CD44v3 and CD44v6 isoforms on T cells are able to discriminate different disease activity degrees and phenotypes in systemic lupus erythematosus patients.

BACKGROUND: Adhesion molecule CD44 contributes to T cell migration into target organs. A higher expression of CD44v3 and v6 isoforms has been identified on T cells from systemic lupus erythematosus (SLE) patients. The aim of this study was to investigate the expression of CD44v3/v6 on T cells of SLE patients in order to evaluate their correlation with clinical features. METHODS: Sixteen healthy subjects (HSs) and 33 SLE female patients were enrolled. Fifteen patients were in remission (Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) = 0) and 18 patients had an active disease (SLEDAI-2K ≥ 4). Experiments were conducted by flow cytometry. RESULTS: Expression of CD44v3 on CD4+ and CD8+ T cells was higher in active patients compared to HSs ( p = 0.0097 and p = 0.0096). CD44v3 on CD8+ T cells was also higher in active patients compared to patients in remission ( p = 0.038). CD44v6 was higher on CD4+ and CD8+ T cells from active patients compared to HSs ( p = 0.003 and p = 0.0036) and to patients in remission ( p = 0.01 and p = 0.02). In active patients the ratio CD44v3/v6 was unbalanced towards isoform v6 on both T cell populations. In a receiver operating characteristic curve analysis, CD44v6 on CD4+ T cells was the most sensitive and specific one (specificity of 81.8%, sensitivity of 75%). Expression of CD44v6 on CD4+ and CD8+ T cells correlated with the SLEDAI-2K ( p = 0.03, r = 0.38 and p = 0.02, r = 0.39). CD44v6 and CD44v3 on CD8+ T cells associated with nephritis and arthritis ( p = 0.047 and p = 0.023). CONCLUSIONS: CD44v3/v6 can be used as biomarkers of disease activity and phenotypes; isoform v6 on CD4+ T cells can be useful as a diagnostic biomarker.

Rituximab in relapsing and de novo MPO ANCA-associated vasculitis with severe renal involvement: a case series.

BACKGROUND: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a group of diseases associated in most cases with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs). Rituximab- based remission induction has been proven effective in ANCA associated vasculitis but scarce data exist in forms with severe renal involvement. In this case series, we report the outcomes in patients with de novo or recurrent MPO-AAV and severe renal involvement treated with rituximab without cyclophosphamide (CYC). METHODS: In this single centre retrospective study, we analysed patients with a clinical diagnosis of de novo or recurrent AAV who met the following criteria: detection of P-ANCA, creatinine clearance lower than 30 ml/min, induction of remission therapy with rituximab without concomitant CYC and a follow up period of at least 6 months. The primary outcomes were complete remission after induction therapy, renal function recovery and mortality after the induction treatment. RESULTS: Eight patients met the inclusion criteria. The M:F ratio was 1:7, the average age was 54 years old and the median follow up was 10 months (7-72); in 2 patients there was a MPA renal limited vasculitis. A renal biopsy was performed in 7 patients. The median BVAS score at rituximab induction was 14(range 6-21). Two patients required haemodialysis before the induction treatment. Four patients developed end stage renal disease (ESRD) that required haemodialysis. These data show a remission of the disease, associated with a stabilization of the kidney function in 50% of patients. In 3 patients who did not show a response, there was also no response to CYC. CONCLUSIONS: This study shows a partial efficacy of rituximab in renal function recovery and a low risk of infectious complications in patients with MPO vasculitis with severe renal involvement, in particular in the short term. The optimal treatment in this subgroup of patients still has to be established because data are lacking.

Asthma and comorbid medical illness.

Asthma is associated with several comorbidities but the magnitude of the association has not been clearly defined. We aimed to examine the relationship between asthma and comorbidities using information obtained from the Health Search Database (HSD) owned by the Italian College of General Practitioners (Società Italiana Medici Generici, Florence, Italy). We conducted a population-based retrospective study using information obtained from the HSD. The software system used codes of all the diagnostic records using the 9th revision of the International Classification of Diseases. Asthma appeared to be weakly associated with cardiovascular and hypertensive diseases. Intriguingly, the odds ratio of acute or old myocardial infarction was 0.84 (95% CI 0.77-0.91). Asthma was also weakly associated with depression, diabetes mellitus, dyslipidaemia, osteoporosis and rhinosinusitis. In contrast, it was strongly associated with gastro-oesophageal reflux disease (GORD) and, particularly, allergic rhinitis. Age did not influence the association of asthma with comorbidities whereas sex had a different impact according to the specific comorbidity. Our results indicate that asthma is weakly associated with several comorbidities, whereas its association with allergic rhinitis or GORD is stronger.

Evidence of impaired sense of smell in hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is an autosomal-dominant disorder resulting from C1-inhibitor (C1INH) deficiency. Smell impairments were found in patients affected with systemic lupus erythematosus, that, similarly to HAE, is characterized by the activation of the classical complement pathway with C4 consumption. In this study, we aimed at evaluating the sense of smell in patients with HAE. METHODS: Thirty patients with HAE and 30 healthy age- and sex-matched controls were evaluated for olfactory functions using the 3-stages Sniffin'-Sticks kit (threshold, discrimination, and identification [TDI]). TDI scores were analyzed according to complement levels (C1INH, C3, C4 and CH50), Beck depression inventory (BDI-II) and danazol treatment. RESULTS: A significant decrease in olfactory function was observed in patients affected with HAE compared with controls in total TDI score (P < 0.001), and in the discrimination (P < 0.001) and identification scores (P = 0.012). Anosmia was present only in patients with HAE (3.3%) who also exhibited more frequently hyposmia (53.3%vs 3.3%, P < 0.0001). Complement levels were reduced in patients with HAE. C4 serum levels showed positive correlation with total TDI score (P < 0.001), and with discrimination (P = 0.002) and identification (P = 0.011) scores. CH50 complement levels showed positive correlation with total TDI score (P < 0.001), and with threshold (P = 0.002) and discrimination (P = 0.011) scores. Sex, age, danazol treatment, BDI-II scores were not different between the patients and controls and did not influence TDI scores significantly. CONCLUSION: Evidence for an impaired sense of smell was found in patients with HAE. The reduction in olfactory function in these cases seems to correlate with complement C4 and CH50 levels. Immune and genetic mechanisms might play a role in this defect.

Inhibition of the complement system by glutathione: molecular mechanisms and potential therapeutic implications.

Glutathione (GSH), a component of the antioxidant defence system, plays a role in autoimmunity and the complement system is often responsible for tissue damage in autoimmune diseases. The aim of this study is to evaluate the effects of GSH on the complement system. The complement system was examined in the normal human sera (NHS) of 30 healthy subjects. Increasing quantities of GSH (1, 2, 10, 20 mg) were incubated in 1 ml of each NHS. The mixtures were evaluated for complement activities (THC, CPA and APA) and for the presence of cleavage fragments of activation of C3 and B. GSH was also incubated with human complement in the presence of classical and alternative pathway activators. The results showed an inhibitory effect of GSH on the complement system starting from a dosage of GSH≥1 mg/ml. Indeed, when NHS was incubated with GSH at such dosage, a significant reduction of the complement activities THC, CPA, and APA was observed (P<0.0001, P<0.005, P=NS, respectively), and no cleavage fragments of C3 or B were found. Further analysis demonstrated that the inhibition was exerted on C3-9 and to a lower extent on classical and alternative pathway C3-convertases. Our results indicate that GSH is capable of inhibiting the complement system. These findings are relevant for the design of interventions aimed at modulation of GSH metabolism to inhibit complement-mediated damage in autoimmune diseases.

Complement system and rheumatoid arthritis: relationships with autoantibodies, serological, clinical features, and anti-TNF treatment.

Autoantibodies (rheumatoid factor, RF; anti-citrullinated-protein antibodies, ACPA) and complement system are involved in rheumatoid arthritis (RA). ACPA and anti-TNF agents are capable of in vitro modulating complement activity. We investigated the relationships between complement, autoantibodies, and anti-TNF treatment in vivo. One-hundred fourteen RA patients (89F/25M), diagnosed according to 1987 ACR criteria, and 30 healthy controls were enrolled. Serological analysis included ESR, CRP, complement C3, C4 and CH50, RF and ACPA (ELISA, cut-off>20 U/ml). Split-products (SP) of C3 and B were studied by immunoelectrophoresis/counterimmunoelectrophoresis. Seventy-six patients started anti-TNF treatment and were studied at baseline and after 22 weeks. Disease activity was measured with DAS28 and response to therapy with EULAR criteria. At baseline, RA patients showed significantly higher levels of C3 and C4 than controls (C3 127.9±26.5 vs 110±25 mg/dl, P=0.0012; C4 29.7±10.2 vs 22.7±8.3mg/dl, P=0.0003). No differences in C3, C4 and CH50 levels were observed between ACPA+ (n=76) and ACPA- (n=38) patients. After 22 weeks of anti-TNF, C3, C4 and RF were significantly reduced (P<0.003, <0.005 and <0.04, respectively) and RF changes showed negative correlation with CH50. SP of C3 and B were observed neither at baseline nor after 22 weeks. DAS28 significantly improved after 22 weeks. Patients showing higher baseline C3 or lower reduction of C3 levels after 22 weeks had a worse EULAR outcome (X2=22.793, P<0.001). RF levels seem to correlate with complement CH50. The presence of high levels of C3 in RA patients may reflect a pro-inflammatory status and represent a negative prognostic factor for anti-TNF therapy.

Relationships between headache and sleep in a non-clinical population of children and adolescents.

BACKGROUND: Headache and sleep are related in different ways and alterations of chronobiological mechanisms are involved in headache. We investigated the relationships between headache and sleep quality in a large non-clinical population of children and adolescents and evaluated the relationship between headache and circadian typologies. METHODS: A total of 1073 children and adolescents (50.9% males; mean age=10.56; range=8-15 years) were recruited from four schools in Rome. They filled out the questionnaires individually in classrooms, after brief group instruction about answer formats. The questionnaires included (a) a self-report headache questionnaire to collect information on different aspects of headache attacks based on the International Classification of Headache Disorders-2nd edition (ICHD-2); (b) the School Sleep Habits Survey that incorporated questions about sleep habits, the Sleep-Wake Problems Behaviour Scale (SWPBS), the Sleepiness Scale (SLS) and the Morningness/Eveningness Questionnaire (MEQ). RESULTS: According to ICHD-2 criteria, we classified 70 (6.5%) children as Migraine Group (MG), 135 (12.7%) as Non-Migraine Headache Group (NMG), and the remaining 868 (80.8%) were classified as Headache-Free Group (HFG). No clear differences have been found between MG and NMG regarding the frequency of the attacks, although MG showed a significantly increased frequency of long-lasting attacks. The modality of onset of pain and the location of pain was similar in both groups. The most frequent triggering factor for headache in MG and NMG was "a bad sleep" (32.2%) followed by emotional distress (27.8%). No differences have been found between MG, NMG and HFG in sleep schedule or sleep duration. MG and NMG showed significantly higher scores on the SWPBS vs. HFG, while MG presented higher scores on the SLS compared to NMG and HFG. MG presented lower MEQ scores, indicating a more pronounced eveningness. CONCLUSIONS: The relationships between headache and sleep problems are evident even in a non-clinical population of children and adolescents, with MG showing poorer sleep quality, sleepiness and a tendency toward eveningness.

Lymphnode metastasis of thyroid cancer misinterpreted as lateral aberrant thyroid 40 years before identification of primary tumor. Case report and review of the literature.

The differential diagnosis between lateral ectopic thyroid tissue with orthotopic normal gland and metastatic thyroid carcinoma is challenging. Lateral cervical site is a very rare location for ectopic tissue since only a few cases have been reported. The peculiarity of this clinical case is the finding of a thyroid carcinoma forty years after surgical resection of the ectopic thyroid lesion. This asynchronous association, never reported in literature, raises the question of the differential diagnosis between a true ectopic aberrant thyroid and an early lymph node metastasis from an occult thyroid carcinoma, evident in the primitive site many years later. Several elements, which will be matter of discussion, seem to favour the latter hypothesis.This case, although isolated, suggests that any lateral cervical mass, comprising thyroid tissue, should be regarded as a metastasis of thyroid carcinoma until proven otherwise. Carefull investigation of thyroid gland is mandatory.

Microparticles and autophagy: a new frontier in the understanding of atherosclerosis in rheumatoid arthritis.

Microparticles (MPs) are small membrane vesicles released by many cell types under physiological and pathological conditions. In the last years, these particles were considered as inert cell debris, but recently many studies have demonstrated they could have a role in intercellular communication. Increased levels of MPs have been reported in various pathological conditions including infections, malignancies, and autoimmune diseases, such as rheumatoid arthritis (RA). RA is an autoimmune systemic inflammatory disease characterized by chronic synovial inflammation, resulting in cartilage and bone damage with accelerated atherosclerosis increasing mortality. According to the literature data, also MPs could have a role in endothelial dysfunction, contributing to atherosclerosis in RA patients. Moreover many researchers have shown that a dysregulated autophagy seems to be involved in endothelial dysfunction. Autophagy is a reparative process by which cytoplasmic components are sequestered in double-membrane vesicles and degraded on fusion with lysosomal compartments. It has been shown in many works that basal autophagy is essential to proper vascular function. Taking into account these considerations, we hypothesized that in RA patients MPs could contribute to atherosclerosis process by dysregulation of endothelial autophagy process.

Oil Red O Is a Useful Tool to Assess Donor Liver Steatosis on Frozen Sections During Transplantation.

Oil Red O is a useful tool to assess donor liver steatosis on frozen sections during transplantation. Steatosis is a frequent finding in liver evaluation during transplantation, accounting for 9% to 26% of biopsied donor liver. The degree of macrovesicular steatosis is classified as mild, moderate, and severe; the latter is considered an absolute contraindication to liver transplantation because it is associated with poor allograft outcome. Because of the scarcity of organs, there is a debate whether livers with less severe macrovesicular steatosis are still suitable for transplant. Consequently, tools or methods that allow a more accurate intraoperative assessment of steatosis on frozen sections are mandatory. The aim of this study is to improve intraoperative evaluation of steatosis during transplantation using Oil Red O stain on liver biopsies. METHODS: Twenty consecutive liver biopsies of donors were collected during transplantation procedures from September 2017 to February 2018 at the Institute of Pathology of the University and Hospital Trust of Verona, Italy. Each liver biopsy was cut at a different thickness (3, 5, and 8 µm) and stained with both Oil Red O and conventional hematoxylin and eosin for intraoperative consultation. The degree (percentage of hepatocytes involved) of fatty changes was recorded. The results obtained during the intraoperative consultation were finally compared with the formalin-fixed and paraffin-embedded permanent section. RESULTS: Assessment of steatosis on hematoxylin and eosin frozen sections was reported as mild in 17 cases (85%), moderate in 2 cases (10%) and severe in 1 case (5%). Oil Red O frozen sections reported the following results: mild steatosis in 16 cases (80%), moderate in 2 cases (10%), and severe in 2 cases (10%). The percentage of liver steatosis obtained with Oil Red O was consistent in all cases with that of the permanent sections. The staining procedure for Oil Red O required approximately 18 minutes. CONCLUSIONS: Oil Red O special stain is a fast and inexpensive tool to improve the assessment of steatosis on frozen biopsies during liver transplantation.

The impact of thyroidectomy on psychiatric symptoms and quality of life.

INTRODUCTION: Existing trials investigated the impact of medical treatment of thyroid disorders on health-related quality of life (QOL) and psychiatric symptoms. The aim of this prospective study is to analyze the impact of thyroid surgery on QOL and severity of psychiatric symptoms. MATERIALS AND METHODS: Forty-seven patients undergoing thyroid surgery (TS) were assessed before thyroidectomy (T0) and 37 also after surgery, >or=6 months after euthyroidism was achieved (T1). QOL and psychiatric symptoms were evaluated at T0 and T1 using the Medical Outcomes Study Short Form Survey (SF-36) and the Symptom Checklist-90 (SCL-90-R). Scores at T0 were compared with those of patients undergoing surgery for non-thyroidal disease and the SF-36 scores were also compared with the normative Italian sample. Changes in QOL and psychiatric symptoms between T0 and T1 were also examined. RESULTS: Health-related QOL in TS patients before surgery was poorer than in the comparison group on the SF-36 mental component summary measure and social functioning. Mental health improved significantly after surgery but social functioning remained markedly impaired. A significant reduction in the severity of psychiatric symptoms was observed. DISCUSSION: Our results indicate that even long after euthyroidism is achieved after surgery, patients show a significant improvement of mental health and a reduction of psychiatric symptoms. Nevertheless, patients continue to have a poorer QOL compared to the Italian normative sample.

Intractable pruritus in patients with hepatitis C virus.

Intractable pruritus is one of the most common symptoms of chronic liver disease, especially experienced by patients with prolonged cholestasis. It can become the most distressing symptom in patients affected by chronic liver disease, causing a reduction in quality of life, interfering with daily activities, and leading to sleep deprivation or contributing to psychological disturbances up to suicide ideation. Therefore, pruritus that does not respond to medical therapy is an indication for liver transplantation. We treated nine patients with hepatitis C virus affected by intractable pruritus with the molecular adsorbent recirculating system. In each patient, liver function, renal function, and hemodynamic variables were evaluated before and after the treatment. Before undergoing the treatment each patient underwent abdominal ultrasound or computed tomography scan to exclude organic causes for pruritus. We observed a decrease in total bilirubin, creatinine, and bile acids together with a significant improvement in Visual Analog Scale for staging of pruritus in all the patients. Due to the small number of patients the results were not significant.

Autoantibodies in inflammatory arthritis.

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides.

One hundred sixteen cases of acute liver failure treated with MARS.

The various definitions of acute liver failure do not accurately reflect the differences in clinical signs and prognosis. Liver support devices to improve the clinical condition before liver transplantation (LT) were used in 13 patients with primary nonfunction, 24 with fulminant hepatitis, 17 were affected by delayed nonfunction, and 56 of acute on chronic hepatic failure. The average age of these patients was 41.8 years. The average number of applications of molecular absorbing recirculating system (MARS) was about 6 (range: 1-24). The mean length of application was about 9 hours (range: 8-20). MARS treatment was carried out in HLF patients with continuous acute-on-chronic hepatic failure dialisate flow similar to continuous veno venus hemofiltration (CVVH), albumin flow < 20% of hematic flow, heparin 5/10 UI/kg. In acute on chronic hepatic failure (AoCHF) patients, 6- to 11-hour (average 8.5) treatments were performed for a minimum of three treatments. The majority of patients were treated in the intensive care unit (ICU). Laboratory results were also monitored and showed progressive modification: bilirubin (before treatment 22.37 +/- 11.6 mg/dL, after treatment 11.36 +/- 7.5 mg/dL) and ammonium (before treatment 238.2 +/- 19 microg/dL, after treatment 115.4 +/- 12 microg/dL) showed significant change (P < .01). Lactates (before treatment 3.48 +/- 1.3 mmol/L, after treatment 1.76 +/- 1.1 mmol/L) and creatinine (before treatment 2.36 +/- 0.18 mg/dL, after treatment 1.26 +/- 0.67 mg/dL) also showed significant changes (P < .02 and P < .04). Glasgow Coma Score (GCS) went from 8.6 +/- 1.4 to 11.9 +/- 3.9 (P < .05). The mean middle cerebral artery flow (V media) went from 46 cm/s/26-59) to 73 cm/s (52-106) representing decreased cerebral edema, a difference that was not significant. INR scores (before treatment 2.4 after treatment 1.8) also showed no significant change. The MARS can be applied with tolerability for long periods for patients with PDF and FH as a bridge to transplant. In patients with PDF, it is used for a waiting recovery of the transplanted organ. Therefore MARS can also limit the necessity to perform further transplants.

Molecular adsorbent recirculating system treatment for acute hepatic failure in patients with hepatitis B undergoing chemotherapy for non-Hodgkin's lymphoma.

Hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface (HBsAg) antigen-positive patients treated with chemotherapy. Because the hepatitis is related to HBV virological reactivation, application of effective antiviral therapy, such as Lamivudine, has been attempted. Despite the use of these antiviral agents at the time of clinical hepatitis, some HBsAg-positive patients still develop hepatic failure and die. We used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock, Germany) to treat 5 HBsAg-positive lymphoma patients with acute hepatic failure due to chemotherapy despite lamivudine treatment. Before and after each treatment we monitored the parameters of neurological status (EEG, cerebral CT and Glasgow coma score), hemodynamic parameters, acid-base equilibrium and blood gases as well as hepatic and renal function. The inclusion criteria were these of the King's College Hospital. Statistical analysis by Student t method showed significant results (P < .01). Three of 5 patients are alive without signs of reactivation of viral or hematological diseases at 1 year follow-up. The 2 patients died because MARS treatment was started too late, with Glascow coma score grade IV, hemodynamic instability, and mechanical ventilator assistance. Despite the limited number of cases, we believe that MARS can be applied to patients with a high tolerance and yield good results, but the treatment has to start at the first signs of hepatic failure.

Post-procedure bleeding in interventional radiology.

Following interventional radiology procedures, bleeding can occur in 0.5 to 4% of the cases. Risk factors are related to the patient, to the procedure, and to the end organ. Bleeding is treated usually by interventional radiologists and consists mainly of embolization. Bleeding complications are preventable: before the procedure by checking hemostasis, during the procedure by ensuring the accurate puncture site (with ultrasound or fluoroscopy guidance) or by treating the puncture path using gelatin sponge, curaspon(®), biological glue or thermocoagulation, and after the procedure by carefully monitoring the patients.

Ruptured visceral artery aneurysms.

Visceral artery aneurysms are rare but their estimated mortality due to rupture ranges between 25 and 70%. Treatment of visceral artery aneurysm rupture is usually managed by interventional radiology. Specific embolization techniques depend on the location, affected organ, locoregional arterial anatomy, and interventional radiologist skill. The success rate following treatment by interventional radiology is greater than 90%. The main complication is recanalization of the aneurysm, showing the importance of post-therapeutic monitoring, which should preferably be performed using MR imaging.

Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma.

The distinction between pleural epithelial mesothelioma and peripheral lung adenocarcinoma involving the pleura is still an important diagnostic problem for surgical pathologists. The aim of our study was to identify the most specific and sensitive markers for the positive identification of mesothelioma to select a limited, appropriate panel of antibodies to differentiate between mesothelioma and adenocarcinoma. Forty-two cases of epithelial mesotheliomas and 23 cases of pulmonary adenocarcinomas were stained with the following antibodies: anticalretinin, antithrombomodulin, anti-CD44H, and monoclonal antibody HBME-1. We also studied the value of other markers in current use: cytokeratins AE1/AE3 and CAM5.2, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Ber-EP4, B72.3, and CD15. Of the mesotheliomas, 42 stained for calretinin, 39 (92.8%) for thrombomodulin, 42 stained for CD44H, and 41 (97.6%) stained for HBME-1. Among negative markers, 4 (9.5%) mesothelioma cases stained for CEA, 5 (11.9%) stained for Ber-EP4, 6 (14.2%) stained for B72.3, and 2 (4.7%) stained for CD15. Of the lung adenocarcinomas, 2 (8.7%) cases showed reactivity for calretinin, 5 (21.7%) for thrombomodulin, 13 (56.5%) for CD44H, all for HBME-1, 22 (95.6%) for CEA, 22 (95.6%) for Ber-EP4, 8 (34.7%) for B72.3, and all for CD15. In conclusion, calretinin and thrombomodulin were the most specific positive mesothelial markers, whereas CD44H and HBME-1 showed high sensitivity but very low specificity. Among negative markers, we advocate the use of CEA and CD15 which were the most specific in differentiating mesotheliomas from adenocarcinomas.

Microvessel density and clinicopathological characteristics in hepatitis C virus and hepatitis B virus related hepatocellular carcinoma.

AIMS: To compare intratumorous microvessel density (MVD) and clinicopathological features in two different groups of hepatocellular carcinoma (HCC), namely: hepatitis B virus (HBV) related HCC (B-HCC) and HCV related HCC (C-HCC). METHODS: Fifty consecutive cases each of B-HCC and of C-HCC were studied. Microvessel numbers were assessed by staining for the antigen CD34; in each case, three areas with the highest numbers of microvessels were counted in both the intratumorous and the surrounding non-tumorous tissue; the mean value represented the final MVD. RESULTS: Patients with B-HCC were significantly younger than those with C-HCC (mean age, 60.1 (SD, 4.1) v 66.4 (4.3) years); no significant differences were seen for sex or Child's class distribution. The tumour diameter was larger in B-HCCs than in C-HCCs (mean, 5.6 (SD, 1.8) v 3.8 (1.8) cm). Tumour microsatellite formation was significantly higher in C-HCCs (12 v 4 cases). No differences were found for histological subtype, degree of differentiation, tumour encapsulation, and vascular invasion. The mean MVD value was significantly higher in tumorous (mean, 54 (SD, 13.8) v 38 (8.9)) and in the surrounding non-tumorous liver tissue (mean, 15 (SD, 4.3) v 7 (3.1)) of C-HCCs. CONCLUSIONS: C-HCCs present as smaller tumours in older patients, with a higher incidence of tumour microsatellite formation and higher MVD values both in the tumorous and the non-tumorous areas, suggesting a link between HCV infection, angiogenesis, and hepatocarcinogenesis.