Histologic and sonographic features of holmium laser in the treatment of chronic venous disease

A new holmium laser (HOL) has been introduced to the market. The device is able to reduce the great saphenous vein (GSV) caliber in a tumescence-free procedure, favoring an effective sclerotherapy of large vessels. Aim of the present investigation is to provide the first in vivo data about the effect of HOL on GSV histology

Effect of SARS-CoV-2 infection in pregnancy on CD147, ACE2 and HLA-G expression

Introduction: Recent studies reported a differential expression of both ACE2 and CD147 in pregnant women associated to SARS-CoV-2 placental infection. The aim of this study is to further investigate the placental SARS-CoV-2 infection and the potential effect on protein expression (ACE2, CD147, HLA-G and CD56). Methods: The study was on three subgroups: i) 18 subjects positive for SARS-CoV-2 swab at delivery; ii) 9 subjects that had a positive SARS-CoV-2 swab during pregnancy but resulted negative at delivery; iii) 11 control subjects with physiological pregnancy and with no previous or concomitant SARS-CoV-2 swab positivity. None of the subjects were vaccinated for SARS-CoV-2 infection. The placenta samples were analyzed for SARS-CoV-2 NP (Nucleocapsid protein) positivity and the expression of ACE2, CD147, HLA-G and CD56. Results: We observed a higher percentage of SARS-CoV-2 NP positive placenta samples in the group of SARS-CoV-2 PCR positive at delivery in comparison with SARS-CoV-2 PCR negative at delivery. The localization of SARS-CoV-2 NP positivity in placenta samples was mainly in syncytiotrophoblast (ST) of SARS-CoV-2 PCR positive at delivery group and in extra-villous trophoblast (EVT) of SARS-CoV-2 PCR negative at delivery group. CD147, HLA-G positivity was higher in ST of SARS-CoV-2 PCR positive at delivery group, while CD56-expressing immune cells were decreased in comparison with control subjects. Discussion: We confirmed the ability of SARS-CoV-2 to infect placenta tissues. The simultaneous SARS-CoV-2 swab positivity at delivery and the positivity of the placenta tissue for SARS-CoV-2 NP seems to create an environment that modifies the expression of specific molecules, as CD147 and HLA-G. These data suggest a possible impact of SARS-CoV-2 infection during pregnancy, that might be worthy to be monitored also in vaccinated subjects

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

Assessment of MLH1 promoter methylation and BRAF gene mutation in colorectal carcinomas with microsatellite instability

Background: Recent studies indicate that analysis of MLH1 promoter methylation and especially evaluation of BRAF gene mutational status can be employed to differentiate hereditary from sporadic MSI-H MLH1-negative colorectal carcinomas. In particular BRAF was demontrated to be frequently mutated in MSI-H sporadic but not in hereditary carcinomas. Design: The study was conducted on a consecutive series of 2162 colorectal adenocarcinomas surgically resected from January 2004 to June 2010. Mismatch repair (MMR) status has been prospectively evaluated by immunohistochemical analysis of MMR protein expression (MLH1, MSH2, MSH6 and, in selected cases, PMS2) and microsatellite instability (MSI) analysis, using a fl uorescent PCR method and the Bethesda panel markers (BAT25, BAT26, D2S123, D5S346, D17S250) plus BAT40. Tumors were classifi ed as MSI-H, MSI-L and MSS according to the guidelines of the International Workshop of Bethesda. In MMR-defi cient (MMR-D) tumors, analysis of MLH1 promoter methylation (C- region) was assessed by methylation specifi c PCR and evaluation of V600E BRAF mutation was investigated by direct DNA sequencing. Results: 316 (14.6%) carcinomas were classifi ed as MMR-D (loss of MMR protein expression and/or MSI-H). Most MMR-D tumors showed loss of MLH1 expression (256, 81%). MLH1 methylation was detected in 196/219 (89%) MLH1-negative carcinomas and in 2/50 (4%) MMR-D MLH1-positive carcinomas. V600E BRAF mutations were observed in 108/158 (68%) MLH1-negative and in only 1/42 (2%) MLH1-positive MMR-D cancers. BRAF mutations were identifi ed only in tumors showing MLH1 promoter methylation (107/142, 75%). All the MLH1-negative carcinomas without MLH1 methylation examined (15 cases) did not demonstrate BRAF mutation. Both MLH1 promoter methylation and BRAF mutation were more frequently observed in older patients. Conclusions: Our results confi rm that MLH1 promoter methylation and BRAF mutation occur in a large fraction of MMR-defi cient MLH1-negative colorectal carcinomas and are closely associated. Furthermore our data indicate that assessment of MLH1 promoter methylation and especially of BRAF mutation might be used in the selection of colorectal cancer patients with presumptive Lynch syndrome

Pathologic features of colorectal cancers detected by population screening in the province of Ferrara

Background and aim: Aim of the present study was to evaluate the histopathologic and clinical characteristics of colorectal carcinomas detected by means of the regional screening program in the province of Ferrara. Material and methods: The study included 92 infiltrating adenocarcinomas, 62 removed by surgery and 30 (32%) by endoscopic resection. Twenty-one patients with endoscopically removed malignant polyps subsequently underwent surgical resection with lymphadenectomy. Results: Most of the endoscopically removed malignant polyps (n=29) were localized in the distal colon (7 in the descending colon, 17 in the sigmoid colon and 5 in the rectum) and only one in the proximal colon. With regard to colorectal carcinomas removed by surgery, 16 were localized in the proximal colon (10 in the right and 6 in the transverse colon) and 46 in the distal colon (5 in the descending and 21 in the sigmoid colon and 20 in the rectum). Among the surgically removed tumors, 20 have been classified as TNM stage I, 18 as TNM stage II (all of them stage IIa), 18 as TNM stage III (6 stage IIIa, 7 IIIb and 5 IIIc) and 5 as TNM stage IV. Among the 21 carcinomas treated by endoscopic resection and subsequent surgical resection, two cases displayed metastases to lymph nodes (pN1). Analyzing all the adenocarcinomas identified by the screening program, 48 tumors (52.7%) were found to belong to the category with excellent prognosis, 26 (28.6%) to the category with good prognosis and only 17 (18.7%) to the category with poor prognosis. Most tumors were submitted to molecular analysis for microsatellite instability evaluation by means of a fluorescence-based PCR method and to immunohistochemical analysis to assess mismatch repair proteins expression (MLH1, MSH2, MSH6 and PMS2). These analyses allowed us to identify four MSI-H adenocarcinomas with loss of MMR protein expression (MLH1 in one case, MSH2 in one case and MSH6 in two cases), probably removed from patients with hereditary disease (Lynch syndrome). Conclusions: Our results indicate that the screening program allows to detect a large number of early stage colorectal carcinomas with excellent prognosis. This fact should contribute to obtain a mortality reduction for this neoplasm in the population

Morphology and Molecular features of rare colorectal carcinoma histotypes

Several histopathological variants of colorectal carcinoma can be distinguished, some associated with specific molecular profiles. However, in routine practice, ninety/ninety-five percent of all large bowel tumors are diagnosed as conventional adenocarcinoma, even though they are a heterogeneous group including rare histotypes, which are often under-recognized. Indeed, colorectal cancer exhibits dierences in incidence, location of tumor, pathogenesis, molecular pathways and outcome depending on histotype. The aim is therefore to review the morphological and molecular features of these rare variants of intestinal carcinomas which may hold the key to dierences in prognosis and treatment

Prognostic significance of DNA ploidy in patients with stage II and stage III colon carcinoma: a prospective flow cytometric study

BACKGROUND. The prognostic value of flow cytometric DNA ploidy in colorectal carcinoma has not been defined clearly. Most previous studies were conducted retrospectively using archival formalin fixed, paraffin embedded tumor samples. Conversely, few data on prospective studies employing fresh or frozen tissue speci-mens are available. There is general agreement that fresh/frozen material is more reliable than paraffin embedded tissue for DNA ploidy analysis by flow cytometry. METHODS. In the current investigation we evaluated the prognostic significance of nuclear DNA content in a prospective series of 191 patients with curatively resected TNM Stage II (n Å 107) or Stage III (n Å 84) sporadic colon carcinomas. DNA ploidy status was assessed by flow cytometry utilizing multiple frozen tumor samples. Mean follow-up in surviving patients was 48.5 months (median, 46.9 months; range, 29–77 months). The Cox proportional hazards model was used to adjust for several clinical and pathologic covariates. RESULTS. Of the 191 carcinomas examined, 47 (24.6%) were classified as DNA diploid and 144 (75.4%) as DNA aneuploid. DNA ploidy pattern was significantly related to tumor site (P õ 0.0001), histologic type (P Å 0.0002), and grade of differentiation (P Å 0.009), but not to other clinical and pathologic variables. Patients with DNA diploid tumors showed a better disease free (P Å 0.013) and overall survival (P Å 0.021) than patients with DNA aneuploid adenocarcinomas. In particular, patients with Stage II DNA diploid tumors (n Å 30) had an excellent clinical outcome, with an overall 5-year survival rate of 97%. When patients were analyzed according to the anatomic site of the tumor, a significant relationship between DNA ploidy status and disease free and overall survival was observed in the group of patients with carcinomas of the proximal colon (n Å 84) (P Å 0.004 and P Å 0.002, respectively), but not among patients whose tumors were sited distally to the splenic flexure (n Å 107). In multivariate analysis, nuclear DNA content was demonstrated to be an independent prognostic variable for both disease free and overall survival. Furthermore, in the group of patients with tumors of the proximal colon, DNA ploidy pattern was the single most important prognostic factor. CONCLUSIONS. Our results confirm that flow cytometric DNA ploidy status is a significant and independent prognostic factor in patients with colon carcinoma These findings may have clinical implications for the management of affected patients, especially those with Stage II disease

Chromosome 18q allelic loss and prognosis in stage II and III colon cancer

The prognostic significance of chromosome 18q allelic loss was evaluated in a series of 118 patients with curatively resected TNM stage II or stage III colon cancer. Chromosome 18q status was determined on frozen tumour samples, using microsatellite markers and the polymerase chain reaction (PCR). tumour site, extramural venous invasion, flow cytometric nuclear DNA content and p53 protein expression. When patients were stratified by tumour stage, a significant survival advantage for patients whose tumour had no allelic loss on chromosome 18q was observed in stage II as well as in stage III disease. In multivariate analysis, status of chromosome 18q was the only significant independent prognostic factor for both disease-free and overall survival. These results indicate that assessment of chromosome 18q status provides relevant prognostic information in colon cancer and might be employed in the selection of patients for adjuvant therapy

Merkel cell carcinomas arising in autoimmune disease affected patients treated with biologic drugs including anti-TNF

open12siThis study has been supported in parts by Associazione Italiana per la Ricerca sul Cancro (AIRC), grant IG16046; Associazione Sammarinese per la Lotta contro le Leucemie e le Emopatie Maligne (ASLEM), grant CFR/2015; LIONS Club International, District 108 TB, Italy, grant UNIFE 2015; and Fondazione Cassa di Risparmio di Cento, grant 2014 (all to M. Tognon).Purpose: The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arisen in patients affected by autoimmune diseases and treated with biologic drugs. Experimental Design: Serum samples from patients with MCC were analyzed for the presence and titer of antibodies against antigens of the oncogenic Merkel cell polyomavirus (MCPyV). IgG antibodies against the viral oncoproteins large T (LT) and small T (ST) antigens and the viral capsid protein-1 were analyzed by indirect ELISA. Viral antigens were recombinant LT/ST and virus-like particles (VLP), respectively. MCPyV DNA sequences were studied using PCR methods in MCC tissues and in peripheral blood mononuclear cells (PBMC). Immunohistochemical (IHC) analyses were carried out in MCC tissues to reveal MCPyV LT oncoprotein. Results: MCPyV DNA sequences identified in MCC tissues showed 100% homology with the European MKL-1 strain. PBMCs from patients tested MCPyV-negative. Viral DNA loads in the three MCC tissues were in the 0.1 to 30 copy/cell range. IgG antibodies against LT/ST were detected in patients 1 and 3, whereas patient 2 did not react to the MCPyV LT/ST antigen. Sera from the three patients with MCC contained IgG antibodies against MCPyV VP1. MCC tissues tested MCPyV LT-antigen–positive in IHC assays, with strong LT expression with diffuse nuclear localization. Normal tissues tested MCPyV LT–negative when employed as control. Conclusions: We investigated three new MCCs in patients affected by rheumatologic diseases treated with biologic drugs, including TNF. A possible cause–effect relationship between pharmacologic immunosuppressive treatment and MCC onset is suggested. Indeed, MCC is associated with MCPyV LT oncoprotein activity.openRotondo, John Charles; Bononi, Ilaria; Puozzo, Andrea; Govoni, Marcello; Foschi, Valentina; Lanza, Giovanni; Gafa, Roberta; Gaboriaud, Pauline; Touzã©, Françoise Antoine; Selvatici, Rita; Martini, Fernanda; Tognon, MauroRotondo, John Charles; Bononi, Ilaria; Puozzo, Andrea; Govoni, Marcello; Foschi, Valentina; Lanza, Giovanni; Gafa, Roberta; Gaboriaud, Pauline; Touzã©, Françoise Antoine; Selvatici, Rita; Martini, Fernanda; Tognon, Maur