Breast cancer and the steadily increasing maternal age: are they colliding?

BACKGROUND: Pregnancy-related cancers are mostly breast cancers, and their incidence is likely to increase as a result of the modern trend of delaying childbearing. In particular, advanced maternal age increases breast cancer risk, and younger breast cancer patients are more likely to die and metastasize. This study compared a population with a high incidence of delayed childbearing with another population with a lower mean age at childbirth in order to determine whether breast cancer diagnosis and childbearing age overlap. METHODS: We retrospectively analyzed multiple data sources. The Surveillance, Epidemiology, and End Results (SEER) program, the United States National Center for Health Statistics as part of the National Vital Statistics System, the United Nations Population Division, the GLOBOCAN Cancer Observatory, the CLIO-INFRA project database, the Human Fertility Database, and anonymized local data were used. RESULTS: As women's age at delivery increased, the convergence between their age distribution at breast cancer diagnosis and childbearing increased. In addition, the overlap between the two age distributions increased by more than 200% as the average age at delivery increased from 27 to 35 years. CONCLUSIONS: As women's average childbearing age has progressively risen, pregnancy and breast cancer age distributions have significantly overlapped. This finding emphasizes the need for increased awareness and educational efforts to inform women about the potential consequences of delayed childbearing. By providing comprehensive information and support, women can make more informed decisions about their reproductive health and cancer prevention strategies.

Assisted Reproductive Technology and Breech Delivery: A Nationwide Cohort Study in Singleton Pregnancies.

Since essential factors have changed in recent years in assisted reproduction technologies (ARTs), this study reassessed the association between ART and breech presentation. We primarily aimed to estimate the correlation between ART and breech at delivery. Secondary purposes were to evaluate the correlation between other subfertility treatments (OSTs) and breech and to assess possible confounding factors and temporal trends. This study investigated the 31,692,729 live birth certificates from US states and territories in the 2009-2020 period. The inclusion criteria were singleton births reporting the method of conception and the presentation at delivery. The outcome was the breech presentation at delivery, while the primary exposure was ART, the secondary exposure was OST, and the potential confounding factors from the literature were considered. ART (OR 2.32 CI.95 2.23-2.41) and OST (OR 1.79 CI.95 1.71-1.87) were independent and significant risk factors for breech at delivery (p < 0.001). This study confirmed breech presentation risk factors maternal age, nulliparity, tobacco smoke, a previous cesarean delivery (CD), neonatal female sex, gestational age, and birth weight. Black race and Hispanic origin were verified to be protective factors. We found breech prevalence among ART and OST to be stable during the study period. Meanwhile, newborn birth weight was increased, and the gap between breech and other presentations in ART was reduced. Our results indicate that singleton pregnancies conceived by ART or OST were associated with a higher risk of breech at delivery. Well-known risk factors for the breech presentation were also confirmed. Some of these factors can be modified by implementing interventions to reduce their prevalence (e.g., tobacco smoke and previous CD).

Repeated Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Selected Patients Affected by Peritoneal Metastases: Italian PSM Oncoteam Evidence.

The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still questioned regarding safety and effectiveness. This study evaluates the safety, efficacy, and associated factors of iterative CRS combined with HIPEC. This multicentric retrospective study collected data from four surgical oncology centers, on iterative HIPEC. We gathered data on patient and cancer characteristics, the peritoneal cancer index (PCI), completeness of cytoreduction (CC), postoperative complications, and overall survival (OS). In the study period, 141 CRS-plus-HIPECs were performed on 65 patients. Nine patients underwent three iterative procedures, and one underwent five. No increased incidence of complications after the second or third procedure was observed. Furthermore, operative time and hospitalization stay were significantly shorter after the second than after the first procedure (p < 0.05). Optimal cytoreduction was achieved in more than 90% of cases in each procedure, whether first, second, or third. A five-year (5 y) OS represented 100% of the cases of diffuse malignant-peritoneal-mesotheliomas, 81.39% of pseudomyxoma peritonei, 34.67% of colorectal cancer (CRC), and 52.50% of ovarian cancer. During the second CRS combined with HIPEC, we observed a lower rate of complete cytoreduction and a non-significantly better survival in cases with complete cytoreduction (5 y-OS CC-0 56.51% vs. 37.82%, p = 0.061). Concomitant hepatic-CRC-metastasis did not compromise the CRS-plus-HIPEC safety and efficacy. This multicentric experience encourages repeated CRS-plus-HIPEC, showing promising results.

Risk-Reducing Breast and Gynecological Surgery for BRCA Mutation Carriers: A Narrative Review.

This narrative review aims to clarify the role of breast and gynecological risk-reduction surgery in BRCA mutation carriers. We examine the indications, contraindications, complications, technical aspects, timing, economic impact, ethical issues, and prognostic benefits of the most common prophylactic surgical options from the perspectives of a breast surgeon and a gynecologist. A comprehensive literature review was conducted using the PubMed/Medline, Scopus, and EMBASE databases. The databases were explored from their inceptions to August 2022. Three independent reviewers screened the items and selected those most relevant to this review's scope. BRCA1/2 mutation carriers are significantly more likely to develop breast, ovarian, and serous endometrial cancer. Because of the Angelina effect, there has been a significant increase in bilateral risk-reducing mastectomy (BRRM) since 2013. BRRM and risk-reducing salpingo-oophorectomy (RRSO) significantly reduce the risk of developing breast and ovarian cancer. RRSO has significant side effects, including an impact on fertility and early menopause (i.e., vasomotor symptoms, cardiovascular disease, osteoporosis, cognitive impairment, and sexual dysfunction). Hormonal therapy can help with these symptoms. Because of the lower risk of developing breast cancer in the residual mammary gland tissue after BRRM, estrogen-only treatments have an advantage over an estrogen/progesterone combined treatment. Risk-reducing hysterectomy allows for estrogen-only treatments and lowers the risk of endometrial cancer. Although prophylactic surgery reduces the cancer risk, it has disadvantages associated with early menopause. A multidisciplinary team must carefully inform the woman who chooses this path of the broad spectrum of implications, from cancer risk reduction to hormonal therapies.

Quantification of Women Who Could Benefit from Hormone Therapy after Endometrial Cancer Treatment: An Analysis of SEER Data.

Our primary aim was to estimate the magnitude of stage I endometrial cancer (EC) survivors that could benefit from hormonal therapy (HT). Our secondary aims were to assess EC incidence in women below 50 and below 60 over the years, and analyze the overall survival and any influencing factors. We analyzed the endometrioid EC data from the Surveillance, Epidemiology, and End Results (SEER) program according to women's age, tumor stage, and grade. We analyzed the proportions of EC survivors below 50 and below 60 years of age and stratified those age groups by race. For age distribution and survival analysis SEER, 18 registries' research data (2000-2018) were analyzed. We analyzed the SEER 12 registries' research data (1992-2019) for incidence time trends. Our investigation found a 14% and 40% cumulative prevalence of stage I EC that occurs in women below 50 or 60 years, respectively. EC's prevalence has progressively risen in recent decades, but cancer-specific mortality remains low. The increasing number of women affected by EC in premenopause or early postmenopause face an 18 years-survival rate of 96.86% and 95.73%, respectively. A significant proportion of low-grade EC survivors can potentially benefit from HT treatment, and this requires awareness of other aspects of their health or quality of life, in addition to cancer treatments.

Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review.

Nanotechnology, the art of engineering structures on a molecular level, offers the opportunity to implement new strategies for the diagnosis and management of pregnancy-related disorders. This review aims to summarize the current state of nanotechnology in obstetrics and cancer in pregnancy, focusing on existing and potential applications, and provides insights on safety and future directions. A systematic and comprehensive literature assessment was performed, querying the following databases: PubMed/Medline, Scopus, and Endbase. The databases were searched from their inception to 22 March 2022. Five independent reviewers screened the items and extracted those which were more pertinent within the scope of this review. Although nanotechnology has been on the bench for many years, most of the studies in obstetrics are preclinical. Ongoing research spans from the development of diagnostic tools, including optimized strategies to selectively confine contrast agents in the maternal bloodstream and approaches to improve diagnostics tests to be used in obstetrics, to the synthesis of innovative delivery nanosystems for therapeutic interventions. Using nanotechnology to achieve spatial and temporal control over the delivery of therapeutic agents (e.g., commonly used drugs, more recently defined formulations, or gene therapy-based approaches) offers significant advantages, including the possibility to target specific cells/tissues of interest (e.g., the maternal bloodstream, uterus wall, or fetal compartment). This characteristic of nanotechnology-driven therapy reduces side effects and the amount of therapeutic agent used. However, nanotoxicology appears to be a significant obstacle to adopting these technologies in clinical therapeutic praxis. Further research is needed in order to improve these techniques, as they have tremendous potential to improve the accuracy of the tests applied in clinical praxis. This review showed the increasing interest in nanotechnology applications in obstetrics disorders and pregnancy-related pathologies to improve the diagnostic algorithms, monitor pregnancy-related diseases, and implement new treatment strategies.

Survivin, sonic hedgehog, krüppel-like factors, and p53 pathway in serous ovarian cancer: an immunohistochemical study.

Survivin was previously associated with tumor stage and grade in ovarian cancer and interfered with the tumor's drug sensitivity. In addition, Survivin expression was found to be regulated by the Sonic hedgehog (Shh) pathway, Krüppel-like factor (KLF) family proteins, and p53 pathway. The main aim of this study was to assess the prognostic values of immunohistochemical expression of Survivin, Klf5, Klf11, Shh, p53, p21, and Mdm2 in a cohort of high-grade ovarian serous cancers. Other aims were comparison between high- and low-grade ovarian serous cancer and between platinum-resistant and the other cases. The last aim was to assess the correlations among the immunohistochemical expression of the studied proteins. Retrospective cohort study to assess immunohistochemical expression of Survivin, Klf5, Klf11, Shh, p53, p21, and Mdm2 in a tissue microarray of primary tumor samples among 73 women affected by high-grade ovarian serous cancer and 9 by low-grade ovarian serous cancer. Klf5 and Shh cytoplasmic staining were associated with short overall survival (HR 6.38, 95% CI 2.25-18.01, P < .05 and 2.25, 95% CI 1.19-4.23, P < .05, respectively). In addition, cytoplasmic Klf5 staining, high Klf11, and p53 nuclear staining were associated with platinum resistance (P < .05). Cytoplasmic Shh score was significantly correlated to the immunohistochemical expression of Klf5, Klf11, Mdm2, and Survivin. Our data highlight the possible role of Klf5 and Shh as prognostic markers, meanwhile confirming the role of the KLF family proteins and p53 in ovarian cancer drug resistance. Moreover, Shh appeared to play an important role in the intracellular network of ovarian neoplasia.

One-Step Nucleic Acid Amplification System in Comparison to the Intraoperative Frozen Section and Definitive Histological Examination Among Breast Cancer Patients: A Retrospective Survival Study.

Simple Summary: Implementing intraoperative assessment of sentinel lymph nodes by one-step nucleic acid amplification in early breast cancer can reduce the surgical burden to the patient and the costs to the health system. However, only limited data are available in terms of long-term disease-free survival and overall survival. Therefore, this study aims to compare disease-free survival and overall survival between one-step nucleic acid amplification, frozen section, and definitive histology. These results could impact the healthcare community, adding further proof to the body of evidence supporting the broader adoption of this innovative technology that enables a safe reduction in patient surgical burden and healthcare costs. Background: The one-step nucleic acid amplification (OSNA) system is a novel molecular technique, which consents to quick intraoperative detection of sentinel lymph node metastases by the amplification of cytokeratin 19 mRNA. Our study aims to evaluate the OSNA method in comparison with frozen section (FS) and definitive histological examination of the sentinel lymph node biopsy among early breast cancer patients considering disease-free survival (DFS) and overall survival (OS). Methods: In this study, we included all women who underwent sentinel lymph node biopsy (SLNB) for breast cancers classified as TNM stage I and II in our center between January 2005 and January 2017, and the follow-up was collected up to January 2019. We divided patients among three groups based on SLNB evaluation: definitive histological examination, intra-operative FS, or OSNA. Results: We included 2412 SLNBs: 727 by definitive histological examination, 697 by FS, and 988 by OSNA. Isolated tumor cells were found in 2.32% of cases, micrometastasis in 9.12%, and macrometastases in 13.64%. Surgical procedure duration was significantly shorter in OSNA than in FS (42.1 minutes ±5.1 vs. 70.1 minutes ±10.5, p <0.05). No significant differences have been observed among the three groups regarding OS, DSF, cumulative local, or distant metastases. In particular 5-year DFS was 96.38% in definitive histology (95% C.I. 95.02-97.75%), 96.37% in FS (95% C.I. 94.98-97.78%), and 96.51% in OSNA group (95% C.I. 95.32-97.72%). Conclusions: No difference in OS and DFS was found comparing OSNA, FS, and definitive histology. Furthermore, reduced operative time was found in the OSNA group.

Incidence and Risk Factors for Venous Thromboembolism in Female Patients Undergoing Breast Surgery.

Albeit it does not have the highest venous thromboembolism (VTE) incidence compared to other neoplasms, breast cancer contributes to many VTE events because it is the most diagnosed tumor in women. We aim to analyze the occurrence and timing of VTE during the follow-up of patients who underwent breast surgery, the possible correlated factors, and the overall survival. This retrospective study included all female patients diagnosed with mammary pathology and surgically treated in our clinic between January 2002 and January 2012. Of 5039 women who underwent breast surgery, 1056 were found to have no evidence of malignancy, whereas 3983 were diagnosed with breast cancer. VTE rate resulted significantly higher in patients with invasive breast cancer than in women with benign breast disease or carcinoma in situ. Invasive cancers other than lobular or ductal were associated with a higher VTE rate. In addition, chronic hypertension, high BMI, cancer type, and evidence of metastasis turned out to be the most significant risk factors for VTE in women who underwent breast surgery. Moreover, VTE occurrence significantly impacted survival in invasive breast cancer patients. Compared to women with benign mammary pathology, VTE prevalence in women with breast cancer is significantly higher. The knowledge about the risk factors of VTE could be helpful as prognostic information, but also to eventually target preventive treatment strategies for VTE, as far as the co-existence of invasive breast cancer and VTE has a significantly negative impact on survival.

TFEB, SIRT1, CARM1, Beclin-1 expression and PITX2 methylation in breast cancer chemoresistance: a retrospective study.

BACKGROUND: Breast cancer chemoresistance is attributed to a wide variety of mechanisms, including autophagy. Transcription factor EB (TFEB) has been recently identified and characterized as one major regulator of autophagy and lysosomal genesis. OBJECTIVE: This study aims to evaluate the prognostic impact of TFEB and its pathway in breast cancer chemoresistance. METHODS: This retrospective study analyzes the expression of TFEB, CARM1, SIRT1, and Beclin-1 and the methylation of PITX2 in breast carcinoma. A group of breast cancer patients treated with chemotherapy, who relapsed within 12 months from treatment initiation, were compared to a sub-cohort of chemo-treated patients who did not recur within 12 months of follow-up. The expression of TFEB, CARM1, SIRT1, and Belcin-1 was analyzed using immunohistochemistry or RT-PCR on formalin-fixed paraffin-embedded samples. PITX2 methylation was tested with the diagnostic CE-marked kit Therascreen PITX2 RGQ PCR. In the final model, 136 cases of chemo-treated breast cancer were included. RESULTS: A higher TFEB and Beclin-1 expression correlate with shorter survival in patients with chemo-treated invasive breast cancer (respectively HR 3.46, CI.95 1.27-9.47, p < 0.05 and 7.11, CI.95 2.54-19.9). TFEB, CARM1, and SIRT1 are positively correlated with Beclin-1. The protein expression of SIRT1 is significantly associated with TFEB and CARM1 so that a very low SIRT1 expression (lower than the first quartile of the H-score distribution) correlates with a low expression of TFEB and CARM1 and with longer survival. SIRT1 seems to have a lower H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. Beclin-1 and TFEB seem to have a higher H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. PITX2 methylation analysis was feasible only in 65% of the selected samples, but no significant differences between cases and controls were found, and there was also no correlation with the expression of the TFEB pathway. CONCLUSIONS: TFEB, SIRT1, and Beclin-1 seem to have a potential prognostic significance in patients with chemo-treated breast cancer, likely because of their role in the regulation of autophagy. In addition, no correlation between TFEB and PITX2 methylation was found, likely because they perform two different roles within the autophagy process.

Hormone Replacement Therapy in Endometrial Cancer Survivors: A Meta-Analysis.

The purpose of this study is to investigate the effect of hormone therapy (HT) on the oncological outcomes of endometrial cancer (EC) survivors. A systematic literature review was conducted in July 2021 to identify studies detailing the effect size for the relationship between HT use in EC and oncological outcomes (survival and disease recurrence). This included studies that evaluated the different recurrence rates among women treated for EC who subsequently underwent HT and those who did not. The collected studies were evaluated for quality, heterogeneity, and publication bias, and a pooled odds ratio (OR) or hazard ratio (HR) was calculated with a confidence interval of 95% (95% CI). In total, 5291 studies were collated, and after the review process, one randomized trial and seven observational studies were included, comprising 1801 EC survivors treated with HT and 6015 controls. The time-dependent analysis could be conducted for four studies, and considering the disease-free survival, the pooled HR of 0.90 (95% CI 0.28 to 2.87) showed no significant differences. However, among Black American women treated with continuous estrogen HT, the HR was 7.58 (95% CI 1.96 to 29.31), showing a significantly increased risk of recurrence for women in this ethnic group. Considering the pooled OR of all included studies 0.63 (95% CI 0.48 to 0.83), a significantly reduced risk of recurrence was found among EC survivors treated with HT. Considering the type of HT, the most risk-reducing was combined estrogen and progestin therapy and the cyclic regimen. Although supporting evidence is based mainly upon observational studies, evidence of no increased risk or even decreased risk was generally found, apart from in Black American women where a significantly increased recurrence risk was evident. The data are rather reassuring for the short-term administration of HT to symptomatic EC survivors. Future studies with a longer follow-up are necessary to better clarify the long-term effects of HT.

Atypical polypoid adenomyoma follow-up and management: Systematic review of case reports and series and meta-analysis.

BACKGROUND: Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative treatment is proposed despite the high recurrence rate and the association with endometrial cancer.Our aim was to assess the risk of recurrence with different conservative treatments in fertile ages and the prevalence of malignant or pre-malignant associated lesions to better address an adequate patient counselling when treatment modalities are discussed. METHODS: This study is a systematic review and meta-analysis of case reports and case series about APA management and follow-up. A literature search was carried from Medline and Scopus for studies published from January 1, 1980 to December 31, 2018. RESULTS: We included 46 observational studies and 296 cases in fertile women. The prevalence of APA relapse was 44% (CI.95 33-57%) and was lower in cases treated with operative hysteroscopy (22%; CI.95 11-39%) than in cases treated with blind curettage and polypectomy (38%; CI.95 15-67%). The prevalence of the concomitant or during the follow-up diagnosis of endometrial carcinoma was 16% (CI.95 9-29%). The risk of cancer development during follow-up was significantly less in cases treated with histeroscopy (10.56% new cumulative diagnosis at 5 years follow up; CI.95 0-23.7%) than blind curettage and polypectomy (35.5% new cumulative diagnosis at 5 years; CI.95 11.65-52.92%; P < .05). Medical treatment with medroxyprogesterone acetate after surgery does not reduce APA recurrence. Pregnancy was observed in 79% cases in which the desire was expressed. CONCLUSION: This review suggests that conservative treatment performed by operative hysteroscopy is the optimal choice because it lowers the risk of recurrence, improves the accuracy of concomitant carcinoma or hyperplasia diagnosis, and leaves the possibility of future pregnancies.

Prognostic Role of Krüppel-Like Factors 5, 9, and 11 in Endometrial Endometrioid Cancer.

BACKGROUND AND OBJECTIVE: Krüppel-like factors (KLFs) are transcription factors with the ability to mediate cross-talk with signaling pathways involved in cell proliferation control, apoptosis, migration, and differentiation. They also appear to influence steroid hormone signaling through transcriptional networks involving steroid hormone receptors and members of the nuclear receptor family of transcription factors. Our study aims to evaluate the potential prognostic role of KLF5, KLF9, and KLF11 in endometrial cancer, and their correlation with hormonal receptor status and cellular proliferation. MATERIALS AND METHODS: Retrospective observational study on cases of endometrioid endometrial adenocarcinoma collected in the period January 2000-December 2011 at the University of Udine. Formalin-fixed, paraffin-embedded tissue samples were all submitted to tissue microarray immunohistochemical study. A survival analysis was performed. RESULTS: One hundred forty seven patients were included in the study with a mean age at surgery of 65.6 years (±10.2). 80.3% of endometrial malignancies were classified as stage FIGO I (118/147). Radiation therapy and chemotherapy were administered in 62.3% (91/146) and 6.2% (9/145) of patients respectively. Five-year overall survival and disease-free survival resulted 85.4% (95% CI, 79.8-91.4%) and 79.4% (95% CI, 73.0-86.4%) respectively. A high Ki-67, cytoplasmatic KLF5 (HR 4.72, CI.95 1.61-13.89, p < 0.05), and nuclear KLF11 (HR 3.04, CI.95 0.99-9.36, p = 0.053) scores correlated with a shorter overall survival. In addition, a high nuclear KLF11 (HR 2.59, CI.95 1.13-5.95, p < 0.05) score correlated with a shorter disease-free survival. CONCLUSIONS: In patients affected by endometrioid endometrial carcinoma, higher staining levels of KLF5 and KLF11 correlated with a poorer prognosis. However, further studies are required in order to better clarify the role of KLFs in the natural history of endometrial cancer.

First Trimester Uterine Rupture: A Case Report and Literature Review.

The aim is to report a case of spontaneous uterine rupture in the first trimester of pregnancy and to review the literature on the topic. METHODS: A literature search was performed using PubMed and Scopus. Relevant English articles were identified without any time or study limitations. The data were aggregated, and a summary statistic was calculated. RESULTS: A 35-year-old gravida 5, para 2 was admitted at our department because of fainting and abdominal pain. The woman had a first-trimester twin pregnancy and a history of two previous cesarean sections (CSs). Suspecting a uterine rupture, an emergency laparotomy was performed. The two sacs were completely removed, and the uterine rupture site was closed with a double-layer suture. The patient was discharged from hospital four days later in good condition. On the basis of this experience, a total of 76 case reports were extracted from PubMed and included in the review. Fifty-three patients out of 76 (69.74%) underwent previous surgery on the uterus. Most women (67.92%) had a CS, and in this group a cesarean scar pregnancy (CSP) or a placenta accreta spectrum (PAS) disorder was found to be the etiology in 77.78% of cases. Furthermore, 35.85% of the women had hysterectomy after uterine rupture. Twenty-three patients out of 76 (30.26%) had an unscarred uterus. Of this group, most women presented a uterine anomaly (43.48%). Moreover, 17.39% of these women had a hysterectomy. CONCLUSION: According to the literature, the current pandemic use of CS explains most cases of first-trimester uterine rupture.

Placental fibronectin staining is unaffected in pregnancies complicated by late-onset intrauterine growth restriction and small for gestational age fetuses.

OBJECTIVE: To investigate the placental staining pattern of fibronectin, an extracellular matrix protein essential for trophoblastic invasion, in pre-eclampsia and fetal growth restriction. METHODS: This was a retrospective study conducted at the University of Udine, including the placentas of women with pre-eclampsia and fetal growth restriction collected between January 1, 2001, and December 31, 2010. Fibronectin was evaluated in placental tissue micro-array by immunohistochemistry, describing localization and intensity of staining. RESULTS: The study included the placentas of 36 women with early-onset (delivery <34 weeks of gestation) pre-eclampsia; 6 with early-onset HELLP syndrome; 17 with early-onset intrauterine growth restriction (IUGR); 14 with late-onset (delivery ≥34 weeks of gestation) pre-eclampsia; 35 with late-onset IUGR; 18 with small for gestational age (SGA) fetuses (birth weight <10th percentile); and 64 controls. Fibronectin was present both at the cell surface and in the cytoplasm. Cytoplasm staining intensity resulted higher in early forms of pregnancy-related complications compared to controls, although this was statistically significant (P<0.05) only for early-onset pre-eclampsia (P=0.085 for HELLP syndrome; P=0.091 for IUGR). Also, late-onset forms of pre-eclampsia had stronger cytoplasmic and pericellular staining compared to controls (P<0.05). Interestingly, staining of both late-onset IUGR and SGA was comparable to controls. CONCLUSION: Fibronectin appeared to be unaffected in women with late-onset IUGR and SGA fetuses, suggesting a peculiar common pathogenetic pattern in these conditions.

Sentinel lymph node biopsy in patients affected by breast ductal carcinoma in situ with and without microinvasion: Retrospective observational study.

With the introduction of an organized mammographic screening, the incidence of ductal carcinoma in situ (DCIS) has experienced an important increase. Our experience with sentinel lymph node biopsy (SLNB) among patients with DCIS is reviewed.We collected retrospective data on patients operated on their breasts for DCIS (pTis), DCIS with microinvasion (DCISM) (pT1mi) and invasive ductal carcinoma (IDC) sized ≤2 cm (pT1) between January 2002 and June 2016, focusing on the result of SLNB.543 DCIS, 84 DCISM, and 2111 IDC were included. In cases of DCIS and DCISM, SLNB resulted micrometastatic respectively in 1.7% and 6.0% of cases and macrometastatic respectively in 0.9% and 3.6% of cases. 5-year disease-free survival and overall survival in DCISM and IDC were similar, while significantly longer in DCIS. 5-year local recurrence rate of DCIS and DCISM were respectively 2.5% and 7.9%, and their 5-year distant recurrence rate respectively 0% and 4%. IDC, tumor grading ≥2 and lymph node (LN) macrometastasis were significant predictors for decreased overall survival. Significant predictors for distant metastases were DCISM, IDC, macroscopic nodal metastasis, and tumor grading ≥2. Predictors for the microinvasive component in DCIS were tumor multifocality/multicentricity, grading ≥2, ITCs and micrometastases.Our study suggests that despite its rarity, sentinel node metastasis may also occur in case of DCIS, which in most cases are micrometastases. Even in the absence of an evident invasive component, microinvasion should always be suspected in these cases, and their management should be the same as for IDC.

Expression and modulation of S100A4 protein by human mast cells.

S100A4 protein is expressed in fibroblasts during tissue remodelling and in cancer stem cells and it induces the metastatic spread of tumor cells. In mast cells (MCs) S100A4 have been found in some pathological conditions, but its function in normal MCs remains to be described. The purpose of this study was to characterize the cellular localization of the S100A4 protein in MCs of human tissues with inflammatory or tumor disorders and, to determine the consequence of reducing its expression in MC response. We found that tissue resident MCs stained positive to S100A4. Both human HMC-1 cell line and resting CD34+-derived MCs expressed S100A4, whose levels were differentially modulated upon MC activation. Downregulation of the S100A4 protein resulted in MC growth inhibition, enhanced apoptosis and deregulation of MMP-1 and MMP-10 production. Our results suggest that S100A4 is also playing a role in the MC life cycle and functions.

Surgical and oncological outcomes of free dermal fat graft for breast reconstruction after breast-conserving surgery.

BACKGROUND: Oncoplastic breast surgery originated in order to improve the esthetic result of breast-conserving surgery (BCS). Autologous free dermal fat graft (FDFG) is an emerging oncoplastic technique to improve the cosmetic outcome of breast-conserving surgery. OBJECTIVES: The aim of this study was to analyze our experience with FDFGs in breast reconstruction after breast-conserving surgery. Oncological outcomes, surgical complications and cosmetic results were considered. MATERIAL AND METHODS: This retrospective chart review study considered all consecutive oncoplastic breast treatment by means of FDFG reconstruction during the period between September 2011 and September 2012 in our Clinic of Surgery (University of Udine, Italy). The data collected included patient and tumor characteristics and outcomes (cosmetic and oncological). RESULTS: During the study period, 37 women were treated by breast cancer surgery and immediate breast reconstruction by FDFG. At a 3-year follow-up, we found no cases of recurrence among breast cancer patients treated by FDFG; at a 18-month follow-up, we found a prevalence of 75.0% of women extremely satisfied with their oncoplastic surgery and a high prevalence of excellent or good cosmetic outcomes (70.3%) according to objective and subjective cosmetic assessment. CONCLUSIONS: Immediate breast reconstruction by FDFG after BCS in a population selected for a low risk of breast cancer recurrence seems to be an oncologically safe option, with a good cosmetic outcome and a high prevalence of women satisfied with the treatment.