Temporal evolution of quality of life in patients endoscopically treated for sinonasal malignant tumors.

BACKGROUND: The aim of our study is to assess which factors may affect the quality of life (QoL) and its fluctuation over time in adult patients who received endonasal endoscopic oncologic sinus surgery (EOSS) for sinonasal malignancies (SNM) in our center. METHODOLOGY: We analyzed EOSS cases for primary SNM from January 2015 to June 2020. For each patient, we have recorded the age at treatment, gender, smoking habits, use of psychotropic drugs for mood disorders, stage, histotype, type of surgical resection, need for skull-base reconstruction, development of postoperative major complications, and the use of adjuvant intensity-modulated radiotherapy (IMRT). We evaluated the patient's performance status pre-treatment using the ECOG scale. Quality of life was measured using three questionnaires (SNOT-22; ASK-9; EORTC QLQ-C30 version 3). RESULTS: Fifty-five patients were enrolled in our study, of whom thirty-two (58.18%) received adjuvant IMRT. Overall, a significant improvement in all QoL outcomes was observed at eighteen months, while, female sex, higher ECOG scores, advanced stage of disease, and adjuvant IMRT were associated with worse QoL. After 18 months the delta in QoL between women and men worsened (in SNOT-22 and EORTC QLQ-GLOBAL) while if only the most fragile patients according to ECOG are considered, this difference was reduced for both tools. CONCLUSION: Our analysis revealed that IMRT is the element that has the greatest impact on patient's quality of life, in association with the female sex, ECOG >2, and advanced stage of the disease.

Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group.

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

The role of Narrow Band Imaging (NBI) in the diagnosis of sinonasal diseases.

BACKGROUND: Narrow band imaging (NBI) endoscopy is an optical method that helps to characterise tissue vasculature. Its appli- cation in sinonasal pathology remains scarce and a systematic study of its application to rhinology is lacking. The aim of this study is to analyse and describe the normal sinonasal mucosa under NBI light and to characterise the microvascular features of various sinonasal pathologies. We also want to suggest a classification of the patterns, peculiar to this district, and to evaluate whether they can be indicative of a specific physiological or pathological condition. METHODS: Digital videos and images under white light and NBI of 103 patients (82 evaluated) with 29 sinonasal pathologies and 55 controls (33 evaluated). were independently analysed by three otolaryngologists and the final pattern was then arranged for each image, reaching an agreement between the individual evaluations. RESULTS: Once the appearance of normal sinonasal (SN) mucosa was established (SN1), four patterns for the pathological mucosa were described and a working classification was proposed (SN2, SN3, SN4, SN5). We calculated specificity (80.6% vs 90.6%), sensi- tivity (20% vs 38.5%), PPV (46.1% vs 50%), NPV (54.7% vs 85.7%) and accuracy (53% vs 80.3%) of the ability of SN4 and SN5 pattern to discriminate between benign and malignant nasal neoformations. CONCLUSIONS: This is the first study to propose a systematic NBI description and a classification of the vasculature of healthy and pathological mucosa in the sinonasal tract. Our preliminary results show that this technique can help in the workup of several rhinologic conditions and especially in distinguishing benign from malignant tumors.

Evaluation of radon exposure risk and lung cancer incidence/mortality in South-eastern Italy.

INTRODUCTION: Radon and its decay products may cause substantial health damage after long-term exposure. The aim of the study was to perform a spatial analysis of radon concentration in the Salento peninsula, province of Lecce (South-eastern Italy) in order to better characterize possible risk for human health, with specific focus on lung cancer. METHODS: Based on previous radon monitoring campaigns carried out in 2006 on behalf of the Local Health Authority (ASL Lecce) involving 419 schools and through the application of kriging estimation method, a radon risk map was obtained for the province of Lecce, in order to determine if areas with higher radon concentrations were overlapping with those characterized by the highest pulmonary cancer incidence and mortality rates. RESULTS: According to our data, areas at higher radon concentrations seem to overlap with those characterized by the highest pulmonary cancer mortality and incidence rates, thus indicating that human exposure to radon could possibly enhance other individual or environmental pro-carcinogenic risk factors (i.e. cigarette smoking, air pollution and other exposures). CONCLUSIONS: The radon risk should be further assessed in the evaluation of the causes resulting in higher mortality and incidence rates for pulmonary cancer in Salento area vs Italian average national data. For these reasons, ASL Lecce in cooperation with ARPA Puglia and CNR-IFC has included the monitoring of individual indoor radon concentrations in the protocol of PROTOS case-control Study, aimed at investigating the role of different personal and environmental risk factors for lung cancer in Salento.

Hepatic fibrinogen storage disease: identification of two novel mutations (p.Asp316Asn, fibrinogen Pisa and p.Gly366Ser, fibrinogen Beograd) impacting on the fibrinogen γ-module.

BACKGROUND: Quantitative fibrinogen deficiencies (hypofibrinogenemia and afibrinogenemia) are rare congenital disorders characterized by low/unmeasurable plasma fibrinogen antigen levels. Their genetic basis is invariably represented by mutations within the fibrinogen genes (FGA, FGB and FGG coding for the Aα, Bß and γ chains). Currently, only four mutations (p.Gly284Arg, p.Arg375Trp, delGVYYQ 346-350, p.Thr314Pro), all affecting the fibrinogen γ chain, have been reported to cause fibrinogen storage disease (FSD), a disorder characterized by protein aggregation, endoplasmic reticulum retention and hypofibrinogenemia. OBJECTIVES: To investigate the genetic basis of FSD in two hypofibrinogenemic patients. METHODS: The mutational screening of the fibrinogen genes was performed by direct DNA sequencing. The impact of identified mutations on fibrinogen structure was investigated by in-silico molecular modeling. Liver histology was evaluated by light microscopy, electron microscopy and immunocytochemistry. RESULTS: Here, we describe two hypofibrinogenemic children with persistent abnormal liver function parameters. Direct sequencing of the coding portion of fibrinogen genes disclosed two novel FGG missense variants (p.Asp316Asn, fibrinogen Pisa; p.Gly366Ser, fibrinogen Beograd), both present in the heterozygous state and affecting residues located in the fibrinogen C-terminal γ-module. Liver sections derived from biopsies of the two patients were examined by immunocytochemical analyses, revealing hepatocyte cytoplasmic inclusions immunoreactive to anti-fibrinogen antibodies. CONCLUSIONS: Our work strongly confirms the clustering of mutations causing FSD in the fibrinogen γ chain between residues 284 and 375. Based on an in-depth structural analysis of all FSD-causing mutations and on their resemblance to mutations leading to serpinopathies, we also comment on a possible mechanism explaining fibrinogen polymerization within hepatocytes.

Correlation between Skp2 expression and nodal metastasis in stage I and II oral squamous cell carcinomas.

PURPOSE: The aim of this study was to investigate the role of S-phase kinase associated protein (Skp2) in the development of nodal metastasis and to assess its influence on prognosis in stage I and II oral squamous cell carcinomas (OSCCs). EXPERIMENTAL DESIGN: Seventy-one patients affected by OSCC (stage I-II) were observed in the period ranging from March 2003 to December 2006. The research was performed using immunohistochemical and histopathological analysis. RESULTS: The overall survival rate was 89.6% at 3 years, 87% at 5 years and 80.7% at 10 years. Patients with vascular or perineural invasion showed no statistically significant survival difference when compared with the ones with no invasion. The tumour depth of invasion did not prove to be related to the metastatic potential. Nine of the seventeen patients with Skp2 positive nuclei (≥20%) developed nodal metastasis. Conversely, only 6 of the 54 patients with a nuclear positivity lower than 20% developed a laterocervical metastasis (P=0.001). When comparing survival curves of Skp≥20% and Skp2<20% OSCCs, no significant P value emerged from the statistical analysis. CONCLUSIONS: This study is the first to report an important correlation between an Skp2 expression lower than 20% and the capability of the tumour not to develop nodal laterocervical metastases (P=0.001).

Autoimmune diseases of the liver and biliary tract and overlap syndromes in childhood.

Autoimmune liver diseases in childhood includes Autoimmune Hepatitis (AIH) and Primary (Autoimmune) Sclerosing Cholangitis (P(A)SC). Both diseases are characterized by a chronic, immune-mediated liver inflammation involving mainly hepatocytes in AIH and bile ducts in PSC. Both diseases, if untreated, lead to liver cirrhosis. AIH could be classified, according to the autoantibodies pattern, into two subtypes: AIH type 1 presents at any age as a chronic liver disease with recurrent flares occasionally leading to liver cirrhosis and liver failure. Characterizing autoantibodies are anti-nuclear (ANA) and anti-smooth muscle (SMA), usually at high titer (>1:100). These autoantibodies are not specific and probably do not play a pathogenic role. AIH type 2 shows a peak of incidence in younger children, however with a fluctuating course. The onset is often as an acute liver failure. Anti-liver kidney microsome autoantibodies type 1 (LKM1) and/or anti-liver cytosol autoantibody (LC1) are typically found in AIH type 2 and these autoantibodies are accounted to have a potential pathogenic role. Diagnosis of AIH is supported by the histological finding of interface hepatitis with massive portal infiltration of mononuclear cells and plasmocytes. Inflammatory bile duct lesions are not unusual and may suggest features of ''overlap'' with P(A)SC. A diagnostic scoring system has been developed mainly for scientific purposes, but his diagnostic role in pediatric age is debated. Conventional treatment with steroids and azathioprine is the milestone of therapy and it is proved effective. Treatment withdrawal however should be attempted only after several years. Cyclosporin A is the alternative drug currently used for AIH and it is effective as steroids. P(A)SC exhibit a peak of incidence in the older child, typically in pre-pubertal age with a slight predominance of male gender. Small bile ducts are always concerned and the histological picture shows either acute cholangitis (bile duct infiltration and destruction) and/or lesions suggesting chronic cholangitis as well (bile duct paucity and/or proliferation, periductal sclerosis). Small bile ducts damage may be associated, at onset or in the following years, with lesions of larger bile ducts with duct wall irregularities, strictures, dilations, and beading resulting in the characteristic ''bead-on-a-string'' appearance. The ''small duct'' (autoimmune) sclerosing cholangitis is also called autoimmune cholangitis. PSC is strictly associated to a particular form of inflammatory bowel disease (IBD) which shows features not typical of ulcerative colitis neither of Crohn's disease. Symptoms related to IBD often are present at onset (abdominal pain, weight loss, bloody stools) but the liver disease is frequently asymptomatic and it may be discovered fortuitously. Treatment of PSC is particularly challenging. In case of ''small duct'' SC or in case of evidence active inflammation on liver biopsy, immunosuppressive treatment is probably useful while in case of large bile ducts non inflammatory sclerosis, immunosuppression is probably uneffective. Ursodeoxycholic acid, however, may leads to an improvement of liver biochemistry even if there's no evidence that it may alter the course of disease. Thus, liver transplantation, is often necessary in the long term follow-up, even with a risk of disease recurrence. In adjunction to these two main disorders, many patients show an''overlap'' disease with features of both AIH and PSC. In such disorders the immune-mediated damage concerns both the hepatocyte and the cholangiocyte with a continuous clinical spectrum from AIH with minimal bile ducts lesions and PSC with portal inflammation and active inflammatory liver damage.

Hepatitis C virus (HCV) genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome.

BACKGROUND AND AIMS: Little is known of hepatitis C virus (HCV) genotypes in HCV infected children. This retrospective, multicentre study investigated genotype distribution and correlation with clinical features and outcome in a large series of Italian children. METHODS: Between 1990 and 2002, 373 HCV RNA positive children, consecutively recruited in 15 centres, were assayed for genotypes by a commercial line probe assay. RESULTS: The following genotype distribution pattern was recorded: genotype 1b = 41%; 1a = 20%; 2 = 17%; 3 = 14.5%; 4 = 5%; other = 2.5%. The prevalence of genotypes 1b and 2 decreased significantly (p<0.001) among children born from 1990 onwards compared with older children (46% v 70%) while the rate of genotypes 3 and 4 increased significantly (from 8% to 30%). Children infected with genotype 3 had the highest alanine aminotransferase levels and the highest rate of spontaneous viraemia clearance within the first three years of life (32% v 3% in children with genotype 1; p<0.001). Of 96 children enrolled in interferon trials during the survey, 22% definitely lost HCV RNA, including 57% of those with genotypes 2 and 3. CONCLUSION: HCV genotypes 1 and 2 are still prevalent among infected adolescents and young adults in Italy but rates of infection with genotypes 3 and 4 are rapidly increasing among children. These changes could modify the clinical pattern of hepatitis C in forthcoming years as children infected with genotype 3 have the best chance of spontaneous viraemia clearance early in life, and respond to interferon in a high proportion of cases.

Enterocyte actin autoantibody detection: a new diagnostic tool in celiac disease diagnosis: results of a multicenter study.

OBJECTIVES: This study describes a new method to detect autoantibodies against actin filaments (AAA) as a serological marker of intestinal villous atrophy (IVA) in celiac disease (CD), and reports the results of an Italian double-blind multicenter study. METHODS: IgA-AAA were analyzed by immunofluorescence using a newly developed method based on intestinal epithelial cells cultured in presence of colchicine. IgA-AAA were blindly evaluated prospectively in 223 antiendomysial antibody (AEA) and/or antitransglutaminase antibody (TGA) positive subjects and in 78 AEA and TGA negative subjects. IgA-AAA positive patients underwent an intestinal biopsy to confirm the diagnosis. Moreover, IgA-AAA were retrospectively investigated in 84 biopsy-proven CD patients and in 2,000 new consecutively collected serum samples from AEA and TGA negative nonbiopsied subjects. RESULTS: IgA-AAA were positive in 98.2% of the CD patients with flat mucosa, in 89% with subtotal villous atrophy, and in 30% with partial villous atrophy. IgA-AAA were present in none of the AEA and TGA negative nonbiopsied controls. In AEA and/or TGA positive CD patients IgA-AAA positivity significantly correlated with IVA (p < 0.000 in the prospective study, p = 0.005 in the retrospective study). In the prospective study, the values of sensitivity, specificity, the positive predictive value, the negative predictive value, and the efficiency of the IgA-AAA test to identify patients with IVA were, respectively, 83.9%, 95.1%, 97.8%, 69.2%, and 87.0%. Furthermore, a significant correlation (p < 0.0001) was found between the IgA-AAA serum titre and the degree of IVA (rs 0.56). CONCLUSIONS: The results of this multicenter study show that the new method for IgA-AAA detection could represent a practical diagnostic tool in AEA and/or TGA positive subjects, which would be especially useful when IVA shows a patchy distribution, when the histological picture is difficult to interpret, or when a biopsy could represent a life-threatening risk.

Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents.

BACKGROUND: Conventional treatment for autoimmune hepatitis results in a significant percentage of failures and several, poorly tolerated, side-effects. Therapy for autoimmune cholangitis and giant cell hepatitis associated with autoimmune haemolysis is poorly documented. Ciclosporin is a promising treatment for all of these diseases. METHODS: We reviewed the records of 12 patients treated in our unit between 1987 and 2001. Eight had autoimmune hepatitis, two had autoimmune cholangitis and two had giant cell hepatitis. Indications for ciclosporin were treatment failure (four patients) and contraindications to/refusal of steroids (eight patients). Ciclosporin was administered in five untreated cases and in seven patients during relapse. The mean duration of ciclosporin administration was 35.6 months (8-89 months). The median follow-up was 6.5 years (1.5-15 years). RESULTS: All patients achieved complete remission in a median period of 4.5 weeks (2-12 weeks). No treatment withdrawal due to side-effects occurred. Three patients required a combination of ciclosporin with conventional treatment due to severe liver function impairment. Tolerance to ciclosporin was excellent. A 20% transient elevation of serum creatinine occurred in one case, gingival hypertrophy in two and moderate hypertrichosis in two. CONCLUSIONS: Ciclosporin may be considered as a safe treatment for all autoimmune liver diseases and as an effective alternative for front-line therapy.

Guidelines for the screening and follow-up of infants born to anti-HCV positive mothers.

Hepatitis C virus infection in infancy largely depends on vertical transmission. The transfer of hepatitis C virus from mother to child is almost invariably restricted to children whose mother is viremic, and the rate of transmission seems to be influenced by maternal virus load, although, in the single patient, the levels of viremia cannot be used as predictors of pediatric infection. In fact, the flow-chart for screening children at risk for vertically transmitted hepatitis C virus infection takes into account maternal viremia. In children born to anti-hepatitis C virus antibody positive, hepatitis C virus-RNA negative mothers, alanine aminotransferase and anti-hepatitis C virus should be investigated at 18-24 months of life. If alanine aminotransferase values are normal and anti-hepatitis C virus is undetectable, follow-up should be interrupted. In children born to hepatitis C virus-RNA positive mothers, alanine aminotransferase and hepatitis C virus RNA should be investigated at 3 months of age: (1) hepatitis C virus-RNA positive children should be considered infected if viremia is confirmed by a second assay performed within the 12th month; (2) hepatitis C virus-RNA negative children with abnormal alanine aminotransferase should be tested again for viremia at 6-12 months, and for anti-hepatitis C virus at 18 months; (3) hepatitis C virus-RNA negative children with normal alanine aminotransferase should be tested for anti-hepatitis C virus and alanine aminotransferase at 18-24 months, and should be considered non-infected if alanine aminotransferase is normal and anti-hepatitis C virus undetectable; (4) anti-hepatitis C virus seropositivity beyond the 18th month in a never-viremic child with normal alanine aminotransferase is likely consistent with past hepatitis C virus infection.

Antigranulocyte monoclonal antibody immunoscintigraphy in inflammatory bowel disease in children and young adolescents.

AIM: Diagnostic delay for inflammatory bowel disease (IBD) is frequent, especially in paediatric patients. Scintigraphy with labelled leucocytes has been proposed as a very sensitive diagnostic tool for detecting bowel inflammation. The aim of this study was to evaluate the sensitivity and specificity of immunoscintigraphy in the diagnosis and follow-up of children with IBD and to compare this technique with other diagnostic techniques. METHODS: Sixty-six children with histologically confirmed IBD were enrolled in the study. Twenty-one children in whom IBD was suspected but subsequently not confirmed were used as controls. A total of 138 immunoscintigraphies were performed using 99mTechnetium-labelled monoclonal anti-granulocyte antibodies. Immunoscintigraphy was also compared with other diagnostic techniques. RESULTS: Overall sensitivity of monoclonal antibody immunoscintigraphy (MoAb-IS) in patients with clinically active disease was 94% for Crohn's disease (CD) and 85% for ulcerative colitis (UC). Ultrasonography, endoscopy and radiology were carried out at the same time in 29 patients with CD and in 6 patients with UC: sensitivity of IS was 90% compared with 76% of colonoscopy, 75% for enemas, and 55% for sonography. IS was negative (specificity) in 24% of patients with CD and in 67% of patients with UC during remission, and in 64% of controls with other causes of intestinal inflammation. Diagnostic delay was significantly shorter when compared with a historical cohort of patients. CONCLUSION: Immunoscintigraphy is a highly sensitive detector of intestinal inflammation in young patients with IBD and can be useful for reducing diagnostic delay. However, its specificity is low and all positive cases must be confirmed histologically.

Cholestasis as a presenting feature of acute Epstein-Barr virus infection.

Biochemical evidence of hepatic involvement in Epstein-Barr virus disease is common but clinical features of cholestasis are rare in children. We present three children with cholestasis as a presenting feature of Epstein-Barr virus disease.

An epidemiological survey of hepatitis C virus infection in Italian children in the decade 1990-1999.

BACKGROUND: A retrospective-prospective survey of Italian children with hepatitis C virus (HCV) infection was planned in 1998 to explore the epidemiologic features of infection during the past decade. METHODS: Anti-HCV-positive patients (or HCV RNA-positive infants) aged 1 month to 16 years, consecutively observed in 20 pediatric Institutions, were considered. An anonymous epidemiologic questionnaire based on clinical records was used. RESULTS: From 1990 through March 1999, 606 patients were observed (296 boys, average age 5.8 years). Maternal infection (46% of cases) and blood transfusions (34%) were the most frequent risk factors. Of 279 infected mothers, 61% did not recall a putative source of infection (by history, many could possibly have had exposure through routes such as therapeutic injections with nondisposable material), whereas 94 (34%) admitted drug abuse, including 49 (17%) coinfected with human immunodeficiency virus (HIV). Only 157 (26%) children were born after 1991: 90% of their mothers were infected (11% were HIV coinfected vs. 25% mothers of older children, P < 0.01). CONCLUSIONS: Maternal infection is a prominent source of pediatric HCV infection in Italy. The fact that most mothers had a history of covert exposure to HCV, probably through percutaneous routes that are no longer operating, and that the number of those with HIV coinfection has decreased suggests that the frequency of pediatric infection could decrease in the future.

Bartonella henselae and inflammatory bowel disease.

Sustained fever and increased thickness of the distal ileum on ultrasound suggested Crohn's disease in an adolescent boy. Bartonella henselae infection was diagnosed by specific serology and the patient recovered. Ileitis could be related to B. henselae infection.