Vulvar Inspection During Cervical Cancer Screening Procedures: The Ugly Reality.

ABSTRACT: Vulvar examination during procedures for cervical carcinoma screening (CCS) can be a valid chance for early diagnosis of vulvar diseases and precancerous lesions. With this aim an online questionnaire was sent to the members of the Italian Cervical Carcinoma Screening Group (GISCi) from either first level group (FLG, Pap/human papillomavirus test sampling) or second level group (SLG, colposcopy and treatments) to assess if and how vulvar examination was performed. 86% of FLG and 90.2% of SLG report performing vulvar examination prior to CCS procedures. 15% of SLG cannot manage basic vulvar diseases and they refer patients to specialized center. 54.3% underline lack of standardized protocol in case of vulvar disease detection. Despite most health care professionals report examining the vulva during CCS procedures, vulvar cancer early diagnosis is still challenging.

The Consensus Project: Participation in cervical cancer screening by the first cohorts of girls offered HPV vaccination at age 15-16 years in Italy.

OBJECTIVE: To evaluate the association between human papillomavirus vaccination status and participation in cervical cancer screening (at age 25) by the first cohorts of girls who were offered vaccination at the age of 15 to 16 years in Italy. METHODS: Women born in 1993, 1994 and 1995 were invited to participate in cervical cancer screening between 2018 and 2020. We report participation in screening by vaccination status in three large areas, Florence province, Piedmont region and Savona province, where the Consensus Project was carried out. The relative risk of participation among vaccinated (≥2 doses) and unvaccinated women was estimated. Odds ratios (OR) of participation by vaccination status were estimated by logistic regression, adjusted by birthplace and birth cohort. RESULTS: Overall, 34,993 women were invited for screening: 13,006 (37.2%) participated and 10,062 of these agreed to participate in the Consensus intervention study. Among the invited women and screening participants, vaccinated women were 51.0% and 60.6%, respectively. Comparing vaccinated and unvaccinated women, the adjusted OR of screening participation was 1.80 (95% confidence interval (CI): 1.72-1.89), 2.17 (95% CI: 1.94-2.42), 1.59 (95% CI: 1.50-1.68) and 1.15 (95% CI: 0.86-1.54) for overall, Florence, Piedmont and Savona, respectively. About 33% of the invited women were unvaccinated and did not participate in screening: 25.8%, 59.5% and 64.2% of women born in Italy, in high migration pressure countries and in advanced development countries, respectively. CONCLUSIONS: Screening participation was higher among vaccinated than unvaccinated women. Active policies are needed to reduce inequalities, targeting the unscreened and unvaccinated population, particularly non-native women, to accelerate cervical cancer elimination in Italy.

A rare case of syncronous solitary para-pharyngeal metastasis of clear cell carcinoma in a patient with small renal mass.

INTRODUCTION: Unusual metastatic sites of renal cell carcinoma (RCC) are not infrequent. We report a rare case of solitary pharyngeal metastasis as first presentation of RCC. CASE DESCRIPTION: A 74 years-old man was referred to our hospital due to rapidly progressive dyspnoea and dysphagia. Physical examination showed a large right para-pharyngeal mass. Imaging findings showed a 5.5 cm mass, suspicious for malignancy, which extended to right para and retro-pharyngeal spaces with compression of the major right cervical vessels, C2-C3 vertebral bodies osteolysis, dural sac compression and dislocation. Futhermore, a small (2.6 × 2 cm) mass located at the upper pole of the right kidney was shown. Patient underwent partial trans-oral removal of the mass. Pathological examination and immunochemistry resulting strongly suggestive for metastatic RCC. Considering the metastatic stage of the tumour and the rapidly progressive clinical worsening with poor performance status, we offered the patient a palliative treatment with tyrosine kinase and cytoreductive radiotherapy on vertebral bodies. The patient developed a rapidly progressive multifocal metastatic disease and died 4 months after the presentation. CONCLUSION: We think that our case is noteworthy for some aspects. Firstly, pharyngeal localizations of RCC are very rare and this is the first case of solitary pharyngeal metastasis. Secondly, this metastatic lesion was really particular because it was synchronous and twice as big than the primary tumour. Thirdly, this case is consistent with previous evidence that synchronous compared with metachronous metastasis RCC is associated with adverse effect on outcome and response to targeted treatment.

Cancer Diagnostic Delay in Northern and Central Italy During the 2020 Lockdown Due to the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: We performed data collection concerning the coronavirus disease 2019 (COVID-19) pandemic-related delay in the diagnosis of cancers to individuate proper corrective procedures. METHODS: A comparison was made among the number of first pathologic diagnoses of malignancy made from weeks 11 to 20 of 2018, 2019, and 2020 at seven anatomic pathology units serving secondary care hospitals in northern-central Italy. RESULTS: Cancer diagnoses fell in 2020 by 44.9% compared with the average number recorded in 2018 and 2019. Melanoma and nonmelanoma skin cancer represented 56.7% of all missing diagnoses. The diagnostic decrease in colorectal (-46.6%), prostate (-45%), and bladder (-43.6%) cancer was the most relevant among internal malignancies; for prostate, however, high-grade tumors were only moderately affected (-21.7%). CONCLUSIONS: Diagnosis of cutaneous malignancies was mostly affected by the lockdown; among internal malignancies, corrective actions were mostly needed for colorectal cancer and invasive bladder cancer.

[Cervical cancer screening with primary HPV-DNA test in the Local Health Authority 2 of Savona (Liguria Region, Northern Italy): a population-based study]. / Screening cervicovaginale con test HPV-DNA primario nella ASL 2 savonese: uno studio di popolazione.

OBJECTIVES: to describe the performance and the impact on the population coverage of a population-based organised screening programme with primary HPV-DNA test. DESIGN: population-based cohort study. SETTING AND PARTICIPANTS: organised screening programme for women aged 30-64 years. MAIN OUTCOME MEASURES: coverage of the target population with Pap test and HPV-DNA test, compliance to invitation, positivity at HPV-DNA testing, proportion of positive Pap test (squamous cells of undetermined significance or more severe, ASC-US+), referral for colposcopy, positive predictive value (PPV) of the cytology triage for grade-2 or more severe intraepithelial neoplasia (CIN2+), detection rate of CIN2+. Regarding coverage, seasonally adjusted trends of the PASSI surveillance from 2008 to 2014 were analysed. To evaluate performance, data of the information screening system were used. RESULTS: from December 2011 to December 2014, 48,852 women were invited for screening and 22,991 participated (48.4%); in addition, 968 women spontaneously participated in the programme, achieving a total of 23,959 screened women. The HPV test resulted positive for 2,000 women (8.4%). After triage 1,049 women were referred for colposcopy because of ASC-US+ (No. 968) or inadequate result (No. 81). The compliance at 12 months retesting among women with positive HPV test and negative triage was 79.3%, and the HPV positive rate was 60.4%. In the whole, 1,322 women were referred for colposcopy (5.5%) and 1,221 were actually tested. The overall detection rate for CIN2+ was 6.2/1,000. From 2011 to 2014, spontaneous Pap tests passed from 7,461/year to 2,491/year; the test coverage achieved a positive trend and it settles in recent years to 83%, including 43% of HPV-DNA. CONCLUSIONS: compliance to screening of invited women was satisfactory compared to previous experiences in Liguria Region (Northern Italy). Performance indicators confirm what was observed in other Italian experiences.

A two-clones tumor model: Spontaneous growth and response to treatment.

The paper aims at providing a general theoretical frame bridging the macroscopic growth law with the complex heterogeneous structure of real tumors. We apply the "Phenomenological Universality" approach to model the growth of cancer cells accounting for "populations", which are defined not as biologically pre-defined cellular ensemble but as groups of cells behaving homogeneously with respect to their position (e.g. primary or metastatic tumor), growth characteristics, response to treatment, etc. Populations may mutually interact, limit each other their growth or even mutate into another population. To keep the description as simple and manageable as possible only two populations are considered, but the extension to a multiplicity of cell populations is straightforward. Our findings indicate that the eradication of the metastatic population is much more critical in the presence of mutations, either spontaneous or therapy-induced. Furthermore, a treatment that eradicates only the primary tumor, having a low kill rate on the metastases, is ultimately not successful but promotes a "growth spurt" in the latter.

Prognostic significance of high-grade prostatic intraepithelial neoplasia (HGPIN): risk of prostatic cancer on repeat biopsies.

OBJECTIVES: To verify prognostic significance of high-grade prostatic intraepithelial neoplasia (HGPIN) in 65 patients who underwent repeat biopsies with a mean follow-up of 36 months. METHODS: In June 2007, after a retrospective revision of the biopsy reports that were performed between January 2002 and December 2006 because of prostate specific antigen (PSA) values greater than 4 ng/mL, but no clinical or ultrasonographic parameters indicative of prostatic cancer (CaP), we selected 65 patients (group 1) (mean age 63.4 years) with initial HGPIN diagnosis and a control group of another 65 patients (group 2) (mean age 64.5 years) with initial diagnosis of benign prostatic tissue (BPT). All the patients underwent rebiopsies 3 to 12, 13 to 24, 25 to 36, and 37 to 48 months after biopsy. After each rebiopsy, 3 diagnoses were made: BPT, HGPIN, and CaP. Prognostic significance of PSA and HGPIN focality at biopsy were also assessed. RESULTS: Overall, CaP was detected in 14 of 65 (21.5%) group 1 patients and in 15 of 65 (23.0%) group 2 patients. No significant difference was reported between the 2 groups in terms of risk for CaP. Low-medium risk cancer was reported in 12 of 14 (85.7%) cases in group 1 and in 12 of 15 (80.0%) of group 2, mainly after the second rebiopsy. PSA and HGPIN focality at biopsy did not seem to predict CaP diagnosis. CONCLUSIONS: The risk for cancer after HGPIN diagnosis (21.5%) was not higher than the risk reported after BPT diagnosis (23.0%). PSA and HGPIN focality at biopsy do not enhance cancer predictivity. Patients with a HGPIN diagnosis do not seem to need any different follow-up rebiopsy strategy than patients with a BPT diagnosis.

Population screening for coeliac disease in a low prevalence area in Italy.

OBJECTIVE: A screening program was proposed for the village of Carcare (population 5700), located in a region of Italy with an apparently low prevalence of coeliac disease (CD): only 1 patient diagnosed out of 2557 inhabitants. The study group comprised 1002 individuals (568 F, 434 M, age range 13-90 years) recruited from blood donors, secondary school pupils and people referred to the local outpatient facilities for routine blood chemistry. MATERIAL AND METHODS: Total IgA, IgA anti-tissue transglutaminase (tTG) (ELISA, recombinant human antigen) and IgA antiendomysium (EMA) (IFI, umbilical cord substrate) antibodies were measured in the serum of all participants. All patients with IgA deficiency were investigated for IgG tTG antibodies, and in the case of disagreement between tTG and EMA, they were typed for HLA DQ2-DQ8 haplotypes. RESULTS: Thirteen subjects were positive and 988 negative for autoantibodies (3/988 had IgA deficiency). One serum sample was positive for tTG antibodies but negative for EMA. Ten out of 13 positive subjects consented to undergo duodenal biopsy, which invariably produced evidence of CD despite the absence of clinical signs/symptoms. A post-diagnostic clinical investigation provided evidence showing mild iron deficiency (4 subjects) and osteoporosis (2 subjects). After counselling, all subjects accepted a gluten-free diet. CONCLUSIONS: The prevalence of CD in the study group was 1:100 (1.0%; 95% CI: 0.5-1.8%): this indicates that CD is largely underdiagnosed in Carcare. Our results suggest that the low prevalence of CD observed in some regions is likely to be due to underdiagnosis.

Management of patients with gastrointestinal stromal tumors: experience from an Italian hospital.

Gastrointestinal stromal tumors are malignancies originating from stromal/mesenchymal tissues, most commonly in the stomach and small intestine, although they can be located everywhere in the gastrointestinal tract. Diagnosis is based on histological and immunohistochemical examination, and these rare tumors are characterized by c-kit (CD117) staining. Complete removal of the tumor is often curative in localized gastrointestinal stromal tumors and is always recommended. Clinically, their behavior is difficult to predict, and mitotic count and tumor size seem to be the most effective prognostic factors. We performed a retrospective analysis of clinical presentation and course, surgical management and pathological features of patients with gastrointestinal stromal tumors treated in our institution from 1995 to 2003. Twenty-two patients were enrolled in the study, and all of them underwent surgery. There were two perioperative deaths, and global morbidity was about 13%. Nineteen patients were followed (mean, 31 months): 4 patients had disease progression/recurrence and died, and one patient experienced a local recurrence and was reoperated with a curative intent; 14 patients were disease free. Our experience shows that histological and immunohistochemical examinations are fundamental for a definitive diagnosis and to assess the risk of aggressive behavior. Moreover, our results confirm that in stromal tumors complete surgical resection remains the mainstay of treatment in localized gastrointestinal stromal tumors, although the recurrence rate is relatively high. It is conceivable that treatment and prognosis of metastatic and non-resectable gastrointestinal stromal tumors, as well as the adjuvant treatment of high-risk, radically excised gastrointestinal stromal tumors will be strongly impacted by the c-kit target therapy.