Stereotactic Magnetic Resonance-Guided Daily Adaptive SABR (SMART) for Localised Non-Metastatic Pancreatic Cancer: First Reported Clinical Outcomes From the UK.

AIMS: Prognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the disease's proximity to radiosensitive organs at risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has demonstrated promise in delivering ablative doses safely. We sought to report clinical outcomes from a UK-based Compassionate Access Programme that provided access to SMART to patients with LAPC. MATERIALS AND METHODS: This was a registry retrospective study conducted at a single centre with access to SMART. Patients with LAPC were treated with prescription dose of 40 Gy in 5 fractions. The planning objective was that 98% of PTV received ≥95% of the prescribed dose, prioritising duodenal, stomach and bowel UK SABR consortium constraints. Daily online adaptation was performed using magnetic resonance guidance and on-table re-optimisation. 0-3 months and > 3-month post-treatment-related toxicities, local progression-free survival, metastatic-free survival and overall survival were evaluated. RESULTS: 55 patients were treated with SMART at our institution from 2020 to 2022. Median follow-up from date of diagnosis was 17 months (range 5-37 months). Median age was 69.87% of patients underwent induction chemotherapy. 71% of patients reported 0-1 grade acute toxicity only. No grade >3 acute toxicity was reported. 5 patients (9%) reported a grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal stricture). No grade >3 toxicity after 3 months was reported. 6 (10%) of patients had grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal haemorrhage). Median local PFS post diagnosis was 17 months (95% CI 15.3-18.7). Median OS post diagnosis was 19 months (95% CI 15.9-22.1). One-year local control post SMART was 65%. CONCLUSION: This is the first UK-reported experience of MR-guided daily adaptive pancreatic SABR. SMART shows promise in delivering ablative doses with acceptable toxicity rates and good clinical outcomes.

Responsiveness on metabolic syndrome criteria and hepatic parameters after 12 weeks and 24 weeks of multidisciplinary intervention in overweight adolescents.

PURPOSE: This study aimed to evaluate the effect and individual responsiveness after 12 (12wk) and 24 weeks (24wk) of physical exercise (PE) and nutritional guidance (NG) on metabolic syndrome (MetS) criteria and hepatic parameters in overweight adolescents. METHODS: The study comprised 94 overweight adolescents, aged between 10 and 16 years old, from both sexes, allocated into groups: PE and NG (PENGG, n = 64) and control with NG (NGCG, n = 30). Variables were collected at baseline, 12wk, and 24wk. Weight, height, abdominal circumference (AC), blood pressure, and peak oxygen consumption (VO2peak), as well as insulin, triglycerides (TAG), high-density lipoprotein (HDL-c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. HOMA-IR and QUICKI were calculated. PE session consisted of 45 min of indoor cycling, 45 min of walking, and 20 min of stretching, three times a week. The NG consisted of three collective sessions in the first 12wk. Anova, effect size, and prevalence of responders were used for statistical analysis. RESULTS: The PENGG12wk reduced anthropometric and metabolic measurements, while increased VO2peak and HDL-c. The PEG24wk promoted anthropometric, blood pressure, metabolic, and VO2peak improvements, but participants without PE returned to pre-exercise status and presented worsening AST and ALT concentrations. Frequencies of respondents in PENGG12wk versus (vs) NGCG12wk were, respectively, AC (69.1% vs 17.6%, p < 0.01), HDL-c (87.2% vs 23.5%, p < 0.01), TAG (67.3% vs 41.7%, p = 0.05) and ALT (45.5% vs 5,9%; p = 0.003). CONCLUSION: Interventions with PE were effective to reduce MetS components in 12wk and maintenance in 24wk, showing anthropometric, metabolic, and VO2peak improvements. Higher individual responses were observed in 12wk and in 24wk, important changes in overweight adolescent's therapy. LEVEL OF EVIDENCE: Level I, evidence obtained from well-designed controlled trials randomization. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Brazilian Registry of Clinical Trials (RBR-4v6h7b) and date of registration April 4th, 2020.

Prediction of a positive circumferential resection margin at surgery following neoadjuvant chemotherapy for adenocarcinoma of the oesophagus.

Background: A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma. Methods: Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed. Results: A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3-4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT-assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c-index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4-5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092). Conclusion: The presence of advanced cT status, poor tumour differentiation, and CT-assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy.

Antecedentes: Un margen de resección circunferencial (circumferential resection margin, CRM) positivo se ha asociado con tasas más elevadas de recidiva locorregional y peor supervivencia en el cáncer de esófago. El objetivo de este estudio fue establecer si las variables clínico­patológicas y radiológicas podrían predecir la positividad del CRM en el adenocarcinoma de esófago tras quimioterapia neoadyuvante antes de la cirugía. Métodos: Se realizó un análisis multivariable de las características clínico­patológicas y de la tomografía computarizada (computed tomography, CT) que se consideraron potencialmente predictivas de CRM en la estadificación inicial y tras la quimioterapia neoadyuvante. Se construyeron modelos de predicción. Se evaluó el área bajo la curva (area under curve, AUC) con el i.c. del 95% a partir de 1.000 muestras bootstrap. Resultados: Se incluyeron 223 pacientes en el estudio. Una pobre diferenciación (razón de oportunidades, odds ratio, OR 2,84, i.c. del 95% 1,39­6,01) y un estadio clínico T avanzado (T3­4) (OR 2,93, i.c. del 95% 1,03­9,48) se asociaron de forma independiente con un riesgo aumentado de CRM en el diagnóstico. La falta de respuesta en la CT (estable o enfermedad en progresión) tras la quimioterapia se correspondía de forma independiente con un riesgo aumentado de CRM positivo (OR 3,38, i.c. del 95% 1,43­8,50). Además, la evidencia por CT de invasión local y un mayor volumen del tumor en CT (14 cm3) mejoraron el funcionamiento del modelo predictivo, incluyendo todos los parámetros previamente señalados; con AUC (índice c) de 0,76 (0,68­0,83). Las variables asociadas de forma significativa con tasas más elevadas de recidiva locorregional fueron el estado de los ganglios linfáticos patológicos (P = 0,002), la invasión linfovascular (P = 0,007) y la respuesta pobre a la quimioterapia (Mandard 4 y 5 (P = 0,006)). La positividad del CRM se asoció con una tasa de recidiva locorregional más elevada pero sin alcanzar significación estadística (P = 0,09). Conclusión: La presencia de un estadio clínico T avanzado, tumor pobremente diferenciado, falta de respuesta a la quimioterapia en la TC, mayor volumen del tumor en la TC e invasión local pueden ser utilizados para identificar pacientes en riesgo de un CRM positivo tras quimioterapia neoadyuvante.

Distance from home to the nearest park and the use of the parks for physical activity: the mediator role of road safety perception in adolescents.

OBJECTIVE: The objective of the study is to examine whether adolescents' road safety perception (RSP) acts as a mediator on the association between the distance from home to the nearest park and the use of the parks for physical activity (PA). STUDY DESIGN: This is a cross-sectional study. METHODS: The evaluation was through a random sample of 1130 adolescents (534 male), corresponding to 47.3%, 14-20 years old, from Porto Alegre, Brazil. RSP was assessed through some questions of the Neighborhood Environment Walkability Scale for Youth. Park use, socioeconomic status, age, and sex were measured using a questionnaire. Distance from home to the nearest park was evaluated through geographic information system. Data analysis was performed using Pearson correlation, and linear regression models were fitted as per the Baron and Kenny procedures for mediation analyses. All analyses were adjusted for sex and socioeconomic status. RESULTS: Road safety perception is independently associated with less distance from home to the nearest park (P = 0.04) and use of the parks for PA (P = 0.02). Road safety perception is a mediator and explains 16% of the association between park use and distance from home to the park (indirect Effect = -40.9966; 95% confidence interval [CI]: 119.3733-2.2455). CONCLUSION: Our findings indicated that RSP is a mediator on the association between the distance from home to the nearest park and the use of the parks for PA. Future studies should take this into consideration frequency and intensity of PA and other environmental characteristics, such as crime, aesthetics, and neighborhood facilities.

Impact of incremental circumferential resection margin distance on overall survival and recurrence in oesophageal adenocarcinoma.

BACKGROUND: Previous analyses of the oesophageal circumferential resection margin (CRM) have focused on the prognostic validity of two different definitions of a positive CRM, that of the College of American Pathologists (tumour at margin) and that of the Royal College of Pathologists (tumour within 1 mm). This study aimed to analyse the validity of these definitions and explore the risk of recurrence and survival with incremental tumour distances from the CRM. METHODS: This cohort study included patients who underwent resection for adenocarcinoma of the oesophagus between 2000 and 2014. Kaplan-Meier and Cox regression analyses were performed to determine the hazard ratio (HR) with 95 per cent confidence intervals for recurrence and mortality in CRM increments: tumour at the cut margin, extending to within 0·1-0·9, 1·0-1·9, 2·0-4·9 mm, and 5·0 mm or more from the margin. RESULTS: A total of 444 patients were included in the study. Kaplan-Meier and unadjusted analyses showed a significant incremental improvement in overall survival (P < 0·001) and recurrence (P for trend < 0·001) rates with increasing distance from the CRM. Tumour distance of 2·0 mm or more remained a significant predictor of survival on multivariable analysis (HR for risk of death 0·66, 95 per cent c.i. 0·44 to 1·00). Multivariable analysis of overall survival demonstrated a significant difference between a positive and negative CRM with the Royal College of Pathologists' definition (HR 1·37, 1·01 to 1·85), but not with the College of American Pathologists' definition (HR 1·22, 0·90 to 1·65). CONCLUSION: This study demonstrated an incremental improvement in survival and recurrence rates with increasing tumour distance from the CRM.

Acquired erythropoietic uroporphyria secondary to myelodysplastic syndrome with chromosome 3 alterations: a case report.

Congenital erythropoietic porphyria is a rare autosomal recessive disease caused by a deficiency of uroporphyrinogen III synthase, owing to mutations in UROS in chromosome 10. Occasionally, patients show a mild, late-onset disease, without germline UROS mutations, associated with haematological malignancies. We report a 65-year-old patient with photosensitivity, overexcretion of porphyrins and thrombocytopenia. Bone marrow analysis gave a diagnosis of myelodysplastic syndrome (MDS) with the presence of a derivative chromosome 3, possibly due to an inversion including 3q21 and 3q26 break points. After allogeneic stem-cell transplantation, complete remission of MDS and uroporphyria was achieved. To our knowledge, this is the first reported case of acquired erythropoietic uroporphyria associated with MDS, with chromosome 3 alterations.

Patient-derived xenografts effectively capture responses to oncology therapy in a heterogeneous cohort of patients with solid tumors.

BACKGROUND: While patient-derived xenografts (PDXs) offer a powerful modality for translational cancer research, a precise evaluation of how accurately patient responses correlate with matching PDXs in a large, heterogeneous population is needed for assessing the utility of this platform for preclinical drug-testing and personalized patient cancer treatment. PATIENTS AND METHODS: Tumors obtained from surgical or biopsy procedures from 237 cancer patients with a variety of solid tumors were implanted into immunodeficient mice and whole-exome sequencing was carried out. For 92 patients, responses to anticancer therapies were compared with that of their corresponding PDX models. RESULTS: We compared whole-exome sequencing of 237 PDX models with equivalent information in The Cancer Genome Atlas database, demonstrating that tumorgrafts faithfully conserve genetic patterns of the primary tumors. We next screened PDXs established for 92 patients with various solid cancers against the same 129 treatments that were administered clinically and correlated patient outcomes with the responses in corresponding models. Our analysis demonstrates that PDXs accurately replicate patients' clinical outcomes, even as patients undergo several additional cycles of therapy over time, indicating the capacity of these models to correctly guide an oncologist to treatments that are most likely to be of clinical benefit. CONCLUSIONS: Integration of PDX models as a preclinical platform for assessment of drug efficacy may allow a higher success-rate in critical end points of clinical benefit.

Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum.

BACKGROUND: In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection. METHODS/DESIGN: This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4-12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy. DISCUSSION: In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT) and/or fluorouracil (5FU)-based CRT in a future randomised phase III trial. TRIAL REGISTRATION: Clinical trial identifier BACCHUS: NCT01650428.

Rectal tumour volume (GTV) delineation using T2-weighted and diffusion-weighted MRI: Implications for radiotherapy planning.

PURPOSE: To compare the rectal tumour gross target volume (GTV) delineated on T2 weighted (T2W MRI) and diffusion weighted MRI (DWI) images by two different observers and to assess if agreement is improved by DWI. MATERIAL AND METHODS: 27 consecutive patients (15 male, range 27.1-88.8 years, mean 66.9 years) underwent 1.5T MRI prior to chemoradiation (45Gy in 25 fractions; oral capecitabine 850mg/m(2)), including axial T2W MRI (TR=6600ms, TE=90ms) and DWI (TR=3000ms, TE=77ms, b=0, 100, 800s/mm(2)). 3D tumour volume (cm(3)) was measured by volume of interest (VOI) analysis by two independent readers for the T2W MRI and b800 DWI axial images, and the T2W MRI and DWI volumes compared using Mann-Whitney test. Observer agreement was assessed using Bland-Altman statistics. Significance was at 5%. RESULTS: Artefacts precluded DWI analysis in 1 patient. In the remaining 26 patients evaluated, median (range) T2W MRI MRI and DWI (b=800s/mm(2)) 3D GTVin cm(3) were 33.97 (4.44-199.8) and 31.38 (2.43-228), respectively, for Reader One and 43.78 (7.57-267.7) and 42.45 (3.68-251) for Reader Two. T2W MRI GTVs were slightly larger but not statistically different from DWI volumes: p=0.52 Reader One; p=0.92 Reader Two. Interobserver mean difference (95% limits of agreement) for T2W MRI and DWI GTVs were -9.84 (-54.96 to +35.28) cm(3) and -14.79 (-54.01 to +24.43) cm(3) respectively. CONCLUSION: Smaller DWI volumes may result from better tumour conspicuity but overall observer agreement is not improved by DWI.

3 Different types of strength training in older women.

The objective of the present study was to evaluate and compare the neuromuscular, morphological and functional adaptations of older women subjected to 3 different types of strength training. 58, healthy women (67 ± 5 year) were randomized to experimental (EG, n=41) and control groups (CG, n=17) during the first 6 weeks when the EG group performed traditional resistance exercise for the lower extremity. Afterwards, EG was divided into three specific strength training groups; a traditional group (TG, n=14), a power group (PG, n=13) that performed the concentric phase of contraction at high speed and a rapid strength group (RG, n=14) that performed a lateral box jump exercise emphasizing the stretch-shortening-cycle (SSC). Subjects trained 2 days per week through the entire 12 weeks. Following 6 weeks of generalized strength training, significant improvements occurred in EG for knee extension one-repetition (1RM) maximum strength (+19%), knee extensor muscle thickness (MT, +15%), maximal muscle activation (+44% average) and onset latency ( -31% average) for vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) compared to CG (p<0.05). Following 6 more weeks of specific strength training, the 1RM increased significantly and similarly between groups (average of +21%), as did muscle thickness of the VL (+25%), and activation of VL (+44%) and VM (+26%). The onset latency of RF (TG=285 ± 109 ms, PG=252 ± 76 ms, RG=203 ± 43 ms), reaction time (TG=366 ± 99 ms, PG=274 ± 76 ms, RG=201 ± 41 ms), 30-s chair stand (TG=18 ± 3, PG=18 ± 1, RG=21 ± 2) and counter movement jump (TG=8 ± 2 cm, PG=10 ± 3 cm, RG=13 ± 2 cm) was significantly improved only in RG (p<0.05). At the end of training, the rate of force development (RFD) over 150 ms (TG=2.3 ± 9.8 N·s(-1), PG=3.3 ± 3.2 N·s(-1), RG=3.8 ± 6.8 N·s(-1), CG=2.3 ± 7.0 N·s(-1)) was significantly greater in RG and PG than in TG and CG (p<0.05). In conclusion, rapid strength training is more effective for the development of rapid force production of muscle than other specific types of strength training and by consequence, better develops the functional capabilities of older women.

Association of leisure time physical activity and sports competition activities with high blood pressure levels: study carried out in a sample of Portuguese children and adolescents.

BACKGROUND: A better understanding of the different domains and characteristics of children's and adolescent's physical activity (PA) could be a strategy to clarify the association of this behaviour with the early development of cardiovascular risk factors. OBJECTIVES: To examine the relationship between leisure time physical activity (LTPA) and sports competition activities (SCA) with high blood pressure (HBP) levels in a sample of children and adolescents from Porto, Portugal. STUDY DESIGN: This is a cross-sectional study, which comprised 503 boys and 572 girls, aged 8-17 years old. LTPA and SCA were assed by self-reported. Students were assigned as active and non-active in SCA or LTPA according to their self-reported participation. Participants were classified as HBP when they are above of the last quartile for systolic and/or diastolic BP adjusted for gender and age. RESULTS: Do not be engaged in LTPA (OR: 1.47; 95% CI: 1.12; 1.93) and SCA (OR: 1.36; 95% CI: 1.02; 1.81) was significantly associated with the likelihood of being HBP. However, when cardiorespiratory fitness (CRF) (OR: 1.23; 95% CI: 0.91; 1.67) and body mass index (BMI) (OR: 1.31; 95% CI: 0.98; 1.75) were included on SCA model, the association between SCA with HBP did not showed significant results. CONCLUSION: Children and adolescents who are not engaged in SCA or LTPA are more likely to be classified as having HBP; however, the relationship between SCA and HBP was dependent of CRF and BMI. Further, PA strategies should take these differences on the relationship between HBP, SCA and LTPA.

A Phase Ib trial of CA4P (combretastatin A-4 phosphate), carboplatin, and paclitaxel in patients with advanced cancer.

BACKGROUND: The vascular disrupting agent combretastatin A4 phosphate (CA4P) causes major regression of animal tumours when given as combination therapy. METHODS: Patients with advanced cancer refractory to standard therapy were treated with CA4P as a 10-min infusion, 20 h before carboplatin, paclitaxel, or paclitaxel, followed by carboplatin. RESULTS: Combretastatin A4 phosphate was escalated from 36 to 54 mg m(-2) with the carboplatin area under the concentration curve (AUC) 4-5, from 27 to 54 mg m(-2) with paclitaxel 135-175 mg m(-2), and from 54 to 72 mg m(-2) with carboplatin AUC 5 and paclitaxel 175 mg m(-2). Grade 3 or 4 neutropenia was seen in 17%, and thrombocytopenia only in 4% of 46 patients. Grade 1-3 hypertension (26% of patients) and grade 1-3 tumour pain (65% of patients) were the most typical non-haematological toxicities. Dose-limiting toxicity of grade 3 hypertension or grade 3 ataxia was seen in two patients at 72 mg m(-2). Responses were seen in 10 of 46 (22%) patients with ovarian, oesophageal, small-cell lung cancer, and melanoma. CONCLUSION: The combination of CA4P with carboplatin and paclitaxel was well tolerated in the majority of patients with adequate premedication and had antitumour activity in patients who were heavily pretreated.

Stereotactic body radiotherapy: a review.

Stereotactic body radiotherapy (SBRT) combines the challenge of meeting the stringent dosimetric requirements of stereotactic radiosurgery with that of accounting for the physiological movement of tumour and normal tissue. Here we present an overview of the history and development of SBRT and discuss the radiobiological rationale upon which it is based. The published results of SBRT for lung, liver, pancreas, kidney, prostate and spinal lesions are reviewed and summarised. The current evidence base is appraised and important ongoing trials are identified.

Salvage chemotherapy with alternating MINE-ESHAP regimen in relapsed or refractory Hodgkin's lymphoma followed by autologous stem-cell transplantation.

BACKGROUND: High-dose chemotherapy (HDT) followed by autologous stem-cell transplantation (ASCT) is considered the gold standard in the treatment of patients with relapsed or refractory Hodgkin's lymphoma (HL). However, the optimal salvage regimen has not yet been established. PATIENTS AND METHODS: We retrospectively analyzed the efficacy and toxicity of MINE (mesna, ifosfamide, mitoxantrone, and etoposide) alternated with ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in the treatment of 61 relapsed or refractory HL patients after ABVD-based chemotherapy. RESULTS: Overall, 25 patients (41%) achieved a complete response (CR), 23 (38%) a partial response (PR), 4 (7%) a stable disease, and 8 (13%) progressed for an overall response rate of 79%. Response to first-line chemotherapy was the most important prognostic factor for response to MINE-ESHAP (P = 0.041). No grade 4 extrahematologic toxic effects or toxic deaths were observed. Adequate peripheral blood stem-cell collection was achieved in 56 of 59 (95%) mobilized patients. Overall survival and event-free survival after HDT and ASCT were significantly higher for patients achieving CR/PR in comparison with those refractory to MINE-ESHAP (46% and 35% versus 74% and 69%, respectively). CONCLUSION: MINE-ESHAP results in a high response rate with acceptable toxicity in patients with HL having failed ABVD-based treatment.

A 3-year longitudinal analysis of changes in Body Mass Index.

The aim of this study was to analyse whether Physical Activity Index (PAI), Physical Fitness, Screen Time (watching TV and computer use), Socio-economic Status and Commuting to School made a significant contribution to longitudinal changes in Body Mass Index (BMI) in youth. This longitudinal study was carried out over a period of 3 years with 345 students (147 boys) who were between 11 and 16 years old at the beginning of the study. Students were invited to perform tests from FITNESSGRAM Battery for Curl-Ups, Push-Ups, Back-Saver Sit and Reach, and 20 m Shuttle-Run (CRF). Fitness tests were categorized in "Healthy Zone" (HZ) and "Under Healthy Zone" (UHZ), PAI in "less active" and "active"; Socio-economic Status, in low, middle and high education level, and Commuting in active and passive. BMI was corrected for age and gender meaning that we subtracted the age-and-sex-specific cut points for overweight. Corrected body mass index was used as dependent variable in a Linear Mixed Model. The main result was the strong positive and independent association of individuals with CRF performances UHZ with corrected body mass index. In conclusion, the results of this longitudinal study showed markedly an important relationship of lower fitness levels with the risk of being overweight/obese, in particular CRF and abdominal strength.

Relationship between human tumour angiogenic profile and combretastatin-induced vascular shutdown: an exploratory study.

Combretastatin-A4-phosphate (CA4P) acts most effectively against immature tumour vasculature. We investigated whether histological angiogenic profile can explain the differential sensitivity of human tumours to CA4P, by correlating the kinetic changes demonstrated by dynamic MRI (DCE-MRI) in response to CA4P, with tumour immunohistochemical angiogenic markers. Tissue was received from 24 patients (mean age 59, range 32-73, 18 women, 6 men). An angiogenic profile was performed using standard immunohistochemical techniques. Dynamic MRI data were obtained for the same patients before and 4 h after CA4P. Three patients showed a statistically significant fall in K(trans) following CA4P, and one a statistically significant fall in IAUGC(60). No statistically significant correlations were seen between the continuous or categorical variables and the DCE-MRI kinetic parameters other than between ang-2 and K(trans) (P=0.044). In conclusion, we found no strong relationships between changes in DCE-MRI kinetic variables following CA4P and the immunohistochemical angiogenic profile.

Skeletal muscle pathways of contraction-enhanced glucose uptake.

Muscle contraction acutely increases glucose transport in both healthy and type 2 diabetic individuals. Since glucose uptake during muscle contraction has been observed in the absence of insulin, the existence of an insulin-independent pathway has been suggested to explain this phenomenon. However, the exact mechanism behind the translocation of GLUT4 vesicles through the sarcolemma during muscle contraction is still unknown. Some substances, such as AMPK and calcium activated proteins, have been suggested as potential mediators but the exact mechanisms of their involvement remain to be elucidated. A hypothetical convergence point between the insulin cascade and the potential pathways triggered by muscle contraction has been suggested. Therefore, the earliest concept that two different routes exist in skeletal muscle has been progressively modified to the notion that glucose uptake is induced by muscle contraction via components of the insulin pathway. With further consideration, increased glucose uptake and enhanced insulin sensitivity observed during/after exercise might be explained by a metabolic- and calcium-dependent activation of several intermediate molecules of the insulin cascade. This paper aimed to review the literature in order to examine in detail these concepts behind muscle contraction-induced glucose uptake.