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Purpose The aim of this study was to create and validate dynamic nomograms to predict overall survival (OS) and disease-free survival (DFS) at different time points during follow-up in patients who had undergone resection of primary retroperitoneal sarcoma (RPS). Methods Patients with primary RPS operated upon between 2002 and 2017 at four and six referral centres comprised the development and external validation cohorts, respectively. Landmark analysis and multivariable Cox models were used to develop dynamic nomograms. Variables were selected using two backward procedures based on the Akaike information criterion. The prediction window was fixed at 5 years. Nomogram performances were tested in terms of calibration and discrimination on the development and validation cohorts. Results Development and validation cohorts totalled 1357 and 487 patients (OS analysis), and 1309 and 452 patients (DFS analysis), respectively. The final OS model included age, landmark time (TLM), tumour grade, completeness of resection and occurrence of local/distant recurrence. The final DFS model included TLM, histologic subtype, tumour size, tumour grade, multifocality and the interaction terms between TLM and size, grade and multifocality. For OS, Harrell C indices were higher than 0.7 in both cohorts, indicating very good discriminative capability. For DFS, Harrell C indices were between 0.64 and 0.72 in the development cohort and 0.62 and 0.68 in the validation cohort. Calibration plots showed good agreement between predicted and observed outcomes. Conclusion Validated nomograms are available to predict the 5-year OS and DFS probability at different time points throughout the first 5 years of follow-up in RPS survivors.

Background Percutaneous core needle biopsy (PCNB) has become an accepted method to collect tumour tissue samples given its safety, minimal invasiveness, high accuracy and cost-effectiveness. Procedure It is a single centre, retrospective evaluation of 213 ultrasound (US) or computed tomography (CT) guided PCNBs of paediatric solid tumours performed from 2005 to 2017. Safety, diagnostic yield, accuracy, and efficacy assessments of the PCNB procedure were performed. Univariate logistic models were applied to assess the relation of the diagnostic yield with patient, procedure and lesion features. Results The image-guide was US in 91.08% of biopsies; the needle gauge was ≥16 G in 69.01% of the biopsies. The anatomical site of lesion was deep in 113 biopsies (53.05%). The nature of the lesion was the only factor associated with diagnostic yield (OR: 4.04; 95% CI 1.23–13.28; p: 0.022), with benign lesion as an unfavourable factor. Complication incidence was 1.41%. Overall, the diagnostic yield of PCNB was 93.90% (95% CI: 89.79-96.71%), the diagnostic accuracy was 96.86% (95% CI: 93.29–98.84%) and the diagnostic efficacy was 93.33% (95% CI: 86.75–97.28%). Sensitivity was 97.94% (95% CI: 92.75–99.75%) and specificity 100% (95% CI: 66.37–100%). Conclusion PCNB can be recommended as the first-choice method for solid tumours diagnosis in paediatric, adolescent and young adult patients because of its high diagnostic success, safety and accessibility.

Aims To evaluate the effects of high intra-abdominal pressure (IAP) during hyperthermic intraperitoneal chemotherapy (HIPEC) on cisplatin uptake by residual tumor and normal tissues, pharmacokinetics, and short-term surgical outcomes. Patients & methods Patients with peritoneal metastasis from colorectal cancer or pseudomyxoma peritonei were randomized to closed-abdomen HIPEC with low-IAP or high-IAP, after complete cytoreduction. High-IAP was obtained increasing the volume of perfusate maintaining constant the cisplatin concentration (42 mg/L). We determined the Platinum concentration using an Inductive Coupled Plasma Mass Spectrometry System. Randomization was stratified according to tumor type. To consider the multiple sampling in the three tissues types of interest, we performed linear mixed models to assess the differences of cisplatin concentration between study arms. We also compared AUC perfusate/plasma ratios (Wilcoxon-Mann-Whitney) and perioperative severe complication rates (chi-square) between study arms. Results 38 cases were randomly assigned to IAP arms (n = 19 each). Median IAPs were 19 mmHg and 11 mmHg in the high and low arms, respectively. Cisplatin concentrations did not differ in the tumor residual tissues and in the muscular fascia [22.8 ng/mg (SD: 25.5) vs. 15.9 ng/mg (SD: 13.3), p = 0.181] and [50.3 ng/mg (SD: 40.1) vs. 42.0 ng/mg (SD: 38.3), p = 0.426, respectively], whereas in the mesenteric peritoneum it did [5.4 ng/mg (SD: 7.82) vs. 2.7 ng/mg (SD: 2.9), p = 0.048]. Pharmacokinetic advantage did not differ between the two arms. High-IAP did not increase perioperative severe complications rate (NCI-CTCAE.v3). Conclusions high-IAP HIPEC increases cisplatin distribution in the mesenteric peritoneum, is safe, and could be considered to obtain microscopic cytoreduction.

Objective The aim of this study was to investigate the oncologic and surgical outcomes of patients treated with inferior vena cava (IVC) or iliac vein (IV) resection for retroperitoneal sarcoma (RPS). Surgery is the only curative option for patients with primary RPS. The IVC or IV can be directly invaded by RPS or can be the organ of origin of retroperitoneal leiomyosarcoma. In both cases, resection of the IVC or IV is required to achieve a complete resection. Methods Patients who underwent IVC or IV resection for primary or recurrent RPS between 2000 and 2016 at a single referral institution were included in this retrospective study. The oncologic outcome was explored in terms of overall survival and crude cumulative incidence (CCI) of local recurrence and distant metastasis. Surgical outcomes were explored in terms of complications, renal function, lower limb edema, and vascular graft patency. Results Sixty-seven patients were included: 24 IV resections (IV group), 39 IVC resections, and 4 IVC and IV resections (IVC group). The most frequent histologic types were leiomyosarcoma (63%) and liposarcoma (27%). Five-year overall survival, CCI of local recurrence, and CCI of distant metastasis (95% confidence interval) were 56.2% (43.6-72.4), 12.4% (5.2-29.5), and 51.5% (39.3-67.5). IVC was circumferentially resected in 38 of 43 patients; 32 were treated with graft reconstruction (22 with interposition of banked venous homograft [BVH] and 10 with polytetrafluoroethylene [PTFE] graft) and 6 with ligation only, mostly dependent on the presence of an adequate collateral vessel network. Patients with preoperative IVC obstruction treated with ligation only (n = 6) did not develop severe postoperative lower limb edema. IVC graft primary patency at 5 years was 100% in IVC PTFE grafts and 76.7% in IVC BVHs. Fifteen patients (22.4%) suffered a Clavien-Dindo grade ≥3 complication within 60 days of surgery. Conclusions IVC or IV resection in the context of RPS surgery is of value in achieving long-term survival. A policy of vascular grafting in case of circumferential resection of a patent IVC or IV is rewarding. For IVC reconstruction, both BVHs and PTFE grafts offer good results in terms of high patency rate and low risk of infection.

The treatment of patients with refractory/relapsed B cell non-Hodgkin lymphoma (NHL) is evolving because of the availability of novel drugs. Allogeneic stem cell transplantation (alloSCT) can be curative, but its morbidity and mortality remain a matter of concern. We conducted a multicenter prospective phase II trial to evaluate the benefit of including only 1 dose of rituximab in the conditioning regimen before alloSCT. The primary endpoint was progression-free survival. The study enrolled 121 patients with relapsed/refractory B cell lymphomas. The conditioning regimen consisted of thiotepa, cyclophosphamide, fludarabine, and rituximab (500 mg/m2). Rabbit antithymocyte globulin was administered only in case of unrelated donors. Sixty-seven (55%) and 54 (45%) patients received grafts from related and unrelated donors, respectively. The crude cumulative incidence (CCI) of nonrelapse mortality (NRM) was 21% at 3 years. The CCIs of chronic graft-verus-host disease (GVHD) at 3 years were 54% and 31% in recipients of matched sibling and unrelated grafts, respectively. At a median follow-up of 41 months, the estimated 3-year progression-free and overall survival were 50% and 61%, respectively. Long-term outcome was also evaluated with the composite endpoint of GVHD-free and relapse-free survival (GRFS). This is the first work evaluating the GRFS in a prospective trial of lymphoma patients: the 1-year and 3-year GRFS were 40% and 34%, respectively. AlloSCT can cure a fraction of patients with rather low NRM and an encouraging PFS and GRFS.

Preterm infants complete their development in Neonatal Intensive Care Unit being exposed to environmental stimuli that lead to the early maturation of the sensory systems. It is known that the fetus perceives sounds and reacts to them with movements since the 26th-28th week of gestational age. Maternal voice represents a source of sensory stimulation for the fetus.To investigate the effect of the exposure to maternal voice, administered by bone conduction, on preterm infants autonomic and neurobehavioral development.Longitudinal, explorative, case control study.71 preterm infants with birth weight1500g, born adequate for gestational agevital and neurobehavioral parameters at term, neurofunctional assessment at 3 and 6months of corrected age.Infants in the treatment group had lower heart rate values and a higher proportion of stable skin color at each study point as compared to the control group. The scores in the visual attention performance and in the quality of the general movements at term were better in the treatment group than in the control one. Neurofunctional assessment score at 3months of corrected age was higher in the treatment group whereas no difference between the two groups was detected at 6months of corrected age.Early exposure to maternal voice exerts a beneficial effect on preterm infants autonomic and neurobehavioral development.

Epigenetics is believed to play a role in Alzheimer's disease (AD). DNA methylation, the most investigated epigenetic hallmark, is a reversible mechanism that modifies genome function and chromosomal stability through the addition of methyl groups to cytosine located in CpG dinucleotides to form 5 methylcytosine (5mC). Methylation status of repetitive elements (i.e. Alu, LINE-1 and SAT- α) is a major contributor of global DNA methylation patterns and has been investigated in relation to a variety of human diseases. However, the role of methylation of repetitive elements in blood of AD patients has never been investigated so far. In the present study, a quantitative bisulfite-PCR pyrosequencing method was used to evaluate methylation of Alu, LINE-1 and SAT- α sequences in 43 AD patients and 38 healthy donors. In multivariate analysis adjusting for age and gender, LINE-1 was increased in AD patients compared with healthy volunteers (ADs: 83.6 %5mC, Volunteers: 83.1 %5mC, p-value: 0.05). The group with best performances in mini mental state examination (MMSE) showed higher levels of LINE-1 methylation compared to the group with worst performances (MMSE>22: 83.9 %5mC; MMSE