Background: Purpose: The purpose of our study is to demonstrate that intensified neoadjuvant chemo-radiotherapy (CRT) treatment in locally advanced rectal cancer (LARC), aimed at further enhancing the complete pathological response and local disease control, is feasible and well tolerated. Materials and methods: From January 2011 to December 2015, 62 patients (women 21, men 41, mean age 61,5, range 36-84) with LARC (cT2-3 cNO-2) were enrolled in our institution. All patients performed an intensified neo-adjuvant CRT treatment according to the following scheme: FOLFOX4 induction chemotherapy for 3 cycles, followed by a concomitant radio-chemotherapy, with concomitant boost pelvic radiotherapy to a total dose to the primary of 54 Gy and daily continuous infusion of 5-Fluorouracil. After 6-8 weeks pts were re-evaluated by means of colonoscopy, body TC and pelvic MRI. Results: Intensified CRT compliance was 90%. Grade I-II proctitis according to CTCAE v4.0 was 43%, grade III diarrhea was 10%, grade I-II genito-urinary toxicity was 29%. Eleven patients (19%) had a complete pathological response (pCR), 37 patients had a partial response. Sixty patients received surgery, two refused it: sphincter-saving procedure was performed in 85% of patients, Miles' surgery in 15% of them. Fifty-nine patients are alive, after a median follow-up time of 43 months. Six patients experienced a distant metastatic disease, and two patients a local relapse. Conclusion: This study has shown that the intensification of preoperative systemic therapy, together with intensification of radiotherapy, was feasible, well tolerated and has obtained high rates of local disease control (96,5%), with 19% of pCR rate.

There is strong evidence that the determination of autoantibodies against filaggrine is a very useful tool for the diagnosis of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide antibodies (Anti-CCP)-ELISA appear to be the most efficient test among those available for the detection of antifilaggrine autoantibodies, as it has the best diagnostic accuracy for the diagnosis of RA. Furthermore, the anti-CCP-ELISA determination in early arthritis is a good predictor of disease persistence and radiographic joint damage. The positivity of Anti-CCP some years before the onset of the RA and the high concentration of autoantibodies in synovial fluid suggest a possible pathogenetic role of citrullination. However, at present, it is unclear whether anti-CCP antibodies have a better diagnostic performance than rheumatoid factor in recent onset synovitis and if they confer any additional value to the prognostic evaluation obtained with validated predictors of outcome (FR, joint count, duration of disease).

Décrire les signes cliniques et radiologiques observés à la main dans la sclérodermie. Nous avons réalisé une étude descriptive transversale chez 41 Sardes souffrant de sclérodermie (32 femmes et neuf hommes ; médiane de 58,9 ans avec des extrêmes de 31 et 81 ans), depuis 11,8 ans en moyenne (extrêmes, 1–36 ans). La maladie était diffuse chez 26 malades et limitée chez 15 malades. Une radiographie des mains a été réalisée chez chaque malade. Les radiographies ont été interprétées de façon indépendante par deux radiologues tenus dans l’ignorance du diagnostic. Les radiologues ont classé les radiographies en quatre catégories : aspect normal ou subnormal, arthrose, arthrite inflammatoire et anomalies périarticulaires. Nous avons ensuite recherché des corrélations entre les catégories radiographiques et les signes cliniques et sérologiques. Malgré l’absence de groupe témoin et le caractère transversal de l’étude, les résultats confirment la fréquence des anomalies ostéoarticulaires à la main dans la sclérodermie : des signes cliniques ont été mis en évidence chez 30 (73 %) malades et des signes radiographiques chez 33 (80 %) malades. Les anomalies périarticulaires (résorption de la phalangette, calcifications des parties molles et/ou flessum) prédominaient (14/41, 34,1 %). Le flessum des doigts et la résorption osseuse étaient corrélés à la présence d’une pneumopathie interstitielle, à une réduction de la capacité vitale forcée, à une atteinte œsophagienne et au traitement par la prostacycline. La calcinose (29,2 % des malades) était liée à la présence d’érosions, suggérant un lien pathogénique. Un aspect radiologique inflammatoire s’est avéré fréquent (8/41, 19,5 %). Toutefois, les érosions, situées ailleurs qu’aux interphalangiennes distales, ont été observées principalement chez les malades qui présentaient un tableau frontière polyarthrite rhumatoïde-sclérodermie. La calcinose était plus fréquente en cas de sclérodermie limitée, mais il n’y avait pas entre les deux groupes d’autres différences dans la prévalence des anomalies radiologiques.

Objective: To assess the clinical and radiographic features of hand involvement in patients with systemic sclerosis (SSc).Methods: Forty-one unselected Sardinian SSc patients (32 women, 9 men; mean age 58.9, range 31-81 years; mean disease duration 11.8 years, range 1-36 years) were evaluated in this observational cross-sectional study. Twenty-six patients had diffuse scleroderma (ISSc) and 15 limited scleroderma (ISSc). Radiological examination of the hands was performed and the films were read by two independent rheumatologists blinded to the diagnosis using a classification system of four predefined radiological patterns (normal/minimal changes, articular degenerative, articular inflammatory and periarticular pattern). Correlations between radiological pattern, clinical and serological features were assessed.Results: The skeletal and articular involvement of the hand was frequent in SSc, being clinically evident in 30/41 (73%) and radiologically in 33/ 41 (80%) of patients. The periarticular pattern (defined as the occurrence of bone resorption of ungueal tufts, soft tissue calcifications and/or flexion deformities) was the most frequent pattern detected (14/41, 34.1%) and finger flexion contractures and bone resorptions were significantly associated with interstitial lung disease, reduced FVC, oesophagus involvement and prostacycline therapy. Calcinosis (29.2%) was found to be associated with erosions, suggesting a pathogenic link. An inflammatory pattern was also radiologically frequent (8/41, 19.5%), but erosions, with the exception of those localized at distal interphalangeal joints, were demonstrated mainly in patients with clinical picture of rheumatoid arthritis overlapped with SSc. We found no significant differences in terms of radiographic findings between ISSc and dSSc with the exception of calcinosis, which was more frequent in patients with ISSc.Conclusion: This cross-sectional study confirms that the skeletal and articular involvement of the hand is frequent in SSc. (c) 2008 Elsevier Masson SAS. All rights reserved.

Background. Helicobacter pylori is a microorganism able to stimulate a robust inflammatory and systemic immune response.Aim. The aim of our study was to evaluate autoimmune markers in dyspeptic patients positive for H. pylori infection compared to a control group of non-H. pylori-infected subjects. The kinetics of cryoglobulins and autoantibodies was evaluated after treatment of the infection.Patients and methods. Dyspeptic patients with active H. pylori infection and age- and sex-matched healthy H. pylori-negative controls were studied. Markers of immunity were compared, in H. pylori-infected patients before, 6 months and 1 year after the end of therapy. Results were also compared between those with and without successful eradication therapy.Results. Eighty-six individual were entered (43 H. pylori-infected). H. pylori-infected patients had higher levels of IgG and/or IgA and/or IgM (22/43 versus 2/43). Circulating immune complexes and cryoglobulins were detected in patients more often than controls (p <.05 for both). Autoantibodies were observed in 13 patients (30% versus 5% in controls) and antithyroid antibodies in 12 (p <.04 versus controls). Lower levels of C3 and/or C4 complement fractions were observed in infected patients with respect to controls (7/43 versus 1/43; p=.014). After 1 year of follow-up, the markers of autoimmunity dramatically improved in patients eradicated for H. pylori infection compared to those in whom therapy failed. No patient developed a clinical autoimmune disorder.Conclusions. Additional studies are necessary to ascertain the clinical significance of the modifications of autoimmune markers in patients with H. pylori infection.

SUMMARY There is strong evidence that the determination of autoantibodies against filaggrine is a very useful tool for the diagnosis of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide antibodies (Anti-CCP)-ELISA appear to be the most efficient test among those available for the detection of antifilaggrine autoantibodies, as it has the best diagnostic accuracy for the diagnosis of RA. Furthermore, the anti-CCP-ELISA determination in early arthritis is a good predictor of disease persistence and radiographic joint damage. The positivity of Anti-CCP some years before the onset of the RA and the high concentration of autoantibodies in synovial fluid suggest a possible pathogenetic role of citrullination. Hower, at present, it is unclear whether anti-CCP antibodies have a better diagnostic performance than FR in recent onset synovitis and if they confer any additional value to the prognostic evaluation obtained with validated predictors of outcome (FR, joint count, duration of disease).

In the past decade, different modalities of antiviral therapy have been adopted aimed at eradicating hepatitis C virus infection. Initially, interferon was used in monotherapy, then interferon combined with ribavirin and amantadine. Recently, interferon has been conjugated with polyethylene glycol to allow optimization of its pharmacokinetic properties and to improve its antiviral activity. This study focused on the characteristics of the skin reactions that we observed in 27 patients with naïve hepatitis C who received polyethylene glycol interferon-ribavirin-amantadine or polyethylene glycol interferon-ribavirin and in 10 previous non-responders to interferon monotherapy who were retreated with triple therapy. In 9 patients (7 on triple therapy) dermatitis-like lesions were observed, and in 5 the severity of the lesions necessitated withdrawal from therapy.

The aim of this study was to evaluate the distribution and clinical significance of hepatitis C virus (HCV) genotypes in European patients with compensated cirrhosis due to hepatitis C (Child class A) seen at tertiary referral centres. HCV genotypes were determined by genotype-specific primer PCR in 255 stored serum samples obtained from cirrhotics followed for a median period of 7 years. Inclusion criteria were biopsy-proven cirrhosis, absence of complications of cirrhosis and exclusion of all other potential causes of chronic liver disease. The proportion of patients with types 1b, 2, 3a, 1a, 4 and 5 were 69%, 19%, 6%, 5%, 0.5% and 0.5%, respectively. Kaplan-Meier 5-year risk of hepatocellular carcinoma (HCC) was 6% and 4% for patients infected by type 1b and non-1b, respectively (P=0.8); the corresponding figures for decompensation were 18% and 7% (P=0.0009) and for event-free survival were 79% and 89% (P=0.09), respectively. After adjustment for baseline clinical and serological features, HCV type 1b did not increase the risk for HCC [adjusted relative risk=1.0 (95% confidence interval=0.47-2.34)], whereas it increased the risk for decompensation by a factor of 3 (1.2-7.4) and decreased event-free survival by a factor of 1.7 (0.9-3.10). In conclusion, type 1b and, to a lesser extent, type 2, are the most common HCV genotypes in European patients with cirrhosis. HCV type 1b is not associated with a greater risk for HCC, but increases the risk for decompensation by threefold in patients with cirrhosis.

Ogana, Graziella M.D.; Tocco, Andreina M.D.; Garrucciu, Giovanni M.D.; Branca, Barbara M.D.; Azara, Vittoria M.D.; Manzoni, Noemi E. M.D.; Deplano, Angelo M.D.; Solinas, Antonio M.D. Author Information

We evaluated the agreement between wedgedhepatic vein pressure (WHVP), portal vein pressure(PVP), and its relationship with portal hemodynamics in21 patients with HCVrelated cirrhosis with esophageal varices. Direct measurements of theportohepatic gradient (HVPG) were obtained byultrasound-guided fine needle puncture of the righthepatic and the portal veins. In five cases PVP was6.4-10.4 mm Hg higher than WHVP. In 12 cases measurements weresimilar (WHVP-PVP ≤ 3 mm Hg). In the remaining fourcases WHVP was 3.6-9.6 mm Hg higher than PVP. WHVP andPVP agreement was not related to HVPG mean value,Child-Pugh score, or grading of esophageal varices. Bycontrast, the difference between WHVP and PVP wasinversely related to the portal flow velocity (P =0.053) and directly related to the portal vascularresistance (P = 0.02). Whereas the portal branches werevisualized in patients with WHVP lower or similar toPVP, a predominant left portosystemic collateral flowwas observed in patients with WHVP > PVP. Our data point out that, in patients with cirrhosis dueto hepatitis C virus infection, discrepant HVPG valuesreflect true hemodynamic differences.

To examine the morbidity of compensated cirrhosis type B, a cohort of 349 Western European, white patients (86% men; mean age, 44 years) with biopsy-proven cirrhosis was followed up for a mean period of 73 months and was studied for occurrence of hepatocellular carcinoma (HCC) and decompensation. At entry into the study all patients were tested for hepatitis B e antigen (HBeAg; 34% of patients were HBeAg-positive) and antibody to hepatitis delta virus (anti-HDV; 20% of patients were anti-HDV-positive); 48% of 252 patients tested were hepatitis B virus (HBV)-DNA-positive. During follow-up HCC developed in 32 (9%) of the 349 patients and decompensation was observed in 88 (28%) of 317 tumor-free patients. Five years after diagnosis, the probability of HCC appearance was 6% and the probability of decompensation was 23%. After the first episode of decompensation the probability of survival was 35% at 5 years. Cox's regression analysis identified three variables that independently correlated with HCC: age, serum levels of platelets, and liver firmness on physical examination. HBV (HBeAg or HBV-DNA) and HDV (anti-HDV) markers at presentation had no prognostic value for the development of HCC. In conclusion, a high proportion of patients with HBsAg-positive compensated cirrhosis do not experience worsening of their condition for several years, but once decompensation occurs life expectancy is poor. European, white patients with compensated cirrhosis type B are at consistent risk for HCC. Prognostic factors for HCC reflect an advanced stage of cirrhosis and support the hypothesis that development of a tumor could be the likely consequence of long-standing hepatic disease.