Practice parameters for the diagnosis and treatment of anal intraepithelial neoplasia (AIN) on behalf of the Italian Society of Colorectal Surgery (SICCR).

Squamous cell carcinoma (SCC) of the anus is a human papilloma virus (HPV) related malignancy that is preceded by anal intraepithelial neoplasia (AIN) making this cancer, at least theoretically, a preventable disease. In the past 10 years the diagnosis, management and nomenclature of AIN has dramatically changed. Increased life expectancy in human immunodeficiency virus (HIV) positive patients due to highly active antiretroviral therapy (HAART) has caused an increase in the incidence of SCC of the anus. While many experts recommend screening and treatment of anal high-grade squamous intraepithelial lesion (HSIL), there is no consensus on the optimal management these lesions. Therefore, there is a need to review the current evidence on diagnosis and treatment of AIN and formulate recommendations to guide management. Surgeons who are members of the Italian Society of Colorectal Surgery (SICCR) with a recognized interest in AIN were invited to contribute on various topics after a comprehensive literature search. Levels of evidence were classified using the Oxford Centre for Evidence-based Medicine of 2009 and the strength of recommendation was graded according to the United States (US) preventive services task force. These recommendations are among the few entirely dedicated only to the precursors of SCC of the anus and provide an evidence-based summary of the current knowledge about the management of AIN that will serve as a reference for clinicians involved in the treatment of patients at risk for anal cancer.

Short-term additional enfuvirtide therapy is associated with a greater immunological recovery in HIV very late presenters: a controlled pilot study.

OBJECTIVES: To evaluate whether the addition of enfuvirtide to standard highly active antiretroviral therapy (HAART) could confer immunovirological benefits in human immunodeficiency virus (HIV)-infected very late presenters. The current study is an open comparative therapeutic trial of standard protease inhibitor (PI)-based HAART ± additional enfuvirtide in treatment-naïve deeply immunologically impaired HIV-positive patients. METHODS: Very late presenters (CD4 <50/mm(3)), without tuberculosis and neoplasms, were alternatively allocated to two nucleoside reverse transcriptase inhibitors (NRTIs) and lopinavir/ritonavir without (control arm, CO) or with (ENF arm) enfuvirtide 90 mg bid. Enfuvirtide was administered until the achievement of viral load <50 copies/ml and for at least 24 weeks. The primary objective was the magnitude of CD4+ cell recovery at 6 months. HIV RNA was intensively monitored in the first month, and, thereafter, monthly, as for CD4+ cell count and percentage, clinical data, and plasma drug concentrations. RESULTS: Of 22 enrolled patients (11 per arm), 19 completed the study (10 in the ENF arm). Baseline CD4+ cell counts and % were comparable, with 20 CD4+/mm(3) (12-37) and a percentage of 3.3 (1.7-7.1) in the ENF arm, and 16 CD4+/mm(3) (9-29) and a percentage of 3.1 (2.3-3.8) in the CO arm, respectively. The baseline viral load was also comparable between the two arms, with 5.77 log10 (5.42-6) and 5.39 log10 (5.06-6) in the ENF and CO arms, respectively. Enfuvirtide recipients had higher CD4+ percentage at week 8 (7.6 vs. 3.6%, p = 0.02) and at week 24 (10.7 vs. 5.9%, p = 0.02), and a greater CD4+ increase at week 24 (207 vs. 134 cells/mm(3), p = 0.04), with 70% of enfuvirtide intakers versus 12.5% of controls who achieved a CD4+ cell count >200/mm(3) (p = 0.01). At 48 weeks, patients in the ENF arm had CD4+ cell counts higher than controls (251 vs. 153cells/mm(3), p = 0.04) and were also found to be faster in reaching a CD4 cell count over 200/mm(3): 18 (8-24) versus 48 (36-108) weeks (p = 0.01). Viral load decay at week 4 was greater in the ENF arm (-3 vs. -2.2 log, p = 0.04), while the proportion of patients with viral load <50 copies/ml at week 24 was comparable. CONCLUSIONS: In this pilot study, the addition of enfuvirtide to a lopinavir-based HAART was shown to be associated with a significantly faster and greater immunological recovery in newly discovered HIV-positive patients with very low CD4+ cell counts. Induction strategies using an enfuvirtide-based approach in such subjects warrant further investigation.

Immunostimulation to reduce recurrence after surgery for anal condyloma acuminata: a prospective randomized controlled trial.

AIM: Human papillomavirus is the most common cause of sexually transmitted disease. It is associated with immunosuppression and shows a marked tendency to recur. We investigated a natural immunostimulant aimed to reduce recurrence. METHOD: A randomized controlled study was carried out including 261 patients allocated to surgical excision alone (control group; n = 122) and surgical excision plus postoperative immunostimulation for 30 days with a natural product (STET; study group; n = 139). Patients with HIV positivity were excluded. All patients gave fully informed consent. RESULTS: The patients were followed for 6 months after surgery. Recurrence occurred in 7.2% (10/139) in the study group and in 27.1% (33/122) in the control group (P < 0.0001). There were no significant differences in the sex, sexual orientation, number of lesions, time to diagnosis and treatment or localization of lesions in the two groups. CONCLUSIONS: Immunostimulation using a natural product significantly reduced the incidence of recurrence of anal condylomata in patients undergoing surgical excision.

Performance and costs of a rapid syphilis test in an urban population at high risk for sexually transmitted infections.

INTRODUCTION: Rapid syphilis screening could facilitate case-identification in populations at high risk for sexually transmitted infections (STI). The aim of this study was to compare the performance and the cost-effectiveness of a rapid immunochromatography syphilis test with a traditional ELISA screening test in patients with suspected infectious syphilis or patients at high risk for STI/syphilis. METHODS: Consecutive patients attending a STI clinic cosensually underwent serological testing with two different tests. Sensitivity, specficity, Positive Predictive Values, Negative Predictive Values and effectiveness of the two tests were evaluated with respect to definitive diagnosis. RESULTS: In our population, the immunochromatography essay (Abbott Determine Syphilis TP) had a sensitivity of 95.0% (95% CI 88.7-97.8) and a specificity of 97.7% (95% CI 94.7-99.0). The ELISA test had a sensitivity of 95.0% (95% CI 88.8-97.9) and a specificity of 97.2% (95% CI 94.1-98.7). The Positive Predictive Value for ELISA was 94.1% (95% CI 87.6-97.3) and 95.0% (95% CI 88.7-97.8) for the rapid test. The Negative Predictive Value was 97.7% (95% CI 94.7-99) for both ELISA and the rapid tests. The cost-effectiveness analysis showed that the rapid test was less expensive than ELISA (EUR 26.46 vs EUR 40.57) and yielded a similar number of right diagnoses. CONCLUSIONS: The Abbott Determine Syphilis TP test is an accurate, easy and inexpensive test that could facilitate the rapid detection of syphilis in high-risk urban patients.

Culture proven Legionella pneumophila pneumonia in a HIV-infected patient: case report and review.

We report the first culture proven case of Legionella pneumonia in a HIV-positive patient in Italy. The laboratory diagnosis was obtained by isolation of Legionella pneumophila serogroup 1, serology, urinary antigen detection and PCR. Culture first allowed diagnosis of the infection, that probably would have been unrecognized. Since Legionellosis in HIV-positive patients with respiratory symptoms is rare and difficult to confirm, we strongly suggest that all available laboratory tests, and particularly culture, should be performed. A review of literature on culture proven cases is also provided.

The Karpas AIDS Cell Test compared with an enzyme-linked immunosorbent assay for detecting antibody to the human immunodeficiency viruses (HIV-I and HIV-2).

We have compared the Karpas AIDS Cell Test for antibodies to the human immunodeficiency viruses (HIV) with a commercial enzyme-linked immunosorbent assay (ELISA) (Organon Teknika) by testing serum samples from 324 intravenous drug abusers in Turin. The cell test was found to be more sensitive and as specific as the ELISA with the serum samples from the drug abusers. In Lisbon, 30 samples were tested on slides containing cells infected with HIV-1 and/or HIV-2. All 15 samples, which were positive for HIV-2 alone (in the HIV-2 Elavia test and by the Western blotting technique), were also positive in the Karpas AIDS test. In contrast, only one of the 15 samples (7%) gave a positive reading in the ELISA for HIV-1. Results of 30 samples tested in Turin and Lisbon by the Western blotting technique agreed closely with those obtained with the Karpas AIDS Cell Test. We were also able to show that the entire test can be performed at room temperature and completed within 1 hour. Moreover, the cell test requires minimal skill and simple equipment and is inexpensive. It also includes non-infected cells as a control and the specificity of positive samples may be verified with a bench microscope. Furthermore, this test which detects antibodies to both HIV-1 and HIV-2 allows rapid typing of the infecting strain.

Sexually transmitted infections in Italy: an overview.

In Italy more than 240,000 and 500,000 cases of gonorrhoea and syphilis, respectively, were reported in 1936 but the incidence progressively fell to about 200-300/year by the early 1990s; data available now are probably 100-150% underestimated. An inefficient notification system, diversion of public funding to other fields, and the progressive decline in importance of dermatovenereological centres are responsible for this decline. The advent of the HIV epidemic (with more than 47,000 AIDS reported cases) has drained most public health resources away from the very limited interventions for the control of traditional sexually transmitted infections (STIs). This has led some groups to attempt alternative approaches to the HIV/STI prevention and treatment policies; the potential of these new experiences need to be assessed. A change in culture of the medical body politic is now essential in order to support medical professionals, administrators and programme managers seeking to implement proper STI control programmes.

[HHV-8 infection. Update on pathogenesis and epidemiology]. / Infezione da HHV-8. Attualità su patogenesi ed epidemiologia.

HHV-8 (Human Herpesvirus 8) is a human lymphotropic and transforming virus closely associated to the development of Kaposis's sarcoma, Castleman's disease and Primary Effusion Lymphoma among immunosuppressed patients. Prevalence of infection varies according to different geographic area and to ethnic group or to risk factors. No effective treatments are available at present.

Lymphogranuloma venereum: an old, forgotten re-emerging systemic disease.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection endemic in parts of Africa, Asia, South America, and the Caribbean, but once was rarely observed in Western countries, where most cases were considered to be imported. However, recent outbreaks have been reported in Europe, Australia, New Zealand, the United States and Canada, mainly among HIV positive men who have sex with men, signaling LGV re-emergence. The etiological agent of LGV is Chlamydia trachomatis serotypes L1, L2 and L3, and current outbreaks are mostly sustained by L2b type. The clinical course can be classically divided into three stages: an initial papule, which may ulcerate at the site of inoculation, followed by regional lymphoadenopathy (second stage, generally unilateral). In the tertiary stage, lymphatic obstruction, with elephantiasis of genitalia, and rectal involvement can lead to the formation of strictures and fistulae that may require surgical treatment. Recent cases are observed mainly among HIV positive people, often co-infected with HCV and others STIs, engaging in high-risk sexual practices. The main clinical picture is a relative new entity characterized by progressive ulcerative proctitis, the so called anorectal syndrome. Diagnosis is often delayed, requires a high index of clinical suspicion and must rely on the use of nucleic acid amplification tests. The differential diagnosis of proctitis should include LGV infection. Gastroenterologists, coloproctologists, dermatologists and other specialists need to be aware of LGV proctitis to avoid diagnostic delay and progression of disease to the tertiary stage.

Cefixime and ceftriaxone susceptibility of Neisseria gonorrhoeae in Italy from 2006 to 2010.

Neisseria gonorrhoeae resistance to cephalosporins, the currently recommended treatment, and treatment failures with cefixime have been reported worldwide. The purposes of the present study were (i) to examine the susceptibility of N. gonorrhoeae isolates isolated in Italy from 2006 through 2010 to cefixime (n = 293) taking into account both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical And Laboratory Standards Institute (CLSI) criteria for categorization; (ii) to determine the contribution to decreased/resistant susceptibility of mutations in the penA, mtrR, ponA and porB1b genes in a subsample of isolates; and (iii) to genotype the isolates showing decreased susceptibility or resistance to cefixime, by N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and by pulsed-field gel electrophoresis (PFGE) to identify the predominant genotypes. Minimum inhibitory concentrations (MICs) were determined by the E-test and agar dilution method on 293 isolates and results were interpreted according to both EUCAST 2010 (MIC R >0.12 mg/L) and CLSI 2008 (MIC R >0.25 mg/L) criteria. All isolates showed full susceptibility to ceftriaxone, whereas those with a MIC for cefixime ≥0.125 mg/L were on the increase from 2008 through 2010. The same penA gene alterations were found among isolates with MICs close to the EUCAST breakpoint as the resistant ones, and they belong to ST1407. Seven isolates, belonging to various sequence types, showed a different por allele, though similar to the por 908 allele present in ST1407. PFGE divided strains ST1407 into two main groups confirming their genetic relationship.

Phenotypic and genotypic characterization of Neisseria gonorrhoeae in parts of Italy: detection of a multiresistant cluster circulating in a heterosexual network.

Data concerning Neisseria gonorrhoeae infections in Italy are scarce, and there is little information on the phenotypic and genotypic characteristics of the circulating strains. In this study, 326 isolates collected from 397 patients, with or without concurrent human immunodeficiency virus (HIV) infection, were cultured and characterized by serovar and antimicrobial susceptibility to five antimicrobials. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was also performed for strain characterization and to identify a transmission network. Gonococcal infection was diagnosed in 364 males and 33 females, 296 of whom were Italian and 96 of whom were foreigners (nationality was unknown in five cases). Among the 364 males, 197 were heterosexual, and the median age was 31 years. Approximately 8.3% of all the investigated patients were HIV-1-positive. The isolates were assigned to three different serovars (IA, IB, IA/IB), IB being the most frequently encountered. A significant rate of resistant gonococci was also observed; 34%, 25.5% and 19.1% of ciprofloxacin-resistant, penicillin-resistant and tetracycline-resistant phenotypes, respectively, were detected, and 10.2% of strains were multidrug-resistant. Together with the presence of different sequence types (STs), identified by NG-MAST, a multidrug-resistant cluster, ST661, was detected in a heterosexual network in a precise geographical area of the country. In particular, all strains belonging to ST661 showed identical profiles according to pulsed-field gel electrophoresis (PFGE), all were serotype IB, and all were resistant to penicillin, ciprofloxacin and tetracycline.

Tracheobronchial aspergillosis in a patient with AIDS treated with aerosolized amphotericin B combined with itraconazole.

The clinical features of a tracheobronchial infection due to Aspergillus flavus in an AIDS patient with a normal neutrophil count is described. Diagnosis was made by culture and microscopic examination of biopsies obtained from bronchial vegetations seen at bronchoscopy. Radiographic examination of the neck revealed the presence of large endoluminal fungal masses. Initially the patient was treated with a combination of itraconazole, flucytosine and aerosolized amphotericin B, then only with itraconazole plus aerosolized amphotericin B. A good therapeutic response was observed.

[Cardiac complications in HIV infections]. / Complicazioni cardiache nella infezione HIV.

UNLABELLED: Cardiological involvement in HIV infection is relatively rare but it presents important clinical aspects that are still open questions. We report our experience with HIV patients who underwent cardiological evaluation, Doppler echocardiography and follow-up. MATERIAL AND METHOD: We selected 127 patients (9%) on the basis of clinical suspicion of heart disease, taking them from the 1398 admitted for HIV infection between 1992 and 1995. Ninety-six patients had AIDS (group A) and 31 were in pre-AIDS phase (group B). The age was 21-52 years: 83 were males, 44 were females and 91% of the patients had been drug addicts. Echocardiography was executed with Hp Sonos 1000 and Sonos 2500 devices. Follow-up was 6-36 months. RESULTS: Ninety-two patients (6.5% on total admitted patients) had heart disease. Thirty-five patients were normal on echocardiography. Other diseases were: pericardial effusion in 38 cases (30%), with CD4+ number significantly lower (p < 0.005); dilated cardiomyopathy in 20 patients (16%), with a low CD4+ number (p < 0.005); reversible segmental or diffuse hypokinesia compatible with clinical myocarditis was seen in 11 patients (9%), especially in group A (p < 0.005); infective endocarditis in 17 patients (13%), especially group B (p < 0.005); right ventricular dilatation in 7; discrete right ventricular mass in 3 patients. Sixty-five patients (51%) died during follow-up (group A only). There were 19 cardiac deaths (15%), which represents 1.3% of the total number of patients. Nine of these (47%) were in patients with cardiomyopathy. Total mortality was 85% in patients with dilated cardiomyopathy, 73% in myocarditis cases, 71% in pericarditis cases (especially extracardiac), 66% in right ventricular dilatation cases, 18% in endocarditis cases, 34% in normal cases. CONCLUSIONS: Cardiac complications assume clinical importance, especially in the AIDS phase of HIV infection, but early diagnosis in the pre-AIDS phase is important for treatment. Clinical evaluation and echocardiography are corner-stones of the diagnosis. Prognosis depends especially on the clinical stage of HIV infection and myocardial involvement.