Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

Matter of margins.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer, it represents a significant economic burden to health services because of a large volume of affected patients. Surgical excision with histological assessment of the surgical margins is widely considered as the mainstay of BCC treatment. Incomplete removal, in fact, should be considered a poor prognostic indicator, as incomplete removal of lesions is at risk of local recurrence. Actually, dermatological surgeries are carried out by a variety of different types of practitioners, such as plastic surgeons, maxillofacial surgeons, otorhinolaryngologists, ophthalmologists and finally dermatologists. Incomplete removal of the tumour ranges from 6.3% to 25%, depending on the improper intra-operative evaluation of the extent of the tumour. It depends on the clinical knowledge derived from both training and daily experience. In this sense, the majority of the largest studies derive from plastic surgeons, while dermatologists have small case series, albeit with a higher therapeutic efficacy in terms of complete surgical excision. OBJECTIVES: We conducted a retrospective analysis of the surgical activity, more specifically we evaluated both our therapeutic accuracy and analyzed the prognostic factors related to incomplete excisions. METHODS: A retrospective review of all BCC removals was performed. A total of 4523 BCC removals were included; other neoplasm, benign lesions and biopsies were also excluded. Each BCC's size diameter, localization, histology and histological presence of complicating factors was assessed, then the percentage of the incomplete removal was calculated. RESULTS: Incomplete resections occurred in 225 (4.97%) BCCs of the cases. Thirteen areas were categorized into in three different levels that rank the risk of incomplete removals. Sub-analysis indicates that just over a third had no complicating factors with the lateral/deep margins. The most frequent complicating factor is ulceration (22.9%), while vascular invasion or seborrheic keratoses were not found. Actinic keratoses, scabs and scars held the most responsibility for the involvement of the lateral margins, while perineural invasion is the main factor leading to deep margin involvement. Finally, a different trend for the involvement of lateral or deep margins according different histological sub-types was highlighted; lateral involvement is more frequent for the infiltrative/morpheic type, while the deep margin is more involved in the nodular type.

Reconstruction of nasal skin cancer defects with local flaps.

Reconstruction of nasal defects must preserve the integrity of complex facial functions and expressions, as well as facial symmetry and a pleasing aesthetic outcome. The reconstructive modality of choice will depend largely on the location, size, and depth of the surgical defect. Individualized therapy is the best course, and numerous flaps have been designed to provide coverage of a variety of nasal-specific defects. We describe our experience in the aesthetic reconstruction of nasal skin defects following oncological surgery. The use of different local flaps for nasal skin cancer defects is reported in 286 patients. Complications in this series were one partial flap dehiscence that healed by secondary intention, two forehead flaps, and one bilobed flap with minimal rim necrosis that resulted in an irregular scar requiring revision. Aesthetic results were deemed satisfactory by all patients and the operating surgeons. The color and texture matches were aesthetically good, and the nasal contour was distinct in all patients. All scars were inconspicuous and symmetrical. No patient had tenting or a flat nose.

Photodynamic therapy for basal cell carcinoma: clinical and pathological determinants of response.

BACKGROUND: Photodynamic therapy (PDT) is increasingly used in the treatment of basal cell carcinoma (BCC). However, scant information is available about the impact of both patient- and lesion-related characteristics on the effectiveness of therapy. Therefore, on the basis of the current data, it is difficult to draw clear-cut indications to use PDT for treatment of BCC in clinical practice. OBJECTIVE: To investigate the clinical and pathological determinants of response of BCC to PDT with methylaminolevulinate (MAL) and red light. METHODS: The clinical and pathological characteristics of 194 BCCs in 135 patients, treated with MAL-PDT, were evaluated. Lesions were treated with MAL-PDT according to established methods and the response was assessed by clinical follow-up of the patients. RESULTS: Complete response to PDT was 62%, with a better response for superficial BCC (95/116, 82%) than nodular BCC (26/78, 33%). When determinants of response were analysed, the nodular type and the location on the limbs emerged as significant clinical predictors of failure. Among the pathological characteristics, the nodular and infiltrative histotypes, as well as ulceration and tumour thickness were associated with a lower response to therapy. Patients' age and gender, as well as the size of the lesions, were not found to be significant predictors. CONCLUSIONS: Optimization of PDT procedure for BCC requires a careful selection of the lesions. In particular, superficial BCCs, preferentially located on the trunk, show the best therapeutic response.

Anti-tumor necrosis factor alpha therapy normalizes fibrinolysis impairment in patients with active rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with increased cardiovascular risk and involvement of inflammation, coagulation and fibrinolysis. Treatment with infliximab, a tumour necrosis factor-alpha (TNF-alpha) blocking chimeric monoclonal antibody, induces a long-term reduction of inflammation and coagulation, but its effect on fibrinolysis is still unknown. We carried out an observational study investigating plasma biomarkers of inflammation and fibrinolysis in RA patients before and after 14 weeks of infliximab treatment given according to the therapeutic guidelines for RA. METHODS: We studied 20 selected patients with active RA and without any other atherosclerosis risk factor as well as 40 healthy controls. Patients, treated with a stable dose of methotrexate, received infliximab (3 mg/kg) at week 0, 2, 6 and 14. At week 0 and 14, we assessed clinical, inflammatory and fibrinolyitic parameters. RESULTS: At baseline, plasminogen activator inhibitor (PAI-1) antigen, PAI-1 activity and tissue-type plasminogen activator (t-PA) antigen were significantly higher in RA patients than in controls (p=0.01, p=0.001 and p=0.0001 respectively). After 14 weeks of infliximab treatment, the levels of PAI-1 antigen, PAI-1 activity and t-PA antigen significantly decreased till normalization (p=0.0001). Plasma levels of C reactive protein (CRP) and interleukin-6 (IL-6) were directly correlated with levels of PAI-1 antigen (p=0.011 and p=0.0001), PAI-1 activity (p=0.013 and p=0.027) and t-PA antigen (p=0.017 and p=0.040). CONCLUSIONS: This study provides evidence that TNF-alpha blockade by infliximab not only decreases inflammation, but also reduces the inhibition of fibrinolysis. Such a combined effect may be pivotal in reducing the whole thrombotic risk in these patients.

Focus on adverse events of tumour necrosis factor alpha blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients.

OBJECTIVE: To report adverse events (AEs) seen in a large cohort of patients with juvenile idiopathic arthritis (JIA) treated with tumour necrosis factor (TNF)alpha blockers (infliximab and etanercept). METHODS: All patients with JIA treated with infliximab or etanercept at the Paediatric Rheumatologic Centre of the G Pini Institute (Milan, Italy) from November 1999 to February 2006, were enrolled in an open, single-centre, long-term prospective study RESULTS: In all, 163 patients (68 infliximab, 95 etanercept) were enrolled. Mean (SD) age of onset was 6.4 (4.8) years, mean age 17.1 (9.2) years, mean therapy duration 22.9 (17.6) months. A total of 45 patients (32 infliximab, 13 etanercept) failed to respond to or did not tolerate the first therapy and switched to a second one. In all, 208 treatments (81 infliximab, 127 etanercept) were performed. A total of 71 AEs occurred in 51 (62.9%) patients on infliximab and led to discontinuation in 26 (32.1%); 133 AEs occurred in 69 (54.3%) patients on etanercept and led to discontinuation in 18 (14.2%). Some AEs, such as thrombocytopoenia, neuropsychiatric disorders, new onset of Crohn disease and new onset or flare-up of chronic iridocyclitis (CIC), are unusual and have rarely been described before, yet proved to be significant in frequency and/or clinically noteworthy in the large population we followed. CONCLUSIONS: In our 6-year study, anti-TNFalpha agents infliximab and etanercept were well tolerated and safe, and were associated with only few serious, but all reversible, AEs. However, such inhibitors are associated with various and numerous AEs. Children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during anti-TNFalpha therapy as much as possible.

[Biological therapy with TNF-inhibitors in pediatric rheumatology. Review of the literature and personal experience]. / Le terapie biologiche con inibitori del TNF in reumatologia pediatrica. Revisione della letteratura ed esperienza personale.

The therapeutic approach to JIA is sometimes very troublesome and progression to erosive polyarthritis may occur in all JIA categories. Only Methotrexate has shown efficacy and safety in a large controlled trial. Nevertheless, in many cases, drug resistance or intolerance has led to try other therapeutic options, with still debatable results. Therefore, there has been space, in the last few years, for new therapies as the TNF-inhibitors. This therapeutic approach has shown a dramatic clinical benefit in active polyarticular refractory JIA: the rate and rapidity of response have exceeded those of all other studied DMARDs. Preliminary data show that they are efficacious also for other pediatric rheumatic disease (spondyloarthropathies, autoimmune uveitis, dermatomyositis, Kawasaki syndrome and some autoinflammatory diseases). TNF-inhibitors in JIA have demonstrated a favourable benefit-to-risk profile. However, as their use has increased worldwide, some unusual, usually not serious, adverse events have emerged. Severe infections, including TB, and deaths have been reported. Long-lasting active disease, systemic disease, concurrent and previous immunosuppressive therapies, all contribute to risk of infection and other serious AEs. Given the evidence that TNF has a primary role in the pathogenesis of JIA, particularly in joint destruction, neutralizing this cytokine early, within the window of opportunity, could halt or delay progression of joint damage and debilitating consequences of the disease. Thus, for JIA patients whose disease is not quickly controlled with MTX, TNF blockers may be considered as first-line treatment, although long-term safety data still need to be established.

[Simultaneous ultrasonography and arthroscopy for the study of the joint environment: indications and limits]. / Ecografia e artroscopia in contemporanea per lo studio dell'ambiente articolare: indicazioni e limiti.

Arthroscopy is a mini-invasive technique that allows the direct observation of the joint cavity and the execution of diagnostic and therapeutic procedures; arthroscopy needs a very long learning-time curve as well as dedicated spaces and instruments. Ultrasonography is an imaging technique that enables to perform an immediate extension of the standard physical examination. The opportunity to visualize soft tissues, to obtain multiplanar and dynamic images in real time makes this practice easy repeatable at low costs. Ultrasonography allows to detect a variety of changes during inflammatory processes. The wide experience in arthroscopy of rheumatic patients acquired through the years by our team at the G. Pini Institute led us to study in vivo, during arthroscopy, the correspondence between arthroscopic and ultrasonographic images. Up to now three knee arthroscopies have been conducted with the double equipment (ultrasonographic and arthroscopic devices) in operating room. In our experience, the combination of the two methods in operating room may improve the validation of ultrasonography with arthroscopy as gold standard, helps to train the ultrasonographer to give immediate answers in order to clear the doubts aroused by ultrasonographic images; it also allows the arthroscopist to visualize the deeper layers of the synovial membrane making double guided targeted biopsies possible. Limits are the complexity of the procedure (instruments, operators, spaces, training of the doctors), the loose of power-doppler signal with the blood tourniquet and the always difficult evaluation of cartilage.

Primary antiphospholipid syndrome associated with small aorta syndrome: a case report.

It has been widely accepted that the antiphospholipid syndrome (APS) is an autoimmune hypercoagulability syndrome in which a variety of venous and arterial thrombotic events may occur. Peripheral obliterating arterial disease characterized by aortoiliac steno-occlusion occurring in young women, is reported in the literature under the name of Small Aorta Syndrome (SAS). Although it remains unclear whether SAS represents a separate entity, the small size of the distal aorta increases the risk for aortoiliac occlusive disease. A 41-year old white woman was admitted with acute digital ischemia of the left foot. She had positive lupus anticoagulant and IgG anti-cardiolipin antibodies (61 UI/mL), but antinuclear antibodies and anti-ds-DNA antibodies were negative. She previously had two deep venous thromboses of the legs and, despite the oral anticoagulant therapy, pulmonary embolism occurred. Shortly thereafter, abdominal angio-magnetic resonance imaging suggested that the infra-renal aorta was narrowed more than 50%, without thrombotic occlusion of the terminal aorta and common iliac arteries. These findings were compatible with the features of SAS. There were no atherosclerotic changes in the artery wall and no other prediposing risk factors such as smoking, oral contraceptive or hyperlipidemia. After adequate anticoagulation and intravenous prostacyclin treatment the patient's symptoms and the ischemic lesions improved markedly. To our knowledge this is the first report of the association of SAS and primary APS. The occurrence of SAS in patients with APS may dramatically increase the risk of trombothic events.

A comparison of response criteria to evaluate therapeutic response in patients with juvenile idiopathic arthritis treated with methotrexate and/or anti-tumor necrosis factor alpha agents.

OBJECTIVE: There are no validated criteria to evaluate clinical response in juvenile idiopathic arthritis (JIA). The purpose of this study was to compare 4 sets of criteria (2 from the American College of Rheumatology [ACR] and 2 from the European League Against Rheumatism [EULAR]) for clinical response evaluation in JIA patients treated with methotrexate and/or anti-tumor necrosis factor alpha drugs. METHODS: Seventy-five patients with JIA were evaluated at baseline and after 6 months of therapy with second-line drugs. Mean age at study onset was 12.8 years (range 2-32.9 years). Diagnoses were systemic JIA (n = 16), rheumatoid factor-positive JIA (n = 5), rheumatoid factor-negative JIA (n = 9), persistent oligoarticular JIA (n = 10), extended oligoarticular JIA (n = 33), and psoriatic arthritis (n = 2). Clinical response was evaluated with the ACR Pediatric 30 criteria and the ACR 20% response criteria (ACR20), and with the EULAR Disease Activity Score (DAS) and 28-joint DAS (DAS28). Patients with EULAR criteria responses of "good" or "moderate" were classified as responders. Responders and nonresponders according to the different criteria were then compared. RESULTS: For patients younger than 16 years, Cohen's kappa varied between 0.51 and 0.72, with a good-to-excellent reproducibility index for all comparisons, except for the DAS28/ACR20 comparison. The best agreement was obtained by comparing the DAS and the ACR Pediatric 30. For patients older than 16 years, the reproducibility index was good or excellent in only 2 cases, i.e., comparing the DAS and the ACR Pediatric 30 and comparing the DAS and the DAS28 (as expected). CONCLUSION: Our study shows a good agreement overall for the different criteria tested. The highest concordance was observed between the DAS and the ACR Pediatric 30, the lowest between the DAS28 and the ACR20. Our data suggest that the ACR Pediatric 30 criteria can be used also in adult patients affected by JIA, and that the original DAS can be an alternative to the ACR Pediatric 30 in both children and young adults with JIA.

[Temporomandibular joint involvement in juvenile idiopathic arthritis: treatment with an orthodontic appliance]. / Trattamento con un dispositivo ortodontico per l'impegno temporomandibolare nell'artrite idiopatica giovanile. Osservazioni su 72 casi.

OBJECTIVE: About 65% of children suffering from juvenile idiopathic arthritis (JIA) shows a more or less marked involvement of temporo-mandibular joint (TMJ) with altered mandibular growth, resorption of the condyles, occlusary instability, reduced chewing ability and facial dysmorphia. The purpose of our study is to prevent and to treat the progressive evolution of JIA on craniofacial growth and morphology with a functional appliance; surgery should be considered only in so far as the adequacy of TMJ movement is concerned. METHODS: From 1992 until now 72 children with proved JIA and TMJ involvement have been treated (50 females, 22 males, aged 6 to 16 years old). TMJ involvement was bilateral in 61% and unilateral in 39% of patients. A diagnostic workup was carried out involving tomograms of TMJ and cephalometric radiograph and analysis. The authors used a bimaxillary activator in the attempt to modify the unfavourable growth pattern and provide a gradual ante-rotation of the jaw. RESULTS: Almost all JIA patients showed satisfactory long term results, easing of pain, reduced skeletal discrepancy, increased function and good facial profile. CONCLUSIONS: The long term results of this study indicate that orthopaedic therapy might control the vicious circle of the malocclusion in children with JIA, preventing exacerbation of mandibular clockwise rotation. Surgical intervention for the improvement of TMJ function should be considered only if a severe restricted state is imminent.

[Arthroscopic synovectomy in chronic inflammatory rheumatism: clinical and functional aspects]. / La sinovialectomia artroscopica in corso di reumatismi infiammatori cronici: aspetti clinici e funzionali.

By now many authors regard arthroscopic synovectomy an integral part of therapeutic treatment of many rheumatic diseases with favourable results on post operating course and clinical picture in the long term. The pathologic synovial tissue during articular inflammatory rheumatism is well known to have a damaging effect responsible of early cartilage injury, as well as symptomatic action (e.g. articular stiffness, effusion, pain, functional limitation). Therefore to value the removal of such a tissue you should think of the secondary prevention of cartilage injury, besides the symptomatic point of view. Since 1996 we performed 190 arthroscopic synovectomy, the adopted criteria of judgement were: pain (spontaneous, during active and passive movements), effusion or swelling presence, articular range and cartilage state (evaluated during arthroscopy according to Outerbridg's classification). 70% of the cases showed good results and six years later the beginning of this activity we retain arthroscopic synovectomy as a valid help in articular inflammatory rheumatism treatment.

[Role of chemokines in the pathogenesis of chronic synovitis during rheumatoid arthritis]. / Ruolo delle chemochine nella patogenesi della sinovite cronica in corso di artrite reumatoide.

Chemokines play a central role in the pathogenesis of rheumatoid arthritis (RA) synovitis which is characterised by new blood vessel formation, thickening of the lining layer and infiltration of immune cells. The inflammatory infiltrate is generated by a series of events which include the recruitment of leukocytes from the blood stream into the tissue, their local retention and activation to effector cells. All these processes are finely regulated by the interplay of different cell adhesion molecules (CAMs) and chemoattractant factors called chemokines (CK). CK are a superfamily of small proteins that play a crucial role in immune and inflammatory reactions. These chemoattractant cytokines share structural similarities including four conserved cysteine residues which form disulphide bonds in the tertiary structure of the proteins. CK mediate their effects by binding specific receptors (CK-R) characterised by a domain structure which spans the cell membrane seven times and signal through heterotrimeric GPT-binding proteins. Activation of the CK network results in an amplification of the inflammatory cascade and consequently in the progressive destruction of RA joints. The recognition of the central role of CK in inflammation has paved the way to the development of new agents capable of interfering with CK and CK-R. This review will focus in particular on the role of CK in regulating leukocyte trafficking in RA joints.

Reversal of CSF positivity for JC virus genome by cidofovir in a patient with systemic lupus erythematosus and progressive multifocal leukoencephalopathy.

We report the case of a 36-year-old woman affected by systemic lupus erythematosus who developed rapidly progressive multifocal leukoencephalopathy. Cidofovir therapy induced disappearance of JC virus genome from the cerebrospinal fluid and stabilization of the MRI picture. Despite the fatal outcome after a few months of disease, cidofovir treatment deserves further testing as single antiviral therapy in HIV-negative PML patients.

Retrospective clinical analysis of stented vs. stentless porcine aortic bioprostheses.

OBJECTIVE: The study was designed to compare hemodynamic performance, structural failure and survival of patients undergoing aortic valve replacement (AVR) with a composite aortic stented or stentless porcine bioprosthesis. METHODS: From January 1990 to June 1999, the clinical data of 725 patients undergoing AVR with stented porcine aortic bioprosthesis were reviewed. We defined two groups of patients with similar clinical characteristics: 202 patients receiving aortic stented and 205 patients stentless valves. The two patients groups were similar in age, sex, valve lesion, valve size, preoperative New York Heart Association (NYHA) class status and follow-up. RESULTS: The number of patients available for follow-up, excluding hospital and late mortality, reoperations and patients lost to follow-up, was 157 for the stented and 175 for the stentless group. There was a higher incidence of rheumatic heart disease in the stented (59%) vs. stentless group (44%), (P=0.003). Fewer patients had prior aortic bioprosthetic dysfunction in the stented (7.6%) compared to the stentless group (25%) (P<0.001). The mean intensive care unit stay, hospital mortality and late mortality were similar (P, NS). The total complication rate was higher in the stented (12%) than the stentless (3.4%)(P=0.005). Valve related death was higher in the stented (2.5%) than the stentless (0%) (P=0. 049). Postoperatively, the aortic effective orifice area (AEOA) was larger (P<0.001) and the transvalvular peak and mean gradients were lower in the stentless group (P<0.001). The leaflet tissue degeneration analysis was 8.0% in patients at risk for stented and 0. 6% for stentless (P=0.001). Actuarial analysis disclosed no statistical difference in patient survival between groups (P=0.18). Reoperations were less frequent in the stentless group (P=0.010). CONCLUSIONS: Hemodynamic benefits in the stentless group were evident and expressed by larger AEOA, lower gradients, better left ventricular remodeling with significant decrease of the left ventricular mass. Lower complication rates, lower reoperation rates, less leaflet tissue degeneration, and lower valve related mortality rates were seen in the stentless group. A controlled clinical comparison trial with longer follow-up will be required to confirm these clinical and hemodynamic benefits.

[Malignant mesothelioma in the industrial area of Colleferro]. / Mesotelioma maligno nel comprensorio industriale di Colleferro.

The study describes the occurrence of pleural and peritoneal malignant mesothelioma in the Colleferro industrial area (Province of Rome, 9 municipalities, population 63,000, period 1993-98) which is the site of a large chemical plant (BPD) producing organic chemicals, acid mixtures, insecticides, explosives and dynamite, and was involved in manufacturing/maintenance of railroad rolling stock. Asbestos was extensively used in these plants in the past. Mesothelioma cases were actively searched from data in files of pathology archives, hospital admission and discharge (records), and death certificates recorded at local health authority register. 23 potential cases were identified for whom clinical charts and pathological slides were reviewed. A multidisciplinary evaluation of all collected information confirmed 18 cases of cyto-histologically proven malignant mesothelioma (pleural/peritoneal ratio of 2.75:1) among residents and/or workers at BPD. The remaining 5 cases were defined as not mesothelioma; however, two were cases of lung cancer (both occupationally exposed to asbestos). All subjects with malignant mesothelioma had been occupationally exposed to asbestos (14 males and 3 females), except one (1 female with domestic exposure). No mesothelioma case was attributable to environmental exposure. Of the 17 cases with occupational asbestos exposure, 15 occurred in BPD workers employed in manufacturing/maintenance of railroad rolling stock (3 cases), general maintenance services (5 cases), or in the armaments sector (7 cases) and 2 in residents but not BPD workers (1 baker, 1 pipefitter). The incidence rate in residents of the 9 municipalities was 5.5 in males and 1.3 in females (standardized on the Italian population x100,000, census 1981). For Colleferro municipality only, the incidence was 10.1 in males and 4.1 in females, which are the highest rates reported so far in Italy. Besides confirming the risk of mesothelioma risk in railroad rolling stock manufacturing and asbestos-insulated pipe maintenance workers, this study identifies a cluster of malignant mesothelioma in explosives production workers.