, and standard radiochemotherapy treatment. Recurrence/progression disease during temozolomide (TMZ) received cisplatin (CDDP; 30 mg/m(2) on days 1, 8, 15), fotemustine (FTM; 40 mg/m(2) on days 2, 9, 16), and concurrent LD-FRT (0.3 Gy twice daily); recurrence/progression after 4 months from the end of adjuvant TMZ were treated by TMZ (150/200 mg/m(2) on days 1-5) concomitant with LD-FRT (0.4 Gy twice daily). Primary endpoints were safety and toxicity.Results: A total of 32 patients were enrolled. Hematologic toxicity G1-2 was observed in 18.7 % of patients and G3-4 in 9.4 %. One patient (3.1 %) had complete response, 3 (9.4 %) had partial response, 8 (25 %) had stable disease for at least 8 weeks, while 20 patients (62.5 %) experienced progressive disease. The clinical benefit was 37.5 %. Median progression-free survival (PFS) and overall survival (OS) were 5 and 8 months, respectively. Survival rate at 12 months was of 27.8 %.Conclusion: LD-FRT and chemotherapy for recurrent/progressive GBM have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted. [ABSTRACT FROM AUTHOR]

Copyright of Acta Chirurgica Iugoslavica is the property of Association of Yugoslav Surgeons and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the last two decades we have seen major advances in the strategy of the treatment of rectal cancer. Important studies were published to confirm the role of imaging MRI in the treatment plan and in detecting the prognostic factors, the improved outcome of the new surgical technique based on total mesorectal excision and the combined treatments. Many studies demonstrated that MRI is equivalent to histology in measurement of extramural depth, is also highly accurate in staging advanced rectal cancer, in the assessment of mesorectal fascia infiltration and to distinguish cT3 from cT4, in the measuring the distance from the anorectal ring. With the introduction of total mesorectal excision the local recurrence rate is dramatically reduced, especially in selected centres. Preoperative radiotherapy ± in combination with chemotherapy still reduces this rates respect to only surgery or postoperative treatment. In this time of changing therapeutic approaches, a common standard for large heterogeneous patient groups will likely be substituted by more individualised therapies. It will depend from new evidence of more tailored diagnosis, surgery, radiotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Copyright of Acta Chirurgica Iugoslavica is the property of Association of Yugoslav Surgeons and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Results For discriminating high risk category vs the other categories one random forest model from the radiomics features (radiomics model), and two logistic regression models from clinical and ultrasound features (clinical-ultrasound model), and from clinical, ultrasound and radiomics features (mixed model) were created. Aim of this study was to develop and validate ultrasound-based radiomics models, aiming to differentiating high risk category, as defined by ESMO-ESGO-ESTRO in 2016, vs the remaining categories of risk. OC10.01: *Developing and validating ultrasound-based radiomics models for predicting high-risk category in endometrial cancer patients. [Extracted from the article]

Two cases of chronic encapsulated intracerebral haematoma are reported. The patients presented with progressive neurological deficits. Computed tomography scan showed a roundish, intracerebral lesion, that revealed ring blush after contrast infusion, with mass effect. At operation a thick, fibrous, brownish capsule, containing clots in different states of formation, was removed. The hypothesis of capsule formation due to an exuberant proliferation of arachnoidal fibroblasts, is discussed. Differentiation between encapsulated intracerebral haematoma and other chronic intracerebral blood collections is considered mandatory for appropriate treatment. [ABSTRACT FROM AUTHOR]

Immunohistochemical staining with anti-bromo-deoxyuridine (BrdU) monoclonal antibody was performed on a variety of human tissues following in vitro incubation with BrdU. The effect of different fixatives and DNA denaturation techniques on the reactivity with anti-BrdU was investigated. Optimal preservation of the antigenicity of BrdU incorporated into the DNA of proliferating cells was seen in tissues fixed in Bouin's fluid, while samples which had been fixed with cross-linking reagents, such as formalin, were usually unreactive. Positivity for BrdU was restored in formalin fixed tissues after digestion with pepsin, but this was usually associated with loss of morphological details. Acid and thermal DNA denaturation techniques gave similar results. It is concluded that Bouin fixation followed by acid or thermal denaturation of DNA is the method of choice for the in situ detection of cells in S-phase using anti-BrdU monoclonal antibody. [ABSTRACT FROM PUBLISHER]

Purpose: The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence. However, a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis. In these patients, local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity. The aim of this multicenter phase II study is to evaluate the response rate, resectability rate, local control, and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis. Methods and Materials: Patients with histologically proven pelvic recurrence of rectal carcinoma, with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses ≤55 Gy; age ≥18 years; performance status (PS) (Karnofsky) ≥60, and who gave institutional review board–approved written informed consent were treated by preoperative chemoradiation. Radiotherapy was delivered to a planning target volume (PTV2) including the gross tumor volume (GTV) plus a 4-cm margin, with a dose of 30 Gy (1.2 Gy twice daily with a minimum 6-h interval). A boost was delivered, with the same fractionation schedule, to a PTV1 including the GTV plus a 2-cm margin (10.8 Gy). During the radiation treatment, concurrent chemotherapy was delivered (5-fluorouracil, protracted intravenous infusion, 225 mg/m2/day, 7 days per week). Four to 6 weeks after the end of chemoradiation, patients were evaluated for tumor resectability, and, when feasible, surgical resection of recurrence was performed between 6–8 weeks from the end of chemoradiation... [Copyright &y& Elsevier]

To assess the effects of dietary conjugated linoleic acids (CLA) on meat composition and intramuscular collagen (IMC), 144 New Zealand White rabbits, half males half females, 55 days old (1.8 kg LW), were assigned to three weight- and sex- balanced groups and given the following dietary supplements: 0.5% sunflower oil, (C); 0.25% sunflower oil plus 0.25% CLA (T1); and 0.5% CLA (T2). The CLA was prepared from sunflower oil and contained 65% CLA isomers, half cis-9, trans-11 and half trans-10, cis-12. Six males and six females from each group (total 36) were slaughtered at 76, 90 and 104 days of age (corresponding to 2.5, 2.8, and 3.1 kg BW, respectively). The lean fraction was higher and the water content significantly higher in the meat of T2 compared to C and T1 for all ages combined. At the third slaughtering (104 days) the meat fat content was significantly lower in group T2. For all ages combined, IMC content, IMC hydroxylysylpyridinoline (HLP) concentration (index of collagen cross-linking) and IMC maturity (HLP/IMC) were significantly lower in the intermediate supplementation group (T1) compared to C and T2, and were also lower in animals slaughtered at 90 days. CLA supplementation has limited effects on the chemical composition of rabbit meat, with positive effects on meat texture and tenderness after supplementation up to 35 days at 0.25%, and a significant decrease in fat content only at high slaughter weight and high supplementation level (0.5%). [Copyright &y& Elsevier]

Abstract: In Italy, like everywhere in the world, the organ shortage for transplantation is a real problem. It is well known that lung donors (LD) are particularly difficult to procure and that management of the organ do not care during the diagnosis of cerebral death represents a difficult challenge. In this context, the salvage of the so-called “marginal donors” may increase the pool of donors, favoring organ retrieval. To increase lung procurement, the intensivist must recognize “marginal donors,” optimizing organ selection and function. The aim of our study was to review LD procured in 2008, as identified by the unrestricted criteria, of the Nord Italian Transplant program Center (NITp). Particularly, the age and habits of donors and the presence of a parenchyma contusion were not sufficient per se to exclude donation. We revisited lung ventilation and monitoring modalities during cerebral death before retrieval. In 2008, the application of enlarged criteria for LD enabled us to collect 21 LD, namely 33% of all cerebral deaths, versus 13% in 2007. Seeking to maintain good gas exchange and lung function, we implemented a safe ventilation program avoided high peak pressures, and fluid therapy properly guided by the cardiac index and extravascular lung water index monitoring. Specific actions to improve LD procurement may help cope with the organ-donor shortage. Although our series was small, our results were encouraging; they underline the necessity to continuously review donor criteria and care, allowing good donor/recipient matching. [Copyright &y& Elsevier]

Abstract: The effects of lycopene-enriched extenders on motility, viability, osmotic resistance, DNA integrity and lipid peroxidation of rabbit sperm were examined after both chilled and frozen storage. Five pools of semen diluted in extenders containing 0, 0.05 or 0.1mg/mL of lycopene were refrigerated at 5°C for 48h or cryopreserved. Sperm quality was generally compromised after storage, especially post-freezing, however lycopene limited the amount of sperm lipid peroxidation after chilling and freezing. In chilled sperm, the highest dose of lycopene was provided to maintain the viability, acrosome and DNA intactness similar to that of fresh semen and contained the reduction of sperm motility, whereas in cryopreserved semen lycopene protected the DNA integrity of sperm, even if not in a dose-dependent way. So lycopene diminished sperm lipid peroxidation during refrigeration and cryopreservation, prolonging the survival of rabbit sperm after liquid storage, but it had a limited effect on sperm cryosurvival. [Copyright &y& Elsevier]

Abstract: The effect of different dietary energy levels, with or without injections of vitamin E, on growth, carcass traits and intramuscular collagen (IMC) characteristics of growing lambs was studied. Twenty-four Ile de France ram lambs were evaluated in a 2×2 factorial design involving different DL-α-tocopheryl acetate injections (C, control=0 and V=150IU/wk, i.m. for eight wk) and energy level (N, normal=7.61 and L, low=6.47MJ/kg DM). Growth and slaughter performance, and IMC characteristics were not influenced by diet. DL-α-tocopheryl acetate increased ADG during suckling, while it did not affect live weight, carcass weight and dressing percentage. Vitamin E injections reduced carcass shrinkage but also had a negative effect on pelvic limb percentage. The Longissimus muscle pH values were higher in V than in C lambs. DL-α-tocopheryl acetate reduced IMC maturity and muscle hydroxylysylpyridinoline crosslink concentration, more markedly in lambs fed low energy diets. [Copyright &y& Elsevier]

Background: The antiepidermal growth factor receptor (antiEGFR) monoclonal antibodies cetuximab and panitumumab have good clinical activity in about 10% of patients with metastatic colorectal cancer that is resistant to chemotherapy. The molecular mechanisms underlying clinical response or resistance to these agents are unknown.Methods: Tumours from 31 patients with metastatic colorectal cancer who had either an objective response (n=10) or stable disease or progressive disease (n=21) after treatment with cetuximab or panitumumab were screened for genetic changes in EGFR or its immediate intracellular effectors. Specifically, we assessed the EGFR copy number and the mutation profile of the EGFR catalytic domain and of selected exons in KRAS, BRAF, and PIK3CA.Results: Eight of nine of patients with objective responses who were assessable by fluorescence in-situ hybridisation (FISH) had an increased EGFR copy number. By contrast, one of 21 non-responders assessable by FISH had an increased EGFR copy number (p<0.0001 for responders vs non-responders, Fisher's exact test). The mutation status of the EGFR catalytic domain and its immediate downstream effectors PIK3CA, KRAS, and BRAF did not correlate with disease response. In colorectal-cancer cell lines, the concentration of cetuximab that completely inhibited proliferation of cells with amplified EGFR copy number did not affect proliferation of cells with unamplified EGFR.Interpretation: We propose that the response to antiEGFR treatment has a genetic basis and suggest that patients might be selected for treatment on the basis of EGFR copy number. [ABSTRACT FROM AUTHOR]