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Diffuse large B-cell lymphoma (DLBCL) is an aggressive, heterogeneous neoplasm where prognostication and therapeutic decision are challenging. The available prognostic tools are not able to identify all patients refractory to treatment. MicroRNAs, small RNAs frequently deregulated in cancer, stably circulate in biofluids, representing interesting candidates for non-invasive biomarkers. Here we validated serum miR-22, an evolutionarily conserved microRNA, as a prognostic/predictive biomarker in DLBCL. Moreover, we found that its expression and release from DLBCL cells are related to therapy response and adversely affect cell proliferation. These results suggest that miR-22 is a promising complementary or even independent non-invasive biomarker for DLBCL management.

Colorectal cancer (CRC), despite the advances in screening and surveillance, remains the second most common cause of cancer death worldwide. The biological inadequacy of pre-clinical models to fully recapitulate the multifactorial etiology and the complexity of tumor microenvironment and human CRC’s genetic heterogeneity has limited cancer treatment development. This has led to the development of Patient-derived models able to phenocopy as much as possible the original inter- and intra-tumor heterogeneity of CRC, reflecting the tumor microenvironment’s cellular interactions. Implantation of patient tissue into immunodeficient mice hosts and the culture of tumor organoids have allowed advances in cancer biology and metastasis. This review highlights the advantages and limits of Patient-derived models as innovative and valuable pre-clinical tools to study progression and metastasis of CRC, develop novel therapeutic strategies by creating a drug screening platform, and predict the efficacy of clinical response to therapy.

Hsa-mir-143 and hsa-let-7c have been reported to be deregulated in multiple neoplasms. The main purpose of this study was to investigate the expression of these miRNAs in bladder cancer (BCa) and to analyze the association between their expression profiles and clinical and epidemiological parameters. Ninety BCa specimens were included. Expression patterns of miR-143 and let-7c were assessed by qRT-PCR using Taqman specific probes. Validated and predicted targets of these miRNA's were identified using CSmiRTar and DAVID tools, respectively. miR-143 was downregulated in tumors compared to controls (mean fold-change (FC) = 0.076). Its expression was significantly higher in MIBC compared to NMIBC (p = 0,001). Its value as a potential biomarker discriminating non invasive tumors from the invasive ones was confirmed by ROC curve (AUC = 0.768; p = 0.0001). Also, this down-regulation positively correlates with frequency of tobacco use (p = 0,04) and chronic alcohol consumption (p = 0,04). Let-7c was overexpressed in BCa samples (mean (FC = 9.92) compared to non tumoral ones but was not associated to clinical and epidemiological parameters. A comprehensive overview of miR-143 targets and pathways implicated in BCa initiation, diagnosis or prognosis using bioinformatical analysis, was conducted. While both deregulated miRNAs may contribute to urothelial tumorigenesis, the deregulation of miR-143 was significantly correlated to epidemiological and clinical parameters.

Nontypeable Haemophilus influenzae (NTHi) is commonly isolated from airways of patients suffering from chronic respiratory diseases, such as COPD or cystic fibrosis (CF). However, to what extent NTHi long-term infection contributes to the lung inflammatory burden during chronic airway disease is still controversial. Here, we exploited human respiratory samples from a small cohort of CF patients and found that patients chronically infected with NTHi had significantly higher levels of interleukin (IL)-8 and CXCL1 than those who were not infected. To better define the impact of chronic NTHi infection in fuelling inflammatory response in chronic lung diseases, we developed a new mouse model using both laboratory and clinical strains. Chronic NTHi infection was associated with chronic inflammation of the lung, characterised by recruitment of neutrophils and cytokine release keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), granulocyte colony-stimulating factor (G-CFS), IL-6, IL-17A and IL-17F) at 2 and 14 days post-infection. An increased burden of T-cell-mediated response (CD4+ and γδ cells) and higher levels of pro-matrix metalloproteinase 9 (pro-MMP9), known to be associated with tissue remodelling, were observed at 14 days post-infection. Of note we found that both CD4+IL-17+ cells and levels of IL-17 cytokines were enriched in mice at advanced stages of NTHi chronic infection. Moreover, by immunohistochemistry we found CD3+, B220+ and CXCL-13+ cells localised in bronchus-associated lymphoid tissue-like structures at day 14. Our results demonstrate that chronic NTHi infection exerts a pro-inflammatory activity in the human and murine lung and could therefore contribute to the exaggerated burden of lung inflammation in patients at risk., The pathological impact of long-term infection by nontypeable Haemophilus influenzae (NTHi) is still debated. Chronic NTHi infection fuels lung inflammation in human samples and in a new mouse model of bacterial long-term persistence. https://bit.ly/3lvyvge

Highlights • Hyperinflammation in COVID-19 activates blood coagulation increasing thrombotic risk. • Tocilizumab blocks IL-6 receptor and may improve inflammatory-induced hypercoagulability. • Tocilizumab was associated with rapid and sustained coagulation improvement. • These benefits were consistent independently of thromboprophylaxis dose., Background Many COVID-19 patients develop a hyperinflammatory response which activates blood coagulation and may contribute to the occurrence of thromboembolic complications. Blockade of interleukin-6, a key cytokine in COVID-19 pathogenesis, may improve the hypercoagulable state induced by inflammation. The aim of this study was to evaluate the effects of subcutaneous tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 receptor on coagulation parameters. Methods Hospitalized adult patients with laboratory-confirmed moderate to critical COVID-19 pneumonia and hyperinflammation, who received a single 324 mg subcutaneous dose of tocilizumab on top of standard of care were enrolled in this analysis. Coagulation parameters were measured before tocilizumab and at day 1, 3, and 7 after treatment. All patients were followed-up for 35 days after admission or until death. Results 70 patients (mean age 60 years, interquartile range 52-75) were included. Treatment with tocilizumab was associated with a reduction in D-dimer levels (-56%; 95% confidence interval [CI], -68% to -44%), fibrinogen (-48%; 95%CI, -60% to -35%), C-reactive protein (-93%; 95%CI, -99% to -87%), prothrombin time (-4%; 95%CI,-9% to 0.8%), and activated thromboplastin time (-4%; 95%CI,-8.7% to 0.8%), and an increase in platelet count (34%; 95%CI, 23% to 45%). These changes occurred already one day after treatment with sustained reductions throughout day 7. The improvement in coagulation was consistently observed in patients receiving prophylactic or therapeutic dose anticoagulants, and was paralleled by a rapid improvement in respiratory function. Conclusions Subcutaneous tocilizumab was associated with significant improvement of blood coagulation parameters independently of thromboprophylaxis dose.

Gliomas are diffusely growing tumours arising from progenitors within the central nervous system. They encompass a range of different molecular types and subtypes, many of which have a well-defined profile of driver mutations, copy number changes and DNA methylation patterns. A majority of gliomas will require surgical intervention to relieve raised intracranial pressure and reduce tumour burden. A proportion of tumours, however, are located in neurologically sensitive areas and a biopsy poses a significant risk of a deficit. A majority of gliomas recur after surgery, and monitoring tumour burden of the recurrence is currently achieved by imaging. However, most imaging modalities have limitations in assessing tumour burden and infiltration into adjacent brain, and sometimes imaging is unable to discriminate between tumour recurrence and pseudo-progression. Liquid biopsies, obtained from body fluids such as cerebrospinal fluid or blood, contain circulating nucleic acids or extracellular vesicles containing tumour-derived components. The studies for this systematic review were selected according to PRISMA criteria, and suggest that the detection of circulating tumour-derived nucleic acids holds great promises as biomarker to aid diagnosis and prognostication by monitoring tumour progression, and thus can be considered a pathway towards personalized medicine.

Highlights • Early treatment with low-dose tocilizumab TCZ (324 mg, administered subcutaneously in two simultaneous 162 mg injections) was used to prevent progression of disease in a subgroup of patients with moderate COVID-19 pneumonia and hyperinflammation. • Low-dose subcutaneous tocilizumab TCZ (324 mg) was well-tolerated with no significant adverse effects. • Low-dose subcutaneous tocilizumab TCZ (324 mg) was associated with a rapid and significant reduction in C reactive protein (CRP) paralleled by a progressive improvement in oxygenation as reflected by the ratio of partial pressure of oxygen to fraction of inspired oxygen (P/F) ratio. • None of the TCZ-treated patients had disease progression, suggesting that IL-6 receptor blockade with subcutaneous TCZ may prevent COVID-19 progression when administered early in the course of disease., Aim The aim of the study was to evaluate the safety and efficacy profile of low-dose tocilizumab (TCZ) administered subcutaneously to patients with moderate COVID-19 pneumonia and hyperinflammation to prevent disease progression. Methods We retrospectively analyzed clinical characteristics and outcomes of patients with laboratory-confirmed bilateral COVID-19 pneumonia, hyperinflammation (C reactive protein ≥20 mg/dl), no hypoxemia (oxygen saturation >90%) and no contra-indications to TCZ, who were treated with subcutaneous TCZ (324 mg) administered within 48 hours from hospitalization on top of standard of care (SOC), and compared them with matched controls treated with SOC only before TCZ was available at our center. Clinical data were available for all patients until death or, for those discharged from hospital, until day 35. Findings Ten consecutive patients (6 males, median age 55 years) treated with TCZ on top of SOC, and ten patients (6 males, median age 56 years) treated with SOC only were included. TCZ was well-tolerated, with no clinically relevant adverse events. TCZ was associated with a reduction in CRP at day 1 (−50%, IQR −28 to −80) and day 3 (−89%, IQR −79 to −96; P = 0.005 for within-group), whereas there was no significant change in CRP values in the SOC group (P

•AbstractNontypeable Haemophilus influenzae (NTHi) is commonly isolated from airway of cystic fibrosis (CF) patients. However, to what extent NTHi persistence contributes to the lung inflammatory burden during CF chronic airway disease is controversial. Here, we aimed at determining the pathological role of NTHi persistence in a cohort of CF patients and in a newly generated mouse model of NTHi persistence.In our study cohort, we found that CF patients chronically colonized by NTHi had significantly higher levels of IL-8 and CXCL1 than those who were not colonized. To better define the impact of NTHi persistence in fuelling inflammatory response, we developed a new mouse model using both laboratory and CF clinical strains. NTHi persistence was associated with chronic inflammation of the lung, characterized by recruitment of neutrophils and cytokine release (KC, G-CFS, IL-6 and IL-17A) at 2 and 14 days postinfection. An increased burden of T cell mediated response (CD4+ and γδ cells) and higher levels of matrix metalloproteinase 9, known to be associated with tissue remodelling, were observed at 14 days post-infection. Of note we found that both CD4+IL-17+ cells and levels of IL-17 cytokine were enriched in mice at advanced stage of NTHi chronic infection. Moreover, by immunohistochemistry we found CD3+, B220+ and CXCL-13+ cells localized in bronchus-associated lymphoid tissue-like structures at day 14.Our results demonstrate that NTHi persistence exerts a pro-inflammatory activity in the human and murine lung, and could therefore contribute to the exaggerated burden of lung inflammation in CF patients.

Chronic diseases such as hypertension and rheumatoid arthritis are persistent ailments that require personalized lifelong therapeutic management. However, the difficulty of adherence to strict dosing schedule compromises therapeutic efficacy and safety. Moreover, the conventional one-size-fits-all treatment approach is increasingly challenged due to the intricacies of inter- and intra-individual variabilities. While accelerated technological advances have led to sophisticated implantable drug delivery devices, flexibility in dosage and timing modulation to tailor precise treatment to individual needs remains an elusive goal. Here we describe the development of a subcutaneously implantable remote-controlled nanofluidic device capable of sustained drug release with adjustable dosing and timing. By leveraging a low intensity electric field to modify the concentration driven diffusion across a nanofluidic membrane, the rate of drug administration can be increased, decreased or stopped via Bluetooth remote command. We demonstrate in vitro the release modulation of enalapril and methotrexate, first-line therapeutics for treatment of hypertension and rheumatoid arthritis, respectively. Further, we show reliable remote communication and device biocompatibility via in vivo studies. Unlike a pulsatile release regimen typical of some conventional controlled delivery systems, our implant offers a continuous drug administration that avoids abrupt fluctuations, which could affect response and tolerability. Our system could set the foundation for an on-demand delivery platform technology for long term management of chronic diseases.

Background High grade non-muscle-invasive bladder cancer (HG-NMIBC) is a heterogeneous disease with variable risk of progression. Urinary microRNAs are promising biomarkers for BC detection and surveillance. Let-7c-5p miRNA, clustered with miR-99a-5p and -125b-5p, is deregulated in cancer, including BC. The aim of this study is to evaluate urinary let-7c cluster expression in Ta/T1 HG-NMIBC patients and its impact on progression-free survival (PFS). Methods Quantitative Real-Time-Polymerase-Chain-Reaction (qRT-PCR) was used to analyze the let-7c cluster expression in 57 urine and 49 neoplastic paired tissue samples prospectively collected from transurethral resection (TUR) HG-NMIBC patients. Twenty urine and 10 bladder tissue samples were collected and analyzed as normal controls. QRT-PCR was also used to detect intra−/extra-cellular let-7c cluster in BC cells. Receiver Operating Characteristic (ROC) curves were used to identify urinary miRNAs cut-off values predicting T-stage and PFS. Uni/multivariable Cox regression was performed to identify predictors of PFS. A nomogram predicting progression risk and a decision curve analysis (DCA) were performed. Results Urinary let-7c was significantly up-regulated in patients compared with controls, while the whole cluster was down-regulated in tumor tissues. Supporting these findings, in vitro comparison of extra−/intra-cellular ratios of cluster levels between BC cells, showed a higher ratio for let-7c in HG-NMIBC versus low-grade cells. Urinary let-7c cluster expression was increased in higher T-stage and was an independent predictor of progression. Lower EORTC-score and downregulation of urinary cluster were predictors of higher PFS on univariable Cox regression, while on multivariable analysis only cluster expression was an independent progression predictor. On DCA, a benefit was evident for patients with a PFS probability > 20%. Conclusions Urinary let-7c cluster evaluation may improve prognosis, identifying patients at risk of progression and addressing early radical treatment.

Effetti dell’applicazione di spray liposomiale con vitamine A ed E nelle riniti allergiche.Scopo del nostro studio è stato indagare la relazione tra ostruzione nasale e citologia nasale in pazienti con rinite allergica trattati con spray nasale liposomiale con vitamine A ed E. Lo studio è prospettico, controllato in doppio cieco. I 106 pazienti affetti da rinite allergica, che hanno rifiutato la terapia anti-allergica, ammessi nello studio sono stati assegnati a uno dei due gruppi: G (gruppo di studio, n = 53) che ha assunto uno spray nasale liposomiale con vitamine A ed E e C (gruppo controllo, n = 53) che ha assunto uno spray di soluzione salina (NaCl) 0,9%. Entrambi gli spray nasali sono stati assunti mattina e sera per 30 giorni. La prima visita è stata effettuata al tempo zero (T0) e la seconda visita al termine dello studio (T1). In entrambe le visite sono stati valutati i segni (citologia nasale) e i sintomi (SNOT-22 e VAS) della rinite allergica. Lo spray nasale liposomiale con vitamine A ed E è risultato efficace nel migliorare la sintomatologia nasale e nel ridurre la conta cellulare in pazienti affetti da rinite allergica. Nel nostro studio abbiamo evidenziato un miglioramento significativo della scala VAS (p0,0001), un’importante riduzione del punteggio del test SNOT-22 (p0,0001) e una rilevante riduzione della conta delle cellule infiammatorie della mucosa nasale, soprattutto neutrofili ed eosinofili (p0,0001). Alla luce dei risultati rilevati è possibile affermare che lo spray nasale liposomiale si è dimostrato in grado di migliorare i sintomi della rinite allergica. I pazienti hanno manifestato un’ottima compliance al trattamento proposto per la percezione di un favorevole rapporto tra efficacia e scarsi effetti collaterali. La riduzione della conta cellulare infiammatoria è risultata rilevante, confermando la stretta associazione tra infiltrazione eosinofila e ostruzione nasale. Questi risultati potrebbero avere implicazioni per la pratica clinica.The aim of this study was to investigate the relationship between nasal obstruction and nasal cytology in patients with allergic rhinitis (AR) treated with a liposomal based nasal spray containing vitamins A and E. This is a prospective double-blind, controlled study. A total of 106 patients with AR, who rejected anti-allergic therapy, were randomly divided into two groups: G (study group, n = 53) received liposomal nasal spray and C (control group, n = 53) received 0.9% sodium chloride solution nasal spray. Both nasal sprays were applied two times a day, in the morning and at night, in both nasal cavities. The study lasted for 30 days. The first ENT evaluation was performed the first day (T0) and the second evaluation was performed at the end of the study (T1). Symptoms (SNOT-22 test with VAS) and signs (nasal cytology) of both groups were recorded at T0 and T1. Liposomal nasal spray was effective in improving both nasal symptoms and cytology in patients suffering from perennial AR. Treatment with liposomal nasal spray with vitamins A and E was followed by a significant improvement of VAS scale (p0.0001), a significant decrease in SNOT-22 (p0.0001) and a significant decrease in inflammatory cell count (p0.0001). In conclusion, our study provides evidence that liposomal nasal spray improves the nasal symptoms of AR. The patients were compliant to this therapy because of limited side effects. The reduction in inflammatory cells count was remarkable and confirmed the close association between eosinophil infiltration and nasal airflow impairment. These results may have implications for clinical practice.

Electric power can be wirelessly transferred to power supply medical devices, in order to reduce the size of the implants and increase their lifetime. The inductive power transmission, through the interaction between two coils, is substitute by a novel magnetoelectric (ME) technology. In this case, the external coil delivers the energy to a ME receiver, made with an electroactive (e.g piezoelectric) material, bonded between two magnetostrictive layers. The maximum power density obtained is 175 mW/cm3, that means 25 times more than current state of the art. This new technology can increase the power density and overpass the issues of directionality, present in the inductive transmission technique, and open new prospective for wireless powering medical implants.

Unlike allogeneic transplant, autologous stem cell transplantation (ASCT) represents a procedure with a low-risk of cytomegalovirus (CMV) symptomatic reactivation-infection/end-organ disease (CMV complications) and invasive fungal disease (IFD). However, novel drugs for the treatment of lymphoproliferative malignancies could cause an increase of such opportunistic infections, even after ASCT. To the best of our knowledge, there are no published data demonstrating an association between CMV and IFD in the autologous setting, while this association has been widely reported in allogeneic transplantation. We have reviewed our series of 347 ASCT in myeloma and lymphoma patients performed over a period of 14 years with the aim of investigating the descriptive and analytical epidemiology of bacterial, CMV and IFD complications, focusing on the association between CMV and IFD. Patients with myeloma have significantly fewer bacterial infections and IFD than patients with lymphoma, but a similar rate of CMV complications. Descriptive epidemiological data are consistent with the literature, indicating an overall incidence of 36%, 3.5% and 15.5% for bacterial infections, IFD and CMV complications, with a case mortality rate of 4%, 16.7% and 3.7%, respectively. A strong correlation between CMV and IFD exists, with 8 cases of IFD out of a total of 12 presenting a CMV complication. At multivariate analysis, a diagnosis of lymphoma, ≥3 previous treatment lines and age ≥60 years were found to be independent risk factors for IFD. Duration of neutropenia (ANC < 500/mm3) ≥7 days represents an independent risk factor for CMV complications, where neutropenia most likely represents a crude surrogate biomarker indicating a deeper and longer state of overall immunosuppression. From our data we conclude that (1) myeloma patients are at lower risk of bacterial infections and IFD as compared with lymphoma patients but are at equal risk of CMV complications, most likely as a consequence of a selective impact of bortezomib on Herpes Viruses infection control; (2) a significant association exists between CMV and IFD, although a possible cause-effect relationship remains to be determined; (3) IFD is a rare complication after ASCT but burdened by a mortality rate of about 17%, with peak rates in older lymphoma patients who underwent more intensive therapeutic regimens.

Background Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of tumors, with aggressive clinical course that renders prognostication and choice of treatment strategy difficult. Chemo-immunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) is the current first-line treatment. MicroRNAs (miRNAs) are under investigation as novel diagnostic and prognostic biomarkers in several malignancies, including malignant lymphomas. While tissue miRNAs in DLBCL patients have been extensively studied as biomarkers, only few reports to date have evaluated the role of circulating/serum miRNAs as potential prognostic factors. Here circulating/serum miRNAs, including miR-22, were investigated as potential non-invasive biomarkers, with the aim of a better prognostic stratification of DLBCL patients. Methods MiRNAs were selected by global expression profile of serum miRNAs of DLBCL patients, The Cancer Genome Atlas (TCGA) analysis and literature research. Serum and tissues miRNA expression profile in de novo DLBCL patients, consecutively enrolled for this study, were detected by quantitative real-time polymerase chain reaction. Relative expression was calculated using the comparative Ct method. Statistical significance was determined using the Mann-Whitney rank sum and Fisher’s exact test. Survival analysis was conducted through the use of Kaplan-Meier method. Spearman’s Rho was applied to study the correlation between miRNA distributions and days to first relapse. Experimentally validated miRNA-target interactions were assessed by miRTarBase database. Negative miRNA-mRNA correlation was evaluated in TCGA DLBCL dataset. Pathway analysis was performed by the functional annotation clustering DAVID tool. Results We showed a significant modulation of serum miR-22 after R-CHOP treatment compared with basal values but no difference between baseline serum miRNAs values of DLBCL patients and healthy controls. High expression level of serum miR-22 in DLBCL at diagnosis (n = 36) is associated with a worse PFS and is independent of the currently used clinical prognostic index. Integrative and pathways analysis of miR-22 identified target genes involved in different important pathways such as p53 signaling. Conclusions Our data suggest that miR-22 is of potential interest as non-invasive biomarker to predict clinical outcome in DLBCL patients. Characterization of miR-22 pathways can pave the way to the development of targeted therapy approaches for specific subgroups of DLBCL patients. Electronic supplementary material The online version of this article (10.1186/s13046-018-0768-5) contains supplementary material, which is available to authorized users.

The pathophysiological mechanisms driving exaggerated inflammation and tissue damage associated to un-resolved airway infections during chronic lung diseases remain to be elucidated. Recent reports...

In numerous pathologies, implantable drug delivery devices provide advantages over conventional oral or parenteral approaches. Based on the site of implantation and release characteristics, implants can afford either systemic delivery or local administration, whereby the drug is delivered at or near the site of intended action. Unfortunately, current implantable drug delivery systems provide limited options for intervention in the case of an adverse reaction to the drug or the need for dosage adjustment. In the event that drug delivery must be terminated, an urgent surgical retrieval may be the only reliable option. This could be a time sensitive and costly effort, requiring access to trained professionals and emergency medical facilities. To address such limitations, here we demonstrate, in vitro and ex vivo, a novel microsystem for the rapid and effective switch off of drug delivery from an implantable nanofluidic system, by applying a safe external electromagnetic field in the FDA approved dose range. This study represents a proof of concept for a technology with potential for broad applicability to reservoir-based delivery implants for both complete interruption or remote titration of drug administration.

Purpose To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. Methods and Materials The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28–83) provided informed consent. T 2 - and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm 2 /s) were acquired before, during (mean 12 days), and 6–8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Results Low pretreatment ADCs ( −3 mm 2 /s) were correlated with TRG 4 scores ( p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders ( p 23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different ( p = .0012) between the patients with and without downstaging (preoperative ADC ≥1.4 × 10 −3 mm 2 /s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2–4 groups were not significantly different. Conclusion Diffusion-weighted magnetic resonance imaging seems to be a promising tool for monitoring the response to CRT.

The past decade has seen significant advances in the evaluation of the small bowel, long considered as the “black box” in gastroenterology. The development of several endoscopic techniques, including capsule endoscopy (CE) and double (DBE)- and single (SBE)-balloon enteroscopy, has improved the evaluation of this part of the gut and led to reach a more precise preoperative diagnosis of small-bowel tumors. These rare tumors were previously diagnosed only after laparotomy, although laparoscopic advanced surgery can be used for minimally invasive therapeutic approach in these patients. This study was designed to evaluate the diagnostic and therapeutic impact of endoscopic procedures on small-bowel tumors. During October 2010, 148 SBE procedures were performed; in 14 patients (7 males and 7 females, mean age 58.8 years; range 37–82 years) who suffered from obscure gastrointestinal bleeding, with previous negative upper and lower GI endoscopy, a diagnosis of small-bowel tumor was suspected according to CT scan (7 cases) and/or CE (11 patients). Then, an enteroscopy was performed. Multiple biopsies were taken in 9 cases; endoscopic tattoos were performed in 11 cases. After endoscopic procedures, histological examination showed melanoma in one case, adenocarcinoma in seven, and adenoma in one case. In 11 of 14 patients, a laparoscopic partial resection of small bowel involved was possible due to endoscopic tattoos. In one patient, the involvement of colic segment precluded a laparoscopic resection. In two patients, the laparoscopic resection was not possible for technical problems. Histological findings on resected specimens were indicative for melanoma in one case, gastrointestinal stromal tumor (GIST) in four cases, gastrointestinal autonomic nerve tumor (GANT) in one case, adenoma in one, and adenocarcinoma in seven cases. New development of different endoscopic approaches to the small bowel has led to reach an earlier diagnosis of small-bowel tumors and a preoperative diagnosis with consequent minimally invasive surgical approach.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm with diverse genetic abnormalities and outcomes. To date, DLBCL is invasively diagnosed by tissue biopsy and few biomarkers are available to predict patient outcome, treatment response and progression. The identification of patient-specific biomarkers would allow a "personalized medicine" approach for DLBCL patients. In this regard, "liquid biopsies" hold great promise, capturing the entire genetic landscape of the tumour and allowing a rapid and dynamic management of cancer. Liquid biopsy studies particularly focus on cell-free nucleic acids, such as cell-free DNA (cfDNA) and microRNAs, which are easy to collect and analyse. In accordance with the PRISMA criteria, we performed a systematic review on circulating nucleic acids as potential biomarkers for DLBCL management. The results suggest that combining information from the genetic (cfDNA) and epigenetic (microRNAs) landscape of the disease could lead to developing an integrated network of non-invasive biomarkers for the better management of DLBCL.