Benefit of adjuvant chemotherapy in patients with special histology subtypes of triple-negative breast cancer: a systematic review.

PURPOSE: Breast cancer (BC) is a leading cause of morbidity, disability, and mortality in women, worldwide; triple-negative BC (TNBC) is a subtype traditionally associated with poorer prognosis. TNBC special histology subtypes present distinct clinical and molecular features and sensitivity to antineoplastic treatments. However, no consensus has been defined on the best adjuvant therapy. The aim of the review is to study the evidence from literature to inform the choice of adjuvant treatments in this setting. METHODS: We systematically searched literature assessing the benefit of adjuvant chemotherapy in patients with TNBC special histotypes (PROSPERO: CRD42020153818). RESULTS: We screened 6404 records (15 included). All the studies estimated the benefit of different chemotherapy regimens, in retrospective cohorts (median size: 69 patients (range min-max: 17-5142); median follow-up: 51 months (range: 21-268); mostly in Europe and USA). In patients with early-stage adenoid cystic TNBC, a marginal role of chemotherapy was reported. Similar for apocrine TNBC. Medullary tumors exhibited an intrinsic good prognosis with a limited role of chemotherapy, suggested to be modulated by the presence of tumor-infiltrating lymphocytes. A significant impact of chemotherapy on the overall survival was estimated in patients with metaplastic TNBC. Limitations were related to the retrospective design of all the studies and heterogeneous treatments received by the patients. CONCLUSIONS: There is potential opportunity to consider treatment de-escalation and less intense therapies in some patients with early, special histology-type TNBC. International efforts are indispensable to validate prospective clinical decision models.

Painful bone metastasis in elderly treated with radiation therapy: Single- or multiple-fraction regimen? A multicentre retrospective observational analysis.

BACKGROUND: Bone metastases are a frequent complication of advanced oncologic disease. Pain associated to bone metastasis is a major cause of morbidity in cancer patients, especially in elderly. AIMS: The aim of this multicentric retrospective observational study is to evaluate the efficacy of different schedules of radiation therapy in elderly patients in terms of pain relief. METHODS: 206 patients over the age of 60 were enrolled in 1 year time for a multicentre retrospective observational study. Patients were treated with palliative purposes for painful bone metastases. RESULTS: Pain intensity difference (PID) was found in 72% of patients. Reported PID was statistically significant for p < 0.01. Pain intensity measured by a point numeric rating scale was statistically significant reduced for p < 0.05 by one-fraction regimen compared to other two regimens. DISCUSSION: In recent years, numerous studies have evaluated the most appropriate regimen of fractionation in individual cases, despite this, a consensus about the best schedule is still debated. CONCLUSIONS: On our analysis, single-fractionation scheme (8 Gy) confirmed to be statistical significant effective in providing pain reduction due to bone metastases. Radiation therapy provides significant pain relief of symptomatic bone metastases, but appropriate radiotherapy scheduled is needed in order to get significant response to treatment. Multidisciplinary approach is warranted to value the balance between the therapeutic objectives and the patient quality of life.

Characteristics and clinical outcomes of breast cancer in young BRCA carriers according to tumor histology.

BACKGROUND: Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer. METHODS: This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival. RESULTS: Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index. CONCLUSIONS: In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis.

Safety of mRNA-COVID-19 Vaccines in Patients With Thoracic Cancers.

BACKGROUND: Pivotal trials of COVID-19 vaccines did not include cancer patients with questions remaining in this population. Particularly in patients with thoracic malignancies receiving anticancer treatments, the safety of these vaccines has so far been little investigated. METHODS: This is a prospective trial of patients with thoracic cancer receiving anticancer treatments and COVID-19 vaccines at the Division of Thoracic Oncology of European Institute of Oncology between February and September 2021. RESULTS: A total 207 patients affected by thoracic cancers (199 lung cancers and 8 mesotheliomas) had received Covid-19 vaccines (206 mRNA vaccines and 1 virus-vectored vaccine). The majority of patients had at least one comorbidity (76.3%). They were concomitantly treating with targeted therapy (TT) (45.9%), immunotherapy (IO) (22.7%), and chemotherapy (CT) (14%). A total of 64 AEs (15.6%) were observed after administration of Sars-Cov-2 vaccine. The majority of AEs were grade 1 [G1] (6.3%) and G2 (8.8%), only two events were G3 (0.5%). The median follow-up was 9 months (range 1-22 months), during this follow-up 21 patients (10.1%) had a positive nasal swab, most of the patients were asymptomatic (67%) and the symptomatic ones (33%) had mild symptoms and fewer complications and hospitalizations. CONCLUSIONS: COVID-19 m-RNA vaccines appear to be safe in the cohort of patients with thoracic malignances in active treatment, including those receiving immunotherapy. Considering the high morbidity and mortality associated with COVID-19 in patients with lung cancer receiving active treatments, our study supports the current vaccine prioritization, third and/or fourth dose, of all cancer patients with active treatment.

Clinical development and current role of margetuximab for the treatment of breast cancer.

Up to 20% of breast cancers overexpress HER2, a molecular alteration conferring these tumors a particularly aggressive behavior. However, targeting HER2 has radically changed the prognosis of this disease in the last 2 decades, with multiple anti-HER2 compounds shown to improve disease outcomes both in the early and advanced setting. The latest anti-HER2 compound to be approved by the U.S. Food and Drug Administration (FDA) was margetuximab, an Fc-engineered monoclonal antibody with an improved binding to FcγRIIIA receptor, which leads to a greater antibody-dependent cellular cytotoxicity (ADCC) activation compared with trastuzumab. Margetuximab was shown to slightly improve progression-free survival compared with trastuzumab when combined with chemotherapy for the treatment of advanced HER2-positive breast cancer patients, and is now included among the available treatment options for pretreated HER2-positive breast cancer patients. In this monograph we recapitulate the clinical development, current role and future perspectives of margetuximab for the treatment of breast cancer.

Improvement of body composition and bone mineral density after enteral nutrition in pediatric Crohn disease.

BACKGROUND: The relationship between exclusive enteral nutrition (EEN) and bone status is poorly defined in pediatric Crohn disease (CD). AIMS: The aim of this study was to investigate the impact of EEN on body composition, nutritional status, and bone mineral density (BMD) in an incident CD cohort. METHODS: 18 newly diagnosed CD children starting EEN for 8 weeks were prospectively enrolled and evaluated at baseline and after 8 (T8), 26 (T26) and 52 weeks (T52) from diagnosis. The Fat Free Mass (FFM) and the Resting Energy Expenditure (REE) were measured through Bioelectrical Impedance (BIA) and the BMD was assessed by dual-energy X-ray (DXA). We compared DXA data of IBD patients to the data obtained in 15 healthy controls. RESULTS: CD children had a significant lower BMD compared to healthy control both at baseline (p<0.0001), and after EEN therapy at T52 (p=0.0004); although at this latest time point CD children had a significant increase of BMD compared to baseline (p=0.0015). The BIA analysis showed a significant increase at T26 and T52 of FFM and REE. T52. FFM measured by BIA and BMD measured by DXA were significantly correlated. CONCLUSION: EEN improves nutritional status and bone mineral composition.

Mediterranean diet improves sexual function in women with the metabolic syndrome.

In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7+/-3.1 to a mean post-treatment value of 26.1+/-4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.

Association of body weight with sexual function in women.

Sexual difficulties in women appear to be widespread in society; the relationship between female sexual function and obesity is unclear. This study aimed to investigate the relationship between body weight, the distribution of body fat and sexual function in women. Fifty-two, otherwise healthy women with abnormal values of female sexual function index (FSFI) score (< or =23) were compared with 66 control women (FSFI >23), matched for age and menopausal status. All women were free from diseases known to affect sexual function. FSFI strongly correlated with body mass index (BMI) (r=-0.72, P=0.0001), but not with waist-to-hip ratio (r=-0.09, P=0.48), in women with sexual dysfunction. Of the six sexual function parameters, desire and pain did not correlate with BMI, while arousal (r=-0.75), lubrication (r=-0.66), orgasm (r=-0.56) and satisfaction (r=-0.56, all P<0.001) did. FSFI score was significantly lower in overweight women as compared with normal weight women, while cholesterol and triglyceride levels were higher. On multivariate analysis, both age and BMI explained about 68% of FSFI variance, with a primacy of BMI over age (ratio 4:1). In conclusion, obesity affects several aspects of sexuality in otherwise healthy women with sexual dysfunction.

Endothelial microparticles correlate with erectile dysfunction in diabetic men.

Cell-derived microparticles are supposed to be involved in endothelial dysfunction and atherogenesis. This study aimed to evaluate circulating microparticles in diabetic subjects with erectile dysfunction (ED) and their relation with endothelial dysfunction. Thirty diabetic men with ED and 20 age-matched control subjects without ED were assessed for circulating microparticles and endothelial dysfunction. Flow cytometry was used to assess microparticles by quantification of circulating endothelial (EMP, CD31(+)/CD42b(-)) and platelet (PMP, CD31(+)/CD42b(+)) microparticles in peripheral blood. Endothelium-dependent flow-mediated dilation (FMD) was evaluated in the right brachial artery after reactive hyperemia. Compared with non-diabetic subjects, diabetic men presented significantly higher numbers of EMP (P=0.001), and reduced FMD (P=0.01), with a significant inverse correlation between the number of circulating EMP and the International Index of Erectile Function (IIEF) score (r=-0.457, P=0.01). Multivariate analysis correcting for age, anthropometric indices, glucose and lipid parameters, FMD and PMP identified EMP as the only independent predictor for IIEF score (P=0.03). EMP are elevated in impotent diabetic subjects and independently involved in the pathogenesis of ED.

Efficacy of a standardized extract of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) in infantile colic: An open randomized controlled trial.

BACKGROUND: Infant colic (IC) is a prevalent physiological event of infants, which can disrupt the child's home environment. We aimed to investigate the effectiveness of a mixture of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) compared with Lactobacillus reuteri DSM 17938 and with simethicone for the treatment of IC. METHODS: A multicenter randomized comparative study was conducted in infants with colic, according to Rome III criteria, who were randomly assigned to receive M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) (Colimil® Plus® ; Milte Italia Spa, Milan, Italy) (Group A), L. reuteri DSM 17938 (Group B) and simethicone (Group C). Treatment was given to subjects for 28 days. KEY RESULTS: One-hundred and seventy-six patients completed the study. Mean daily crying time at day 28 was significantly lower in group A (-44, 95% CI: -58 to -30, P<.001) and group B (-35, 95% CI: -49 to -20, P<.001) when compared to group C. No significant difference was observed between Group A and Group B (mean difference: -9 minutes, 95% CI -23 to +5, P=.205). At day 28, 39 of 57 (68.4%) of infants in Group C responded to the treatment compared with 57 out of 60 patients (95%) of Group A and 51 out of 59 (86.4%) of Group B (P<.001). CONCLUSIONS: This study suggests that administration of M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) and L. reuteri DSM 17938 are significantly more effective than simethicone in IC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02708238.

Dietary factors in erectile dysfunction.

The role of dietary factors in erectile dysfunction (ED) has never been addressed. In the present case-control study, we investigated the relation of the Mediterranean diet with ED. A total of 100 men with ED were compared with 100 age-matched men without ED. A scale indicating the degree of adherence to the Mediterranean diet was constructed: the total Mediterranean diet score ranged from 0 (minimal adherence to the Mediterranean diet) to 9 (maximal adherence). The percentage of physical inactivity was greater in the ED group (35 vs 19%, P=0.04), whereas the diet score was lower (4.7+/-0.5 vs 5.4+/-0.5, P<0.01), indicating a reduced adherence to the Mediterranean diet. In analyses adjusted for the prevalence of associated risk factors (hypertension, hypercholesterolemia), body mass index, waist, physical inactivity and total energy intake, the intake of fruits and nuts, and the ratio of monounsaturated lipids to saturated lipids remained the only individual measures associated with ED. In conclusion, the results of the present study show that dietary factors may be important in the development of ED: adoption of healthy diets would hopefully help preventing ED.

Mediterranean diet improves erectile function in subjects with the metabolic syndrome.

Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.

Detection of a numeric value predictive of increased dose to left anterior descending coronary artery (LAD) in radiotherapy of breast cancer.

PURPOSE: We have evaluated thoracic conformation of patients in order to derive a numeric value predictive of an increased dose to left anterior descending coronary artery (LAD), critical structure for the development of late radio induced cardiac morbidity. METHODS: We have evaluated 91 patients (36-88 years) affected by breast cancer stage I-II (Tis-T1-2 N0-1), undergoing adjuvant radiotherapy with conventional fractionation. For each patient on CT images was measured the distance between the back face of the sternum (manubrium) and the anterior face of body of the corresponding vertebra (a), and the distance measured on the line at 45° between the vertebral body of the same vertebra and the back face of the rib corresponding (b). The a/b ratio showed values between 0.626 and 1.123. We used the median value (0.821) as cut-off to divide the patients in two groups. We calculated in both groups: Volume (Vol) heart, Vol LAD with an expansion of 0.6 mm; Dmean LAD (Gy); Dmax LAD (Gy); V10-V20-V30 (%) LAD and we correlated these values with parametric and non-parametric tests. RESULTS: The Pearson test has showed a statistically significant correlation between Vol breast and V10, V20, V30 with borderline significance (p = 0.006; p = 0.02; p = 0.05). The data were confirmed by testing non-parametric Kendall (tau = 0.004; tau = 0.015; tau = 0.016) and Spearman (rho = 0.003; rho = 0.016; rho = 0.015). We conducted categorizing into quartiles of breast volume and evaluated the correlation with a/b. We have found a significative correlation (p = 0.01) between small Vol breast (≤660.23 cc) and a/b < 0.0821 and greater Vol breast (>660.23 cc) with a/b > 0.0821. From the evaluation of the distribution of V10 in the two groups taking account of the Dmean ≤5 or >5 significance was found with a/b; Chi square 0.009 (0.01). Values ≤5 were observed in women with a/b < 0.0821. Values >5 in women with a/b > 0.0821. CONCLUSIONS: The geometric conformity of chest thorax considering a/b and the value of 0.0821 can reveals an important parameter in the selection of patients suitable for radiation therapy on left breast in order to evaluate the risk of late cardiac events. This consideration during treatment planning can change the technique or the set-up allowing the development of a customized plan.

Interferometric measurement of preheating in laser shocks.

We present a preliminary study of preheating in laser shocks using an interferometric diagnostic. A low energy probe laser divided in two by a biprism produces an interference pattern on the rear side of a target. The expansion due to preheating causes a fringe shift before shock arrival. A streak camera produces time-resolved images of the target rear side, which are filtered to reduce noise and correct for instrumental effects. Results are compared with an analytical model, which assumes that preheating is due to x rays, and with results from reflectivity measurements.

Influenza vaccination coverage in elderly people, Campania (Italy), 1999.

A study on the coverage of influenza vaccination among elderly people was carried out. Fity-six per cent of those interviewed had been vaccinated (weighted coverage 50%), compared with the target of 75%, but higher rates were reported in those older than 74 years and those with chronic diseases.

[New orientations in the treatment of proclaimed tetanus: use of continuous peridural anesthesia]. / Nuovi orientamenti nel trattamento del tetano conclamato: uso della peridurale continua

Notes on the typical infectious and toxis picture associated with tetatus and the physiopathological aspects of the disease are followed by the presentation of continuous C8-L2 peridural anaesthesia, giving antalgic relief and partial motor block, as a primary form of therapeutic management. A classic two catheter technique is employed and fractioned doses are used so as to exploit the action of the local anaesthetic absorbed by the patient over several days. Sedation of the orthosympathetic leads to reduced catecholamine production, hypometabolism and cardiac sedation. Analgesia and relaxation are achieved by blocking the local and general spasms typical of the disease. Success with the method in serious cases is mentioned and its use in all forms is recommended.

Determinants of erectile dysfunction in type 2 diabetes.

This study was designed to evaluate the prevalence and correlates of ED in a population of diabetic men. Consecutive patients with type 2 diabetes were recruited among outpatients regularly attending Diabetes Clinics. Inclusion criteria for the initial selection of patients were a diagnosis of type 2 diabetes for at least 6 months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher: a total of 555 (90.8%) of the 611 men were analyzed in this study. ED was assessed by the IIEF-5 instrument. Approximately, 6 in 10 men in our sample of diabetic men had varying degrees of erectile dysfunction: mild 9%, mild to moderate 11.2%, moderate 16.9% and severe 22.9%. The prevalence of severe ED increased with age. Higher hemoglobin A1c (HbA1c) levels were associated with ED; similarly, the presence of metabolic syndrome, hypertension, atherogenic dyslipidemia (low levels of HDL-cholesterol and high levels of triglycerides) and depression was associated with ED. Physical activity was protective of ED; men with higher levels of physical activity were 10% less likely to have ED as compared with those with the lowest level. In conclusion, among subjects with type 2 diabetes glycemic control and other metabolic covariates were associated with ED risk, whereas higher level of physical activity was protective. These results encourage the implementation of current medical guidelines that place intensive lifestyle changes as the first step of the management of type 2 diabetes.

Determinants of female sexual dysfunction in type 2 diabetes.

Studies assessing sexual dysfunction in type 2 diabetic women are scanty. This study was designed to evaluate the prevalence and correlates of female sexual function in a quite large population of diabetic women. A total of 595 women with type 2 diabetes completed a questionnaire of self-report measures of sexual dysfunction and were analyzed in this study. Their age was 57.9+/-6.9 (mean and s.d.), duration of diabetes was 5.2+/-1.5 years and mean hemoglobin A1c (HbA1c) level was 8.3+/-1.3%. Female sexual dysfunction (FSD) was assessed by the Female Sexual Function Index instrument with a cut-off score of 23. The overall prevalence of FSD among the diabetic women was 53.4%, significantly higher in menopausal women (63.9%), as compared with nonmenopausal women (41.0%, P<0.001). There was no association between HbA1c, duration of diabetes, hypertension, or cigarette smoking status and FSD; on the contrary, age, metabolic syndrome and atherogenic dyslipidemia were significantly associated with FSD. Both depression and marital status were independent predictors of FSD, while physical activity was protective. Further studies are needed to elucidate in full the mechanisms underlying the evident differences between male and female sexual function. In the meantime, evaluation of female sexuality should become a routine evaluation in women with type 2 diabetes, such as other diabetic complications.

Health related quality of life after radical cystectomy: comparison of ileal conduit to continent orthotopic neobladder.

AIMS: To compare health related quality of life (HRQOL) between patients with two different types of urinary diversion, ileal conduit and orthotopic neobladder, and between them and an age-matched population of healthy subjects. MATERIALS AND METHODS: Eighty eight patients treated with radical cystectomy for bladder cancer at our institutions between 2002 and 2007 were contacted for this survey. All of them had a follow-up of more than 12 months after surgery and were recurrence free. The SF-36 questionnaire was provided to each patient during a follow-up visit at outpatient clinics. Overall, 79 patients (90%) returned the questionnaire and were included in this analysis. They were divided into two groups: group 1 comprised 44 patients with an ileal conduit diversion, and group 2 included 35 patients with a neobladder. As a control, normative values of an age-matched healthy Italian population were considered. RESULTS: No significant difference was found in scale scores between the neobladder and ileal conduit groups. Scale scores for role-physical functioning, social functioning and role-emotional functioning in both the neobladder and ileal conduit groups were significantly below the Italian population norm. Patients with a neobladder 65 years old or older (n=18) had significantly lower scores for role-physical functioning and role-emotional functioning than those younger than 65 years (n=17; p<0.05). CONCLUSION: Few differences between ileal conduit and orthotopic bladder substitution have been detected. Thus, the assumption that continent reconstruction provides better HRQOL than ileal conduit diversion cannot be supported. Patient education and active participation in treatment decisions seem to be the key to postoperative satisfaction.