Accuracy of dementia diagnosis—a direct comparison between radiologists and a computerized method

There has been recent interest in the application of machine learning techniques to neuroimaging-based diagnosis. These methods promise fully automated, standard PC-based clinical decisions, unbiased by variable radiological expertise. We recently used support vector machines (SVMs) to separate sporadic Alzheimer's disease from normal ageing and from fronto-temporal lobar degeneration (FTLD). In this study, we compare the results to those obtained by radiologists. A binary diagnostic classification was made by six radiologists with different levels of experience on the same scans and information that had been previously analysed with SVM. SVMs correctly classified 95% (sensitivity/specificity: 95/95) of sporadic Alzheimer's disease and controls into their respective groups. Radiologists correctly classified 65–95% (median 89%; sensitivity/specificity: 88/90) of scans. SVM correctly classified another set of sporadic Alzheimer's disease in 93% (sensitivity/specificity: 100/86) of cases, whereas radiologists ranged between 80% and 90% (median 83%; sensitivity/specificity: 80/85). SVMs were better at separating patients with sporadic Alzheimer's disease from those with FTLD (SVM 89%; sensitivity/specificity: 83/95; compared to radiological range from 63% to 83%; median 71%; sensitivity/specificity: 64/76). Radiologists were always accurate when they reported a high degree of diagnostic confidence. The results show that well-trained neuroradiologists classify typical Alzheimer's disease-associated scans comparable to SVMs. However, SVMs require no expert knowledge and trained SVMs can readily be exchanged between centres for use in diagnostic classification. These results are encouraging and indicate a role for computerized diagnostic methods in clinical practice

Precursor lesions of early onset pancreatic cancer

Early onset pancreatic cancer (EOPC) constitutes less than 5% of all newly diagnosed cases of pancreatic cancer (PC). Although histopathological characteristics of EOPC have been described, no detailed reports on precursor lesions of EOPC are available. In the present study, we aimed to describe histopathological picture of extratumoral parenchyma in 23 cases of EOPCs (definition based on the threshold value of 45 years of age) with particular emphasis on two types of precursor lesions of PC: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs). The types, grades, and densities of precursor lesions of PC were compared in patients with EOPCs, in young patients with neuroendocrine neoplasms (NENs), and in older (at the age of 46 or more) patients with PC. PanINs were found in 95.6% of cases of EOPCs. PanINs-3 were found in 39.1% of EOPC cases. Densities of all PanIN grades in EOPC cases were larger than in young patients with NENs. Density of PanINs-1A in EOPC cases was larger than in older patients with PC, but densities of PanINs of other grades were comparable. IPMN was found only in a single patient with EOPC but in 20% of older patients with PC. PanINs are the most prevalent precursor lesions of EOPC. IPMNs are rarely precursor lesions of EOPC. Relatively high density of low-grade PanINs-1 in extratumoral parenchyma of patients with EOPC may result from unknown multifocal genetic alterations in pancreatic tissue in patients with EOPCs

Intraductal papillary mucinous neoplasm of the pancreas (IPMN): clinico-pathological correlations and surgical indications

<p>Abstract</p> <p>Background</p> <p>Intraductal papillary mucinous neoplasms (IPMNs) are increasingly recognized entities, whose management remains sometimes controversial, due to the high rate of benign lesions and on the other side to the good survival after resection of malignant ones.</p> <p>Methods</p> <p>Retrospective analysis of a prospectively collected Western series of IPMN.</p> <p>Results</p> <p>Forty cases of IPMN were analysed (1992-2007). Most patients were symptomatic (72.5%); cholangio-MRI had the best diagnostic accuracy both for the tumour nature (83.3%) and for the presence of malignancy (57.1%). ERCP was done in 8 cases (20%), and the results were poor. Thirteen patients were treated by pancreatic resection and 27 were maintained in follow-up. Total pancreatectomy was performed in 46% of the cases; in situ and invasive carcinoma were recognized in 15.4% and 38.4% of the cases, respectively. The mean follow-up was 42 months (range 12-72). One only patients with nodal metastases died 16 months after the operation for disease progression, while 91.6% of the operated patients are disease free. Out of the 27 not resected patients, 2 out of 4 presenting a lesion at high risk for malignancy died, while the remaining are in good conditions and disease free, with a mean follow-up of 31 months.</p> <p>Conclusion</p> <p>Therapeutic indication for IPMNs is mainly based upon radiological evaluation of the risk of malignancy. While the main duct tumours should be resected, preserving whenever possible a portion of the gland, the secondary ducts tumours may be maintained under observation, in absence of radiological elements of suspicion such as size larger than 3 cm, or a wall greater than 3 mm or nodules or papillae in the context of the cyst.</p

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with &#60;5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

Composition of human islet cell preparations for transplantation

To study the cellular composition of human islet cell isolates for transplantation, formalin-fixed and paraffin-embedded cell pellets were stained by the immunoperoxidase method with a panel of antibodies characterising endocrine, epithelial, soft tissue and haematolymphoid components. Immediately after separation, the isolates contained 30-80% islet cells, differing mainly in the content of islet and acinar cells, whereas the soft tissue, ductal/ductular and haematolymphoid elements comprised a relatively constant 10-20%. After 1 week in culture the islet cell content of less highly purified isolates (30-40% islets) dropped dramatically to 5%. The highly purified isolates (70-80% islets) showed only a minimal change in cellular composition; however, approximately two-thirds of islet cells were degranulated and did not stain for insulin. Haematolymphoid components were still present in all cultured isolates. We conclude that primarily mechanical purification methods and short-term culture are not sufficient to eliminate highly immunogenic cells. In addition, short-term culture is deleterious to the isolate if a significant number of acinar cells is still present after enrichment. © 1992 Springer-Verlag

Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies

INTRODUCTION: Prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association. METHODS AND ANALYSIS: We will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal. PROSPERO REGISTRATION NUMBER: CRD42018091627

Minimally invasive versus open distal pancreatectomy for pancreatic neuroendocrine tumors: An analysis from the U.S. neuroendocrine tumor study group

BackgroundTo determine shortâ and longâ term oncologic outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for the treatment of pancreatic neuroendocrine tumor (pNET).MethodsThe data of the patients who underwent curative MIDP or ODP for pNET between 2000 and 2016 were collected from a multiâ institutional database. Propensity score matching (PSM) was used to generate 1:1 matched patients with MIDP and ODP.ResultsA total of 576 patients undergoing curative DP for pNET were included. Two hundred and fourteen (37.2%) patients underwent MIDP, whereas 362 (62.8%) underwent ODP. MIDP was increasingly performed over time (2000â 2004: 9.3% vs 2013â 2016: 54.8%; Pâ <â 0.01). In the matched cohort (nâ =â 141 in each group), patients who underwent MIDP had less blood loss (median, 100 vs 200â mL, Pâ <â 0.001), lower incidence of Clavienâ Dindoâ â ¥â III complications (12.1% vs 24.8%, Pâ =â 0.026), and a shorter hospital stay versus ODP (median, 4 versus 7 days, Pâ =â 0.026). Patients who underwent MIDP had a lower incidence of recurrence (5â year cumulative recurrence, 10.1% vs 31.1%, Pâ <â 0.001), yet equivalent overall survival (OS) rate (5â year OS, 92.1% vs 90.9%, Pâ =â 0.550) compared with patients who underwent OPD.ConclusionPatients undergoing MIDP over ODP in the treatment of pNET had comparable oncologic surgical metrics, as well as similar longâ term OS.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150595/1/jso25481_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150595/2/jso25481.pd

OGX-427 inhibits tumor progression and enhances gemcitabine chemotherapy in pancreatic cancer

Despite many advances in oncology, almost all patients with pancreatic cancer (PC) die of the disease. Molecularly targeted agents are offering hope for their potential role in helping translate the improved activity of combination chemotherapy into improved survival. Heat shock protein 27 (Hsp27) is a chaperone implicated in several pathological processes such as cancer. Further, Hsp27 expression becomes highly upregulated in cancer cells after chemotherapy. Recently, a modified antisense oligonucleotide that is complementary to Hsp27 (OGX-427) has been developed, which inhibits Hsp27 expression and enhances drug efficacy in cancer xenograft models. Phase II clinical trials using OGX-427 in different cancers like breast, ovarian, bladder, prostate and lung are in progress in the United States and Canada. In this study, we demonstrate using TMA of 181 patients that Hsp27 expression and phosphorylation levels increase in moderately differentiated tumors to become uniformly highly expressed in metastatic samples. Using MiaPaCa-2 cells grown both in vitro and xenografted in mice, we demonstrate that OGX-427 inhibits proliferation, induces apoptosis and also enhances gemcitabine chemosensitivity via a mechanism involving the eukaryotic translation initiation factor 4E. Collectively, these findings suggest that the combination of Hsp27 knockdown with OGX-427 and chemotherapeutic agents such as gemcitabine can be a novel strategy to inhibit the progression of pancreas cancer