Estimating the impact of an organised screening programme on cervical cancer incidence: A 26-year study from northern Italy

The impact of the organised cervical cancer (CC) screening programmes implemented in Europe since the 1990s has been insufficiently evaluated. We investigated the changes in CC incidence following the introduction of a screening programme in the Emilia-Romagna Region (northern Italy). The study period was 1988–2013. The programme, targeting women aged 25–64 years (1,219,000 in 2018), started in 1998. The annual incidence rates that would be expected in 1998–2013 in the absence of screening were estimated, first, by analysing the annual rates in 1988–1997 with a log-linear model and, second, by analysing the annual rates in 1988–2013 with an age-period model in which the period effect was enforced to be linear. Cervical adenocarcinoma incidence trend over the entire period was used to validate both estimates. Observed annual rates were compared to the two series of expected ones with the incidence rate ratio (IRR). Incidence remained stable during 1988–1997, peaked in 1998 and then decreased until 2007, when it stabilised. The two series of expected rates were virtually coincident and their trends roughly paralleled the stable adenocarcinoma incidence trend. After 2007, the median IRR was 0.60 (95% confidence interval, 0.45–0.81) based on the log-linear model and 0.58 (95% confidence interval, 0.34–0.97) based on the age-period model. Thirty-six to seventy-five CC cases were prevented annually for an average annual frequency of 6.5 per 100,000 women in the target population. In summary, consistent circumstantial evidences were obtained that the organised screening programme brought about a 40% reduction in annual CC incidence after 10 years

Small cell neuroendocrine tumor of the breast in a 40 year-old woman: a case report

Abstract Introduction Small cell neuroendocrine cancer of the breast is a rare tumor with less than 30 cases reported in the literature. The morphological and immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung. For this reason, it is often difficult to distinguish a primary small cell neuroendocrine cancer of the breast from a metastatic lesion from other sites. Case presentation We report and characterize with immunohistochemical techniques a case of primary small cell neuroendocrine cancer of the breast occurring in a 40-year-old Caucasian woman. A palpable and mobile 3.0 cm tumor was located in the upper-outer quadrant of her right breast. Lumpectomy and subsequent radical mastectomy with axillary lymph node resection were performed. Microscopically, the tumor consisted predominantly of a diffuse proliferation of small oat cells. The tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. One of 16 lymph nodes was metastatic. A correct treatment needs to be chosen. Conclusions It has recently been demonstrated that early small cell neuroendocrine cancer of the breast shows a good prognosis with adjuvant treatments with high disease free survival. Our patient is alive and well without disease eight years after treatment. We performed an adjuvant therapy with the classic scheme doxorubicin and cyclophosphamide, followed by carboplatin and etoposide. A more extensive review is required to define a standard treatment protocol for this rare neoplasm.</p

Prediction of nodal metastasis and prognosis of breast cancer by ANN-based assessment of tumour size and p53, Ki-67 and steroid receptor expression

Background: Tumour stage and the appropriate course of treatment in patients with breast cancer are primarily characterized by the state of metastasis in the axillary lymph nodes. In recent years, substantial research has focused on the prediction of lymph node status based on various pathological and molecular markers in order to obviate the necessity to carry out axillary dissection. In the present study, artificial neural network (ANN) is employed as the analysis platform to examine the prognostic significance of a group of well-established prognostic markers for breast cancer outcome prediction in terms of nodal status. Furthermore, we investigated existing interactions between these markers. Patients and Methods: The data set contained 66 patient records, where 5 pathological and molecular markers including tumour size, oestrogen receptor status (ER), progesterone receptor status (PR), Ki-67 and p53 expression had been assessed for each patient. The spread of metastasis to the axillary lymph nodes was clinically diagnosed and patients were accordingly categorized into node-positive and node-negative groups. The aforementioned markers were analyzed using a probabilistic neural network (PNN) for nodal status prediction which was considered as the network output. Furthermore, the interactions between these markers were evaluated using different marker combinations as the network input for finding the best marker arrangement for nodal predication. Results: The best prediction accuracy was obtained by a 3-marker combination including tumour size, PR and p53 with 71% accuracy for nodal prediction. Leaving out ER and PR from the full marker set showed approximately the same variations in the results, which is an indication of the direct correlation of these two markers. Furthermore, tumour size was proved to be the most significant individual marker for predicting nodal metastasis. However, when used in combination with Ki-67 the prediction results drop significantly. Conclusion: The results presented here indicate that molecular and pathological markers can provide useful information for early-stage prognosis. However, the interactions between these markers must be considered in order to achieve accurate and reliable prediction

Annual mammography at age 45-49 years and biennial mammography at age 50-69 years: comparing performance measures in an organised screening setting

Objective To compare the results of 5 years of annual mammography screening at age 45–49 with the results of 5 years of biennial screening at age 50–54 and 55–69. Methods In an Italian screening programme, data from 1,465,335 mammograms were analysed. Recall rates, invasive assessment rates, surgical biopsy (including excisional biopsy and definitive surgical treatment) rates, and cancer detection rates were calculated for the first screen (first) and, cumulatively, for the second and subsequent screens (second+). Results The rate ratios between younger women and the two groups of older ones were (in parentheses, original figures per 1000 mammograms if not otherwise specified): recall rate: first 1.11 (103.6 vs. 93.5) and 1.11 (vs. 93.2), second+ 2.10 (208.9 vs. 99.7) and 2.77 (vs. 75.5); invasive assessment rate: first 0.94 (23.0 vs. 24.5) and 0.94 (vs. 24.6), second+ 1.63 (35.8 vs. 22.0) and 1.56 (vs. 23.0); surgical biopsy rate: first 0.68 (5.9 vs. 8.6) and 0.45 (vs. 13.2), second+ 1.35 (11.5 vs. 8.5) and 0.88 (vs. 13.0); total detection rate: first 0.63 (4.3 vs. 6.7) and 0.37 (vs. 11.7), second+ 1.30 (8.9 vs. 6.8) and 0.74 (vs. 12.0); total positive redictive value of surgical biopsy: first 0.93 (72.8% vs. 78.0%) and 0.82 (vs. 88.9%), second+ 0.96 (77.2% vs. 80.5%) and 0.83 (vs. 92.7%). Conclusion Younger women experienced two to threefold higher cumulative recall rates at second+ screens and limited differences in surgical biopsy rate. Albeit encouraging, these results must be completed with further investigation, especially on interval cancer incidence

Results of Compliant Participation in Five Rounds of Fecal Immunochemical Test Screening for Colorectal Cancer

BACKGROUND &amp; AIMS: We investigated the magnitude and temporal patterns of the decreasing trend in main performance measures of fecal immunochemical test (FIT) screening for colorectal cancer (CRC) observed in second and subsequent rounds.METHODS: We followed up 494,187 participants from the first round of a regional biennial FIT screening program in Italy (cut-off value for positivity, 20 mug hemoglobin/g feces) for 5 total rounds (2005-2016). At each round, only compliant participants were eligible. Performance measures from the first, third, fourth, and fifth round were compared with those from the second round (the first incidence round) using rate ratios from multivariate Poisson regression models and relative risk ratios from multinomial logistic regression models.RESULTS: Between the second and the third round, a significant 20% to 30% decrease was found in the proportion of men with a positive FIT result (from 5.2% to 4.3%) and in detection rates of advanced adenoma (from 13.4 to 10.2 per 1000), CRC (from 1.7 to 1.4 per 1000), and advanced neoplasia (from 15.1 to 11.6 per 1000). Positive predictive values (PPVs) decreased by 10% or less between the second and third rounds. Detection rates and PPVs for adenoma stabilized by the fourth and fifth rounds. The PPVs for advanced adenoma, CRC, and advanced neoplasia decreased slightly in men and women by the fourth and fifth rounds. The detection rate of proximal colon cancer stabilized after the second round, whereas the detection rate of distal CRC decreased until the fourth round in men (from 0.7 to 0.3 per 1000), and the fifth round in women.CONCLUSIONS: These findings support the notion that FIT screening prevents progression of a subset of advanced adenomas. Screening intensity could be modulated based on results from previous rounds, with a risk-based strategy

How a faecal immunochemical test screening programme changes annual colorectal cancer incidence rates: an Italian intention-to-screen study

BACKGROUND: This study aimed to evaluate the effectiveness of a biennial faecal immunochemical test (FIT) screening programme in reducing annual colorectal cancer (CRC) incidence in its dynamic target population.METHODS: The target population included over 1,000,000 persons aged 50-69 living in a region of northern Italy. The average annual response rate to invitation was 51.4%. Each observed annual age-standardised (Europe) rate per 100,000 persons between 2005, the year of introduction of the programme, and 2016 was compared with each expected annual rate as estimated with age-period-cohort (men) and age-period (women) models.RESULTS: For both sexes, the rates observed in 1997-2004 and those expected in 2005-2016 were stable. Observed rates increased in 2005, peaked in 2006 (the first full year of screening), dropped significantly below the expected level in 2009, and continued to decrease until 2013 (the eighth full year), after which no further significant changes occurred. In the pooled years 2013-2016, the observed incidence rate per 100,000 persons was 102.2 [95% CI: 97.4, 107.1] for men, 75.6 [95% CI: 71.6, 79.7] for women and 88.4 [95% CI: 85.3, 91.5] for both sexes combined, with an observed:expected incidence rate ratio of 0.68 [95% CI: 0.65, 0.71], 0.79 [95% CI: 0.76, 0.82] and 0.72 [95% CI: 0.66, 0.81], respectively.DISCUSSION: The study provided multiple consistent proofs of a causal relationship between the introduction of screening and a stable 28% decrease in annual CRC incidence after eight years

Invitation strategies for colorectal cancer screening programmes: The impact of an advance notification letter

AIM: To estimate the impact of an advance notification letter on participation in sigmoidoscopy (FS) and fecal immunochemical test (FIT) screening. METHODS: Eligible subjects, invited in 3 Italian population based programmes using FS and in 5 using FIT, were randomised (1:1:1), within GP, to: A) standard invitation letter; B) advance notification followed after 1month by the standard invitation; and C) B+indication to contact the general practitioner (GP) to get advice about the decision to be screened. We calculated the 9-month attendance and the incremental cost of each strategy. We conducted a phone survey to assess GP's utilization and predictors of participation. RESULTS: The advance notification was associated with a 20% increase in the attendance among 15,655 people invited for FS (B vs A - RR: 1.17, 95% CI: 1.10-1.25; C vs A - RR: 1.19, 95% CI: 1.12-1.27); the incremental cost ranged between 10 and 9 Euros. Participation in FIT screening (N=23,543) was increased only with simple pre-notification (B vs A - RR: 1.06, 95% CI: 1.02-1.10); the incremental cost was 22.5 Euros. GP consultation rate was not increased in group C. CONCLUSIONS: An advance notification represents a cost-effective strategy to increase participation in FS screening; its impact on the response to FIT screening was limited