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The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy.Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models.Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945.The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Background The European guidelines for quality assurance in colorectal cancer (CRC) screening recommend that interval cancer rate be expressed as a proportion of background incidence rate. Aim To determine the crude and adjusted proportional incidence of interval CRC in an Italian regional two-yearly faecal immunochemical test (FIT) screening programme. Methods The programme (year of implementation, 2005) is targeted at over 1,000,000 people aged 50–69 years. The test is a one-sample OC-Sensor (Eiken Chemical Co., Tokyo, Japan). The study covered one-third of the regional area. Excerpts of 434,295 eligible negative FIT records dated 2005–2012 from 193,193 subjects were retrieved from the regional CRC screening data warehouse. By 31 December 2013, the cohort accumulated 198,302 man-years and 235,370 woman-years. Interval CRCs were identified by record-linkage with the local population-based cancer registry. Their number was divided by the expected number, estimated with age-period-cohort models, to obtain the proportional incidence. Results The proportional incidence of interval CRC for men and women was, respectively, 0.06 (95% confidence interval (CI), 0.04–0.09) and 0.17 (95% CI, 0.13–0.23) in the first interval year, and 0.21 (95% CI, 0.16–0.26) and 0.28 (95% CI, 0.22–0.36) in the second year. Conclusions The results were acceptable and in line with previous studies.

Background An increased risk of death by suicide in cancer patients has been documented since decades. We evaluated the risk of death by suicide in an Italian population-based cancer case series and added the results to a systematic review and meta-analysis of the literature. Methods The Italian series, including 127,042 primary cancer patients diagnosed between 1996 and 2014, was obtained from the Romagna Cancer Registry (northern Italy). Standardised mortality ratios (SMRs) were calculated. Regarding the systematic review and meta-analysis, the PubMed database was searched for English language studies published up to 2017. Fifty-seven potentially eligible papers were reviewed in full, and 19 of them were selected for analysis. The SMR was the first outcome, replaced by rate ratio if the SMR was not available. Findings In the Italian case series, an increased suicide risk was found for both sexes combined (SMR = 1.5; 95% confidence interval [CI]: 1.3–1.8), for males (SMR = 1.6; 95% CI: 1.4–1.9) but not females (SMR = 1.1; 95% CI: 0.7–1.7), for patients aged ≥55 years, with poor prognosis and advanced-stage disease and during the first year after diagnosis. The absolute excess risk of suicide was 0.9 per 10,000 patient-years. Multivariate analysis confirmed the role of univariate factors except for poor prognosis. Meta-analysis showed a strong heterogeneity between studies. The risk was significantly elevated for both sexes combined (pooled SMR = 1.7; 95% CI: 1.5–1.9), men (pooled SMR = 1.8; 95% CI: 1.6–2.0) and women (pooled SMR = 1.4; 95% CI: 1.3–1.6). There was no evidence for small-study effects. Interpretation The Italian study confirmed the previous common finding that cancer patients are at increased risk for suicide. A clinical multidisciplinary approach to support them is needed.

Background and aims The article presents a population-based registry designed to estimate incidence and prevalence of inflammatory bowel disease (IBD) in the area of Forli (north-eastern Italy). Methods The registry included all patients with IBD ulcerative colitis (UC) and Crohn’s disease (CD) in the Forli area from 1993 to 2013. A data manager matched records from various sources. Results Seven hundred ninety-one patients were registered during the study period, 564 (71.3%) with UC and 227 (28.7%) with CD. The standardized annual incidence rate for UC was 12.8 per 100,000 females (95% CI 11.1–14.4) and 15.7 per 100,000 males (95% CI 13.9–17.5). That of CD was 7.0 per 100,000 for females (95% CI 5.7–8.3) and 5.4 per 100,000 males (95% CI 4.3–6.4). The prevalence of CD and UC on 1 January 2014 was 109.2 per 100,000 inhabitants (95% CI 94.3–124.2) and 266.4 per 100,000 inhabitants (95% CI 243.4–289.7), respectively. Conclusions Although further studies are needed, the data suggest that incidence and prevalence of IBD in Italy are underestimated.

Background The worldwide decrease in gastric cancer incidence is due to a birth-cohort-dependent decrease in exposure to major risk factors. Methods In an area of northern Italy with a historically strong internal geographical gradient in gastric cancer incidence, variations in rates by municipality and age group between 1987 and 2008 were evaluated. The study period was divided into three nonadjacent periods. End points included: age- and sex-standardised incidence rates; incidence rate ratio between age- and sex-standardised incidence rates; smoothed relative risks of gastric cancer incidence, and posterior probabilities of the relative risk being >1. Results In 1987–1990, the estimate of posterior probabilities of relative risk being >1 showed a higher incidence in hilly/mountainous areas. Between 1987–1990 and 2005–2008, a uniform decrease of more than 50% was observed (incidence rate ratio: plain, 0.45 (95% confidence interval 0.40–0.51); hill, 0.44 (0.34–0.58); mountain, 0.48 (0.22–1.02)). The decrease in the mountainous area was weak in the middle time period, with an incidence rate ratio of 0.92 (0.46–1.84), and intensified afterwards. The decrease occurred earlier and was more pronounced among younger people. In 2005–2008, gastric cancer risk was uniform across ages and municipalities. Conclusions The observed changes in gastric cancer incidence is the epilogue of a birth-cohort-dependent decrease in exposure to major risk factors.

Background Although it is hypothesised that human papillomavirus (HPV) testing may have a role in surveillance of patients conservatively treated for stage IA squamous cell cervical carcinoma, research on this topic has been minimal. Objectives To determine: (1) the changes in HPV test result from treatment onward; (2) the time to viral clearance; and (3) the negative predictive value (NPV) and positive predictive value (PPV) of HPV test result for the detection of CIN2 or worse (CIN2+) during follow-up. Study design In a multicentre retrospective follow-up study of a consecutive series (1997–2009) of 91 patients, longitudinal outcome measures were estimated as cumulative probabilities using the Kaplan–Meier method. Results For patients testing HPV-positive at the first follow-up visit ( n = 44), the probability of change to negative rose from 0 to 0.78 between 7 and 21 months after treatment. For HPV-negative patients ( n = 47), the probability of change to positive rose to 0.13 between 9 and 26 months. After a median follow-up of 50 months (range, 2–80), the NPV for CIN2+ was 1.00. The PPV was 0.60 (95% confidence interval, 0.43–0.77) after 26 months. The median time to detection was 5 months. Conclusions If adequately confirmed, these findings would indicate that HPV testing is capable to identify the patients who have had their lesions fully removed, and would make it possible to focus follow-up efforts on a subset of patients at high risk of residual or progressive disease.

The aim of this study was to determine whether the excess risk of axillary lymph node metastases (N+) differs between interval breast cancers arising shortly after a negative mammography and those presenting later. In a registry-based series of pT1a–pT3 breast carcinoma patients aged 50–74years from the Italian screening programmes, the odds ratio (OR) for interval cancers ( n =791) versus the screen-detected (SD) cancers ( n =1211) having N+ was modelled using forward stepwise logistic regression analysis. The interscreening interval was divided into 1–12, 13–18, and 19–24months. The prevalence of N+ was 28% among SD cancers. With a prevalence of 38%, 42%, and 44%, the adjusted (demographics and N staging technique) OR of N+ for cancers diagnosed between 1–12, 13–18, and 19–24months of interval was 1.41 (95% confidence interval 1.06–1.87), 1.74 (1.31–2.31), and 1.91 (1.43–2.54), respectively. Histologic type, tumour grade, and tumour size were entered in turn into the model. Histologic type had modest effects. With adjustment for tumour grade, the ORs decreased to 1.23 (0.92–1.65), 1.58 (1.18–2.12), and 1.73 (1.29–2.32). Adjusting for tumour size decreased the ORs to 0.95 (0.70–1.29), 1.34 (0.99–1.81), and 1.37 (1.01–1.85). The strength of confounding by tumour size suggested that the excess risk of N+ for first-year interval cancers reflected only their higher chronological age, whereas the increased aggressiveness of second-year interval cancers was partly accounted for by intrinsic biological attributes.

Objectives To evaluate the frequency and correlates of non-adherence to follow-up among patients conservatively treated for CIN2-3. Study design Study population comprised 1560 patients aged 25–64 years from a screening programme in northern Italy. The regional standard protocol was used as a reference. Multinomial logistic regression analysis was used to estimate the odds ratio probability of a patient being lost to follow-up (no check-ups within 27 months of treatment) or incompletely followed-up (1–3 negative check-ups) versus having 4 negative check-ups. Results Three hundred twenty-six patients (21%) were lost to follow-up, 678 (43%) were incompletely followed-up, 352 (23%) presented for 4 negative check-ups and 204 (13%) were diagnosed with persistent disease. The probability of no or incomplete follow-up was greater for patients who lived in the urban district, who were treated in private settings (versus screening centres), who exhibited a visibile squamocolumnar junction on pre-treatment colposcopy, who were treated with cold knife excision and local destructive therapy (versus loop diathermy excision), and whose surgical specimens had positive excision margins. Conclusions Adherence to the reference protocol was poor. Factors involved in follow-up failures require greater clinical attention.

Objective The goal of this study was to determine the clinical factors independently associated with inaccuracy of colposcopically directed punch biopsy in defining extent and severity of epithelial lesions of the cervix. Methods The study was conducted in a colposcopy clinic devoted to the management of patients with abnormal Pap smear and/or histology diagnosis of cervical intraepithelial neoplasia (CIN) on punch biopsy or endocervical curettage. Seven hundred and thirty-nine patients (median age, 33 years; range, 18–83 years) referred with a punch biopsy diagnosis of CIN2–3 and treated with electrosurgical conization were evaluated. Cone histology diagnosis was assumed to supply the correct diagnosis. Two types of deviation of biopsy diagnosis were considered: (1) unconfirmed high-grade CIN diagnosis, defined as a cone diagnosis of CIN1 and reactive/reparative changes, and (2) nondiagnosis of carcinoma, defined as a cone diagnosis of microinvasive and invasive squamous carcinoma. Multinomial logistic regression analysis was used to assess the determinants of the probability of each type of deviation. Results The probability of unconfirmed high-grade CIN diagnosis ( n = 190, 25.7%) was inversely related to number of quadrants involved, severity of referral Pap smear, and grade of biopsy. The probability of nondiagnosis of carcinoma ( n = 43, 5.8%) was positively related to patient age, invisibility of the squamocolumnar junction, number of quadrants involved, and cone width. Endo-ectocervical location, cone depth, and time period had no effect whatsoever. Conclusions The study confirmed previous observations regarding the positive association of patient age and invisibility of squamocolumnar junction with the probability of nondiagnosis of carcinoma. The concomitant positive effects of number of quadrants involved and cone width were suggested to mirror the effect of circumferential development and, respectively, surface area of CIN. Severity of referral Pap smear and grade of biopsy were shown to be inversely related to the probability of a cone diagnosis of CIN1 and benign changes.

Objective. Cone margin status has been reported to be the most important predictor of residual disease in patients with cervical intraepithelial neoplasia (CIN) undergoing electrosurgical excisional treatment. The primary aim of this study of patients treated with electrosurgical conization was to evaluate the association of cone margin status and other clinical and pathologic factors with the probability of residual disease. Methods. The study population comprised 699 patients with at least one follow-up visit within 12 months of conization. Residual disease was defined as a histology diagnosis of CIN within 3 years of conization. Multivariate associations were evaluated with multiple logistic regression analysis. Results. Attendance to follow-up was 97% for the second visit and 34% for the third visit. Residual disease was detected in a total of 38 patients (5.4%). The detection rate was 3.3% at the first visit, 2.1% at the second visit, and 0.4% at the third visit. An increased probability of residual disease was associated with a referral Pap smear reported as high-grade squamous intraepithelial neoplasia and carcinoma (odds ratio, 2.9; reference category, low-grade squamous intraepithelial neoplasia). A decreased probability was associated with a squamocolumnar junction entirely visible at the first follow-up visit (odds ratio, 0.2; reference category, squamocolumnar junction not visible). Patient age, time period, lesion size, lesion site, grade of CIN, cone width, cone depth, and margin status had no influence. Conclusions. The determinants of residual disease in this study differed from those generally reported so far. Factors associated with effectiveness of electrosurgical treatment of CIN need further research.

The purpose of epiluminescence microscopy (ELM), also referred to as dermoscopy, dermatoscopy , or skin surface microscopy , is to complement the clinical examination of pigmented skin lesions (PSLs) to improve the differential diagnosis between nonmelanocytic and melanocytic lesions and the recognition of early cutaneous malignant melanoma (CMM). 14 In three sections, this article addresses the relationship between Breslow thickness and ELM features of CMM. Section one suggests the essential theoretical background of the association between Breslow thickness and ELM features of the disease. The main events of histogenesis, 3, 4, 6 particularly in the intraepidermal phase and the initial invasion of dermis, can be considered the rationale for interpreting the ELM characteristics of CMM in relation to tumor thickness. The second section briefly reviews previous clinical studies that have reported the relationship between thickness and ELM presentation. Generally, such a crucial issue has been the subject of a limited number of specific reports. Some studies have formally considered the prevalence of ELM features according to thickness 1, 5 ; others have focused on a detailed morphologic analysis of ELM structures and features in relation to thickness, with no statistical evaluation of the observed differences between thin and thick lesions. 8, 10, 11 Some reports have addressed the ELM characteristics of CMM as a function of the histologic type of the lesion, 23 or have compared in situ lesions with invasive CMM 13, 16 ; although indirectly, the latter type of studies has provided useful and important details for the purposes of this review. The third section consists of selected iconographic material from the Skin Cancer Clinic of Ravenna 19, 20, 21, 22 and is aimed at providing thickness-specific ELM images to further clarify the ELM features of CMM in different growth phases. The images have been captured with digital ELM equipment consisting of a Leica Wild M-650 stereomicroscope (Leica AG, Heerbrugg, Switzerland), a Sony 3CCD DXC-930P color video camera, an AT-Vista Videographics adapter, an IBM personal computer, a Sony Trinitron Analog PVM-2043MD monitor, and the DBDERMO MIPS software (Dell'Eva/Burroni, Florence/Siena, Italy). 19, 20, 21, 22 The digital images were processed at 768 × 576 pixels and 16 bytes per pixel.

Background : The poor accuracy of the clinical examination of pigmented skin lesions (PSLs) is a major limitation of secondary prevention strategies for cutaneous melanoma (CMM). In the last few years, the epiluminescence microscopy (ELM) technique has been used increasingly as an adjunct to clinical examination in the dermatology practice. Although the question of training has emerged as a priority, the diffusion, the effects, and the correlates of educational programmes in ELM have seldom been studied. Methods : Thirty ELM images of PSLs (11 CMMs, 14 melanocytic nevi (MN), and 5 nonmelanocytic lesions (NMLs) each matched with the corresponding clinical or plain photographic image were independently diagnosed before and after a one-day workshop by 83 Italian dermatologists participating in a nationwide educational programme on ELM. The original histology diagnosis was assumed as a gold standard. The overall effect of training on a set of accuracy measures by PSL type was evaluated. The association of the professional sector (public/private), number of years of general experience in dermatology (1–10/>10), average weekly number of PSLs seen (≤10/11–20/>20), routine use of ELM (no/yes), and area of residence (northern/southern Italy) with the mean number of PSLs correctly diagnosed before and after training was evaluated with the general factorial analysis of variance. The factors associated with improvement between the two tests were evaluated with the analysis of variance for repeated measures. Results : Compared with pretraining data, the average percentage of exact diagnosis increased significantly for all PSLs (CMMs, 72% vs 55%; MN, 68% vs 64%; NMLs, 67% vs 58%; total lesions combined, 69% vs 60%). Baseline as well as final accuracy were independent from the professional sector and the years of experience but were greater among those subjects who reported >20 PSLs per week compared with the reference group (≤10 PSLs). The routine use of ELM was associated with a slight advantage in pretraining accuracy. The area of residence was the strongest determinant of baseline as well as final accuracy. The effect of training was independent from all factors studied with the exception of the area of residence with a 13% increase in the frequency of exact diagnosis in northern Italy (from 66–79%) and 6% in southern Italy (from 55–61%). Conclusions : Though insufficient in absolute terms, a measurable increase in ELM accuracy can be achieved even with intense training sessions of short duration. Medical education to ELM in southern Italy should be a priority.

Cervicography and HPV DNA testing have been proposed as intermediate triage techniques for the management of patients with Pap smear showing minor-grade atypia. The aims of the present study of 221 patients with positive Pap smear (ages 16-65) were (1) to evaluate the association of cervicography and HPV DNA test with the probability of biopsy and final histology diagnosis of CIN2 or worse, (2) to identify the combinations of results on cervicography and HPV DNA test associated with the absence of such lesions, and (3) to estimate the cost of a potential triage protocol for patients with HPV-CIN1 smear. The probability of biopsy showed a univariate association with the severity of the smear result and the cervicography classification but not the HPV DNA test. In the multivariate analysis, only the cervicography result was a significant predictor of biopsy. The final histology diagnosis showed a univariate association with each of the three tests and a multivariate association with the degree of cytology positivity and the cervicography result. Among patients with HPV-CIN1 smears, only a negative cervicography (with any HPV DNA test result) was always associated with the absence of severe histologic lesions. This pattern accounted only for 7% of such patients. The additional costs of a potential triage protocol based on cervicography were estimated to exceed the savings resulting from the reduced colposcopy rate.

In an external quality assurance (EQA) scheme, 110 selected cervical smears were independently reported by seven cytology laboratories using the 1988 Bethesda System. In one of these, a random sample of 60 study smears was independently classified by five cytologists before undergoing joint examination according to EQA protocol. Internal agreement (i.e., among these cytologists) was compared with external agreement (between these cytologists and the other six laboratories) and with interlaboratory agreement (among these laboratories). The kappa value for internal agreement on sample adequacy (0.57) was considerably greater than those for external (0.16) and interlaboratory agreement (0.10). For interpretation of epithelial abnormalities, internal kappa was excellent (0.80) but not substantially greater compared with external kappa (0.66) and interlaboratory kappa (0.70). Calculation of class-specific kappa values revealed (a) that superiority of internal agreement on sample adequacy was restricted to the notations of "less than optimal" and of "satisfactory," and (b) that internal increase in agreement on cytologic abnormalities was substantial for the diagnosis of "atypical cells of undetermined significance."

Background: Available information on the effect of sun exposure on the biologic activity and morphologic characteristics of nevi is based on a few cross-sectional studies. According to these, nevi excised in summer show a higher mitotic count, a greater extent of the junctional component, and more frequent regression and inflammation. Objective: Our goals were to obtain data on the seasonal prevalence of digital epiluminescence microscopy (D-ELM) patterns in acquired melanocytic nevi (AMN) and to test the reliability of D-ELM as a substitute for histology in prospective studies of the morphologic response of AMN to sun exposure. Methods: Two independent series of AMN located on intermittently sun-exposed body sites and undergoing D-ELM in winter ( n = 121) and in summer ( n = 116) were compared for the prevalence of major ELM patterns. Results: Cases in the summer series showed a greater frequency of a broad and prominent pigment network; black dots with varied size, irregular distribution, and peripheral location; and peripheral depigmentation. Conclusion: On the basis of known histologic correlates of D-ELM features, our findings were consistent with studies of seasonal histologic changes in AMN. D-ELM may be a useful tool in the prospective evaluation of effects of sun exposure on AMN morphology.