The microbiota of the bilio-pancreatic system: A cohort, STROBE-compliant study

Background: The gut microbiota play an essential role in protecting the host against pathogenic microorganisms by modulating immunity and regulating metabolic processes. In response to environmental factors, microbes can hugely alter their metabolism. These factors can substantially impact the host and have potential pathologic implications. Particularly pathogenic microorganisms colonizing pancreas and biliary tract tissues may be involved in chronic inflammation and cancer evolution. Purpose: To evaluate the effect of bile microbiota on survival in patients with pancreas and biliary tract disease (PBD). Patients and Methods: We investigated 152 Italian patients with cholelithiasis (CHL), cholangitis (CHA), cholangiocarcinoma (CCA), gallbladder carcinoma (GBC), pancreas head carcinoma (PHC), ampullary carcinoma (ACA), and chronic pancreatitis (CHP). Demographics, bile cultures, therapy, and survival rates were analyzed in cohorts (T1 death <6 months; T2 death <12 months; T3 death <18 months, T3S alive at 18 months). Results: The most common bacteria in T1 were E. coli, K. pneumoniae, andP. aeruginosa. In T2, the most common bacteria were E. coli and P. aeruginosa. InT3, there were no significant bacteria isolated, while in T3S the most common bacteria were like those found in T1. E. coli and K. pneumoniae were positive predictors of survival for PHC and ACA, respectively. E. coli, K. pneumoniae, andP. aeruginosa showed a high percentage of resistant bacteria to 3CGS, aminoglycosides class, and quinolone group especially at T1 and T2 in cancer patients. Conclusions: An unprecedented increase of E. coli in bile leads to a decrease in survival. We suggest that some strains isolated in bile samples may be considered within the group of risk factors in carcinogenesis and/or progression of hepato-biliary malignancy. A better understanding of bile microbiota in patients with PBD should lead to a multifaceted approach to rapidly detect and treat pathogens before patients enter the surgical setting in tandem with the implementation of the infection control policy

Fever with perinasal and tongue lesions: A diagnostic challenge

The diagnosis may be challenging, and high suspicion index should be maintained in immunosuppressed patients with unusual mucocutaneous lesions, even in non-endemic areas for mucocutaneous leishmaniasis

TTF-1/p63-positive poorly differentiated NSCLC: A histogenetic hypothesis from the basal reserve cell of the terminal respiratory unit

TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (∆Np63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as “TTF-1+ p63+ adenocarcinoma”. The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as “adenocarcinoma, solid variant”, in keeping with the presence of TTF-1 expression and p40 negativity. A “wild type” genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these “basal-type tumors” like those in the better known “basal-like” cancer of the breast

A solitary fibrous tumor of the parotid gland: Case report

Introduction: Solitary fibrous tumor is a rare neoplasm that can affect any part of the body, also head and neck region. Etiology is unknown. The incidence is slightly higher in males, the age ranges from 11 to 79 years. Presentation of case: It's the first case in our country of left parotid solitary fibrous tumor, removed by partial parotidectomy with facial nerve preservation. Histology examination showed diffuse spindle-shaped cells proliferation, moderate polymorphism, low mitotic index (<4 mitoses per 10 HPF), partially bordered by fibrous capsule. Immunohistochemistry showed STAT6, CD34, CD99 positivity. Six-months follow-up didn't show sign of recurrence. Discussion: Solitary fibrous tumor is a mesenchymal spindle cell neoplasm with fibroblastic differentiation ubiquitous in soft tissues, that involved the head and neck region in 6 % of cases. Etiology is unknown. The possible pathogenesis is NAB2-STAT6 gene fusion. It's asymptomatic or symptoms are related to space-occupying mass. Diagnostic work up involves imaging, immunohistochemistry, histology. Radiographic finding may lead to incorrect assessment of the mass: the same imaging features are present in pleomorphic adenoma, the most frequent tumor of salivary glands. Conclusion: This case report aims to stress that, although rare, solitary fibrous tumor should be considered in differential diagnosis in case of indolent salivary gland mass, since it may require more invasive approach (e.g., total parotidectomy, adjuvant radiotherapy). It would like to highlight the role of multidisciplinary team to define the best therapy, tailored for the patient, as well as to give awareness to a rare but sometimes aggressive tumor

Immune-mediated desquamative gingivitis and optical coherence tomography diagnostic patterns: Clinical implication from a systematic review

Desquamative Gingivitis (DG) comprises heterogeneous clinical manifestations of numerous immune-mediated muco-cutaneous diseases. Optical Coherence Tomography (OCT) has been proposed as a valuable diagnostic support even if, to date, there are no standardized OCT-diagnostic patterns applicable to DGs. A systematic review was performed to detect existing data on in vivo OCT diagnostic patterns of the most common immune-mediated DGs (i.e., pemphigus vulgaris, mucous membrane pemphigoid and oral lichen planus). It has been found that OCT exhibits specific patterns that address the diagnosis of DG by pemphigus vulgaris (i.e., intraepithelial unilocular blister, reduced epithelial thickness, presence of acantholytic cells in the blister) and by mucous membrane pemphigoid (i.e., subepithelial multilocular blister, presence of inflammatory infiltrate), but not by oral lichen planus. These patterns could offer an attractive diagnostic OCT framework to support the clinical preliminary assessment and monitoring of these complex pathological conditions

Successful intravenous immunoglobulin treatment for steroid-resistant eosinophilic enteritis in a patient with systemic lupus erythematosus.

Eosinophilic gastroenteritis is a rare condition of unknown etiology characterized by eosinophilic infiltration of the bowel. Corticosteroids are the mainstay of EG therapy. Although rare, steroid-resistant EG could be a life-threatening condition with tissue destructive evolution. Associations of eosinophilic gastroenteritis with systemic lupus erythematosus have rarely been reported. In this report we describe a case of successful IVIG treatment in a patient with systemic lupus erythematosus and steroid-refractory eosinophilic gastroenteritis

PathVisio Analysis: An Application Targeting the miRNA Network Associated with the p53 Signaling Pathway in Osteosarcoma

MicroRNAs (miRNAs) are small single-stranded, non-coding RNA molecules involved in the pathogenesis and progression of cancer, including osteosarcoma. We aimed to clarify the pathways involving miRNAs using new bioinformatics tools. We applied WikiPathways and PathVisio, two open-source platforms, to analyze miRNAs in osteosarcoma using miRTar and ONCO.IO as integration tools. We found 1298 records of osteosarcoma papers associated with the word "miRNA". In osteosarcoma patients with good response to chemotherapy, miR-92a, miR- 99b, miR-193a-5p, and miR-422a expression is increased, while miR-132 is decreased. All identified miRNAs seem to be centered on the TP53 network. This is the first application of PathVisio to determine miRNA pathways in osteosarcoma. MiRNAs have the potential to become a useful diagnostic and prognostic tool in the management of osteosarcoma. PathVisio is a full pathway editor with the potentiality to illustrate the biological events, augment graphical elements, and elucidate all the physical structures and interactions with standard external database identifiers

MULTIPLE PLURIPOTENT STEM CELL MARKERS IN HUMAN ANAPLASTIC THYROID CANCER: THE PUTATIVE UPSTREAM ROLE OF SOX-2

Background: Anaplastic Thyroid Carcinoma (ATC) is a rare and aggressive endocrine tumor, with highly undifferentiated morphology. It has been suggested that cancer stem cells (CSCs) might play a central role in ATC. The objectives of this study were the following: 1) to characterize CSCs from ex vivo ATC specimens by investigating the expression of several pluripotent stem cell markers; 2) to evaluate in vitro drug resistance modifications after specific CSC transcription factor switch off. Methods: Ex vivo: eight formalin-fixed, paraffin-embedded ATC specimens were analyzed by RT and qRT-PCR and immunohistochemistry. In vitro: in ATC SW1736 cells the expression levels of OCT-4, NANOG and ABCG2 and the sensitivity to either cisplatin or doxorubicin were evaluated after silencing. Results: OCT-4, KLF4 and SOX2 transcription factors and C-KIT and THY-1 stem surface antigens showed variable up-regulation in all ATC cases. The SW1736 cell line was characterized by a high percentage of stem population (10.4 \ub1 2.1 % of cells were aldehyde dehydrogenase positive) and a high expression of several CSC markers (SOX2, OCT4, NANOG, C-MYC, SSEA4). SOX2 silencing down-regulated OCT-4, NANOG and ABCG2. SOX2 silencing sensitized SW1736 cells, causing a significant cell death increase (1.8 fold) in comparison to control cells with 10 \ub5M cisplatin (93.9\ub13.4% vs. 52.6\ub19.4%, p<0.01) and 2.7 fold with 0.5\ub5M doxorubicin (45.8\ub19.9% vs. 17.1\ub13.4% p<0.01). ABCG2 silencing caused increased cell death with both cisplatin (74.9\ub11.4%) and doxorubicin treatment (74.1\ub10.1%) vs. no-target-treated cells (respectively, 45.8\ub11.0% and 48.6\ub11.0%, p<0.001). Conclusions: The characterization of CSCs in ATC through the analysis of multiple pluripotent stem cell markers might be useful in identifying cells with a stem-like phenotype capable of resisting conventional chemotherapy. In addition, our data demonstrate that SOX2 switch-off through ABCG2 transporter down-regulation has a major role in overcoming CSC chemotherapy resistance

Prognostic Implications of the Complement Protein C1q in Gliomas

The contribution of the complement system in the pathophysiology of brain cancers has been recently considered in light of its well-known involvement in carcinogenesis. Complement system represents an important component of the inflammatory response, which acts as a functional bridge between the innate and adaptive immune response. C1q, the first recognition subcomponent of the complement classical pathway, has recently been shown to be involved in a range of pathophysiological functions that are not dependent on complement activation. C1q is expressed in the microenvironment of various types of human tumors, including melanoma, prostate, mesothelioma, and ovarian cancers, where it can exert a protective or a harmful effect on cancer progression. Despite local synthesis of C1q in the central nervous system, the involvement of C1q in glioma pathogenesis has been poorly investigated. We, therefore, performed a bioinformatics analysis, using Oncomine dataset and UALCAN database in order to assess whether the expression of the genes encoding for the three chains of C1q (C1qA, C1qB, and C1qC) could serve as a potential prognostic marker for gliomas. The obtained results were then validated using an independent glioma cohort from the Chinese Glioma Genome Atlas datasets. Our bioinformatics analysis, coupled with immunohistochemistry and fluorescence microscopy, appears to suggest a positive correlation between higher levels of C1q expression and unfavorable prognosis in a diverse grade of gliomas

Dynamic Responsive Inguinal Scaffold Activates Myogenic Growth Factors Finalizing the Regeneration of the Herniated Groin

Background: Postoperative chronic pain caused by fixation and/or fibrotic incorporation of hernia meshes are the main concerns in inguinal herniorrhaphy. As inguinal hernia is a degenerative disease, logically the treatment should aim at stopping degeneration and activating regeneration. Unfortunately, in conventional prosthetic herniorrhaphy no relationship exists between pathogenesis and treatment. To overcome these incongruences, a 3D dynamic responsive multilamellar scaffold has been developed for fixation-free inguinal hernia repair. Made of polypropylene like conventional flat meshes, the dynamic behavior of the scaffold allows for the regeneration of all typical inguinal components: connective tissue, vessels, nerves, and myocytes. This investigation aims to demonstrate that, moving in tune with the groin, the 3D scaffold attracts myogenic growth factors activating the development of mature myocytes and, thus, re-establishing the herniated inguinal barrier. Methods: Biopsy samples excised from the 3D scaffold at different postoperative stages were stained with H&amp;E and Azan–Mallory; immunohistochemistry for NGF and NGFR p75 was performed to verify the degree of involvement of muscular growth factors in the neomyogenesis. Results: Histological evidence of progressive muscle development and immunohistochemical proof of NFG and NFGRp75 contribution in neomyogenesis within the 3D scaffold was documented and statistically validated. Conclusion: The investigation appears to confirm that a 3D polypropylene scaffold designed to confer dynamic responsivity, unlike the fibrotic scar plate of static meshes, attracts myogenic growth factors turning the biological response into tissue regeneration. Newly developed muscles allow the scaffold to restore the integrity of the inguinal barrier