Patients with cancer who will be cured and projections of complete prevalence in Italy from 2018 to 2030.

BACKGROUND: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking. MATERIALS AND METHODS: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis. RESULTS: A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and ∼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2 million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1 - cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%). CONCLUSIONS: Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning.

The burden of cutaneous adnexal carcinomas and the risk of associated squamous cell carcinoma: a population-based study.

BACKGROUND: Recent studies have shown an increasing incidence of cutaneous adnexal carcinomas (CACs). OBJECTIVES: The aim of our study was to evaluate incidence and survival for cases of CACs and investigate their association with other skin neoplasms. METHODS: We conducted a population-based study. Data on incident cases of CACs were obtained from the Tuscany Cancer Registry between 1985 and 2010. In order to determine whether the occurrence of squamous cell carcinoma (SCC) among patients with CAC is higher or lower than expected in the general population, the standardized incidence ratio (SIR) was calculated. RESULTS: A total of 242 patients with CAC were observed; the age-standardized incidence rate was 3·8 cases per million person-years. From 1997 to 2010 crude incidence rates increased by 159%. Age-specific incidence was higher in men over 80 years old than in women of the same age and younger individuals. Carcinomas of sweat gland origin prevailed; the most common histotype was porocarcinoma and the most frequently affected site was the head/neck. Overall, 88% of CACs were diagnosed at a localized stage. The 5-year overall survival and disease-specific survival rates were 59% [95% confidence interval (CI) 53-65] and 94% (95% CI 91-98), respectively. In the observation cohort, the number of SCCs was significantly higher than expected as the SIR was calculated to be 33·7 (P < 0·001). CONCLUSIONS: Increasing incidence warrants awareness and early diagnosis of CACs. Increased SCC incidence among patients with these tumours highlights the relevance of careful skin examination and follow-up.

How staging of thin melanoma is changed after the introduction of TNM 7th edition: a population-based analysis.

INTRODUCTION: In 2009, the American Joint Committee on Cancer (AJCC) incorporated the tumor mitotic rate in the melanoma pathological TNM staging system. To investigate the effect of this change on the pT1 substaging of primary cutaneous melanomas, we reclassified the cases collected by a cancer registry according to the 6th and the 7th editions of AJCC melanoma staging. METHODS: Patients with pathological T1 melanoma diagnosed in the period 2000-2008 were selected from Tuscan Cancer Registry. The histological reports were reviewed and pT1 melanomas classified according to both the 6th and the 7th editions of the AJCC staging system. The shift of melanomas between pT1 substages was analyzed. RESULTS: Among the 242 pT1 melanomas collected in the study period and with mitotic index available, there were 202 (83 % of all pT1) and 175 (72 %) pT1a, according to the 6th and the 7th editions of the AJCC melanoma staging, respectively. When the 7th edition was used, 20 % of all pT1a melanomas shifted to pT1b, and 32 % of all pT1b melanomas shifted to pT1a. A poor level agreement between the two TNM staging systems, measured by the Cohen's kappa coefficient, was found (K = 0.37). CONCLUSIONS: The addition of mitotic activity to the pathological staging resulted in an increase in pT1b proportion and in a change in the classification of some cases. This modification could influence the clinical approach, with a different use of the sentinel lymph node biopsy, and underlines the role of mitosis evaluation in the management of thin melanoma patients.

Long-term survival, prevalence, and cure of cancer: a population-based estimation for 818 902 Italian patients and 26 cancer types.

BACKGROUND: Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking. PATIENTS AND METHODS: Data on 818 902 Italian cancer patients diagnosed at age 15-74 years in 1985-2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds. RESULTS: The cure fractions ranged from >90% for patients aged <45 years with thyroid and testis cancers to <10% for liver and pancreatic cancers of all ages. Five- or 10-year CRS >95% were both reached in <10 years by patients with cancers of the stomach, colon-rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. For breast cancer patients, 5- and 10-year CRSs reached >95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained <95% for >25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%. CONCLUSIONS: A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective.

Trends in colorectal incidence by anatomic subsite from 1985 to 2005: a population-based study.

BACKGROUND: Conflicting results on the shift of right-left ratio in colon cancer incidence have been reported. We examine incidence trends by subsite in a population-based study. MATERIALS AND METHODS: Colorectal cancer cases diagnosed in the 1985-2005 period were identified through the Tuscany Cancer Registry. Colon subsite was defined as proximal and distal; gender, age at diagnosis, histology, and stage were analyzed. Average annual incidence and age-specific rates according to subsite were calculated. RESULTS: A total of 21,160 colorectal cancer cases were extracted; in 18,311 cases, the subsite was identified: 6,916 rectal, 5,239 proximal, and 6,156 distal. A larger proportion of distal colon cancers presented as early stage when compared with proximal. Incidence of rectal and distal colon cancer remained stable, while proximal colon cancer incidence increased. CONCLUSIONS: Proximal colon cancer incidence rate increased through the period. Temporal variations in the incidence rate by subsite could suggest different carcinogenic pathways of right- and left-sided colon cancer.

Population-based survival of penile cancer patients in Europe and the United States of America: no improvement since 1990.

INTRODUCTION: Penile cancer is a rare neoplasm in Western countries, and detailed studies on trends in population-based survival of penile cancer have never been published before. We examined population-based trends in survival in Europe and the United States of America (USA). METHODS: Data from 3297 European and 1820 American penile cancer patients, contributed by 12 European cancer registries and the Surveillance, Epidemiology, and End Results (SEER) Program of the USA were included in this study. Period analysis techniques were used to examine relative survival trends overall, as well as for four geographic regions in Europe, and for the age groups 15-54, 55-64, 65-74 and 75+ for both populations between 1990-1995 and 2002-2007. Survival trends were assessed in a multiple regression model of relative excess risk including period of diagnosis, age and continent. RESULTS: The 5-year relative survival of penile cancer patients increased statistically non-significantly from 65% to 70% in Europe and decreased (significantly) from 72% to 63% in the USA. Trends in age-specific 5-year relative survival did not find any significant improvement in either Europe or the USA. The multiple regression analysis confirmed the lack of survival trend, and found significantly higher relative excess risk with age, and, apparently due to lower survival before 2002-2007, higher risk in Europe. CONCLUSION: Survival for penile cancer patients has not improved in either Europe or the USA since at least 1990. The reasons for the decrease of survival in the USA remain unknown and to be explored. Stronger international cooperation in clinical research may be important to facilitate clinical progress in treatment and thereby improvement of survival of this rare malignancy.

Invasive breast cancer: a significant correlation between histological types and molecular subgroups.

INTRODUCTION: The special types of breast cancer seem to have not only distinct morphological features but also distinct biological features. MATERIALS AND METHODS: Women diagnosed with a first primary invasive breast cancer in the 2004-2005 period were identified through Tuscan Cancer Registry. Information on age, tumor size, lymph node status, histological type and grade, hormonal receptors, HER2 immunohistochemical expression were collected. Five subtypes were defined: luminal A, luminal B HER2+, luminal B HER2-, triple negative, and HER2 positive. The association between the histological type and molecular subgroups was assessed by a Fisher's exact test, and a multinomial logistic regression model was used. RESULTS: Out of 1,487 patients, 34 % were luminal A subtype, 25 % luminal B HER2-, 11 % luminal B HER2+, 19 % triple negative, and 10.2 % HER2+; 58.5 % of cancers were ductal NOS types. With luminal A as reference, histological types distribution was significantly different between the subgroups. Mucinous, tubular, and cribriform histotypes were found among luminal A cancers more than in other subgroups; all medullary carcinomas were triple negative cancers. Pathological stage at diagnosis was more advanced, and histological grade was lower among subgroups other than luminal A. CONCLUSIONS: Significant association between breast cancer histotypes and molecular subgroups was found.

Biological characteristics of interval cancers: a role for biomarkers in the breast cancer screening.

INTRODUCTION: In a population-based screening program, a percentage of tumors remain undetected; these tumors comprise a heterogeneous group, and they are more likely to have adverse prognostic features. The aim of this study was to identify differences in biological characteristics of screen-detected versus interval breast cancers in a population-based screening program according to molecular subtypes. MATERIALS AND METHODS: We analyzed the population-based data from a long-running screening program in the area of Florence. Data on screening history and on age, T and N status, grade, histotype, hormonal status and Ki-67 and HER2 expression were retrieved. Subtypes of breast cancer were defined on the expression of ER, PR, Ki-67 and HER2: luminal A if ER/PR+, HER2- and Ki67 <14 %, luminal B (HER2 negative) if ER/PR+, HER2- and Ki67 ≥14 %, luminal B (HER2 positive) if ER/PR+ and HER2+, triple negative if ER/PR-and HER2-, HER2 positive if ER/PR- and HER2+. Association between molecular subtypes and mode of detection will be evaluated by a logistic regression model adjusted for the potential confounding variables. RESULTS: Information about biomarkers was known for 277 cases, 211 screening-detected and 66 interval cancers. Among interval cases, the triple-negative cancers were more represented than luminal A (OR = 3.52; CI, 1.112-11.13; p = 0.0319), while the proportion of HER2+ was quite similar (OR = 1.57; p = 0.4709). CONCLUSION: Although made on a small number of cases, our results suggest a difference in distribution of molecular subtypes according to mode detection, confirming the results of earlier studies.

Typical and atypical carcinoid tumours: 20-year experience with 89 patients.

AIM: The aim of this study was to conduct a retrospective clinical and pathological analysis of the authors' 20-year experience on treatment of typical and atypical carcinoid tumours. METHODS: A retrospective clinical and pathological analysis was conducted on 89 patients treated for bronchial carcinoid neoplasms at the Division of Thoracic Surgery, Hospital of Florence (Italy) between January 1986 and January 2006. They were 47 male (52.8%) and 42 female patients, age ranging from 22 to 77 years (average: 55.5 years). Diagnosis was made with radiological methods such as plain chest roentgenography, computed tomography (CT), and bronchoscopy. On the basis of bronchoscopic findings 63 carcinoids (70.8%) were centrally located and 26 (29.2%) were classified as peripheral. In 38 cases of central lesion the diagnosis was obtained by endobronchial biopsy. A correct pathological diagnosis was obtained before surgery in 58 patients; in the others resected cases the correct diagnosis was determined by intraoperative histology during surgery. All operation were performed through a thoracotomy, with sparing muscle in last ten years. Surgical procedures utilized were lobectomy, pneumonectomy, segmentectomy, wedge resections, sleeve resections and bronchoplastic procedures. A radical mediastinal lymphadenectomy was performed in every operation. RESULTS: There were 63 (70.8%) typical carcinoid (TC) and 26 (29,2%) atypical carcinoid (AC). No operative or postoperative mortality was seen. Ten patients (11.7%) experienced complications: 4 prolonged air leaks, 2 bleeding requiring re-operation, 1 chylothorax, 1 pulmonary embolism, 2 late cicatricial bronchial stenosis after sleeve lobectomy treated successfully by laser therapy. Four patients (4.5%) were treated with endoscopy plus surgery. In all that patients a Laser Nd-YAG coagulation and excision of the lesion was performed. Four patients (4.5%) were treated only with endoscopy, overall because of bad general condition. On the basis of the hystopatological documentation of all patients operated before 1999 (60 patients) the authors observed that in 4 cases (6.6%) the diagnosis has changed from AC to TC while only 1 case (1.6%) of AC was classified as TC with new criterias. During median 122-month follow-up 7 relapses (8.2%) were diagnosed in operated patients; recurrent cancer developed preferentially in AC (N=4, 16.6%) than TC (N=3, 4.9%). The overall survival at 10 and 15 years was 92% and 82% respectively. CONCLUSIONS: Anatomical resection, including formal lobectomy (or pneumonectomy when indicated) and radical mediastinal lymphadenectomy, should be performed in carcinoid tumours.

Gender differences in non-small cell lung cancer: a population-based study.

BACKGROUND: A retrospective study including all patients with non-small cell lung cancer carcinoma in a population-based registry was performed to characterize gender differences in lung cancer and to analyze the factors influencing prognosis in women. METHODS: We retrieved through the Tuscan Cancer Registry (RTT) archive 2,523 lung tumor cases diagnosed during the period 1996-1998 in the provinces of Florence and Prato, central Italy. We compared the prognosis within 464 non-small lung cancer women and 1,798 men in a population-based case series. The influence of the following variables on postoperative survival were analyzed: age, cell type, pathologic T and N status, site of tumor and type of surgical resection. RESULTS: The age at diagnosis was similar in women and in men. Women were significantly more likely to have adenocarcinoma but less likely to have squamous cell carcinoma compared with men. Fewer pneumonectomies were performed in women than in men. Nevertheless, prognosis was similar in both sexes and type of surgical resection was significant prognostic factor. CONCLUSIONS: Lung cancer was more frequent in men than in women, but overall survival is similar. Differences in lung cancer histology and rate of pneumonectomies were found between men and women.

Inducible cyclooxygenase (COX-2) in glioblastoma--clinical and immunohistochemical (COX-2-VEGF) correlations.

Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme responsible for the first step in the prostaglandin synthesis. COX-2 upregulation is demonstrated in different tumors. COX-2 products may modulate tumoral growth, apoptosis, metastasis, multidrug resistance and angiogenesis. Moreover, the antitumoral effect of the COX inhibitors has been documented. We studied the immunohistochemical expression and the prognostic value of COX-2 on 43 surgical specimens of glioblastoma-affected patients. Furthermore, we evaluated the correlation between the immunohistochemical expression of COX-2 and vascular endothelial growth factor (VEGF). Of the glioblastomas, 63% resulted as COX-2-positive. Median survival of the patients with COX-2-positive lesions was 10 months; median survival of the patients with COX-2 negative glioblastoma was 21 months (NS). All 4 patients who survived longer than 24 months had COX-2 negative lesions (p = 0.017). Concordance between COX-2 and VEGF was documented in 60% of the cases. Our findings show that glioblastoma can immunohistochemically express COX-2 and that its expression is unrelated with VEGF and significantly less frequent in the long survivors. Nevertheless, the absence of statistical correlation with survival time advises further studies on larger series to ascertain the concrete prognostic value of COX-2 in glioblastoma.

[BCL-2 in primary central nervous system lymphomas. Immunohistochemistry and molecular biology]. / La BCL-2 nei linfomi primitivi del sistema nervoso centrale. Immunoistochimica e biologia molecolare.

BCL-2 is a membrane protein known to be an apoptosis inhibitor. It is the product of the bcl-2 gene located on chromosome 18. Several different tumors show BCL-2 over-expression as result of a translocation or independently from it. More than 85% of follicular lymphomas and a smaller number of diffuse large cell B lymphomas contain t(14;18) (q32;q21). The aim of this study was to investigate the immunohistochemical expression of the BCL-2 protein and to ascertain, by means of traditional PCR (Polimerase Chain Reaction), its possible dependence from t(14;18) (q32;q21) in 9 primary central nervous system lymphomas. Six cases (67%) shoved immunohistochemical BCL-2 over-expression and 3 cases (33%) had t(14;18). Precisely: 2 cases (22%) had immunohistochemical BCL-2 over-expression and t(14;18) (q32;q21); 4 cases (44%) had BCL-2 over-expression without translocation; 1 case (11%) did not show diffuse BCL-2 over-expression in presence of the traslocation; the remaining 2 cases (22%) did not demonstrate BCL-2 over-expression or t(14;18) (q32;q21). In conclusion, our results indicate primary central nervous system lymphomas frequently show BCL-2 over-expression that in some case may be related to t(14;18) (q32;q21). Nevertheless, t(14;18) (q32;q21), as evaluated by traditional PCR, may not correspond to diffuse immunohistochemical BCL-2 positivity.

[Thin-layer cytology in endometrial diagnosis]. / La citologia su strato sottile nella diagnostica endometriale.

Our purpose was to test the liquid-based thin layer method on the endometrial cytology. One hundred sixty two consecutive patients before the hysterectomy (55 women because of various causes; 107 asymptomatic postmenopausal women because of prolapsed uterus) had the endometrial cytology (all women) and the biopsy (107 postmenopausal women prolapsed uterus affected). Cytohistologic concordance was 98%: all endometrial neoplasms and atypical hyperplasia (10 cases) and 15 of the 18 (83%) simple hyperplasias were diagnosed by thin layer endometrial cytology. In asymptomatic postmenopausal women cytology gave sufficient material for the diagnosis significantively more often than endometrial biopsy (respectively 82% and 24%; p = 0.000).

Oligodendroglioma: CD44 as a possible prognostic opportunity.

CD44, in its standard form as well in its isoforms, is a cell surface adhesion glycoprotein which occurs in a wide variety of non-neoplastic and neoplastic cells. CD44 has been considered to be implicated in tumoral growth and in metastatic potential. We studied the immunohistochemical expression of CD44 standard in 30 oligodendrogliomas (19 primary lesions and 11 recurrences) in order to verify its possible prognostic role. Twelve primary oligodendrogliomas (63%) and 8 recurrences (73%) were CD44-positive. Three of 9 (33%) primary oligodendrogliomas with a Smith grade A-B and 9 of 10 (90%) primary oligodendrogliomas with a Smith grade C-D were found to be in CD44H-positive (p = 0.020). Three of 9 (33%) primary oligodendrogliomas that had not relapsed and 9 of 10 (90%) successively relapsed primary lesions were found to be CD44H-positive (p = 0.020). Median survival of the patients with a CD44H-positive lesion was 84 months; median survival of the patients with a CD44H-negative lesion was 91 months. We conclude that CD44H could have prognostic value regarding the occurrence of relapses.

[Thin-layer cytology in urinary diagnosis]. / La citologia su strato sottile nella diagnostica urinaria.

To evaluate the thin-layer method in urinary cytology we have compared cytospin smears, filter and thin layer. Cellularity, cellular morphology and background were evaluated. Thin layer method in urinary cytology improve cell recovery and cell preservation, reducing background artefact. Cytohistologic correlations with thin layer method were better than with filter and cytospin; an higher capacity to detect low grade transitional cell carcinomas, frequently undiscovered by cytology, was demonstrated.

[Atypical, aplastic, and unusual meningiomas. Morphology and incidence in 300 consecutive cases]. / Meningiomi atipici, anaplastici ed inusuali. Morfologia ed incidenza in 300 casi consecutivi.

We morphologically studied 300 consecutive and primitive meningiomas surgically treated between march 1997 and april 2002 in order to evaluate the incidence of atypical, anaplastic, and morphologically unusual meningiomas. Two hundred and fifty-five meningiomas (85%) were WHO I, 33 (11%) were WHO II, 9 (3%) were WHO III; the remaining 3 meningiomas (1%) showed clear and diffuse oncocytic differentiation without cytologic or architectural atypia (oncocytic meningiomas). Forty-five of 255 WHO I meningiomas (18%) were infrequent histological subtypes: 18 (7%) psammomatous, 9 (4%) metaplastic, 9 (4%) secretory, 6 (2%) angiomatous, and 3 (1%) microcystic. Thirty of 33 WHO II meningiomas (91%) were atypical, 2 (6%) were clear cell meningiomas, and 1 (3%) was chordoid meningioma. Seven of 9 WHO III meningiomas (78%) were anaplastic and 2 (22%) were papillary. We evidenced the high morphological variability and the discrete occurrence of WHO I and WHO II meningiomas.

[Estrogen and progesterone receptors in meningiomas: immunohistochemical (Mib-1, p53) and clinico-morphological correlations]. / Recettori estro-progestinici nei meningiomi: correlazioni immunoistochimiche (Mib-1, p53) e clinicomorfologiche.

We studied 98 meningiomas including 89 benign, 5 atypical, and 4 anaplastic tumors to determine the immunohistochemical expression of estrogen and progesterone receptors and its prognostic value in comparison to histological grade, Mib-1 and p53. Estrogen and progesterone receptor positivity was observed in 63% and 5% of the cases, respectively. In 79% of meningiomas only a minimal proliferative activity was documented, whereas in 36% we detected an overexpression of the p53 oncoprotein. Anaplastic meningiomas were constantly negative for PgR, ER, and highly positive for Mib-1; 75% were positive for p53. A statistical correlation was demonstrated between p53 protein and Mib-1. Specifically the p53-negative meningiomas were frequently negative for Mib-1 (p = 0.002); conversely the lesions strongly positive for Mib-1 were p53-positive (p = 0.001).