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Benign tumours of salivary glands represent 2%–3% of all tumours and parotid gland is most often affected. Keratocystoma is a rare benign tumour with multilocular cystic lesions filled with keratin materials. Histologically, it is characterised by solid epithelium islands containing keratinised lamellae with multicystic spaces. We report a case of a woman in her mid-70s with painless mass in her left parotid gland which increased in size over 1 year. Ultrasound scan revealed a 38×20 mm diameter hypoanechoic mass. Neck CT with contrast medium and fine needle aspiration were performed with diagnostic hypothesis of Warthin tumour. So, extracapsular parotid dissection with no facial nerve damage was performed. Histological examination revealed a keratocystoma. The patient had a 16-month follow-up without signs of relapse or malignancy. Despite its rarity, keratocystoma must be considered among the possible differential diagnostic hypotheses when we find parotid masses, to ensure the best treatment to the patient.

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.

Optical Coherence Tomography (OCT) is an emerging non-invasive method for oral diagnostics, proving to be a practicable device for epithelial and subepithelial evaluation. The potential validity of OCT in oral cancer assessment has been explored but, to date, there are very few investigations conducted with a systematic comparison between clinical/histological and OCT parameters, especially in strict reference to the anatomical site-codification of the oral mucosa. In this regard, our study performed a two-steps evaluation (in vivo OCT and histological investigations) of suspected OSCCs, progressively recruited, using as references the OCT images of the same site-coded healthy mucosa, to provide as much as possible site-specific determinants. Thirty histologically confirmed OSCCs were recruited. Specific OCT mucosal features (SEL—Stratified Epithelial Layer; BM—Basement Membrane; LP—Lamina Propria) were registered and processed using the SRQR (Standards for Reporting Qualitative Research) statement. The systematic dual descriptive OCT analysis revealed that OSCC scans present a complete alteration of epithelial (KL, SEL) and subepithelial (BM, LP) layers with a site-specificity characteristic; moreover, peculiar OCT configurations such as “icicle-like” structures could be strongly suggestive of neoplastic infiltration. This study supports the OCT use for the development of more specific optical structural models applied to oral carcinogenesis.

To evaluate the accuracy of preoperative contrast-enhanced magnetic resonance imaging (MRI) in the assessment of radiological depth of invasion (rDOI) and bone invasion in patients with oral cavity cancer, and the prognostic value of preoperative rDOI.This retrospective study included patients with surgically resected oral cavity cancer and preoperative MRI acquired within four weeks before surgery. Two readers evaluated the MRI to assess the superficial and deep bone invasion, preoperative T stage, and measured the rDOI. The rDOI was compared to the histopathological DOI (pDOI), used as reference standard. Prognostic value of preoperative features for the disease-specific survival was evaluated using the Kaplan-Meier curve and multivariable Cox proportional hazards analysis.The final population included 80 patients (50 males, mean age 67.7 ± 13.6 years). There was a strong statistically significant correlation between the rDOI (median 10 mm) and the pDOI (median 9 mm) (ρ: 0.978, p 0.001). The agreement between MRI and histopathological T stage was excellent (k = 0.93, 95% CI 0.86, 0.99). The sensitivity and specificity of preoperative MRI were 93.3% and 98.8% for deep bone invasion, while they were 75.0% and 95.8% for superficial bone invasion, respectively. The rDOI 10 mm was associated with poorer disease-specific survival (log-rank p = 0.016). The rDOI remained the only independent preoperative predictor associated with poorer disease-specific survival at multivariable analysis (hazard ratio 5.5; 95% CI 1.14, 26.58; p = 0.033).Preoperative MRI is accurate for the assessment of DOI and bone invasion. The rDOI is an independent preoperative predictor of disease-specific survival in patients with oral cavity cancer.

Aims: The emerging biliary colonization of microorganisms in patients with biliary diseases may be devastating. Recent evidence suggests that age and gender may influence changes in the microbial composition of gut microbiota. To study the relationship between these parameters on bile microbiota, we retrospectively reviewed positive bile cultures following an endoscopic retrograde cholangiopancreatography (ERCP) in a QA-certified academic surgical unit of a single institution. Methods: 449 positive bile cultures from 172 Italian patients with diseases of the biliopancreatic system hospitalized from 2006 through 2017 were investigated for aerobic, anaerobic, and fungal organisms. The patients were stratified into four age intervals (22−66, 67−74, 75−81, and 82−93 years) and followed up for five years. Results: Gram-positive bacteria (GPB) was negatively associated with age only in multivariate analysis (Rpartial = −0.114, p = 0.017), with younger patients prone to harbor GPB and older patients likely to have Gram-negative bacteria (GNB). There was a definite link with the male gender using both univariate and multivariate analysis (p < 0.001). Enterococcus spp. was the most common strain identified in patients with GPB except for patients aged 67−74 years for male (95.2%) and female (80.9%) patients. Escherichia coli and Klebsiella spp. were most frequent than others in every group analyzed. Analogous results were found for bacteria Non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas spp. and Stenotrophomonas spp. apart of the 2nd quartile. Conclusions: Our study strengthens the bond of age and gender with bile microbiota composition and suggests that further investigations may be required in targeting the aging microbiome. Other studies should also focus on Mediterranean epidemiological characteristics and antibiotic resistance surveillance system strategies

Una donna caucasica di 18 anni si presentava all’osservazione presso il Settore di Medicina Orale (Università degli Studi di Palermo) data la comparsa di una neoformazione localizzata in zona trigono retromolare destro. L’anamnesi patologica non evidenziava la presenza di patologie sistemiche attuali o pregresse. La paziente era in buone condizioni di salute, riferiva di non assumere farmaci e di non avere subito alcun intervento chirurgico; dichiarava di non avere mai fumato. La paziente riferiva un lento e progressivo accrescimento della lesione, in assenza di sintomatologia algica. L’esame obiettivo extra-orale non evidenziava linfoadenopatie latero-cervicali o altre anomalie. All’esame obiettivo intra-orale si rilevava una neoformazione esofitica a larga base di impianto, distalmente all’elemento 4.7. La lesione aveva circa 1 cm di diametro, la mucosa di rivestimento era di colorito rossastro, con aree di ipercheratosi e di erosione. La lesione risultava mobile rispetto ai piani sottostanti. Alla palpazione si apprezzava una consistenza fibrosa duro-elastica. La paziente esibiva una radiografia endorale in cui si apprezzava la presenza di una radio-opacità con margini netti all’interno della lesione. In considerazione della crescita della lesione e dell’aspetto clinico-radiografico benigno, si prescriveva alla paziente un’ortopantomografia (OPT).

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

Osteonecrosis of the jaw (ONJ) is an adverse drug reaction described as the progressive destruction and death of bone that affects the mandible and maxilla of patients exposed to the treatment with medications known to increase the risk of disease, in the absence of a previous radiation treatment. Tooth extraction often precedes the manifestation of ONJ; indeed, it is sometimes called trigger event and it have also been considered as risk factors for the onset of ONJ. As a consequence, some of the guidelines recommend avoiding tooth extractions in patients at risk of ONJ; however, a growing body of evidence indicates that dental/periodontal infection prior to extraction, rather than dental extraction may represent the main local risk factor for ONJ. Ten patients at risk of ONJ have undergone tooth extractions. They were identified and included in our retrospective monocentric clinical investigation. Patients underwent tooth extractions with standardized procedures (PROMaF protocol), and bone biopsies were taken. Extractions were performed due to symptomatic, non-restorable teeth in patient at risk of ONJ; histological findings of ONJ were observed in all samples. This outcome may highlight that the proof of non‐exposed ONJ might be the histopathologic confirmation of necrotic bone, as stated by European task force on MRONJ. Additionally, alveolar biopsy should possibly be taken in every case of suspected ONJ, which needs an proper and prompt management for successful healing.

Objective: To investigate whether MRI-based texture analysis improves diagnostic performance for the diagnosis of parotid gland tumors compared to conventional radiological approach. Methods: Patients with parotid gland tumors who underwent salivary glands MRI between 2008 and 2019 were retrospectively selected. MRI analysis included a qualitative assessment by two radiologists (one of which subspecialized on head and neck imaging), and texture analysis on various sequences. Diagnostic performances including sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of qualitative features, radiologists’ diagnosis, and radiomic models were evaluated. Results: Final study cohort included 57 patients with 74 tumors (27 pleomorphic adenomas, 40 Warthin tumors, 8 malignant tumors). Sensitivity, specificity, and AUROC for the diagnosis of malignancy were 75%, 97% and 0.860 for non-subspecialized radiologist, 100%, 94% and 0.970 for subspecialized radiologist and 57.2%, 93.4%, and 0.927 using a MRI radiomics model obtained combining texture analysis on various MRI sequences. Sensitivity, specificity, and AUROC for the differential diagnosis between pleomorphic adenoma and Warthin tumors were 81.5%, 70%, and 0.757 for non-subspecialized radiologist, 81.5%, 95% and 0.882 for subspecialized radiologist and 70.8%, 82.5%, and 0.808 using a MRI radiomics model based on texture analysis of T2 weighted sequence. A combined radiomics model obtained with all MRI sequences yielded a sensitivity of 91.5% for the diagnosis of pleomorphic adenoma. Conclusion: MRI qualitative radiologist assessment outperforms radiomic analysis for the diagnosis of malignancy. MRI predictive radiomics models improves the diagnostic performance of non-subspecialized radiologist for the differential diagnosis between pleomorphic adenoma and Warthin tumor, achieving similar performance to the subspecialized radiologist. Advances in knowledge: Radiologists outperform radiomic analysis for the diagnosis of malignant parotid gland tumors, with some MRI qualitative features such as ill-defined margins, perineural spread, invasion of adjacent structures and enlarged lymph nodes being highly specific for malignancy. A radiomic model based on texture analysis of T2 weighted images yields higher specificity for the diagnosis of pleomorphic adenoma compared to a radiologist non-subspecialized in head and neck radiology, thus minimizing false-positive pleomorphic adenoma diagnosis rate and reducing unnecessary surgical complications.

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.

Biologic response to hernia prostheses represents a continuous source of debate. Conventional hernia meshes, in their typical static, passive configuration have been used for decades to reinforce the herniated abdominal wall. These flat implants, mainly fixated with sutures or tacks, induce poor quality fibrotic ingrowth that shrinks the mesh. In groin hernia repair, flat meshes are applied in the delicate inguinal surrounding where uncontrolled development of a scar plate can impair movement and may incorporate the sensitive nerves crossing this area. Complications deriving from mesh fixation and nerve entrapment are frequent and unpleasant for patients. To remedy these problems, a multilamellar shaped 3D device with a dynamic responsive behavior has recently been developed to repair inguinal hernia. Its inherent dynamic compliance during inguinal movements has shown to induce enhanced biological response with ingrowth of newly formed connective tissue, muscle fibers, and nerves. The function of these highly specialized tissue structures is supported by the contextual development of newly formed arteries and veins. The scope of the study was to assess quantity and quality of vessels, which had ingrown in the 3D hernia device in the short-term, medium-term, and long-term post-implantation, in biopsy specimens gathered from inguinal hernia patients operated with the 3D device. Starting from an early stage, widespread angiogenesis was evident within the 3D structure. Arteries and veins increased in quantity showing progressive development until full maturation of all specific vascular components throughout the mid-term, to long-term, post-implantation. High quality biologic ingrowth in hernia prosthetics needs an adequate vascular support. The broad network of mature arteries and veins evidenced herewith seems to confirm the enhanced biological features of the dynamic responsive 3D device whose features resemble a regenerative scaffold, an ideal feature for the treatment of the degenerative source of inguinal hernia disease.

Gastroesophageal reflux disease (GERD) is a common digestive disorder that causes esophagitis and injuries to the esophageal mucosa. GERD symptoms are recurrent during pregnancy and their treatment is focused on lifestyle changes and nonprescription medicines. The aim of this study was to characterize the mechanism of action of a new patented medical device, an oral formulation containing hyaluronic acid, rice extract, and amino acids dispersed in a bioadhesive polymer matrix, by assessing its protective effects in in vitro and ex vivo models of esophageal mucosa damage. Acidic bile salts and pepsin cocktail (BSC) added to CP-A and COLO-680 N esophagus cells were used as an in vitro GERD model to evaluate the binding capacities, anti-inflammatory effects and reparative properties of the investigational product (IP) in comparison to a viscous control. Our results showed that the IP prevents cell permeability and tight junction dysfunction induced by BSC. Furthermore, the IP was also able to down-regulate IL-6 and IL-8 mRNA expression induced by BSC stimulation and to promote tissue repair and wound healing. The results were confirmed by ex vivo experiments in excised rat esophagi through the quantification of Evans Blue permeability assay. These experiments provided evidence that the IP is able to bind to the human esophagus cells, preventing the damage caused by gastroesophageal reflux, showing potential anti-irritative, soothing, and reparative properties.

Highlights • Femoral lipoma can be mistaken with femoral hernia. • Differential diagnosis between femoral lipoma and femoral hernia can result challenging. • The occurrence of femoral pain can lead to misinterpretation of the symptoms., Introduction Lipoma of the femoral fossa is uncommon. Often asymptomatic, femoral lipoma may growth within the circumscribed space of the femoral fossa causing pain and discomfort. A worsening pain caused by a lipomatous mass in the femoral area is a clinical feature that can mislead the diagnosis, resembling the more common condition of femoral hernia. Methods Two cases of symptomatic lipomas of the femoral fossa mimicking an incarcerated femoral hernia are presented. In both, Caucasian female, patients clinical examination and ultrasound of the femoral region revealed a painful neoplasm suspected for incarcerated femoral hernia. Results Intraoperatively, a mass of encapsulated fat arising from the bottom of the fossa femoralis was found. No visceral protrusion through the femoral ring could be documented. The neoplasms were removed in toto. Histology of the excised specimens evidenced the diagnosis of femoral lipomas suffering by chronic compressive damages. In a midterm postoperative follow up, both patients were symptom- free. Discusion A correct preoperative diagnosis of femoral lipoma is challenging, even following an accurate diagnostic pathway. The cases highlighted herewith seem to confirm that lipoma of the femoral fossa can be mistaken with a femoral hernia. Conclusions The clinical and histological features evidenced could result helpful in the differentiation of a lipomatous mass of the femoral fossa from a genuine femoral hernia.

Purpose: Double ipsilateral inguinal ("pantaloon") hernias and also the more advanced "combined" inguinal hernia involve disruption of the inguinal floor. In the case of pantaloon hernias, the medial boundary of the internal ring remains intact but in combined hernias this is fully disrupted, producing a single hernial protrusion. Deepening the pathophysiology of these hernias may be helpful in addressing hernia genesis, thus improving strategies for the treatment of this disease. Materials and Methods: A cohort of 22 patients who underwent inguinal hernia repair showed double ipsilateral (pantaloon) hernia, comprising distinct direct and indirect protrusions separated by a tissue septum. In 19 patients, the septal arrangement dividing the 2 hernias showed macroscopically evident structural damages, then excised and histologically studied. Different tissue markers were used for the identification of the structural damages. Results: Macroscopically, the divisor septum represents the boundary between internal ring and Hesselbach's triangle. Anteriorly it is composed by fibers of the internal oblique and transverse muscles, which form a complex with the inferior epigastric vessels on the corresponding posterior side of the inguinal floor. In the patient cohort studied, this anatomical structure showed a progressive sufferance characterized by chronic compressive damage. Conclusion: The anatomical structure which separates the indirect and direct components of a pantaloon hernia, herein referred to as the "septum inguinalis", has been shown progressively alter in both macro- and microscopically until it f undergoes disruption with development of a combined hernia. Understanding of this anatomical concept may help surgeons to perform sound repairs of these complex hernias.

AimsTo evaluate the contribution of light microscopy to detecting Candida spp infection in patients with complicated intra-abdominal infections (IAIs) admitted for acute abdomen to a quality assurance (QA)-certified surgical emergency ward.MethodsWe conducted a retrospective study (2008–2012) of 809 abdominal intraoperative or biopsy tissue specimens obtained from patients admitted with acute abdomen and microbiological samples positive for Candida spp. Demographic data, mortality, comorbidities, specimen type, microscopy results, special histological staining performed, antimicrobial therapy were collected and analysed. Any comments at the multidisciplinary team meeting was recorded in minutes of and approved.ResultsSixty-six patients with complicated IAIs due to Candida spp were identified (39 male, 27 female, mean±SD age 75±20 years). Candida albicans was isolated in 35 cases and Candida non-albicans spp in 31 cases. Candida spp were isolated from blood in 50% of all selected microbiological specimens. Patients were stratified according to Candida spp (albicans vs non-albicans), underlying cancer disease and no previous antimicrobial administration, and a positive correlation with C. albicans isolation was found (p=0.009 and p=0.048, respectively). Out of 41 cases with microscopic evaluation, we identified yeast forms, pseudohyphae or both, indicative of Candida spp, in 23. Identification of Candida spp in histological specimens was higher in C. albicans cases than in C. non-albicans cases (73% vs 37.5%). Microscopy allowed prompt treatment of all patients.ConclusionsLight microscopy still has great diagnostic significance, being a solid QA step. It provides rapid information and clues in patients who may harbour impaired defence mechanisms, concurrent chronic conditions and/or cancer.

Objective To investigate the expression and tissue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA-B27-positive patients with ankylosing spondylitis (AS), patients with Crohn's disease (CD), and healthy controls. Expression and tissue distribution of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohistochemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among peripheral blood, lamina propria, and synovial fluid mononuclear cells. The functional relevance of IL-9R expression on epithelial cells was assessed in functional in vitro studies. Th9 cells in synovial tissue from patients with PsA were also studied. Results Subclinical gut inflammation in PsA patients was characterized by a clear Th17 and Th22, but not Th1, polarized immune response. Unlike AS and CD, a strong and significant up-regulation of IL-9 was observed in PsA gut, especially among infiltrating mononuclear cells, high endothelial venules, and Paneth cells. IL-9-positive mononuclear cells were demonstrated to be in large part Th9 cells. IL-9 overexpression was accompanied by significant Paneth cell hyperplasia. Paneth cells strongly overexpressed IL-9R, and stimulation of epithelial cells, isolated from PsA patients, with IL-9 resulted in overexpression of α-defensin 5 and IL-23p19. Peripheral and synovial expansion of α4β7+ Th9 cells was also observed in patients with PsA. Increased expression of IL-9 and IL-9R was also found in synovial tissue. Conclusion Strong IL-9/Th9 polarization seems to be the predominant immunologic signature in patients in PsA.

There is currently a growing interest in new diagnostic tools of the oral cavity and mucosa which are non-invasive, repeatable and reliable. A diagnosis of a suspected, autoimmune pathology was made regarding a 57-year-old patient with desquamative gingivitis. However, a negative Nikolsky's sign did not seem to indicate a diagnosis of mucous membrane pemphigoid neither was there any indication as to the optimum location for an incisional biopsy. As an imaging method, the use of optical coherence tomography (OCT) has enabled the obtaining of tomographic (cross-sectional) scans of tissue. Such images are acquired prior to and after verifying Nikolsky's sign, thereby enabling the clinician to identify the presence (or not) of subepithelial bullae. Thereafter, an assessment of changes in the subepithelium (the split) can be performed, even in the absence of a suitable clinical picture, such as, for example, a negative Nikolsky's sign. Histological analysis and the use of indirect immunofluorescence have facilitated a diagnosis of mucous membrane pemphigoid, an autoimmune pathology, which can be confirmed with the appearance of subepithelial bullae. OCT was found to be a valid, non-invasive, auxiliary diagnostic device, capable of revealing in vivo and real-time bullae, which were hitherto clinically undetectable.

Objectives To investigate the expression of IL-34 in labial salivary glands (LSGs) of patients with primary SS (p-SS) and its role in inducing a pro-inflammatory monocyte phenotype. Methods LSG biopsies were obtained from 20 patients with p-SS and 10 patients with non-Sjogren's sicca syndrome (n-SS). The expression of IL-34, IL-1β, TNF-α, IL-17 and IL-23 was assessed by real-time PCR. IL-34 expression was also investigated in LSGs by immunohistochemistry. The frequencies of subpopulations of CD14(+) monocytes were evaluated by flow cytometry among isolated mononuclear cells from peripheral blood and salivary glands from both patients and controls. The role of recombinant IL-34 on isolated peripheral blood mononuclear cells was also evaluated. Results IL-34 m-RNA was overexpressed in the inflamed salivary glands of p-SS and associated with increased expression of TNF-α, IL-1β, IL-17 and IL-23p19. The increased expression of IL-34 was confirmed by immunohistochemistry in paraffin-embedded salivary glands from p-SS patients. IL-34 expression was accompanied by the expansion of pro-inflammatory CD14(bright)CD16(+) monocytes in the salivary glands. In vitro stimulation of peripheral blood mononuclear cells with IL-34 induced the expansion of both CD14(+)CD16(-) cells and CD14(bright)CD16(+) cells in p-SS and non-SS subjects. Conclusion IL-34 seems to be involved in the pathogenesis of salivary gland inflammation in p-SS.

Introduction Identification of a combined hernia is a common occurrence in the course of inguinal hernia repair. This type of protrusion disease seems to affect the elderly, in particular. Very few investigations have been carried out to ascertain the structural changes that occur in the groin affected by this clinical condition. Method Analysis of intraoperative findings of combined inguinal hernias evidenced in the elderly, from the most recent 100 groin hernia repair procedures carried out by a single operator, represents the basis of the article. Protrusions that presumably represent the forerunner of this type of hernia were also analyzed: double ipsilateral inguinal hernias composed of a direct and an indirect protrusion. The gross anatomical, as well as histological, modifications occurring during the development of combined protrusions were also evaluated. Results Combined hernia was the most frequent protrusion in patients over 65 years, accounting for 36% of the total in this patient group. In the same patient cohort, double inguinal hernia further involves 22% of elderly subjects. Macroscopically, progressive disruption of the inguinal back wall and degenerative reabsorption of the inferior epigastric vessels were evidenced. Histologically, inflammatory infiltrate, significant nerve and vascular injuries, along with severe muscle degeneration were recognized. Conclusions The results seem to confirm that inguinal hernia is an unremitting progressive disease caused by chronic compressive structural damage. Combined hernias represent a frequent clinical condition in the elderly consequent to long-term degenerative damage. Therapy of combined protrusions must consider the impact of visceral vector forces.

Aims To evaluate the contribution of light microscopy to detecting Candida spp infection in patients with complicated intra-abdominal infections (IAIs) admitted for acute abdomen to a quality assurance (QA)-certified surgical emergency ward. Methods We conducted a retrospective study (2008–2012) of 809 abdominal intraoperative or biopsy tissue specimens obtained from patients admitted with acute abdomen and microbiological samples positive for Candida spp. Demographic data, mortality, comorbidities, specimen type, microscopy results, special histological staining performed, antimicrobial therapy were collected and analysed. Any comments at the multidisciplinary team meeting was recorded in minutes of and approved. Results Sixty-six patients with complicated IAIs due to Candida spp were identified (39 male, 27 female, mean±SD age 75±20 years). Candida albicans was isolated in 35 cases and Candida non-albicans spp in 31 cases. Candida spp were isolated from blood in 50% of all selected microbiological specimens. Patients were stratified according to Candida spp (albicans vs non-albicans), underlying cancer disease and no previous antimicrobial administration, and a positive correlation with C. albicans isolation was found (p=0.009 and p=0.048, respectively). Out of 41 cases with microscopic evaluation, we identified yeast forms, pseudohyphae or both, indicative of Candida spp, in 23. Identification of Candida spp in histological specimens was higher in C. albicans cases than in C. non-albicans cases (73% vs 37.5%). Microscopy allowed prompt treatment of all patients. Conclusions Light microscopy still has great diagnostic significance, being a solid QA step. It provides rapid information and clues in patients who may harbour impaired defence mechanisms, concurrent chronic conditions and/or cancer.

Mature cystic teratoma is the most frequent benign ovarian neoplastic lesion in adolescents and is generally composed of fully differentiated tissue arising from multipotential three germinal layers. It accounts for approximately 50% of benign ovarian tumors in childhood. Rarely, a bilateral, synchronous, or metachronous presentation can be observed, supporting a conservative approach as the first surgical approach. We report a case of an ovarian mature cystic incarcerated in indirect inguinal hernia in a 15-year-old girl undergoing ovary-sparing surgery. To our knowledge this is the first case of such lesion incarcerated in an inguinal hernia reported in literature. Mature cystic teratoma is the most frequent benign ovarian neoplastic lesion in adolescents and is generally composed of fully differentiated tissue arising from multipotential three germinal layers. It accounts for approximately 50% of benign ovarian tumors in childhood. Rarely, a bilateral, synchronous, or metachronous presentation can be observed, supporting a conservative approach as the first surgical approach. We report a case of an ovarian mature cystic incarcerated in indirect inguinal hernia in a 15-year-old girl undergoing ovary-sparing surgery. To our knowledge this is the first case of such lesion incarcerated in an inguinal hernia reported in literature.

It is not easy to reach a differential diagnosis between keratoacanthoma (KA) and squamous cell carcinoma (SCC) and furthermore there is still considerable discussion about the relationship of these 2 tumors with immunity. To facilitate such a diagnosis, we assessed the Glut-1 antibody, reported to be strongly and diffusely expressed in SCC but never assessed in KA. We studied 43 lesions of immunocompetent patients: 17 SCCs, 13 typical KAs (tKAs), and 13 atypical KAs (aKAs), with histologic features of SCC in less than 30% of the lesions. In tKA, Glut-1 stained only the basal layers of the squamous nests (basal pattern) whereas in SCC the squamous nests were randomly and diffusely stained (diffuse pattern). In aKA, a biphasic pattern was observed, with the typical KA areas showing the basal pattern and the SCC-like areas showing the diffuse pattern. Glut-1, therefore, helps to distinguish tKAs from SCCs and highlights the intermediate aKA group, supporting the hypothesis of a progression from KA to SCC. Finally, we used CD1a, CD57, CD4, CD8, CD3, and CD20 antibodies to assess whether or not the progression might be related to an in situ immunologic deficit. Significant differences were found both in CD1a + cells, more numerous in tKA than in SCC and in CD57+ cells, more numerous in tKA than in aKA and in SCC. This suggests a local immunological failure in aKA and SCC, probably related to the action of UV rays, leading us to consider KA as a model for the study of the interaction of skin cancer and immunity. Copyright © 2011 by Lippincott Williams & Wilkins.

Hypoxia-inducible factor-1α is found frequently overexpressed in solid tumors cells, exerting an important role in angiogenesis, glucose metabolism, cell proliferation, survival and invasion. In thyroid carcinomas, hypoxia-inducible factor-1α expression was found increased in differentiated, poorly differentiated, medullary and anaplastic variants. Hypoxia represents the principal stimulus responsible for hypoxia-inducible factor-1α induction. Other nonhypoxic stimuli increase hypoxia-inducible factor-1α synthesis through the activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in a cell-type-specific manner. We have previously shown the role of BRAFV600E mutation in papillary thyroid cancer cells as a factor that facilitates tumor cell growth and progression. In this study, we tested the hypothesis that BRAFV600E mutation influences hypoxia-inducible factor-1α expression in papillary thyroid carcinoma cells. We analyzed 27 papillary thyroid carcinomas, 13 of which presented BRAFV600E mutation. In tumor tissues, immunoreactivity for hypoxia-inducible factor-1α was detected in the majority of analyzed BRAFV600E mutated cases. Transcriptional analyses revealed elevated hypoxia-inducible factor-1α levels with significant differences between wild-type and mutated group. A BRAF wild-type papillary thyroid carcinoma cell line and a BRAFV600E mutated papillary thyroid carcinoma cell line were selected to study the effects of BRAF mutation on hypoxia-inducible factor-1α expression in vitro. Knockdown of mutant BRAFV600E or both the wild type and the BRAFV600E by RNA interference induced a significant reduction of hypoxia-inducible factor-1α expression at mRNA and protein levels. Pharmacological inhibition of BRAF significantly reduces hypoxia-inducible factor-1α expression levels in papillary thyroid carcinoma cell line harboring BRAFV600E mutation. Our results suggest that hypoxia-inducible factor-1α is expressed in papillary thyroid carcinomas and is regulated not only by hypoxia but also by BRAFV600E-mediated signaling pathway.

Galectins, soluble intracellular and extracellular β-galactoside–binding proteins, are known to be involved in the progression and metastasis of various cancers, including prostate adenocarcinoma, but the detailed mechanism of their biological roles remains elusive. In the prostate cancer cell lines PC-3 and DU-145, galectin 3 (gal3) is present at normal levels, whereas in LNCaP, its expression is silenced. In LNCaP, the gal3 promoter was heavily methylated, whereas PC-3 or DU-145 cells showed negligible or no methylation in the gal3 promoter indicating a negative correlation between gal3 promoter methylation and its expression. On immunohistochemical analysis of normal and tumor prostate tissues, gal3 was found expressed both in nucleus and cytoplasm of benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, and stage I. The expression of the gal3 was found drastically downregulated in advanced stages and, interestingly, mostly in the cytoplasm. On methylation analysis, the gal3 promoter in stage II prostate adenocarcinoma (PCa) was found heavily methylated, whereas in stages III and IV, it was only lightly methylated. However, in stage I PCa, both heavy and light methylations were observed in the gal3 promoter. In normal and benign prostatic hyperplasia tissues, the gal3 promoter was almost unmethylated. The differential cytosine methylation in the gal3 promoter in stages I to IV PCa enabled us to develop and validate a methylation-specific polymerase chain reaction–based sensitive assay specific for stages I and II PCa. These stages are considered the critical stages for successful intervention, thus underscoring the significance of this diagnostic assay. Translational Oncology (2009) 2, 146–156 Galectins, soluble intracellular and extracellular β-galactoside- binding proteins, are known to be involved in the progression and metastasis of various cancers, including prostate adenocarcinoma, but the detailed mechanism of their biological roles remains elusive. In the prostate cancer cell lines PC-3 and DU-145, galectin 3 (gal3) is present at normal levels, whereas in LNCaP, its expression is silenced. In LNCaP, the gal3 promoter was heavily methylated, whereas PC-3 or DU-145 cells showed negligible or no methylation in the gal3 promoter indicating a negative correlation between gal3 promoter methylation and its expression. On immunohistochemical analysis of normal and tumor prostate tissues, gal3 was found expressed both in nucleus and cytoplasm of benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, and stage I. The expression of the gal3 was found drastically downregulated in advanced stages and, interestingly, mostly in the cytoplasm. On methylation analysis, the gal3 promoter in stage II prostate adenocarcinoma (PCa) was found heavily methylated, whereas in stages III and IV, it was only lightly methylated. However, in stage I PCa, both heavy and light methylations were observed in the gal3 promoter. In normal and benign prostatic hyperplasia tissues, the gal3 promoter was almost unmethylated. The differential cytosine methylation in the gal3 promoter in stages I to IV PCa enabled us to develop and validate a methylation-specific polymerase chain reaction-based sensitive assay specific for stages I and II PCa. These stages are considered the critical stages for successful intervention, thus underscoring the significance of this diagnostic assay.

Visceral solitary myofibromas are uncommon in childhood. We report a case of a solitary asymptomatic visceral myofibroma of the bladder trigone occurring in a 3-month-old boy. Once malignancies were ruled out by cystoscopy, radical excision was performed in order to avoid any potential impairment of bladder dynamic. Postoperative course was uneventful and patient was discharged on day 3 after surgery. After 36 months of follow-up, the patient is toilet-trained and remains well; bladder function is normal.

TLRs are main actors of the innate immune response against HPV. There are very few studies on the role of TLRs mediated HPV clearance in Head and Neck oncology. Our aim was to evaluate whether TLR4 expression identifies HPV infection and/or HR-HPV integration status in oral and oropharyngeal cancers. By immunohistochemistry we assessed TLR4 levels in OSCC/OPSCC. To detect viral integration or episomic status In situ hybridization for HPV-DNA and Pyro-sequencing techniques have been performed. The relationship between TLR4 expression with HPV infection status has been investigated. ISH HPV positive samples have reported lower levels of TLR4 intensity than negative samples (p = .002). There was no statistical correlation between TLR4 intensity and PCR HPV results (p more than 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). These data have shown that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA.

SUMMARY Aims To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti-viral therapy on insulin resistance and serum levels of adipocytokines. Methods Clinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in ‘naive’ patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. Results Forty-eight patients were included (M/F 28/20; mean age 50.0 ± 12.6 years; 62.5% genotype-1). Body mass index was 26.4 ± 4.0 kg/m2, and visceral obesity was present in 24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to older age (1.08; 1–1.18), necroinflammatory activity (17.67; 1.6–194.46), and raised insulin levels (1.39; 1.1–1.77). Fibrosis was related to necroinflammatory activity (25.73; 2.54–261.11), and steatosis (6.47; 1.09–38.29). Sustained viral response was achieved by 62.5% of patients and was associated with younger age (0.92; 0.85–0.99), genotype non-1 (10.61; 1.52–73.76) and absence of visceral obesity (13.78; 2.36–80.29). At the end of follow-up, insulin and the homeostasis model assesment for insulin resistance were reduced and adiponectin increased when compared with baseline, all unrelated to the outcome of treatment. Conclusions Visceral obesity correlates with the degree of steatosis and fibrosis, and it negatively affects treatment response. Significant changes of insulin resistance and adipocytokines occur under treatment, irrespective of virological outcome.

We have attempted to identify those subgroups of patients most likely to develop lymph node metastases from squamous cell carcinoma of the lower lip (LLSSC). A total of 97 subjects, who did not undergo elective neck dissection, were recruited into the 60-month disease-free survival study. After univariate analysis, tumour size, histological grading, maximal thickness, perineural invasion and immunoreactivity to cyclin D1 and p27Kip1 proteins proved to be significant factors. Tests of the effect of interaction between p27Kip1 LI and tumour thickness yielded that the impact of tumour thickness on the risk of lymph node metastases was modified by the percentage of p27Kip1 positive cells. Subsequent to models of multivariate analysis, tumour size, positive cyclin D1 protein expression, maximal thickness (>5 mm), p27Kip1 LI (%) and the interaction term between p27Kip1 LI and tumour thickness retained strong independent predictive values for lymph node metastases. We suggest that immunohistochemistry for cyclin D1 and p27Kip1 may prove to be valuable ancillary tests for identifying LLSSC with metastatic potential.

Objective. To investigate the expression and tis- sue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods. Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA2B272positive patients with ankylosing spondylitis (AS), patients with Crohn’s disease (CD), and healthy controls. Expression and tissue distribu- tion of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohisto- chemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among periph- eral blood, lamina propria, and synovial fluid mononuclear cells. The functional relevance of IL-9R expression on epithelial cells was assessed in functional in vitro studies. Th9 cells in synovial tissue from patients with PsA were also studied. Results. Subclinical gut inflammation in PsA patients was characterized by a clear Th17 and Th22, but not Th1, polarized immune response. Unlike AS and CD, a strong and significant up-regulation of IL-9 was observed in PsA gut, especially among infiltrating mononuclear cells, high endothelial venules, and Pan- eth cells. IL-92positive mononuclear cells were demon- strated to be in large part Th9 cells. IL-9 overexpression was accompanied by significant Paneth cell hyperplasia. Paneth cells strongly overexpressed IL-9R, and stimula- tion of epithelial cells, isolated from PsA patients, with IL-9 resulted in overexpression of a-defensin 5 and IL-23p19. Peripheral and synovial expansion of a4b71 Th9 cells was also observed in patients with PsA. Increased expression of IL-9 and IL-9R was also found in synovial tissue. Conclusion. Strong IL-9/Th9 polarization seems to be the predominant immunologic signature in patients in PsA.

Background: Therapy of chronic hepatitis C non- responders to interferon monotherapy with standard doses of interferon plus ribavirin is usually ineffective. Aim: To evaluate the efficacy and tolerability of high-dose prolonged combination retreatment in non- responder patients. Methods: Patients were retreated for 6 months with 6 MU αIFN on alternate days and 1000 or 1200 mg/day ribavirin. HCV-RNA negative patients continued therapy for an additional 6 months. Results: Forty patients (29 males, mean age 49.7 years, 34 genotype 1b, 11 with F3 fibrosis) were treated. At 6 months, 20 (50%) patients were HCV-RNA negative but six of them discontinued therapy because of adverse events. A sustained response was achieved in 28% of patients (11/40). A sustained response was more frequent among patients with genotype non-1b than in those with genotype 1b (67 vs. 21%, P=0.005) and clearance of HCV-RNA in the first 3 months had a high predictive value for sustained response (100% of sustained responders vs. 24% of non-responders, P=0.0001). Conclusions: High-dose prolonged combination therapy in non-responders to IFN monotherapy leads to a higher rate of sustained response than the standard combination regimen. Tolerability may be a rate-limiting factor. Maximal effectiveness can be predicted in patients with non-1b genotype and in those who clear HCV-RNA soon after starting retreatment.