Marco Bononi

Outcome of chronic pilonidal disease treatment after ambulatory plain midline excision and primary suture.

BACKGROUND Pilonidal sinus (PS) is a common chronic disorder of the sacrococcygeal region. The optimal treatment for PS remains controversial, and recent reports have advocated different surgical approaches. METHODS A prospective study was performed on 103 patients with nonrecurrent quiescent chronic discharging sinus. Excision with primary closure was performed on all patients. Patients were subdivided randomly into 2 groups. In group A, the excision was associated with drainage of the wound; in group B, the wound was not drained. RESULTS Excision with primary closure and drainage was performed in 53 patients (group A). Drainage was omitted in 50 patients (group B). Minor wound complications occurred in 3 patients in group A and in 36 patients in group B. No complete dehiscence of the wound was observed in patients in group A and in 8 patients in group B. Complete healing was fastest in patients in group A. Sinus recurrence occurred in 1 patient in group A and in 2 patients in group B. CONCLUSION Short- and long-term results suggest that limited midline excision with primary closure and wound drainage is a simple and effective procedure in the surgical treatment of uncomplicated PS. More demanding flap techniques and plasties should be reserved for complicated PS, which requires a wider excision.

Incidence and circumstances of cervical hematoma complicating thyroidectomy and its relationship to postoperative vomiting

Cervical hematoma is hardly a predictable complication of thyroid surgery. Postoperative vomiting has been reported as a likely risk factor.

Unusual breakage of a plastic biliary endoprosthesis causing an enterocutaneous fistula.

OBJECTIVE The objective of our study was to illustrate a case of endoscopically placed biliary stent breakage. METHODS A72-year-old woman with a prolonged history of cholangitis following laparoscopic cholecistectomy was referred to our institution 8 years ago. Dilatation of the intra- and extrahepatic biliary tree and a benign stricture at the cystic confluence were observed at US and endoscopic retrograde cholangiopancreatography (ERCP). A 12-F gauge plastic endoprosthesis was placed. In the absence of any symptoms, breakage of the stent was revealed 18 months later at plain radiology. Eight years later an enterocutaneous fistula occurred originating from a jejunal loop containing the indwelled distal part of the stent. Surgery was undertaken and the distal part of the stent removed with the perforated jejunal loop. The proximal part was successively endoscopically removed. CONCLUSIONS Disruption of a biliary endoprosthesis is observed in patients in whom the stent is kept in situ for a long period or consequent to exchange. The removal and exchange is mandatory when the stent disruption is followed by cholangitis. In the current case, because of the absence of any symptoms the removal of the stent was not attempted. Immediate endoscopic removal of the prosthetic fragments seems to be the treatment of choice for replacement of a new stent.

Isolated intestinal neurofibromatosis of colon. Single case report and review of the literature

Isolated intestinal neurofibromatosis of the colon is a most unusual disease: from 1937 to 1999 only 12 cases have been reported. The differential diagnosis and treatment of this lesion are very difficult. A review of the literature is made and personal experience in the diagnosis and treatment of a case in a 68-year-old female is described.

Cost-Effectiveness Analysis of Universal Human Papillomavirus Vaccination Using a Dynamic Bayesian Methodology: The BEST II Study

BACKGROUND Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context.

Effects of selective inhibitors of Aurora kinases on anaplastic thyroid carcinoma cell lines

Aurora kinases are serine/threonine kinases that play an essential role in cell division. Their aberrant expression and/or function induce severe mitotic abnormalities, resulting in either cell death or aneuploidy. Overexpression of Aurora kinases is often found in several malignancies, among which is anaplastic thyroid carcinoma (ATC). We have previously demonstrated the in vitro efficacy of Aurora kinase inhibitors in restraining cell growth and survival of different ATC cell lines. In this study, we sought to establish which Aurora might represent the preferential drug target for ATC. To this end, the effects of two selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) on four human ATC cell lines (CAL-62, BHT-101, 8305C, and 8505C) were analysed. Both inhibitors reduced cell proliferation in a time- and dose-dependent manner, with IC50 ranges of 44.3-134.2 nM for MLN8237 and of 9.2-461.3 nM for AZD1152. Immunofluorescence experiments and time-lapse videomicroscopy yielded evidence that each inhibitor induced distinct mitotic phenotypes, but both of them prevented the completion of cytokinesis. As a result, poliploidy increased in all AZD1152-treated cells, and in two out of four cell lines treated with MLN8237. Apoptosis was induced in all the cells by MLN8237, and in BHT-101, 8305C, and 8505C by AZD1152, while CAL-62 exposed to AZD1152 died through necrosis after multiple rounds of endoreplication. Both inhibitors were capable of blocking anchorage-independent cell growth. In conclusion, we demonstrated that either Aurora-A or Aurora-B might represent therapeutic targets for the ATC treatment, but inhibition of Aurora-A appears more effective for suppressing ATC cell proliferation and for inducing the apoptotic pathway.

Expression and prognostic value of the cell polarity PAR complex members in thyroid cancer

Establishment and maintenance of the apical-basal cell polarity, required for proper replication, migration, specialized functions and tissue morphogenesis, relies on three evolutionary conserved complexes: PAR, CRUMBS and SCRIBBLE. Loss of cell polarity/cohesiveness (LOP/C) is implicated in cancer progression, and members of the polarity complex have been described as either oncogenes or oncosuppressors. However, no information on their role in thyroid cancer (TC) progression is available. In the present study, we evaluated the gene expression of the PAR complex members aPKCι, PARD3α/β and PARD6α/β/γ in 95 papillary TC (PTC), compared to their normal matched tissues and in 12 anaplastic TC (ATC). The mRNA and protein levels of investigated genes were altered in the majority of PTC and ATC tissues. In PTC, univariate analysis showed that reduced expression of aPKCι, PARD3β and PARD6γ mRNAs is associated with increased tumor size, and the reduced expression of PARD3β mRNA is associated also with recurrences. Multivariate analysis demonstrated that the presence of lymph node metastasis at diagnosis and the reduced expression of PARD3β are independent risk factors for recurrences, with hazard ratio, respectively, of 8.21 (p=0.006) and 3.04 (p=0.029). The latter result was confirmed by the Kaplan-Meier analysis, which evidenced the association between decreased PARD3β mRNA levels and shorter disease-free interval. In conclusion, we demonstrated that the expression of PAR complex components is deregulated in the majority of PTC and there is a general trend towards their reduction in ATC tissues. Moreover, a prognostic value for the PARD3β gene in PTCs is suggested.

Considerations: When More is Not Necessarily Better

The erroneous perception that the more procedures are performed the more is the economic income of a surgical unit can lead some surgeons to be less observant to the international guidelines. We would like to address the attention of the readers over 3 intriguing topics of vascular surgery. Carotidsurgeryisapreventiontreatmentforischemicstrokein asymptomaticpatients.Nowadays,itisdemonstratedthatthereis arealbenefitofsurgeryoverconservativemedicaltherapyonlyin male patients with asymptomatic carotid stenosis 70% and younger than 75 years. We should remember that the benefit, in termsofabsoluteriskreductioninstrokeisonly1%peryear,and it increases with subsequent years of follow-up. 1 Therefore, life expectancy and a lower than 3% cumulative mortality and morbiditycomplicationrateofthecentershouldbekeptinmindwhen patients affected with an asymptomatic carotid artery stenosis undergo tromboendarterectomy or stent positioning. 2 How many

The effect of herd immunity in different human papillomavirus vaccination strategies : an economic evaluation of the Best II Study

PCN101 The effeCT of herd ImmuNITy IN dIffereNT humaN PaPIllomavIrus vaCCINaTIoN sTraTegIes: aN eCoNomIC evaluaTIoN of The BesT II sTudy Haussler K.1, Marcellusi A.2, Mennini F.S.3, Favato G.4, Picardo M.5, Garganese G.6, Bononi M.7, Scambia G.8, Capone A.9, Baio G.1 1University College London, London, UK, 2University of Rome “La Sapienza”, Italy, Rome, Italy, 3University of Rome “Tor Vergata”, Italy, Rome, Italy, 4Kingston University, Kingston, UK, Kingston, UK, 5San Gallicano Dermatological Institute (IRCCS), Rome, Italy, 6Catholic University, 7University of Rome “La Sapienza”, 8University of the Sacred Heart, Rome, Italy, 9Kingston University London, London, UK Objectives: Italian recommendations for human papillomavirus (HPV) immunization currently consider females only. However, males can be vectors in viral transmission and at risk of infection. The BEST II study was designed to evaluate: the cost-effectiveness (CE) of different interventions targeting females as well as males; and the economic impact of vaccination on a wide range of HPV-induced diseases. MethOds: A dynamic Bayesian Markov model was developed to investigate the transmission between sexual partners and the cost-effectiveness of vaccination targeting female and male cohorts in comparison to screening and female cohorts only. A range of HPV-induced diseases was considered (cervical, vaginal, vulvar, anal, head and neck and penile cancer, the associated pre-cancerous stages and anogenital warts). The process of sexual mixing was calculated based on age, gender and sexual behavioural specific matrices to estimate th force of infection dynamically. Increased susceptibility to the virus, associated with early sexual début, a high number of partners, smoking and previous STDs, were included. We considered several scenarios; the baseline assumes universal vaccination to be implemented for 12-year-old females and males. The follow-up period was 55 years. Results: According to our preliminary analysis, universal vaccination resulted in incremental CE ratios (ICERs) corresponding to € 910 and € 5,770, when compared to screeningonly and female-only vaccination, respectively. We performed extensive sensitivity analysis, which confirmed the good CE profile of universal vaccination in Italy. cOnclusiOns: A universal HPV vaccination of male and female programme is more cost-effective than screening and female-only vaccination when accounting for all HPV-related diseases. Universal vaccination programme increase herd immunity and provide indirect protection to unvaccinated girls against HPV. The herd immunity plays a significant role in the economic evaluation of HPV immunization programmes. A universal vaccination may be further useful considering that males are both at risk of infection and vectors in viral transmission.

Assessment of surgical treatment in elderly patients with breast cancer

AIMS AND BACKGROUND The incidence of breast cancer increases with advancing age and in clinical practice approximately 50% of new cases occur in women over the age of 65 years. Although breast cancer in elderly patients presents more favorable biological characteristics than similar-stage cancer in younger women, disease control still remains uncertain and is becoming a major health problem. PATIENTS AND METHODS Between 1984 and 2006, 133 patients aged over 65 with operable breast cancer underwent surgical treatment. Patients with ductal or lobular carcinoma in situ, bilateral breast cancer or a previous malignancy were excluded. The mean age was 72.8 years (range, 66-89). Breast-conserving surgery was performed in patients with early breast cancer (T1, T2 < 2.5 cm), while most patients with advanced tumors (T2 >2.5 cm, T3, T4) were treated by modified radical mastectomy. RESULTS The pathological stage was I in 44, IIA in 54, IIB in 18, IIIA in 10 and IIIB in 7 patients. Postoperative complications occurred in 13 patients (9%); there were no postoperative deaths. Eighty-nine patients underwent adjuvant therapy (chemotherapy, hormonal therapy). After a median follow-up of 96 months (range, 5-266), disease progression was observed in 21 patients (15.8%). The overall mortality from breast cancer was 11%, whereas the cancer-unrelated mortality was 9%. CONCLUSION There is no evidence that breast cancer has a more favorable prognosis in the elderly and surgical procedures should be carried out as has been established in younger women. At present, elderly patients are much less likely to be entered into randomized clinical trials and are often undertreated. However, in the absence of serious comorbid disease, they are able to withstand standard multimodal treatment options as well as do younger patients.