Platelet Lysate-Derived Neuropeptide y Influences Migration and Angiogenesis of Human Adipose Tissue-Derived Stromal Cells.

Neuropeptide Y (NPY), a powerful neurotransmitter of the central nervous system, is a key regulator of angiogenesis and biology of adipose depots. Intriguingly, its peripheral vascular and angiogenic powerful activity is strictly associated to platelets, which are source of clinical hemoderivates, such as platelet lysate (PL), routinely employed in several clinical applications as wound healing, and to preserve ex vivo the progenitor properties of the adipose stromal cells pool. So far, the presence of NPY in PL and its biological effects on the adipose stromal cell fraction (ASCs) have never been investigated. Here, we aimed to identify endogenous sources of NPY such as PL-based preparations and to investigate which biological properties PL-derived NPY is able to exert on ASCs. The results show that PL contains a high amount of NPY, which is in part also excreted by ASCs when stimulated with PL. The protein levels of the three main NPY subtype receptors (Y1, Y2, Y5) are unaltered by stimulation of ASCs with PL, but their inhibition through selective pharmacological antagonists, considerably enhances migration, and a parallel reduction of angiogenic features of ASCs including decrease in VEGF mRNA and intracellular calcium levels, both downstream targets of NPY. The expression of VEGF and NPY is enhanced within the sites of neovascularisation of difficult wounds in patients after treatment with leuco-platelet concentrates. Our data highlight the presence of NPY in PL preparations and its peripheral effects on adipose progenitors.

Eribulin for metastatic breast cancer (MBC) treatment: a retrospective, multicenter study based in Campania, south Italy (Eri-001 trial).

BACKGROUND: On the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease. METHODS: In our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC. RESULTS: Eribulin as monotherapy provided benefit in terms of progression-free survival (PFS), response rate (RR) and disease control rate (DCR) independently of its use as second or late-line therapy. The overall RR and DCR were 17.5% and 64%, respectively. In particular, DCR and overall RR were 50% and 13.6%, 65.4% and 21.1%, 70.4% and 14.8% and 66.7% and 16.7% in second, third, fourth and further lines of treatment, respectively. Median PFS (mPFS) according to the line of therapy was 5.7, 6.3, 4.5 and 4.0 months in patients treated with eribulin in second, third, fourth and over the fourth line, respectively. No significant difference in terms of mPFS was found between the various BC subtypes. Overall, eribulin resulted safe and most adverse events were of grade 1 or 2 and easily manageable. Grades 3-4 toxicities were neutropaenia and neurotoxicity. CONCLUSIONS: With the limitations due to the observational nature of our findings, eribulin was shown to be an effective and safe therapeutic option in heavily pretreated patients with aBC.

Neutrophil to lymphocyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: a propensity score-matched analysis.

OBJECTIVE: To assess the correlation between presurgery neutrophil to lymphocyte ratio (NLR) and distant metastasis-free survival (DMFS) in patients with early breast cancer. DESIGN: Retrospective analysis. PARTICIPANTS: 300 Caucasian patients with early (T1-2, N0-1, non-metastatic) breast cancer who were followed from July 1999 to June 2015 at our Institution. MAIN OUTCOME MEASURES: Distant metastasis-free survival (DMFS). RESULTS: Of whole populations (300 patients), 134 and 166 patients were grouped as low and high NLR, respectively, on the basis of NLR value of 1.97, as established by receiver operating characteristic (ROC) curve analysis (area under curve (AUC)=0.625, p=0.0160). The DMFS rates for 1, 3, 6, 9, 12 and 15 years were better in low NLR patients (100%, 98.9%, 91.7%, 82.7%, 82.7%, 82.7%, respectively), than in high NLR patients (99.4%, 94.3%, 84.5%, 69.2%, 66.0%, 51.4%, respectively), with a statistically significant association. On multivariate analysis, premenopausal status (HR=2.78, 95% CI 1.36 to 5.67, p=0.0049), N1 stage (HR=2.31, 95% CI 1.16 to 4.60, p=0.0167) and a high NLR value (HR=2.64, 95% CI 1.22 to 5.638, p=0.0133) were shown to be independent prognostic factors related to poor recurrence rate. To avoid risk of confounding bias, a propensity score-matched analysis was performed and multivariate analysis according to the Cox model confirmed premenopausal status (HR=2.94, 95% CI 1.25 to 6.93, p=0.0136), N1 stage (HR=2.77, 95% CI 1.25 to 6.12, p=0.0117) and high NLR values (HR=2.52, 95% CI 1.11 to 5.73, p=0.0271), as independent prognostic variables of worse outcome. CONCLUSIONS: This is the first study, to our knowledge, to show a significant correlation between high NLR and worse prognosis in Caucasian patients with early breast cancer by means of propensity score-matched analysis. Further well designed prospective trials with a large sample size are needed to verify our findings and to justify introducing NLR assessment in clinical practice for prediction of cancer recurrence.

Breast conserving treatment for ductal carcinoma in situ in the elderly: can radiation therapy be avoided? Our experience.

INTRODUCTION: Ductal Carcinoma In Situ (DCIS) is a heterogeneous, pre-malignant disease accounting for 15-20% of all new breast cancers. If appropriately managed, DCIS has a small chance of impacting on patient life expectancy. Despite the possibility of a further recurrence or of a development in an invasive form, we are unable to select treatment of choice especially in the elderly. In particularly we risk an overtreatment of women at low risk of progression to invasive breast cancer. The aim of this study was to retrospectively evaluate the outcome of elderly patients affected by DCIS not undergoing Radiation Therapy (RT) after Breast Conserving Surgery (BCS). MATERIAL AND METHODS: We reviewed our prospectively-maintained database from 1998 to 2013, selecting all women over 65 years old diagnosed with DCIS who did not receive RT for personal choice. We considered two groups, according to the risk of local recurrence (Low Risk (Group 1) vs. High Risk (Group 2)). RESULTS: We identified 44 cases of DCIS treated with surgery alone or with surgery followed by adjuvant tamoxifen. 24 patients presented low risk of local recurrence (Group 1) and 20 had characteristics associated to high risk of local recurrence (Group 2). At a median follow-up of 66.3 months, no local recurrences have been described in group 1. No patients presented distant metastases, while 4 patients died for other causes. At a median follow-up of 72 months we observed 5 local recurrences in the second group (p < 0.05). CONCLUSION: Our results suggest that radiation therapy can be safely avoided in a selected group of elderly patients affected by DCIS.

Post-operative peritonitis due to anastomotic dehiscence after colonic resection. Multicentric experience, retrospective analysis of risk factors and review of the literature.

INTRODUCTION: Intraperitoneal sepsis due to anastomotic leakage significantly affects the outcomes of intestinal surgery. The aim of this retrospective review is to examine retrospectively general and local factors involved in anastomotic leakage and their prognostic value. MATERIALS AND METHODS: Between April 1998 and April 2008, 367 patients underwent elective (217=59%) or emergency (150=41%) primary colonic resection for benignan (77=21%) or malignant (290=79%) disease in our department. We performed the following operations; 124 right colon resections with immediate anastomoses (primary resection), 65 (52.4%) of which were emergency and 59 (47.6%) elective procedures; 171 left colon resections, 73 (42.7%) of which were emergency and 98 (57.3%) elective procedures, and 72 primary rectal resections, 12 (16.7%) of which were emergency and 60 (83.3%) elective procedures. The considered variables were stapled or manual anastomoses, protective stomas and medical comorbidities. RESULTS: The perioperative mortality rate was 6.6% for emergency and 3.6% for elective procedures. The leak rate was 8.7% (32/367), 13.3% for emergency and 5.5% for elective procedures. Fistula was observed in 7/124 (5.6%) ileocolic, 13/171 (7.6%) colo-colic and 12/72 (16.6%) colo-rectal anastomoses, 8 of which were fashioned during emergency surgery. Twenty-one patients with anastomotic dehiscence were treated conservatively (3 underwent reoperation), while 11, with severe dehiscence, in all cases in the left colon, underwent an emergency Hartmann's procedure, with a perioperative mortality rate of 35.7%. CONCLUSIONS: In our experience, the site of colonic anastomosis represents the risk factor most strictly related to the anastomotic leak rate, while other technical factors seem weakly associated with leakage. A significantly high percentage of patients (65.6%) with anastomotic fistulas have medical comorbidities.

[Antibiotic prophylaxis in breast surgery. Preliminary resuls of a multicenter randomized study on 1400 cases]. / Antibiotico profilassi in Chirurgia Senologica. Risultati preliminari di uno studio multicentrico randomizzato su 1400 casi trattati.

UNLABELLED: Breast surgery is classified among the procedures performed in clean surgery and is associated with a low incidence of wound infection (3-15%). The objective of this study was to evaluate the advantages antibiotic prophylaxis in patients undergoing breast surgery. A multicenter randomized controlled study was performed between January 2008 and November 2008. One thousand four hundred patients were enrolled in prospective randomized study; surgical wound infection was found in 41 patients (2.93%). In our RCT we have shown that in breast surgery antibiotic prophylaxis does not present significant advantages in patients with potential risk of infection (17 patients, 2.42%, subjected to antibiotic prophylaxis vs 24 patients, 3.43%, without antibiotic prophylaxis) (P = 0.27). In patients with drainage there is a significant minor incidence of wound infections in patients receiving antibiotic prophylaxis (5 patients, 0.92%, subjected to antibiotic prophylaxis vs 14 patients, 3.09%, without antibiotic prophylaxis) (P = 0.02). CONCLUSION: This study is only a preliminary RCT to be followed by a study which should be enrolled more patients in order to get the results as statistically significant.

Antibiotic prophylaxis in thyroid surgery: a preliminary multicentric Italian experience.

Post-operatory wound infections are a very uncommon finding after thyroidectomy. For these reasons international guidelines do not routinely recommend systemic antibiotic prophylaxis. The benefits of this antibiotic prophylaxis is not supported by clinical evidence in the literature. We have conducted a multicentric randomized double-blind trial on 500 patients who had undergone thyroidectomy for goitre or thyroid carcinoma. The 500 patients enrolled in the study (mean age 47 years) were randomized in two subgroups of 250 patients. 250 patients were treated with standard antibiotic prophylaxis with sulbactam/ampicillin 1 fl (3 gr.) 30 min before surgery. No antibiotic prophylaxis was instituted in the remainder 250 patients. Our RCT showed that prophylactic antibiotic treatment is not beneficial in patients younger than eighty years old, with no concomitant metabolic, infective and hematologic disease, with no cardiac valvulopathies, not under steroidal or immunosuppressive treatment, and not severely obese. Our study should be regarded only as a preliminary RCT, and should be followed by a study in which a larger number of patients should be enrolled so that statistically significant data can be obtained.

Effectiveness of fibrin glue in conjunction with collagen patches to reduce seroma formation after axillary lymphadenectomy for breast cancer.

BACKGROUND: Axillary lymphadenectomy remains an integral part of breast cancer treatment, yet seroma formation occurs in 15% to 85% of cases. Among methods employed to reduce seroma magnitude and duration, fibrin glue has been proposed in numerous studies, with controversial results. METHODS: Fifty patients underwent quadrantectomy or mastectomy with level I/II axillary lymphadenectomy; a suction drain was fitted in all patients. Fibrin glue spray and a collagen patch were applied to the axillary fossa in 25 patients; the other 25 patients were treated conventionally. RESULTS: Suction drainage was removed between postoperative days 3 and 4. Seroma magnitude and duration were significantly reduced (P = .004 and .02, respectively) and there were fewer evacuative punctures in patients receiving fibrin glue and collagen patches compared with the conventional treatment group. CONCLUSIONS: Use of fibrin glue with collagen patches does not always prevent seroma formation, but it does reduce seroma magnitude and duration, as well as necessary evacuative punctures.

Solid-cystic pseudopapillary tumor of pancreas: description of two cases and literature review.

The authors report the cases of two young female patients aged 17 and 27 years who underwent surgery for a rare tumor of the pancreas, Frantz's tumor or solid-cystic pseudopapillary tumor. Solid-cystic pseudopapillary tumor of the pancreas is a rare tumor, accounting for 2.7% of pancreatic exocrine tumors. About 90% of these tumors occur in young women and they can reach very large dimensions. Due to their rareness and behavior, they are often associated with diagnostic and therapeutic problems. In most cases surgical treatment is curative and neither chemotherapy nor radiotherapy should be added. In the few cases where surgery is not possible, radiotherapy can be used because these tumors appear to be radiosensitive.