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Objective: Rare disease Background: Intrapancreatic accessory spleen, or splenunculus, is a congenital condition that occurs in up to 2% of the population, with the tail of the pancreas being the second most common site. Imaging alone may not confirm the diagnosis as this can mimic a hypervascular tumor on contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). This report presents a challenging case of intrapancreatic accessory spleen in the tail of the pancreas in a 64-year-old man. Case Report: A 64-year-old man was admitted for a space-occupying lesion in the tail of the pancreas. CT, MRI, and positron emission tomography-CT could not confirm the diagnosis. Endoscopic ultrasound-guided fine-needle aspiration biopsy was not performed given the potential for greater risk. The mass in the patient's pancreatic tail was considered benign or low-grade malignant. The patient then underwent a robotic pancreatectomy to remove the tumor in the tail of the pancreas. We performed intraoperative ultrasound scanning and detected a hypoechoic nodule in the body of the pancreas. This nodule had a clear boundary, and color Doppler flow imaging showed that there was no definite blood flow signal in it. The pathology diagnosis after surgery was intrapancreatic accessory spleen. The patient recovered without other complications and was discharged 5 days later. Conclusions: This report highlights the importance of considering the diagnosis of intrapancreatic accessory spleen in hypervascular lesions seen on imaging alone and of confirming the diagnosis with definitive cytopathology or histopathology. [ABSTRACT FROM AUTHOR]

Purpose: The detection of pancreatic cystic lesions (PCL) causes uncertainty for physicians and patients, and international guidelines are based on low evidence. The extent and perioperative risk of resections of PCL in Germany needs comparison with these guidelines to highlight controversies and derive recommendations. Methods: Clinical data of 1137 patients who underwent surgery for PCL between 2014 and 2019 were retrieved from the German StuDoQ|Pancreas registry. Relevant features for preoperative evaluation and predictive factors for adverse outcomes were statistically identified. Results: Patients with intraductal papillary mucinous neoplasms (IPMN) represented the largest PCL subgroup (N = 689; 60.6%) while other entities (mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine tumors, pseudocysts) were less frequently resected. Symptoms of pancreatitis were associated with IPMN (OR, 1.8; P = 0.012) and pseudocysts (OR, 4.78; P < 0.001), but likewise lowered the likelihood of MCN (OR, 0.49; P = 0.046) and SCN (OR, 0.15, P = 0.002). A total of 639 (57.2%) patients received endoscopic ultrasound before resection, as recommended by guidelines. Malignancy was histologically confirmed in 137 patients (12.0%), while jaundice (OR, 5.1; P < 0.001) and weight loss (OR, 2.0; P = 0.002) were independent predictors. Most resections were performed by open surgery (N = 847, 74.5%), while distal lesions were in majority treated using minimally invasive approaches (P < 0.001). Severe morbidity was 28.4% (N = 323) and 30d mortality was 2.6% (N = 29). Increased age (P = 0.004), higher BMI (P = 0.002), liver cirrhosis (P < 0.001), and esophageal varices (P = 0.002) were independent risk factors for 30d mortality. Conclusion: With respect to unclear findings frequently present in PCL, diagnostic means recommended in guidelines should always be considered in the preoperative phase. The therapy of PCL should be decided upon in the light of patient-specific factors, and the surgical strategy needs to be adapted accordingly. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine tumors are typically solid neoplasms but in rare instances may present as cystic lesions. Preoperative diagnosis of a cystic pancreatic lesion is challenging and requires a multidisciplinary and multimodal approach. We hereby describe an elderly female who came with complaints of abdominal lump. Radiologically, it appeared to be a pancreatic hydatid cyst located at the head of the pancreas, following which resection was done. Histopathological study of the lesion turned out to be a cystic pancreatic neuroendocrine tumor. Thus, we present this unique case due to its rarity and diagnostic challenge. [ABSTRACT FROM AUTHOR]

With the liberal use of CT scan for clinical diagnosis, clinicians are faced with an increasing number of pancreatic incidentalomas. Compared with other incidentalomas, pancreatic incidentalomas have higher chances of future malignant transformation. There are many differential diagnoses, and epidermoid cyst in an intrapancreatic accessory spleen (ECIPAS) is extremely rare, with only a handful of reports. Preoperative diagnosis is often complicated, and the final diagnosis is usually only made after surgical resection. We report a 34-year-old man who had an incidentally noted 2.8 cm pancreatic tail cystic lesion on a CT scan done for urinary symptoms. The lesion had a solid nodular component that was worrisome for malignancy, and the patient underwent further evaluation with an MRI scan and endoscopic ultrasound of the pancreas. The differential diagnoses of cystic degeneration of neuroendocrine tumour, branch-duct intraductal papillary mucinous neoplasm with worrisome features or ectopic intrapancreatic spleen were made. A multidisciplinary tumour board recommended surgical resection given risk features of malignancy. The patient subsequently underwent a laparoscopic distal pancreatectomy with splenectomy, and histology confirmed the diagnosis of ECIPAS. Imaging characteristics of ECIPAS are non-specific, and most patients have a diagnosis made only after surgery. Therefore, more evidence is warranted for accurate preoperative imaging diagnosis to avoid unnecessary pancreatic surgery, which is not without its risks. [ABSTRACT FROM AUTHOR]

Cystic pancreatic lesions (CPLs) are frequently casual findings in radiological examinations performed for other reasons in patients with unrelated symptoms. As they require different management according to their histological nature, differential diagnosis is essential. Radiologist plays a key role in the diagnosis and management of these lesions as imaging is able to correctly characterize most of them and thus address to a correct management. The first step for a correct characterization is to look for a communication between the CPLs and the main pancreatic duct, and then, it is essential to evaluate the morphology of the lesions. Age, sex and a history of previous pancreatic pathologies are important information to be used in the differential diagnosis. As some CPLs with different pathologic backgrounds can show the same morphological findings, differential diagnosis can be difficult, and thus, the final diagnosis can require other techniques, such as endoscopic ultrasound, endoscopic ultrasound-fine needle aspiration and endoscopic ultrasound-through the needle biopsy, and multidisciplinary management is important for a correct management. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for motor symptoms of Parkinson's disease (PD) when L-DOPA therapy induces disabling side effects. Classical inflammatory activation of glial cells is well established in PD, contributing to the progressive neurodegenerative state; however, the role of DBS in regulating the inflammatory response remains largely unknown. To understand the involvement of astrocytes in the mechanisms of action of DBS, we evaluated the effect of STN–DBS in regulating motor symptoms, astrocyte reactivity, and cytokine expression in a 6-OHDA-induced PD rat model. To mimic in vivo DBS, we investigate the effect of high-frequency stimulation (HFS) in cultured astrocytes regulating cytokine induction and NF-κB activation. We found that STN-DBS improved motor impairment, induced astrocytic hyperplasia, and reversed increased IFN-γ and IL-10 levels in the globus pallidus (GP) of lesioned rats. Moreover, HFS activated astrocytes and prevented TNF-α-induced increase of monocyte chemoattractant protein-1 (MCP-1) and NF-κB activation in vitro. Our results indicate that DBS/HFS may act as a regulator of the inflammatory response in PD states, attenuating classical activation of astrocytes and cytokine induction, potentially through its ability to regulate NF-κB activation. These findings may help us understand the role of astrocyte signaling in HFS, highlighting its possible relationship with the effectiveness of DBS in neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine tumors (PNETs) are typically solid neoplasms but, in very rare cases, present as cystic lesions. We describe a case of a cystic neuroendocrine tumor that developed as a small cystic lesion. Case presentation: In 2011, a 66-year-old Japanese woman underwent computed tomography (CT) that revealed a cystic lesion in the tail of the pancreas measuring 9 mm. She did not have any symptoms. She underwent a CT scan every year thereafter. The cystic lesion gradually increased and was 40 mm in 2019; endoscopic retrograde pancreatography (ERP) was then performed. Cytological examination demonstrated class IIIb adenocarcinoma, and we conducted laparoscopic distal pancreatectomy. Pathological examination showed PNET. Conclusion: Although cystic change of PNET is generally caused by ischemia or necrosis inside the tumor, in our case, PNET occurred as a small cyst that increased without changing form. [ABSTRACT FROM AUTHOR]

Cellular plasticity, a feature associated with epithelial-to-mesenchymal transition (EMT), contributes to tumor cell survival, migration, invasion, and therapy resistance. Phenotypic plasticity of the epithelium is a critical feature in multiple phases of human cancer in an oncogene- and tissue-specific context. Many factors can drive epithelial plasticity, including activating mutations in KRAS , which are found in an estimated 30% of all cancers. In this review, we will introduce cellular plasticity and its effect on cancer progression and therapy resistance and then summarize the drivers of EMT with an emphasis on KRAS effector signaling. Lastly, we will discuss the contribution of cellular plasticity to metastasis and its potential clinical implications. Understanding oncogenic KRAS cellular reprogramming has the potential to reveal novel strategies to control metastasis in KRAS-driven cancers. [ABSTRACT FROM AUTHOR]

In this review, combined post-mortem brain magnetic resonance imaging (MRI) and histology studies are highlighted, illustrating the relevance of translational approaches to define novel MRI signatures of neuropathological lesions in neuroinflammatory and neurodegenerative disorders. Initial studies combining post-mortem MRI and histology have validated various MRI sequences, assessing their sensitivity and specificity as diagnostic biomarkers in neurologic disease. More recent studies have focused on defining new radiological (bio)markers and implementing them in the clinical (research) setting. By combining neurological and neuroanatomical expertise with radiological development and pathological validation, a cycle emerges that allows for the discovery of novel MRI biomarkers to be implemented in vivo. Examples of this cycle are presented for multiple sclerosis, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. Some applications have been shown to be successful, while others require further validation. In conclusion, there is much to explore with post-mortem MRI and histology studies, which can eventually be of high relevance for clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Alexander Disease (AxD) is a degenerative disorder caused by mutations in the GFAP gene, which encodes the major intermediate filament of astrocytes. As other cells in the CNS do not express GFAP, AxD is a primary astrocyte disease. Astrocytes acquire a large number of pathological features, including changes in morphology, the loss or diminution of a number of critical astrocyte functions and the activation of cell stress and inflammatory pathways. AxD is also characterized by white matter degeneration, a pathology that has led it to be included in the “leukodystrophies.” Furthermore, variable degrees of neuronal loss take place. Thus, the astrocyte pathology triggers alterations in other cell types. Here, we will review the neuropathology of AxD and discuss how a disease of astrocytes can lead to severe pathologies in non‐astrocytic cells. Our knowledge of the pathophysiology of AxD will also lead to a better understanding of how astrocytes interact with other CNS cells and how astrocytes in the gliosis that accompanies many neurological disorders can damage the function and survival of other cells. [ABSTRACT FROM AUTHOR]

Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine tumors (PNETs) are relatively rare; however, the incidence has increased over the last few decades. They are classified as functional or non-functional tumors according to the presence of associated clinical symptoms. The majority are nonfunctional tumors. For classification and staging, the World Health Organization 2010 classification system is the most commonly accepted. Chromogranin A is the most sensitive marker but has insufficient specificity. In general, PNETs are hypervascular tumors, and multiphasic contrast-enhanced computed tomography is considered the first choice for imaging study. Multiphasic magnetic resonance imaging can detect PNETs smaller than 2 cm and small liver metastasis compared with other modalities. Somatostatin receptor scintigraphy is often used in cases where functional PNETs are suspected. Positron emission tomography (PET) scan with 18F-fluorodeoxyglucose cannot visualize PNETs, but PET with 68-Ga DOTATATE can. Endoscopic ultrasonography can characterize smaller PNETs using contrast and confirm histology through fine needle aspiration or biopsy. In this article, we review the characteristics of grading systems and diagnostic modalities commonly used for PNETs. [ABSTRACT FROM AUTHOR]

Rationale: Pancreatic tail cystic lesions are increasingly encountered in clinical practice, however, it is difficult to make a correct diagnosis preoperatively because there are many types of pancreatic neoplastic and non-neoplastic cysts. Epidermoid cyst in an intrapancreatic accessory spleen (ECIPAS) is a rare non-neoplastic cyst locating in the pancreatic tail, and it is commonly misdiagnosed as another cystic neoplasm., Patient Concerns: A 51-year-old man was admitted for investigation of abdominal pain. The physical examination and laboratory tests found no abnormalities, except for an elevation of carbohydrate antigen (CA)19-9. Imaging revealed a cystic lesion within the pancreatic tail, and the solid component surrounding the cyst was enhanced similarly to those of the splenic tissue., Diagnosis: ECIPAS was diagnosed based on the pathology after surgery. The mass was composed of a cyst and brown solid spleen-like tissue. The microscopic analysis demonstrated that the solid component was accessory splenic tissue, and the cyst wall was lined with a thin stratified squamous epithelium., Interventions: Laparoscopic spleen-preserving distal pancreatectomy was performed., Outcomes: The patient was discharged on day 5 postoperatively after an uneventful recovery. CA19-9 returned to normal after surgery. During a 2-years follow-up, there was no evidence of tumor recurrence., Lessons: Although rare ECIPAS should be considered in the differential diagnosis of pancreatic tail cystic lesions, and the typical imaging features might facilitate the preoperative diagnosis. Laparoscopic distal pancreatectomy is a safe and effective approach for treating ECIPAS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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Rapid On-Site Evaluation (ROSE) has been well documented in its ability to improve the diagnostic yield and accuracy of fine needle aspirations across many sites, resulting in better quality of patient management and a simultaneous reduction in treatment costs. Telecytology makes it possible for cytology laboratories to offer ROSE in a cost effective manner, whilst employing only a small number of trained cytopathologists to cover many sites from a single connected location. However, the adoption of telecytology for ROSE has been lackluster. We believe that this reluctance is not only due to barriers such as technology limitations and financial obstacles, but also due to overlooked psychological factors. This article discusses the unaddressed psychological considerations of telecytology for ROSE. [ABSTRACT FROM AUTHOR]

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon lymphoma that accounts for 3-8% of all Hodgkin lymphomas. NLPHL typically presents as early stage disease with localized peripheral lymphadenopathy. Involvement of extranodal sites at the time of presentation occurs in 6% of cases and most commonly involves the spleen, liver, bone marrow, and Waldeyer ring. Primary extranodal NLPHL is exceedingly rare. We describe the first reported case involving the thyroid and review the six other previously described cases of primary extranodal NLPHL.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) using an MRI-guided and MRI-verified technique without microelectrode recording is an effective and safe surgical treatment for patients with Parkinson's disease (PD). Objectives: To assess the anatomical accuracy of lead placement after MRI-guided, MRI-verified STN DBS using post-mortem histology and high-field MRI at 9.4 T. Methods: We conducted post-mortem analysis of a patient's brain who had had MRI-guided, MRI-verified STN DBS for PD, using 9.4-T MRI and histology. After death, the brain was retrieved and a block including the electrode tracks down to the mesencephalon was examined with high-field MRI at 9.4 T and histological analysis. Results: High-field MRI images and corresponding histological examination showed that each electrode track ended within the intended target area, and that DBS did not cause significant neuroparenchymal tissue damage. Conclusions: This study supports the anatomical accuracy of the MRI-guided and MRI-verified method of STN DBS. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine tumors (pNETs) are rare and comprise only 1-2 % of all pancreatic neoplastic disease. Although the majority of these tumors are sporadic (90 %), pNETs can arise in the setting of several different hereditary genetic syndromes, most commonly multiple endocrine neoplasia type 1 (MEN1). The presentation of pNETs varies widely, with over 60 % having malignant distant disease at the time of initial diagnosis involving the liver or other distant sites. Functioning pNETs represent approximately 10 % of all pNETs, secrete a variety of peptide hormones, and are responsible for several clinical syndromes caused by profound hormonal derangement. Surgery remains the cornerstone of therapy and the only curative approach. It should be pursued for localized disease and for metastatic lesions amenable to resection. Multimodality therapies, including liver-directed therapies and medical therapy, are gaining increasing favor in the treatment of advanced pNETs. Their utility is multifold and spans from ameliorating symptoms of hormonal excess (functional pNETs) to controlling the local and systemic disease burden (non-functional pNETs). The recent introduction of target molecular therapy has promising results especially for the treatment of progressive well-differentiated G1/G2 tumor. In this review, we summarize the current knowledge and give an update on recent advancements made in the therapeutic strategies for pNETs. [ABSTRACT FROM AUTHOR]

Introduction: Therapy-associated onset of stemness-maintenance in surviving tumor-cells dictates tumor relapse/recurrence. Recently, we recognized the anti-pancreatic cancer (PC) potential of seaweed polyphenol manifolds and narrowed down three superior drug-deliverables that could serve as adjuvants and benefit PC cure. Utilizing the PC- cancer stem cells (PC-CSCs) grown ex vivo and mouse model of residual-PC, we investigated the benefits of seaweed polyphenols in regulating stemness-maintenance. Methods: ALDH+CD44+CD24+ PC-CSCs from Panc-1, Panc-3.27, MiaPaCa-2, or BxPC-3 cells-derived xenografts grown ex vivo were either mock-irradiated, exposed to fractionated irradiation (FIR, 2Gy/D for 5 days), treated with polyphenols (100 μg/ml) of Hormophysa triquerta (HT-EA), Spatoglossum asperum (SA-EA) or Padina tetrastromatica (PT-EA) with/without FIR were examined for cell viability, transcription of 93 stem-cell-related molecules (QPCR profiling). Polyphenol-dependent regulation of FIR-transactivated Oct4, Zic3, EIF4C, Nanog, and LIF (QPCR) and functional translation of Nanog, SOX2, and OCT3/4 (immunoblotting) were examined in Panc-1/Panc-3.27/MiaPaCa-2/BxPC- 3-xenografts derived PC-CSCs. Effect of seaweed-polyphenols in the regulation of EMT (N-Cadherin), pluripotency- (SOX2, OCT3/4, Nanog) and stemness-maintenance (PI3KR1, LIF, CD44) in therapy (FIR, 2Gy/D for 5D/wk for 3-weeks) resistant residual tumors were examined by tissue microarray construction and automated immunohistochemistry. Results: Ex vivo exposure of PC-CSCs to SA-EA, PT-EA and HT-EA exhibit dose-dependent inhibition of cell viability. FIR amplified the transcription of 69, 80, 74 and 77 stem-cell related genes in MiaPaCa-2-, Panc-1-, Panc- 3.27- and BXPC3-established xenograft-derived ALDH+CD44+CD24+PC-CSCs. Treatment with SA-EA, PT-EA, or HT-EA completely suppressed FIR-activated stem-cell transcriptional machinery in ALDH+CD44+CD24+PC-CSCs established from MiaPaCa-2, Panc-1, Panc-3.27 and BXPC3 xenografts. QPCR validated EIF4C, OCT3/4, Nanog, LIF, and ZIC3 transcriptional profile outcomes. Nanog, Sox2, and OCT3/4 immunoblotting affirmed the PC-CSC radiosensitizing benefit of seaweed polyphenols. Residual-PC tissues microarrayed and immunostained after in vivo treatments recognized complete regulation of FIR-induced SOX2, OCT3/4, Nanog, LIF, CD44, PIK3R1, N-Cadherin, and E-Cadherin with SA-EA, PT-EA, and HT-EA. Conclusions: These data, for the first time, documented the EMT/stemness-maintenance in therapy-resistant PC-CSCs. Further, the data suggest that seaweed polyphenols may inhibit PC relapse/recurrence by targeting therapy-orchestrated stem-cell signaling in residual cells. [ABSTRACT FROM AUTHOR]

Cystic neoplasms of the pancreas are found with increasing prevalence, especially in elderly asymptomatic individuals. Although the overall risk of malignancy is very low, the presence of these pancreatic cysts is associated with a large degree of anxiety and further medical investigation due to concerns about malignancy. This review discusses the different cystic neoplasms of the pancreas and reports diagnostic strategies based on clinical features and imaging data. Surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines, is also discussed, with special reference to intraductal papillary mucinous neoplasm (IPMN; particularly the branch duct variant), which is the lesion most frequently identified incidentally. IPMN pathology, its risk for development into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk are discussed. Finally, surgical treatment, strategies for surveillance of pancreatic cysts, and possible future directions are discussed. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is an aggressive disease accounting for more than 260,000 cancer cases diagnosed and 128,000 deaths worldwide. A large majority of cancer deaths result from cancers that have metastasized beyond the primary tumor. The relationship between genetic changes and clinical outcome can reflect the biological events that promote cancer’s aggressive behavior, and these can serve as molecular markers for improved patient management and survival. To this end, epithelial-mesenchymal transition (EMT) is a major process that promotes tumor invasion and metastasis, making EMT-related proteins attractive diagnostic biomarkers and therapeutic targets. In this study, we used immunohistochemistry to study the expression of a panel of transcription factors (TWIST1, SNAI1/2, ZEB1 and ZEB2) and other genes intimately related to EMT (CDH1 and LAMC2) at the invasive tumor front of OSCC tissues. The association between the expression of these proteins and clinico-pathological parameters were examined with Pearson Chi-square and correlation with survival was analyzed using Kaplan Meier analysis. Our results demonstrate that there was a significant differential expression of CDH1, LAMC2, SNAI1/2 and TWIST1 between OSCC and normal oral mucosa (NOM). Specifically, CDH1 loss was significantly associated with Broder’s grading, while diffused LAMC2 was similarly associated with non-cohesive pattern of invasion. Notably, co-expression of TWIST1 and ZEB2 in OSCC was significantly associated with poorer overall survival, particularly in patients without detectable lymph node metastasis. This study demonstrates that EMT-related proteins are differentially expressed in OSCC and that the co-expression of TWIST1 and ZEB2 could be of clinical value in identifying patients with poor survival for appropriate patient management. [ABSTRACT FROM AUTHOR]

There is uncertainty concerning the circuit connections by which the superior colliculus interacts with the basal ganglia. To address this issue, anterograde and retrograde tracers were placed, respectively, into the superior colliculus and globus pallidus of Sprague-Dawley rats. In this two-tracer experiment, the projections from the superior colliculus terminated densely in the ventral zona incerta (ZIv), but did not overlap the labeled neurons observed in the subthalamic nucleus. In cases in which anterograde and retrograde tracers were placed, respectively, in sensory-responsive sites in the superior colliculus and posteromedial (POm) thalamus, the labeled projections from superior colliculus innervated the ZIv regions that contained the labeled neurons that project to POm. We also confirmed this colliculo-incertal-POm pathway by depositing a mixture of retrograde and anterograde tracers at focal sites in ZIv to reveal retrogradely labeled neurons in superior colliculus and anterogradely labeled terminals in POm. When combined with retrograde tracer injections in POm, immunohistochemical processing proved that most ZIv projections to POm are GABAergic. Consistent with these findings, direct stimulation of superior colliculus evoked neuronal excitation in ZIv and caused inhibition of spontaneous activity in POm. Collectively, these results indicate that superior colliculus can activate the inhibitory projections from ZIv to the POm. This is significant because it suggests that the superior colliculus could suppress the interactions between POm and the dorsolateral striatum, presumably to halt ongoing behaviors so that more adaptive motor actions are selected in response to unexpected sensory events. [ABSTRACT FROM AUTHOR]

Key points We have developed a unique prototype to perform brain stimulation in mice., This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits)., This new micro-stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue., The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation., Abstract Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease. [ABSTRACT FROM AUTHOR]

Plasma cells (PCs) are essentially characterized by the co-expression of CD138 and CD38, which allows their identification in flowcytometry in bone marrow(BM), peripheral blood, or cell suspensions from tissues. These terminally differentiated B-cells may lose the expression of surface CD19 and that of CD20 while retaining CD27. When malignant, they can gain a number of other markers such as CD28, CD33, CD56, or CD117 and lose CD27. Moreover, since each PC is only able to produce a single type of immunoglobulins (Igs), they display isotypic restriction and clonal malignant PCs can be further characterized by their homogeneous expression of either kappa or lambda light chains. In multiple myeloma (MM), such PC clones produce the Ig identified in plasma as an abnormal peak. In the BM where they essentially accumulate, these PCs may however display various immunophenotypes. The latter were explored in a two-way approach. Firstly, the various subsets delineated by the selective or common expression of CD19 together with combined CD56/CD28 were explored in normal and MM BM. Then, other aberrant markers' expression was investigated, i.e., CD20, CD27, CD33, CD56, CD117. These data were compared to literature information. They underline the vast heterogeneity of MM PCs possibly accounting for the various answers to therapy of MM patients. [ABSTRACT FROM AUTHOR]

Cutaneous focal mucinosis (CFM) is a localized form of cutaneous dermal mucinosis clinically presenting as an asymptomatic skin-colored papule or nodule. The etiopathogenesis of CFM is unclear, but it is thought to represent a reactive lesion. Although trauma has been suspected as a triggering factor, it has never been proven in cases of CFM. We report 2 male patients with trauma-induced CFM arising at the mammary areola, which is an unusual site for CFM. Both male patients presented with a solitary nodular lesion of up to 2 cm in diameter at the right areola. Histology was characterized by circumscribed abundant dermal mucin deposits in a polylobulated pattern without an increased number of fibroblasts or capillaries and with absence of an inflammatory infiltrate. Alcian blue stain at pH 2.5 highlighted the mucin deposits. Immunohistochemistry showed partial expression of FXIIIa by 30% of the stromal cells, but no reactivity for CD34, smooth muscle actin, desmin, CD68 and S-100. A history of trauma (laser-based epilation, piercing) preceded the development of CFM in both patients. Surgical excision resulted in complete remission without recurrence. Follow-up in both our patients did not reveal recurrences. CFM has to be distinguished from benign and malignant myxoid neoplasms. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

While fine needle aspiration (FNA) is certainly not a new biopsy technique, recent developments in advanced imaging techniques, molecular testing, and targeted therapies have coincided with a rapid increase in the number of FNA procedures being performed. Concurrently, the demand for on-site evaluation of adequacy (OSEA) has also increased, outstripping the capacity of available cytopathologists at some institutions. Among the several alternatives to cytopathologist-performed OSEA, cytotechnologist-attended OSEA stands out because it preserves the representation of the pathology service at the time of the procedure. Herein, we review the current literature about OSEA and the necessity of cytotechnologists to expand access of this useful pathology service to a broader patient population. We also examine how cytotechnologists are likely to fit into the emerging practice of telecytology. [ABSTRACT FROM AUTHOR]

Background: The dorso-lateral part of the subthalamic nucleus (STN) is considered as the usual target of deep brain stimulation for Parkinson's disease. Nevertheless, the exact anatomical location of the electrode contacts used for chronic stimulation is still a matter of debate. The aim of this study was to perform a systematic review of the existing literature on this issue. Method: We searched for studies on the anatomical location of active contacts published until December 2012. Results: We identified 13 studies, published between 2002 and 2010, including 260 patients and 466 electrodes. One hundred and sixty-four active contacts (35 %) were identified within the STN, 117 (25 %) at the interface between STN and the surrounding structures, 184 (40 %) above the STN and one within the substantia nigra. We observed great discrepancies between the different series. The contra-lateral improvement was between 37 and 78.5 % for contacts located within the STN, between 48.6 and 73 % outside the STN, between 65.3 and 66 % at the interface. The authors report no clear correlation between anatomical location and stimulation parameters. Conclusions: Post-operative analysis of the anatomical location of active contacts is difficult, and all the methods used are debatable. The relationship between the anatomical location of active contacts and the clinical effectiveness of stimulation is unclear. It would be necessary to take into account the volume of the electrode contacts and the diffusion of the stimulation. We can nevertheless assume that the interface between dorso-lateral STN, zona incerta and Forel's fields could be directly involved in the effects of stimulation. [ABSTRACT FROM AUTHOR]

Deguelin is known to suppress the growth of cancer cells; however, its anti-metastatic effects have not been studied so far in any cancer model. In the present study, we aimed to evaluate the anti-metastatic potential of deguelin in vivo and in tumor growth factor-β1 (TGFβ1)-stimulated cells. Our results demonstrate that tumor growth, peritoneal dissemination and liver/lung metastasis of orthotopically implanted PanC-1-luc cells were significantly reduced in deguelin-treated mice along with the induction of apoptosis. Furthermore, deguelin-treated tumors showed increased epithelial signature such as increased expression of E-Cadherin and cytokeratin-18 and decreased expression of Snail. Similar observations were made when PanC-1, COLO-357 and L3.6pl cells were treated in vitro with deguelin. Moreover, E-cadherin was transcriptionally upregulated and accumulated in the membrane fraction of deguelin-treated cells, as indicated by increased interaction of E-Cadherin with β-catenin. TGFβ1-induced downregulation of E-Cadherin and upregulation of Snail were abrogated by deguelin treatment. In addition, deguelin inhibited TGFβ1-induced Smad3 phosphorylation and Smad4 nuclear translocation in PanC-1 cells. Furthermore, when TGFβ1-induced nuclear factor kappa B (NFκB) activation was inhibited, TGFβ1-induced Snail upregulation or E-Cadherin downregulation was blocked. Deguelin also significantly downregulated the constitutive phosphorylation and DNA binding of NFκB in a dose-dependent manner. Interestingly, overexpression of either NFκB or Snail completely abrogated deguelin-mediated epithelial-to-mesenchymal transition (EMT) inhibition, whereas overexpression of NFκB but not Snail rescued cells from deguelin-induced apoptosis. Hence, deguelin targets NFκB to induce reversal of EMT and apoptosis but downstream effectors might be different for both processes. Taken together, our results suggest that deguelin suppresses both pancreatic tumor growth and metastasis by inducing apoptosis and inhibiting EMT. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) has emerged as a powerful surgical therapy for the management of treatment-resistant movement disorders, epilepsy and neuropsychiatric disorders. Although DBS may be clinically effective in many cases, its mode of action is still elusive. It is unclear which neural cell types are involved in the mechanism of DBS, and how high-frequency stimulation of these cells may lead to alleviation of the clinical symptoms. Neurons have commonly been a main focus in the many theories explaining the working mechanism of DBS. Recent data, however, demonstrates that astrocytes may be active players in the DBS mechanism of action. In this review article, we will discuss the potential role of reactive and neurogenic astrocytes (neural progenitors) in DBS. [ABSTRACT FROM AUTHOR]

Background: Epitheliomesenchymal transition (EMT) is the process where cancer cells attain fibroblastic features and are thus able to invade neighboring tissues. Transcriptional factors zeb1, snai1 and twist regulate EMT. Methods: We used immunohistochemistry to investigate the expression of zeb1, twist and snai1 in tumor and stromal compartments by in a large set of breast carcinomas. The results were compared with estrogen and progesterone receptor status, HER2 amplification, grade, histology, TNM status and survival of the patients. Results: Nuclear expression for twist was seen in the epithelial tumor cell compartment in 3.6% and for snai1 in 3.1% of the cases while zeb1 was not detected at all in these areas. In contrast, the tumor stromal compartment showed nuclear zeb1 and twist expression in 75% and 52.4% of the cases, respectively. Although rare, nuclear expression of twist in the epithelial tumor cell compartment was associated with a poor outcome of the patients (p = 0.054 log rank, p = 0.013, Breslow, p = 0.025 Tarone-Ware). Expression of snai1, or expression of zeb1 or twist in the stromal compartment did not have any prognostic significance. Furthermore, none of these factors associated with the size of the tumors, nor with the presence of axillary or distant metastases. Expression of zeb1 and twist in the stromal compartment was positively associated with a positive estrogen or progesterone receptor status of the tumors. Stromal zeb1 expression was significantly lower in ductal in situ carcinomas than in invasive carcinomas (p = 0.020). Medullary carcinomas (p = 0.017) and mucinous carcinomas (p = 0.009) had a lower stromal expression of zeb1 than ductal carcinomas. Stromal twist expression was also lower in mucinous (p = 0.017) than in ductal carcinomas. Conclusions: Expression of transcriptional factors zeb1 and twist mainly occur in the stromal compartment of breast carcinomas, possibly representing two populations of cells; EMT transformed neoplastic cells and stromal fibroblastic cells undergoing activation of zeb1 and twist due to growth factors produced by the tumor. However, epithelial expression of twist was associated with a poor prognosis, hinting at its importance in the spread of breast carcinoma. [ABSTRACT FROM AUTHOR]

In a previous study it was found that the therapeutic effects of QLT0267, a small molecule inhibitor of integrin-linked kinase (ILK), were influenced by Her2/neu expression. To understand how inhibition or silencing of ILK influences Her2/neu expression, Her2/neu signaling was evaluated in six Her2/neu-positive breast cancer cell lines (LCC6Her2, MCF7Her2, SKBR3, BT474, JIMT-1 and KPL-4). Treatment with QLT0267 engendered suppression (32-87%) of total Her2/neu protein in these cells. Suppression of Her2/neu was also observed following small interfering RNA-mediated silencing of ILK expression. Time course studies suggest that ILK inhibition or silencing caused transient decreases in P-AKTser473, which were not temporally related to Her2/neu downregulation. Attenuation of ILK activity or expression was, however, associated with decreases in YB-1 (Y-box binding protein-1) protein and transcript levels. YB-1 is a known transcriptional regulator of Her2/neu expression, and in this study it is demonstrated that inhibition of ILK activity using QLT0267 decreased YB-1 promoter activity by 50.6%. ILK inhibition was associated with changes in YB-1 localization, as reflected by localization of cytoplasmic YB-1 into stress granules. ILK inhibition also suppressed TWIST (a regulator of YB-1 expression) protein expression. To confirm the role of ILK on YB-1 and TWIST, cells were engineered to overexpress ILK. This was associated with a fourfold increase in the level of YB-1 in the nucleus, and a 2- and 1.5-fold increase in TWIST and Her2/neu protein levels, respectively. Taken together, these data indicate that ILK regulates the expression of Her2/neu through TWIST and YB-1, lending support to the use of ILK inhibitors in the treatment of aggressive Her2/neu-positive tumors. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a major health problem worldwide responsible for 500 000 deaths annually. A number of risk factors are associated with either the induction of the disease or its progression; these include infection with hepatitis B or C virus, alcohol consumption, non-alcoholic steatohepatitis and certain congenital disorders. In around 80% of the cases, HCC is associated with cirrhosis or advanced fibrosis and with inflammation and oxidative stress. In this review we focus firstly on the different risk factors for HCC and summarize the mechanisms by which each is considered to contribute to HCC. In the second part we look at the molecular processes involved in cancer progression. HCC development is recognized as a multistep process that normally develops over many years. Over this period several mutations accumulate in the cell and that stimulate malign transformation, growth, and metastatic behavior. Over the recent years it has become evident that not only the tumor cell itself but also the tumor microenviroment plays a major role in the development of a tumor. There is a direct link between the role of inflammation and cirrhosis with this microenviroment. Both in vitro and in vivo it has been shown that tumor formation and metastatic properties are linked to epithelial-mesenchymal transition (EMT), a process by which facillitates the tumor cell's attempts to migrate to a more favourable microenviroment. Several groups have analyzed the gene expression in HCC and its surrounding tissue by microarray and this has resulted in the molecular classification into a distinct number of classes. Here we also found a role for hypoxia induced gene expression leading to a clinically more aggressive gene expression in HCC. Molecular analysis also helped to identify important cellular pathways and possible therapeutic targets. The first molecule that in this way has shown clinical application for liver cancer is the multikinase inhibitor sorafenib, others are currently in different stages of clinical studies like the mTOR inhibitor everolimus. [ABSTRACT FROM AUTHOR]

The most common neoplasm of the endocrine system is found in the thyroid gland with a significant increase in recent decades largely due to modern diagnostic methods. Thyroid tumors generally have a favorable evolution, but there are also aggressive variants with a poor prognosis. In these aggressive tumors, the most reliable method of detecting and making a differential diagnosis is represented by ultrasound-guided fine-needle cytopuncture, confirmed by histopathological examination. Although fine-needle aspiration puncture and cytological examination are considered to have a high sensitivity and specificity, diagnostic certainty is established later only by histopathological examination. Fine-needle aspiration cytopuncture of the thyroid gland correlated with histopathological examination has played a crucial role in recognizing and identifying variants of papillary carcinoma known to have aggressive biological behavior, especially in cases of poorly differentiated carcinoma. Recognition of aggressive variants of papillary carcinoma is of major importance in the prognosis and clinical management of patients. The aim of this study was to present the correlations found in a series of thyroid tumors from patients treated in surgery and oncology departments, as well as tumors accidentally detected during autopsies in the department of forensics. All the cases selected in the study benefited from a complex histopathological diagnosis adapted to each case in order to ensure maximum efficiency. [ABSTRACT FROM AUTHOR]

A letter to the editor and a reply is presented to the article "Limitations of widely used high-risk human papillomavirus laboratory-developed testing in cervical cancer screening " in the 2012 issue.

The article provides an answer to a question regarding the medical condition of a 58-year-old male with asymptomatic nodule on the anterior aspect of left leg.

Background: An epidermoid cyst in an intrapancreatic accessory spleen (ECIPAS) in the pancreas head is an extremely rare condition. The natural course of this condition is not well known, and it is difficult to diagnose before surgery due to the lack of specific imaging findings.Case Presentation: A tumor was found in the head of the pancreas in a 68-year-old man with abdominal distension and discomfort. Magnetic resonance imaging (MRI) suggested a malignant tumor, such as a colloid cancer. The tumor was removed surgically, with pathologic examination showing that it was an ECIPAS.Conclusion: ECIPAS cannot be easily distinguished from other pancreatic cystic tumors, making it necessary to include ECIPAS in the differential diagnosis of these tumors. Unnecessary surgical resection may be avoided by more accurate preoperative diagnosis based on clinical and imaging characteristics. [ABSTRACT FROM AUTHOR]

Background: An epithelial cyst in an intrapancreatic accessory spleen (ECIPAS) is rare. We report a case of ECIPAS that was treated with robot-assisted distal pancreatectomy with splenectomy.Case Presentation: The case was a 59-year-old woman who was referred to our hospital after a pancreatic tail tumor was found on computed tomography prior to surgery for small bowel obstruction at another hospital. A cystic lesion in the pancreatic tail was discovered and evaluated by magnetic resonance imaging and endoscopic ultrasonography. Based on clinical and radiological features, mucinous cystic neoplasm was included in the differential diagnosis. The patient underwent robot-assisted distal pancreatectomy with splenectomy. The postoperative course was uneventful. Pathological evaluation revealed a 20-mm ECIPAS in the pancreatic tail.Conclusions: If a pancreatic tail tumor is present, ECIPAS should be included in the differential diagnosis. However, preoperative diagnosis is difficult, and a definitive diagnosis is often not obtained until after surgery. Surgery should be minimally invasive. Laparoscopic distal pancreatectomy has become a standard surgical procedure because it is minimally invasive. Robot-assisted surgery is not only minimally invasive, but also advantageous, because it has a stereoscopic magnifying effect and allows the forceps to move smoothly. Robot-assisted distal pancreatectomy may be a good option, when performing surgery for a pancreatic tail tumor. [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine tumors (PNET) are rare, with a significant malignant potential. This study aimed to determine outcomes of patients with resected PNETs according to the cystic component and confirm the accuracy of preoperative staging. Methods: From 1997 to 2016, 106 patients underwent resection of PNETs, including 73 purely solid (S-PNETs, 69%), 21 mixed (M-PNETs, 20%), and 12 purely cystic lesions (C-PNETs, 11%). To ensure consistent comparisons of overall (OS) and disease-free (DFS) survival outcomes between the 3 groups, the patients were matched according to the World Health Organization (WHO) grade and tumor height. Results: Overall, the rate of correlation between the preoperative and pathological diagnoses was low in the C-PNET group (33%, P = 0.03). None of the 24 patients (23%) with metastatic disease at the time of surgery were in the C-PNET group. Furthermore, significantly more parenchyma-sparing resections (P = 0.039) and fewer enlarged resections (P = 0.019) were achieved in the C-PNET group. C-PNET group had a significantly lower node invasion rate than the S-PNET and M-PNET groups (8% vs. 41% and 24%, P = 0.004). Although median OS was comparable in all 3 groups before (P = 0.3) and after (P = 0.18) matching, higher median DFS was observed in the C-PNET group than in the other groups after matching (P = 0.038). Conclusion: C-PNET was associated with a better prognosis than PNET with a solid component. The results support a wait-and-see policy in cases wherein a reliable preoperative diagnosis remains challenging. [ABSTRACT FROM AUTHOR]

Background: Intrapancreatic accessory spleen (IPAS) is an uncommon finding of pancreatic mass. Differential diagnosis with pancreatic tumor, especially with non-functional neuroendocrine tumor (NF-NET), may be very hard and sometimes it entails unnecessary surgery. A combination of CT scan, MRI, and nuclear medicine can confirm the diagnosis of IPAS. 68-Ga-Dotatoc PET/CT is the gold standard in NET diagnosis and it can allow to distinguish between IPAS and NET. Case presentation: A 69-year-old man was admitted to our hospital for an incidental nodule in the tail of the pancreas with focal uptake of 68-Ga-dotatate at PET/CT. NET was suspected and open distal splenopancreatectomy was performed. Pathologic examination revealed an IPAS. Conclusion: This is the second IPAS case in which a positive 68Ga-Dotatoc uptake led to a false diagnosis of pancreatic NET. Here is a proposal of a literature review. [ABSTRACT FROM AUTHOR]