Relationship Between Thymidylate Synthase and p53 and Response to FEC Versus Taxane Adjuvant Chemotherapy for Breast Carcinoma

Many drugs can be used for adjuvant therapy of breast cancer, including anthracyclines, cyclophosphamide, 5-fluorouracil (5-fU) and, recently, taxanes (TXT) have shown promising results. 5-FU blocks thymidylate synthase (TS) which cross-links p53 mRNA, inhibiting its synthesis. TS overexpression is one of the main mechanisms involved in 5-FU drug resistance. Enough p53 mutations can confer resistance to chemotherapy using anthracyclines and 5-FU, while are associated with improved responses to TXT. The aim of this study was to examine the TS and p53 levels in tumor samples and to compare the efficacy of FEC (5-FU, epirubicin, cyclophosphamide) and TXT chemotherapy in a group of patients wit…

Fundoplicatio sec. Nissen videolaparoscopica e metaplasia intestinale in esofago: osservazioni preliminari

The aim of this preliminary study conducted in a few cases was the retrospective evaluation of the effects of laparoscopic Nissen fundoplication on oesophageal intestinal metaplasia. Seventy-seven patients with hiatal hernia underwent digital videofluorography, endoscopy with biopsies, motility studies and 24-h oesophageal pH-monitoring. On the basis of the results of the diagnostic procedures and considering the patients' ages and response to proton-pump inhibitor treatment, 8 patients underwent laparoscopic Nissen fundoplication; in 5 cases intestinal metaplasia was present at histopathological examination. Two of these had Barrett's oesophagus at endoscopy and intestinal metaplasia was a…

Granulomatous reactions from silicone: a diagnostic trap for the dermatophalogist.

Un raro caso di sindrome ipoglicemica ipoinsulinemica: S. di Doege-Potter (SDP)

Laparoscopic Nissen fundoplication and short segment Barrett's esophagus

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease

Aliment Pharmacol Ther 2012; 35: 238–247 Summary Background  Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Aims  To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. Methods  One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and H…

Steatosis affects the performance of liver stiffness measurement for fibrosis assessment in patients with genotype 1 chronic hepatitis C.

Background & Aims: In Chronic Hepatitis C (CHC), the influence of steatosis on liver stiffness measurement (LSM) is still debated. We assessed the impact of steatosis and its ultrasonographical sign – bright liver echo pattern (BLEP) – on LSM values and on transient elastography (TE) accuracy for the diagnosis of liver fibrosis, in a cohort of consecutive patients with Genotype 1 (G1) CHC. Methods: Patients (n = 618) were assessed by clinical, ultrasonographic and histological (Scheuer score) features. TE was performed using the M probe. Results: Male gender (p = 0.04), steatosis as continuous variable (p <0.001), severity of necroinflammation (p = 0.02) and stage of fibrosis (p <0.001) wer…

Barium study associated with water siphon test in gastroesophageal reflux disease and its complications.

PURPOSE: The aim of this study was to evaluate the role of digital cineradiography associated with the water siphon test (WST) in the diagnosis of gastroesophageal reflux and to compare the results with oesophageal motility study, pH monitoring and endoscopy associated with biopsy and histology. MATERIALS AND METHODS: One hundred and sixty consecutive patients underwent digital cineradiography with WST, motility study, pH monitoring and endoscopy with biopsy. The presence of gastroesophageal reflux, oesophagitis, Barrett''s oesophagus and intestinal metaplasia was evaluated. RESULTS: WST vs. pH monitoring showed sensitivity of 71%, specificity of 31%, positive predictive value (PPV) of 53% …

Evaluating the association of serum ferritin and hepatic iron with disease severity in non‐alcoholic fatty liver disease

Background & Aims Hyperferritinemia, with or without increased hepatic iron, represents a common finding in non‐alcoholic fatty liver disease (NAFLD). However, it is unclear whether it reflects hepatic inflammation or true iron‐overload and, in case the latter is confirmed, whether this influences disease progression. We therefore explored the association between serum ferritin, degree and pattern of hepatic iron deposition and liver disease severity in patients with NAFLD. Methods We selected 468 patients with biopsy‐proven NAFLD from 2 European centres. Iron, hepatic and metabolic parameters were collected at the time of liver biopsy. Iron deposits in hepatocytes and reticuloendothelial c…

Caucasian lean subjects with non-alcoholic fatty liver disease share long-term prognosis of non-lean: Time for reappraisal of BMI-driven approach?

[Objective] The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD.

Low cell proliferation marker and low thymidylate synthase levels in the highly aggressive signet ring cell variant histotype of colorectal carcinoma

Fever and dyspnoea in a tracheostomised patient

A 65-year-old man was referred for evaluation of acute onset of fever, productive cough and dyspnoea. He had previously received a diagnosis of laryngeal carcinoma, which had been treated with laryngectomy and bilateral laterocervical lymphadenectomy, followed by chemotherapy. He underwent plastic surgery of the laryngocutaneous fistula, and a positron emission tomography (PET)- computed tomography (CT) examination performed during follow-up showed 18-FDG (2-fluoro-2-deoxyd- glucose) lung uptake in the apical right portion. He had a smoking history and his regular medications included dexamethasone, metoclopramide, omeprazole, furosemide, cholecalciferol and pregabalin. He had a history of …

HIGH PREVALENCE OF VULVAL LICHEN PLANUS IN A COHORT OF ORAL LICHEN PLANUS AFFECTED PATIENTS.

The histological or ultrasonographic detection of steatosis affects the performance of LSM in patients with chronic HCV genotype 1 infection

Hsp60 quantification in human gastric mucosa shows differences between pathologies with various degrees of proliferation and malignancy grade

Background: Stomach diseases are an important sector of gastroenterology, including proliferative benign

Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C.

Iron overload and hepatitis virus C infection cause liver fibrosis in thalassemics. In a monocentric retrospective analysis of liver disease in a cohort of 191 transfusion-dependent thalassemics, in 126 patients who had undergone liver biopsy (mean age 17.2 years; 58 hepatitis virus C-RNA positive and 68 hepatitis virus C-RNA negative) the liver iron concentration (median 2.4 mg/gr dry liver weight) was closely related to serum ferritin levels (R = 0.58; p<0.0001). Male gender (OR 4.12) and serum hepatitis virus C-RNA positivity (OR 11.04) were independent risk factors for advanced liver fibrosis. The majority of hepatitis virus C-RNA negative patients with low iron load did not develop liv…

IL28B and PNPLA3 Polymorphisms Affect Histological Liver Damage in Patients with Non-alcoholic Fatty Liver Disease.

Background & Aims: Genetic background may affect liver damage in patients with non-alcoholic fatty liver disease (NAFLD). The main outcomes of the study were to assess whether IL28B rs12979860 and rs8099917 polymorphisms, together with PNPLA3 rs738409 C>G polymorphism, are associated with lobular inflammation and fibrosis, in NAFLD patients. Methods: One hundred sixty consecutive NAFLD patients were assessed by liver biopsy (Kleiner score); anthropometric, and biochemical and metabolic features were included. IL28B rs12979860 C>T, IL28B rs8099917 G>C, and PNPLA3 rs738409 C>G single nucleotide polymorphisms were tested. Results: Seventy-four (46.2%) patients had IL28B rs12979860 CC polymorph…

Association of vitamin D serum levels and its common genetic determinants, with severity of liver fibrosis in genotype 1 chronic hepatitis C patients.

Background and aims: Lower 25-Hydroxyvitamin D (25[OH]D) serum lev- els have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reduc- tase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Material and methods: Two hundred sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels wer…

A case of bowel schistosomiasis not adhering to endoscopic findings

Schistosomiasis is a chronic worm infection caused by a species of trematodes, the Schistosomes. We may distinguish a urinary form from Schistosomes haematobium and an intestinal-hepatosplenic form mainly from Schistosomes mansoni characterized by nausea, meteorism, abdominal pain, bloody diarrhea, rectal tenesmus, and hepatosplenomegaly. These infections represent a major health issue in Africa, Asia, and South America, but recently S mansoni has increased its prevalence in other continents, such as Europe countries and North America, due to international travelers and immigrants, with several diagnostic and prevention problems. We report a case of a 24-year-old patient without HIV infecti…

Cellular schwannoma of the retroperitoneum with cystic degeneration, mimicking an ovarian cyst, with CKAE1/AE3 and desmin expression.

Schwannoma is an encapsulated benign tumour usually presenting as a solitary mass on the flexor surfaces of the extremities, neck, mediastinum, posterior spinal roots and cerebellopontine angle, an...

RELATIONSHIP BETWEEN THYMIDYLATE SYNTHASE EXPRESSION AND p53 LEVELS WITH THE TREATMENT BY CYCLOPHOSPHAMIDE, 5-FLUOROURACIL CHEMOTHERAPY (CMF) VERSUS DOCETAXEL IN THE LOCALLY ADVANCED CARCINOMA OF THE BREAST.

Are Long Noncoding RNAs New Potential Biomarkers in Gastrointestinal Stromal Tumors (GISTs)? The Role of H19 and MALAT1

Long noncoding RNAs (lncRNAs) are emerging as key regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies described lncRNA alterations in patients with solid tumors. In particular, HOTAIR upregulation has been associated with tumor aggressiveness, metastasis, and poor survival in gastrointestinal stromal tumor (GIST) patients. We analyzed expression levels of other lncRNAs, H19 and MALAT1, in FFPE tissue specimens from 40 surgically resected and metastatic GIST patients, using real-time PCR analysis. H19 and MALAT1 were both upregulated in 50% of GIST patients. MALAT1 lncRNA expression levels seem to be cor…

Multimodal surgical and medical treatment for extensive rhinocerebral mucormycosis in an elderly diabetic patient: a case report and literature review

Diabetes is a well-known risk factor for invasive mucormycosis with rhinocerebral involvement. Acute necrosis of the maxilla is seldom seen and extensive facial bone involvement is rare in patients with rhino-orbital-cerebral mucormycosis. An aggressive surgical approach combined with antifungal therapy is usually necessary. In this report, we describe the successful, personalized medical and surgical management of extensive periorbital mucormycosis in an elderly diabetic, HIV-negative woman. Mono- or combination therapy with liposomal amphotericin B (L-AmB) and posaconazole (PSO) and withheld debridement is discussed. The role of aesthetic plastic surgery to preserve the patient’s physical…

Metastatic seeding of colon adenocarcinoma manifesting as synchronous breast and chest wall localization: report of a case.

Colon carcinoma rarely metastasizes to the breast and it is usually associated with a poor prognosis. Even rarer is metastatic seeding of colon cancer cells in an intramammary location after surgery. Including a primary breast malignancy in the differential diagnosis of such cases is mandatory. We report a rare case of double seeding implantation of colon adenocarcinoma inside the breast parenchyma and intercostal muscles 6 years after resection of a pulmonary metastasis from colon adenocarcinoma. The metastasis was revealed by the presence of bone metaplasia in the intercostal muscles. We discuss how negative immunostaining for estrogen receptors, progesterone receptors, and HER-2, along w…

Primary biliary cirrhosis and hereditary hemorrhagic telangiectasia: When two rare diseases coexist

Primary biliary cirrhosis is a slowly progressive cholestatic autoimmune liver disease that mainly affects middle- aged women with an estimated prevalence ranging from 6.7 to 402 cases per million. Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease, is an autosomal dominant disorder characterized by angiodysplastic lesions (telangiectases and arteriovenous malformations) that can affect many organs, including liver, with a prevalence of 1-2 cases per 10000. We describe the coexistence, for the first time to our knowledge, of these two rare diseases in a 50-year old Caucasian woman. In this setting, the relevance of an accurate medical history, the role of liver histology an…

TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate–severe if ≥30%. Anthropometric and metaboli…

Hepatic and circulating levels of PCSK9 in morbidly obese patients: Relation with severity of liver steatosis

Non-alcoholic fatty liver disease (NAFLD) is becoming the main cause of liver disease in Western countries, especially in morbidly obese patients (MOPs). The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently studied because of its possible involvement in the pathogenesis of NAFLD, but its role, at least in MOPs, is still controversial. The aim of this study was to clarify the correlation between the circulating levels of the PCSK9 protein (cPCSK9) and its hepatic expression with the severity of liver damage in a population of MOPs with NAFLD undergoing bariatric surgery. PCSK9 mRNA was positively correlated with FASN, PPARγ and PPARα mRNAs, while no significant differe…

Associations between Notch-2, Akt-1 and HER2/neu expression in invasive human breast cancer: a tissue microarray immunophenotypic analysis on 98 patients.

&lt;i&gt;Objective:&lt;/i&gt; We aimed to investigate the existence of associations between well-established and newly recognized biological and phenotypic features of breast cancer involved in tumor progression and prognosis. &lt;i&gt;Methods:&lt;/i&gt; Ninety-eight cases of invasive breast cancer were assessed for the immunohistochemical expression of estrogen and progesterone receptors, Ki-67, HER2, Akt-1, and Notch-2, using the tissue microarray technique. Data regarding tumor histotype, histological grade, tumor size and lymph node status were collected for each patient and included in the analysis. &lt;i&gt;Results:&lt;/i&gt; Several significant associations between histological and/o…

Clinical anatomic, immunomorphologic and molecular anatomic data suggest interplay of thyroidal molecules, autoantibodies and Hsp60 in Hashimoto’s disease

Hsp60 is, typically, a mitochondrial protein, but it also occurs in the cytosol, vesicles, and plasma membrane, and in the intercellular space and biological fluids, e.g., blood. Changes in the levels and distribution of Hsp60 are linked to several pathologies, including cancer and chronic inflammatory and autoimmune disorders. What is the histopathological pattern of Hsp60 in the thyroid of Hashimoto’s patients? Are there indications of a pathogenic role of Hsp60 that may make Hashimoto’s thyroiditis a chaperonopathy? Experiments reported here provide information regarding those questions. We found by various immunomorphological techniques increased levels of Hsp60 in the thyroid from HT p…

Visceral adiposity index is associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1.

Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its association with host and viral factors and its link to both histological findings and sustained virological response (SVR). Two hundred thirty-six consecutive G1 CHC patients were evaluated by way of liver biopsy and anthropometric and metabolic measurements, including insulin resistance (IR), homeostasis model assessment (HOMA), and VAI using waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol. All biopsies were scored by on…

A Case of Follicular Tumor of Uncertain Malignant Potential (FT-UMP) with Glomeruloid Features Showing Capsular Mucinous Degeneration

The most recent revision of the World Health Organization (WHO) Classification of Tumours of Endocrine Organs introduced a new variant of follicular thyroid carcinoma (FTC). It is characterized by a “glomeruloid” architectural pattern of growth. We present a case of follicular tumor with glomeruloid features, with Alcian Blue positive mucinous stromal degeneration in foci of questionable capsular microinvasion. At our knowledge, this the second case of glomeruloid follicular tumor in the literature and the first case in which Alcian Blue staining was used to investigate capsular invasion. Moreover, RAS mutation further supports that this is a variant of follicular tumor with uncertain malig…

Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis

AbstractAmphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF-α converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also ass…

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyz…

The accuracy of sentinel lymph node biopsy in the treatment of multicentric invasive breast cancer using a subareolar injection of tracer.

BACKGROUND: The aim of this study was to evaluate the feasibility and the accuracy of sentinel lymph node biopsy in multicentric breast cancer (MBC) performed by means of a subareolar (SA) injection of both 99Tc-labeled human albumin colloid and lymphazurin. METHODS: Between January 2002 and October 2007, 34 patients with MBC with clinically negative axilla underwent sentinel lymph node biopsy (SLNB) followed by total axillary node dissection (AD). Overall successful identification rate of SLN was 100%; there were no false negatives and overall accuracy rate was 100%. RESULTS: The mean number of sentinel lymph nodes (SLNs) identified was 1.8 +/- 0.88 (range = 1-4); the mean number of axilla…

A cholestatic pattern predicts major liver-related outcomes in patients with non-alcoholic fatty liver disease

NAFLD patients usually have an increase in AST/ALT levels, but cholestasis can also be observed. We aimed to assess in subjects with NAFLD the impact of the (cholestatic) C pattern on the likelihood of developing major liver-related outcomes (MALO).

Additional file of Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin

Additional file of Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin

Rare localization of low grade fibromyxoid sarcoma to the nail region.

CARCINOMA CON CELLULE CON CASTONE INSORTO SU POLIPO GASTRICO

AIM: The authors signal a case of gastric polypoid signet ring cell carcinoma, of particular interest for its rarity like show from the review of the literature, which is the first to have been described after Tabaru's citation. METHODS: The study has been carried out at the Department of Surgical and Oncological Sciences of the University of Palermo. It has been based on 2000 cases analysed from June 2001 to December 2003. RESULTS: The authors advance some and emphasizes the diagnostic flow chart and therapeutic choices adopted. CONCLUSIONS: We agree that the endoscopic polypectomy is surgical procedure of first approach, but modifying the therapeutic guideline in relation to histologic ex…

Histological features and ki-67 index in cervical atypical lesions

One of the most frequent challenges in routine diagnostic assessment of cervical biopsies consists of some lesions in which histological features of HPV infection are either inconsistently present or only mildly/focally evident. We named them Atypical Lesions (AL) because differential diagnosis with metaplastic/reactive lesions and LSIL is difficult. It would be important to identify among them those lesions that are really HPV-associated. We studied 52 AL cases to evaluate whether the morphological features and the proliferation index, assessed by Mib1 (Ki67) immunostaining, would be useful to better understand the real nature of AL, with relation to the HPV presence and to the proliferati…

Aurora-A overexpression as an early marker of reflux-related columnar mucosa and Barrett's oesophagus.

Abstract BACKGROUND: The development of oesophageal adenocarcinoma is generally closely associated with the presence of a specialised intestinal-type epithelium such as that found in Barrett's oesophagus (BO). A particular histological condition is when the distal oesophagus showing cardiac and/or fundic mucosa without intestinal metaplasia cannot be defined as 'Barrett's mucosa' [condition that we call 'columnar-lined oesophagus' (CLO)] and up till now, there has been no agreement in literature about the management of this condition. Aurora-A overexpression leads to centrosome amplification, chromosomal instability and aneuploidy in mammalian cells. PATIENTS AND METHODS: A prospective stud…

P53 e Glut-1 nei tumori della muscolatura liscia uterina di incerto potenziale maligno e loro significato nella progressione neoplastica

Serological, immunomorphological and bioinformatics analyses suggest Hsp60 is involved in Hashimoto’s thyroiditis pathogenesis.

TargetPlex FFPE-Direct DNA Library Preparation Kit for SiRe NGS panel: An international performance evaluation study

AimNext generation sequencing (NGS) represents a key diagnostic tool to identify clinically relevant gene alterations for treatment-decision making in cancer care. However, the complex manual workflow required for NGS has limited its implementation in routine clinical practice. In this worldwide study, we validated the clinical performance of the TargetPlex FFPE-Direct DNA Library Preparation Kit for NGS analysis. Impressively, this new assay obviates the need for separate, labour intensive and time-consuming pre-analytical steps of DNA extraction, purification and isolation from formalin-fixed paraffin embedded (FFPE) specimens in the NGS workflow.MethodsThe TargetPlex FFPE-Direct DNA Libr…

Relationship between Thymidylate synthase and p53 and response versus taxane adjuvant chemotherapy for breast carcinoma

Many drugs can be used for adjuvant therapy of breast cancer, including anthracyclines, cyclophosphamide, 5-fluorouracil (5-fU) and, recently, taxanes (TXT) have shown promising results. 5-FU blocks thymidylate synthase (TS) which cross-links p53 mRNA, inhibiting its synthesis. TS overexpression is one of the main mechanisms involved in 5-FU drug resistance. Enough p53 mutations can confer resistance to chemotherapy using anthracyclines and 5-FU, while are associated with improved responses to TXT. The aim of this study was to examine the TS and p53 levels in tumor samples and to compare the efficacy of FEC (5-FU, epirubicin, cyclophosphamide) and TXT chemotherapy in a group of patients wit…

Difference in ki67 and Thimidylate Synthase expressin in primary tumour compared with metastatic nodes in breast cancer patients

A Cholestatic Pattern Predicts Liver-Related Events in Patients with Nonalcoholic Fatty Liver Disease

Background & Aims: Liver test alteration patterns can be categorized as: predominantly hepatocellular(H), with an ALT/ALP ratio>5; predominantly cholestatic pattern(C) with a ratio 55 years(HR2.55,95%C.I.1.17-5.54;p=0.01), platelets<150,000/mmc(HR0.14,95%C.I.0.06-0.32;p<0.001), albumin<4g/L(HR0.62,95%C.I.0.35-1.08;p=0.09), C vs M pattern(HR7.86,95%C.I.1.03-60.1;p=0.04), C vs H pattern(HR12.1,95% C.I.1.61-90.9;p=0.01) and fibrosis F3-F4(HR35.8,95%C.I.4.65-275.2;p<0.001) were independent risk factors for LRE occurrence. C vs M pattern(HR14.3,95%C.I.1.90-105.6;p=0.008) and C vs H pattern(HR15.6,95%C.I. 2.10-115.1;p=0.0068) were confirmed independently associated with LRE occurrence in the vali…

Variant "Pyogenic granuloma-like" of Kaposi's Sarcoma in ACRAL location: our experience.

Features in tubercular meningoencephalitis diagnosis: 18 childhood cases

The aim of this research is to illustrate clinical and instrumental features of central nervous system tuberculosis (CNS-TB) in childhood in order to allow prompt diagnosis and adequate patient management. TB remains one of the most important communicable diseases and represents a major global health problem. Although pulmonary TB tends to be the most common form of the disease, the highest mortality and morbidity occurs with TB of the central nervous system (CNS-TB), which develops in 4% of children with tuberculosis. It has a high fatality rate and causes serious sequelae, especially during childhood. CT and MR imaging studies of 18 patients (11 female, 7 male, mean age 45.72 months) were…

Usefulness of immunohistochemistry in the differential diagnosis between papillary carcinoma in the ectopic laterocervical location and node metastases

High liver RBP4 protein content is associated with histological features in patients with genotype 1 chronic hepatitis C and with nonalcoholic steatohepatitis.

Abstract Background and aim To investigate the hepatic expression of retinol-binding protein-4 (RBP4) in chronic hepatitis C (CHC) and nonalcoholic steatohepatitis (NASH) patients, and its association with biochemical and histological patterns of liver damage. Materials and methods Sixty-six genotype 1 CHC and 32 NASH patients were tested for hepatic RBP4 expression. Liver expression at immunostaining was scored as 0 (slight), 1 (mild), 2 (moderate), and 3 (intense). In addition, the mRNA and the quantitative protein expressions of RBP4 were tested by PCR and by western blot, respectively, in 12 NASH and 28 CHC patients. Twelve subjects undergoing elective cholecystectomy served as controls…

Effectiveness and safety of lomitapide in a patient with familial chylomicronemia syndrome

Background: Familial chylomicronemia syndrome (FCS) is characterized by severe fasting hypertriglyceridemia, abdominal pain, and recurrent acute pancreatitis. Available triglyceride-lowering drugs are insufficient to avoid pancreatitis. Therefore, there is a significant unmet medical need for effective triglyceride-lowering drugs for patients with FCS. Case report: We report the second case of a patient with FCS and recurrent pancreatitis treated with lomitapide. Lomitapide treatment resulted in a reduction of fasting TG levels from 2897 mg/dL (32.71 mmol/L) to an average of 954 mg/dL (10.77 mmol/L) on the 30 mg lomitapide equating to a 67% reduction from baseline. After 26 months of lomita…

Insulin resistance is a major determinant of liver stiffness in nondiabetic patients with HCV genotype 1 chronic hepatitis.

BACKGROUND: In patients with chronic hepatitis C (CHC), liver stiffness measurement (LSM) by transient elastography (TE), is closely related to the stage of fibrosis, but may be affected by necroinflammation. Other factors, such as insulin resistance (IR), might influence the performance of LSM. AIMS: To evaluate in a cohort of nondiabetic patients with genotype 1 CHC, whether IR and other anthropometric, biochemical, metabolic and histological factors contribute to LSM and to identify the best cut-off values of LSM for predicting different stages of fibrosis. METHODS: Nondiabetic patients with genotype 1 CHC (n = 156) were evaluated by liver biopsy (Metavir score), anthropometric, biochemi…

Virus-related insulin resistance in HCV genotype 1 chronic hepatitis C : a major disease modifier

Relationship between thymidylate synthase expression and p53 levels with the treatment of cyclophsphamide, methotrexate, 5-fluorouracil chemotherapy ( CMF)versus docetaxel ( TXT) in locally advanced carcinoma of the breast

10546 Background: Adjuvant chemotherapy is used in the treatment of breast carcinoma independently of axillar node involvement. Different drug combinations such as CMF, FAC, FEC are still used; recently new drugs such as TXT (NEJM 332:1004,1997) show activity and are used also in adjuvant chemotherapy. 5 Fluorouracil (5Fu), a drug involved in main therapeutic regimens, blocks Thymidylate Synthase (TS), an enzyme involved in the DNA synthesis. TS not only links its own mRNA, but also p53 mRNA, inhibiting post transcriptional p53 protein synthesis. TS protein overexpression (Cancer Res 55:1407,1995), and/or its absence (Cancer Res 61:1421,2001) are some of the main mechanisms of 5-Fu drug re…

Secretory breast carcinoma with metastatic sentinel lymph node

Abstract Background Secretory mammary carcinoma is a rare breast neoplasia originally described in children but sometimes also found in adults. It presents a more favourable outcome than more common histological types of breast carcinoma; published literature in fact reports only a few cases with axillary lymph node metastases and only four cases with distant metastases. Clinical presentation In this paper we report a rare case of secretory breast carcinoma with axillary lymph node metastases in a 33-year-old woman. To our knowledge, this is the first case of secretory carcinoma involving biopsy of the sentinel lymph node and investigation of the e-cadherin expression. We found positivity f…

TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

Summary.  The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate–severe if ≥30%. Anthropometric an…

Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE) - lack of interference by iron deposition.

The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-beta-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0.70; P > 0.001) independently of liver iron concentration (r = 0.01; P = 0.932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0.997 (95% confidence interval [CI]: 0.925-1.000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69.0-100.0) and 95% specificity (95% CI: 84.2-99.3). Transient elastography is a reliable non-invasive too…

Predictive role of histological features and Ki67 pattern on high-risk HPV presence in atypical cervical lesions

The most frequently detected alterations of squamous cervical epithelia consist of metaplastic/reactive conditions and human papillomavirus (HPV)-related dysplastic lesions. These latter are traditionally identified as cervical intraepithelial neoplasia (CIN1, 2 or 3) or, in the Bethesda System, as low-grade squamous intraepithelial lesions (LSIL), including CIN1, and high-grade SIL, including CIN2 and CIN3. Some HPV-induced lesions, which are not characterized by obvious dysplasia, are often diagnosed as LSIL. In these lesions, which are hereafter referred to as cervical atipical lesions (CAL), histological features of HPV infection (namely, koilocytosis, multinucleation, acanthosis, papil…

Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease

SUMMARY Background Hyperuricemia has been associated with metabolic disorders. In this line recent studies observed an independent link between higher uric acid serum levels and clinical diagnosis of non-alcoholic fatty liver disease (NAFLD). Mean uric acid serum level was 5.75 mg ⁄ dL, and about 20% of patients had hyperuricemia, that was independently associated with younger age (OR 0.951, 95% CI 0.918-0.984, P = 0.004), lobular inflammation (OR 2.144, 95% CI 1.055-4.357, P = 0.03) and steatosis grade (OR 1.859, 95% CI 1.078-3.205, P = 0.02), by multivariate logistic regression analysis. Female gender (OR 2.656, 95% CI 1.190-5.928, P = 0.01), higher HOMA index (OR 1.219, 95% CI 1.043- 1.4…

Carcinosarcoma of monoclonal origin arising in a dermoid cyst of ovary: a case report.

Abstract Background Transformation of a cystic benign teratoma of the ovary into a "carcinosarcoma" has very rarely been reported and its histogenetic origin is still debated. Case presentation A case of carcinosarcoma arising from a dermoid cyst is reported. The tumor showed cystic areas delimited by normal squamous epithelium, with transitional areas through dysplastic epithelium to "in situ" and infiltrating squamous cell carcinoma (SCC). The sarcomatous component showed compact tissue composed of round cells concentrically arranged around small vessels, spindle, and pleomorphic cells with a high nuclear-cytoplasmic ratio. Positive staining for vimentin, alpha smooth muscle actin and CD1…

Glut-3 expression in laringeal carcinoma: is really a prognostic indicator?

Additional file of Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin

Additional file of Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin

Retinol-binding protein 4 (RBP4) : a new marker of G1 HCV-induced steatosis

DIFFERENCE IN KI67 AND THYMIDYLATE SYNTHASE, P53 LEVELS AND THE TREATMENT BY CMF DRUG COMBINATION VERSUS TAXANES IN THE LOCALLY ADVANCED CARCINOMA OF THE BREAST

Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease

Background: Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Aim: To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD. Methods: We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass…

Biological aggressiveness evaluation in prostate carcinomas: immunohistochemical analysis of PCNA and p53 in a series of Gleason 6 (3+3) adenocarcinomas

We selected 63 prostate tumors with Gleason's grade 6 (3+3), commonly showing both tubular and cribrous patterns. We compared in both patterns the expression of two of the most used biologic markers: PCNA and p53, with the aim to verify the validity of the Gleason's grading system to compare the morphologic grade with biologic aggressiveness and prognostic value. We did not find any statistical difference in the protein immunopositivity, indicating that both patterns could have identical biologic behaviour; then we confirmed the validity of Gleason's system for considering both tubular and cribrous patterns as an intermediate grade of tumoral differentiation. Moreover, we found a linear rel…

Has videofluorography a value in detecting GERD and Its Complications ?.

PNPLA3 GG genotype and carotid atherosclerosis in patients with non-alcoholic fatty liver disease.

Background and Aim To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. Methods We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results we…

Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE) - lack of interference by iron deposition.

The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-b-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0Æ70; P > 0Æ001) independently of liver iron concentration (r = 0Æ01; P = 0Æ932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0Æ997 (95% confidence interval [CI]: 0Æ925–1Æ000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69Æ0–100Æ0) and 95% specificity (95% CI: 84Æ2–99Æ3). Transient elastography is a reliable non-invasive tool f…

Solitary Necrotic Nodule of the Liver: Different Pathological Findings Express a Different Histogenesis

Solitary necrotic nodule of the liver is a rare benign lesion the histogenesis of which is still debated. We here report the case of a patient who underwent laparoscopic cholecystectomy for gallstones and who was accidentally found to have a solitary necrotic nodule of 2 cm in the fifth segment of the liver. On the basis of the histological findings, the hypothesis that different pathogenetic mechanisms could be involved in the histogenesis of this lesion is discussed.

Molecular chaperones expression levels and localization in non-tumoral and tumoral thyroid tissues

Papillary thyroid carcinoma (PTC) is the most frequently occurring subtype of thyroid cancer. Exosomes (EXs) secreted from cells to the extracellular environment play an important role in intercellular communication in normality and pathology. Recent data indicates that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment(1). Heat Shock Protein (HSPs) are often overexpressed during carcinogenesis and different studies shown that they can be released by tumors cells and that the mechanism of release is mediated by EXs pathway. In this project we performed an immunomorphological study to investigate Hsp60, 90,70,27 levels expression profile…

Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C

Summary.  Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All p…

Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis C virus genotype 1.

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR). We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n = 143) or NAFLD (n = 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild &lt;30%, or moderate-severe &gt; or =30%. Thirty nondiabetic, nonobese blood donors served as controls. …

Vitamin D levels and IL28B polymorphisms are related to rapid virological response to standard of care in genotype 1 chronic hepatitis C.

BACKGROUND: Genotype 1 (G1) chronic hepatitis C (CHC) patients achieving a rapid virological response (RVR) on pegylated interferon (PEG-IFN) plus ribavirin have a high chance of sustained virological response (SVR), influenced by IL28B status, viral load, fibrosis and insulin resistance. We assessed whether 25-hydroxyvitamin D (25[OH]D) serum levels are linked to RVR and can be used together with IL28B to construct a pretreatment model to predict RVR. METHODS: A total of 117 consecutive patients with G1 CHC were evaluated by biopsy and anthropometric and metabolic measurements. 25(OH)D serum levels were measured by HPLC. IL28B rs12979860 and rs8099917 polymorphisms were also evaluated. All…

Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature

Abstract Background Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first case of pleural angiosarcoma with lymphatic differentiation following radiometabolic therapy for thyroid carcinoma. Case presentation A 50-year-old man showed diffuse pleural thickening and effusion. Nine years earlier, he underwent thyroidectomy and radiometabolic therapy for thyroid carcinoma with lymph node metastases. Histologically, the tumor consisted of a solid proliferation of atypical epithelioid cells and anastomosed vascular spaces, lacking of red blood c…

CARCINOSARCOMA ARISING IN A DERMOID CYST OF OVARY: A CASE REPORT

BACKGROUND: Transformation of a cystic benign teratoma of the ovary into a "carcinosarcoma" has very rarely been reported and its histogenetic origin is still debated. CASE PRESENTATION: A case of carcinosarcoma arising from a dermoid cyst is reported. The tumor showed cystic areas delimited by normal squamous epithelium, with transitional areas through dysplastic epithelium to "in situ" and infiltrating squamous cell carcinoma (SCC). The sarcomatous component showed compact tissue composed of round cells concentrically arranged around small vessels, spindle, and pleomorphic cells with a high nuclear-cytoplasmic ratio. Positive staining for vimentin, alpha smooth muscle actin and CD10, as w…

Prevalence of vulval lichen planus in a cohort of women with oral lichen planus: an interdisciplinary study

Summary Background  Lichen planus (LP) is a mucocutaneous inflammatory dermatosis that frequently involves the oral and genital mucosae. Patients with LP affecting these sites are often seen by oral medicine specialists or gynaecologists who work in isolation and depend heavily on histopathologists to help them in confirming the diagnosis. There are few studies in the literature combining the experiences of these specialists who share the care of patients with both oral and genital LP. Objectives  To estimate the prevalence of vulval LP (VLP) in a cohort of patients with histologically confirmed oral LP (OLP). Methods  The study group consisted of 42 women histologically diagnosed with OLP.…

Diagnostic performance of 2D-shear wave elastography in the diagnosis of breast cancer: a clinical appraisal of cutoff values

Purpose To assess the role of 2D-shear wave elastography (2D-SWE) in differentiating benign from malignant focal breast lesions (FBLs), providing new vendor-specific cutoff values. Methods 158 FBLs (size: 3.5-50 mm) detected in 151 women (age: 21-87 years) were prospectively evaluated by means 2D-SWE. For each lesion, an expert radiologist assessed US BI-RADS category and calculated the following four 2D-SWE parameters: (1) elasticity maximum (E-max); (2) mean elasticity (E-mean); (3) minimum elasticity (E-min); (4) elasticity ratio (E-ratio). US-guided core-biopsy was considered as standard of reference for all the FBLs classified as BI-RADS 4 or 5. For each 2D-SWE parameter, the optimal c…

Visceral adiposity index is associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1.

Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its association with host and viral factors and its link to both histological findings and sustained virological response (SVR). Two hundred thirtysix consecutive G1 CHC patients were evaluated by way of liver biopsy and anthropometric and metabolic measurements, including insulin resistance (IR), homeostasis model assessment (HOMA), and VAI using waist circumference, body mass index, triglycerides, and highdensity lipoprotein cholesterol. All biopsies were scored by one …

Quantitative immunomorphological analysis of heat shock proteins in thyroid follicular adenoma and carcinoma tissues reveals their potential for differential diagnosis and points to a role in carcinogenesis

Hsp27, Hsp60, Hsp70, and Hsp90 are chaperones that play a crucial role in cellular homeostasis and differentiation, but they may be implicated in carcinogenesis. Follicular neoplasms of the thyroid include follicular adenoma and follicular carcinoma. The former is a very frequent benign encapsulated nodule, whereas the other is a nodule that infiltrates the capsule, blood vessels and the adjacent parenchyma, with a tendency to metastasize. The main objective was to assess the potential of the Hsps in differential diagnosis and carcinogenesis. We quantified by immunohistochemistry Hsp27, Hsp60, Hsp70, and Hsp90 on thin sections of human thyroid tissue with follicular adenoma or follicular ca…

Malignant tumor-like gastric lesion by Candida albicans.

Body Mass Index and Liver Stiffness Affect Accuracy of Ultrasonography in Detecting Steatosis in Patients With Chronic Hepatitis C Virus Genotype 1 Infection

Background & Aims: Few studies have evaluated the accuracy of ultrasonography in detecting steatosis in patients with chronic hepatitis C. We assessed its accuracy in detecting steatosis and factors that affect its diagnostic performance in consecutive patients with chronic hepatitis C virus genotype 1infection. Methods: We analyzed data from 515 patients with chronic hepatitis C, confirmed by liver biopsy, assessing anthropometric, biochemical, metabolic, virologic, and ultrasonography features. Transient elastography was performed to measure liver stiffness. Steatosis was identified with ultrasonography based on detection of a bright liver echo pattern. Results: Ultrasonography identified…

Post-bronchoscopy fatal endobronchial hemorrhage in a woman with bronchopulmonary mucormycosis: a case report

Abstract Introduction During infection, Mucorales fungi invade major blood vessels, leading to extensive necrosis, and in cases of extensive pulmonary disease, bleeding into the lungs may occur. Case presentation We report an unexpected event of post-bronchoscopy fatal endobronchial hemorrhage in a 62-year-old HIV-negative Italian woman with well controlled diabetes mellitus who presented with diffuse cavitated pulmonary lesions. Fiberoptic bronchoscopy revealed bilateral obstruction of the segmental bronchi. Fatal massive bleeding occurred after standard biopsy procedures. Histologic examination showed that the hyphae were more deeply colored by hematoxylin-eosin (H&E) than by other stains…

Reliability of liver stiffness measurement in non-alcoholic fatty liver disease: the effects of body mass index.

Background Liver stiffness measurement (LSM) using transient elastography (TE) is used to stage fibrosis in patients with liver disease, diagnostic reliability and the factors affecting its performance in patients with non-alcoholic fatty liver disease (NAFLD) are incompletely understood. Aim To assess LSM. Methods Consecutive NAFLD patients (n = 169), assessed by liver biopsy (Kleiner score), anthropometrical, biochemical and metabolic features, underwent LSM using TE with standard M probe. Results Liver stiffness measurement was not reliable in 23 patients (14%) due to obesity. Among patients with a reliable TE, a LSM value >7.25 kPa was the best cut-off for predicting significant fibrosi…

Difference in ki67 and thymidylate synthase expression in primary tumour compared with metastastic nodes in breast cancer patients. european society for the study of purine and pyrimidine metabolism in man

Industrial, not fruit fructose intake is associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients.

Background & Aims: Unhealthy food intake, specifically fructose, has been associated with metabolic alterations and with the severity of liver fibrosis in patients with non-alcoholic fatty liver disease. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of fructose intake with the severity of liver histology. Methods: Anthropometric and metabolic factors, including waist circumference (WC), waist-to-hip ratio (WHR), dorso-cervical lipohypertrophy and HOMA were assessed in 147 consecutive biopsy-proven G1 CHC patients. Food intake, namely industrial and fruit fructose, was investigated by a three-day structured interview and a computed database. …

INSULIN RESISTANCE AND SEVERITY OF FIBROSIS IN HCV GENOTYPE 1 CHRONIC HEPATITIS.

‘Pyogenic granuloma-like Kaposi's sarcoma’ on the hands: immunohistochemistry and human herpesvirus-8 detection

Letter to Editor

Surgical pathology and the diagnosis of invasive visceral yeast infection: two case reports and literature review

Invasive mycoses are life-threatening opportunistic infections that have recently emerged as a cause of morbidity and mortality following general and gastrointestinal surgery. Candida species are the main fungal strains of gut flora. Gastrointestinal tract surgery might lead to mucosal disruption and cause Candida spp. to disseminate in the bloodstream. Here we report and discuss the peculiar clinical and morphological presentation of two cases of gastrointestinal Candida albicans lesions in patients who underwent abdominal surgery. Although in the majority of cases reported in the literature, diagnosis was made on the basis of microbiological criteria, we suggest that morphological feature…

OC.03.2 THE PRESENCE OF WHITE MATTER LESIONS IS ASSOCIATED WITH THE HISTOLOGICAL SEVERITY OF NON-ALCOHOLIC FATTY LIVER DISEASE

Utilità dell'immunoistochimica nel differenziare un carcinoma papillare della tiroide insorto su tessuto ectopico da una metastasi laterocervicale

Solid variant of mammary "adenoid cystic carcinoma with basaloid features" merging with "small cell carcinoma"

We describe a rare case of a solid variant of a mammary adenoid cystic carcinoma with basaloid features (sbACC) and its coexistence with a "small cell" carcinoma (SCC), identified and confirmed by histological and immunohistochemical observations: the absence of glandular structures and PAS-positive globules, positivity for neuroendocrine markers (NSE, synaptophysin and chromogranin), and negativity for 34betaE12 and SMA actin were the aspects suggesting the presence of SCC. Furthermore, positivity for CD10 was found both in sbA CC and in SCC, supporting the hypothesis that the two components share the same histogenetic myoepithelial origin and represent an example of dedifferentiation alon…

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-…

Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C

UNLABELLED 25-Hydroxyvitamin D (25[OH]D) can potentially interfere with inflammatory response and fibrogenesis. Its role in disease progression in chronic hepatitis C (CHC) and its relation with histological and sustained virological response (SVR) to therapy are unknown. One hundred ninety-seven patients with biopsy-proven genotype 1 (G1) CHC and 49 healthy subjects matched by age and sex were consecutively evaluated. One hundred sixty-seven patients underwent antiviral therapy with pegylated interferon plus ribavirin. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. Tissue expression of cytochrome (CY) P27A1 and CYP2R1, liver 25-hydroxylating enzymes, were as…

PERCUTANEOUS RADIOFREQUENCY THERMAL ABLATION 8 RFTA) OF SMALL HEPATOCELLUALR CARCINOMA: A PROSPECTIVE STUDY

PERCUTANEOUS RADIOFREQUENCY THERMAL ABLATION 8 RFTA) OF SMALL HEPATOCELLUALR CARCINOMA: A PROSPECTIVE STUDY Data: 2004 Dettaglio tipologia d'Ateneo: 3a - Articoli su riviste ISI (anche on line)

Matrix metalloproteinase-1 is differentially expressed in signet ring cell, and intestinal colorectal carcinomas histotypes

14564 Background: Signet ring cell colorectal carcinoma ( SRCC) pure is an infrequent and highly malignant variant of colorectal cancer, while this histological component is present in 30% of all colorectal carcinomas. In our previous studies we compared the E- Cadherin, β- Catenin, Fibronectin, Ki 67 and Thymidylate Synthase (TS) expression of SRCC, the intestinal type of colorectal carcinoma (ICRC) to try to explain the pathogenesis, the aggressiveness and the low 5 Fluorouracil (5FU) responsiveness of these tumours. We found that all SRCCs had very low levels of all markers and were in the post- mitotic phase of the cell cycle. To understand their high metastatic capability we assessed …

Predictive Role of the p16 Immunostaining Pattern in Atypical Cervical Biopsies with Less Common High Risk HPV Genotypes

P16 immunostaining is considered a useful surrogate of transcriptionally active high-risk (hr) HPV infection. Only strong and widespread “block-like” immunoreactivity is considered specific, whereas weak/focal p16 positive immunostaining is considered not specific, and follow-up and HPV molecular detection is not indicated. The aim of the study was to evaluate the presence of HPV DNA and Ki67 immunostaining in 40 cervical atypical biopsies (CALs) with mild and focal histological features suggestive of HPV infection—20 cases with weak/focal p16 positive immunoreactivity and 20 cases negative for p16 expression. In 16/20 weak/focal p16 positive CALs (80%), the INNO-LiPA HPV genotyping detecte…

Gastric and Rectal Metastases from Malignant Melanoma Presenting with Hypochromic Anemia and Treated with Immunotherapy

The authors present a case of an 80-year-old Caucasian male with multiple gastric and rectal metastases from malignant melanoma presenting with hypochromic anemia as the sole symptom of disease without evidence of cutaneous and ocular tumor localization. The patient had a medical history positive for malignant lentigo melanoma of the occipital region of the scalp and early stage laryngeal squamous cell carcinoma and prostatic carcinoma treated with radiation therapy. The authors make some considerations on intestinal involvement by metastatic melanoma and discuss the choice of not treating with endoscopic procedures the gastric metastatic lesions most likely responsible for the clinical sig…

CD10 and HHF35 actin in the differential diagnosis between Collagenous Spherulosis and Adenoid-Cystic Carcinoma of the breast

Collagenous Spherulosis (CS) and Adenoid-Cystic Carcinoma (AdCC) of the breast consist of cribriform proliferations of epithelial and myoepithelial cells with an immunophenotypic overlap of some myoepithelial markers, such as p63 and smooth muscle actin (SMA). To our knowledge, CD10 and HHF35 actin have not been assessed in the differential diagnosis of these two breast lesions. We performed an immunohistochemical study on 6 cases of CS and 9 cases of AdCC. We found CD10, muscle-specific actin (HHF35), Estrogen and Progesterone receptors (ER and PR) to be strongly expressed in CS, but not in AdCC; C-kit was diffusely positive in AdCC and scanty in CS; SMA, p63 and Cytokeratine 5/6 (CK5/6) w…

Anomalous Origin and Course of the Right Coronary Artery

Coronary anomalous origin from the wrong aortic sinus has been thought to be a risk factor for ischemia because of acute takeoff from the aorta and flow between the aorta and the pulmonary artery.1–4 A 30-year-old man suddenly died within an hour of waking. His clinical history revealed no evidence of any disease, and the postmortem toxicological examination was negative. Autopsy ruled out violent or natural noncardiac causes …

Epicardial Fat, Cardiac Geometry and Cardiac Function in Patients with Nonalcoholic Fatty Liver Disease: Association with the Severity of Liver Disease

Background & Aims Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular risk, including coronary artery disease and cardiac dysfunction. In addition, recent evidence highlighted the possible role of epicardial fat as a new cardiometabolic risk factor. We tested the correlation between epicardial fat, alterations in cardiac geometry and function, and severity of liver damage, in patients with biopsy-proven NAFLD. Methods The anthropometric, biochemical and metabolic features were recorded in 147 consecutive biopsy-proven NAFLD cases (Kleiner score). Epicardial fat thickness was measured by echocardiography. Results Epicardial fat was higher in patients w…

Decreased expression of thymidylate synthase and low proliferation index by Ki67 in "signet ring cell component of colorectal carcinoma"

Morphological and biomolecular charachteristics of subcentimetric invasive breast carcinomas: a sicilian multicentric retrospective analysis

Overexpression of cyclin D1 and interaction between p27Kip1 and tumour thickness predict lymph node metastases occurrence in lower lip squamous cell carcinoma

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. Subse…

The severity of steatosis influences liver stiffness measurement in patients with nonalcoholic fatty liver disease

In nonalcoholic fatty liver disease, the influence of severity of steatosis on liver stiffness measurement (LSM) is poorly studied and still debated. We assessed the impact of steatosis severity and its ultrasonographic (US) sign, severe bright liver echo pattern, on LSM values and on transient elastography accuracy for the diagnosis of liver fibrosis in a cohort of consecutive patients with nonalcoholic fatty liver disease. Patients (n = 253) were assessed by clinical, US, and histological (Kleiner score) features. Transient elastography was performed using the M probe. Among patients with low amounts of fibrosis (F0-F1 and F0-F2), median LSM values, expressed in kilopascals, were signific…

PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non-obese subjects with hepatitis C

Summary Background The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC). Aim To test in genotype 1(G1)-CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis. Methods Four hundred and thirty-four consecutively biopsied Caucasian G1-CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of s…

Unexpected high frequency of genital involvement in women with clinical and hostological features of oral lichen planus

The main aims of this cross-sectional study were: (i) to assess the frequency of genital (vulval) lichen planus (VLP) and vulval lichen sclerosus (VLS) in women affected with oral lichen planus (OLP), regardless of the genital symptoms reported; and (ii) to verify whether any demographic, clinical, or histological features of OLP are associated with a higher risk of vulvo-vaginal involvement. Fifty-five women, presenting OLP, consecutively underwent gynaecological examination and, if they demonstrated positive clinical signs of VLP, underwent biopsy. After a drop-out of 14 subjects, 31/41 (75.6%) were found to have signs of genital involvement, of which 13/31 (44.0%) were asymptomatic. Foll…

Cervico-Facial Actinomycosis: Epidemiological and clinical comments

In a retrospective investigation performed in the department of Surgical Odontostomatology of Palermo University Polyclinic from 1997-2006, the authors examined 12 cases of cervico-facial actinomycosis, taking into consideration age range, gender distribution, predisposing factors and symptoms. In concordance with reports in literature, they found that the disease was perimandibular in 65%, they also report the diagnostic methods and therapeutic approaches used in the study

Autoimmune hepatitis following Epstein-Barr virus infection

We describe a case of a young man with autoimmune hepatitis (AIH) following Epstein–Barr virus (EBV) infection, in whom a long follow-up showed favourable outcome with complete clinical recovery and failure to relapse after cessation of immunosuppressive therapy. The study underlines the importance of the differential diagnosis between primary EBV associated hepatitis with features of autoimmunity, in which there is a direct pathogenetic role of the virus, and EBV related AIH, in which EBV could act as the trigger of the immune mediated damage with probable differences between the two conditions with regard to the prognosis and the responsiveness to immunosuppressive treatment. The favourab…

Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease.

Background Hyperuricemia has been associated with metabolic disorders. In this line recent studies observed an independent link between higher uric acid serum levels and clinical diagnosis of non-alcoholic fatty liver disease (NAFLD). Aims We aimed to assess the potential association between uric acid serum levels and histological liver damage in a homogeneous cohort of biopsy-proven NAFLD patients. Methods Consecutive NAFLD patients (n = 166), assessed by liver biopsy (Kleiner score), anthropometric, biochemical and metabolic features, were included. Enzymatic colorimetric test was used for serum uric acid assays (Roche Diagnostics GmbH, Mannheim, Germany). Hyperuricemia was diagnosed when…

HER2 status in advanced gastric carcinoma: A retrospective multicentric analysis from Sicily.

According to the ToGA trial, HER2 has been shown to be predictive for the success of treatment with trastuzumab in advanced gastric cancer (AGC). A number of studies have analyzed HER-2/neu overexpression in gastric carcinoma and identified the rate of HER2 positivity to be markedly varied. To date, the prevalence of HER2 overexpression in Sicilian people with AGC is unknown. Therefore, in the present study, a retrospective immunohistochemical analysis of HER2 was performed in a cohort of 304 AGC samples that were obtained from the archives of 10 Sicilian anatomopathological diagnostic units in order to verify the positive rate of HER2-positive cases. Furthermore, the characteristics of his…

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase ( KIT) exon 11 PV were included in the study. We analyzed the t…

Difference in Ki67 and thymidylate synthase expression in primary tumour compared with metastatic nodes in breast cancer patients.

Breast cancer is a heterogeneous disease, so therapeutic predictive biological markers need to be identified. To date an accurate evaluation of predictive markers is mainly done at the primary site; however, the main goal of adjuvant therapy for breast cancer is the control of micrometastases. The aim of this study is to assess as therapeutic and/or prognostic marker, the proliferation status of primary tumors and involved nodes as measured by Ki67 and thymidylate synthase (TS) expression, in 30 breast cancer node positive patients. TS is the main target of 5-fluorouracil (5-FU) activity, and its overexpression is one of the mechanisms of 5-FU drug resistance; however, in some studies its a…

Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects

Accumulation of senescent cells may drive age-associated alterations and pathologies. Senolytics are promising therapeutics that can preferentially eliminate senescent cells. Here, we performed a high-throughput automatized screening (HTS) of the commercial LOPAC®Pfizer library on aphidicolin-induced senescent human fibroblasts, to identify novel senolytics. We discovered the nociceptin receptor FQ opioid receptor (NOP) selective ligand 1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-[(3R)-3-piperidinyl]-1H-benzimidazole (MCOPPB, a compound previously studied as potential anxiolytic) as the best scoring hit. The ability of MCOPPB to eliminate senescent cells in in vitro models was further tested…

L'Herpes Zoster

Lichen Planus Vulvare - Uno studio su popolazione selezionata

KA and SCC: GLUT1, CD1a, and CD57 different expression

Erratum to “Gastric and Rectal Metastases from Malignant Melanoma Presenting with Hypochromic Anemia and Treated with Immunotherapy”

Fibronectin Type III Domain–Containing Protein 5 rs3480 A&gt;G Polymorphism, Irisin, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Context Contrasting data have been reported on the role of irisin, a novel myokine encoded by the fibronectin type III domain-containing protein 5 (FNDC5) gene, in nonalcoholic fatty liver disease (NAFLD) pathogenesis. We tested in patients with suspected nonalcoholic steatohepatitis (NASH) the association of FNDC5 variants, hepatic expression, and circulating irisin with liver damage (F2 to F4 fibrosis as main outcome). We also investigated whether irisin modulates hepatocellular fat accumulation and stellate cell activation in experimental models. Methods We considered 593 consecutive patients who underwent liver biopsy for suspected NASH and 192 patients with normal liver enzymes and wit…

Relationship between the thymidiylate synthase, P53 levels and the treatment by CMF drug combination versus taxanes in the locally advanced carcinoma of the breast

High rate of misclassification of fibrosis stage using transient elastography thresholds to prioritize HCV patients for antiviral treatment

Carotid atherosclerosis and chronic hepatitis C: A prospective study of risk associations

BACKGROUND AND AIMS: There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. MATERIALS AND METHODS: One hundred seventy-four consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements. One hundred seventy-four patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of > 1.3 mm a…

D2-40 negative pyogenic granuloma-like Kaposi's sarcoma: Diagnostic features and histogenetic hypothesis of an uncommon skin tumor in HIV-negative patients

Locate full-text(opens in a new window)|View at Publisher| Export | Download | Add to List | More... Pathology Research and Practice Volume 211, Issue 7, July 01, 2015, Pages 528-532 D2-40 negative pyogenic granuloma-like Kaposi's sarcoma: Diagnostic features and histogenetic hypothesis of an uncommon skin tumor in HIV-negative patients (Article) Cabibi, D.a, Giannone, A.G.a , Guarnotta, C.a, Schillaci, O.b, Franco, V.a a Department of Sciences for Promotion of Health and Mother and Child Care, University of Palermo, Palermo, Italy b Servizio di Anatomia Patologica, Dipartimento Oncologico di III livello, La Maddalena Casa di Cura di Alta Specialità, Palermo, Italy View references (20) Abst…

Type and gene location of kit mutations predict progression-free survival to first-line imatinib in gastrointestinal stromal tumors: A look into the exon

In previous studies on localized GISTs, KIT exon 11 deletions and mutations involving codons 557/558 showed an adverse prognostic influence on recurrence-free survival. In the metastatic setting, there are limited data on how mutation type and codon location might contribute to progression-free survival (PFS) variability to first-line imatinib treatment. We analyzed the type and gene location of KIT and PDGFRA mutations for 206 patients from a GIST System database prospectively collected at an Italian reference center between January 2005 and September 2020. By describing the mutational landscape, we focused on clinicopathological characteristics according to the critical mutations and inve…

Serum γ-glutamyl transferase levels, insulin resistance and liver fibrosis in patients with chronic liver diseases.

Background and Aims: Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis. Methods: 843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and…

Time-course of insulin resistance during antiviral therapy in non-diabetic non-cirrhotic patients with genotype 1 HCV infection

Clinical relevance of thymidylate syntetase expression in the signet ring cell histotype component of colorectal carcinoma

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and…

Quantification of fibrosis by collagen proportionate area predicts hepatic decompensation in hepatitis C cirrhosis.

SummaryBackground It is unclear whether the course of cirrhosis and its prognosis are related to the amount of collagen in the liver. Aim To determine whether fibrosis, assessed by collagen proportionate area (CPA) in patients with compensated cirrhosis, is associated with the presence of oesophageal varices, and predict disease decompensation during the follow-up period. Methods We prospectively evaluated 118 consecutive patients with compensated cirrhosis to correlate fibrosis, assessed by CPA in liver biopsies, with the presence of oesophageal varices (OV) and with the rate of liver decompensation (LD) development during a median follow-up of 72 months. Results At baseline 38 (32.2%) pat…

Breast and chest wall metastatic seeding of adenocarcinoma of the colon with bone metaplasia: immunohistochemical study and differential diagnosis

Retinol-binding protein 4 (RBP4): A new marker of G1 HCV-induced steatosis

High prevalence of vulvar liche planus in a cohort of oral liche planus affected patients

Liver follicular helper T-cells predict the achievement of virological response following interferon-based treatment in HCV-infected patients.

Background Here, we assessed the presence of intrahepatic follicular helper T-cells (TFH) in a cohort of consecutive genotype 1 (G1) chronic hepatitis C (CHC) patients comprising non-responders (NRs), relapsers (RRs) or those with sustained virological response (SVR) to pegylated interferon and ribavirin, and tested their relation with the response to antiviral treatment. Methods A total of 78 patients with G1 CHC (30 SVR, 15 RR and 33 NR), comparable for sex, age, viral load and fibrosis were evaluated by immunohistochemistry for liver content of PD1+Bcl6+ TFH cells. The number of TFH cells in the immunostained sections was counted out of five representative high-power microscopic fields (…

Accuracy of the water-siphon test associated to barium study in a high prevalence gastro-oesophageal reflux disease population: a novel statistical approach

Summary Rationale, aims and objectives  Gastro-oesophageal reflux disease (GORD) is ‘a condition which develops when the reflux of gastric content causes troublesome symptoms or complications’. Instrumental diagnostic tests generally used for GORD are 24-hour pH-metry and upper gastrointestinal (GI) endoscopy but barium study associated with provocative manoeuvres such as the water-siphon test (WST), has also been used for GORD. The aim of this paper was to estimate the accuracy of several tests in patients with GORD in a tertiary care setting, focusing on WST, which is rapid and non-invasive, simple to perform and well-tolerated by patients. Method  A total of 172 consecutive patients, sym…

The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease.

Background & Aims The accuracy of noninvasive tools for the diagnosis of severe fibrosis in patients with nonalcoholic fatty liver disease(NAFLD) in clinical practice is still limited. We aimed at assessing the diagnostic performance of combined noninvasive tools in two independent cohorts of Italian NAFLD patients. Methods We analysed data from 321 Italian patients(179 Sicilian-training cohort, and 142 northern Italy-validation cohort) with an histological diagnosis of NAFLD. Severe fibrosis was defined as fibrosis ≥ F3 according to Kleiner classification. The APRI, AST/ALT, BARD, FIB-4, and NFS scores were calculated according to published algorithms. Liver stiffness measurement(LSM) was …

Relationdhip between the thymidylate synthase, P53 levels and the treatment by CMF drug combination versus taxanes in the locally advanced carcinoma of breast

A diagnostic trap for the dermatopathologist: granulomatous reactions from cutaneous microimplants for cosmetic purposes.

We present a case of late granulomatous reactions from silicone that first appeared in a site different from that of the injection causing an incorrect diagnosis of liposarcoma in the beginning. The histological picture was a cystic-macrophagic granuloma in both the injection site (upper lip) and the migrating site (paranasal regions). We think that the foreign body has undergone an antigravity migration from the upper lip to the right paranasal region. To our knowledge, such a phenomenon has not been yet reported in literature.

Vitamin D levels and IL28B polymorphisms are related to rapid virological response to standard of care in genotype 1 chronic hepatitis C.

Background Genotype 1 (G1) chronic hepatitis C (CHC) patients achieving a rapid virological response (RVR) on pegylated interferon (PEG-IFN) plus ribavirin have a high chance of sustained virological response (SVR), influenced by IL28B status, viral load, fibrosis and insulin resistance. We assessed whether 25-hydroxyvitamin D (25[OH]D) serum levels are linked to RVR and can be used together with IL28B to construct a pretreatment model to predict RVR. Methods A total of 117 consecutive patients with G1 CHC were evaluated by biopsy and anthropometric and metabolic measurements. 25(OH)D serum levels were measured by HPLC. IL28B rs12979860 and rs8099917 polymorphisms were also evaluated. All p…

Fine-Needle Aspiration (FNAB) Molecular Analysis for the Diagnosis of Papillary Thyroid Carcinoma through BRAFv600E mutation and RET/PTC rearrangement

Objective: To evaluate BRAFV600E mutation on consecutive fine-needle aspiration biopsy (FNAB) specimens in order to assess FNAB’s usefulness in preoperative papillary thyroid carcinoma (PTC) diagnosis with the contemporaneous analysis of RET=PTC1 and RET=PTC3 rearrangements obtained from ex vivo thyroid nodules. Design: Thyroid FNABs from 156 subjects with nodules and 49 corresponding surgical samples were examined for the presence of BRAF mutation by real-time allele-specific polymerase chain reaction, confirmed with the use of a laser pressure catapulting system. Samples were also examined for RET=PTC rearrangements. The results were compared with the cytological diagnosis and histopathol…

The oral melanoma: atypical immunophenotype in the metastatic area.Melanoma Res. 2008 Feb;18(1):70-2.

Possible role of differential metalloproteinase 1 expression in signet ring cell and intestinal colorectal carcinoma histotypes

Background: Pure signet ring cell colorectal carcinoma ( SRCC) is an infrequent and highly malignant histological variant of colorectal cancer (CRC), while it is present as a histological component in colorectal carcinomas more frequently. Materials and Methods: The aim of this was to widen the knowledge of the biological factors involved in the pathogenesis and aggressiveness of SRCC by the identification and evaluation of possible molecular abnormalities. By means of immunohistochemistry the expression of the proteolytic degradation enzyme matrix metalloprotease (MMP)-1, that is a collagenase specifically degrading collagens I, II, III and of the adhesion proteins E-cadherin, B-catenin an…

BRAF(V600E) mutation influences hypoxia-inducible factor-1alpha expression levels in papillary thyroid cancer

Abstract Hypoxia-inducible factor-1alpha 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-1alpha expression was found increased in differentiated, poorly differentiated, medullary and anaplastic variants. Hypoxia represents the principal stimulus responsible for hypoxia-inducible factor-1alpha induction. Other nonhypoxic stimuli increase hypoxia-inducible factor-1alpha synthesis through the activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in a cell-type-specific manner. We have previously s…

CD1A-positive cells and HSP60 (HSPD1) levels in keratoacanthoma and squamous cell carcinoma.

CD1a is involved in presentation to the immune system of lipid antigen derived from tumor cells with subsequent T cell activation. Hsp60 is a molecular chaperone implicated in carcinogenesis by, for instance, modulating the immune reaction against the tumor. We have previously postulated a synergism between CD1a and Hsp60 as a key factor in the activation of an effective antitumor immune response in squamous epithelia. Keratoacantomas (KAs) are benign tumors that however can transform into squamous cell carcinomas (SCCs), but the reasons for this malignization are unknown. In a previous study, we found that CD1a-positive cells are significantly more numerous in KA than in SCC. In this study…

INSULIN RESISTANCE, STEATOSIS AND PROGRESSION OF FIBROSIS IN PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C

Background and aim: Insulin resistance (IR) and steatosis have been associated with fibrosis severity in chronic hepatitis C (CHC), but only few studies investigate their role as predictors of disease evolution. We aimed to assess in patients with CHC if IR and steatosis are linked to progression of fibrosis over time. Material and methods: 86 consecutive G1 HCV infected patients with two paired liver biopsies over a period 67±30 months (range, 13-135), were evaluated at baseline by anthropometric and metabolic measurements, including IR (IR= HOMA-IR >2.7). All biopsies were scored by one pathologist for staging and grading (Scheuer). Steatosis was considered significant if =10. Results: At…

The value of intraoperative frozen section examination of sentinel lymph nodes in surgical management of breast carcinoma.

PURPOSE: In breast cancer staging, the need for intraoperative sentinel lymph node (SLN) evaluation has still not been adequately established. This study investigates the impact of intraoperative frozen section (FS) evaluation of SLN to avoid subsequent axillary lymph node dissection (ALND) in patients with positive SLN. METHODS: A retrospective review of 364 breast cancer patients undergoing SLN biopsy with intraoperative FS evaluation of SLN was performed. RESULTS: Sensitivity and accuracy of FS examination of SLN were 76.4% and 94.2%, respectively. The sensitivity was significantly higher in larger tumors (p < 0.01). No significant correlation was found between FS and histologic type. A …

High sCD36 plasma level is associated with steatosis and its severity in patients with genotype 1 chronic hepatitis C

Soluble CD36 (sCD36) plasma levels, a known marker of cardiometabolic disorders, are associated with surrogate markers of steatosis, while experimental and human studies show a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). One hundred and seventy-five consecutive biopsy-proven patients were studied. sCD36 plasma levels were assessed by an in-house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer) and graded for steatosis, which was considered moderate-severe i…

Glypican-3 and Hep Par-1 are Useful Biomarkers in the Cytologic Assessment of Ascites.

Till date, the utility of cytologic assessment of ascites for the identification of hepatocellular carcinoma (HCC) cells is still debated and the usefulness of immunocytochemistry for glypican-3 (GPC3) and Hep Par-1 in this setting has not been reported. Liquid-based cytology of ascitic fluid of 28 cirrhotic patients was performed and the spots obtained were stained with hematoxylin and eosin, papanicolau, and with GPC3 and Hep Par-1 antibodies. GPC3 and Hep Par-1 antibodies stained positively the atypical cells in the ascites of 2 patients with HCC showing an exophytic growth pattern. The specimens of the patients with nonexophytic HCC, other non-HCC cancers, or cirrhosis stained negativel…

Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial

Background: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications. Patients and methods: Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculate…

Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. A minority of affected patients develops inflammation, subsequently fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCC is a leading cause of cancer-related death. An increased number of senescent cells correlate with age-related tissue degeneration during NAFLD-induced HCC. Senolytics are promising agents that target selectively senescent cells. Previous studies showed that whereas a combination of the senolytic drugs dasatinib and quercetin (D + Q) reduced NAFLD in mice, D + Q lacked efficacy in removing doxorubicin-induced…

Non-functioning parathyroid cystic tumour: malignant or not? Report of a case

Parathyroid carcinoma (PC) is a very rare endocrine tumour, usually characterized by symptoms such as a neck mass, dysphonia, severe hypercalcemia exceeding 140 mg/L and elevated serum parathyroid hormone levels, even more than 5 times the upper limit of normal. Non-functioning parathyroid cancer is extremely rare and, in this case, its pre-operative diagnosis is often difficult. A 54-year old female patient, referring dysphagia and dysphonia, underwent neck ultrasound and neck CT. A left thyroid nodule, probably cystic, was found. It presented caudal extent on anterior mediastinum causing compression of the left lateral wall of the trachea. The preoperative calcemia was into the normal ran…

Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C

Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients un…

espressione della citocheratina 7 come marker precoce di danno da reflusso nella muocsa colonnare dell'esofago in assenza di metaplasia intestinale

Relationship between the thymidylate synthase, p53 levels with the treatment by Cyclophosphamide, Metotrexate, 5-Fluorouracil chemotherapy (CMF) versus Docetaxel (TXT) in the locally advanced carcinoma of breast.

Increased expression of transketolase-like-1 in papillary thyroid carcinomas smaller than 1.5 cm in diameter is associated with lymph-node metastases.

BACKGROUND. Patients with small papillary thyroid carcinoma (PTC) may have a high incidence of regional lymph-node (LN) metastases at presentation, and these are considered to be an independent risk factor for tumor recurrence. A mutated transketolase transcript (TKTL1) has been found up-regulated in different human malignancies, and strong TKTL1 protein expression has been associated with aggressiveness and poor patient survival in several epithelial cancers. METHODS. TKTL1 protein expression was analyzed in 256 consecutive cases of PTCs ≤1.5 cm by immunohistochemistry with a specific anti-TKTL1 antibody. RNA analysis was performed by real-time polymerase chain reaction (PCR) in all cases …

Cystic mucinous adenocarcinoma of the lung: a case report.

Abstract Mucinous cystic tumors of the lung are uncommon, the preoperative pathologic diagnosis is difficult and their biological behavior is still controversial. We report the case of a patient with a clinically benign cystic lesion that post-operatively showed to be consistent with an invasive adenocarcinoma arising in a mucinous cystadenoma of the lung, We underline the difficulty of the clinical pre-operative diagnosis of this cystic neoplasia radiologically mimicking a hydatid cyst, and we report the negative TTF1 immunostaining potentially misleading in the differential diagnosis with metastatic mucinous carcinomas. Finallly, we evidence the presence of a pre-existing mucinous benign …

The Hepatic Expression of Vitamin D Receptor Is Inversely Associated With the Severity of Liver Damage in Genotype 1 Chronic Hepatitis C Patients

BACKGROUND/AIMS: Low 25-hydroxyvitamin D serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC), and experimental evidence suggested a hepatoprotective role of vitamin D via interaction with hepatic vitamin D receptor (VDR). We assessed the hepatic expression of VDR protein and its association with liver disease severity. METHODS: Ninety-one consecutive patients with biopsy-proven G1CHC and available frozen liver tissue were evaluated. Ten subjects without chronic liver diseases and nine patients with autoimmune hepatitis served as controls. The hepatic expression of VDR protein was assessed by Western blot for quantification…

751 RETINOL-BINDING PROTEIN 4 (RBP4): A NEW MARKER OF G1 HCV-INDUCED STEATOSIS

Decreased expression of thymidylate synthase and low proliferation index assessed by ki67 in " signet ring cell component" of colorectal carcinomas

Morphological and biomolecular characteristics of subcentimetric invasive breast carcinomas in Sicily: A multicentre retrospective study in relation to trastuzumab treatment

Little information from clinical trials is available regarding the efficacy of trastuzumab treatment in subcentimetric breast carcinomas (BCs). The aim of this study was to verify the existence of correlations between HER2 and hormone receptor status, Ki67 values, grade, histotype and node involvement in a cohort of pT1a,b BCs from an area not widely covered by screening campaigns. A total of 410 pT1a,b BC formalin-fixed paraffin-embedded samples collected from eight Sicilian Anatomo-Pathological Units (APUs) were classified according to the WHO classification and tumour grading was established. Estrogen and progesterone receptor status, Ki67 labelling index and HER2 status were available. …

Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection.

BACKGROUND AND AIMS: Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. MATERIAL AND METHODS: One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was def…

Time course of insulin resistance during antiviral therapy in non-diabetic, non-cirrhotic patients with genotype 1 HCV infection

Background Genotype 1 (G1) hepatitis C virus (HCV) is associated with insulin resistance (IR) and its clearance seems to improve insulin sensitivity. We aimed to evaluate the time course of IR in response to antiviral therapy in non-diabetic, non-cirrhotic G1 HCV patients and to assess the effect of metabolic factors on sustained virological response (SVR). Methods A total of 83 consecutive treatment-naive G1 chronic hepatitis C (CHC) patients were evaluated by anthropometric and metabolic measurements, including IR using the homeostasis model assessment (HOMA). Patients were considered to have IR if HOMA was &gt;2.7. All cases had a liver biopsy scored for staging, grading and steatosis. A…

The Presence of White Matter Lesions Is Associated With the Fibrosis Severity of Nonalcoholic Fatty Liver Disease

Abstract We tested whether nonalcoholic fatty liver disease (NAFLD) and/or its histological severity are associated with vascular white matter lesions (WML) in patients with biopsy-proven NAFLD and in non-NAFLD controls. Data were recorded in 79 consecutive biopsy-proven NAFLD, and in 82 controls with normal ALT and no history of chronic liver diseases, without ultrasonographic evidence of steatosis and liver stiffness value  45 years (OR 3.09, 95% CI: 1.06–9.06, P = 0.03; and OR 11.1, 95% CI: 1.14–108.7, P = 0.03), and F2–F4 fibrosis (OR 3.36, 95% CI: 1.29–8.73, P = 0.01; and OR 5.34, 95% CI: 1.40–20.3, P = 0.01) were independently associated with WML (mostly of mild grade) by multivariate…

Fatal Pulmonary Hemorrhage Through Fiberoptic Broncoscopy in a Well Controlled Diabetic Female With Mucormycosis

A rare case of invasive pulmonary mucormycosis complicated by fatal massive haemoptysis through bronchoscopy in a patient with a well controlled diabetes is reported. Histological features of infection are reported and the characteristic aspects of the staining are discussed. Fiberoptic bronchoscopy revealed bilateral obstruction of the segmental bronchi and fatal massive bleeding occurring because of biopsy sampling. Caution is warranted in the use of bronchoscopy sampling in patients with radiological features of cavitated lesions of fungal origins. Better preventive and early therapeutic antifungal treatments are needed to avoid this serious complication.

DIFFERENT EXPRESSION OF E-CADERINE, BETA CATENIN AND FIBRONECTIN IN SIGNET RING CELL AND INTESTINAL CARCINOMA.

GDF11 induces mild hepatic fibrosis independent of metabolic health

BACKGROUND & AIMS: Growth Differentiation Factor 11 (GDF11) is an anti-aging factor, yet its role in liver diseases is not established. We evaluated the role of GDF11 in healthy conditions and in the transition from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). RESULTS: GDF11 mRNA levels positively correlated with NAFLD activity score and with CPT1, SREBP, PPAR? and Col1A1 mRNA levels, and associated to portal fibrosis, in morbidly obese patients with NAFLD/NASH. GDF11-treated mice showed mildly exacerbated hepatic collagen deposition, accompanied by weight loss and without changes in liver steatosis or inflammation. GDF11 triggered ALK5-dependent SMAD2/…

Images in cardiovascular medicine. Anomalous origin and course of the right coronary artery.

Coronary anomalous origin from the wrong aortic sinus has been thought to be a risk factor for ischemia because of acute takeoff from the aorta and flow between the aorta and the pulmonary artery.1–4 A 30-year-old man suddenly died within an hour of waking. His clinical history revealed no evidence of any disease, and the postmortem toxicological examination was negative. Autopsy ruled out violent or natural noncardiac causes of death and revealed an underlying congenital heart disease, which was characterized by a congenital bicuspid aortic valve and an anomalous origin of the right coronary artery just above the median raphe of the anterior cusp

Discordance rate of HER2 status in primary breast carcinomas versus synchronous axillary lymph node metastases: a multicenter retrospective investigation.

Antonio Ieni,1 Valeria Barresi,1 Rosario Caltabiano,2 Anna Maria Cascone,3 Rachele Del Sordo,4 Daniela Cabibi,5 Pio Zeppa,3 Salvatore Lanzafame,2 Angelo Sidoni,4 Vito Franco,5 Giovanni Tuccari1 1Department of Human Pathology Gaetano Barresi, Section of Anatomic Pathology, University of Messina, Messina, 2Department GF Ingrassia, Section of Anatomic Pathology, University of Catania, Catania, 3Department of Medicine and Surgery, University of Salerno, Salerno, 4Institute of Pathologic Anatomy and Histology, Division of Cancer Research, University of Perugia, Perugia, 5Department of Human Pathology, Section of Anatomic Pathology, University of Palermo, Palermo, Italy Background: Human epiderma…

NUPR1 protects liver from lipotoxic injury by improving the endoplasmic reticulum stress response

AbstractBackground and AimsNon-alcoholic fatty liver disease and related hepatic syndromes affect up to one third of the adult population. The molecular mechanisms underlying NAFL etiology remain elusive. Nuclear Protein 1 (NUPR1) expression increases upon cell injury in all organs and recently we report its active participation in the activation of the Unfolded Protein Response (UPR). The UPR typically maintains protein homeostasis, but downstream mediators of the pathway regulate metabolic functions, including lipid metabolism. NUPR1 and UPR increase have been reported in obesity and liver pathologies and the goal of this study was to investigate the roles of NUPR1 in this context.Methods…

The molecular changes driving the carcinogenesis in Barrett's esophagus: which came first, the chicken or the egg?

Esophageal adenocarcinoma originates from columnar metaplastic epithelium of the distal esophagus. Various steps for this carcinogenetic process are known. Before the onset of high-grade dysplasia and adenocarcinoma, endoscopic surveillance is possible. However, because of the high cost of long-term surveillance, predictive factors for cancer are being evaluated to identify subjects with metaplasia who have a higher risk of developing malignancy. Molecular changes seem suitable for this purpose, but could require a high resource expenditure. While trying to identify the best predictive factors for cancer risk, molecular changes and differences in miRNA expression profile between the various…

ISTIOCITOMA FIBROSO ANGIOMATOIDE: DESCRIZIONE DI UN CASO ED INQUADRAMENTO NOSOGRAFICO

Hyperuricaemia: another metabolic feature affecting the severity of chronic hepatitis because of HCV infection.

Background Several works observed a link between uric acid serum levels and clinical and histological features of nonalcoholic fatty liver disease. An association between chronic hepatitis C (CHC) and uric acid levels has been poorly investigated. Aims To assess the potential association between uric acid serum levels and both histological features of liver damage and sustained virological response (SVR) in a homogeneous cohort of CHC patients. Methods Consecutive biopsy-proven CHC patients were included. Hyperuricaemia was diagnosed with uric acid serum levels >7 mg/dl in men, and >6 mg/dl in women. Patients underwent therapy with pegylated interferon plus ribavirin. Results Hyperuricaemia…

Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study

BACKGROUND: No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. AIM OF THE STUDY: We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. MATERIALS AND METHODS: The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (R…

Antimitochondrial antibody -M2 positive autoimmune hepatitis during standard of care for chronic hepatitis C

The current standard of care (SoC) for chronic hepatitis C, i.e. the combination of a pegylated-interferon (PEG-IFN) with ribavirin (RBV), may activate underlying autoimmune conditions. Particularly, interferon (IFN) has been known to induce or exacerbate autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) in hepatitis C virus patients. We describe a severe, acute-onset antimitochondrial antibody (AMA)-M2 positive AIH appearing during the last weeks of SoC in a woman with chronic hepatitis C and no previous history of autoimmunity, and resolving on protracted steroids. In this context, the relevance of the characterization of the immunoglobulin isotype of portal plasma cells for …

Comparison of Histochemical Stainings in Evaluation of Liver Fibrosis and Correlation with Transient Elastography in Chronic Hepatitis.

Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a debated topic. This study aimed to compare Masson’s trichrome (MT), Sirius Red (SR), and orcein stainings in evaluating liver fibrosis in chronic HCV hepatitis (CHC) with semiquantitative and quantitative methods (Collagen Proportionate Area (CPA) by Digital Image Analysis (DIA)) and correlate them with transient elastography (TE).Methods. Liver stiffness evaluation of 111 consecutive patients with CHC was performed by TE. Semiquantitative staging by Metavir score system and CPA by DIA were assessed on liver biopsy stained with MT, SR, and orcein.Results. MT, SR, and orcein staining showed concord…

Immunohistochemistry Differentiates Papillary Thyroid Carcinoma Arising in Ectopic Thyroid Tissue from Secondary Lymph Node Metastases

Objective: To verify whether immunohistochemistry might be useful in the distinction between a true laterocervical metastasis of an undetected thyroid carcinoma and a primary tumor outside the gland. Design: Galectin-3, cytokeratin 19, and HBME-1 were assessed in six cases (group A) of laterocervical masses harboring papillary thyroid carcinoma (PTC) but without a thyroid tumor, and in eight cases (group B) showing PTC both in the thyroid and in the laterocervical masses. In both groups, normal-looking follicles adjacent to the laterocervical neoplasia were present. Main outcome: We found that the apparently normal follicles in group A were negative for all the antibodies, while group B sho…

Glut-1 Expression and In Situ CD1a/CD57 Immunologic Deficit in Keratoacanthoma and Squamous Cell Carcinoma of Immunocompetent Patients

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 (…

Immunomorphological Patterns of Chaperone System Components in Rare Thyroid Tumors with Promise as Biomarkers for Differential Diagnosis and Providing Clues on Molecular Mechanisms of Carcinogenesis

Hurthle cell (HC), anaplastic (AC), and medullary (MC) carcinomas are low frequency thyroid tumors that pose several challenges for physicians and pathologists due to the scarcity of cases, information, and histopathological images, especially in the many areas around the world in which sophisticated molecular and genetic diagnostic facilities are unavailable. It is, therefore, cogent to provide tools for microscopists to achieve accurate diagnosis, such as histopathological images with reliable biomarkers, which can help them to reach a differential diagnosis. We are investigating whether components of the chaperone system (CS), such as the molecular chaperones, can be considered dependabl…

Thyroid sarcoidosis as a unique localization.

Sarcoidosis is a systemic disorder characterized by granulomatous lesions, principally affecting the lungs. There are numerous reports in the literature of an associated involvement of the thyroid, much more frequently in hypothyroid than in hyperthyroid subjects. The present case report refers to a woman presenting with thyroid nodules and normal biochemical levels and thyroid function parameters, while histology revealed sarcoid-type lesions. Subsequent investigations and a long follow-up showed no evidence of involvement of other sites, including the lungs. Consequently, after a long period of normal health associated with the negative results of the examinations, a diagnosis of sarcoido…

Primary small cell neuroendocrine carcinoma of the breast: The histogenetic diatribe

The article entitled “Primary small cell neuroendocrine carcinoma of the breast: a report of two cases and review of the literature” by Spinelli et al. [1]. The authors stated that “the histogenesis is still unclear because the presence of neuroendocrine cells in normal breast has not been proved conclusively”. Moreover they reported two histogenetic hypotheses, the first one stating that “small cell neuroendocrine carcinoma (SCNC) is a variant of metaplastic carcinoma arising from a lobular or ductal carcinoma”, the second one claiming that “it is a distinct type of breast carcinoma different from the usual type”. We appreciate this case report and we agree with the authors on the histogen…

Immunomorphological Pattern of Molecular Chaperones in Normal and Pathological Thyroid Tissues and Circulating Exosomes: Potential Use in Clinics

The thyroid is a major component of the endocrine system and its pathology can cause serious diseases, e.g., papillary carcinoma (PC). However, the carcinogenic mechanisms are poorly understood and clinical useful biomarkers are scarce. Therefore, we determined if there are quantitative patterns of molecular chaperones in the tumor tissue and circulating exosomes that may be useful in diagnosis and provide clues on their participation in carcinogenesis. Hsp27, Hsp60, Hsp70, and Hsp90 were quantified by immunohistochemistry in PC, benign goiter (BG), and normal peritumoral tissue (PT). The same chaperones were assessed in plasma exosomes from PC and BG patients before and after ablative surg…

Liver eosinophilic infiltrate is a significant finding in patients with chronic hepatitis C.

Eosinophilic infiltrate of liver tissue is described in primary cholestatic diseases, hepatic allograft rejection and drug-induced liver injury, but its significance and its implications in chronic hepatitis C are unknown. The aim of this study was to investigate the clinical significance of eosinophilic liver infiltrate in patients with chronic hepatitis C. We retrospectively evaluated 147 patients with chronic hepatitis C. The presence of eosinophilic infiltrate was investigated in liver biopsies, and a numeric count of eosinophilic leucocytes in every portal tract was assessed. An eosinophilic infiltrate of liver tissue (> or =3 cells evaluated in the portal / periportal spaces) was obse…

Differing expression of metalloprotease and of adhesion molecules in signet-ring cell and intestinal colorectal carcinoma.

Abstract. Background: Pure signet-ring cell colorectal carcinoma (SRCC) is an infrequent and highly malignant histological variant of colorectal cancer (CRC), while it is present as a histological component in colorectal carcinomas more frequently. Materials and Methods: The aim of this work was to widen the knowledge of the biological factors involved in the pathogenesis and aggressiveness of SRCC by the identification and evaluation of possible molecular abnormalities. By means of immunohistochemistry the expression of the proteolytic degradation enzyme matrix metalloprotease (MMP)-1, that is a collagenase specifically degrading collagens I, II, III and of the adhesion proteins Ecadherin,…

The presence of white matter lesions is not associated with non-alcoholic fatty liver disease but with its histological severity

Interferon lambda 4 rs368234815 TT&gt;δG variant is associated with liver damage in patients with nonalcoholic fatty liver disease

Background and Aims: The IFNL3/4 locus influencing innate immunity regulation has been associated with the severity of hepatitis and fibrosis progression during chronic hepatitis C infection, while contrasting results were reported in NAFLD. In this study, we examined whether rs12979860 and the linked causal rs368234815 variant encoding for the alternative IFNL4 protein variant are associated with liver fibrosis and damage in a large multicenter cohort of patients at risk of NASH. To clarify the mechanism, we also evaluated the impact on interferon-stimulated gene (ISG) hepatic expression in a subset of patients. Methods: We considered 946 consecutive Italian individuals at risk of NASH wit…

Abstract 448: Molecular analysis of BRAF gene and PTEN gene expression in metastatic colorectal cancer patients: Feasibility study

Abstract Introduction There are numerous causes triggering CRC. 25-80% of CRC shown a deregulation in Epidermal Growth Factor Receptor (EGFR) pathway. Two signaling pathways downstream of the EGFR are dysregulated in CRC the mitogen-activated protein kinase (MAPK) and the phosphoinositide-3-kinase (PI3K) pathway. Activating mutations in KRAS and BRAF (MAPK pathway) and PIK3CA affect prognosis and/or response to anti-EGFR MoAb. PTEN is a downstream effector of EGFR pathway and is involved in PI3K pathway. Loss of PTEN protein expression can occur through epigenetic silencing and mutation or allelic loss. Immunohistochemistry (IHC) is the most effective way to assay for loss of PTEN expressio…

Clinical features and outcomes of patients with drug-induced autoimmune hepatitis: a retrospective cohort study.

Abstract Background Drugs and herbal products can induce autoimmune hepatitis. We assessed frequency and clinical outcomes of patients suffering from drug-induced autoimmune hepatitis. Methods All patients with drug-induced liver injury admitted between 2000 and 2011 were retrospectively studied. Diagnoses of drug-induced autoimmune hepatitis and idiopathic autoimmune hepatitis were made according to simplified criteria. After discharge, all patients had regular follow-up and were contacted to update outcomes. Results Among 10,270 in-hospital patients, 136 (1.3%) were diagnosed with drug-induced liver injury. Among them, 12 (8.8%) were diagnosed as drug-induced autoimmune hepatitis (41.7% m…

P0760 : PNPLA3 rs738409 I748M is associated with steatohepatitis in non obese subjects with hepatitis C

The presence of White Matter Lesions is not associated with Non-alcoholic Fatty Liver Disease but with its histological severity

MALIGNANT TUMOR-LIKE GAASTRIC LESION DUE TO CANDIDA ALBICANS IN A DIABETIC PATIENT TREATED WITH CYCLOSPORIN: A CASE REPORT AND REVIEW OF THE LITERATURE

The gastrointestinal tract of healthy individuals is colonized by hundreds of saprophytes and mycetes, especially the Candida species, are habitual ones. Under certain conditions, the fungal flora may overgrow, resulting in lesions of the digestive mucosa which, rarely, can have a local diffusion and/or spread to the lympho-hematogenous system. Mycotic infections of the stomach can sometimes look like benign gastric ulcers. Here, we present the case report of a woman, aged 64, who presented with type II diabetes mellitus and psoriasis, on chronic treatment with cyclosporin A and with endoscopic evidence of an ulcerated, vegetating gastric lesion secondary to Candida albicans infection. Alth…

CLINICAL COURSE OF NIMESULIDE-INDUCED LIVER INJURY

Gastric and Rectal Metastases from Malignant Melanoma Presenting with Hypochromic Anemia and Treated with Immunotherapy

The authors present a case of an 80-year-old Caucasian male with multiple gastric and rectal metastases from malignant melanoma presenting with hypochromic anemia as the sole symptom of disease without evidence of cutaneous and ocular tumor localization. The patient had a medical history positive for malignant lentigo melanoma of the occipital region of the scalp and early stage laryngeal squamous cell carcinoma and prostatic carcinoma treated with radiation therapy. The authors make some considerations on intestinal involvement by metastatic melanoma and discuss the choice of not treating with endoscopic procedures the gastric metastatic lesions most likely responsible for the clinical sig…

TM6SF2 rs58542926 is not associated with steatosis and fibrosis in largecohort of patients with genotype 1 chronic hepatitis C

Background & Aims We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients. Methods A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (<5%), mild-moderate(5–29%) and severe(≥30%), Fibrosis was considered severe if=F3-F4. Results Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosi…

Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease.

[Background & Aims] Non-invasive scoring systems (NSS) are used to identify patients with non-alcoholic fatty liver disease (NAFLD) who are at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extrahepatic complications or death and their concordance in cross-sectional and longitudinal risk stratification remain uncertain.

The Prevalence of NAFLD and Fibrosis in Bariatric Surgery Patients and the Reliability of Noninvasive Diagnostic Methods

Background. Bariatric surgery patients have a higher prevalence of nonalcoholic fatty liver (NAFL) than the general population; however, its assessment and the accurate staging of fibrosis are often complicated because noninvasive tests are not very accurate in patients with morbid obesity, and liver biopsy cannot be performed as a routine exam. The aim of this study was to evaluate (A) the histological prevalence of NAFL, nonalcoholic steatohepatitis (NASH), and fibrosis in patients undergoing bariatric surgery; (B) the reliability of ultrasound (US) in diagnosing NAFL; and (C) the reliability of various fibrosis scoring systems for defining fibrosis. Methods. US and intraoperative liver b…

Comparison of Histochemical Staining Methods and Correlation with Transient Elastography in Acute Hepatitis.

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To compare Masson's trichrome (MT), Sirius red (SR) and orcein staining in acute hepatitis (AH) and to correlate them with&lt;b&gt; &lt;/b&gt;transient elastography (TE),&lt;b&gt; &lt;/b&gt;a noninvasive method to assess hepatic fibrosis. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We evaluated liver stiffness by TE in a cohort of 34 consecutive patients and assessed MT-, SR- and orcein-stained biopsies using the METAVIR scoring system and digital image analysis (DIA). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; MT and SR both showed severe fibrosis (stage III-IV, DIA = 12.7%). Orcein showed absent or mild fibrosis (stage 0-II, DIA = 4.…

BRAFV600E Mutation and p27kip1 Expression in Papillary Carcinomas of the Thyroid ≤1 cm and Their Paired Lymph Node Metastases

BACKGROUND. BRAFV600E mutation and p27kip1 expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas. METHODS. Tissue samples from 214 consecutive patients who underwent total or near-total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) ≤1 cm were analyzed for BRAFV600E mutation by a real-time, allele-specific amplification and for p27kip1 expression by immunohistochemistry. RESULTS. The BRAFV600E mutation was detected in 88 of the tumors examined, with significant differences between groups with and without lymph node (LN) metastases; the mean age of patients with BRAFV600E …

Immunohistochemical/histochemical double staining method in the study of the columnar metaplasia of the oesophagus

Intestinal metaplasia in Barrett’s oesophagus (BO) represents an important risk factor for oesophageal adenocarcinoma. Instead, few and controversial data are reported about the progression risk of columnar-lined oesophagus without intestinal metaplasia (CLO), posing an issue about its clinical management. The aim was to evaluate if some immunophenotypic changes were present in CLO independently of the presence of the goblet cells. We studied a series of oesophageal biopsies from patients with endoscopic finding of columnar metaplasia, by performing some immunohistochemical stainings (CK7, p53, AuroraA) combined with histochemistry (Alcian-blue and Alcian/PAS), with the aim of simultaneousl…

Glucokinase Regulatory Protein Gene Polymorphism Affects Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

BACKGROUND AND AIMS: Variant in glucokinase regulatory protein (GCKR), associated with lipid and glucose traits, has been suggested to affect fatty liver infiltration. We aimed to assess whether GCKR rs780094 C-->T SNP influences the expression of steatosis, lobular inflammation and fibrosis in NAFLD patients, after correction for PNPLA3 genotype. METHODS: In 366 consecutive NAFLD patients (197 from Sicily, and 169 from center/northern Italy), we assessed anthropometric, biochemical and metabolic features; liver biopsy was scored according to Kleiner. PNPLA3 rs738409 C>G and GCKR rs780094 C>T single nucleotide polymorphisms were also assessed. RESULTS: At multivariate logistic regression an…

STAGING OF FIBROSIS BY LIVER STIFFNESS MEASUREMENT IN THALASSEMICS WITH IRON OVERLOAD

LncRNA H19, HOTAIR and MALAT1 as prognostic molecular biomarkers in GIST

Fibrospleen: Measuring spleen stiffness by transient elastography increases accuracy of staging of liver fibrosis and of portal hypertension in chronic viral hepatitis

Collagenous spherulosis and adenoid-cystic carcinoma of the breast: immunohistochemistry and usefulness of CD10 and HHF35 actin

Nodular histiocytic/mesothelial hyperplasia as consequence of chronic mesothelium irritation by sub-phrenic abscess.

Nodular histiocytic/mesothelial hyperplasia (NHMH) is a benign localized alteration, first described in 1975 by Rosai in the hernia sac [1]. Few pulmonary cases have been reported in literature [2–6]. Sometimes it has been reported in the pericardium [7,8] or presenting as an inguinal mass [9]. The ‘mesothelial/monocytic incidental cardiac excrescence’, first described by Weinot et al. in 1994 [10] is now considered a similar lesion to NHMH [11]. It consists of a reactive proliferation of histiocytes and mesothelium secondary to chronic irritation and it has been observed in pleura-damaging processes, such as pneumothorax [5], or as consequence of cardiac catheterization, inflammation, mech…

PNPLA3 rs738409 C&gt;G SNP is associated with histological features of NASH in genotype 1 chronic hepatitis C patients

Current Role of Intraoperative Frozen Section Examination of Sentinel Lymph Node in Early Breast Cancer.

Background/Aim: The aim of this study was to evaluate the current role of frozen section in identifying patients who could benefit from an immediate axillary lymph node dissection (ALND), following the criteria of the ASOCOG Z0011 and IBCSG 23-10 trials. Patients and Methods: A retrospective review was performed involving 2,079 patients with early breast cancer who underwent conservative surgery or total mastectomy with sentinel lymph node biopsy. Results: Sensitivity and diagnostic accuracy were 63.8% and 90.3%, respectively. Sensitivity was significantly higher (p&lt;0.001) in finding macrometastases (81.8%) compared to micrometastases (11.9%). Frozen section was useful only in 7.7% of th…

BRAF mutation influences hypoxia-inducible factor-1α expression levels in papillary thyroid cancer

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 BRAFV600…

Mediastinal syndrome from plasmablastic lymphoma in human immunodeficiency virus and human herpes virus 8 negative patient with polycythemia vera: a case report

Background: Plasmoblastic lymphoma is a rare and aggressive subtype of diffuse large B cell lymphoma, which occurs usually in the jaw of immunocompromised subjects. Case presentation: We describe the occurrence of plasmoblastic lymphoma in the mediastinum and chest wall skin of an human immunodeficiency virus-negative 63-year-old Caucasian man who had had polycytemia vera 7 years before. At admission, the patient showed a superior vena cava syndrome, with persistent dyspnoea, cough, and distension of the jugular veins. Imaging findings showed a 9.7 × 8 × 5.7 cm mediastinal mass. A chest wall neoformation biopsy and ultrasound-guided fine-needle aspiration biopsy of the mediastinal mass allo…

Columnar-Lined Esophagus CK7 Positive is an Early Marker of Gastroesophageal Reflux Disease

LETTER TO EDITOR

DIFFERENT EXPRESSION OF E-CADHERINE, BETA-CATENIN, AND FIBRONECTIN IN SIGNET RING CELL AND INTESTINAL COLORECTAL CARCINOMA.

Expression of Cytokeratin 7 and 20 in Pathological Conditions of the Bile Tract

Expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) helps to establish the origin of biliary and metastatic carcinomas. We investigated the expression of CK7 and CK20 in inflammatory, metaplastic and neoplastic conditions of the bile ducts, and evaluated possible relationships between the CK expression pattern and extrahepatic bile duct/gallbladder carcinomas (EBDCs) or intrahepatic bile duct carcinomas (IBDCs). We used immunohistochemistry for the investigation of 48 formalin-fixed, paraffin-embedded specimens grouped as: A) lithiasic or inflamed surgically resected extrahepatic bile ducts/gallbladders: all were CK7+/CK20+; B) percutaneous liver biopsies from patients with chronic …

Recurrent ossifying fibroma of the maxillary sinus in an adult patient.

In some aspects, the terminology of fibro-osseous lesions of the head remain equivocal. The WHO classification suggested to group cemento-ossifying fibroma and ossifying fibroma under the term "ossifying fibroma". Based on the different age of onset, localization and risk of recurrence, two types have been described: "juvenile ossifying fibroma", with early age of onset, which needs to be treated with wide surgical resection due to the high risk of recurrence; and "adult ossifying fibroma", arising in adult patients, with low recurrence rate, properly treated by conservative surgery. We describe a case of an "adult ossifying fibroma" of a 57-yearold woman with several relapses, for whom con…

Akt-1 a Notch-2 identificano due distinte popolazioni di carcinoma invasivo della mammella

The aetiological pattern of hepatocellular carcinoma ( HCC) in Italy is changing

The aetiological pattern of hepatocellular carcinoma ( HCC) in Italy is changing.

Presence of Serum Antinuclear Antibodies Does Not Impact Long-Term Outcomes in Nonalcoholic Fatty Liver Disease

Introduction We investigated the longitudinal impact of antinuclear antibody (ANA) on clinical outcomes and survival in nonalcoholic fatty liver disease (NAFLD). Methods ANA were found in 16.9% of 923 biopsy-proven NAFLD patients, but none of them had histologic autoimmune hepatitis (AIH) or developed AIH after a mean follow-up of 106±50 months. Results Although ANA-positive cases had a higher prevalence of nonalcoholic steatohepatitis at baseline, the occurrence of liver-related events, hepatocellula carcinoma, cardiovascular events, extrahepatic malignancy, and overall survival were similar to ANA-negative. Discussion Once AIH has been ruled out, the long-term outcomes and survival are un…

Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases.

Abstract Background/Aim Plasma cells infiltrate in the liver is a prototype lesion of autoimmune liver diseases. The possible role of plasma cells isotyping (IgM and IgG) in the liver in the diagnostic definition of autoimmune liver disease, and particularly in variant syndromes such as autoimmune cholangitis and the primary biliary cirrhosis/autoimmune hepatitis overlap syndrome, is less defined. Methods We analysed the clinical, serological and histological features of 83 patients with autoimmune liver disease (40 primary biliary cirrhosis, 20 autoimmune hepatitis, 13 primary sclerosing cholangitis, 4 autoimmune cholangitis and 6 overlap syndrome) compared to 34 patients with chronic hepa…

Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection

Background and aims: Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. Material and methods: One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was def…

Non-invasive assessment of the liver fibrosis by transient elastography (TE) in patients with transfusion-dependent thalassemia

P1030 : The presence of white matter lesions is not associated with non-alcoholic fatty liver disease but with its histological severity

Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis.

The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto’s thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on …

Reliability of liver stiffness measurement in non-alcoholic fatty liver disease: the effects of body mass index

Summary Background  Liver stiffness measurement (LSM) using transient elastography (TE) is used to stage fibrosis in patients with liver disease, diagnostic reliability and the factors affecting its performance in patients with non-alcoholic fatty liver disease (NAFLD) are incompletely understood. Aim  To assess LSM. Methods  Consecutive NAFLD patients (n = 169), assessed by liver biopsy (Kleiner score), anthropometrical, biochemical and metabolic features, underwent LSM using TE with standard M probe. Results  Liver stiffness measurement was not reliable in 23 patients (14%) due to obesity. Among patients with a reliable TE, a LSM value >7.25 kPa was the best cut-off for predicting signifi…

Additional file of Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin

Additional file of Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin