Laparoscopic Treatment of Bulky Nodes in Primary and Recurrent Ovarian Cancer: Surgical Technique and Outcomes from Two Specialized Italian Centers.

(1) Background: Minimally invasive surgery (MIS) represents a feasible approach in early-stage ovarian cancer, while this question is still unsolved for advanced and recurrent disease. (2) Methods: In this retrospective, multicenter study, we present a series of 21 patients who underwent MIS for primitive or recurrent epithelial ovarian cancer (EOC) with bulky nodal metastasis and discuss surgical technique and outcomes in relation to the current literature. (3) Results: Complete cytoreduction at primary debulking surgery was obtained in 86% of cases. No complication occurred in our patients intraoperatively and only 11.1% of our patients experienced grade 2 and 3 postoperative complications. Notably, all the patients with isolated lymph nodal recurrence (ILNR) were successfully treated with a minimally invasive approach with no intra- or postoperative complications. (4) Conclusions: The results of our study are consistent with those reported in the literature, demonstrating that MIS may represent a safe approach in advanced and recurrent EOC with nodal metastasis if performed on selected patients by expert surgeons with an adequate setting and appropriate technique.

Clinical, Pathological, and Prognostic Features of Male Breast Cancer: A Multicenter Study.

Male breast cancer (BC) represents less than 1% of male tumors. Little is known about male BC characteristics, management, and survival, with many studies based on a small number of cases. Consequently, the treatment of male BC lacks specific guidelines. The aims of the study are to compare male and female breast cancer (FBC) in terms of cancer clinical and anatomopathological features and treatment approach, and to identify differences between male BC and FBC in terms of survival. Patients and methods: Data from 2006 to 2018 were retrospectively acquired. Amounts of 49 males and 680 postmenopausal females with primary non-metastatic BC who underwent breast surgery at Mauriziano Hospital or IRCCS Candiolo (TO-Italy) were included. The mean age at diagnosis for male BC was 68.6 years, and males presented a smaller tumor size than women (p < 0.05) at diagnosis. Most male BC patients received adjuvant endocrine therapy (AET) with tamoxifen (73.5%). AET drop-out rate due to side effects was 16.3% for males compared to 7.6% for women (p = 0.04). Comparing FBC and male BC, no differences have been identified in terms of DFS and OS, with a similar 10-year-relapse rate (12% male BC vs. 12.4% FBC). Propensity Score Matching by age, nodal status, pT, and molecular subtype had been performed and no differences in OS and DFS were seen between male BC and FBC. In conclusion, male BC and FBC have similar prognostic factors and survival outcomes. The drop-out rate of AET was higher in males, and side effects were the main reason for drug discontinuation.

Emerging evidence on the role of breast microbiota on the development of breast cancer in high-risk patients.

Cancer is a multi-factorial disease, and the etiology of breast cancer (BC) is due to a combination of both genetic and environmental factors. Breast tissue shows a unique microbiota, Proteobacteria and Firmicutes are the most abundant bacteria in breast tissue, and several studies have shown that the microbiota of healthy breast differs from that of BC. Breast microbiota appears to be correlated with different characteristics of the tumor, and prognostic clinicopathologic features. It also appears that there are subtle differences between the microbial profiles of the healthy control and high-risk patients. Genetic predisposition is an extremely important risk factor for BC. BRCA1/2 germline mutations and Li-Fraumeni syndrome are DNA repair deficiency syndromes inherited as autosomal dominant characters that substantially increase the risk of BC. These syndromes exhibit incomplete penetrance of BC expression in carrier subjects. The action of breast microbiota on carcinogenesis might explain why women with a mutation develop cancer and others do not. Among the potential biological pathways through which the breast microbiota may affect tumorigenesis, the most relevant appear to be DNA damage caused by colibactin and other bacterial-derived genotoxins, ß-glucuronidase-mediated estrogen deconjugation and reactivation, and HPV-mediated cancer susceptibility. In conclusion, in patients with a genetic predisposition, an unfavorable breast microbiota may be co-responsible for the onset of BC. Prospectively, the ability to modulate the microbiota may have an impact on disease onset and progression in patients at high risk for BC.

Adherence to Adjuvant Endocrine Therapy in Breast Cancer Patients.

BACKGROUND: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality of women with hormone-receptor-positive tumors, but poor adherence remains a significant problem. The aim of this study was to analyze AET side effects and their impact on adherence to treatment. METHODS: A total of 373 breast cancer patients treated with AET filled out a specific questionnaire during their follow up visits at the Breast Unit of our Centre. RESULTS: Side effects were reported by 81% of patients, 84% of those taking tamoxifen and 80% of those taking aromatase inhibitors (AIs). The most common side effect in the tamoxifen group was hot flashes (55.6%), while in the AI group it was arthralgia (60.6%). The addition of GnRH agonists to both tamoxifen and AI significantly worsened all menopausal symptoms. Overall, 12% of patients definitively discontinued AET due to side effects, 6.4% during the first 5 years and 24% during extended therapy. Patients who had previously received chemotherapy or radiotherapy reported a significantly lower discontinuation rate. CONCLUSIONS: AET side effects represent a significant problem in breast cancer survivors leading to irregular assumption and discontinuation of therapy. Adherence to AET may be improved by trustful patient-physician communication and a good-quality care network.

Bone modifying agents in postmenopausal breast cancer patients treated with aromatase inhibitors: beyond bone protection?

Estrogen-receptor positive tumours represent the majority of breast cancers in postmenopausal women. Adjuvant endocrine therapy with aromatase inhibitors (AIs), continued for up to 10 years in high-risk patients, reduces by 40% the risk of recurrence. However, this therapy, among other side effects, is burdened with a higher incidence of osteoporotic bone fractures. To date, both bisphosphonates and denosumab are recognized as first-line drugs in the primary prevention of osteoporotic fractures in patients treated with AIs. They have demonstrated their effectiveness in increasing bone mineral density and in reducing the incidence of fractures, but they have also been shown to improve disease free survival (DFS).

Axillary dissection in patients with preoperative positive nodal cytology: Genuine need or overtreatment?

Recent studies demonstrated the possibility to avoid axillary dissection (ALND) in selected patients with one or two metastatic nodes. Otherwise, patients with positive nodal ultrasound-guided fine-needle aspiration cytology (US-FNAC) currently undergo ALDN. The aim of this study is to quantify the nodal burden in patients with positive US-FNAC treated with ALND and to evaluate if clinical or pathological characteristics associated with low nodal involvement can be identified. This is a multicentric retrospective study involving 297 patients who underwent ALND because of a positive preoperative US-FNAC. A total of 157 patients showed bulky axillary lymph nodes at diagnosis, and 70% of them had three or more metastatic nodes. One hundred and forty patients had a clinically negative axilla and in 50% of them, 4 or more metastatic nodes were found with axillary dissection. Overall, the median number of metastatic nodes was 5. Favorable pathological characteristics of tumors were found in patients with only one or two metastatic nodes: smaller primary tumor, a lower proportion of grade 3, invasive lobular carcinomas and a higher proportion of low-Ki67 tumors. In the group of patients with clinically negative axilla and potentially meeting ACOSOG Z0011 criteria, 22 (31%) showed less than three metastatic axillary nodes. A preoperative positive axillary FNAC is associated with a metastatic nodal burden significantly higher than in patients with positive sentinel lymph node biopsy (SLNB). Nevertheless, about 30% of patients with cN0 axilla, positive axillary FNAC performed because of suspicious nodes on imaging, T1-2 primary tumor and breast-conserving surgery showed less than three metastatic axillary nodes, thus meeting ACOSOG Z0011 trial's criteria and therefore would be eligible for skipping ALND according to current guidelines.

The prognostic role of Gender-Age-Physiology system in idiopathic pulmonary fibrosis patients treated with pirfenidone.

INTRODUCTION: Gender, age, physiology (GAP) system have proven to be an easy tool for predicting disease stages and survival in idiopathic pulmonary fibrosis (IPF) patients. OBJECTIVE: To validate mortality risk as determined by the GAP system in a real-life multicentre IPF population treated with pirfenidone. METHODS: The study included patients who received pirfenidone for at least 6 months. The GAP calculator and the GAP index were determined. The primary outcome was all-cause mortality. The prognostic accuracy of the GAP system was evaluated with respect to calibration and discrimination. RESULTS AND CONCLUSION: Sixty-eight IPF patients were enrolled in the study. The median follow-up was 2.4 years (range 0.1-7.4 years). A total of 22 deaths as first event (32%) and of 10 lung transplantation (15%) were recorded. The cumulative incidence of mortality at 1, 2 and 3 years was 10.4%, 22.4% and 38.4%, respectively. The differences between the predicted and observed mortality were not significant for the GAP index while the observed mortality become comparable to that predicted by the GAP calculator only in the third year of follow-up. The C-index for the GAP index was 0.74 (95% CI 0.57-0.93) while the C-statistic value for the GAP calculator was 0.77 (95% CI 0.59-0.95).

State of the art in interstitial pneumonia with autoimmune features: a systematic review on retrospective studies and suggestions for further advances.

The term interstitial pneumonia with autoimmune features (IPAF) has been proposed to define patients with interstitial lung disease (ILD) associated with autoimmune signs not classifiable for connective tissue diseases (CTDs). This new definition overcomes previous nomenclatures and provides a uniform structure for prospective studies through specific classification criteria.This work evaluates the characteristics of IPAF patients reported in the literature, to highlight potential limits through a comparative analysis and to suggest better performing classification criteria.Four retrospective studies on the IPAF population have been considered. The study subjects differed in age, sex, smoking habit, ILD pattern and outcomes. Another important difference lies in the diverse items considered in the classification criteria. The retrospective design of the studies and the absence from some of them of a rheumatologist clearly involved in the diagnosis may have influenced the data, but current IPAF criteria seem to include a rather heterogeneous population. To overcome these discrepancies, this review suggests a limitation in the use of single items and the exclusion of extremely specific CTD criteria. This should avoid the definition of IPAF for those diseases at different stages or at early onset. The investigation of a functional or morphological cut-off of pulmonary involvement would be useful.

A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis.

BACKGROUND: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. OBJECTIVES: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. METHODS: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. RESULTS: Forty-one patients with a forced vital capacity (FVC) ≤50% and/or a diffusing capacity of the lung for carbon monoxide (DLCO) ≤35% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute DLCO at the -6-month, T0, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. CONCLUSIONS: This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted DLCO but does not have significant impact on FVC or other lung parameters.

Ticagrelor: Long-Term Therapy in Patients with Coronary Artery Disease.

INTRODUCTION: Atherothrombosis and coronary artery disease affect more than 13 million individuals only in the United States, about 8 millions in Europe and are the major causes of death worldwide. In particular chronic stable angina impairs patient quality of life, is associated with an important health spending and increased patient mortality; it is a prominent symptom of coronary artery disease (CAD), the latter being prevalent worldwide in patients. A key role in pathophysiology of cardiovascular acute events is played by activated platelets. Aspirin and adenosine diphosphate antagonist in addition to it is recommended for 1 year for reduction of cardiovascular events in patients with prior myocardial infarction with a weak recommendation to continue thereafter. P2Y12 receptor antagonists, in addition to aspirin, have been shown in the last years, to reduce ischemic events in patients with acute coronary syndrome but their role in secondary prevention is still new and unclear. The aim of our paper is to review the long-term effect of therapy with ticagrelor on the basis of recent evidence based data. METHODS: We performed an online search on the major search engines. All the randomized controlled trials were summarized in the table. RESULTS: We included in our paper six randomized controlled trials and we mentioned about ten post - hoc analysis, sub studies and registries. All studies included the type the therapy and a mid or long term clinical follow up. CONCLUSIONS: The studies reported in our paper and in particular PEGASUS - TIMI 54 study showed the merit to placing attention of prevention secondary ischemic events after acute coronary syndrome in the context of treatment with dual anti - platelet therapy; it proved a clinical benefit in patients treated with ticagrelor (60 mg x 2) for 3 years. Nevertheless, the effectiveness of these results cannot be generalized to patients with higher bleeding risk or low ischemic risk. In fact prolonged therapy with ticagrelor 60 mg in combination with aspirin could be considered valuable in patients with repeated acute ischemic events or with several coronary revascularizations over time (especially in patients with lower bleeding risk).

[Giant aneurysm of the right coronary artery: an unusual treatment]. / Aneurisma gigante della coronaria destra: un trattamento inusuale.

Coronary artery aneurysm (CAA) is an uncommon disease observed in only 0.15-4.9% of patients undergoing coronary angiography. CAA are defined as dilated coronary artery sections exceeding by 1.5 times the diameter of normal adjacent segments or of the patient's largest coronary vessel. Occasionally, CAA enlarge enough to be called giant CAA. We report the case of a 78-year-old man, with known chronic ischemic cardiomyopathy and a history of prior coronary artery bypass surgery (with a left internal mammary artery graft to the left anterior descending coronary artery and saphenous venous graft to the obtuse marginal branch), who was referred to our cardiology department for progressive dyspnea. Echocardiography showed severe mitral regurgitation suggesting replacement; coronary angiography revealed three-vessel coronary artery disease, left internal mammary artery patency, saphenous vein graft occlusion and an aneurysm of the mid right coronary artery. Cardiac magnetic resonance confirmed this finding, showing a giant CAA (65 x 75 mm) with a large endoluminal thrombus. Treatment is not standardized and may include medical therapy, percutaneous treatment and surgical intervention; our patient underwent percutaneous coil embolization. One-month angiographic follow-up showed successful obliteration. The patient underwent surgical mitral valve replacement without any complications. At 9-month clinical follow-up, he was asymptomatic; transthoracic echocardiography showed an ejection fraction of 44% without prosthetic mitral regurgitation.

Ticagrelor: a novel drug for an old problem.

Cardiovascular disease and in particular, acute coronary syndromes are one of the principle causes of death in the industrialized countries. In the setting of acute coronary syndromes (both ST - segment or non ST - segment elevation myocardial infarction), platelets aggregation plays a key and central role in their development. Platelets are the mediators of hemostasis at sites of vascular injury, but they also mediate pathologic thrombosis; activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion promoting atherothrombotic disease. Recent patent relates to the methods and devices for treating atherosclerosis and to prevent in-stent restenosis or thrombosis. Because of the importance of platelets involvement in the initiation and propagation of thrombosis, antiplatelet drugs have a source of research; in the recent past, new antiplatelet drugs (such as ticagrelor) have been studied and placed in the routine therapy. The aim of this paper is to summarize the pharmacological properties and the clinical characteristics of ticagrelor.

Intracoronary injection of drugs to treat no--reflow phenomenon and microcirculatory dysfunction.

In a variant proportion of patients presenting with chest pain and electrocardiographic changes characteristic for ST - elevation myocardial infarction, percutaneous coronary intervention achieves epicardial coronary artery reperfusion but not the myocardial reperfusion (ranging from 5% to 50%). Furthermore, prolonged myocardial ischemia often breaks down the coronary microvasculature and the flow to the infarct myocardium may seem to be markedly reduced. This condition is known as no reflow - phenomenon. The no reflow - phenomenon is associated with an increased incidence of malignant ventricular arrhythmias, heart failure and 30-days mortality. In the recent years in literature, several articles (subsequently discussed in the present review) have been published and made relevant to the study of the pathophysiology regarding no reflow - phenomenon. This knowledge has assisted in the development of new treatment strategies, such as prophylactic use of vasodilators, mechanical devices and drugs inhibiting platelet. The review has focused on the current literature about intra - coronary injection of drugs to treat no - reflow and microvascular dysfunction.

Levosimendan preoperative.

During the last years an increasing number of patients with high perioperative risk and decreased left ventricular function are referred to cardiac and non-cardiac surgery. In this subgroup of patients, heart failure is the major cause of perioperative morbidity and mortality. In order to prevent and treat this type of complications several therapeutic attempts have been tried involving intra aortic balloon pump and inotropic agents infusion (such as beta-adrenergic agonists and phosphodiesterase inhibitors) Levosimendan is new inotropic agent; it is a calcium-sensitising inotropic agent and a vasodilator used in the treatment of heart failure. In the last ten years several reports have been published on levosimendan. The inotropic efficacy of levosimendan is dose-dependent and equal or even superior to any of the other commercially available inotropic agents. The aim of the present review is to describe experimental and clinical effects of perioperative treatment with levosimendan.

Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction.

Endothelial progenitor cell (EPC) mobilization has been reported following tissue damage, whereas no data are available regarding the mobilization of hematopoietic progenitor cells (HPCs). We performed the phenotypic and functional analysis of circulating CD34+ progenitor cells in patients with acute myocardial infarction (AMI), assessed from admission up to 60 days, in patients with stable angina pectoris (SA), and in healthy controls (CTRLs). In patients with AMI at admission (T0), the number of circulating CD34+ cells was higher (P < .001) than in CTRLs and became comparable with CTRLs within 60 days. Both the number of CD34+ cells coexpressing CD33, CD38, or CD117 and the number of HPCs was higher (P < .02 for all) in patients with AMI at T0 than in CTRLs, as was the number of hematopoietic colonies (P < .03). Patients with AMI (T0) had a significantly increased number of CD34+ vascular endothelial growth factor receptor 2-positive (VEGFR-2+) cells (P < .002) with respect to CTRLs, including CD34(+) CD133(+)VEGFR-2+ and CD34+ CD117(+)VEGFR-2+ EPCs. The number of endothelial colonies was higher in patients with AMI (T0) than in CTRLs (P < .05). No significant difference was documented between patients with SA and CTRLs. Spontaneous mobilization of both HPCs and EPCs occurs within a few hours from the onset of AMI and is detectable until 2 months.