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Among all cancers, colorectal cancer (CRC) is the 3rd most common and the 2nd leading cause of death worldwide. New therapeutic strategies are required to target cancer stem cells (CSCs), a subset of tumor cells highly resistant to present-day therapy and responsible for tumor relapse. CSCs display dynamic genetic and epigenetic alterations that allow quick adaptations to perturbations. Lysine-specific histone demethylase 1A (KDM1A also known as LSD1), a FAD-dependent H3K4me1/2 and H3K9me1/2 demethylase, was found to be upregulated in several tumors and associated with a poor prognosis due to its ability to maintain CSCs staminal features. Here, we explored the potential role of KDM1A targeting in CRC by characterizing the effect of KDM1A silencing in differentiated and CRC stem cells (CRC-SCs). In CRC samples, KDM1A overexpression was associated with a worse prognosis, confirming its role as an independent negative prognostic factor of CRC. Consistently, biological assays such as methylcellulose colony formation, invasion, and migration assays demonstrated a significantly decreased self-renewal potential, as well as migration and invasion potential upon KDM1A silencing. Our untargeted multi-omics approach (transcriptomic and proteomic) revealed the association of KDM1A silencing with CRC-SCs cytoskeletal and metabolism remodeling towards a differentiated phenotype, supporting the role of KDM1A in CRC cells stemness maintenance. Also, KDM1A silencing resulted in up-regulation of miR-506-3p, previously reported to play a tumor-suppressive role in CRC. Lastly, loss of KDM1A markedly reduced 53BP1 DNA repair foci, implying the involvement of KDM1A in the DNA damage response. Overall, our results indicate that KDM1A impacts CRC progression in several non-overlapping ways, and therefore it represents a promising epigenetic target to prevent tumor relapse., (© 2023. The Author(s).)

Background: The aim of the study is to identify the advantages, if any, of post-operative MRIs performed at 48 h compared to MRIs performed after 48 h in glioblastoma surgery., Materials and Methods: To assess the presence of a residual tumor, the T1-weighted Contrast Enhancement (CE), Apparent Diffusion Coefficient (ADC), and Cerebral Blood Volume (rCBV) in the proximity of the surgical cavity were considered. The rCBV ratio was calculated by comparing the rCBV with the contralateral normal white matter. After the blind image examinations by the two radiologists, the patients were divided into two groups according to time window after surgery: ≤48 h (group 1) and >48 h (group 2)., Results: A total of 145 patients were enrolled; at the 6-month follow-up MRI, disease recurrence was 89.9% (125/139), with a mean patient survival of 8.5 months (SD 7.8). The mean ADC and rCBV ratio values presented statistical differences between the two groups ( p < 0.05). Of these 40 patients in whom an ADC value was not obtained, the rCBV values could not be calculated in 52.5% (21/40) due to artifacts ( p < 0.05)., Conclusion: The study showed differences in CE, rCBV, and ADC values between the groups of patients undergoing MRIs before and after 48 h. An MRI performed within 48 h may increase the ability of detecting GBM by the perfusion technique with the calculation of the rCBV ratio.

Background: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes., Methods: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate., Results: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞)., Conclusions: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection., (© 2022. The Author(s).)

Background: The plasma cell disease is been studying by the whole-body MRI technology. However, the time requested to learn this radiological technique is unknown., Purpose: To esteem, quantitatively and qualitatively, the essential time to learn the whole-body MRI diffusion-weighted imaging with background body signal suppression in patients with plasma cell disease., Materials and Methods: Between January 2015 and February 2017, three readers in-training with different levels of experience examined the anonymised and randomised whole-body MRI images of 52 patients with a diagnosis of plasma cell disease and analysed their morphological (T1w, T2w with and without fat suppression) and functional sequences. Reports of an expert radiologist were considered the standard of reference. Images were analysed in two sessions, during which each reader was timed. Readers reported the number of segments with lesions and staged the disease using the Durie-Salmon PLUS staging system. Weighted Cohen's ĸ and Z-test were used to compare the trainees' reports with those of the expert radiologist, and learning curves were drawn up to show changes between the two sessions., Results: Weighted Cohen's ĸ of number of lesioned segments increased from 0.536 ± 0.123 to 0.831 ± 0.129 (Prob > Z under 0.005), thus approaching the goal of ĸ > 0.8. Trainees reached the level of experienced radiologist in terms of time by the 33rd patient. Agreement concerning the Durie-Salmon PLUS increased from 0.536 ± 0.123 to 0.831 ± 0.129 (Prob > Z under 0.005)., Conclusions: The findings of this study demonstrate that whole-body MRI with DWIBS can be learned in about 80 reports and leads to a high level of inter-observer concordance when using the Durie-Salmon PLUS staging system., (© 2021. The Author(s).)

Background: The development of resolution recovery (RR) algorithms has made it possible to preserve the good quality of cardiac images despite a reduced number of counts during study acquisition., Objective: Our purpose was to evaluate the performance of three different software packages in the quantification of left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) from gated perfusion SPECT, applying a resolution recovery (RR) algorithm (GE Myovation Evolution), with respect to cardiac MRI (cMRI) as a gold standard., Methods: We retrospectively enrolled 21 patients, with suspected or known coronary heart disease. Images at rest were reconstructed by filtered back projection (FBP) and by an iterative protocol with the RR algorithm. EDV, ESV, and LVEF were automatically computed employing Quantitative Gated SPECT (QGS), Myometrix (MX), and Corridor 4DM (4DM). Any difference in EDV, ESV, and LVEF calculation between cMRI and the three packages (with FBP and iterative reconstruction with RR) was tested using Wilcoxon or paired t-test, with the assumption of normality assessed using the Shapiro-Wilk test. Agreement between imaging reconstruction algorithms and between gated-SPECT software packages and cMRI was studied with Pearson's (r) or Spearman's (R) correlation coefficients and Lin's concordance correlation coefficient (LCC)., Results: Intra-software evaluation always revealed very strong correlation coefficients (R, r ≥ 0.8) and excellent LCC coefficients (LCC > 0.95), except for the LCC coefficient between MX-FBP and MX-RR in EDV evaluation, nevertheless considered very good (LCC = 0.94). EDV and ESV had significantly lower value when calculated with the RR algorithm with respect to FBP reconstruction in QGS and MX. LVEF estimation did not show significant differences for QGS-FBP, QGS-RR, MX, and 4DM-RR with respect to cMRI., Conclusion: All reconstruction methods systematically underestimate EDV and ESV, with higher underestimation applying only the RR. No significant differences were observed between 4DM - RR and 4DM-FBP, for each parameter, when the 4DM package was used., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: The aim of this study is to compare the short and long-term outcomes of intracorporeal anastomosis (IA) versus extracorporeal anastomosis (EA) during laparoscopic resection of splenic flexure for cancer, in 3 high-volume Italian centers., Materials and Methods: A retrospective analysis was conducted on a multicenter database of a consecutive series of patients who underwent an elective laparoscopic resection of the splenic flexure for colon cancer in 3 high-volume centers between January 2008 and August 2017. Propensity score matching analysis was performed to overcome patients' selection bias between the 2 surgical techniques. Data on patients' demographics, operative details, short-term and long-term outcomes were prospectively recorded., Results: In total, 102 patients were selected. After propensity score match, 72 patients were compared: 36 for the IA group, 36 for the EA group. The IA group showed a significantly shorter median time to first flatus, time to first stool, time to oral feeding, and time to discharge, as well as significantly lower incidence of postoperative severe surgical complications, especially in terms of wound infections, and of incisional hernia (IH).Risk factors for IH on logistic regression were longer operative time, EA, longer incision, postoperative blood transfusions, and longer specimen., Conclusions: The IA in laparoscopic resection of the splenic flexure is feasible and safe in terms of short-term and long-term outcomes. Major advantages are shorter time to first flatus and first stool, complete oral feeding and time to discharge, with minor incidence of severe surgical complications, such as wound infection, and lower incidence of IH.

Background: The aim of this study was to determine whether apparent diffusion coefficient (ADC) bi-component curve-fitting histogram analysis and volume percentage change (VPC) prior to bevacizumab treatment can stratify progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma multiforme (GBM) on first recurrence., Methods: We retrospectively evaluated 17 patients with recurrent GBM who received bevacizumab and fotemustine ( n  = 13) or only bevacizumab ( n  = 4) on first recurrence at our institution between December 2009 and July 2015. Both T2/FLAIR abnormalities and enhancing tumor on T1 images were mapped to the ADC images. ADC-L and ADC-M values were obtained trough bi-Gaussian curve fitting histogram analysis. Furthermore, the study population was dichotomized into two subgroups: patients displaying a reduction in enhancing tumor volume of either >55% or <55% between the mean value calculated at baseline and first follow-up. Subsequently, a second dichotomization was performed according to a reduction in the T2 / FLAIR volume >41% or <41% at first check after treatment. OS and PFS were assessed using volume parameters in a Cox regression model adjusted for significant clinical parameters., Results: In univariate analysis, contrast-enhanced (CE)-ADC-L was significantly predictive of PFS ( p  = 0.01) and OS ( p  = 0.03). When we dichotomized our sample using the 55% cut-off for enhancing tumor volume, CE-VPC was able to predict PFS ( p  = 0.01) but not OS ( p  = 0.08). In multivariate analysis, only the CE-ADC-L was predictive of PFS ( p  = 0.01), albeit not predictive of OS ( p  = 0.14). CE-ADC-M, T2/FLAIR-ADC-L, T2/FLAIR-ADC, and T2/FLAIR VPC were not significantly predictive of PFS and OS ( p  > 0.05) in both univariate and multivariate analysis., Conclusions: CE-ADC and CE-VPC can stratify PFS for patients with recurrent glioblastoma prior to bevacizumab treatment.

The objective is to investigate the short- and long-term outcomes of laparoscopic resections of splenic flexure colon cancers in three Italian high-volume centers. The laparoscopic resection of splenic flexure colon cancers is a challenging procedure and has not been completely standardized, mainly due to the technical difficulty, the arduous identification of major blood vessels, and the problems associated with anastomosis construction. In this retrospective cohort observational study, a consecutive series of patients treated in three Italian high-volume centers with elective laparoscopic resection of the splenic flexure for cancer is analyzed. The observational period was from January 2008 to August 2017. Patient demographics and clinical features, operative data, and short- and long-term outcomes were prospectively recorded in a specific database and were retrospectively analyzed. During the observation period, 117 patients were selected. Conversion to open surgery was necessary in 15 patients (12.8%). Of 102 complete laparoscopic procedures, multi-visceral resection was performed in 13 cases (12.7%). Postoperative surgical complications occurred in 13 patients (12.7%), with 3 cases of anastomotic leak (2.9%) and 3 cases of re-operation (2.9%). The postoperative mortality in this population was null. The 5-year overall survival rate was 84.3%, and the 5-year disease-free survival rate was 87.8%. Laparoscopic resection of the splenic flexure is feasible and safe in high-volume centers. Compared to the results of other laparoscopic colonic resections, the short- and long-term outcomes are similar, but the conversion rate is higher.

Purpose: To quantitatively compare the artefact reduction between standard and metallic artefact reduction (MAR) fast spin echo (FSE) T2 sequences in a low-field magnetic resonance imaging (MRI) scanner (0.3 T) in patients with titanium volar wrist plating., Materials and Methods: Sixteen patients with fractures of the distal radius, treated with titanium volar wrist plating and screws, were examined using a dedicated 0.3 T MRI scanner. Coronal standard FSE T2, FSE T2 high bandwidth (HiBW) and FSE T2 view angle tilting (VAT) sequences were performed. Metallic artefact volume, consisting of both "black" and "bright" artefacts, was calculated for each sequence. Quantitative differences were compared using repeated measures ANOVA test (P < 0.05)., Results: FSE T2 HiBW and FSE T2 VAT showed a significant reduction in artefact volume compared to the standard sequence. Differences between the artefact volume of the standard FSE T2, HiBW and VAT sequences were statistically significant for both the "black" and "bright" artefacts (P < 0.0001). Differences between the 1.5 HiBW and VAT sequences were statistically significant (black P < 0.0001, bright P < 0.0302)., Conclusions: MAR sequences significantly reduced metallic artefacts in vivo using a 0.3 T MRI scanner.

Background: The aim of the study was to evaluate the effectiveness and reliability of a combined computed tomography angiography (CTA) and computed tomography perfusion (CTP) approach in the diagnosis of cerebral vasospasm after subarachnoid hemorrhage., Methods: Nineteen patients with clinical signs of arterial vasospasm and positive transcranial Doppler (TCD) were enrolled and underwent CTP. Mean time transit (MTT), cerebral blood flow (CBF) and cerebral blood volume (CBV) values of 20 standardized ROI (regions of interest) were analyzed, and CTA used to measure the gauge of 26 arterial ramifications. CTA measurements were compared with those taken upon hospitalization. Of the 19 patients, 11 were scheduled for digital subtraction angiography (DSA), performed less than 12 hours after execution of the CTA-CTP protocol. The results were compared with findings of DSA and/or clinical follow-up and CT or TCD., Results: Computed tomography angiography diagnosis of vasospasm was confirmed in all cases (100% sensitivity and 100% specificity), while CTP yielded 3 false negatives (70% sensitivity and 100% specificity). All patients sent for endovascular treatment had received diagnostic confirmation of vasospasm by angiography. CTP thresholds proved reliable in both diagnosis and indicating treatment., Conclusions: Combined one-shot CT angiography and CT perfusion represents a valid alternative to DSA in the diagnosis and management of cerebral vasospasm.

Whole body magnetic resonance imaging (MRI) with diffusion-weighted imaging (WB-MRI-DWI) is currently emerging as a diagnostic technique in the evaluation of bone metastases from breast, prostate, lung, thyroid, and melanoma tumors. The most relevant articles regarding the detection of solid tumor bone metastases with MRI have been reviewed and cited. The imaging methods currently used in the detection of bone metastases are bone scintigraphy, computed tomography (CT), and positron emission tomography (PET/CT) with 2-deoxy-2-[fluorine-18] fluoro-d-glucose (18F-FDG PET/CT). WB-MRI-DWI allows qualitative and quantitative evaluation of focal lesions through signal intensity evaluation on DWI images and the reconstruction of the apparent diffusion coefficient (ADC) map. In prostate and breast cancer, WB-MRI-DWI is useful in assessing the response of bone lesions to therapy and to detecting early non-responders, while in lung cancer the method shows a similar sensitivity to 18F-FDG PET/CT in the detection of bone metastases. In bone metastases of thyroid tumors and melanoma, the WB-MRI-DWI shows a higher sensitivity when compared to 18F-FDG PET/CT. With a standardization of the WB-MRI-DWI protocol, this method seems to play an important role in the diagnosis of bone solid tumor metastases.

Purpose: The aim of this retrospective study was to map the specific ischemic lesion patterns of distribution in patent foramen ovale-related stroke (PFO-stroke) and atrial fibrillation-related stroke (AF-stroke) in patients with idiopatic ischemic stroke., Materials and Methods: 750 ischaemic strokes were screened on basis of diagnostic imaging and tests: patients with known causes were excluded. 171 patients with unknown cause were selected and divided in two groups: AF-stroke (43 patients) and PFO-stroke (128 patients). Vascular territories of ischemic involvement were divided into four classes in each group: the anterior cerebral artery, the middle cerebral artery, the vertebro-cerebral artery (including the posterior cerebral artery) and multisite (MS) involvement., Results: Infarcts in vertebro-basilar territory and multisite represented each one about 32% of infarcts in PFO-stroke group and their involvement are more frequent than AF-stroke group (p = 0.03). Ischemic lesions in PFO-group were predominantly cortical (34.3%), and in AF-group cortical-subcortical (60.4%). Multisite pattern of ischemic lesion was more frequent in patients with severe degree of right to left shunts (37.5%)., Conclusion: In clinical practice, PFO may be considered a cause of cortical stroke on the basis of radiological findings, when VB vascular territory or MS brain involvement is present in younger patients (<50 age).

Novel nanographenes were prepared by a photochemical cyclodehydrochlorination (CDHC) reaction. Chlorinated precursors were irradiated in acetone in the presence of a base or in pure benzene and underwent multiple (up to four) regioselective cyclization reactions to provide rigid π-conjugated molecules. Pure compounds were recovered in good yields by simple filtration at the end of the reaction. The CDHC reaction showed compatibility with both electron-poor and electron-rich substrates, thus allowing the synthesis of pyridine- and thiophene-fused nanographenes. It also enabled the synthesis of sterically hindered contorted π-conjugated molecules without causing full aromatization. A kinetic study showed that the CDHC reaction under the conditions used is a very fast process, and some reactions are completed within minutes. The CDHC reaction thus shows great potential as an alternative to other reactions involving harsher conditions for the preparation of nanographenes., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: Adrenal gland metastasis are the second most common type of adrenal mass lesions after adenomas and they could be related to numerous malignancies; Literature shows that adrenal metastasis deriving from colorectal cancer are very rare., Material of the Study: A 71-year old - male patient, treated two years before with right colectomy and adjuvant chemotherapy for right colon cancer, came to our attention after the diagnosis at follow up, of a left adrenal gland mass; CT scan and CT - PET did not show other pathological findings., Results: The patient underwent left adrenalectomy with trans-peritoneal laparoscopic approach: the definitive histological examination diagnosed metastatic tissue of colonic cancer in left adrenal gland., Conclusions: Adrenal gland metastases are common clinical entities, but which of them arise starting from colonic cancer are very rare and they are generally discovered about 1 year after the first diagnosis of cancer. Early diagnosis, laparoscopic radical excision when feasible and eventual adjuvant radio-chemotherapy are actually the proper clinical management of adrenal gland metastases finalized to better outcomes in terms of longer survival rate and quality of life., Key Words: Adrenal gland, Colorectal cancer, Laparoscopic, Metastasis.