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Background: Chylothorax following pulmonary resection and lymphadenectomy for cancer is a potential severe complication in thoracic surgery. In the present study, we investigated the efficacy of the nonsurgical approach as well as the need for reoperation after conservative approach failure., Methods: Chylothorax was diagnosed when chylous leakage from the chest drainage was observed and confirmed by the presence of triglycerides in the pleural fluid. We initially treated all the patients conservatively with complete oral intake cessation and total parenteral nutrition; if drainage output remained more than 800 mL/d after the first 5 days or major pleural effusion was observed at chest X-ray after chest tube removal, surgical treatment of chylothorax was indicated., Results: Between January 1998 and December 2018, 5,072 patients underwent standard anatomical resection and mediastinal lymph node dissection for cancer at our institution. Among them, 30 patients (0.6%) developed chylothorax: 20 patients were effectively treated only by nil per os and low-fat diet, while 10 patients (33.3%) required surgical treatment. Mean age was 63 years; there were 24 male patients (80%); right-sided chylothorax was more frequent than left-sided chylothorax (22 vs. 8, respectively) although not statistically significant ( p  = 0.38); the only factor that seems to influence the need for reoperation is chylothorax flow rate during conservative treatment ( p  = 0.06)., Conclusion: Conservative treatment is effective in the case of low flow-rate chylothorax (< 800 mL/d); in the case of a higher flow rate, surgical exploration is needed and thoracic duct ligation-with or without lymphatic sites clipping-provides definitive lymphostasis., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme. All rights reserved.)

The purpose of this study is the evaluation of clinical and surgical impact of the Z0011 trial criteria on the management of breast cancer (BC) patients undergoing breast conservative surgery (BCS) at the European Institute of Oncology (IEO). We studied 1386 patients who underwent BCS and sentinel lymph node biopsy (SLNB) from July 2016 to July 2018. Clinical evaluation, breast ultrasound, mammogram, and cyto/histological examination were performed for all patients at the time of diagnosis. Frozen sections of the sentinel lymph node (SLN) were not performed for any patient. Patients who underwent neo-adjuvant therapy were excluded. To evaluate the results before and after the introduction of Z0011 criteria, a group of 1425 patients with the same characteristics who underwent BCS and SLNB from July 2013 to July 2015 were analyzed. We studied the characteristics of the patients by nodal status, and we observed that T stage, tumor grade, and lymphovascular invasion were statistically related with the highest rate of positive SLN. Of the 1386 patients who underwent surgery after the introduction of the Z011 trial, 1156 patients (83.4%) had negative SLN, 230 patients (16.6%) had positive SLN. Subsequent axillary lymph node dissection (ALND) was performed in only 7 cases (3.0%). Of the 1425 patients operated before the introduction of the Z0011 trial, 216 patients had subsequent ALND (15%). The reduction in the number of ALND performed after the introduction of Z0011 is statistically significant, and this could result in a remarkable reduction of the comorbidities of our patients., (© 2020 Wiley Periodicals LLC.)

Background: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation., Patients and Methods: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated., Results: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT., Conclusions: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Background: This study investigated the risk of reconstruction failure after mastectomy, immediate breast reconstruction, and radiotherapy to either a temporary tissue expander or permanent implant., Methods: Records of women treated at a single institution between June of 1997 and December of 2011 were reviewed. Two patient groups were identified based on type of immediate breast reconstruction: tissue expander followed by exchange with a permanent implant and permanent implant. The study endpoint was rate of reconstruction failure, defined as a replacement, loss of the implant, or conversion to flap., Results: The tissue expander/permanent implant and the permanent implant groups consisted of 63 and 75 patients, respectively. The groups were well balanced for clinical and treatment characteristics. With a median follow-up of 116 months, eight implant losses, 50 implant replacements, and four flap conversions were recorded. Reconstruction failure occurred in 22 of 63 patients in the expander/implant group and in 40 of 75 patients in the permanent implant group. A traditional proportional hazards model showed a higher risk of reconstruction failure for the expander/implant group (hazard ratio, 2.01) and a significantly shorter time to reconstruction failure compared with the permanent implant group (109.2 months versus 157.7 months; p = 0.03); however, according to a competing risk model, the between-groups cumulative incidences were not significantly different (hazard ratio, 1.09)., Conclusions: Radiotherapy to either a tissue expander or a permanent implant presented a fairly large risk of reconstruction failure over time. The expander/implant group was not more likely to develop reconstruction failure compared to permanent implant group, but the timing of onset was shorter. More complex techniques should be investigated to lower the risk of reconstruction failure., Clinical Question/level of Evidence: Therapeutic, III.

Background/aim: The role of anti-PD1/PD-L1 therapy (IO) in NSCLC harboring driver mutations is questionable. This study aimed to examine the efficacy of IO in patients with non-small cell lung cancer (NSCLC) with a KRAS mutation (KRAS + )., Patients and Methods: We retrospectively identified NSCLC patients harboring KRAS mutation treated with IO in our Institution. We analyzed the results in comparison to non-KRAS patients., Results: Among 328 consecutive KRAS + NSCLC patients, 43 (13.1%) received IO in our Institution. In parallel 117 non-KRAS NSCLC patients treated with IO were selected for comparison. The baseline characteristics were similar between the two groups. No significant difference was observed between KRAS + and non-KRAS patients in terms of mPFS (4.6 vs. 3.3 months, p=0.58) or OS (8.1 vs. 13.0 months, p=0.38)., Conclusion: KRAS mutations seem to be irrelevant for selecting patients for IO that could be therefore considered an effective therapy for NSCLC patients, independently of KRAS status., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: The aim of the study was to investigate the distribution of high-risk (HR) human papillomavirus (HPV) genotypes and the role of multiple infection in preneoplastic and neoplastic cervical lesions, according to histology, age, and the number of genotypes per infection., Materials and Methods: Nine hundred eighty-eight women affected by known HPV-related cervical lesions and attending the European Institute of Oncology, Milan, Italy, from December 2006 to December 2014, were selected for a cross-sectional study. Prevalence of HPV genotypes was calculated by histology and the number of genotypes per infection. Univariate and multivariable cervical intraepithelial neoplasia (CIN) 2-3 versus CIN 1 risks were estimated by logistic regression models., Results: Overall, HPV 16 (53.1%), HPV 31 (15.1%), and HPV 58 (6.4%) were the most frequent genotypes in precancerous lesions. At multivariable analysis, HPV 16 (p = .02), 18 (p = .013), and 56 (p = .01) were significantly associated to worsen histology, whereas HPV 39 (p = .03) and 45 (p = .03) were statistically correlated only to the increasing number of genotypes per infections. Human papillomavirus 33 was the only genotype significantly related to both the number of genotypes per infection (p = .005) and age (p = .03). Infections by HR-HPV (odds ratio [OR] = 9.48, 95% CI = 3.77-23.8, p < .001), HPV genotypes covered by current vaccines (OR = 6.28, 95% CI = 4.05-9.75, p < .001), single HPV genotype (OR = 8.13, 95% CI = 4.12-16.0, p < .001), as well as age (OR = 1.13, 95% CI = 1.07-1.19, p < .001) were significantly associated to higher risk of CIN 2-3., Conclusions: The most of CIN 2+ lesions are sustained by HR-HPV genotypes, especially the ones covered by 9-valent vaccine; therefore, the widespread use of prophylactic HPV vaccines could significantly reduce the incidence of preneoplastic and neoplastic cervical lesions.

Background: Testing for circulating biomarkers in lung cancer is hampered by the insufficient specificity. We aimed to assess the relative diagnostic accuracy of pro-gastrin-releasing peptide (ProGRP) for the differential diagnosis of small cell lung cancer and compare it with more conventional biomarkers., Methods: We enrolled a cohort of 390 patients with a clinical suspicion of lung cancer and for whom a histologic assessment was available. Serum or plasma samples were assessed for ProGRP, carcinoembryonic antigen, CYFRA 21-2, and neuron-specific enolase. The performance of each biomarker in discriminating the small cell lung cancer and squamous cell carcinoma/adenocarcinoma from non-malignant lung disease, and small cell lung cancer from squamous cell carcinoma/adenocarcinoma, was assayed by receiver operating characteristic curve analysis., Results: At the cut-off levels suggested by the manufacturers, ProGRP and neuron-specific enolase showed an almost identical sensitivity of 55.2% and 55.6%, respectively, in discriminating small cell lung cancer with respect to non-malignant lung disease. In order to quantify the added value of ProGRP to other conventional markers, we ran a multivariable logistic regression analysis, but the results showed that no markers improve the performance of ProGRP., Conclusions: ProGRP and neuron-specific enolase individually appear more accurate than other conventional biomarkers for small cell lung cancer, but the union of two markers does not increase the accuracy. The very small target group of patients with small cell lung cancer is a limitation of this study, which can explain why ProGRP alone does not show a sensitivity higher than neuron-specific enolase, as reported by other authors.

Neutron-rich material ejected from neutron star-neutron star (NS-NS) and neutron star-black-hole (NS-BH) binary mergers is heated by nuclear processes to temperatures of a few hundred keV, resulting in a population of electron-positron pairs. Some of the positrons escape from the outer layers of the ejecta. We show that the population of low-energy positrons produced by NS-NS and NS-BH mergers in the Milky Way can account for the observed 511-keV line from the Galactic center (GC). Moreover, we suggest how positrons and the associated 511-keV emission can be used as tracers of recent mergers. Recent discovery of 511-keV emission from the ultrafaint dwarf galaxy Reticulum II, consistent with a rare NS-NS merger event, provides a smoking-gun signature of our proposal.

We study the gravitational-wave peak luminosity and radiated energy of quasicircular neutron star mergers using a large sample of numerical relativity simulations with different binary parameters and input physics. The peak luminosity for all the binaries can be described in terms of the mass ratio and of the leading-order post-Newtonian tidal parameter solely. The mergers resulting in a prompt collapse to black hole have the largest peak luminosities. However, the largest amount of energy per unit mass is radiated by mergers that produce a hypermassive neutron star or a massive neutron star remnant. We quantify the gravitational-wave luminosity of binary neutron star merger events, and set upper limits on the radiated energy and the remnant angular momentum from these events. We find that there is an empirical universal relation connecting the total gravitational radiation and the angular momentum of the remnant. Our results constrain the final spin of the remnant black hole and also indicate that stable neutron star remnant forms with super-Keplerian angular momentum.

A number of pharmacogenetic studies have been carried out in non-small-cell lung cancer (NSCLC) to identify and characterize genes involved in chemotherapy activity. However, the results obtained so far are controversial and no reliable biomarker is currently used to predict clinical benefit from platinum-based chemotherapy, which represents the cornerstone of treatment of advanced NSCLC. This study investigated the expression levels of ERCC1 and of six genes (RRM1, RRM2, hENT1, dCK, cN-II and CDA) involved in gemcitabine metabolism in locally/advanced NSCLC patients treated with gemcitabine/platinum combination. Gene expression was assessed by quantitative-PCR in laser-microdissected specimens and correlated with tumor response. Frequency distribution of responses above and below the median expression level of biomarkers was compared using a two-sided Fisher's test. 5'-nucleotidase (cN-II) was the only gene differently expressed ( p = 0.016) in the responders (complete/partial-response) compared to non-responders (stable/progressive disease). In the multivariate analysis, overexpression of this catabolic enzyme of gemcitabine remained a significant negative predictive factor. Patients with low cN-II had a modest trend toward increased survival, while both survival and progression-free survival were significantly longer in a more homogenous validation cohort of 40 advanced NSCLC (8.0 vs. 5.1 months, p = 0.026). Moreover, in vitro studies showed that silencing or pharmacological inhibition of cN-II increased the cytotoxicity of gemcitabine. This is the first study demonstrating the role of cN-II as a predictor of response to gemcitabine/platinum combinations in NSCLC. Its validation in prospective studies may improve clinical outcome of selected patients., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Objectives: To evaluate quantification of iodine uptake in metastatic and non-metastatic lymph nodes (LNs) by dual-energy CT (DECT) and to assess if the distribution of iodine within LNs at DECT correlates with the pathological structure., Methods: Ninety LNs from 37 patients (23 with lung and 14 with gynaecological malignancies) were retrospectively selected. Information of LNs sent for statistical analysis included Hounsfield units (HU) at different energy levels; decomposition material densities fat-iodine, iodine-fat, iodine-water, water-iodine. Statistical analysis included evaluation of interobserver variability, material decomposition densities and spatial HU distribution within LNs., Results: Interobserver agreement was excellent. There was a significant difference in iodine-fat and iodine-water decompositions comparing metastatic and non-metastatic LNs (p < 0.001); fat-iodine and water-iodine did not show significant differences. HU distribution showed a significant gradient from centre to periphery within non-metastatic LNs that was significant up to 20-30% from the centre, whereas metastatic LNs showed a more homogeneous distribution of HU, with no significant gradient., Conclusions: DECT demonstrated a lower iodine uptake in metastatic compared to non-metastatic LNs. Moreover, the internal iodine distribution showed an evident gradient of iodine distribution from centre to periphery in non-metastatic LNs, and a more homogeneous distribution within metastatic LNs, which corresponded to the pathological structure., Key Points: • This study demonstrated a lower iodine uptake in metastatic than non-metastatic LNs. • Internal distribution of HU was different between metastatic and non-metastatic lymph nodes. • The intranodal iodine distribution disclosed a remarkable correlation with the histological LN structure.

Objectives: Assessment of deep (>50%) myometrial invasion by dual-energy CT (DECT) and Trans-Vaginal US (TVUS) in patients with endometrial cancer., Methods: We retrospectively enrolled patients with endometrial cancer who underwent DECT and TVUS for pre-surgical staging. Three sets of images were evaluated: 70 keV (routine CT images), 50 keV, and iodine-water reconstructions. The gold standard was pathology after surgery. The agreement between the different imaging modalities and the gold standard was estimated. Sensitivity, specificity and accuracy for each imaging modality were evaluated with 95% confidence intervals (CI)., Results: Thirty-nine patients were included. Median time from CT and TVUS to surgery was 23 and 18 days, respectively. The best agreement between evaluation of myometrial infiltration and the gold standard was 0.88 (0.72, 1.00) for the 50 keV images; the worst agreement was 0.43 (0.00, 0.88) for the 70 keV images. CT iodine reconstructions and US agreement were comparable. Specificity, sensitivity and accuracy were 0.91, 1.00, 0.94; 0.57, 0.86, 0.71; 0.82, 1.00, 0.87; 0.91, 0.77, 0.86 for 50 keV, 70 keV, iodine reconstructions and ultrasound, respectively., Conclusions: DECT is a promising tool for assessment of myometrial invasion in endometrial cancer patients, with a special focus on 50 keV images.

Background: The role of primary tumour surgery in pancreatic neuroendocrine tumours (PNETs) with unresectable liver metastases is controversial and international guidelines do not recommend surgery in such cases. Resectability of the primary tumour has never been considered in outcome comparisons between operated and non-operated patients., Methods: From two institutional prospective databases of patients affected by PNET and unresectable liver metastases, 63 patients who underwent a left-pancreatectomy at diagnosis were identified and compared with a group of 30 patients with a potentially resectable but not-resected primary tumour located in the body or tail. The endpoint was overall survival (OS)., Results: The two groups significantly differed at baseline with regard to liver tumour burden Ki-67 labelling index, site of pancreas, results of the 18 FDG PET-CT and age. In the operated patients, surgical morbidity comprised 7 cases of pancreatic fistula. Postoperative mortality was nil. Median OS for patients undergoing left-pancreatectomy was 111 months vs 52 for the non operated patients (p = 0.003). At multivariate analysis after propensity score adjustment, no surgery as well as liver tumour burden>25% and higher Ki-67 index were associated with an increased risk of death during follow-up. In patients with unresectable primary tumour, OS was similar in comparison to that in the resectable but non-resected patients, and significantly worse than that in the resected patients (p = 0.032)., Conclusion: In PNETs located in the body or tail and diffuse liver metastases distal pancreatectomy may be justified in selected patients. Randomized studies may be safely proposed in future on this topic., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Borderline ovarian tumors are generally diagnosed in young women. Because of the young age of patients at first diagnosis and at recurrence, and given the good prognosis of borderline ovarian tumors, a conservative surgical approach in those women who wish to preserve their fertility is advised. In this scenario, transvaginal ultrasound examination plays a key role in the detection of borderline ovarian tumor recurrence, and in assessment of amount of normal functioning parenchyma remaining. To date, no data are available about the natural history of borderline ovarian tumor recurrence., Objective: The aim of the study was to determine growth rate of recurrent ovarian cysts by a scheduled follow-up by ultrasound examination, in women previously treated with fertility-sparing surgery due to borderline ovarian tumors., Study Design: In this prospective observational study, we collected data from 34 patients previously treated with fertility-sparing surgery due to borderline ovarian tumors, who had a suspicious recurrent lesion. The patients underwent transvaginal ultrasonographic examination every 3 months, until the clinical setting recommended proceeding with surgery. According to cyst size at study entry, they were categorized into 3 groups: ≤10 mm, 10-20 mm, and >20 mm. Summary statistics for cyst size, growth rate, and the probability of remaining within the same dimension category at first ultrasound during the follow-up were also obtained. For each cyst the growth rate was calculated as the slope of the linear interpolation between 2 consecutive measurements., Results: Follow-up timing (P < .001), cyst size (P < .001), and micropapillary pattern (P < .001) were factors significantly affecting the cyst growth both in univariate and multivariate analysis. According to size category at first ultrasound, growth rate ranges from a minimum of 0.06 mm/mo for cysts <10 mm up to 1.92 mm/mo for cysts >20 mm. The final histology of all recurrent lesions confirmed the same histotype of primary borderline ovarian tumors., Conclusion: This article represents the first observational study that describes the trend in the growth rate of borderline ovarian tumor recurrence in relation to their size detected at the first ultrasound examination. The findings of this study seem to confirm, in selected patients, that a thorough ultrasonographic follow-up of borderline ovarian tumor recurrence has proven to be safe and feasible. The final goal of such management is to maximize the impact on fertility potential of these young women without worsening their prognosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The Glasgow prognostic score (GPS) is an inflammation-based score based on albuminemia and C-reactive protein concentration proved to be associated with cancer-specific survival in several neoplasms. The present study explored the immediate postoperative value of the GPS for patients undergoing pneumonectomy for lung cancer., Methods: The value of the GPS preoperatively was studied in 250 patients undergoing pneumonectomy for non-small cell lung cancer (NSCLC). We analyzed overall postoperative complications, pulmonary and cardiac complications, 30-day postoperative death, reoperation for early complications, intensive care unit (ICU) length of stay and total length of hospital stay., Results: Patients with a GPS of 0 and 1 had a mean ICU length of stay of 0.8 days, whereas patients with a GPS of 2 had a mean ICU stay of 5.0 days (p = 0.004). The postoperative mortality rate in patients with a GPS of 2 was much higher than in patients with a GPS of 1 and 2, although it was not statistically significant (p = 0.083)., Conclusions: A preoperative GPS of 2 effectively predicts a prolonged ICU stay in patients who undergo pneumonectomy for cancer. The score may be proposed as an easy-to-determine, economical, and fast preoperative tool to plan and optimize ICU admissions after elective pneumonectomy., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: A low burden of disease represents an independent favorable prognostic factor of response to peptide receptor radionuclide therapy (PRRT) in patients affected by gastro-entero-pancreatic neuroendocrine tumors. However, it is not clear whether this is due to a lower diffusion of the disease or thanks to debulking surgery., Methods: From 1996 to 2013 those patients diagnosed with G1-G2 pancreatic neuroendocrine tumor (PNET) and synchronous liver metastases who were not deemed eligible for liver radical surgery but were eligible to receive upfront PRRT were prospectively included in the study. Two groups of comparison were identified: those submitted for primary tumor resection before PRRT and those who were not. The outcome was evaluated as: objective response to PRRT (OR), progression-free survival (PFS), and overall survival (OS)., Results: Of the 94 subjects, 31 were previously submitted for primary tumor resection. After propensity score adjustments, patients who underwent surgery before PRRT showed higher stabilization or objective responses after PRRT (p = .006), and this translated into a better median PFS (70 vs. 30 months; p = .002) and OS (112 vs. 65 months; p = .011), for operated versus nonoperated patients, respectively. At multivariate analysis, operated patients showed a statistically significantly improved PFS: HR, 5.11 (95 % CI 1.43-18.3); p = .012, whereas Ki-67 in continuous fashion was correlated significantly with OS: 1.13 (95 % CI 1-1.27); p = .048., Conclusions: Primary tumor resection prior to PRRT can be safely proposed in G1-G2 PNETs with diffuse liver metastases because it seems to enhance response to PRRT and to improve significantly PFS.

Background: The number of melanoma survivors has been increasing for decades due to early diagnosis and improved survival. These patients have an increased risk of developing a second primary cancer (SPC); also, melanoma is frequently diagnosed among patients firstly diagnosed with an extracutaneous malignancy., Objective: We evaluated the risk of developing a SPC among 1537 melanoma patients, and the risk of second primary melanoma (SPM) in 52 354 extracutaneous cancer patients, who were treated at the European Institute of Oncology in Milan, Italy, during 2000-2010., Material and Methods: We calculated standardized incidence ratios (SIR) by applying gender-, age-, year- and region-specific reference rates to the follow-up time accrued between the diagnosis of the first and the second primary malignancies., Results: Seventy-six SPC were diagnosed during a median follow-up of 4 years, of which 49 (64%) during the first 2 years upon melanoma diagnosis. The SIR was increased for cancer of breast (4.10, 95% CI 2.79-6.03), thyroid (4.67, 95% CI 1.94-11.22), brain (6.13, 95% CI 2.30-16.33) and for non-Hodgkin lymphoma (3.12, 95% CI 1.30-7.50). During a median follow-up of 4 years, 127 SPM were diagnosed: thick lesions were less frequent than for melanoma diagnosed as first cancer. The SIR was increased for cancer of breast (5.13, 95%CI 3.91-6.73), thyroid (16.2, 95%CI: 5.22-50.2), head and neck (5.62, 95%CI 1.41-22.50), soft tissue (8.68, 95%CI 2.17-34.70), cervix (12.5, 95% CI 3.14-50.20), kidney (3.19, 95%CI 1.52-6.68), prostate (4.36, 95%CI 2.63-7.24) and acute myeloid leukaemia (6.44, 95%CI 2.42-17.20)., Conclusions: The most likely causes of these associations are the clustering of lifestyle risk factors in the same subgroups of population, mainly on a sociocultural basis and surveillance bias. This raises important questions about how to best follow cancer survivors by avoiding an inefficient use of resources and an excessive medicalization of these patients' lives., (© 2016 European Academy of Dermatology and Venereology.)

Background: Subjects referred to genetic counselling for cancer may have heightened perceptions of illness and death, even though they are healthy and this may cause anxiety and reluctance to follow through with consultation. We investigated such perceptions before and after counselling and genetic testing for cancer in a cohort of Italian women. We sought to understand the situation of the women referred by designing questionnaires administered to women at high risk of breast and/or ovarian cancer (those who had had a pathogenic mutation identified in a family member via diagnostic testing). We also assessed women after the diagnosis of breast cancers, but free of disease, to help determine risks in their families., Methods: The first questionnaires were administered before initial counselling, and the second were completed within 20 days after the counselling. When a genetic test was proposed, the individual was asked to fill in a third questionnaire; the final questionnaire was administered after the person had received the results of the genetic test., Results: We evaluated 204 subjects. Before counselling, 89 % of the subjects were worried about their risk of disease, 52 % felt "different" because of their personal and family history, and 39 % declared that their life choices were influenced by their fear of cancer. After counselling, 82 % of the subjects felt more relived about their pre-existing fears and stated that this process of being seen in a clinic with genetic expertise had clarified the meaning of disease risk for them, and for 50 %, this experience had positively influenced their life choices. Thirty percentage of the subjects had a positive test; all of them felt safer in being cared for by specifically trained staff. Fifty percentage had a less informative test (e.g. "wild-type" gene found); 84 % of them were not worried by the uncertainty, and overall, 96 % considered counselling to be very useful., Conclusion: Candidates for genetic counselling frequently had heightened their perception of being ill, which influenced their ability to make life decisions. Genetic counselling often improves this perception, especially in subjects who have negative tests and this knowledge facilitates their life plans. After testing, most women felt satisfied and safer because of being properly followed by professionally trained and sympathetic staff. In conclusion, knowledge of the real individual risk, the presence of a professional team, and the possibility of entering a programme of controlled screening enable patients rather than living in fear and uncertainty to be less anxious about their state of health and to live with the knowledge that they are doing everything possible to care for themselves, aided by a specialized team, and that, if necessary, they would be able to take part in investigational studies.

Introduction: Breast cancer is the leading cause of cancer death among women in the industrialized countries. The incidence of local recurrences after mastectomy and breast-conserving therapy varies between 5% and 40% depending on risk factors and primary therapy., Methods: From April 1999 to April 2011, 40 patients underwent chest wall resection and reconstruction for locally recurrent breast carcinoma with chest wall invasion. The main goal of surgery was local disease control to palliate clinical symptoms., Results: Local radical resection was achieved in 26 patients (65%). One, 2 and 5 year overall survival rates were 94.4%, 82.0% and 68.5%; 1, 2 and 5 year disease-free survival rates were 94.4%, 73.6% and 45.5% respectively. Univariate analysis indicated age (p = 0.002) and synchronous distant metastases (p = 0.020) as factors having a negative impact on overall survival; multivariate analysis disclosed age (p = 0.052) and synchronous metastases (p = 0.059) as factors with a slight negative impact on overall survival. Older age was associated with improved overall survival. Univariate analysis indicated synchronous distant metastases (p = 0.029) and the need of post resectional additional treatments (p = 0.022) as factors adversely conditioning disease-free survival or time to progression; multivariate analysis disclosed the need of post resectional additional treatments (p = 0.036) as the only factor adversely conditioning disease-free survival or time to progression., Conclusions: Chest wall resection and reconstruction for locally recurrent breast cancer is a feasible and safe procedure providing adequate local disease control and an excellent palliation of very disabling symptoms in a selected group of patients., (Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Purpose: The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs., Methods: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples., Results: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome., Conclusion: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors., (© 2016 S. Karger AG, Basel.)

Magnetohydrodynamic turbulence is important in many high-energy astrophysical systems, where instabilities can amplify the local magnetic field over very short timescales. Specifically, the magnetorotational instability and dynamo action have been suggested as a mechanism for the growth of magnetar-strength magnetic fields (of 10(15) gauss and above) and for powering the explosion of a rotating massive star. Such stars are candidate progenitors of type Ic-bl hypernovae, which make up all supernovae that are connected to long γ-ray bursts. The magnetorotational instability has been studied with local high-resolution shearing-box simulations in three dimensions, and with global two-dimensional simulations, but it is not known whether turbulence driven by this instability can result in the creation of a large-scale, ordered and dynamically relevant field. Here we report results from global, three-dimensional, general-relativistic magnetohydrodynamic turbulence simulations. We show that hydromagnetic turbulence in rapidly rotating protoneutron stars produces an inverse cascade of energy. We find a large-scale, ordered toroidal field that is consistent with the formation of bipolar magnetorotationally driven outflows. Our results demonstrate that rapidly rotating massive stars are plausible progenitors for both type Ic-bl supernovae and long γ-ray bursts, and provide a viable mechanism for the formation of magnetars. Moreover, our findings suggest that rapidly rotating massive stars might lie behind potentially magnetar-powered superluminous supernovae.

Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, has been shown to be active in newly diagnosed and relapsed patients with follicular lymphoma (FL), both as monotherapy and in combination with chemotherapy. Many studies suggest that the prognosis of patients with FL may improve when it is used in combination with chemotherapy. Despite these advances, the disease remains essentially incurable with standard therapy, and novel approaches to treatment are needed because optimal therapy is not defined. The combination of chlorambucil-rituximab is one of several standard treatment options for FL. Here, we considered data arising from 75 patients with newly diagnosed FL at the European Institute of Oncology treated with the combination of rituximab plus chlorambucil. The aim of this study was to evaluate the efficacy and safety of chlorambucil and rituximab, delivered 6 mg/m(2) /day orally for 6 weeks and 375 mg/m(2) in a standard 4-weekly schedule, respectively. Patients responding to the induction therapy received a prolonged therapy with four additional cycles of chlorambucil plus rituximab. Seventy-one patients (94.6%) completed the treatment; four patients discontinued treatment because of grade 3-4 hematological toxicity. The overall response rate was 97.3% including 74.7% of complete responses. Only two patients had a stable disease at revaluation after treatment. With a median follow-up of 57 months, 72 patients (96%) are alive. Median event-free survival (EFS) and median overall survival (OS) were not reached; 5-year OS rate was 98.4%. The 5-year EFS was 71.3%. By univariate and multivariate analyses, elevated beta-2 microglobulin levels and partial responses to therapy were correlated with worse EFS. These results suggest that the combination of chlorambucil and rituximab is an active and safe regimen in patients with newly diagnosed FL, principally in those with low tumour burden and favourable prognostic factors., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background and Purpose: Charcot-Marie-Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed., Methods: The relative responsiveness of clinical scales of the Italian-UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness)., Results: Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM -0.31 and -0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28)., Conclusions: Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients., (© 2015 EAN.)

Background: Anxiety and depression are common in people with multiple sclerosis (MS), but data on emotional communication during MS consultations are lacking. We assessed patient expressions of emotion and neurologist responses during first-ever MS consultations using the Verona Coding Definitions of Emotional Sequences (VR-CoDES)., Methods: We applied VR-CoDES to recordings/transcripts of 88 outpatient consultations (10 neurologists, four MS Italian centers). Before consultation, patients completed the Hospital Anxiety and Depression Scale (HADS). Multilevel sequential analysis was performed on the number of cues/concerns expressed by patients, and the proportion of reduce space responses by neurologists., Results: Patients expressed 492 cues and 45 concerns (median 4 cues and 1 concern per consultation). The commonest cues were verbal hints of hidden worries (cue type b, 41%) and references to stressful life events (type d, 26%). Variables independently associated with number of cues/concerns were: anxiety (HADS-Anxiety score >8) (incidence risk ratio, IRR 1.08, 95% CI 1.06-1.09; p<0.001); patient age (IRR 0.98, 95% CI 0.98-0.99; p<0.001); neurologist age (IRR 0.94, 95% CI 0.92-0.96; p=0.03); and second opinion consultation (IRR 0.72, 95% CI 0.60-0.86; p=0.007). Neurologists reacted to patient emotions by reducing space (changing subject, taking no notice, giving medical advice) for 58% of cues and 76% of concerns. Anxiety was the only variable significantly associated with 'reduce space' responses (odds ratio 2.17, 95% CI 1.32-3.57; p=0.003)., Conclusions: Patient emotional expressions varied widely, but VR-CoDES cues b and d were expressed most often. Patient anxiety was directly associated with emotional expressions; older age of patients and neurologists, and second opinion consultations were inversely associated with patient emotional expression. In over 50% of instances, neurologists responded to these expressions by reducing space, more so in anxious patients. These findings suggest that neurologists need to improve their skills in dealing with patient emotions.

Background: A previously carried out randomized phase IIb, placebo-controlled trial of 1 year of inhaled budesonide, which was nested in a lung cancer screening study, showed that non-solid and partially solid lung nodules detected by low-dose computed tomography (LDCT), and not immediately suspicious for lung cancer, tended to regress. Because some of these nodules may be slow-growing adenocarcinoma precursors, we evaluated long-term outcomes (after stopping the 1-year intervention) by annual LDCT., Patients and Methods: We analyzed the evolution of target and non-target trial nodules detected by LDCT in the budesonide and placebo arms up to 5 years after randomization. The numbers and characteristics of lung cancers diagnosed during follow-up were also analyzed., Results: The mean maximum diameter of non-solid nodules reduced significantly (from 5.03 mm at baseline to 2.61 mm after 5 years) in the budesonide arm; there was no significant size change in the placebo arm. The mean diameter of partially solid lesions also decreased significantly, but only by 0.69 mm. The size of solid nodules did not change. Neither the number of new lesions nor the number of lung cancers differed in the two arms., Conclusions: Inhaled budesonide given for 1 year significantly decreased the size of non-solid nodules detected by screening LDCT after 5 years. This is of potential importance since some of these nodules may progress slowly to adenocarcinoma. However, further studies are required to assess clinical implications., Clinical Trial Number: NCT01540552., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In overwork weakness (OW), muscles are increasingly weakened by exercise, work or daily activities. Although it is a well-established phenomenon in several neuromuscular disorders, it is debated whether it occurs in Charcot-Marie-Tooth disease (CMT). Dominant limb muscles undergo a heavier overload than non-dominant and therefore if OW occurs we would expect them to become weaker. Four previous studies, comparing dominant and non-dominant hand strength in CMT series employing manual testing or myometry, gave contradictory results. Moreover, none of them examined the behaviour of lower limb muscles., Methods: We tested the OW hypothesis in 271 CMT1A adult patients by comparing bilateral intrinsic hand and leg muscle strength with manual testing as well as manual dexterity., Results: We found no significant difference between sides for the strength of first dorsal interosseous, abductor pollicis brevis, anterior tibialis and triceps surae. Dominant side muscles did not become weaker than non-dominant with increasing age and disease severity (assessed with the CMT Neuropathy Score); in fact, the dominant triceps surae was slightly stronger than the non-dominant with increasing age and disease severity., Discussion: Our data does not support the OW hypothesis and the consequent harmful effect of exercise in patients with CMT1A. Physical activity should be encouraged, and rehabilitation remains the most effective treatment for CMT patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: No randomized trials have so far investigated the cost effectiveness of different methods for implantation and use of central venous ports in oncology patients., Patients and Methods: Overall, 403 patients eligible for receiving intravenous chemotherapy for solid tumours were randomly assigned to implantation of a single type of port, either through a percutaneous landmark access to the internal jugular vein, an ultrasound (US)-guided access to the subclavian vein, or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Insertion and maintenance costs were estimated by obtaining the charges for an average implant and use, while the costs of the management of complications were analytically assessed. The total cost was defined as the purchase cost plus the insertion cost plus the maintenance cost plus the cost of treatment of the complications, if any., Results: A total of 401 patients were evaluable-132 with the internal jugular vein, 136 with the subclavian vein and 133 with the cephalic vein access. No differences were found for the rate of early complications. The US-guided subclavian insertion site had significantly lower failures. Infections occurred in 1, 3, and 3 patients (internal jugular, subclavian, and cephalic access, respectively; p = 0.464), whereas venous thrombosis was observed in 15, 8, and 11 patients, respectively (p = 0.272). Mean cost for purchase, implantation, diagnosis and treatment of complications in each patient was 2,167.85 for subclavian US-guided, 2,335.87 for cephalic, and 2,384.10 for internal jugular access, respectively (p = 0.0001)., Conclusion: US real-time guidance to the subclavian vein resulted in the most cost-effective method of central venous port placement and use.

Background/aims: Recently, pelvic anatomy has been taken into consideration and related to surgical outcome indicators after low anterior resection (LAR). Several pelvimetric parameters have been matched with conversion rate, postoperative complications and duration of surgery in laparoscopic series, and with the quality of specimen and pathologic outcomes in further open surgical series., Methodology: In 97 consecutive patients submitted to sphincter-saving LAR with total mesorectal excision (TME) five pelvic dimensions were measured by abdominal computed tomography scan: anteroposterior and transverse diameters in the pelvic inlet (IAP and ITRA), anteroposterior and transverse diameters in the pelvic outlet (OAP and OTRA), and the pelvic depth. The endpoint evaluated was anastomotic leakage (AL) rate., Results: There were 51 open, 12 laparoscopic and 34 robotic LARs. The sum of IAP OAP and OTRA (Pelvic Index) significantly predicted AL showing that starting from the cut-point of 290 mm down to a PI of 278 mm the odds-ratio of having an AL increased from 2.63 (95% CI: 1.10,5.47) to 5.07 (95% CI: 1.35,8.02)., Conclusions: The sum of the 3 pelvic dimensions which we termed “Pelvic Index” was associated to AL following sphinctersaving LAR. This may be considered in planning the surgical strategy for rectal cancer patients.

Introduction: Charcot-Marie-Tooth (CMT) disease type 1A is the most common form of CMT. The main clinical features are distal weakness, sensory loss, and skeletal deformities. Although pain is a frequent complaint, small fiber involvement in CMT1A has not been studied extensively., Methods: We assessed pain and small fiber involvement in 49 CMT1A patients using a variety of pain scales, pain questionnaires, and thermal thresholds., Results: Forty-three of 49 patients (88%) complained of pain. The pain was localized to the feet in 61% of patients. Only 18% of patients had neuropathic pain. Cold and warm detection thresholds were elevated in 53% and 12% of patients, respectively., Conclusions: Our findings confirm that CMT1A patients have significant pain, which is more likely to be multifactorial in origin and suggests that a proportion of patients have small fiber dysfunction affecting mainly thinly myelinated Aδ fibers., (Copyright © 2014 Wiley Periodicals, Inc.)

Background: The SIMS-Trial showed that the 'Sapere Migliora' information aid (IA) for newly diagnosed people with multiple sclerosis (PwMS) effectively improved patient knowledge and satisfaction with care., Objectives: The objectives of this paper are to assess the effectiveness of the IA in clinical practice and to compare the whole IA with the take-home booklet/website component alone., Methods: After updating the IA and replacing the CD with a website, a prospective, open-label non-randomised controlled trial compared the whole IA (group A, five SIMS-Trial centres) to take-home (group B, 16 centres). One month after the intervention, participants completed the MS Knowledge Questionnaire (MSKQ), care satisfaction questionnaire (COSM-R) (primary study outcomes), Hospital and Anxiety Depression Scale, and ad hoc questionnaire appraising the IA., Results: We enrolled 159 newly diagnosed PwMS (May 2012-March 2013). Drop-outs were four of 77 (5%, group A) and 11/82 (13%, group B). Primary endpoint (highest tertile both for MSKQ and COSM-R section 2 scores) was achieved by 38/77 (49%) group A and 33/82 (40%) group B (p = 0.25). Attainment of secondary outcomes was also similar between groups., Conclusions: This study shows that the entire IA is not superior to the booklet/website alone, and that both are comparable in efficacy to the intervention arm of the SIMS-Trial., Trial Registration Number: ISRCTN78940214., (© The Author(s) 2014.)

Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with increased gene dosage for PMP22. Therapeutic approaches are currently aiming at correcting PMP22 over-expression. It is unknown whether PMP22 can be used as a biological marker of disease progression and therapy efficacy. We performed quantitative real-time polymerase chain reaction on skin biopsies of 45 patients with CMT1A, obtained at study entry and after 24-months of treatment either with ascorbic acid or placebo. Data of a subgroup of patients were also compared with matched healthy subjects. Finally, we analysed PMP22 messenger RNA levels in sural nerve biopsies. We did not find significant differences in the levels of any known PMP22 transcripts in treated or untreated patients with CMT1A, thus confirming that ascorbic acid does not impact on the molecular features of CMT1A. Most importantly, we did not observe any correlation between PMP22 messenger RNA levels and the different clinical and electrophysiological outcome measures, underscoring the weakness of PMP22 to mirror the phenotypic variability of patients with CMT1A. We did not find increased PMP22 messenger RNA levels in skin and sural nerve biopsies of patients with CMT1A compared with relative controls. In conclusion, this study shows that ascorbic acid does not impact on PMP22 transcriptional regulation and PMP22 is not a suitable biomarker for CMT1A., (© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Strong evidences shows that HPV testing is more sensitive than cytology in detecting high-grade CIN. HPV test can be performed on samples collected by women themselves by means of self-sampling devices. This study compares the results of self-sampled HPV tests with the results of liquid based cytology (LBC)., Study Design: Seven hundred women scheduled for cervical cytology self-collected a cervicovaginal sample for HPV testing and then underwent a clinician-collected LBC at the European Institute of Oncology. The HPV and LBC results were compared with the McNemar test., Results: All HSIL (N=5) resulted hrHPV positive. LBC resulted LSIL or worse in 38 (5.4%) women (out of 700). Self-sampled HPV was positive in 96 women (13.7%). A LSIL or worse LBC result was found in 15 (2.5%) patients, out of the 604 hrHPV negative women and in 23 (24%) patients, out of the 96 hrHPV positive women. Positive cytology after a self-sampled HPV positive result had an Odds Ratio of 12.4 (95% CI: 5.8-26.6)., Conclusion: Self-collected HPV testing identifies a group of women at high risk of positive LBC and high grade SIL., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Background: This study was done to compare the growth of pathogens in paired aerobic/anaerobic blood culture bottles versus the use of only aerobic bottles, and to analyze the time to growth in both atmospheres., Methods: We retrospectively evaluated the results of all blood cultures collected over a 2-y period for the diagnosis of central venous catheter-related bloodstream infections or other severe infections in oncology patients., Results: Among the 487 isolates, 174 (35.7%), all aerobic, grew only in the aerobic bottle; 250 (51.3%), all aerobic, grew in both bottles; and 63 (12.9%) grew only in the anaerobic bottle, of which 24 were anaerobic and 39 were aerobic microorganisms (8% of positive blood cultures). Of these 39 aerobic microorganisms, 12 were Gram-negative, 17 staphylococci (4 were Staphylococcus aureus), 5 streptococci, 2 Gram-positive bacilli, and 3 mixed growth. Though the mean time to positivity of pathogens grown in both atmospheres was significantly lower in the aerobic bottle than in the anaerobic bottle, in 71 cases (28.4%) the pathogens developed earlier in the anaerobic bottle than in the aerobic bottle - in 36 of these cases at least 1 h earlier, which is significant for starting targeted therapy., Conclusions: The use of paired aerobic/anaerobic blood culture bottles allowed the diagnosis of a percentage of bacteraemia due to either anaerobic or aerobic pathogens that would have been missed, as they grew only in the anaerobic atmosphere. Moreover in 8% of bacteraemia we identified a significant decrease in the time to detection, resulting in the opportunity to better manage the infections without an increase in costs.

Objective: In a previous study, we found that patients who were offered the possibility of participation in a clinical trial had unexpressed concerns and fears that prevented them from making free or fully knowledgeable choices about their trial participation. In a selected population of patients who were offered participation in a phase I trial, we prospectively investigated whether a face-to-face discussion about their unexpressed fears might lead to a more conscious decision about whether to accept/refuse participation in the trial., Methods: After the presentation of the trial, a questionnaire was administered to assess the presence of specific fears. Before the patients decided whether to participate in the trial, they discussed any fears that they had; finally, the impact of the discussion on the patients' choice to participate was evaluated., Results: The majority (86%) of the patients thought that physicians conduct clinical trials for scientific interest, 13% felt exploited as 'guinea pigs' and 20% believed they were offered participation because they had no further hope for improvement. These existing fears were not elicited during the trial interview because the patients were themselves unaware of having them (28%) and because of fear of the doctors (3%). The possibility of discussing these fears was felt as an opportunity and made patients feel more conscious (92%) and freer (97%) when making their choice., Conclusions: Recognising and discussing misconceptions and fears, often unexpressed, make patients freer and more aware when facing the choice of whether or not \to participate in a phase I clinical trial., (Copyright © 2013 John Wiley & Sons, Ltd.)

We evaluated clinical activity of ⁹⁰Yttrium-ibritumomab (⁹⁰Y-ibritumomab) tiuxetan in extranodal marginal-zone lymphoma. From May 2004 to April 2011, 30 patients affected by relapsed/refractory marginal-zone lymphoma--arisen at any extranodal site--received ⁹⁰Y-ibritumomab tiuxetan at the activity of 0.4 mCi/kg. Median age was 57 years. At time of treatment, 13 out of 30 patients had disseminated disease (stage III/IV). All patients had received a previous treatment with a maximum of 7. Overall response rate was 90%: 23 patients achieved a complete response (77%); partial response occurred in 4 patients (13%), stable disease in 2 patients (7%) and 1 progression (3%). With a median follow-up of 5.3 years, median time to relapse was not reached; 2 patients relapsed after complete response; 18 out of 23 complete responses are still responders after >3 years, 12 of them after >5 years. ⁹⁰Y-ibritumomab tiuxetan seems to be active in patients with extranodal marginal-zone lymphoma relapsed/refractory to conventional treatment including radiotherapy. These results suggest that radioimmunotherapy could represent a possible option for the treatment in this subset of patients., (Copyright © 2013 John Wiley & Sons, Ltd.)

Since squamous cell carcinoma antigen (SCC-Ag) testing became commercially available on the Architect platform, the previously established method on the Abbott IMx platform has been progressively replaced. Aim of this work was to compare SCC-Ag values obtained with the 2 methods. Clinical and laboratory data of 188 patients for whom SCC-Ag determination was requested, were reviewed. IMx was used to determine the levels of SCC-Ag from June 2007 to May 2009, while the Architect system was used from June 2009 to April 2011. Only patients consistently diagnosed with no evidence of disease, for whom at least 2 determinations with each analyzer were available were used. Comparison of the results obtained with the 2 systems was then performed. Mean values for SCC-Ag were 0.56 ng/mL (Standard Error (SE): 0.08) with the IMx method, and 1.08 ng/mL (SE 0.10) with Architect (p<0.0001). False positive results were found in 4.8% of patients with the IMx method and in 9.5% of patients with Architect (p=0.049). The values of SCC-Ag determined on the Architect platform are higher than those obtained on the IMx, with a higher percentage of false positive results.

Objectives: The aim of the study is to evaluate the response to neoadjuvant chemotherapy (NACHT) of patients with recurrent cervical cancer who were poor candidates for pelvic exenteration (PE), and the impact on DFS and OS., Methods: A retrospective data collection extracted from medical records of 61 patients submitted to pelvic exenteration was performed: 30 underwent up-front exenterative procedure whereas 31 received NACHT., Results: The median tumor size was significantly (P=0.0006) larger in the NACHT group compared to the up-front PE one (43.9 mm vs 28 mm), and a significant (P=0.04) higher percentage of patients (45 vs 20%) had lateral pelvic wall invasion in the NACHT group. No statistically significant difference in early and late complications was observed in the two groups. Median overall survival in study population was 42.9 months (95% CI: 22.2, 180.8). Median overall survival times as well as recurrence free survival times were not significantly different between NACHT (42.9 months and 36.1 months for OS and DFS respectively) vs. No NACHT (111.9 months and 48.1 months for OS and DFS respectively). There was an overall significant difference in DFS between negative and positive margins but the curves were similar for NACHT and up-front PE groups stratified by resection margin status., Conclusions: In our series, though small and retrospective, NACHT prior to PE represents a feasible therapeutic option without intra-operative and early post-operative mortality or worsening of early and late complication rate and with acceptable long-term survival and DFS for recurrent cervical cancer patients who are poor candidates for up-front pelvic exenteration., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Purpose: Granulocyte colony-stimulating factors (G-CSFs), filgrastim and lenograstim, are recognised to be useful in accelerating engraftment after autologous stem cell transplantation. Several forms of biosimilar non-glycosylated G-CSF have been approved by the European Medicines Agency, with limited published data supporting the clinical equivalence in peripheral blood stem cell mobilisation and recovery after autologous stem cell transplantation., Method: With the aim of comparing cost-effective strategies in the use of G-CSF after autologous stem cell transplantation, we retrospectively evaluated 32 patients consecutively treated with biosimilar filgrastim XM02 (Tevagrastim) and 26 with lenograstim. All patients received G-CSF (biosimilar or lenograstim) at a dosage of 5 mcg/kg/day subcutaneously from day 5 to absolute neutrophil count of 1500/mmc for three days., Results: The median time to absolute neutrophil count engraftment was 11 days for the filgrastim XM02 group and 12 days for the lenograstim group. As for platelets recovery, the median time was 12 days in both groups. The median number of G-CSF vials used for patients was 9.5 for Tevagrastim and 10.5 for lenograstim, reflecting a mean estimated cost of about 556.1 euros for Tevagrastim versus 932.2 euros for lenograstim (p< 0.001). The median days of febrile neutropenia were 1.5 and 1 for filgrastim XM02 and lenograstim, respectively. No adverse event related to the use of XM02 filgrastim was recorded., Conclusion: In our experience, filgrastim XM02 and lenograstim showed comparable efficacy in shortening the period of neutropenia after cytoreduction and autologous stem cell transplantation, with a favourable cost effect for filgrastim XM02.

Background: The Control Preference Scale (CPS) is the most frequently used measure of patients' preferred roles in treatment decisions. We revised the original CPS and developed a new computerized patient self-administered version (eCPS). We used the eCPS to assess role preferences, and their determinants, in Italian and German people with multiple sclerosis (MS)., Methods: New cartoons were produced, based on MS health professional and patient input/feedback and previous findings, and pilot tested on 26 Italian and German MS patients. eCPS acceptability and reliability (weighted kappa statistic, wK) in comparison to the original tool, was determined in 92 MS patients who received both CPS versions in random order., Results: The new cartoons were well accepted and easily interpreted by patients, who reported they based their choices mainly on the text and considered the images of secondary importance. eCPS reliability was moderate (wK 0.53, 95% confidence interval [CI] 0.40-0.65) and similar to the test-retest reliability of face-to-face administration assessed in a previous publication (wK 0.65, 95% CI 0.45-0.81). Higher education (odds ratio [OR] 3.74, 95% CI 1.00-14.05) and German nationality (OR 10.30, 95% CI 3.10-34.15) were associated with preference for an active role in the logistic model., Conclusions: The newly devised eCPS was well received and considered easy to use by MS patients. Reliability was in line with that of the original version. Role preference appears affected by cultural characteristics and (borderline statistical significance) education.

Background and Purpose: Few data are available on the health status of people with multiple sclerosis (PwMS) in the community. We assessed changes in self-perceived health status and health related quality of life of a community-based cohort of PwMS over a decade, and identified predictors of such changes., Methods: In 1999 we started the POSMOS study (Postal Survey of Self-Assessed Health of MS Adults and their Significant Others) on a random sample of 251 adults with MS from the Milan area (mean age 42 years, range 18-71 years), and prospectively assessed changes in self-perceived health status over 11 years. Participants completed the Multiple Sclerosis Quality-of-Life-54 (MSQOL-54) and a general/clinical questionnaire. We re-assessed the cohort in 2004 and 2010, sending the same questionnaires plus the Chicago Multiscale Depression Inventory., Results: There were 205 (86%) respondents in 2004, 171 (74%) in 2010; 28 (11%) died during the study. Severely impaired [self-determined Expanded Disability Status Scale (EDSS) > 6.5] increased from 19% to 32%. One-fifth remained fully ambulatory (EDSS <4.0): 25% women (median age 44 years [interquartile range, IQR 39-53], median years from diagnosis 16 [IQR 12-19]); and 17% men (median age 40 years [IQR 38-45], median years from diagnosis 14 [IQR 12-17]). Changes in MSQOL-54 composite scores were negligible; but among individual scales, change in health, cognitive function and general health worsened, and social function and emotional wellbeing improved significantly. Depressive symptoms were high and stable., Conclusions: Multiple sclerosis had a pervasive but inhomogeneous impact on the lives of our MS sufferers. Notwithstanding overall clinical deterioration and aging, hospital admissions and medical consultations decreased, suggesting reduced use of health care resources. By contrast, housing adaptations and home care increased, psychological burden was high and self-perceived cognitive functioning worsened., (© 2012 The Author(s) European Journal of Neurology © 2012 EFNS.)

Objective: The quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease., Methods: Three hundred and forty-nine pre- and post-menopausal women, aged 18 years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample., Results: Median serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p<0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p=0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients., Conclusions: Data presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To assess decision-making in multiple sclerosis (MS) from third observer and patient perspectives., Method: Audio recordings of first-ever consultations with a participating physician (88 outpatients, 10 physicians) at four tertiary MS care clinics in Italy, were rated by a third observer using the Observing Patient Involvement in Shared Decision Making (OPTION) and by patients using the Perceived Involvement in Care Scale (PICS)., Results: Mean patient age was 37.5, 66% were women, 72% had MS, and 28% had possible MS or other disease. Mean PICS subscale scores (range 0 poor, 100 best possible) were 71.9 (SD 24.3) for "physician facilitation" (PICS-F); 74.6 (SD 22.9) for "patient information exchange" (PICS-I); and only 22.5 (SD 16.2) for "patient decision making" (PICS-DM). Mean OPTION total score (0 poor, 100 best possible) was 29.6 (SD 10.3). Poorest OPTION scores were found for items assessing "preferred patient approach to receiving information" and "preferred patient level of involvement." Highest scores were for "clinician drawing attention to identified problem", "indicating need for decision making," and "need to review the decision." Consultation time, woman physician, patient-physician gender concordance and PICS-F were associated with higher OPTION total score; older physician and second opinion consultation were associated with lower OPTION score., Conclusions: In line with findings in other settings, our third observer findings indicated limited patient involvement abilities of MS physicians during first consultations. Patient perceptions of physician skills were better than third observers', although they correlated. Consultations with women physicians, and younger physicians, were associated with higher third observer and patient-based scores. Our findings reveal a need to empower Italian MS physicians with better communication and shared decision-making skills, and show in particular that attention to MS patient preferences for reception of information and involvement in health decisions, need to be improved.

Background: Despite positive results from large phase III clinical trials proved that it is possible to prevent estrogen-responsive breast cancers with selective estrogen receptor modulators and aromatase inhibitors, no significant results have been reached so far to prevent hormone non-responsive tumors. The Ductal Lavage (DL) procedure offers a minimally invasive method to obtain breast epithelial cells from the ductal system for cytopathologic analysis. Several studies with long-term follow-up have shown that women with atypical hyperplasia have an elevated risk of developing breast cancer. The objective of the proposed trial is to assess the efficacy and safety of a daily administration of nimesulide or simvastatin in women at higher risk for breast cancer, focused particularly on hormone non-responsive tumor risk. The primary endpoint is the change in prevalence of atypical cells and cell proliferation (measured by Ki67) in DL or fine needle aspirate samples, after 12 months of treatment and 12 months after treatment cessation. METHODS-DESIGN: From 2005 to 2011, 150 women with a history of estrogen receptor negative ductal intraepithelial neoplasia or lobular intraepithelial neoplasia or atypical hyperplasia, or unaffected subjects carrying a mutation of BRCA1 or with a probability of mutation >10% (according to BRCAPRO) were randomized to receive nimesulide 100mg/day versus simvastatin 20mg/day versus placebo for one year followed by a second year of follow-up., Discussion: This is the first randomized placebo controlled trial to evaluate the role of DL to study surrogate endpoints biomarkers and the effects of these drugs on breast carcinogenesis. In 2007 the European Medicines Agency limited the use of systemic formulations of nimesulide to 15 days. According to the European Institute of Oncology Ethics Committee communication, we are now performing an even more careful monitoring of the study participants. Preliminary results showed that DL is a feasible procedure, the treatment is well tolerated and the safety blood tests do not show any significant liver toxicity. There is an urgent need to confirm in the clinical setting the potential efficacy of other compounds in contrasting hormone non-responsive breast cancer. This paper is focused on the methodology and operational aspects of the clinical trial., Trial Registration: (ClinicalTrials.gov Identifier: NCT01500577).

Patients with a number of peripheral CD34+ cells ≥20/μL have recently been defined in the literature as "poor mobilizers". We retrospectively reviewed medical records from a total of 248 patients affected by hematological malignancies or solid tumors undergoing peripheral blood stem cell collection following chemotherapy plus G-CSF. On the basis of the CD34+ cell peak in peripheral blood following mobilization therapy, patients were defined as good mobilizers (group A, CD34+ cells ≥20/μL), relative poor mobilizers (group B, CD34+ cells <20 and ≥8/μL) and absolute poor mobilizers (group C, CD34+ cells <8/μL). One hundred and seventy-seven (71%) patients resulted good mobilizers, 35 (14%) patients relative poor mobilizers and 36 (15%) patients absolute poor mobilizers. Target of stem cell collection was ≥2.0×10(6) CD34+cells/kg for each transplantation procedure. All patients in group A, 20 patients in group B (57%) and 1 patient in group C (2.7%) were able to collect ≥2.0×10(6) CD34+cells/kg. The multivariate analysis confirmed that more than three lines of previous chemotherapy and a previous autologous PBSC transplantation negatively affect mobilization of CD34+ cells in peripheral blood. Our data suggest that a number of CD34+ cells ≥20/μL does not always result in a failed stem cell collection and in fact in our patient series more than 70% of the patients defined as poor mobilizers have indeed collected the minimum number of 2.0×10(6) CD34+cells/kg required for a successful transplantation. The use of new agent such as CXCR4 antagonist plerixafor might further improve mobilization efficacy in such patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background and Purpose:  Uncertain prognosis and modest treatment efficacy make multiple sclerosis (MS) a particularly difficult disease to adjust to for both patients and their significant others (SOs). Few studies have assessed health-related quality of life (HRQOL) and depressive symptoms in SOs of people with MS in the community. We assessed, and identified predictors of, HRQOL and depression in SOs of adults with MS., Methods:   POSMOS (postal survey of self-assessed health in MS adults and SOs) is a longitudinal survey on a random sample of 251 people with MS in the Milan area. In 2010, SOs and contemporaneous controls completed the SF-36 and Chicago Multiscale Depression Inventory (CMDI)., Results:   Overall, 142 SOs (mean age 53.1 years; 50% women, 65% partners) and 120 controls (similar to SOs for sex and education, but older) participated. By multivariable modeling of the SO plus control population, SF-36 vitality was lower in SOs (proportional odds ratio 0.45; 95% confidence interval 0.28-0.70), women (0.41; 0.27-0.64), and older subjects (0.98; 0.97-0.99). SF-36 mental health was also lower in SOs (0.62; 0.40-0.96) and women (0.43; 0.28-0.67). Regarding MS characteristics associated with HRQOL and depression in SOs, severe disability [Expanded Disability Status Scale (EDSS > 6.5)] had no effect, whilst depressive symptoms (pathologic CMDI) negatively influenced most SF-36 and all CMDI scores in SOs., Conclusions:   SOs had significantly lower vitality and psychological well-being than controls, identifying a burden in being the companion of a person with MS. This burden was unrelated to physical compromise but associated with depressive symptoms in MS., (© 2012 The Author(s). European Journal of Neurology © 2012 EFNS.)

Background: An antimicrobial dressing containing ionic silver was found effective in reducing surgical-site infection in a preliminary study of colorectal cancer elective surgery. We decided to test this finding in a randomized, double-blind trial., Methods: Adults undergoing elective colorectal cancer surgery at two university-affiliated hospitals were randomly assigned to have the surgical incision dressed with Aquacel Ag Hydrofiber dressing or a common dressing. To blind the patient and the nursing and medical staff to the nature of the dressing used, scrub nurses covered Aquacel Ag Hydrofiber with a common wound dressing in the experimental arm, whereas a double common dressing was applied to patients of control group. The primary end-point of the study was the occurrence of any surgical-site infection within 30 days of surgery., Results: A total of 112 patients (58 in the experimental arm and 54 in the control group) qualified for primary end-point analysis. The characteristics of the patient population and their surgical procedures were similar. The overall rate of surgical-site infection was lower in the experimental group (11.1% center 1, 17.5% center 2; overall 15.5%) than in controls (14.3% center 1, 24.2% center 2, overall 20.4%), but the observed difference was not statistically significant (P = 0.451), even with respect to surgical-site infection grade 1 (superficial) versus grades 2 and 3, or grade 1 and 2 versus grade 3., Conclusions: This randomized trial did not confirm a statistically significant superiority of Aquacel Ag Hydrofiber dressing in reducing surgical-site infection after elective colorectal cancer surgery., Trial Registration: Clinicaltrials.gov: NCT00981110.

In a retrospective study, we investigated the reasons why women accepted to undergo a nipple sparing mastectomy (NSM) and why women who could not keep their nipple areola complex (NAC) decided to reconstruct it. We intended to investigate whether keeping the NAC plays a psychological role, to state possible advantages of NSM. Between 2004 and 2006, 310 women with NAC sparing and 143 patients with successive NAC reconstruction were mailed a single open-ended question at follow-up 12 months after final breast reconstruction surgery or final NAC reconstruction with tattoo. The purpose was to explore personal motivations that drove women to accept NSM or to perform a NAC tattoo reconstruction. Responses were classified into 11 categories by five reviewers. We performed an analysis of the relative frequency of emerging issues. Socio-demographic and clinical data were collected. Among the patients who responded to the open-ended question, 190 patients preserved their NAC, and 100 patients received postponed NAC reconstruction. Women in the NSM group were significantly younger (P = 0.02), more highly educated (P < 0.0001), and more frequently lived in Northern Italy (P = 0.03). The reasons for accepting NSM were more frequently related to body image satisfaction and integrity of the body (P = 0.002), reduction of psychological distress (P = 0.003), and surgeon's influence (P < 0.0001). Esthetic reasons were highly associated to the control group. These results help us to better understand the psychological impact of NAC sparing versus NAC reconstruction. NSM was accepted because it was perceived as a technique that preserved the integrity of the body, reduced the feeling of mutilation, improved the breast cosmetic results, and reduced psychological distress regarding the loss of the breast.

Background: Primary liver tumours (PLTs) are currently a major health problem worldwide. The study's aim was to investigate the feasibility, toxicity, and activity of hepatic intra-arterial chemotherapy (HIAC) in patients with advanced PLTs., Methods: We retrospectively analysed 43 patients with advanced unresectable PLT, who were consecutively treated. HIAC with 5-fluorouracil, cisplatin, and mitomycin-C was administered through a radiologically positioned temporary percutaneous catheter every six weeks until tumour progression or unacceptable toxicity was reached., Results: Partial response was observed in 26% and stable disease in 41% of patients. The median overall survival was 12.3 months. Manageable catheter-related complications occurred in 23% of patients. The grade 3-4 toxicities included neutropenia, thrombocytopenia, and transaminitis. There were no toxic deaths., Conclusion: The results of this retrospective study show that HIAC is feasible, active, and manageable in patients with PLTs. The treatment could be studied in selected patients with advanced progressive HCC/BTC being treated with or ineligible for sorafenib/cisplatin plus gemcitabine.

Introduction: Available information on perioperative blood transfusion practices in oncologic thoracic surgery is scant and outdated. The purpose of this study was to investigate transfusion requirements in patients undergoing curative resection for lung cancer and to identify possible factors predictive of perioperative blood transfusion in our cohort of patients., Methods: From 1st January 2009 to 31st December 2009, 317 patients underwent anatomic pulmonary resection. Patients who received at least 1 unit of red blood cells comprised the "transfused" group. Each case in this group was matched for surgical procedure with a control subject who did not require blood transfusion and was operated on during the same year; these patients comprised the "not transfused" group., Results: A total of 75 patients (23.6%) received at least 1 unit of red blood cells during the perioperative period. Factors conditioning perioperative blood transfusion were: preoperative hemoglobin level (p < 0.0001); procedure duration (p = 0.017); body mass index (p < 0.001); induction therapies (p = 0.017); redo procedure (p = 0.021). Age, sex, histology, stage, ASA score, side, intraoperative blood loss, and fluid infusion did not affect perioperative blood transfusion practices., Conclusions: Preoperative hemoglobin level is the major risk factor for perioperative blood transfusion practices in oncologic thoracic surgery; procedure duration, body mass index, induction therapies, and redo procedure may condition transfusional needs, although they were actually not predictive on multivariate analysis.