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Abstract Background Surgery is still the standard treatment for aggressive fibromatosis (AF); however, local control remains a significant problem and the impact of R0 surgery on cumulative recurrence (CR) is objective of contradictory reports. Methods This is a single-institution study of 62 consecutive patients affected by extra-abdominal and intra-abdominal AF who received macroscopically radical surgery within a time period of 15 years. Results Definitive pathology examination confirmed an R0 situation in 49 patients and an R1 in 13 patients. Five-year CR for patients who underwent R0 vs R1 surgery was 7.1% vs 46.4% (P = 0.04) and for limbs vs other localizations 33.3% vs 9.9% (P = 0.02) respectively. In 17 patients who had intraoperative frozen section (IFS) margin evaluation R0 surgery was more common (17 of 17 vs 32 of 45, P = 0.01) and CR lower (five-year CR 0% vs 19.1%, respectively, P = 0.04). However, in multivariate analysis only limb localization showed a negative impact on CR (HR: 1.708, 95% CI 1.03 to 2.84, P = 0.04). Conclusions IFS evaluation could help the surgeon to achieve R0 surgery in AF. Non-surgical treatment, including watchful follow-up, could be indicated for patients with limb AF localization, because of their high risk of recurrence even after R0 surgery.

Introduction: An institutional and centralized hospital-based tumour registry (TR) is the ideal supporting tool for the organization and management of clinical data in a comprehensive cancer centre. The purpose of this paper is to describe the development of the TR at the European Institute of Oncology (IEO), Milan, Italy, from its origin to its current applications. Material and methods: After a series of meetings with members of administrative, clinical, research and informatics departments, the TR was activated in March 2006 with the aim of collecting data on all the individuals referred to the institute, with or at risk of developing a tumour. It was implemented on an OracleTM-based interface. A minimum dataset of variables was defined and data collection was divided into four forms, which together gather all the relevant data on patients, tumours, treatments and subsequent events. Results: After a six-month pilot period, which involved the training of the tumour registrars, adjustments to the structure of the registry, development of a data quality control procedure and finalization of the operative protocol, since September 2006 the data collection has been fully operative. Five registrars have been chronologically entering data of all individuals who visited the IEO for the first time since 1 January 2000. As of March 2009, data on 69,637 individuals and 43,567 tumours has been reviewed, recoded and registered in the TR. Twenty-two per cent of the tumours (n=9578) were first invasive primaries, diagnosed and treated in the IEO; the most common sites were breast (n=4972), lung (n=627), intestines (n=479) and prostate (n=376). Conclusion: The IEO TR has been proven functional and reliable in monitoring the activity of the hospital, allowing extraction of data from any subpopulation with characteristics of interest. The structured and centralized TR represents an important tool for our research-oriented institution. [ABSTRACT FROM AUTHOR]

Excessive activation of blood coagulation and neutrophil accumulation have been described in several human cancers. However, whether hypercoagulation and neutrophilia are linked and involved in cancer development is currently unknown. Here we show that spontaneous intestinal tumorigenesis correlates with the accumulation of low-density neutrophils with a pro-tumorigenic N2 phenotype and unprompted neutrophil extracellular traps (NET) formation. We find that increased circulating lipopolysaccharide induces upregulation of complement C3a receptor on neutrophils and activation of the complement cascade. This leads to NETosis, induction of coagulation and N2 polarization, which prompts tumorigenesis, showing a novel link between coagulation, neutrophilia and complement activation. Finally, in a cohort of patients with small but not large intestinal cancer, we find a correlation between neutrophilia and hypercoagulation. This study provides a mechanistic explanation for the tumour-promoting effects of hypercoagulation, which could be used as a new biomarker or as a therapeutic target.

Introduction: Patients with small intestine neuroendocrine tumors present with liver metastases in 50-75% of cases at diagnosis. The aim of the present study was to assess prognostic factors in patients with liver metastases from intestinal neuroendocrine tumor after primary tumor surgical removal with or without liver surgery or radiofrequency ablation. The primary endpoint was disease-specific survival., Methods: Data regarding seventy-eight consecutive patients with liver metastases who undergone primary tumor surgical removal between 1996 and 2011 were extracted from the institutional tumor registry and retrospectively analyzed., Results: Liver tumor burden was <25% in 43 (55.1%) 25-50% in 30 (38.5%) and >50% in 5 (6.4%) patients. For the whole cohort of patients disease-specific survival at 3, 5 and 8 years was 93.2%, 83.6% and 77.3%, respectively. Fifteen patients who underwent radical liver surgery were all alive with a median survival of 106 months (range 18-152 months). In multivariate analysis the Ki-67 index in a continuous fashion significantly correlate with prognosis (p = 0.021). Liver tumor burden (p = 0.036) and extrahepatic involvement (p = 0.03), were the most powerful prognosticators for patients who underwent only debulking surgery., Conclusion: The Ki-67 index, the liver tumor burden and the presence of extrahepatic metastases should be carefully considered in the selection criteria for liver debulking in asymptomatic patients., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Introduction: We describe the clinical features, outcome and incidence of druggable targets of lung cancers in patients ≤ 40 years old., Materials & Methods: Young patients were compared with two other groups (41-64 and ≥ 65 years). Neuroendocrine tumors, adenocarcinoma and non-adenocarcinoma/unspecified non-small-cell lung cancer were analyzed separately. Molecular characteristics of adenocarcinoma were evaluated in a subset of young patients., Results: Of 2847 patients with lung cancer, 100 were ≤ 40 years old. The young group contained more women, never-smokers and patients presenting with advanced disease. The commonest tumor in young patients was adenocarcinoma. In total, 19 of 34 young patients with adenocarcinoma had tumors with specific molecular alterations., Conclusion: Lung cancers in young patients have distinctive features but outcomes similar to those in older patients.

The number of cutaneous melanoma survivors has been increasing for years due to improvements in early diagnosis and subsequent prolonged survival. These patients are at increased risk of developing a second melanoma and a second primary malignancy (SPM) at other sites as well. We performed a review of scientific literature and meta-analysis to evaluate the risk of developing a SPM (other than melanoma) among melanoma patients. Twenty-three independent papers and over 350,000 melanoma patients were included. Risk of cancer among melanoma survivors was increased overall (1.57, 95% CI 1.29-1.90) and at several sites: bone (2.09, 95% CI 1.08-4.05), non-melanoma skin cancer (4.01, 95% CI 1.81-8.87), soft tissue (6.80, 95% CI 1.29-35.98), colon-rectum (1.12, 95% CI 1.00-1.25), female breast (1.14, 95% CI 1.07-1.22), kidney (1.34, 95% CI 1.23-1.45), prostate (1.25, 95% CI 1.13-1.37) and non-Hodgkin lymphoma (1.37, 95% CI 1.22-1.54). The overall risk of SPM showed a tendency to decrease as the time from melanoma diagnosis lengthened. Most of our findings may be explained by the tendency of some exposures, which are risk factors for different tumors, to occur simultaneously in the same individuals. These results suggest primary and secondary cancer prevention counselling for melanoma survivors., (Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Pancreatic neuroendocrine tumors (PNETs) present in more than 50% of cases with liver metastases as the only systemic localization. Liver metastases are unresectable in 80% of cases at diagnosis. In the context of a metastatic disease, the benefit of primary tumor removal in terms of survival is controversial., Methods: A single-center series of patients with PNETs presenting with synchronous unresectable hepatic metastases and treated within a framework of a multidisciplinary team was analyzed retrospectively to assess the prognostic factors and the potential benefit of primary tumor resection on long-term survival., Results: At the time of diagnosis, 12 of 43 patients (28%) underwent primary tumor resection. After a median follow-up of 5 years (range, 0.6-14 years), 22 disease-related deaths were observed. The corresponding 5-year survival and median disease-specific duration of survival were 58% and 77 months, respectively. In the operated and nonoperated patients the 5-year disease-specific survival was 82% and 50%, respectively (P = .027). At multivariate analysis, patients with primary tumor removed had an improved survival compared with patients who did not (hazard ratio 0.18; 95% CI 0.05-0.66; P = .010). Other important factors associated with improved survival at multivariate analysis were lesser age, lesser Ki-67 index, and 25% less liver tumor burden., Conclusion: In the present series of patients with PNETs and unresectable liver metastases, resection of the primary tumor was associated with an improved survival. This observation suggests that resection of the primary tumor should be part of a global therapeutic strategy and its indication and timing should be discussed within a multidisciplinary team., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: The etiology of meningioma is largely unknown, although breast cancer has been suggested to play a role., Methods: A monoinstitutional, retrospective analysis was performed at European Institute of Oncology on 12,330 patients with breast cancer. The cumulative incidence of meningioma was estimated using the Kaplan-Meier method and the log-rank test was used to assess differences between groups., Results: In total, 33 patients with meningioma were identified from a study population of 12,330, with a 10-year cumulative incidence of meningioma of 0.37%. We did not find a significantly increased risk of meningioma among patients with breast cancer or an association between the hormonal receptor status and the risk of meningioma (P = 0.65)., Conclusions: Our results do not support a role of breast cancer or endocrine treatments in meningioma development., Impact: This analysis adds new information on a debated topic.

Background: Previous studies have reported an association between sun exposure and improved cutaneous melanoma (CM) survival. We analysed the association of UV exposure with prognostic factors and outcome in a large melanoma cohort., Methods: A questionnaire was given to 289 (42%) CM patients at diagnosis (Group 1) and to 402 CM patients (58%) during follow-up (Group 2). Analyses were carried out to investigate the associations between sun exposure and melanoma prognostic factors and survival., Results: Holidays in the sun two years before CM diagnosis were significantly associated with lower Breslow thickness (p=0.003), after multiple adjustment. Number of weeks of sunny holidays was also significantly and inversely associated with thickness in a dose-dependent manner (p=0.007). However when stratifying by gender this association was found only among women (p=0.0004) the risk of CM recurrence in both sexes was significantly lower in patients (n=271) who had holidays in the sun after diagnosis, after multiple adjustment including education: HR=0.30 (95%CI:0.10-0.87; p=0.03) conclusions: Holidays in the sun were associated with thinner melanomas in women and reduced rates of relapse in both sexes. However, these results do not prove a direct causal effect of sun exposure on survival since other confounding factors, such as vitamin D serum levels and socio-economic status, may play a role. Other factors in sun seeking individuals may also possibly affect these results.

The impact of breast surgery on survival of metastatic breast cancer (MBC) patients is controversial. We addressed the question in a mono-institutional series of MBC patients with synchronous bone metastases. We identified 187 consecutive women diagnosed between 2000 and 2008 with locally operable (T1-T3) MBC, synchronous bone metastases, with no other distant sites being involved. Progression-free survival (PFS) and overall survival (OS) were compared between operated and non-operated patients. Median age was 51 years; 92 % of the women had a hormone-positive tumor. At the time of diagnosis, 131 patients out of 187 (70 %) underwent surgery. Operated and non-operated patients differed in terms of number of bone metastatic sites: a single metastasis was detected in 35 (28 %) operated, and 6 (11 %) non-operated cases (P = 0.01). No other significant differences were observed. The multi-adjusted hazard ratio was 0.63 (95 % CI 0.43-0.92) for PFS and 0.64 (95 % CI 0.41-0.99) for OS in favor of surgery. The 5-year cumulative incidence of ipsilateral breast skin progressions among non-operated patients was 18 %. In this large and homogeneous series of MBC patients with synchronous bone metastases, the role of breast surgery had a favorable impact on both disease progression and mortality.

Background and Purpose: For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial. The purpose of this study was to identify clinical and/or pathological findings related to a worse prognosis in this category of patients., Patients and Methods: We retrospectively analyzed the data of consecutive patients, extracted by an institutional Tumour Registry, admitted to an affiliated University Hospital in Milan (European Institute of Oncology) for adenocarcinoma of the colon (all sites), between 2000 and 2005, and having a final pT3 N0 pathology staging after curative surgery. Adjuvant chemotherapy was decided as a result of a medical decision within a multidisciplinary Tumor Board., Results: Data of 137 patients were obtained, with a median follow-up of 77 months (range 6-131). Patients who received chemotherapy were younger than patients who did not. Nine patients out of 137 (6.5 %) died as a consequence of colon cancer recurrence; four of them had received adjuvant chemotherapy. Only histological grade III and mucinous histotype were found to impact on cumulative incidence of colon-related events (p 0.03 and 0.02, respectively); no impact was found on cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.74 and 0.74, respectively). Number of analyzed LNs (lymph nodes) emerged as a factor possibly affecting the cumulative incidence of colon-related events (p 0.09) as well as the cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.10). The risk of events was inversely proportional to the number of dissected LNs, even over 20 up to about 25 LNs. Never-smokers exhibited a lower incidence of colon-related events, although the difference was not statistically significant (p 0.09). All other analyzed variables did not show any impact on survival rate, including age, gender, ASA score, BMI, site of colonic neoplasm, multifocality, perivascular invasion, and use of adjuvant chemotherapy., Conclusions: Histology grading G3 and mucinous histotype were predictors of worse outcome. Efforts to improve LN evaluation should result in clinically significant improvements in outcome, and also the quality of care for patients with radically resected stage II colon cancer.

Objective: To predict presence of invasive component and nodal involvement in women diagnosed preoperatively with ductal carcinoma in situ (DCIS) by vacuum-assisted breast biopsy (VABB)., Materials and Methods: We retrospectively analyzed 733 patients with preoperatively diagnosed DCIS, investigating the association of clinical-radiological variables with invasive component and nodal involvement., Results: Mammographic size >20 mm and residual lesion on post-VABB mammogram were related to invasive component (both p < 0.0001) and nodal involvement (p = 0.001, p = 0.03). Age <40 years was associated with presence of invasive component (p = 0.003). By multivariate analysis residual disease was associated with invasive component, and mammographic tumor size >20 mm with nodal involvement, both highly significant., Conclusions: Older age, lesion <20 mm, and no residual lesion predict absence of invasion and no nodal involvement in VABB-diagnosed DCIS. However it would be imprudent to routinely forego sentinel node biopsy in such patients as non-negligible proportions of them have invasive disease., (Copyright © 2012 Elsevier Ltd. All rights reserved.)