Early miR-223 Upregulation in Gastroesophageal Carcinogenesis

Objectives: To test miR-223 upregulation during gastric (intestinal-type) and Barrett esophageal carcinogenesis. Methods: miR-223 expression was assessed by quantitative reverse transcription polymerase chain reaction in a series of 280 gastroesophageal biopsy samples representative of the whole spectrum of phenotypic changes involved in both carcinogenetic cascades. The results were further validated by in situ hybridization on multiple tissue specimens obtained from six surgically treated gastroesophageal adenocarcinomas. miR-223 expression was also assessed in plasma samples from 30 patients with early stage (ie, stages I and II) gastroesophageal adenocarcinoma and relative controls. Res…

RISK OF CARDIOVASCULAR DISEASE MORBIDITY AND MORTALITY IN FRAIL AND PRE-FRAIL OLDER ADULTS:RESULTS FROM A META-ANALYSIS AND EXPLORATORY META-REGRESSION ANALYSIS

Frailty is common and associated with poorer outcomes in the elderly, but its role as potential cardiovascular disease (CVD) risk factor requires clarification. We thus aimed to meta-analytically evaluate the evidence of frailty and pre-frailty as risk factors for CVD. Two reviewers selected all studies comparing data about CVD prevalence or incidence rates between frail/pre-frail vs. robust. The association between frailty status and CVD in cross-sectional studies was explored by calculating and pooling crude and adjusted odds ratios (ORs)+/- 95% confidence intervals (CIs); the data from longitudinal studies were pooled using the adjusted hazard ratios (HRs). Eighteen cohorts with a total …

Malignant epithelial/exocrine tumors of the pancreas

Summary Pancreatic malignant exocrine tumors represent the most important cause of cancer-related death for pancreatic neoplasms. The most common tumor type in this category is represented by pancreatic ductal adenocarcinoma (PDAC), an ill defined, stroma-rich, scirrhous neoplasm with glandular differentiation. Here we present the relevant characteristics of the most important PDAC variants, namely adenosquamous carcinoma, colloid carcinoma, undifferentiated carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, signet ring carcinoma, medullary carcinoma and hepatoid carcinoma. The other categories of malignant exocrine tumors, characterized by fleshy, stroma-poor, circumsc…

Extranodal Extension of Nodal Metastases Is a Poor Prognostic Indicator in Gastric Cancer: a Systematic Review and Meta-analysis.

Introduction: The extranodal extension (ENE) of nodal metastases (the extension of neoplastic cells through the nodal capsule into the perinodal soft tissue) is a histological feature that has been considered a prognostic factor in several cancers, but the role in gastric cancer was not yet investigated. We aimed to investigate the prognostic role of ENE in patients affected by gastric cancer through a systematic review and meta-analysis. Material and Methods: Two independent authors searched major databases until 09/30/2015 to identify studies providing data on gastric cancer patients’ prognostic parameters and comparing patients with ENE (ENE+) vs intra-nodal extension (ENE−). The data we…

Prognostic Role of High-Grade Tumor Budding in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis with a Focus on Epithelial to Mesenchymal Transition

This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13-1.88, p = 0.004; HR, 2.65; 95% CI, 1.79-3.91; p < 0.0001) and of recurrence (RR, 1.61; 95% CI, 1.05-2.47, p = 0.03) for PDAC patients with high-grade TB. Moreover, we found that E…

STEM CELLS FOR TREATMENT OF CARDIOVASCULAR DISEASES: AN UMBRELLA REVIEW OF RANDOMIZED CONTROLLED TRIALS

AIMS:\ud \ud Stem cells are a promising therapy for various medical conditions. The literature regarding their adoption for the clinical care of cardiovascular diseases (CVD) is still conflicting. Therefore, our aim is to assess the strength and credibility of the evidence on clinical outcomes and application of stem cells derived from systematic reviews and meta-analyses of intervention studies in CVD.\ud \ud METHODS and RESULTS:\ud \ud Umbrella review of systematic reviews with meta-analyses of randomized controlled trials (RCTs) using placebo/no intervention as control group. For meta-analyses of RCTs, outcomes with a random-effect p-value< 0.05, the GRADE (Grading of Recommendations Ass…

Erratum: Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials

Although higher dietary intakes of magnesium (Mg) seem to correspond to lower diabetes incidence, research concerning Mg supplementation in people with or at risk of diabetes is limited. Thus, we aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes compared with placebo. A literature search in PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials and Clinicaltrials.gov without language restriction, was undertaken. Eligible studies were randomized controlled trials (RCTs) investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or at h…

Pattern of Invasion in Human Pancreatic Cancer Organoids Is Associated with Loss of SMAD4 and Clinical Outcome

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by extensive local invasion and systemic spread. In this study, we employed a three-dimensional organoid model of human pancreatic cancer to characterize the molecular alterations critical for invasion. Time-lapse microscopy was used to observe invasion in organoids from 25 surgically resected human PDAC samples in collagen I. Subsequent lentiviral modification and small-molecule inhibitors were used to investigate the molecular programs underlying invasion in PDAC organoids. When cultured in collagen I, PDAC organoids exhibited two distinct, morphologically defined invasive phenotypes, mesenchymal an…

Correction to: Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases

No data is available on the molecular background of the extra-nodal extension (ENE) of lymph node metastasis (LN) in colorectal cancer (CRC).A series of 22 ENE-positive CRCs was considered and three samples per case were selected (the primary CRC, an ENE-negative and an ENE-positive metastatic LN). Samples (n = 66) were analysed by immunohistochemistry for PD-L1, CD4, CD8, CD68 and CD80. Fifteen out of twenty-two cases were further profiled through a hotspot multigene mutational custom panel, including 164 hotspot regions ofA significantly higher percentage of CD4-, CD8- and CD68-positive cells was observed at the invasive front of both CRCs and in ENE in contrast with what observed at the …

Extranodal extension in N1-adenocarcinoma of the pancreas and papilla of Vater: A systematic review and meta-analysis of its prognostic significance

The aim of the study was to investigate the prognostic role of extranodal extension (ENE) of lymph node metastasis in adenocarcinoma of the pancreas (PDAC) and papilla [cancer of the papilla of Vater (CPV)]. A PubMed and SCOPUS search from database inception until 5 January 2015 without language restrictions was conducted. Eligible were prospective studies reporting data on prognostic parameters in individuals with PDAC and/or CPV, comparing participants with the presence of ENE (ENE +) with those with intranodal extension (ENE). Data were summarized using risk ratios for number of deaths/recurrences and hazard ratios for time-dependent risk related to ENE+, adjusted for potential confounde…

Inflammation and sarcopenia: A systematic review and meta-analysis

Inflammatory cytokines have been shown to prompt muscle wasting, ultimately stimulating protein catabolism and suppressing muscle synthesis. However, the possible association between inflammatory parameters and sarcopenia is poorly understood. We therefore aimed to summarize the current evidence about this topic with a meta-analysis of studies reporting serum inflammatory parameters in patients with sarcopenia vs. people without sarcopenia (controls). An electronic PubMed and Scopus search through to 09/01/2016 and meta-analysis of cross-sectional studies comparing serum levels of inflammatory cytokines between patients with sarcopenia and controls was made, calculating random-effects stand…

Additional file 4: of Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis

Table S3. Methodological quality of cohort studies included in the meta-analysis. This summarizing table shows the method of quality assessment of all the studies included in this systematic review and meta-analysis, using the Newcastle-Ottawa scale. (DOCX 16 kb)

Pulmonary Adenocarcinoma With Enteric Differentiation: Immunohistochemistry and Molecular Morphology

Pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare subtype of lung adenocarcinoma recently recognized in the WHO classification. It is defined as an adenocarcinoma in which the enteric component exceeds 50% and have to show the expression of at least 1 immunohistochemical marker of enteric differentiation. Although the definition of this tumor type is very important, above all in the differential diagnosis between a primary lung tumor and a metastasis of colorectal adenocarcinoma, this cancer still lacks a distinctive immunohistochemical and molecular signature. We recruited the largest series in the literature of PAEDs according to the morphology and the positivity for …

Cell of origin markers identify different prognostic subgroups of lung adenocarcinoma

Strong prognostic markers able to stratify lung adenocarcinoma (ADC) patients are lacking. We evaluated whether a six-immunohistochemical markers panel (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5), defining the putative neoplastic “cell of origin,” allows to identify prognostic subgroups among lung ADC. We screened a large cohort of ADC specimens (2003–2013) from Torino Institutional Repository identifying: (i) marker positivity by immunohistochemistry, (ii) main morphological appearance by light microscopy, (iii) presence of “hotspot” mutations of candidate genes by Sequenom technology. To evaluate possible predictors of survival and time to recurrence, uni- and multivariable-adjusted comp…

Inflammation and frailty in the elderly: A systematic review and meta-analysis

The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n = 3232 frail, n = 11,483 pre-frail and n = 8522 robust, and 563 pre-frail + robust; 3 longitudinal studies n = 3402 participants without frailty at baseline) were meta-analyzed. Cross-sectional studies reported that compared to 6757 robust participa…

Is pain sensitivity altered in people with Alzheimer's disease? A systematic review and meta-analysis of experimental pain research

Background Clinical studies suggest people with Alzheimer's disease (AD) have altered pain sensitivity. Experimental pain research is equivocal. Objective Conduct a meta-analysis to investigate if people with AD have altered pain sensitivity compared to healthy controls (HCs). Methods Three authors searched electronic databases from inception till November 2015 for experimental pain studies in AD vs. HCs. Outcome measures were pain threshold, tolerance, pain ratings, heart rate response to noxious stimuli and the Facial Action Coding System (FACS). Random effect meta-analysis calculating Hedges' g ± 95% confidence intervals (CI) was conducted. Results Thirteen studies were identified, inclu…

Different prognostic roles of tumor suppressor gene BAP1 in cancer: A systematic review with meta-analysis

Biallelic inactivation of the tumor suppressor gene BRCA1-associated protein 1 (BAP1) has been demonstrated in several cancers, but its prognostic role has not been completely explained. We aimed to investigate the risk associated with loss of BAP1 (BAP1-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS were searched from database inception until 09/15/2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of BAP1 (BAP1+) vs. BAP1- were included. Data were summarized using risk ratios (RR) for number of deaths/recurren…

Adherence to a mediterranean diet is associated with lower prevalence of osteoarthritis: Data from the osteoarthritis initiative

Background &amp; aims: The Mediterranean diet appears to be beneficial for several medical conditions, but data regarding osteoarthritis (OA) are not available. The aim of this study was to investigate if adherence to the Mediterranean diet is associated with a lower prevalence of OA of the knee in a large cohort from North America. Methods: 4358 community-dwelling participants (2527 females; mean age: 61.2 years) from the Osteoarthritis Initiative were included. Adherence to the Mediterranean diet was evaluated through a validated Mediterranean diet score (aMED) categorized into quartiles (Q). Knee OA was diagnosed both clinically and radiologically. The strength of the association between…

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas: a distinct entity among pancreatic tumors

Aims Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach. Methods and results PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cance…

Prognostic implications of extranodal extension in node-positive squamous cell carcinoma of the vulva: A systematic review and meta-analysis

Squamous cell carcinoma (SCC) of the vulva is the fourth most common gynecological cancer, usually staged with the TNM or FIGO systems. Since 2009, FIGO staging has taken the extranodal extension (ENE) of lymph node metastases into account. ENE is defined as the spread of a lymph node metastasis into surrounding soft tissue. Although the TNM and FIGO systems acknowledge the importance of ENE in SCC, no comprehensive studies have analyzed the prognostic impact of this parameter. We therefore queried the PubMed and SCOPUS databases from their inception up until 04/01/2015, adopting no language restrictions: all prospective studies reporting on prognostic parameters in patients with vulvar SCC…

Tumor budding as a risk factor for nodal metastasis in pT1 colorectal cancers: a meta-analysis

Worldwide, colorectal cancer (CRC) screening programs have significantly increased the detection of submucosal (pT1) adenocarcinoma. Completion surgery may be indicated after endoscopic excision of these potentially metastasizing early cancers. However, the postsurgical prevalence of nodal implants does not exceed 15%, leading to questions concerning the clinical appropriateness of any post–endoscopy surgery. Eastern scientific societies (Japanese Society for Cancer of the Colon-Rectum, in particular) include tumor budding (TB), defined as the presence of isolated single cancer cells or clusters of fewer than 5 cancer cells at the tumor invasive front, among the variables that must be inclu…

Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis

The Spalt-Like Transcription Factor 4 (SALL4) oncogene plays a central function in embryo-fetal development and is absent in differentiated tissues. Evidence suggests that it can be reactivated in several cancers worsening the prognosis. We aimed at investigating the risk associated with SALL4 reactivation for all-cause mortality and recurrence in cancer using the current literature. A PubMed and SCOPUS search until 1st September 2016 was performed, focusing on perspective studies reporting prognostic parameters in cancer data. In addition, 17 datasets of different cancer types from The Cancer Genome Atlas were considered. A total of 9,947 participants across 40 cohorts, followed-up for abo…

Genomic characterization of undifferentiated sarcomatoid carcinoma of the pancreas

Undifferentiated sarcomatoid carcinoma (USC) of the pancreas is a rare but especially aggressive variant of pancreatic ductal adenocarcinoma (PDAC), composed of at least 80% of sarcomatoid cells. This study aimed to elucidate its clinicopathological and molecular features. The study cohort included 10 patients with pancreatic USC. Clinicopathological parameters were determined for each patient. The molecular profile was investigated using next-generation sequencing (NGS). Histologically, all tumors were hypercellular neoplasms with spindle-shaped or sarcomatoid cells. All patients showed vascular and perineural invasion. Most patients had a poor prognosis. NGS showed important similarities …

Inflammatory and tumor-like lesions of the pancreas

Summary Inflammatory/tumor-like lesions of the pancreas represent a heterogeneous group of diseases that can variably involve the pancreatic gland determining different signs and symptoms. In the category of inflammatory/tumor-like lesions of the pancreas, the most important entities are represented by chronic pancreatitis, which includes alcoholic, obstructive and hereditary pancreatitis, paraduodenal (groove) pancreatitis, autoimmune pancreatitis, lymphoepithelial cyst, pancreatic hamartoma and intrapancreatic accessory spleen. An in-depth knowledge of such diseases is essential, since they can cause severe morbidity and may represent a potential life-threatening risk for patients. Furthe…

Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases

Background: No data is available on the molecular background of the extra-nodal extension (ENE) of lymph node metastasis (LN) in colorectal cancer (CRC). Methods: A series of 22 ENE-positive CRCs was considered and three samples per case were selected (the primary CRC, an ENE-negative and an ENE-positive metastatic LN). Samples (n=66) were analysed by immunohistochemistry for PD-L1, CD4, CD8, CD68 and CD80. Fifteen out of twenty-two cases were further profiled through a hotspot multigene mutational custom panel, including 164 hotspot regions of AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53 genes. Results: A significantly higher percentage of CD4-, CD8- and CD68-pos…

Additional file 6: of Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis

Table S4. Type and number of adjustments (in addiction of ALT status) for each study. This summarizing table shows the different adjustments of all studies, which have investigated ALT status with multivariate analysis. (DOCX 20 kb)

Extranodal extension of nodal metastases is a poor prognostic moderator in non-small cell lung cancer: a meta-analysis

Extranodal extension (ENE) of nodal metastasis is defined as the extension of metastatic cells through the nodal capsule into the perinodal tissue. This morphological parameter, recently proposed as an important prognostic factor in different types of malignancy, has not been included in the TNM staging system for non-small cell lung cancer (NSCLC). In this systematic review with meta-analysis, we weighted the prognostic role of ENE in patients with lymph node-positive NSCLC. Two independent authors searched SCOPUS and PubMed through 28 February 2017. Prospective and retrospective studies on NSCLC, comparing patients with presence of ENE (ENE+) ENE+) vs. only intranodal extension (ENE–) and…

The importance of extranodal extension in metastatic head and neck squamous cell carcinoma, in the light of the new AJCC cancer staging system

Extranodal extension of lymph node metastasis influences recurrence in prostate cancer: a systematic review and meta-analysis

AbstractThe extranodal extension (ENE) of nodal metastasis involves the extension of neoplastic cells through the lymph node capsule into the perinodal adipose tissue. This morphological feature has recently been indicated as an important prognostic factor in various cancer types, but its role in prostate cancer is still unclear. We aimed to clarify it, performing the first meta-analysis on this issue, comparing prognostic parameters in surgically treated, node-positive prostate cancer patients with (ENE+) vs. without (ENE−) ENE. Data were summarized using risk ratios (RRs) for number of deaths/recurrences and hazard ratios (HRs), with 95% confidence intervals (CI), for the time-dependent r…

Weight loss is associated with improvements in cognitive function among overweight and obese people: A systematic review and meta-analysis

Whilst obesity is associated with a higher risk of cognitive impairment, the influence of weight loss on cognitive function in obese/overweight people is equivocal. We conducted a meta-analysis of randomized controlled trials (RCTs) and longitudinal studies evaluating the influence of voluntary weight loss on cognitive function in obese/overweight individuals. Articles were acquired from a systematic search of major databases from inception till 01/2016. A random effect meta-analysis of weight loss interventions (diet, physical activity, bariatric surgery) on different cognitive domains (memory, attention, executive functions, language and motor speed) was conducted. Twenty studies (13 long…

Colorectal cancer with microsatellite instability: Right-sided location and signet ring cell histology are associated with nodal metastases, and extranodal extension influences disease-free survival

Colorectal cancer (CRC) with microsatellite instability (MSI) accounts for 15-18 % of all CRCs and represents the category with the best prognosis. This study aimed at determining any possible clinical/pathological features associated with a higher risk of nodal metastasization in MSI-CRC, and at defining any possible prognostic moderators in this setting. All surgically resected CRCs of the last 20 years (mono-institutional series) with a PCR-based diagnosis of MSI, with and without nodal metastasis, have been retrieved for histological review, which was performed following WHO guidelines. Furthermore, the most important prognostic moderators have been investigated with a survival analysis…

Bone mineral density, osteoporosis, and fractures among people with eating disorders: a systematic review and meta-analysis

Objective: To provide meta-analytical evidence of bone mineral density (BMD), fractures, and osteoporosis rates in eating disorders (ED) vs. healthy controls (HCs). Method: Three independent authors searched major electronic databases from inception till August 2015 for cross-sectional studies reporting BMD in people with ED (anorexia nervosa, (AN); bulimia nervosa, (BN); eating disorders not otherwise specified, (EDNOS)) vs. HCs. Standardized mean differences (SMDs) ±95% and confidence intervals (CIs) were calculated for BMD, and odds ratios (ORs) for osteopenia, osteoporosis, and fractures. Results: Overall, 57 studies were eligible, including 21 607 participants (ED = 6485, HCs = 15 122)…

Hyperuricemia protects against low bone mineral density, osteoporosis and fractures: a systematic review and meta-analysis

Background: Serum uric acid (SUA) accounts for about 50% of extracellular antioxidant activity, suggesting that hyperuricemia may have a protective role in diseases characterized by high levels of oxidative stress, such as osteoporosis. We aimed to meta-analyse data regarding bone mineral density (BMD), osteoporosis and fractures in people with higher SUA vs. lower SUA concentrations. Materials and methods: Two investigators conducted a literature search using PubMed and Scopus, without language restrictions. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used for BMD; risk ratios (RRs) and adjusted odds ratios (ORs) for cross-sectional data. Most possible adju…

Additional file 2: of Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis

Figure S1. PRISMA checklist for this meta-analysis. The PRISMA figure representing all the steps for selecting/screening papers for this systematic-review and meta-analysis is here provided. (DOCX 45 kb)

Additional file 3: of Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis

Table S2. Characteristics of the studies according to Alternative Lengthening of Telomeres (ALT). This summarizing table shows the different features of all studies included in this systematic review and meta-analysis. (DOCX 29 kb)

Monoclonal gammopathy of undetermined significance and bone health outcomes: a systematic review and exploratory meta-analysis.

Monoclonal gammopathy of undetermined significance (MGUS) is a common condition in the elderly. A number of studies have investigated the relationship between MGUS and bone health outcomes including bone mineral density (BMD), osteoporosis and fractures, but no meta-analysis exists. We conducted a systematic review and exploratory meta-analysis comparing bone health outcomes in patients with MGUS. Two independent authors searched PubMed and Scopus from inception until 19 October 2016. A meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD was conducted. Standardised mean differences (SMD) ± 95% confidence intervals (CIs) were calculated for BMD, and risk…

Telomere length and health outcomes: An umbrella review of systematic reviews and meta-analyses of observational studies.

The aim of the present study was to map and grade evidence for the relationships between telomere length with a diverse range of health outcomes, using an umbrella review of systematic reviews with meta-analyses. We searched for meta-analyses of observational studies reporting on the association of telomere length with any health outcome (clinical disease outcomes and intermediate traits). For each association, random-effects summary effect size, 95% confidence interval (CI), and 95% prediction interval were calculated. To evaluate the credibility of the identified evidence, we assessed also heterogeneity, evidence for small-study effect and evidence for excess significance bias. Twenty-one…

PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: A expression patterns and clinical implications

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has a striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1, and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extrapancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas were immunostained using antibodies against PD-1, PD-L1, and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17 (63%) o…

Magnesium Status in Alzheimer's Disease: A Systematic Review

The interest in poor magnesium (Mg) status as risk factor for Alzheimer's disease (AD) is increasing due to its antioxidant and neuroprotective properties. A systematic PubMed literature search of studies investigating Mg status was undertaken comparing AD to healthy controls (HCs) or patients with medical illness (medical controls [MCs]). Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) were calculated for all outcomes. Of 192 potentially eligible studies, 13 were included (559 patients with AD, 381 HCs, and 126 MCs). Compared to HCs, patients with AD had significantly lower Mg in cerebrospinal fluid (2 studies; SMD = -0.35; P =.02) and in hair (2 studies; SMD = -0.75;…

Prognostic impact and implications of extra-capsular lymph node involvement in colorectal cancer: a systematic review with meta-analysis.

The extranodal extension (ENE) of nodal metastasis (i.e. the extension of tumor cells through the nodal capsule into the perinodal adipose tissue) has recently emerged as an important prognostic factor in different types of malignancies. However, the tumor-node-metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a systematic review and meta-analysis to determine the prognostic role of ENE in patients with lymph node-positive colorectal cancer.Two independent authors searched PubMed and SCOPUS until 7 January 2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects wit…

Nephrolithiasis, bone mineral density, osteoporosis, and fractures: a systematic review and comparative meta-analysis

Summary: Our meta-analysis demonstrates that people with nephrolithiasis have decreased bone mineral density, an increased odds of osteoporosis, and potentially an elevated risk of fractures. Introduction: People with nephrolithiasis might be at risk of reduced bone mineral density (BMD) and fractures, but the data is equivocal. We conducted a meta-analysis to investigate if patients with nephrolithiasis have worse bone health outcomes (BMD), osteoporosis, and fractures versus healthy controls (HCs). Methods: Two investigators searched major databases for articles reporting BMD (expressed as g/cm2 or a T- or Z-score), osteoporosis or fractures in a sample of people with nephrolithiasis, and…

Extranodal extension of nodal metastasis is the main prognostic moderator in squamous cell carcinoma of the esophagus after neoadjuvant chemoradiotherapy

Several studies, including comprehensive systematic reviews with meta-analyses of our group of research, have demonstrated the negative prognostic impact of the extranodal extension of nodal metastasis (ENE) in different cancer types, including squamous cell carcinoma (SCC) of the vulva, of the penis and of head and neck, as well as in tumors of the digestive and genitourinary systems, in thyroid cancer and others (1-17).

Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis

Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of …

Female-specific association among I, J and K mitochondrial genetic haplogroups and cancer:A longitudinal cohort study

Recent studies highlighted the role of mitochondrial dysregulation in cancer, suggesting that the different mitochondrial haplogroups might play a role in tumorigenesis and risk of cancer development. Our aim is to investigate whether any mitochondrial haplogroups carried a significant higher risk of cancer development in a large prospective cohort of North American people. The haplogroup assignment was performed by a combination of sequencing and PCR-RFLP techniques. Our specific outcome of interest was the incidence of any cancer during follow-up period. Overall, 3222 participants were included in the analysis. Women having I, J, K haplogroup reported a significant higher incidence of can…

Acetylcholinesterase inhibitors are associated with weight loss in older people with dementia: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis investigating the influence of acetylcholinesterase inhibitors (AChEIs) therapy on nutritional status and weight across observational and interventional studies. Two authors searched major electronic databases from inception until 10/14/2015 for longitudinal, open-label and randomised double-blind placebo controlled (randomised controlled trials (RCTs)) studies of AChEIs in patients with dementia reporting nutritional status outcome data. Out of 3551 initial hits, 25 studies (12 open-label trials, 9 RCTs and 4 longitudinal studies) including 10 792 patients with dementia were meta-analysed. In longitudinal studies (median follow-up 6 months…

Specific expression patterns of epithelial to mesenchymal transition factors in gestational molar disease.

Introduction The epithelial to mesenchymal transition, a well-known and re-emerging model in pathology, has not been completely investigated in the field of gestational pathology. This study aims at improving the comprehension of this process in molar disease, even looking for new possible immunohistochemical markers. Materials and methods We have analysed the immunohistochemical expression of Twist1 and Snai2, two of the most important transcription factors involved in epithelial to mesenchymal transition, in formalin-fixed paraffin-embedded samples of 23 spontaneous abortive pregnancies, 22 molar pregnancies (10 partial and 12 complete) and 7 term placentas. Results Twist1 and Snai2 were …

Additional file 1: of Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis

Table S1. PRISMA checklist. The PRISMA checklist for this systematic-review and meta-analysis is here provided. (DOC 64 kb)

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the…

Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: A systematic review and meta-analysis

Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) has been demonstrated in several cancers, but its prognostic role is unknown. We aimed to investigate the risk associated with loss of ARID1A (ARID1A-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data. Eligible were prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of ARID1A (ARID1A+) vs. ARID1A-, assessed either via immunohistoch…

Social determinants of therapy failure and multi drug resistance among people with tuberculosis: A review

Background Social determinants influence health and the development of tuberculosis (TB). However, a paucity of data is available considering the relationship of social determinants influencing therapy failure and multi drug resistance (MDR). We conducted a review investigating the relationship of common social determinants on therapy failure and MDR in people with TB. Methods PubMed and SCOPUS were searched without language restrictions until February 02, 2016 for studies reporting the association between socioeconomic factors (income, education and alcohol abuse) and therapy failure or MDR-TB. The association between social determinants and outcomes was explored by pooling data with a ran…

Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions

Abstract Background Acetylcholinesterase inhibitors (AceI) and memantine might prove useful in bipolar disorder (BD) given their neuroprotective and pro-cognitive effects, as highlighted by several case reports. We aimed to systematically review the efficacy and safety of AceI and memantine across multiple outcome dimensions in BD. Methods Systematic PubMed and SCOPUS search until 04/17/2015 without language restrictions. Included were randomized controlled trials (RCTs), open label studies and case series of AceI or memantine in BD patients reporting quantitative data on depression, mania, psychotic symptoms, global functioning, or cognitive performance. We summarized results using a best-…

Extra-nodal extension is an important prognostic parameter for both colonic and rectal cancer.

Ki-67 assessment of pancreatic neuroendocrine neoplasms: Systematic review and meta-analysis of manual vs. digital pathology scoring

Ki-67 assessment is a key step in the diagnosis of neuroendocrine neoplasms (NENs) from all anatomic locations. Several challenges exist related to quantifying the Ki-67 proliferation index due to lack of method standardization and inter-reader variability. The application of digital pathology coupled with machine learning has been shown to be highly accurate and reproducible for the evaluation of Ki-67 in NENs. We systematically reviewed all published studies on the subject of Ki-67 assessment in pancreatic NENs (PanNENs) employing digital image analysis (DIA). The most common advantages of DIA were improvement in the standardization and reliability of Ki-67 evaluation, as well as its spee…

Perineural Invasion is a Strong Prognostic Moderator in Ampulla of Vater Carcinoma

Objective Ampulla of Vater carcinoma (AVC) has a broad spectrum of different prognoses. As such, new moderators of survival are urgently needed. We aimed at clarifying the prognostic role of perineural invasion in AVC. Methods Using PubMed and SCOPUS databases, we conducted the first systematic review and meta-analysis on this topic. Results Analyzing 29 articles for a total of 2379 patients, we found that the presence of perineural invasion increased the risk of all-cause mortality more than 2 times (relative risk [RR], 2.07; 95% confidence interval [CI], 1.78-2.42 [P &lt; 0.0001]; hazard ratio [HR], 2.72; 95% CI, 1.86-3.97 [P &lt; 0.0001]), of cancer-specific mortality more than 6 times (…

Significance of the prognostic stratification of extranodal extension in colorectal cancer

Hypovitaminosis D and orthostatic hypotension: A systematic review and meta-analysis

Objectives: Orthostatic hypotension is a common condition among older adults and is associated with a range of deleterious outcomes. Recently, interest has developed in hypovitaminosis D (defined as low 25 hydroxiyVitamin D levels) as a potential risk factor for orthostatic hypotension. We conducted a systematic review and meta-analysis examining the association of orthostatic hypotension between study participants with and without hypovitaminosis D, including the adjustment of potential confounders (age, sex, BMI, renal function, comorbidities, seasonality, use of antihypertensive medications, and supplementation with cholecalciferol). Methods: A systematic literature search of major elect…

Assessing the quality of studies in meta-research: Review/guidelines on the most important quality assessment tools

Systematic reviews and meta-analyses pool data from individual studies to generate a higher level of evidence to be evaluated by guidelines. These reviews ultimately guide clinicians and stakeholders in health-related decisions. However, the informativeness and quality of evidence synthesis inherently depend on the quality of what has been pooled into meta-research projects. Moreover, beyond the quality of included individual studies, only a methodologically correct process, in relation to systematic reviews and meta-analyses themselves, can produce a reliable and valid evidence synthesis. Hence, quality of meta-research projects also affects evidence synthesis reliability. In this overview…

PBRM1 loss is a late event during the development of cholangiocarcinoma

Aims: Somatic mutations in genes encoding chromatin remodellers have been reported recently in several cancer types, including approximately half of cholangiocarcinomas. One of the most commonly mutated chromatin remodellers in cholangiocarcinoma is the Polybromo-1 (PBRM1) gene located on chromosome 3p21, which encodes a subunit of the SWI/SNF complex. The aim of this study was to determine the timing of PBRM1 mutations in biliary carcinogenesis. Methods and results: In order to accomplish this goal, we used immunohistochemistry to assess PBRM1 protein expression in a series of precursor lesions and invasive biliary carcinomas. Previous studies have correlated loss of protein expression on …

Osteoarthritis and mortality: a prospective cohort study and systematic review with meta-analysis

Objectives: Osteoarthritis (OA) is a leading cause of disability, but the relationship with premature mortality remains uncertain. We aimed to investigate the relationship between OA and mortality from any cause and from cardiovascular disease (CVD).\ud \ud Methods: Electronic literature databases searches were conducted to identify prospective studies comparing mortality in a sample of people with and without OA. Risk of all-cause and CVD mortality were summarized using adjusted hazard ratios (HRs) for joint specific (hand, hip, and knee) and joint non-specific OA. New data from the Progetto Veneto Anziani (PRO.V.A.) study were also included. Results: From the PRO.V.A. study (N 1⁄4 2927), …

Liquid biopsy as surrogate for tissue for molecular profiling in pancreatic cancer: A meta-analysis towards precision medicine

Liquid biopsy (LB) is a non-invasive approach representing a promising tool for new precision medicine strategies for cancer treatment. However, a comprehensive analysis of its reliability for pancreatic cancer (PC) is lacking. To this aim, we performed the first meta-analysis on this topic. We calculated the pooled sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio, and diagnostic odds ratio (DOR). A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall accuracy. We finally assessed the concordance rate of all mutations detected by multi-genes panels. Fourteen eligible studies involving 369 patients wer…

Extranodal extension of lymph node metastasis is a marker of poor prognosis in oesophageal cancer: A systematic review with meta-analysis

The extranodal extension (ENE) of nodal metastasis is the extension of neoplastic cells through the nodal capsule into the perinodal adipose tissue. This histological feature has recently been indicated as an important prognostic factor in different types of malignancies; in this manuscript, we aim at defining its role in the prognosis of oesophageal cancer with the tool of meta-analysis. Two independent authors searched SCOPUS and PubMed until 31 August 2015 without language restrictions. The studies with available data about prognostic parameters in subjects with oesophageal cancer, comparing patients with the presence of ENE (ENE+) versus only intranodal extension (ENE-), were considered…

Adherence to the Mediterranean diet is associated with better quality of life: data from the Osteoarthritis Initiative

BACKGROUND The Mediterranean diet has positively influenced various medical conditions, but only a paucity of studies has considered the relation between the Mediterranean diet and quality of life (QOL) among people living in North America. OBJECTIVE We investigated whether a higher adherence to the Mediterranean diet (aMED) was associated with better QOL and decreased pain, stiffness, disability, and depression in a large cohort of North Americans from the Osteoarthritis Initiative. DESIGN aMED was evaluated through a validated Mediterranean diet score categorized into quintiles. Outcomes of interest were QOL [assessed with the 12-Item Short-Form Health Outcome Survey (SF-12)]; disability,…

Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis

Background Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression. ALT has been described in different types of sarcoma, but a comprehensive analysis of its clinical significance is still lacking. Therefore, we provide here the first meta-analysis on this topic. Methods We searched SCOPUS and PubMed through July 2018 to identify all studies that investigated the prognostic role of ALT in sarcomas. We considered the risk of death (risk ratio, RR) calculated as the number of death vs. total participants during follow-up in ALT+ versus ALT- pati…

Additional file 5: of Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis

Figure S2. Funnel plots. Funnel plots for risk ratio (A) and hazard ratio (B) for this systematic review and meta-analysis are here provided. (TIF 1991 kb)