Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma:Review of the literature

Cholangiocarcinoma(CCA) is a malignant tumor of the biliary system and includes, according to the anatomical classification, intra hepatic CCA(iCCA),hilar CCA(hCCA) and distal CCA(dCCA). Hilar CCA is the most challenging type in terms of diagnosis, treatment and prognosis. Surgery is the only treatment possibly providing long-term survival, but only few patients are considered resectable at the time of diagnosis. In fact, tumor's extension to segmentary or subsegmentary biliary ducts, along with large lymph node involvement or intrahepatic metastases, precludes the surgical approach. To achieve R0 margins is mandatory for the disease-free survival and overall survival. In case of unresectable locally advanced hCCA, radiochemotherapy(RCT) as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation. Before liver surgery, RCT is believed to enhance the R0 margins rate. For patients meeting the Mayo Clinic criteria, RCT prior to orthotopic liver transplant(OLT) has proved to produce acceptable 5-years survivals. In this review, we analyze the current role of neoadjuvant RCT before resection as well as before OLT.     

Cotard's Syndrome Triggered by Fear in a Patient with Intellectual Disability: Causal or Casual Link?

Cotard's syndrome is a neuropsychiatric disease characterized by a variety of nihilistic delusions, commonly associated with several psychotic and major affective disorders, and neurological diseases, including stroke, dementia, and mental retardation. A 39-year-old male with mental retardation developed Cotard's syndrome, following an important episode of fear. During admission to our neurological unit, the patient underwent an accurate assessment, including neuroradiological, clinical, and neuropsychological examinations. At the psychiatric evaluation, he presented nihilistic delusions, in which he negated the existence of his body parts and the existence of his family members. The neuropsychological assessment ruled out other possible causes of misidentification, including the post-traumatic stress disorder. Thus, since also organic causes of Cotard's syndrome were excluded, the correlation between fear and the syndrome has been postulated and the patient opportunely treated, using a multidisciplinary approach. Our case suggests that in predisposed individuals negative emotions, including fear, may lead to delusional syndromes.     

Transient mid-ventricular dyskinesia: a variant of Takotsubo syndrome

Takotsubo Cardiomyopathy is characterized by a reversible systolic left ventricular apical ballooning. A new pattern of dyskinesia in the absence of angiographic evidence of coronary artery stenosis has been indicated like a variant of takotsubo cardiomiopathy: mid-ventricular akinesis with preservation of apical and basal contractilities revealed at echocardiograms and ventriculographies. We report the case of a 65 years old patient with this pattern, reverted in 4 weeks.     

Association between γ marker,human leucocyte antigens and killer immunoglobulin‐like receptors and the natural course of human cytomegalovirus infection: a pilot study performed in a Sicilian population

Natural killer (NK) cells provide a major defence against human cytomegalovirus (HCMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin‐like receptors (KIRs), and human leucocyte antigen (HLA) class I molecules. Also γ marker (GM) allotypes, able to influence the NK antibody‐dependent cell‐mediated cytotoxicity, appear to be involved in the immunological control of virus infections, including HCMV. In some cases, their contribution requires epistatic interaction with other genes of the immune system, such as HLA. In the present report, with the aim of gaining insight into the immune mechanisms controlling HCMV, we have studied the possible associations among humoral and NK responses, and HCMV infections. In a previous study we assessed whether the KIR and HLA repertoire might influence the risk of developing symptomatic (n = 60) or asymptomatic (n = 60) disease after primary HCMV infection in the immunocompetent host. In the present study, the immunocompetent patients with primary symptomatic HCMV infection were genotyped for GM3/17 and GM23 allotypes, along with the 60 participants with a previous asymptomatic infection as controls. Notwithstanding the presence of missing data record, advanced missing data recovery techniques were able to show that individuals carrying the GM23 allotypes, both homozygous and heterozygous, GM17/17, HLA‐C2 and Bw4^T KIR‐ligand groups are associated with the risk of developing symptomatic infection. Our findings on the role of both cellular and humoral immunity in the control of HCMV infection should be of value in guiding efforts to reduce HCMV‐associated health complications in the elderly, including immunosenescence, and in transplantation.     

Percutaneous US-guided RF thermal ablation for malignant renal tumors: preliminary results in 13 patients

Minimally invasive treatment for small renal cell carcinoma (RCC) can be necessary in selected patients and, anyway, is desirable. In situ ablation techniques, including RFA, have been developed. The aim of this study is to evaluate the feasibility, safety and short-term local effectiveness of percutaneous US-guided RFA in a small series, as well as mid-term patient outcome. Thirteen patients with a total of 18 tumors (17 small lesions, 35 mm in size or less, and a larger one, 75 mm in size) underwent 19 RFA sessions. Seven patients had a solitary kidney, and three suffered from VHL disease, too. We treated four lesions in a patient with a bilateral tumor. In another patient, three lesions were ablated. Seventeen tumors were RCC; one was a metastasis from lung cancer. Eight lesions were parenchymal, six exophytic, two parenchymal/exophytic, one parenchymal/central and one central. A monopolar RF system with multitined expandable electrode needles was used. The 35-mm lesion underwent two sessions; the 75-mm lesion was treated with transcatheter arterial embolization before RFA. Tumors with complete loss of contrast enhancement at short-term CT (or MR) were considered successfully treated. Percutaneous US-guided RFA was always feasible without major complications. The success rate after a single treatment in tumors less than 35 mm in size was 88.2% (15/17) and rose to 94.1% (16/17) after the second treatment of the largest lesion. After a mean 14-month follow-up, no successfully treated lesions recurred locally. Only the patient with metastasis from lung cancer died from disease progression in a further location, while all other patients are alive, with renal function still sufficient to avoid dialysis. US guidance allows an easy and safe percutaneous approach for RFA of small non-parahilar RCC. The treatment is locally effective and can be proposed as a minimally invasive therapy for patients with contraindications to surgery or to those expressing an informed consent. Based on the results of this study and of the literature, mid-term results on the clinical usefulness are very encouraging.Presented at ECR 2003.     

Hippocampal BOLD response during category learning predicts subsequent performance on transfer generalization

To test a prediction of our previous computational model of cortico‐hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI‐adapted category‐learning task that has two phases, an initial phase in which associations are learned through trial‐and‐error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning‐related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands. Hum Brain Mapp 35:3122–3131, 2014. © 2013 Wiley Periodicals, Inc .     

Anticholinergic drugs rescue synaptic plasticity in DYT1 dystonia: Role of M1 muscarinic receptors

Broad‐spectrum muscarinic receptor antagonists have represented the first available treatment for different movement disorders such as dystonia. However, the specificity of these drugs and their mechanism of action is not entirely clear. We performed a systematic analysis of the effects of anticholinergic drugs on short‐ and long‐term plasticity recorded from striatal medium spiny neurons from DYT1 dystonia knock‐in (Tor1a^+/Δgag) mice heterozygous for ΔE‐torsinA and their controls (Tor1a^+/+ mice). Antagonists were chosen that had previously been proposed to be selective for muscarinic receptor subtypes and included pirenzepine, trihexyphenydil, biperiden, orphenadrine, and a novel selective M₁ antagonist, VU0255035. Tor1a^+/Δgag mice exhibited a significant impairment of corticostriatal synaptic plasticity. Anticholinergics had no significant effects on intrinsic membrane properties and on short‐term plasticity of striatal neurons. However, they exhibited a differential ability to restore the corticostriatal plasticity deficits. A complete rescue of both long‐term depression (LTD) and synaptic depotentiation (SD) was obtained by applying the M₁‐preferring antagonists pirenzepine and trihexyphenidyl as well as VU0255035. Conversely, the nonselective antagonist orphenadrine produced only a partial rescue of synaptic plasticity, whereas biperiden and ethopropazine failed to restore plasticity. The selectivity for M₁ receptors was further demonstrated by their ability to counteract the M₁‐dependent potentiation of N‐methyl‐d ‐aspartate (NMDA) current recorded from striatal neurons. Our study demonstrates that selective M₁ muscarinic receptor antagonism offsets synaptic plasticity deficits in the striatum of mice with the DYT1 dystonia mutation, providing a potential mechanistic rationale for the development of improved antimuscarinic therapies for this movement disorder. © 2014 International Parkinson and Movement Disorder Society