Monitoring renal allograft function after transplantation is key for the early detection of allograft impairment, which in turn can contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising noninvasive technique to assess and characterize renal physiopathology; however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period). The purposes of the current study were to evaluate the reproducibility of mpMRI in transplant patients and to characterize normal values of the measured parameters, and to estimate the labeling efficiency of Pseudo-Continuous Arterial Spin Labeling (PCASL) in the infrarenal aorta using numerical simulations considering experimental measurements of aortic blood flow profiles. The subjects were 20 transplant patients with stable kidney function, maintained over 1 year. The MRI protocol consisted of PCASL, intravoxel incoherent motion, and T1 inversion recovery. Phase contrast was used to measure aortic blood flow. Renal blood flow (RBF), diffusion coefficient (D), pseudo-diffusion coefficient (D*), flowing fraction ( f$$ f $$), and T1 maps were calculated and mean values were measured in the cortex and medulla. The labeling efficiency of PCASL was estimated from simulation of Bloch equations. Reproducibility was assessed with the within-subject coefficient of variation, intraclass correlation coefficient, and Bland-Altman analysis. Correlations were evaluated using the Pearson correlation coefficient. The significance level was p less than 0.05. Cortical reproducibility was very good for T1, D, and RBF, moderate for f$$ f $$, and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f$$ f $$ (r = 0.66), RBF and eGFR (r = 0.64), and D* and eGFR (r = -0.57) were found. Normal values of the measured parameters employing the mpMRI protocol in kidney transplant patients with stable function were characterized and the results showed good reproducibility of the techniques.

Currently, among the possible treatments for hepatocel-lular carcinoma there is group of minimally invasive abla-tion techniques with wide clinical acceptance due to their greater efficacy and safety in comparison to traditional therapies, low cost, and no need of being admitted to hospi-tal (outpatient treatment program). Irreversible electroporation is a non-thermal abla tion technique in which electrical fields are used to create nan-opores in the cell membrane that induce tumor cell death.Irreversible electroporation has shown promising results in numerous clinical trials; however, its control on long-term tumor growth and recurrence is inferior in comparison to that of radiofrequency. Combining irreversible electropora-tion with immunological agents may increase its efficacy in the treatment of focal lesions and metastases. In this work, we present an update on IRE including procedure, mecha-nism of action, application as a treatment for HCC, and the improvements that have been made in the past few years.

Background/Aim. Irreversible electroporation (IRE) showed promising results for small-size tumors and very early cancers. However, further development is needed to evolve this procedure into a more efficient ablation technique for long-term control of tumor growth. In this work, we show that it is possible to increase the antitumor efficiency of IRE by simmultaneously injecting c-di-GMP, a STING agonist, intratumorally. Materials and Methods. Intratumoral administration of c-di-GMP simultaneously to IRE was evaluated in murine models of melanona (B16.OVA) and hepatocellular carcinoma (PM299L). Results. The combined therapy increased the number of tumor-infiltrating IFN-gamma/TNF-alpha-producing CD4 and CD8 T cells and delayed tumor growth, as compared to the effect observed in groups treated with c-di-GMP or IRE alone. Conclusion. These results can lead to the development of a new therapeutic strategy for the treatment of cancer patients refractory to other therapies.

Purpose To evaluate labeling efficiency of pseudo-continuous arterial spin labeling (PCASL) and to find the gradient parameters that increase PCASL robustness for renal perfusion measurements. Methods Aortic blood flow was characterized in 3 groups: young healthy volunteers (YHV1), chronic kidney disease (CKD) patients (CKDP), and healthy controls (HCO). PCASL inversion efficiency was evaluated through numeric simulations considering the measured pulsatile flow velocity profiles and off-resonance effects for a wide range of gradient parameters, and the results were assessed in vivo. The most robust PCASL implementation was used to measure renal blood flow (RBF) in CKDP and HCO. Results Aortic blood velocities reached peak values of 120 cm/s in YHV1, whereas for elderly subjects values were lower by approximately a factor of 2. Simulations and experiments showed that by reducing the gradient average (G(ave)) and the selective to average gradient ratio (G(max)/G(ave)), labeling efficiency was maximized and PCASL robustness to off-resonance was improved. The study in CKDP and HCO showed significant differences in RBF between groups. Conclusion An efficient and robust PCASL scheme for renal applications requires aG(max)/G(ave)ratio of 6-7 and aG(ave)value that depends on the aortic blood flow velocities (0.5 mT/m being appropriate for CKDP and HCO).

Objective: Liver transplantation is one of the treatments for patients with advanced stage chronic liver disease and for selected patients with hepatic tumors. Ultrasonography is the first-choice imaging technique to evaluate liver transplants. This article reviews the surgical technique, anatomy, and normal findings on ultrasonography in the immediate postoperative period in patients who have undergone liver transplantation, which will be used as a reference in follow-up studies. Conclusion: Early vascular (arterial and portal) complications can represent a threat for the graft or the patient. During the period after liver transplantation, the patient is recovering from surgery and the transplanted organ is adapting to its new environment. In this period, ultrasonography can show alterations in the parenchyma or Doppler findings that would be considered abnormal in other situations; these findings are usually transitory. Knowing how to interpret them is key to detecting or ruling out complications.

Objective: To determine the incidence of immune-mediated adverse reactions with and without radiologic manifestations and to correlate them with the response to immunotherapy. Material and methods: We retrospectively included 79 patients with stage IV lung carcinomas (n=24), renal carcinomas (n=11), or melanoma (n=44) treated with immunotherapy. We evaluated the occurrence of immune-mediated adverse reactions, their radiologic manifestations, and the response pattern according to the immune-related response criteria (irRC). We correlated the presence of immune-mediated adverse reactions with the response pattern. Results: Immune-mediated adverse reactions occurred in 27.8%, being most common in patients with melanoma (40.9%). In 59.1% of patients with adverse reactions, there were radiologic manifestations such as pneumonitis, colitis, hypophysitis, thyroiditis, or myocarditis. Pneumonitis was the most common radiologic manifestation of immune-mediated adverse reactions, even in asymptomatic patients. The rate of response to immunotherapy was higher among patients who developed immune-mediated adverse reactions than in those who did not (68.2% vs. 38.6%, respectively, ¿2 5.58; p=0.018). The rate of favorable responses was higher in patients with radiologic manifestations of immune-mediated adverse reactions than in those without radiologic manifestations (84.6% vs. 44.4%, respectively; p=0.023). Conclusions: The presence of immune-mediated adverse reactions is associated with a better response to immunotherapy. The association with a favorable response is even stronger in patients with radiologic manifestations of the immune-mediated adverse reactions.

Objective: To determine the incidence of immune-mediated adverse reactions with and without radiologic manifestations and to correlate them with the response to immunotherapy. Material and methods: We retrospectively included 79 patients with stage IV lung carcinomas (n=24), renal carcinomas (n=11), or melanoma (n=44) treated with immunotherapy. We evaluated the occurrence of immune-mediated adverse reactions, their radiologic manifestations, and the response pattern according to the immune-related response criteria (irRC). We correlated the presence of immune-mediated adverse reactions with the response pattern. Results: Immune-mediated adverse reactions occurred in 27.8%, being most common in patients with melanoma (40.9%). In 59.1% of patients with adverse reactions, there were radiologic manifestations such as pneumonitis, colitis, hypophysitis, thyroiditis, or myocarditis. Pneumonitis was the most common radiologic manifestation of immune-mediated adverse reactions, even in asymptomatic patients. The rate of response to immunotherapy was higher among patients who developed immune-mediated adverse reactions than in those who did not (68.2% vs. 38.6%, respectively, ¿2 5.58; p=0.018). The rate of favorable responses was higher in patients with radiologic manifestations of immune-mediated adverse reactions than in those without radiologic manifestations (84.6% vs. 44.4%, respectively; p=0.023). Conclusions: The presence of immune-mediated adverse reactions is associated with a better response to immunotherapy. The association with a favorable response is even stronger in patients with radiologic manifestations of the immune-mediated adverse reactions.

Background Perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC) has been shown to improve survival compared to an exclusive surgical approach. However, most patients retain a poor prognosis due to important relapse rates. Population pharmacokinetic-pharma-codynamic (PK/PD) modeling may allow identifying at risk-patients. We aimed to develop a mechanistic PK/PD model to characterize the relationship between the type of neoadjuvant therapy, histopathologic response and survival times in locally advanced GC and GEJC patients. Methods Patients with locally advanced GC and GEJC treated with neoadjuvant CT with or without preoperative CRT were analyzed. Clinical response was assessed by CT-scan and EUS. Pathologic response was defined as a reduction on pTNM stage compared to baseline cTNM. Metastasis development risk and overall survival (OS) were described using the population approach with NONMEM 7.3. Model evaluation was performed through predictive checks. Results A low correlation was observed between clinical and pathologic TNM stage for both T (R = 0.32) and N (R = 0.19) categories. A low correlation between clinical and pathologic response was noticed (R = -0.29). The OS model adequately described the observed survival rates. Disease recurrence, cTNM stage >= 3 and linitis plastica absence, were correlated to a higher risk of death. Conclusion Our model adequately described clinical response profiles, though pathologic response could not be predicted. Although the risk of disease recurrence and survival were linked, the identification of alternative approaches aimed to tailor therapeutic strategies to the individual patient risk warrants further research.

Purpose: To evaluate the therapeutic efficacy of irreversible electroporation (IRE) combined with the intratumoral injection of the immunogenic adjuvant poly-ICLC (polyinosinic-polycytidylic acid and poly-L-lysine, a dsRNA analog mimicking viral RNA) inmediately before IRE. Materials and Methods: Mice and rabbits bearing hepatocellular carcinoma tumors (Hepa.129 and VX2 tumor models, respectively) were treated with IRE (2 pulses of 2500V), with poly-ICLC, or with IRE + poly-ICLC combination therapy. Tumor growth in mice was monitored using a digital caliper and by computed tomography in rabbits. Results: Intratumoral administration of poly-ICLC immediately before IRE elicited shrinkage of Hepa.129 cell-derived tumors in 70% of mice, compared to 30% and 26% by poly-ICLC or IRE alone, respectively (P = .0004). This combined therapy induced the shrinkage of VX-2-based hepatocellular carcinoma tumors in 40% of rabbits, whereas no response was achieved by either individual treatment (P = .045). The combined therapy activated a systemic antitumor response able to inhibit the growth of other untreated tumors. Conclusions: IRE treatment, immediately preceded by the intratumoral administration of an immunogenic adjuvant such as poly-ICLC, might enhance the antitumor effect of the IRE procedure. This combination might facilitate the induction of a long-term systemic response to prevent tumor relapses and the appearance of metastases.

Background There is a growing awareness that prevention and early diagnosis may reduce the high mortality associated with cancer, cardiovascular and other diseases. The role of whole-body computed tomography (WB-CT) in self-referred and asymptomatic patients has been debated. Aim To determine frequency and spectrum of WB-CT findings in average-risk subjects derived from a Medical-Check-Up-Unit, to evaluate recommendations reported and distribution according to sex and age-groups. Materials and methods We retrospectively reviewed 6516 subjects who underwent WB-CT (June 2004/February 2015). All were > 40 years and referred by Medical-Check-Up-Unit of our hospital. The main findings were categorized and classified as normal or not. Its distribution according to sex and age-groups was evaluated using Chi-square test and linear-by-linear association test, respectively. Number of recommendations, type and interval of follow-up were recorded. Descriptive statistics were used. Results WB-CT performed in 6516 patients (69% men, 31% women, mean age = 58.4 years) revealed chest (81.4%), abdominal (93.06%) and spine (65.39%) abnormalities. Only 1.60% had completely normal exploration. Abnormal WB-CT in men was significantly higher than women (98.64% vs. 97.87%; p = 0.021), with significant increase as age was higher (40-49 years: 95.65%; 50-59 years: 98.33%; 60-69 years: 99.47%; > 69 years: 99.89%) (p < 0.001). Although most findings were benign, we detected 1.47% primary tumors (96, mai

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