Identification of Psychological Profiles of Cancer Patients Undergoing Fertility Preservation Counseling.

Gonadotoxicity is one of the most distressing side effects of cancer treatment. Fertility preservation strategies should be included during the treatment pathway to prevent the risk of infertility, but the decision to preserve fertility often represents a challenging process that carries an emotional decision-making burden. The aim of this study is to characterize the psychological profiles of women undergoing fertility preservation counseling and to better understand their features. Eighty-two female cancer patients were included in the study. They were asked to complete a battery of self-administered tests which evaluated socio-demographic characteristics, defense mechanisms, depression, anxiety, and representations regarding the importance of parenthood. Based on the psychometric variables, cluster analysis identified four groups which showed significantly different combinations of these psychological characteristics. An additional analysis was performed to evaluate if sociodemographic variables were associated with the four groups, but the results did not show significant differences. These results suggest that very diverse psychological profiles may lead cancer patients to attend oncofertility counseling and choose fertility preservation. For this reason, all patients in childbearing age should have the opportunity to receive appropriate fertility preservation counseling in order to make an informed decision that could have an important impact on their long-term quality of life.

Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia.

Acute myeloid leukemia may be characterized by a fraction of leukemia stem cells (LSCs) that sustain disease propagation eventually leading to relapse. Yet, the contribution of LSCs to early therapy resistance and AML regeneration remains controversial. We prospectively identify LSCs in AML patients and xenografts by single-cell RNA sequencing coupled with functional validation by a microRNA-126 reporter enriching for LSCs. Through nucleophosmin 1 (NPM1) mutation calling or chromosomal monosomy detection in single-cell transcriptomes, we discriminate LSCs from regenerating hematopoiesis, and assess their longitudinal response to chemotherapy. Chemotherapy induced a generalized inflammatory and senescence-associated response. Moreover, we observe heterogeneity within progenitor AML cells, some of which proliferate and differentiate with expression of oxidative-phosphorylation (OxPhos) signatures, while others are OxPhos (low) miR-126 (high) and display enforced stemness and quiescence features. miR-126 (high) LSCs are enriched at diagnosis in chemotherapy-refractory AML and at relapse, and their transcriptional signature robustly stratifies patients for survival in large AML cohorts.

The Experience of COVID-19 in a Sample of Gynecological Cancer Patients Undergoing Chemotherapy: A Focus on the Psychological Implications.

Cancer patients are at an increased risk of developing severe consequences due to the COVID-19 infection. However, psychological outcomes in this population have been overlooked in the literature. The present study aims to identify significant psychological differences between gynecological cancer patients undergoing chemotherapy before and during the pandemic. Additionally, we explore the correlations between COVID-19-related concerns and anxiety, depression, distress, and quality of life levels. Forty-two patients completed the STAI-Y, the EORTC QLQ-C30, the BDI II, the DT, and an ad-hoc questionnaire that investigated COVID-19-related concerns. The analyses did not show significant differences in the psychometric scales between the two groups, highlighting a considerable resilience against mental health and quality of life deterioration during the COVID-19 pandemic in gynecologic cancer patients. However, COVID-19-related concerns were positively associated with anxiety and inversely related to emotional functioning levels. These results emphasize the importance of a comprehensive patient care and the need to implement a multidisciplinary approach that includes psychological support in the treatment plan. Moreover, it is essential to encourage clear communication to convey comprehensive information about the impact of the pandemic on physical and psychological levels, as well as to offer psychoeducational tools to face the pandemic.

Hybrid PET/MRI in Staging Endometrial Cancer: Diagnostic and Predictive Value in a Prospective Cohort.

AIM: The assessment of deep myometrial invasion (MI) and lymph node involvement is of utmost importance in the preoperative staging of endometrial cancer (EC). Imaging parameters derived respectively from MRI and PET have shown good predictive value. The main aim of the present study is to assess the diagnostic performance of hybrid 18F-FDG PET/MRI in EC staging, with particular focus on MI and lymphnodal involvement detection. PATIENTS AND METHODS: Prospective monocentric study including 35 patients with biopsy-proven EC undergoing preoperative 18F-FDG PET/MRI (December 2018-March 2021) for staging purpose. Histological examination was the reference standard. PET (SUVmax, SUVmean with a threshold of 40% of SUVmax-SUVmean40, metabolic tumor volume, total lesion glycolysis) and MRI (volume index [VI], total tumor volume, tumor volume ratio [TVR], mean apparent diffusion coefficient, minimum apparent diffusion coefficient) parameters were calculated on the primary tumor, and their role in predicting EC risk group, the presence of lymphovascular space invasion (LVSI), and MI was assessed. Receiver operating characteristics analysis was used to assess the predictive value of PET and MRI parameters on EC characteristics. RESULTS: Patients' median age was 66.57 years (SD, 10.21 years). 18F-FDG PET/MRI identified the primary tumor in all patients. Twenty-two of 35 patients had high-risk EC and 13/35 low-risk disease; 13/35 presented LVSI, 22/35 had deep MI at histological examination, and 13/35 had p53 hyperexpression.PET/MRI was able to detect lymphnodal involvement with high accuracy and high specificity (sensitivity of 0.8571, specificity of 0.9286, accuracy of 0.9143), also showing a high negative predictive value (NPV) for lymphnodal involvement (NPV of 0.9630, positive predictive value [PPV] of 0.7500).The assessment of deep MI using PET/MRI correctly staged 27 patients (77.1%; sensitivity of 0.7273, specificity of 0.8462, accuracy of 0.7714), with also a good PPV (PPV of 0.8889, NPV of 0.647).MRI-derived total tumor volume, VI, and TVR were significant in predicting EC groups (high-risk vs low-risk patients) (P = 0.0059, 0.0235, 0.0181, respectively). MRI-derived volume, VI, TVR, and PET-derived metabolic tumor volume and total lesion glycolysis were able to predict LVSI (P = 0.0023, 0.0068, 0.0068, 0.0027, 0.01394, respectively). Imaging was not able to predict grading, presence of deep MI, nor hyperexpression of p53. CONCLUSIONS: 18F-FDG PET/MRI has good accuracy in preoperative staging of EC; PET and MRI parameters have synergic role in preoperatively predicting LVSI, with MRI parameters being also predictive for EC risk group.

Toxicity of Hypofractionated Whole Breast Radiotherapy Without Boost and Timescale of Late Skin Responses in a Large Cohort of Early-Stage Breast Cancer Patients.

AIM: To report toxicity of hypofractionated whole-breast radiotherapy in a large cohort of early-stage breast cancer (BCaients. MATERIALS AND METHODS: From 02/2009-05/2017, 1325 consecutive BCa patients were treated with 40.05 Gy/15 fractions, without boost. Median age was 62 (IQR:51.1-70.5) years. Chemotherapy was prescribed for 28% of patients, hormonal therapy for 80.3%, monoclonal antibodies for 8.2%. RESULTS: Median follow-up was 72.4 (IQR: 44.6-104.1) months. Acute RTOG toxicity was: 69.8% Grade (G) 1, 14.3% G2 and 1.7% G3. Late SOMA-LENT toxicities were: edema-hyperpigmentation (E-H): G1 28.67%, G2 4.41%, G3 0.15%; fibrosis-atrophy-telangiectasia-pain (F-A-T-P): G1 14.6%, G2 3.2%, G3 0.8%, G4 0.1%. Median time to first occurrence was 6 and 18 months, respectively. Aesthetic result after surgery was excellent in 28.7%, good in 41.5%, acceptable in 20.3% and poor in 9.5% of patients. Change in breast appearance after radiotherapy was mild in 6.9%, moderate in 2.3% and marked in 1.3% of patients. Concomitant chemotherapy, obesity, smoking, use of bolus and planning target volume (PTV) were associated with higher acute toxicity. Patients ≥55 years old were less likely to experience acute toxicity. PTV and acute G2 toxicity were associated with ≥G2 E-H. PTV, concomitant chemotherapy, hypertension and ≥G2 acute toxicity were associated with increased risk of F-A-T-P. CONCLUSION: Hypofractionated whole-breast radiotherapy without boost demonstrated mild acute and late toxicity in a large cohort of consecutive patients. Moderate and marked changes in breast appearance were registered for 3.6% of patients and occurred between 18 to 42 months.

Evaluation of factors predicting loss of benefit provided by laparoscopic distal pancreatectomy compared to open approach.

Several studies showed safety and feasibility of laparoscopic distal pancreatectomy (LDP) as compared to open distal pancreatectomy (ODP). Patients who underwent LDP or ODP (2015-2019) were included. A 1:1 propensity score matching (PSM) was used to reduce the effect of treatment selection bias. Aim of this study was to identify those factors influencing the loss of benefit (defined as a significantly better outcome compared to ODP) after LDP. Overall, 387 patients underwent DP (n = 250 LDP, n = 137 ODP). After PSM, 274 patients (n = 137 LDP, n = 137 ODP) were selected. LDP was associated with reduced intraoperative blood loss (median: 200 mL vs. 250 mL, p < 0.001), decreased wound infection rate (1% vs. 9%, p = 0.044) and shorter time to functional recovery (TFR) (median: 4 days vs. 5 days, p = 0.002). Consequently, TFR > 5 days and blood loss > 250 mL were defined as loss of benefit after LDP. In the LDP group, age > 70 years [Odds Ratio (OR) 2.744, p = 0.022] and duration of surgery > 208 min (OR 2.957, p = 0.019) were predictors of TFR > 5 days and intraoperative blood loss > 250 mL, respectively. No differences in terms of TFR were found between ODP and LDP groups in patients > 70 years (p = 0.102). Intraoperative blood loss was significantly higher in the ODP group, also when the analysis was limited to surgical procedures with operative time > 208 min (p = 0.003). In conclusion, LDP seems comparable to ODP in terms of TFR in patients aged > 70 years. This finding could be helpful in the choice of the best surgical approach in elderly patients undergoing potentially challenging DPs.

Ten Year Results of Extensive Nodal Radiotherapy and Moderately Hypofractionated Simultaneous Integrated Boost in Unfavorable Intermediate-, High-, and Very High-Risk Prostate Cancer.

AIMS: To report 10-year outcomes of WPRT and HD moderately hypofractionated SIB to the prostate in UIR, HR, and VHR PCa. METHODS: From 11/2005 to 12/2015, 224 UIR, HR, and VHR PCa patients underwent WPRT at 51.8 Gy/28 fractions and SIB at 74.2 Gy (EQD2 88 Gy) to the prostate. Androgen deprivation therapy (ADT) was prescribed in up to 86.2% of patients. RESULTS: Median follow-up was 96.3 months (IQR: 71-124.7). Median age was 75 years (IQR: 71.3-78.1). At last follow up, G3 GI-GU toxicity was 3.1% and 8%, respectively. Ten-year biochemical relapse-free survival (bRFS) was 79.8% (95% CI: 72.3-88.1%), disease-free survival (DFS) 87.8% (95% CI: 81.7-94.3%), overall survival (OS) 65.7% (95% CI: 58.2-74.1%), and prostate cancer-specific survival (PCSS) 94.9% (95% CI: 91.0-99.0%). Only two patients presented local relapse. At univariate analysis, VHR vs. UIR was found to be a significant risk factor for biochemical relapse (HR: 2.8, 95% CI: 1.17-6.67, p = 0.021). After model selection, only Gleason Score ≥ 8 emerged as a significant factor for biochemical relapse (HR = 2.3, 95% CI: 1.12-4.9, p = 0.023). Previous TURP (HR = 3.5, 95% CI: 1.62-7.54, p = 0.001) and acute toxicity ≥ G2 (HR = 3.1, 95% CI = 1.45-6.52, p = 0.003) were significant risk factors for GU toxicity ≥ G3. Hypertension was a significant factor for GI toxicity ≥ G3 (HR = 3.63, 95% CI: 1.06-12.46, p = 0.041). ADT (HR = 0.31, 95% CI: 0.12-0.8, p = 0.015) and iPsa (HR = 0.37, 95% CI: 0.16-0.83, p = 0.0164) played a protective role. CONCLUSIONS: WPRT and HD SIB to the prostate combined with long-term ADT, in HR PCa, determine good outcomes with acceptable toxicity.

Predictors of postoperative hospital length of stay after total knee arthroplasty.

INTRODUCTION: To collect and analyse clinical and functional variables of patients undergoing rehabilitation after total knee arthroplasty (TKA), in order to identify which amongst them could influence the post-operative length of hospital stay (LOS). METHODS: We conducted a retrospective analysis of prospectively collected data of 1,082 consecutive patients (746 females and 336 males) who underwent primary TKA and rehabilitation in our Orthopedic Institute between January 2013 and July 2017. Clinical and anthropometric data were analysed using a multivariate linear regression model. RESULTS: The average LOS was 5.08 ± 2.52 days in the Department of Orthopedic Surgery, and 12.67 ± 5.54 days in the Rehabilitation Unit. Age, female sex and the presence of comorbidities were predictive of a longer stay. The presence of caregiver assistance at home was associated with shorter LOS. There was no evidence of a statistically significant positive association between BMI and LOS. CONCLUSION: An in-depth and early knowledge of these factors may enable the whole multidisciplinary team to plan a patient-tailored rehabilitation path and a better allocation of resources to maximize patients' functional recovery, while reducing LOS and the overall cost of the procedure.

18F-FAZA PET/CT in pretreatment assessment of hypoxic status in high-grade glioma: correlation with hypoxia immunohistochemical biomarkers.

BACKGROUND: To investigate the correlation between 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET data and hypoxia immunohistochemical markers in patients with high-grade glioma (HGG). PATIENTS AND METHODS: Prospective study including 20 patients with brain MRI suggestive for HGG and undergoing 18F-FAZA PET/CT before treatment for hypoxia assessment. For each 18F-FAZA PET scan SUVmax, SUVmean and 18F-FAZA tumour volume (FTV) at 40, 50 and 60% threshold of SUVmax were calculated; hypoxic volume was estimated by applying different thresholds (1.2, 1.3 and 1.4) to tumour/blood ratio. Seventeen patients were analysed. The immunohistochemical analysis assessed the following parameters: hypoxia-inducible factor 1α, carbonic anhydrase IX (CA-IX), glucose transporter-1, tumour vascularity and Ki-67. RESULTS: 18F-FAZA PET showed a single lesion in 15/17 patients and multiple lesions in 2/17 patients. Twelve/17 patients had grade IV glioma and 5/17 with grade III glioma. Bioptic and surgical samples have been analysed separately. In the surgical subgroup (n = 7) a positive correlation was observed between CA-IX and SUVmax (P = 0.0002), SUVmean40 (P = 0.0058), SUVmean50 (P = 0.009), SUVmean60 (P = 0.0153), FTV-40-50-60 (P = 0.0424) and hypoxic volume1.2-1.3-1.4 (P = 0.0058). In the bioptic group (n = 10) tumour vascularisation was inversely correlated with SUVmax (P = 0.0094), SUVmean40 (P = 0.0107), SUVmean50 (P = 0.0094) and SUVmean60 (P = 0.0154). CONCLUSIONS: The correlation of 18F-FAZA PET parameters with CD31 and CA-IX represents a reliable method for assessing tumour hypoxia in HGG. The inverse correlation between tumour vascularisation, SUVmax and SUVmean suggest that highly vascularized tumours might present more oxygen supply than hypoxia.

Dual Tracer 68Ga-DOTATOC and 18F-FDG PET Improve Preoperative Evaluation of Aggressiveness in Resectable Pancreatic Neuroendocrine Neoplasms.

PURPOSE: To define an imaging risk profile in a population of patients affected by Pancreatic neuroendocrine neoplasms (PanNENs) candidates to surgery, by assessing the predictive role of 68Ga-DOTATOC and 18F-FDG PET/CT and PET/MR derived parameters in risk stratification, particularly regarding histological features of aggressive behaviour. PATIENTS AND METHODS: Retrospective study including 83 patients (53 males, 30 females; median age: 60 years, interquartile range 52-66.5), who underwent to 68Ga-DOTATOC (PET/CT: n = 77; PET/MR: n = 6) and, 68/83 patients, also to 18F-FDG PET (PET/CT: n = 65; PET/MR: n = 3) before surgery for PanNEN between 2011 and 2019, with available histological and follow-up data. The PET scans were interpreted with both qualitative (positive vs. negative) and semiquantitative measurements as follows: maximum and mean standardized uptake value (SUVmax and SUVmean) for both 18F-FDG and 68Ga-DOTATOC scans, metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) for 18F-FDG scans and somatostatin receptor density (SRD) and total lesion somatostatin receptor density (TLSRD) for 68Ga-DOTATOC PET. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of several PET parameters in predicting tumour stage or characteristic. For each PET parameter, the optimal cut-off was derived. Logistic regression analysis was used to assess if the PET parameters, categorized with the optimal cut-off values, were able to predict significantly the corresponding tumour stage or characteristic. RESULTS: Overall, 29 (35%) patients had G1, 49 (59%) a G2 and five (6%) had a G3 PanNEN. The median Ki-67 index was 4% (interquartile range: 1-8%). SRD and TLSRD significantly discriminated between pT3 or pT4 PanNEN versus pT1 or pT2, as well as 18F-FDG MTV and TLG. 68Ga-DOTATOC SUVmax was able to significantly predict the presence of distant metastases with a threshold of 51.27 (sensitivity and specificity of 85.7 and 68.1%, respectively). 18F-FDG MTV and TLG were predictors of angioinvasion. The cut-off threshold for MTV was 7.98 (sensitivity and specificity of 69.7 and 82.4%, respectively) (p = 0.0004) whereas the cut-off for TLG was 32.4 (sensitivity and specificity of 69.7% and 82.4%, respectively) (p = 0.0004). CONCLUSION: Dual tracer 68Ga-DOTATOC and 18F-FDG PET scans provide relevant information regarding tumour behaviour and aggressiveness, implementing the diagnostic preoperative work-up.

Outcomes after distal pancreatectomy for neuroendocrine neoplasms: a retrospective comparison between minimally invasive and open approach using propensity score weighting.

BACKGROUND: Pancreatic neuroendocrine neoplasms (PanNEN) are ideal entities for minimally invasive surgery. The advantage of the laparoscopic approach in terms of complications, length of stay (LOS) and cosmetic results has been previously demonstrated. However, scarce data are available on long-term oncological outcomes. Aim of this study was to compare short-term postoperative outcomes, pathological findings and long-term oncological results of minimally invasive distal pancreatectomy (MIDP) and open distal pancreatectomy (ODP) for PanNEN. METHODS: Patients who underwent ODP or MIDP for nonfunctioning PanNEN (NF-PanNEN) were retrospectively analyzed. Inverse probability of treatment weighting using propensity score was performed to compare the outcomes of MIDP and ODP. RESULTS: Overall, 124 patients were included in the study: 84 underwent OPD, whereas 40 were submitted to MIDP. The rate of high-grade postoperative complications was significantly lower in the MIDP group (p = 0.005, grade of complication with highest estimated probability 0 vs 2) and the postoperative LOS was significantly shorter after MIDP (p < 0.001, estimated days 8 versus 10). The number of examined lymph nodes (ELN) in the ODP group was significantly higher (p = 0.0036, estimated number of ELN 13 vs 10). Similar disease-free survival and overall survival were reported for the two groups (p = 0.234 and p = 0.666, respectively). CONCLUSIONS: Although MIDP for PanNEN seems to be associated with a lower number of ELN, long-term survival is not influenced by the type of surgical approach. MIDP is advantageous in terms of postoperative complications and LOS, but prospective studies are needed to confirm the overall oncological quality of resection in this group of neoplasms.

Chest CT-derived pulmonary artery enlargement at the admission predicts overall survival in COVID-19 patients: insight from 1461 consecutive patients in Italy.

OBJECTIVES: Enlarged main pulmonary artery diameter (MPAD) resulted to be associated with pulmonary hypertension and mortality in a non-COVID-19 setting. The aim was to investigate and validate the association between MPAD enlargement and overall survival in COVID-19 patients. METHODS: This is a cohort study on 1469 consecutive COVID-19 patients submitted to chest CT within 72 h from admission in seven tertiary level hospitals in Northern Italy, between March 1 and April 20, 2020. Derivation cohort (n = 761) included patients from the first three participating hospitals; validation cohort (n = 633) included patients from the remaining hospitals. CT images were centrally analyzed in a core-lab blinded to clinical data. The prognostic value of MPAD on overall survival was evaluated at adjusted and multivariable Cox's regression analysis on the derivation cohort. The final multivariable model was tested on the validation cohort. RESULTS: In the derivation cohort, the median age was 69 (IQR, 58-77) years and 537 (70.6%) were males. In the validation cohort, the median age was 69 (IQR, 59-77) years with 421 (66.5%) males. Enlarged MPAD (≥ 31 mm) was a predictor of mortality at adjusted (hazard ratio, HR [95%CI]: 1.741 [1.253-2.418], p < 0.001) and multivariable regression analysis (HR [95%CI]: 1.592 [1.154-2.196], p = 0.005), together with male gender, old age, high creatinine, low well-aerated lung volume, and high pneumonia extension (c-index [95%CI] = 0.826 [0.796-0.851]). Model discrimination was confirmed on the validation cohort (c-index [95%CI] = 0.789 [0.758-0.823]), also using CT measurements from a second reader (c-index [95%CI] = 0.790 [0.753;0.825]). CONCLUSION: Enlarged MPAD (≥ 31 mm) at admitting chest CT is an independent predictor of mortality in COVID-19. KEY POINTS: • Enlargement of main pulmonary artery diameter at chest CT performed within 72 h from the admission was associated with a higher rate of in-hospital mortality in COVID-19 patients. • Enlargement of main pulmonary artery diameter (≥ 31 mm) was an independent predictor of death in COVID-19 patients at adjusted and multivariable regression analysis. • The combined evaluation of clinical findings, lung CT features, and main pulmonary artery diameter may be useful for risk stratification in COVID-19 patients.

Hematopoietic Tumors in a Mouse Model of X-linked Chronic Granulomatous Disease after Lentiviral Vector-Mediated Gene Therapy.

Chronic granulomatous disease (CGD) is a rare inherited disorder due to loss-of-function mutations in genes encoding the NADPH oxidase subunits. Hematopoietic stem and progenitor cell (HSPC) gene therapy (GT) using regulated lentiviral vectors (LVs) has emerged as a promising therapeutic option for CGD patients. We performed non-clinical Good Laboratory Practice (GLP) and laboratory-grade studies to assess the safety and genotoxicity of LV targeting myeloid-specific Gp91phox expression in X-linked chronic granulomatous disease (XCGD) mice. We found persistence of gene-corrected cells for up to 1 year, restoration of Gp91phox expression and NADPH oxidase activity in XCGD phagocytes, and reduced tissue inflammation after LV-mediated HSPC GT. Although most of the mice showed no hematological or biochemical toxicity, a small subset of XCGD GT mice developed T cell lymphoblastic lymphoma (2.94%) and myeloid leukemia (5.88%). No hematological malignancies were identified in C57BL/6 mice transplanted with transduced XCGD HSPCs. Integration pattern analysis revealed an oligoclonal composition with rare dominant clones harboring vector insertions near oncogenes in mice with tumors. Collectively, our data support the long-term efficacy of LV-mediated HSPC GT in XCGD mice and provide a safety warning because the chronic inflammatory XCGD background may contribute to oncogenesis.

Laboratory-Scale Lentiviral Vector Production and Purification for Enhanced Ex Vivo and In Vivo Genetic Engineering.

Lentiviral vectors (LVs) are increasingly employed in gene and cell therapy. Standard laboratory production of LVs is not easily scalable, and research-grade LVs often contain contaminants that can interfere with downstream applications. Moreover, purified LV production pipelines have been developed mainly for costly, large-scale, clinical-grade settings. Therefore, a standardized and cost-effective process is still needed to obtain efficient, reproducible, and properly executed experimental studies and preclinical development of ex vivo and in vivo gene therapies, as high infectivity and limited adverse reactions are important factors potentially influencing experimental outcomes also in preclinical settings. We describe here an optimized laboratory-scale workflow whereby an LV-containing supernatant is purified and concentrated by sequential chromatographic steps, obtaining biologically active LVs with an infectious titer and specific activity in the order of 109 transducing unit (TU)/mL and 5 × 104 TU/ng of HIV Gag p24, respectively. The purification workflow removes >99% of the starting plasmid, DNA, and protein impurities, resulting in higher gene transfer and editing efficiency in severe combined immunodeficiency (SCID)-repopulating hematopoietic stem and progenitor cells (HSPCs) ex vivo, as well as reduced activation of inflammatory responses ex vivo and in vivo as compared to TU-matched, laboratory-grade vectors. Our results highlight the value of accessible purified LV production for experimental studies and preclinical testing.

Interreader variability in prostate MRI reporting using Prostate Imaging Reporting and Data System version 2.1.

OBJECTIVES: To evaluate the agreement among readers with different expertise in detecting suspicious lesions at prostate multiparametric MRI using Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. METHODS: We evaluated 200 consecutive biopsy-naïve or previously negative biopsy men who underwent MRI for clinically suspected prostate cancer (PCa) between May and September 2017. Of them, 132 patients underwent prostate biopsy. Seven radiologists (four dedicated uro-radiologists and three non-dedicated abdominal radiologists) reviewed and scored all MRI examinations according to PI-RADS v2.1. Agreement on index lesion detection was evaluated with Conger's k coefficient, agreement coefficient 1 (AC1), percentage of agreement (PA), and indexes of specific positive and negative agreement. Clinical and radiological features that may influence variability were evaluated. RESULTS: Agreement in index lesion detection among all readers was substantial (AC1 0.738; 95% CI 0.695-0.782); dedicated radiologists showed higher agreement compared with non-dedicated readers. Clinical and radiological parameters that positively influenced agreement were PSA density ≥ 0.15 ng/mL/cc, pre-MRI high risk for PCa, positivity threshold of PI-RADS score 4 + 5, PZ lesions, homogeneous signal intensity of the PZ, and subjectively easy interpretation of MRI. Positive specific agreement was significantly higher among dedicated readers, up to 93.4% (95% CI 90.7-95.4) in patients harboring csPCa. Agreement on absence of lesions was excellent for both dedicated and non-dedicated readers (respectively 85.1% [95% CI 78.4-92.3] and 82.0% [95% CI 77.2-90.1]). CONCLUSIONS: Agreement on index lesion detection among radiologists of various experiences is substantial to excellent using PI-RADS v2.1. Concordance on absence of lesions is excellent across readers' experience. KEY POINTS: • Agreement on index lesion detection among radiologists of various experiences is substantial to excellent using PI-RADS v2.1. • Concordance between experienced readers is higher than between less-experienced readers. • Concordance on absence of lesions is excellent across readers' experience.

Psychological Aspects Associated With Fertility Preservation in Oncology: An Exploratory Study.

OBJECTIVE: Gonadotoxicity is considered one of the most distressing side effects of cancer treatment. Although fertility preservation can be a valid solution, it also involves a challenging process. A clear understanding of the features of women who decide to pursue fertility preservation after cancer diagnosis is missing. The purpose of the present study was therefore to analyze the personality profile of female patients referred to oncofertility prior to gonadotoxic treatment. METHODS: Fifty-two female cancer patients took part in the study. The Temperament and Character Inventory-Revised (TCI-R), the Response Evaluation Measure-71 (REM-71), the Beck Depression Inventory (BDI-II), and the State-Trait Anxiety Inventory-Y Form (STAI-Y) were administered to examine personality characteristics, defense mechanisms, depression and anxiety symptoms. RESULTS: Compared with reference data of the Italian population, our sample reported significantly lower scores in Harm Avoidance and trait anxiety, and significantly higher levels of mature defense mechanisms. Most of the patients reported low scores in immature defense mechanisms, depression, and trait anxiety, and medium scores in state anxiety. CONCLUSIONS: Our findings suggest that these women display functional personality traits and defensive style, in association with low levels of depression and trait anxiety. These features may enable a proactive attitude to cancer and the ability to make long-term plans. This may favor psychological adjustment to cancer and a projection toward the future.

The size of well differentiated pancreatic neuroendocrine tumors correlates with Ki67 proliferative index and is not associated with age.

BACKGROUND: Concerns exist about a conservative management of well-differentiated nonfunctioning small pancreatic neuroendocrine tumors (NF-PanNET) in young patients and when preoperative Ki67 proliferative index is ≥3%. AIM: To evaluate an association between age, tumor size and grading in patients with sporadic NF-PanNET who underwent curative resection. METHODS: Patients who underwent surgery for sporadic NF-PanNET (excluding G3) were retrospectively analyzed. Linear regression analysis was performed to evaluate a possible correlation between continuous variables, whereas multiple logistic regression analysis was performed for determining predictors of NF-PanNET-G2. RESULTS: Overall, 235 patients with NF-PanNET-G1/G2 were included. The median largest radiological diameter was 25 mm. Age correlated neither with tumor size (P = 0.675) nor with Ki67 index (P = 0.376). On multivariate linear regression analysis, factors independently associated with Ki67 index were NF-PanNET size (P = 0.031), perineural invasion (P = 0.004), microvascular invasion (P = 0.001) and necrosis (P = 0.009). The most accurate NF-PanNET size for predicting NF-PanNET-G2 was 25 mm. On multivariate analysis, a NF-PanNET size >25 mm was independently associated with the risk of having a PanNET-G2 (P = 0.025). CONCLUSION: No correlations exist between age and NF-PanNET size or proliferative index. Therefore, an a priori aggressive attitude is not justified in young patients with small NF-PanNET, as a long-life expectancy is probably unlikely to increase the risk of malignant transformation.

Assessment of Remote Myocardium Heterogeneity in Patients with Ventricular Tachycardia Using Texture Analysis of Late Iodine Enhancement (LIE) Cardiac Computed Tomography (cCT) Images.

PURPOSE: Diffuse remodeling of myocardial extra-cellular matrix is largely responsible for left ventricle (LV) dysfunction and arrhythmias. Our hypothesis is that the texture analysis of late iodine enhancement (LIE) cardiac computed tomography (cCT) images may improve characterization of the diffuse extra-cellular matrix changes. Our aim was to extract volumetric extracellular volume (ECV) and LIE texture features of non-scarred (remote) myocardium from cCT of patients with recurrent ventricular tachycardia (rVT), and to compare these radiomic features with LV-function, LV-remodeling, and underlying cardiac disease. PROCEDURES: Forty-eight patients suffering from rVT were prospectively enrolled: 5/48 with idiopathic VT (IVT), 23/48 with post-ischemic dilated cardiomyopathy (ICM), 9/48 with idiopathic dilated cardiomyopathy (IDCM), and 11/48 with scars from a previous healed myocarditis (MYO). All patients underwent echocardiography to assess LV systolic and diastolic function and cCT with pre-contrast, angiographic, and LIE scan to obtain end-diastolic volume (EDV), ECV, and first-order texture parameters of Hounsfield Unit (HU) of remote myocardium in LIE [energy, entropy, HU-mean, HU-median, standard deviation (SD), and mean absolute deviation (MAD)]. RESULTS: Energy, HU mean, and HU median by cCT texture analysis correlated with ECV (rho = 0.5650, rho = 0.5741, rho = 0.5068; p < 0.0005). cCT-derived ECV, HU-mean, HU-median, SD, and MAD correlated directly to EDV by cCT and inversely to ejection fraction by echocardiography (p < 0.05). SD and MAD correlated with diastolic function by echocardiography (rho = 0.3837, p = 0.0071; rho = 0.3330, p = 0.0208). MYO and IVT patients were characterized by significantly lower values of SD and MAD when compared with ICM and IDCM patients, independently of LV-volume systolic and diastolic function. CONCLUSIONS: Texture analysis of LIE may expand cCT capability of myocardial characterization. Myocardial heterogeneity (SD and MAD) was associated with LV dilatation, systolic and diastolic function, and is able to potentially identify the different patterns of structural remodeling characterizing patients with rVT of different etiology.

[Quality of life and chemotherapy: predictive factors in a sample of gynaecological cancer patients.] / Qualità di vita e trattamenti chemioterapici: fattori predittivi in un campione di pazienti con tumori ginecologici.

INTRODUCTION: Diagnosis and treatment of gynaecological cancer still entail significant impairment in quality of life. The present study aims at monitoring it during chemotherapy treatment and at identifying variables significantly associated with it. METHODS: 87 patients who attended the San Raffaele Hospital completed the EORTC QLQ-C30 and the Multidimensional Scale of Perceived Social Support before their first and third chemotherapy infusion. A self-report questionnaire was created in order to collect socio-demographic and medical information. RESULTS: Social and emotional functioning and global quality of life show a significant improvement between the first and third chemotherapy infusion; age and perceived social support appear significantly associated with emotional functioning. A chemotherapy regimen with medium or high emetogenic potential and having a full-time job predict an improvement over time in global quality of life and role functioning, respectively. DISCUSSION: These variables should be taken into consideration in patients care, in order to detect potential difficulties and promote a better adjustment to the disease and its treatment.

Cardiac CT With Delayed Enhancement in the Characterization of Ventricular Tachycardia Structural Substrate: Relationship Between CT-Segmented Scar and Electro-Anatomic Mapping.

OBJECTIVES: This study sought to compare myocardial scars depicted by computed tomography (CT) with electrical features from electro-anatomic mapping (EAM), assessing the potential role of CT integration in ventricular tachycardia (VT) and radiofrequency catheter ablation (RFCA) procedures. BACKGROUND: Imaging-based characterization of VT myocardial substrate is required to plan EAM and, potentially, to guide RFCA. METHODS: Forty-two consecutive patients, 35 of whom had implantable cardioverter-defibrillator, all referred for VT RFCA, underwent pre-procedural CT including an angiographic and a 10-min delayed-enhancement scan. Segmental comparison between scars segmented from CT and low voltages (bipolar voltages <1.5 mV; unipolar voltages <8 mV), late potentials, and RF ablation points on EAM, was carried out. In a subset of 16 consecutive patients, a further point-by-point analysis was performed: a CT-derived 3-dimensional structure including heart anatomy and myocardial scars was integrated with EAM for quantitative comparison. RESULTS: CT scans identified scars in 39 patients and defined left ventricular wall involvement and mural distribution. Overall segmental concordance between CT and EAM was good (κ = 0.536) despite the presence of implantable cardioverter-defibrillator, scar etiologies, and mural distribution. CT identified segments characterized by low voltages with good sensitivity (76%), good specificity (86%), and very high negative predictive value (95%). Late potentials and RF ablation points fell on scarred segments identified from CT in 79% and 81% of cases, respectively. Point-by-point quantitative comparison revealed good correlation between the average area of scar detected at CT and at bipolar mapping (CT = 4,901 mm(2), bipolar voltages-EAM = 4,070 mm(2); R = 0.78; p < 0.0001). In this study, 70% and 84% of low-amplitude bipolar points were mapped at a maximum distance of 5 mm and 10 mm from CT-segmented scar, respectively. CONCLUSIONS: CT with delayed-enhancement provides a 3-dimensional characterization of VT scar substrate together with a detailed anatomic model of the heart. This information may offer assistance to plan EAM and RFCA procedures and is potentially suitable for EAM-imaging integration.