Corrosion Rate and Mechanism of Degradation of Chitosan/TiO2 Coatings Deposited on MgZnCa Alloy in Hank's Solution.

Overly fast corrosion degradation of biodegradable magnesium alloys has been a major problem over the last several years. The development of protective coatings by using biocompatible, biodegradable, and non-toxic material such as chitosan ensures a reduction in the rate of corrosion of Mg alloys in simulated body fluids. In this study, chitosan/TiO2 nanocomposite coating was used for the first time to hinder the corrosion rate of Mg19Zn1Ca alloy in Hank's solution. The main goal of this research is to investigate and explain the corrosion degradation mechanism of Mg19Zn1Ca alloy coated by nanocomposite chitosan-based coating. The chemical composition, structural analyses, and corrosion tests were used to evaluate the protective properties of the chitosan/TiO2 coating deposited on the Mg19Zn1Ca substrate. The chitosan/TiO2 coating slows down the corrosion rate of the magnesium alloy by more than threefold (3.6 times). The interaction of TiO2 (NPs) with the hydroxy and amine groups present in the chitosan molecule cause their uniform distribution in the chitosan matrix. The chitosan/TiO2 coating limits the contact of the substrate with Hank's solution.

Exploring the Role of Immunotherapy-Based Treatments for Advanced Non-Small-Cell Lung Cancer With Novel Driver Alterations.

BACKGROUND: Immunotherapy (IO) single agent or combined with chemotherapy (CT-IO) is the standard treatment for advanced non-small-cell lung cancer (aNSCLC) without driver alterations. IO efficacy in patients with novel driver alterations is not well reported. MATERIALS AND METHODS: Data of aNSCLC patients treated with IO or CT-IO in any line from January 2016 to September 2022 were retrospectively collected. Patients harboring novel driver alterations (m-cohort), including MET exon 14 skipping, BRAF (V600E or atypical), RET rearrangements, HER2 point mutations/exon 20 insertions or uncommon EGFR mutations/EGFR exon 20 insertions, and wild type patients (wt-cohort) were eligible. Clinico-pathological data were extracted from Institutional databases and compared through chi square or Fisher's exact test. Survivals were estimated through Kaplan-Meier method and compared by log-rank test. RESULTS: m-cohort and wt-cohort included 84 and 444 patients, respectively. Progression free survival (PFS) was 5.53 vs. 4.57 months (P= .846) and overall survival (OS) was 25.1 vs. 9.37 months, (P < .0001) for m-cohort compared to wt-cohort. Within the m-cohort, BRAF atypical mutations had the better outcomes (Overall Response Rate [ORR], PFS), targeted agents timing did not affect response to IO and CT-IO had better ORR and disease control rate (DCR) compared to IO single agent (P = .0160 and P = .0152). In the PD-L1≥50% group, first line IO single agent resulted in inferior ORR (P = .027) and PFS (P = .022) in m-cohort compared to wt-cohort. CONCLUSION: IO based treatments seem not detrimental for patients harboring novel driver alteration. Adding CT could improve modest responses to IO alone. Confirmation on larger datasets is required.

Paraneoplastic neurological syndromes in patients affected by SCLC: a case series.

Paraneoplastic syndromes occur in about 0.1% of patients affected by neoplastic diseases. In some types of tumors, such as Small Cell Lung Cancer (SCLC), Thymoma, and particular forms of Plasmacytoma, the association with Paraneoplastic Neurological Syndromes (PNS) is much more frequent. It seems that these syndromes are triggered by tumor production of factors normally expressed only by the individual's nervous system. The immune system stimulates an autoimmune response against these factors that induce neurological symptoms. Also, in light of the latest updates on the relationship between immunotherapy and PNS as well as of the introduction of first-line immunotherapy in SCLC, it seems that the use of immunotherapy in SCLC is associated with concomitant increase in autoimmune neurological syndromes.In this article, we report our experience at Istituto Nazionale Tumori of Milan with three patients affected by SCLC and PNS. Our experience seems to confirm that the oncological treatment scarcely impacts the paraneoplastic neurological deficits. Further research is needed to improve the treatment and recovery of patients affected by PNS.

A Study of the Localized Ceria Coating Deposition on Fe-Rich Intermetallics in an AlSiFe Cast Alloy.

Corrosion inhibiting conversion coating formation is triggered by the activity of micro-galvanic couples in the microstructure and subsequent local increase in pH at cathodic sites, which in the case of aluminium alloys are usually intermetallics. Ceria coatings are formed spontaneously upon immersion of aluminium alloys in a cerium conversion coating solution, the high pH gradient in the vicinity of intermetallics drives the local precipitation of ceria conversion compounds. Cu-rich intermetallics demonstrate a highly cathodic nature and have shown the local precipitation reaction to occur readily. Fe-rich intermetallics are, however, weaker cathodes and have shown varied extents of localized deposits and are in focus in the current work. Model cast Al-7wt.%Si alloys have been designed with 1 wt.% Fe, solidified at different cooling rates to achieve two different microstructures, with big and small intermetallics, respectively. Upon subjecting the two microstructures to the same conversion coating treatment (immersion in a 0.1 M CeCl3 solution) for a short period of 2 h, preferential heavy deposition on the boundaries of the big intermetallics and light deposition on the small intermetallics was observed. Based on these observations, a mechanism of localized coating initiation at these Fe-rich intermetallic particles (IM) is proposed.

The process of EUSOMA certification improves the quality of breast cancer care: the experience of an Italian EUSOMA certificated Breast Unit (BU) according to the results of a cross-sectional study.

INTRODUCTION: The adherence to recognized guidelines and the constant monitoring of performance throughout quality indicators (QIs) are strategic tools to improve the quality of care. The study is aimed to assess the effect of the EUSOMA (European Society of Breast Cancer Specialists) certification process on the quality of breast cancer care of an EUSOMA certified Breast Unit (BU) of Northern Italy. MATERIALS AND METHODS: Seventeen mandatory and recommended EUSOMA QIs, based on 594, were analysed for the years 2015-2018. Univariate logistic regression models were performed to compare QIs performance in the years before and after obtaining the EUSOMA certification (2015-6 vs. 2017-8). RESULTS: Compared to the years 2015-6, the second period of BU activity showed a higher number of QIs achieving both the minimum standard (15 vs. 11) and the 100% of completeness (6 vs. 1). There was a significant improvement of the two QIs evaluating the proportion of Ductal Carcinoma in situ receiving just an operation (from 76% to 95.2%; p=0.033) and the completeness of the prognostic characterisation of invasive cancers (from 94.6% to 99.5%; p=0.022). Conversely, the QI related to the endocrine-sensitive invasive carcinoma receiving adjuvant hormonal therapy dropped from 92.1% to 85.9% (p=0.042) and was significantly lower for patients over 74 compared to those aged ≤54 (73.8% vs. 94.7%; p<0.0001 Fisher's exact test). CONCLUSIONS: The EUSOMA certification process enhanced the clinical practice, promoting a tailored-patient primary systemic or adjuvant therapy and avoiding unnecessary invasive surgical and local-regional treatments.

Association between acute histopathological changes of rectal walls and late radiation proctitis following radiotherapy for prostate cancer.

PURPOSE: The impact of acute histopathological changes (HC) of the rectum on development of late clinical proctitis (LCP) after external radiotherapy (RT) for prostate cancer is poorly explored and was the primary end point of this prospective study. METHODS: In 70 patients, 15 HC of early rectal biopsies after RT were identified, whereby RT was conventional 2D RT in 41 cases and conformational 3D RT in 29. Associations of HC in anterior and posterior rectal walls (ARW, PRW) with LCP, acute endoscopic (AEP) and acute clinical proctitis (ACP) were statistically evaluated considering as explicative variables the patient general characteristics and the HC. RESULTS: The mean patients' follow-up was 123.5 months (24-209). The median prostatic dose was 72 Gy (2 Gy/fraction). For the 41 and 29 patients the ARW and PRW doses were 64 and 49 Gy vs. 63 and 50 Gy, respectively. The incidence of LCP ≥ grade 2 at 10 years was 12.9%. The univariate (p = 0.02) and Kaplan-Meyer methods (p = 0.007) showed that the gland (or crypts) loss in the ARW was significantly associated with LCP. AEP and ACP occurred in 14.3 and 55.7% of cases. At multivariate level AEP significantly correlated with hemorrhoids (p = 0.014) and neutrophilia in ARW (p = 0.042). CONCLUSIONS: Early after RT, substantial gland loss in ARW is predictive of LCP. To reduce this complication with conventional fractionation, we suggest keeping the mean dose to ARW ≤48-52 Gy.

Application of a Molybdenum and Tungsten Disulfide Coating to Improve Tribological Properties of Orthodontic Archwires.

Coatings incorporating nanoparticles of molybdenum and tungsten disulfide (MoS2 and WS2)-known for their lubricating properties-are applied to orthodontic stainless steel wires to verify if there is an improvement in terms of tribological properties during the sliding of the wire along the bracket. To simulate in vitro sliding of the wire along the bracket and evaluate friction 0.019 × 0.025 inches orthodontic stainless steel (SS) wires were subjected to the application, by electrodeposition, of Ni, Ni + MoS2, and Ni + WS2. The samples produced were analyzed with scanning electron microscopy and assessment of resistance to bending. Thirty-two test conditions have been analyzed, arising from the combination of four types of coatings (SS bare wires and strings with three types of coating), two types of self-ligating bracket (Damon Q, Ormco and In-Ovation R, GAC International), two bracket-wire angles (0° and 5°), two environments (dry and wet). Analyses carried out on the samples show acceptable coatings incorporating MoS2 and WS2 and a resistance of coatings after a minimum bending. In "dry conditions" a statistically significant decrease in friction occurs for wires coated with MoS2 and WS2 if associated with the In-Ovation bracket. In "wet conditions" this decrease is observed only in isolated test conditions. Analysis of the wires after sliding tests show little wear of the applied coatings. Nanoparticles are acceptable and similar in their behavior. Improvements in terms of friction are obtained pairing coatings incorporating MoS2 and WS2 with the In-Ovation bracket in dry conditions.

Diagnostic management of occult nodal lymphangioleiomyomatosis detected during pelvic cancer staging. Localized finding or systemic disease?

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a neoplastic disease that generally arises in the lung (pLAM) and may be associated with "Tuberous sclerosis complex" (TSC). Occasionally, LAM can arise at the extrapulmonary sites (eLAM), such as the mediastinum, the retroperitoneum or the lymph nodes. 25-30% of the patients affected by pLAM develop eLAM. In asymptomatic patients, the presence of mediastinal and retroperitoneal eLAM preceded that of pLAM by usually 1-2 years. Nevertheless, some authors reported that the nodal eLAM, detected during pelvic cancer staging, arise in patents without pLAM and/or TSC. In this paper we review the Literature of this rare condition suggesting its diagnostic management. RESULTS: To date, it has been reported 30 cases. The mean age at diagnosis is 55 years and around 30% of patients are postmenopausal. In only 2 cases was diagnosed a following p-LAM. One patient with endometrioid carcinoma and pelvic nodal eLAM reported TSC2 germiline mutation. None case was associated with both p-LAM and TSC. CONCLUSIONS: The retrospective probability to have p-LAM in patients with staging pelvic nodal e-LAM is 6,6% (4/30) lower than the probability to have e-LAM in patients affected by p-LAM (25-30%). In both this association is more probable sporadically than associated with TSC. The association between cancer staging pelvic nodal e-LAM and TSC is low (3%; 1/30). The p-LAM developed are asymptomatic with a behavior, regardless of hormonal status, similar to lesions diagnosed in postmenopausal although further studies are mandatory to confirm it.

Colonic Ewing Sarcoma/PNET associated with liver metastases: A systematic review and case report.

Ewing Sarcoma is a highly lethal undifferentiated tumor of bone. ES is a small round cell tumor with etiological and characteristic chromosomal translocations between TET/FET (TLS/FUS, EWSR1, and TAF15) and ETS (E26 transformation-specific) family genes. Generally, therapeutic approach for metastatic Ewing Sarcoma includes both local (surgery and radiotherapy) and systemic (chemotherapy) disease control with an overall cure rate of 20%. For extra-osseous tumors, the most common primary sites of disease are trunk, extremities, head and neck, retroperitoneum. Among other sites, Ewing Sarcoma/PNET may also rarely arise in colon and rectum. Even if colonic Ewing Sarcoma/PNET have been previously reported in 5 cases, none of those reports came from right side of the colon. In this article, we report the first case of right-sided Ewing Sarcoma with synchronous liver metastases completely responding to first line chemotherapy. Furthermore, we provide a systematic qualitative review of the current literature on adult colorectal Ewing Sarcoma using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Effect of high-pressure torsion on microstructure, mechanical properties and corrosion resistance of cast pure Mg.

High-pressure torsion (HPT) processing was applied to cast pure magnesium, and the effects of the deformation on the microstructure, hardness, tensile properties and corrosion resistance were evaluated. The microstructures of the processed samples were examined by electron backscatter diffraction, and the mechanical properties were determined by Vickers hardness and tensile testing. The corrosion resistance was studied using electrochemical impedance spectroscopy in a 3.5% NaCl solution. The results show that HPT processing effectively refines the grain size of Mg from millimeters in the cast structure to a few micrometers after processing and also creates a basal texture on the surface. It was found that one or five turns of HPT produced no significant difference in the grain size of the processed Mg and the hardness was a maximum after one turn due to recovery in some grains. Measurements showed that the yield strength of the cast Mg increased by about seven times whereas the corrosion resistance was not significantly affected by the HPT processing.

Clear cell colorectal carcinoma: Time to clarify diagnosis.

Primary clear cell colorectal carcinoma (CCC) is a very rare entity accounting for only 35 cases reported in the Literature. CCC is neither classified as a distinct entity nor is it defined as a CRC variant because its ontogeny remains unclear. Most of the reported CCC were found in the distal colon in patients with a mean age of 56 years. Histologically, clear cell change is the main morphologic feature and may present in a "pure" form, composed exclusively of clear cells, or in a "composite" form, admixed with other morphologically different components. It is possible to distinguish two biologically different types of CCC, with different clinical-pathologic features, therapeutic management and diagnostic criteria: a) Intestinal CCC consisting of an aggressive neoplasm, affecting mainly adult men, characterized by an intestinal-type immunoprofile (CK20+, CK7-, CEA+, CDX-2+) and b) Müllerian CCC consisting of an indolent carcinoma of the sigmoid-rectum, affecting young women, characterized by a different (CK7+, CK20-, CEA-, CA125 +) immunoprofile. Considerable diagnostic difficulties can arise in distinguishing CCC and primary or secondary clear cell neoplasms, such as metastases from renal carcinoma, lower urinary tract, female genital tract, adrenal gland, mesothelioma, melanoma and primary intestinal PEComa. In this paper we review the Literature with two additional cases in order to define the diagnostic criteria of CCC.

Case Report of a Well-Differentiated Papillary Mesothelioma of the Tunica Vaginalis in an Undescended Testis With Review of Literature.

Well-differentiated papillary mesothelioma (WDPM) affecting the tunica vaginalis testis is a rare tumor, and very little is known about the clinicopathological spectrum of this variant as a distinct entity. Most patients with WDPM suffer from scrotal pain or swelling, but hydrocele seems to be the most common presenting symptom. These lesions are usually not aggressive and are accompanied by an indolent clinical behavior. In this article, we report the first case known of WDPM in an undescended testis, and in addition, we review the literature for similar cases.

p16 Expression in Prostate Cancer and Nonmalignant Lesions: Novel Findings and Review of the Literature.

BACKGROUND: Prostatic specimens occasionally may contain proliferative foci of the small atypical acini that display some but not all features of prostate carcinoma. p504s is the only prostatic cancer (PC)-specific marker that, in combination with basal cell markers, help in the diagnosis of malignant lesions. Very little is known about the diagnostic importance of p16 in primary prostate carcinoma and nonmalignant elements. MATERIALS AND METHODS: We recruited 137 of routinely diagnostic prostatic specimens (between 2009 and 2013), which consisted of 21 prostatectomy, 15 transurethral prostatic resection, and 101 needle biopsy. We evaluated p16, in comparison with p504s, in prostatic carcinoma and benign glands. In this study, both nuclear and cytoplasmatic p16 expression were considered positive. RESULTS: We observed p16 expression in 86% of PC specimens and 16% of benign elements (P=0.001). Interestingly, p16 alone retained a high diagnostic potential in prostatectomy (95%) and in needle biopsy (84%), exhibiting a close association with PC. p504s had a high sensitivity (97%) and predictive negative value (98%) but a low specificity (71%) and predictive positive value (63%). In contrast, p16-positive expression showed a higher specificity (84%) and predictive positive value (74%) than p504s. Two prostatic carcinoma negative for p504s were positive for p16, whereas 7 cases negative for p16 were positive for p504s, and notably none was negative for both markers. In prostatectomy, p16 showed a higher diagnostic accuracy but not on transurethral prostatic resection. In needle biopsies, both markers were complementary, indicating that their combined detection may help in performing an accurate diagnosis.In conclusion, our data suggest that p16 expression is significantly enhanced in prostate carcinoma as compared with nonmalignant elements. Our results provide evidence that p16 and p504s together could improve the diagnosis of PC in prostatectomy and needle biopsies.

The chromatin remodelling component SMARCB1/INI1 influences the metastatic behavior of colorectal cancer through a gene signature mapping to chromosome 22.

BACKGROUND: INI1 (Integrase interactor 1), also known as SMARCB1, is the most studied subunit of chromatin remodelling complexes. Its role in colorectal tumorigenesis is not known. METHODS: We examined SMARCB1/INI1 protein expression in 134 cases of colorectal cancer (CRC) and 60 matched normal mucosa by using tissue microarrays and western blot and categorized the results according to mismatch repair status (MMR), CpG island methylator phenotype, biomarkers of tumor differentiation CDX2, CK20, vimentin and p53. We validated results in two independent data sets and in cultured CRC cell lines. RESULTS: Herein, we show that negative SMARCB1/INI1 expression (11% of CRCs) associates with loss of CDX2, poor differentiation, liver metastasis and shorter patients' survival regardless of the MMR status or tumor stage. Unexpectedly, even CRCs displaying diffuse nuclear INI1 staining (33%) show an adverse prognosis and vimentin over-expression, in comparison with the low expressing group (56%). The negative association of SMARCB1/INI1-lack of expression with a metastatic behavior is enhanced by the TP53 status. By interrogating global gene expression from two independent cohorts of 226 and 146 patients, we confirm the prognostic results and identify a gene signature characterized by SMARCB1/INI1 deregulation. Notably, the top genes of the signature (BCR, COMT, MIF) map on the long arm of chromosome 22 and are closely associated with SMARCB1/INI1. CONCLUSION: Our findings suggest that SMARCB1/INI1-dysregulation and genetic hot-spots on the long arm of chromosome 22 might play an important role in the CRC metastatic behavior and be clinically relevant as novel biomarkers.

Right-sided rhabdoid colorectal tumors might be related to the serrated pathway.

BACKGROUND: Rhabdoid colorectal tumor (RCT) is a rare, highly aggressive neoplasm recurrent in elderly patients, commonly at the caecum. The molecular mechanisms underlying RCT pathogenesis remain poorly elucidated. The differential diagnosis is with the malignant rhabdoid tumors of infancy characterized by genetic inactivation of SMARCB1 (INI1) or deletions of chromosome 22q12 locus. MATERIALS AND METHODS: To shed light on RCT pathogenesis, we investigated genetic and epigenetic alterations in two cases of pure and composite RCT and compared them with the profiles of matched adenomas and normal mucosa. Immunohistochemical analysis, FISH, methylation specific PCR and DNA sequencing analysis were performed on paraffin-embedded tissues. RESULTS: Loss of epithelial markers, (CK20, CDX2 and E-cadherin) and intense vimentin expression was observed in RCTs but neither in the normal mucosa or adenomas. INI1 expression was detected in normal mucosa, adenomas and retained in pure RCT, while it was undetected in composite RCT. Rearrangement of the 22q12 locus was found only in pure RCT. The APC/ß-catenin pathway was not altered, while MLH1 immunostaining was negative in RCTs and positive in adenomas and normal mucosa. These expression profiles were associated with V600E BRAF mutation, a progressive accumulation of promoter methylation at specific CIMP loci and additional genes from the normal mucosa to tubular adenoma and RCT. CONCLUSIONS: Right-sided RCT could be characterized by epigenetic events and molecular features likely similar to those occurring in the serrated pathway and associated with epithelial-mesenchymal transition. These extremely rare tumors may benefit from the use of new biological molecules specific for colorectal carcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1641385210804556.

Rhabdoid carcinoma of the colon: a distinct entity with a very aggressive behavior: a case report associated with a polyposis coli and review of the literature.

Rhabdoid colon tumors (RCTs) are rare lesions whose existence as an independent distinct entity remains controversial. To date, 6 RCTs have been reported. This study reports a novel case associated with polyposis coli in a 73-year-old woman. Histologically, the neoplasia was heterogeneous consisting of an adenocarcinoma associated with rhabdoid features. In rhabdoid component, an intense expression of MSH2 was noted but MLH1 was negative. A BRAF V600E mutation and no KRAS mutations were identified. The promoter regions of subset of genes highly specific to characterize the CIMP status (NEUROG1, IGF2, RUNX3, SOCS1, including MLH1) were hypermethylated, suggesting the presence of CIMP+ and MSI high tumor. In conclusion, all RCTs have similar clinical features. The presence of polyposis and adenocarcinoma component as well as the expression of mesenchymal marker suggests a sarcomatous dedifferentiation. It is argued that RCT could be a very aggressive entity of colon, which could benefit from new biological colonic treatments.

Axillary lymph node nanometastases are prognostic factors for disease-free survival and metastatic relapse in breast cancer patients.

PURPOSE: Early breast cancer presents with a remarkable heterogeneity of outcomes. Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. Thus, we systematically evaluated the presence of lymph node tumor cell deposits