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Background & Aims: The prevalence and clinical significance of vitamin B12 alterations in patients with cancer are poorly understood. We aimed to assess the prevalence and risk factors of vitamin B12 depletion or hypervitaminosis in patients with cancer., Methods: We retrospectively included hospitalised patients with cancer in 2017-2022. Plasma B12 levels were stratified as very low (VL, <200 pg/ml), low (L, 200-299 pg/ml), normal (N, 300-812 pg/ml), or high (H, ≥813 pg/ml). We collected demographic and several clinical data (e.g., comorbidities, nutritional status, ECOG-PS, cancer site and stage). Univariate and multivariate analyses for factors associated to the vitamin B12 status were fitted., Results: 788 patients (F/M ratio 1.05, median age 72 years, [25th, 75th percentiles 62, 78 years]) were included. Vitamin B12 was VL in 14.1%, L in 19.4%, N in 49.4%, and H in 17.1% cases. Vitamin B12 distribution increased significantly as function of ECOG-PS levels. Patients with breast cancer were characterized by the highest median B12 value, while colorectal cancer patients by the lowest. Vitamin B12 was also significantly higher in advanced compared to early-stage patients as well as in those who had liver failure. Multivariate analysis showed that the probability of H vs. VL B12 levels was significantly increased in patients with hypoproteinemia, hypo-prealbuminemia, and ECOG-PS≥2, and decreased in those with colorectal and gastric cancer., Conclusion: Vitamin B12 impairment is common in cancer patients. Increased vitamin B12 is associated with an impaired clinical status, while vitamin B12 depletion is more common in early-stage cancer and in elderly patients., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A reliable preclinical model of patient-derived organoids (PDOs) was developed in a case study of a 69-year-old woman diagnosed with breast cancer (BC) to investigate the tumour evolution before and after neoadjuvant chemotherapy and surgery. The results were achieved due to the development of PDOs from tissues collected before (O-PRE) and after (O-POST) treatment., Methods: PDO cultures were characterized by histology, immunohistochemistry (IHC), transmission electron microscopy (TEM), scanning electron microscopy (SEM), confocal microscopy, flow cytometry, real-time PCR, bulk RNA-seq, single-cell RNA sequencing (scRNA-seq) and drug screening., Results: Both PDO cultures recapitulated the histological and molecular profiles of the original tissues, and they showed typical mammary gland organization, confirming their reliability as a personalized in vitro model. Compared with O-PRE, O-POST had a greater proliferation rate with a significant increase in the Ki67 proliferation index. Moreover O-POST exhibited a more stem-like and aggressive phenotype, with increases in the CD24 low /CD44 low and EPCAM low /CD49f high cell populations characterized by increased tumour initiation potential and multipotency and metastatic potential in invasive lobular carcinoma. Analysis of ErbB receptor expression indicated a decrease in HER-2 expression coupled with an increase in EGFR expression in O-POST. In this context, deregulation of the PI3K/Akt signalling pathway was assessed by transcriptomic analysis, confirming the altered transcriptional profile. Finally, transcriptomic single-cell analysis identified 11 cell type clusters, highlighting the selection of the luminal component and the decrease in the number of Epithelial-mesenchymal transition cell types in O-POST., Conclusion: Neoadjuvant treatment contributed to the enrichment of cell populations with luminal phenotypes that were more resistant to chemotherapy in O-POST. PDOs represent an excellent 3D cell model for assessing disease evolution., (© 2024. The Author(s).)

Despite the advent of numerous targeted therapies in clinical practice, anthracyclines, including doxorubicin (DOX), continue to play a pivotal role in breast cancer (BC) treatment. DOX directly disrupts DNA replication, demonstrating remarkable efficacy against BC cells. However, its non-specificity toward cancer cells leads to significant side effects, limiting its clinical utility. Interestingly, DOX can also enhance the antitumor immune response by promoting immunogenic cell death in BC cells, thereby facilitating the presentation of tumor antigens to the adaptive immune system. However, the generation of an adaptive immune response involves highly proliferative processes, which may be adversely affected by DOX-induced cytotoxicity. Therefore, understanding the impact of DOX on dividing T cells becomes crucial, to deepen our understanding and potentially devise strategies to shield anti-tumor immunity from DOX-induced toxicity. Our investigation focused on studying DOX uptake and its effects on human lymphocytes. We collected lymphocytes from healthy donors and BC patients undergoing neoadjuvant chemotherapy (NAC). Notably, patient-derived peripheral blood mononuclear cells (PBMC) promptly internalized DOX when incubated in vitro or isolated immediately after NAC. These DOX-treated PBMCs exhibited significant proliferative impairment compared to untreated cells or those isolated before treatment initiation. Intriguingly, among diverse lymphocyte sub-populations, CD8 + T cells exhibited the highest uptake of DOX. To address this concern, we explored a novel DOX formulation encapsulated in ferritin nanocages (FerOX). FerOX specifically targets tumors and effectively eradicates BC both in vitro and in vivo. Remarkably, only T cells treated with FerOX exhibited reduced DOX internalization, potentially minimizing cytotoxic effects on adaptive immunity.Our findings underscore the importance of optimizing DOX delivery to enhance its antitumor efficacy while minimizing adverse effects, highlighting the pivotal role played by FerOX in mitigating DOX-induced toxicity towards T-cells, thereby positioning it as a promising DOX formulation. This study contributes valuable insights to modern cancer therapy and immunomodulation., (© 2024. The Author(s).)

Background: Breast cancer is the most frequent tumour worldwide, and the HR + /HER2 - subtype is the most common. For this tumour type, endocrine therapy (ET) is the mainstay of treatment. The association of ET and CDK4/6 inhibitors (CDK4/6i) represents the gold standard for first-line or second-line therapies. However, the optimal therapeutic strategy after CDK4/6i progression is still a matter of debate, with several randomized clinical trials still ongoing., Patients and Methods: This is an observational, prospective, real-world study including women with HR + /HER2 - metastatic breast cancer progressing to palbociclib plus ET. Patients received either ET or chemotherapy (CT). The primary objective was the evaluation of efficacy of the different therapeutic strategies after palbociclib in terms of median progression-free survival 2. Secondary objectives were the activity of therapeutic strategies measured with the clinical benefit rate, evaluation of the parameters used for the treatment choice, and progression-free survival 1 related to palbociclib plus ET treatment., Results: Overall, 48 patients (median age 53, range 33-78 years) were included. The median progression-free survival 2 was of 5 months in the overall cohort (95% CI 4-48 months) with a statistically significant difference between the two therapeutic strategies adopted (ET versus CT, 10 months versus 5 months, respectively). Regarding secondary objectives, the clinical benefit rate was 55.2% in the CT cohort and 50% in ET. Moreover, women treated with CT had a greater number of visceral metastases and a shorter median progression-free survival 1 than patients who received ET., Conclusions: ET and CT represent two possible therapeutic alternatives for patients progressing on CDK4/6i plus ET. The choice is based on clinical parameters, with a potential preference for ET., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/11/dic.2023-7-5-COI.pdf, (Copyright © 2024 Palumbo R, Quaquarini E, Saltalamacchia G, Malovini A, Lapidari P, Tagliaferri B, Mollica L, Teragni CM, Barletta C, Locati LD, Sottotetti F.)

Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings., Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients., Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units., Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR., Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51-0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44-0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients ( n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)-/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12-0.83; p = 0.02) and ER-/HER2- (OR = 0.41; 95% CI, 0.17-0.97; p = 0.04) BC patients., Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC., Registration: Eudract number NCT05798806., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Background: Advanced breast cancer (ABC) is characterized by multidimensional clinical complexity that is usually not considered in randomized clinical trials. In the present real-life study, we investigated the link between clinical complexity and quality of life of patients with HR + /HER2 - ABC treated with CDK4/6 inhibitors., Methods: We evaluated multimorbidity burden assessed with the Cumulative Illness Rating Scale (CIRS), polypharmacy and patient-reported outcomes (PROs). PROs were assessed at baseline (T0), after 3 months of therapy (T1), and at disease progression (T2) using EORTC QLC-C30 and QLQ-BR23 questionnaires. Baseline PROs and changes between T0 and T1 were evaluated amongst patients with different multimorbidity burden (CIRS <5 and ≥5) and polypharmacy (<2 or ≥2 drugs)., Results: From January 2018 to January 2022, we enrolled 54 patients (median age 66 years, IQR 59-74). The median CIRS score was 5 (IQR 2-7), whilst the median number of drugs taken by patients was 2 (IQR 0-4). No changes in QLQ-C30 final scoring between T0 and T1 were observed in the overall cohort ( p =0.8944). At T2, QLQ-C30 global score deteriorated with respect to baseline ( p =0.0089). At baseline, patients with CIRS ≥5 had worse constipation than patients without comorbidities ( p <0.05) and a lower trend in the median QLQ-C30 global score. Patients on ≥2 drugs had lower QLQ-C30 final scores and worse insomnia and constipation ( p <0.05). No change in QLQ-C30 final score from T0 to T1 was observed ( p >0.05)., Conclusion: Multimorbidity and polypharmacy increase the clinical complexity of patients with ABC and may affect baseline PROs. The safety profile of CDK4/6 inhibitors seems to be maintained in this population. Further studies are needed to assess clinical complexity in patients with ABC.This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special&#95;issues/tackling-clinical-complexity-in-breast-cancer/., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this article. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/05/dic.2023-1-7-COI.pdf, (Copyright © 2023 Tagliaferri B, Mollica L, Palumbo R, Leli C, Malovini A, Terzaghi M, Quaquarini E, Teragni C, Maccarone S, Premoli A, Sottotetti F.)

Tumour markers have no established role in the monitoring of the course of metastatic breast cancer during antineoplastic therapy, yet cancer antigen 15.3 (CA15.3) and carcinoembryonic antigen (CEA) are commonly used in clinical practice to aid in the early detection of progression of disease (PD). In our multicentre, prospective, real-life study, we enrolled 142 consecutive patients with advanced breast cancer receiving endocrine therapy in combination with a CDK4/6 inhibitor from January 2017 to October 2020; 75 patients had PD at the time of database closure. We measured serum marker concentrations at regular 4-month intervals together with radiological tumour response assessments and in cases of clinical suspicion of PD. Appropriate descriptive and inferential statistical methods were used to analyse serum marker level trends amongst prespecified subgroups and at specific time points (baseline, best radiologically documented tumour response and first detection of PD) in the subpopulation of patients with PD at the time of database closure. Notably, the median time from treatment initiation to best tumour response was 4.4 months. We evaluated the presence of an association between baseline CA15.3 and CEA levels and prespecified clinical characteristics but found no clinically meaningful correlation. We assessed marker level variations at the time of best radiologically documented disease response and PD: in the subgroup of patients who responded to treatment before progressing, we detected a statistically significant correlation with tumour marker variation between the time of best response and progression; this finding was not confirmed in the subgroup of patients that did not benefit from treatment. In conclusion, serum tumour marker flares can be useful in the early diagnosis of PD but should not be used as the sole factor prompting a change in treatment strategy without radiological confirmation., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2022/08/dic.2022-1-3-COI.pdf, (Copyright © 2022 Sottotetti F, Ferraris E, Tagliaferri B, Palumbo R, Quaquarini E, Teragni C, Balletti E, Leli C, Premoli A, Mollica L, Puglisi S, Sardi S, Malovini A, Pedrazzoli P, Bernardo A.)

Introduction: Immune checkpoint inhibitors (ICIs) have become the standard of treatment for patients with non-small cell lung cancer (NSCLC). However, there are still many uncertainties regarding the selection of the patient who could benefit more from this treatment. This study aims to evaluate the prognostic and predictive role of clinical and biological variables in unselected patients with advanced NSCLC candidates to receive ICIs., Methods: This is an observational and prospective study. The primary objective is the evaluation of the relationship between clinical and biological variables and the response to ICIs. Secondary objectives included: safety; assessment of the relationship between clinical and biological parameters/concomitant treatments and progression-free survival at 6 months and overall survival at 6 and 12 months. Nomograms to predict these outcomes have been generated., Results: A total of 166 patients were included. An association with response was found in the presence of the high immunohistochemical PD-L1 expression, squamous cell histotype, and early line of treatment, whereas a higher probability of progression was seen in the presence of anemia, high LDH values and neutrophil/lymphocyte ratio (NLR), pleural involvement, and thrombosis before treatment. The nomogram showed that anemia, PD-L1 expression, NLR, and LDH represented the most informative predictor as regards the three parameters of interest., Conclusions: In the era of personalized medicine, the results are useful for stratifying the patients and tailoring the treatments, considering both the histological findings and the clinical features of the patients.

Purpose: The most appropriate therapy for HR + /HER2-positive (HER2 +) advanced breast cancer (ABC) is a matter of debate. Co-targeting of both receptors represents an attractive strategy to overcome the cross-talk between them., Methods: The HERMIONE 9 is an observational retrospective multicentric study which aimed to describe the clinical outcome of patients with HR + /HER2 + ABC who received the combination of Fulvestrant (F) and Trastuzumab (T) as part of their routine treatment at 10 Italian Institutions., Results: Eighty-seven patients were included. Median age was 63 (range, 35-87) years. The median number of previous treatments was 3 (range, 0-10) and F and T were administered as ≥ 3rd line in 67 patients. Among the 86 evaluable patients, 6 (6.9%) achieved CR, 18 (20.7%) PR, and 44 (50.6%) had SD ≥ 24 weeks with an overall CBR of 78.2%. At a median follow-up of 33.6 months, mPFS of the entire cohort was 12.9 months (range, 2.47-128.67). No difference was observed in mPFS between patients treated after progression or as maintenance therapy (mPFS 12.9 and 13.9 months in 64 and 23 patients, respectively), neither considering the number of previous treatment lines (≤ 3 or < 3)., Conclusion: The combination of F and T was active in this cohort at poor prognosis and deserves further investigations possibly in combination with pertuzumab in patients with high ER expression., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 c ases were included between March and September 2020. The median age was 68 years; 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12-218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32-2.15); however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11-0.51, p < 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials., Patients and Methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B)., Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47-79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6-32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively., Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2- MBC, also suggesting a better performance of the combinations in earlier treatment lines., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Background: Progesterone receptor (PgR) negative breast cancer (BC) is an aggressive subtype with poor prognosis and reduced response to endocrine treatments. Several studies have suggested that androgen receptor (AR) expression is associated with a favorable tumor biology, longer recurrence free survival (RFS), and overall survival. In the literature no data exist regarding the role of AR expression in early stage estrogen receptor (ER)+/PgR- BCs. The aim of this study was to evaluate the prognostic role of AR expression in this setting., Patients and Methods: This is a monocentric retrospective study in which 208 patients who underwent surgical intervention for ER+/PgR-/Human Epidermal growth factor Receptor 2 (HER2)- BC were included. The primary objective was to analyze the relationship between AR expression and RFS., Results: At a median follow-up of 77 months, 75 patients (36%) had a disease relapse (all sites included). AR expression was significantly higher in patients who did not relapse compared with those who relapsed with an impact on RFS (hazard ratio [HR] = 0.99, p  = 0.025). Patients with AR expression ⩾80% had a lower risk of relapse compared with those with AR <80% (HR = 0.53, p  = 0.008). In addition, breast tumors with higher AR expression had good biological features (low ki67 and nuclear grade) compared with BCs with lower AR expression, at least partly explaining the different outcome., Conclusions: The results of this study support the potential prognostic role of AR in patients with ER+/PgR- BCs and may contribute to the identification of subgroups of high-risk patients., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

The purpose of this review is to summarize the background and latest evidence for the use of palbociclib, an oral, first-in-class, highly selective cyclin-dependent kinase 4/6 inhibitor, in advanced breast cancer, with a focus on some of the unanswered questions about the performance of this agent in clinical practice. The available clinical data from both controlled clinical trials and real-life experiences concerning palbociclib-based combinations in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic disease, including patient-reported outcomes and subgroup analyses, have been reviewed and discussed. Palbociclib significantly improved progression-free survival and clinical benefit rates when added to letrozole in postmenopausal women as initial endocrine-based therapy, and it prolonged progression-free survival and overall survival when added to fulvestrant in women who progressed on previous endocrine therapy in randomized clinical trials. Tolerability profile was manageable, with neutropenia occurring most commonly, without detrimental impact on quality of life. Available data from real-life experiences confirm the good performance of palbociclib in unselected, heavily pretreated populations. Palbociclib in combination with endocrine therapy is a valuable emerging option for patients with HR+/HER2- advanced or metastatic breast cancer. Further investigation is needed to provide solutions for palbociclib resistance and to identify the best sequence to use for the best patient benefit with a minimal toxicity., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at http://www.drugsincontext.com/wp-content/uploads/2019/06/dic.212579-COI.pdf

Background: Fulvestrant 500 mg (F500) is the most active endocrine single agent in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). Few data are available regarding the effectiveness of the drug in a real-world setting., Patients and Methods: This prospective, multicenter cohort study aimed to describe the patterns of treatment and performance of F500 in a large population of unselected women with MBC, focusing on potential prognostic or predictive factors for disease outcome and response. The primary endpoints were progression-free survival (PFS) and clinical benefit rate., Results: From January 2011 to December 2015, 490 consecutive patients treated with F500 were enrolled. Overall, three different cohorts were identified and analyzed: the first received F500 after progression from previous chemotherapy (CT) or endocrine therapy; the second received the drug for de novo metastatic disease; and the third was treated as maintenance following disease stabilization or a response from a previous CT line. Median overall survival (OS) in the whole population was 26.8 months, ranging from 32.4 in first line to 22.0 and 13.7 months in second line and subsequent lines, respectively. Both the presence of liver metastasis and the treatment line were significantly associated with a worse PFS, while only the presence of liver metastasis maintained its predictive role for OS in multivariate analysis., Conclusions: The effectiveness of F500 was detected in patients treated both upon disease progression and as maintenance. The relevant endocrine sensitivity of 80% of patients included in the study could probably explain the good results observed in terms of outcome., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Introduction: Vinflunine is a microtubule inhibitor approved in Europe as second-line treatment of advanced transitional cell cancer of the urothelium (TCCU). The inability to continue with a first-line platinum-based regimen beyond 6 cycles suggested investigating the use of vinflunine as switch maintenance therapy in patients with response or stable disease after first-line therapy., Methods: Patients with advanced TCCU and documented disease control after 3-6 cycles of first-line platinum-based chemotherapy received vinflunine maintenance therapy within 6 weeks of the last cycle. Our analysis aimed to examine the performance of vinflunine in terms of activity and safety in such a patient population., Results: 28 consecutive patients were studied. After a median follow-up of 25 months, vinflunine was associated with a median progression-free survival of 9 months (range 4 to > 16 months) and a disease control rate of 64%; median overall survival was not reached. Treatment was well tolerated, with no unexpected safety events. The most common adverse events of grade ≥ 3 were neutropenia (21%) and constipation (14%); no toxicity-related death occurred., Conclusions: Our results suggest that vinflunine may be a suitable maintenance treatment option for TCCU patients who received a maximum of 6 cycles of platinum-based chemotherapy commonly used as first-line treatment., (© 2018 S. Karger GmbH, Freiburg.)

Throughout childhood, various developmental phenomena influence the cough reflex. Among these are the modifications in the anatomy and functions of the respiratory tract and the central and peripheral nervous systems. Moreover, after birth, the immunological response undergoes progressive transformations with the acquisition of immune memory processes. These conditions make infections and airway abnormalities the overwhelming cause of chronic cough in children and infants. In children, chronic cough should be treated on the basis of etiology. The aim of this article is to provide thorough research and analysis of the medical literature published up to 2014 on chronic cough in children as a disease entity, including the epidemiologic, etiologic, diagnostic, prognostic, and therapeutic aspects. Our results demonstrate differences in the definition of chronic cough, the characteristics of diagnostic procedures, study settings, and prevalence of the main causes. However, few studies regarding epidemiology and the quality of life have been reported. Many therapeutic approaches that are considered effective in adults with chronic cough seem to be less efficient in children. Regardless of the setting, whether pediatric or non-pediatric, children with chronic cough should be carefully evaluated using child-specific protocols and algorithms. Awareness of the various pathophysiological conditions associated with chronic cough is vital for making a correct diagnosis and providing appropriate treatment. The prevalence of the different causes of chronic cough depends on various issues. Among these are the population under consideration and its age range, infectious disease control and prevention, the diagnostic procedures employed, disease definition criteria, and the local health system. Clinical guidelines for the management of children with chronic cough should take these components into consideration. Further clinical and basic research studies are still needed for better diagnosis, treatment, and prevention of chronic cough in children.

Background: A prospective, multicenter trial was undertaken to assess the activity, safety, and quality of life of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer (MBC)., Patients and Methods: Fifty-two women with HER2-negative MBC who were candidates for second-line chemotherapy for the metastatic disease were enrolled and treated at three centers in Northern Italy. All patients had previously received taxane-based chemotherapy in the adjuvant or first-line metastatic setting. Single-agent nab-paclitaxel was given at the dose of 260 mg/m(2) as a 30-minute intravenous infusion on day 1 each treatment cycle, which lasted 3 weeks, in the outpatient setting. No steroid or antihistamine premedication was provided. Treatment was stopped for documented disease progression, unacceptable toxicity, or patient refusal., Results: All of the enrolled patients were evaluable for the study endpoints. The objective response rate was 48% (95% CI, 31.5%-61.3%) and included complete responses from 13.5%. Disease stabilization was obtained in 19 patients and lasted >6 months in 15 of them; the overall clinical benefit rate was 77%. The median time to response was 70 days (range 52-86 days). The median progression-free survival time was 8.9 months (95% CI, 8.0-11.6 months, range 5-21+ months). The median overall survival point has not yet been reached. Toxicities were expected and manageable with good patient compliance and preserved quality of life in patients given long-term treatment., Conclusion: Our results showed that single-agent nab-paclitaxel 260 mg/m(2) every 3 weeks is an effective and well tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC patients, and that it produced interesting values of objective response rate and progression-free survival without the concern of significant toxicity. Specifically, the present study shows that such a regimen is a valid therapeutic option for that 'difficult to treat' patient population represented by women who at the time of disease relapse have already received the most active agents in the adjuvant and/or metastatic setting (ie, conventional taxanes).

A digital pursuit rotor was used to monitor oral reading costs by time-locking tracking performance to the auditory wave form produced as young and older adults were reading out short paragraphs. Multilevel modeling was used to determine how paragraph-level predictors of length, grammatical complexity, and readability and person-level predictors such as speaker age or working memory capacity predicted reading and tracking performance. In addition, sentence-by-sentence variation in tracking performance was examined during the production of individual sentences and during the pauses before upcoming sentences. The results suggest that dual tasking has a greater impact on older adults' reading comprehension and tracking performance. At the level of individual sentences, young and older adults adopt different strategies to deal with grammatically complex and propositionally dense sentences.

The outcome of patients with metastatic breast cancer (MBC) has clearly improved over the past decades and the proportion of women living with their disease for several years is increasing. However, the usefulness of multiple lines of treatment is still debated and under evaluation. The available data from both randomized trials and large retrospective series are reviewed and discussed in order to analyze management practices, with emphasis on potential prognostic and predictive factors for clinical outcome. At present, evidence-based medicine provides some support for the use of second-line and to a lesser degree and in selected cases, third-line chemotherapy in human epidermal growth factor receptor 2 (HER2) negative MBC. Beyond third-line treatment, messages from recently reported retrospective studies also suggest a clear potential gain for women receiving further therapies after disease progression, since each line can contribute to a longer survival. In HER2-positive disease, the data from observational and retrospective studies support a clinical benefit from the use of trastuzumab beyond disease progression and emerging evidences from randomized controlled trials are leading to the introduction of newer HER2-targeted therapies in multiple lines. The question 'How many lines of treatment should we give patients?' clearly needs further research through prospective, high-quality clinical trials, aiming for a better definition of factors with prognostic and predictive role. In the meantime, the 'optimal' treatment strategy should probably be to use as many therapeutic options as possible, either in sequence or combination, to keep the best efficacy/toxicity balance, considering MBC as a chronic disease.

Background: The purpose of this study was to assess the activity and safety of the combination of vinorelbine (VNR) and capecitabine (CAP) as first-line treatment in HER2-negative (HER(-)) metastatic breast cancer (MBC)., Patients and Methods: Patients (42) enrolled in trial A received intravenous (i.v.) VNR 25 mg/m2 on days 1 and 8 of a 21-day cycle combined with CAP 1000 mg/m2 twice daily for 14 consecutive days followed by 1 week of rest. Trial B (46 patients) followed trial A when the oral formulation of VNR became available at our institution. Patients received oral VNR (60 mg/m(2) on days 1-8) combined with the same CAP schedule as in trial A., Results: The response rate (RR) in trial A was 73.2% (95% confidence interval [CI], 56.4-82.8), including 12.2% complete responses (CRs). Clinical benefit was achieved in 78% of patients (95% CI, 63.2-87.9). In trial B, overall RR was 76% (95% CI, 62.0-86.0), with 13% CRs and clinical benefit of 80.4% (95% CI, 66.8-89.3). In trial A, median progression-free survival (PFS) was 8.2 months (range, 6-14+ months) and median overall survival (OS) was 32.4 months (range, 17-36+ months). In trial B, median PFS and OS were 8.8 months (range, 8-21+ months) and 34.3 months (14-39+ months), respectively. Treatment-related toxicity was manageable. Quality of life assessment showed a statistically significant difference regarding body image (p = .001), sexual functioning (p = .02), and future perspectives (p = .03) in women receiving chemotherapy fully by the oral route., Conclusion: This joint analysis shows that both tested schedules can produce high objective RRs with encouraging PFS, manageable toxicity profile, and suggested benefit on some aspects of quality of life for the fully oral combination., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Sorafenib is the only therapy approved for advanced hepatocellular carcinoma no longer eligible for transcatheter arterial chemoembolization. Hepatic intra-arterial chemotherapy has been shown to be an effective and safe therapy for advanced hepatocellular carcinoma. Cetuximab has been administered intravenously to patients with advanced hepatocellular carcinoma, showing encouraging results in terms of its safety and toxicity profile., Aim: Our purpose was to evaluate the safety and feasibility of hepatic arterial chemotherapy with cetuximab, cisplatin and 5-fluoruracil for patients with advanced hepatocellular carcinoma, not responsive or not eligible for sorafenib therapy., Patients and Methods: From January 2010 to January 2011, 12 patients received a 2-day course of chemotherapy consisting of repeated daily hepatic arterial administration of 20 mg of cisplatin as 2-h infusion, 5-fluorouracil at 500 mg/m(2) as 5-h infusion and cetuximab 500 mg/m(2) as 12-h infusion. Cycles were repeated every 14 days., Results: After a mean of four months of therapy, computed tomography revealed five partial responses, five cases of stable disease and two of progressive disease. The toxicity profile was favourable, with no G4 gastrointestinal, hematologic or skin side-effects, or severe deterioration of liver function., Conclusion: Hepatic intra-arterial chemotherapy with cetuximab is a safe and feasible treatment for advanced hepatocellular carcinoma, with promising results in patients with initial poor prognosis.

Objective: To assess age differences in the costs of language planning and production., Methods: A controlled sentence production task was combined with digital pursuit rotor tracking. Participants were asked to track a moving target while formulating a sentence using specified nouns and verbs and to continue to track the moving target while producing their response. The length of the critical noun phrase (NP) as well as the type of verb provided were manipulated., Results: The analysis indicated that sentence planning was more costly than sentence production, and sentence planning costs increased when participants had to incorporate a long NP into their sentence. The long NPs also tended to be shifted to the end of the sentence, whereas short NPs tended to be positioned after the verb. Planning or producing responses with long NPs was especially difficult for older adults, although verb type and NP shift had similar costs for young and older adults., Discussion: Pursuit rotor tracking during controlled sentence production reveals the effects of aging on sentence planning and production.

Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

Background: Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC) and for adequate preservation of liver function. Although considered relatively safe, TACE has been associated with several complications. The aim of this study was to determine the prevalence of the complications associated with TACE therapy and to correlate it with certain risk factors, either well-known or not yet evaluated., Patients and Methods: A total of 330 chemoembolization procedures performed in 170 patients (117 males and 53 females) over a period of 64 months were retrospectively analysed. Among the patients, 123 had hepatocellular carcinoma, 10 had intrahepatic cholangiocarcinoma and 37 had hepatic metastases. The variables considered were: tumour histotype, bilioenteric anastomosis, previous or combined treatment with radiofrequency thermal ablation, antibiotic prophylaxis, chemotherapeutic agents, use of new drug-eluting microspheres, comorbidities such as diabetes, patient age and the presence of vascular anatomical variations., Results: A total of 30 complications occurred in 27 procedures. The total complication rate per procedure was 9.1% and approximately 75% of patients had postembolization syndrome. The difference in the prevalence of complications was statistically significant in the group of diabetic patients (13.3%) compared to the remaining patients (6.3%) (p = 0.002) and in patients with biliary stents (25%) compared to those without stents (7.75%) (p = 0.027)., Conclusion: These data show that diabetes mellitus and the presence of bilioenteric anastomosis are risk factors for developing complications after TACE. The use of new drug-eluting microspheres did not increase the risk of complications.

Intrahepatic cholangiocarcinoma (ICC) is a rare life-threatening disease, whose only treatment with potential for cure is surgical resection. However, only 27% of patients at most are suitable for surgery when first diagnosed. For patients with unresectable disease, therapeutic options are chemotherapy or chemoradiation. We evaluated the feasibility and safety of oxaliplatin-eluting microspheres transarterial chemoembolization (OEM-TACE) associated with chemotherapy (ChT) in patients affected by unresectable ICC. Between December 2005 and May 2008 we treated nine patients (six female and three male) with unresectable ICC. All patients had undergone OEM-TACE associated with chemotherapy with oxaliplatin and gemcitabine. A retrospective comparison was carried out with a historical group of 11 patients treated with ChT only, estimating the prevalence of adverse effects and the median survival of the two groups. A total of 30 TACEs were performed during the observational time (ranging from one to seven procedures per patient). OEM-TACEs were followed by few adverse effects (AEs), without G4 AEs, according to CTACAE 3.0. According to RECIST criteria, 44% (4/9) of patients achieved partial responses and 56% (5/9) stabilization of disease. Overall survival analysis in the two groups showed a significantly increased survival in patients treated with ChT and OEM-TACE, with respect to those treated with ChT (30 vs. 12.7 months; p=0.004). In conclusion, in our experience OEM-TACE associated with ChT in the treatment of advanced unresectable ICC is a safe and feasible treatment causing no major adverse events. Although RECIST criteria can underestimate the rate of responses in patients treated with locoregional therapies, we achieved very encouraging results. A randomized multicentric trial is warranted to assess the actual superiority of OEM-TACE associated with ChT compared to conventional chemotherapy.

Background: While conventional transhepatic arterial chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC), its use in other hepatic tumors is not supported by randomized studies. Preliminary results have shown that new drug-eluting microspheres (DEM) seem to optimize TACE procedures. The aim of this study was to evaluate the capability of HepaSphere to load oxaliplatin and their pharmacokinetic outcome. The feasibility and safety of treatment with oxaliplatin-eluting microspheres (OEM-TACE) was also evaluated in patients with unresectable liver metastasis of colorectal cancer and unresectable intrahepatic cholangiocarcinoma., Patients and Methods: An inductively coupled plasma mass spectrometer (ICP-MS) was used to quantify the oxaliplatin bound to microspheres and the oxaliplatin in liver biopsies. Fifteen patients (8 with colorectal carcinoma liver metastases, 7 with intrahepatic cholangiocarcinoma) were treated with 27 sessions of OEM-TACE., Results: The data suggested that the microspheres can bind oxaliplatin entirely. The pharmacokinetic parameters were significantly different between the OEM-TACE patients and a control group of patients treated with oxaliplatin chemotherapy. The mean oxaliplatin concentration within the tumor was twenty-times higher than the extratumoral liver concentration in the OEM-TACE patients. According to response evaluating criteria in solid tumors (RECIST), stable disease was observed in 8 out of the 15 patients (53.3%), a partial response in 2 (13.3%) and intrahepatic or extrahepatic tumor progression in 5 out of the 15 patients (33.3%). No major adverse event (AE G3/4) occurred., Conclusion: TACE with oxaliplatin-loaded microspheres is a safe and feasible treatment without major adverse events and with a favorable pharmacokinetic profile.

Mitral annular calcification (MAC) is a common echocardiographic finding. Caseous calcification is a rare variant appearing as a round, tumor-like mass with central echolucent area located in the periannular region. Although occasionally misdiagnosed as a tumor and submitted to exploratory cardiotomy, this lesion appears to carry a benign prognosis. The true significance of caseous calcification is unknown; it might be an early and reversible stage of MAC or an atheroma-like lesion. We describe a case of caseous calcification with spontaneous resolution in a 60-year-old woman-such a finding should be considered in the differential diagnosis of intracardiac masses.

Purpose: Spiral CT, normally a highly accurate diagnostic method to diagnose pulmonary embolism, has its weak point in the synchronisation of contrast medium (CM) injection and the start of the acquisition, essential to obtain optimal vascular enhancement. The aim of this paper is to introduce a method to control the CM injection based on the enhancement of blood vessels in the diagnosis of pulmonary embolism., Materials and Methods: The CARE bolus software pilots an electronic trigger that first monitors the CM passage, then starts the acquisition procedure when the intensity of enhancement reaches a pre-set value. Our spiral CT has a 6-second scan delay between the trigger's "go-ahead" and the start of the acquisition. During this interval, the CM reaches the pulmonary venous system, enhancing it and making the diagnosis of pulmonary embolism more difficult. This problem was overcome by injecting a slow bolus (30 ml; 1.5 ml/s flow rate) before the CM that triggers the start of the scan when the CM is only present in the pulmonary arteries. We examined 80 patients (36 men, 44 women, mean age 66.9, age range 18 to 89 years). All patients were examined for clinically, radiographically or scintigraphically suspected pulmonary embolism. We evaluated the enhancement of pulmonary arteries on a scale from 0 (poor) to 10 (excellent), image quality (excellent, fair, poor), the examination time and patient tolerance. The results were compared with those obtained in a group of 80 patients studied with CARE bolus without a timing bolus., Results: Monitor scans were performed with the ROI that triggers the sequence centred on the right heart (trigger value set at 30/35 HU). There were no diagnostic artefacts caused by the enhancement of pulmonary veins due the timing bolus. The average time per procedure was less than 30 min and the time needed to reach the trigger value was 15 sec (range: 10-24 sec). The average volume of CM injected was 130 ml (timing bolus: 30 ml, scan bolus: 100 ml). There were no adverse events to CM injection. The arterial enhancement scored 7 to 10 for 45 patients (56%), 4 to 6 for 23 (28.5%) and 1 to 3 for 12 (15.0%). Image quality was excellent in 52 patients (65.0%), fair in 18 (22.5%) and poor in 10 (12.5%). Comparing arterial enhancement and image quality, we observed that in the cases where enhancement had scored 7 to 10, image quality was excellent, and in the 7 cases where image quality was poor, so was enhancement (1 to 3). We also made a comparison between procedures carried out with and without the timing bolus. We observed that the use of the timing bolus increases the number of exams with high scores for arterial enhancement, and therefore increases the overall number of examinations with optimal enhancement., Discussion and Conclusions: In order to be diagnostically useful, spiral CT requires good vascular enhancement and synchronisation of the start of acquisitions with the highest concentration of CM, as an incorrect scan delay will lead to artefacts and interpretation errors. The proposed method allows correct timing of the CM injection. The diagnostic bolus is preceded by a slow-flow timing bolus that is intercepted by the electronic trigger, which starts the scan when the CM passes into the right heart and pulmonary arteries. The slow-flow bolus volume was 30 ml injected at 1.5 ml/s, whereas the volume of the real bolus was 100 ml, injected at 4.5 ml/s. Monitor scans were performed with the trigger ROI centred on the right heart (trigger value set at 30/35 HU). The time needed for the complete spiral CT exam did not exceed 30 min. The first low-flow bolus injection takes approximately 10 min, but this time becomes shorter as the operator's experience grows. The correct positioning of the ROI on the right heart is the most time-consuming step in the procedure. The procedure was well accepted by all patients with no complaints due to the CM or to the duration of the procedure. There is a high level of concordance between arterial enhancement and image quality. In conclusion, the proposed method is simple, easy to reproduce, and does not give rise to interpretation problems. It is well accepted by patients and suffers few limitations, mainly represented by patients with severe cardiac arrhythmia.

Background/aims: In this report, the feasibility and efficacy of laparoscopic radiofrequency interstitial thermal ablation of hepatocellular carcinoma has been evaluated in 20 patients., Methodology: The laparoscopic approach with the use of intraoperative ultrasonography allowed us to obtain additional information regarding liver nodules and a complete treatment of the liver lesions., Results: The complication rate was low and there was no operative mortality. A complete necrosis has been obtained in 90% of the cases at 1 month dynamic computed tomography following the treatment., Conclusions: Laparoscopic radiofrequency thermal ablation of hepatocellular carcinoma proved to be a safe and effective technique; its use may be proposed in selected patients. Larger series are needed to accurately assess its role among the other ablative therapies of hepatocellular carcinoma.

Aim of this report is to present a case of acute occlusion of the abdominal aorta recognized by spiral-CT. After a brief description of the etiology and pathology of abdominal aorta acute occlusion, stress is laid on diagnostic role of spiral-CT, based on personal and literature data. The advantage of spiral respect to non-spiral CT is the quicker examination time which is very important, mostly in emergencies. On the contrary, the diagnosis of acute abdominal aorta occlusion is not modified by volumetric CT respect to non-spiral and it is based on the absence of aorta contrast enhancement above the occlusion level.

Purpose: Primary immunodeficiencies (PI) are a heterogeneous and relatively uncommon group of conditions. As a result of one or more immune system abnormalities, PI decrease the body resistance to infections. The respiratory tract is affected in most cases as a result of its natural exposure to pathogenic agents; repeated infections can lead to pulmonary alterations. We investigated the yield of High Resolution CT (HRCT) and Helical CT in pediatric patients with different PI and then correlated the CT patterns with the patients' clinical history and physical status., Material and Methods: We examined 19 pediatric patients with different types of PI. All patients presented recurrent infections (rhinosinusitis, bronchitis, bronchopneumonia) with cough and chronic catarrh for at least 3 months a year. Fifteen patients were examined with HRCT and 4 with Helical CT. Images were evaluated for presence and severity of alveolitis, bronchiectasis, peribronchial thickening, mucous plugs, air trapping, bronchiolitis, consolidation, abscesses, bullae, emphysema and fibrotic changes. All parameters were given a score and a partial and an overall score calculated for each parameter. All scores were compared to study the correlations between CT patterns, clinical history and patients' status and for possible characterization of the different groups by CT patterns. Finally, all alterations were classified by their anatomical distribution in each pulmonary lobe., Results: Scores ranged 0 to 18, with a mean of 8.1 points. There were no correlations between CT patterns, patients' history and clinical status and any disease type. The midlobe was the preferential site for bronchiectasis while lower lobes were more involved by other conditions, such as consolidation, air trapping and alveolitis., Conclusions: Both HRCT and Helical CT proved to be useful tools for monitoring PI patients. The two techniques can be especially valuable in symptomatic patients with negative radiographic findings because they can show (non-)reversible damage, which helps improve planning of drug and/or physical therapy. The scoring system, even if not closely correlated with clinical signs, could be a major tool for PI follow-up and for monitoring treatment success.

We retrospectively evaluated a group of human immunodeficiency virus (HIV)-negative adult patients with hilar and/or mediastinal tubercular adenopathy to assess their epidemiological, clinical and radiological features. Out of 3,003 intrathoracic tuberculosis (TB) cases (of which 745 were immigrants from various developing countries) observed in our Institute from 1986-1996, 8 Italians and 52 immigrants were selected. Case history analysis, and standard chest radiography were performed in all cases, while other investigations such as a tuberculin test, sputum and culture examination for Mycobacterium tuberculosis, computed tomography (CT) scanning and biopsy were performed in the majority of patients. Less frequently, bronchoscopy, mediastinoscopy, and echography were also performed. Right paratracheal adenopathy was found most frequently (29 cases), as previously described. CT scanning showed a central necrosis pattern in 31 cases, while normo/hyperdensity occurred in 11 cases. M. tuberculosis was detected in sputum smear and/or culture in only 16 patients. Our study confirms that, when HIV-positive patients are excluded, this peculiar TB location occurs more frequently in immigrants than in the indigenous Italian population (7.0 versus 0.3%, p < 0.001). People from the Indian subcontinent and Senegal are the most frequently involved nationalities among the immigrants present in Milan.

Bronchioloalveolar carcinoma (BAC) is a relatively uncommon tumor of the lung accounting for 1 to 9% of all pulmonary neoplasms. Its radiologic appearance is characterized by solitary nodular opacity or diffuse air-space consolidation. The aim of this work is to report the different patterns of this neoplasm, particularly in the diffuse form, and to demonstrate the sensitivity and specificity of HRCT in its early identification. We examined 11 patients affected with multifocal bronchioloalveolar carcinoma to identify HRCT signs which could lead to improved diagnostic criteria. These signs are represented by ground-glass opacity (8/11) and alveolar consolidation (6/11), with a plurilobular, segmentary or lobar distribution. The lesions were bilateral in 8/11 cases and abnormal mediastinal lymph nodes were found in 5/11 cases. Air bronchogram was seen in all cases of ground-glass opacity and in 5/11 cases of air-space consolidation. In conclusion, in our experience, HRCT is a useful tool in the study of BAC, which has a long and slow evolution and is underestimated at chest radiograph in its early stage. Moreover, HRCT can help distinguish this condition from other lung diseases characterized by diffuse air-space consolidations, whose clinical history is useless to make an unquestionable diagnosis.

A 71-year-old woman with a solitary kidney who developed acute renal failure with anuria secondary to a spontaneous perirenal hematoma is described. Serum creatinine peaked at 335.9 micromol/L and BUN at 26.4 mmol/L, but neither surgery nor dialysis treatment was performed because renal function gradually improved. In this syndrome, first described by Wunderlich in 1856, anuria was not previously reported. Conservative management must always be considered rather than emergency surgery, which usually results in nephrectomy.

We retrospectively reviewed CT scans of 18 patients (12 males and 6 females; mean age: 43.6 years) with the diagnosis of blunt splenic trauma. All patients underwent CT at different times after the trauma. The cases were divided into 2 groups: according to the time at which the CT was performed, the 1st group consisted of 11 patients scanned within 48 h after the trauma; the 2nd group consisted of 7 patients studied with CT at variable times after the traumatic event (mean time: 6.5 days; range 3-13 days). All lesions in the 1st group (11 patients) had indistinct margins, while lesions of patients in the 2nd group (7 patients) always showed clean-cut and regular edges. Early lesions were always hyperdense, late ones hypodense. CT diagnosis always matched the surgeon's diagnosis. We can confirm the diagnostic value of CT of splenic lesions in blunt abdominal traumas.

342 short-stature patients were examined to assess the agreement between anagraphic and bone ages. 190 men and 152 women (age range: 0 to 17.5 years) underwent conventional radiographs of the left wrist. The radiographs were studied with the TW2 method which provides an index of the skeletal maturity of short and long bones and a global index of the hand. The bone ages thus obtained were compared with anagraphic ages. Patients' statures were compared with their parents' ones. Finally, radiation exposures were evaluated. Anagraphic and bone ages were in agreement in 199 patients and in disagreement in 220. Three patients were adult. The short stature in 78 patients was in agreement with their parents' one, while 253 patients had at least one parent with normal stature. No comparison could be made in 11 patients. In conclusion, TW2 is a simple method to calculate bone age (in months and years) and to select the patients to submit to further examinations and to hormone therapy.

The results of a retrospective review of the conventional radiographs performed on head injury patients are reported. Skull radiography findings were compared with clinical symptoms and CT results, when CT was performed, to investigate the presence of intracranial lesions. The radiographs of 2,285 adult patients of both sexes were evaluated: skull fractures were observed in 21/2,285 patients (0.9%) only. CT was positive for an intracranial lesion in 18 of 21 patients (85.71%). Clinical symptoms were divided into three groups according to lesion severity and to neurologic impairment. 979 patients were asymptomatic and 1,306 were symptomatic: 1,114 patients were included in group I, their symptoms being nausea, vomit and loss of consciousness for less than ten minutes, 124 were included in group II (epistaxis and loss of consciousness for more than 10 minutes) and 68 were included in group III (coma and focal neurologic signs). All the patients in groups II and III and 30 patients in group I were submitted to CT--222 CT exams on the whole. Thirty-five patients in group III and 9 in group II had an intracranial lesion on CT, while CT findings were normal in all group-I patients. Thus, we conclude that the presence of a skull fracture is not always correlated with the presence of intracranial lesions. The latter are more likely to be correlated with clinical symptoms, especially coma and neurologic impairement. Therefore, the higher value is confirmed of the clinical examination than of conventional radiographs in head injury patients.

The CT scans of 18 patients (12 males and 6 females; mean age: 43.6 years) with splenic blunt trauma were reviewed. CT examinations had been made at different times after trauma. The CT images were grouped according to the time of examination and both structure and densitometry were evaluated in all lesions. In all cases CT findings were correlated with surgical and pathologic data. The patients were divided into two groups: group I included 11 subjects in whom CT had been performed within 48 hours following trauma and group II included 7 patients who had undergone CT at different times after trauma (3-13 days; mean: 6.5 days). All the lesions in group I exhibited blurred outlines, while the lesions in group II had clear-cut margins. The lesions in group I were always hyperdense while those in group II were hypodense. CT diagnosis was always in agreement with surgical findings. In conclusion, we confirm the value of CT in the examination of splenic lesions by blunt abdominal trauma. The evolution of splenic lesions is usually typical: CT yields useful information for injury evaluation and is therefore very important to plan treatment. We believe that CT should be performed as soon as possible, even on the basis of minor clinical and laboratory data.

Thirty patients of both sexes (15 males and 15 females) with chronic renal failure who had under gone hemodialysis for 2-184 months (mean 45.1 months) were examined with conventional radiographs of the cervical spine and thin-layer CT of C4-C5-C6 to evaluate the radiographic patterns of destructive spondyloarthropathy. The radiographic patterns obtained with conventional and CT exams were compared with one another and with clinical (carpal tunnel syndrome) and biochemical data (alkaline phosphatase, parathormon, Ca, P, Ca/P, Al, beta 2-microglobulin). DSA (erosion and narrowing of the intervertebral space, collapse of the vertebral body and erosion of the vertebral plates) was recognized in 7 patients with conventional radiographs and in 11 patients with CT thanks to greater CT capabilities to recognize minimal osteolytic lesions of the vertebral body. All the patients with destructive spondyloarthropathy had personal and hemodialysis age higher than those without destructive spondyloarthropathy: 59.3 vs 57.7 years; 49 vs 39 months. Parathormon and alkaline phosphatase were increased while beta 2-microglobulin was normal. Only 2 patients with DSA had carpal tunnel syndrome. In conclusion, CT is a valuable technique for the diagnosis of destructive spondyloarthropathy but it must be performed only after conventional radiographs of the cervical spine or in the presence of clinical signs of destructive spondyloarthropathy (parathormon and beta 2-microglobulin increased, long-term hemodialysis).

The radiological features of one patient, entirely asymptomatic, with a paracardiac mass in the right lower lobe, are presented. Computed tomography (TC) evaluation of the chest has shown with remarkable accuracy a massive hiatal hernia, containing the whole stomach and fatty omental tissue. This case confirms TC validity as an accurate and non invasive method in differential diagnosis of chest radiological opacities and its utility to identify seat and composition of diaphragmatic hernias.

Cholangiographically-enhanced CT scans were performed on nine patients with biliary obstruction or suspected pancreatic masses. The opacification of the biliary tree was obtained by slow infusion of 25 ml of cholangiographic contrast medium diluted in 75 ml of saline and administered 45 mins before the CT examination. Two separate CT sequences were obtained, one with cholangiographic contrast alone, the other with associated parenchymal enhancement. The tolerability of the overall procedure was very good. The measurement of the HU values of the biliary ducts showed a marked increase in bile density. These structures could easily be appreciated within the liver and in the porta hepatis; the pancreatic head and its relationships with the main bile duct were evident. The densitometric measurement of the liver parenchyma before and after contrast enhancement did not show any variation with respect to the standard HU values. Cholangiographically-enhanced CT proved to be useful for the diagnosis of biliary obstruction; it may also be a promising diagnostic tool for the evaluation of pancreatic masses.

Cystic neoplasms of the pancreas are rare lesions. Following the Compagno-Oertel classification, we differentiated serous microcystic adenomas (SMA) from mucinous macrocystic adenomas/adenocarcinomas (MMA). The former are benign tumors with slow growth, composed by innumerable small and tiny cysts with central calcifications, resulting in a "honeycomb" pattern. They have a mixed US structure while CT densitometric values reflect a mixture of connective tissue and proteinaceous fluid. Postcontrast enhancement is frequently seen. MMA are potential (adenoma) or frankly (adenocarcinoma) malignant tumors. They appear as multilocular cystic masses containing septa and/or papillary bulges, with thickened walls. Both US and CT demonstrate their predominantly cystic character, and the eventual presence of excrescences. We report a series of 23 cases (6 SMA, 17 MMA) of cystic neoplasms of the pancreas studied during the past five years. A correct diagnosis of SMA was possible in all 6 cases, while MMA was correctly diagnosed in 17 out of 18 cases. There were no false negatives, and 1 false positive. All differential diagnoses are also discussed.

In this paper the authors report on a new technique--percutaneous transluminal laser angioplasty (PLR) which was performed on 9 patients with iliac and/or femoro-popliteal artery occlusion. All patients were males (mean age: 64.5 years) and had arterial occlusion (mean length: cm 12.5). PLR was performed with an argon laser (max power: 16 Watts). In 8 out of 9 patients (88.8%) a complete recanalization was obtained of the occluded arterial tract, without complications. In one case only (12.2%) there was an arterial wall perforation with unsatisfactory results. In our opinion, PLR has proven a simple methodology, which can be performed on any patient due to the very low incidence of severe complications and distal embolism. Moreover, PLR has quite low costs, and does not prevent eventual surgical/percutaneous interventions.