Exosomes in breast cancer management: Where do we stand? A literature review.

BACKGROUND: Exosomes constitute cellular molecular fingertips that participate in intercellular communication both in health and disease states. Hence, exosomes emerge as critical mediators of cancer development and progression, as well as potential biomarkers and novel therapeutic targets. OBJECTIVE: To review literature data regarding applications of circulating exosomes in breast cancer management. METHODS: This is a literature review of relevant published studies until April 2020 in PubMed and Google Scholar databases. Original papers in the English language concerning exosome related studies were included. RESULTS: Exosomes represent molecular miniatures of their parent cells. Several homeostatic mechanisms control exosomal secretion and synthesis. Exosomal exchange among cells creates an intricate intercellular crosstalk orchestrating almost every tissue process, as well as carcinogenesis. Available data highlight exosomes as major mediators of cancer development and progression. The secretion of specific exosomal molecules, particularly miRNAs, correlates with the underlying processes and can be used as a means of tumor detection and prognostic assessment. CONCLUSIONS: Exosomal miRNAs expression profiles and levels closely relate to cancer extent, type and prognosis. Deep comprehension of such correlations and systematization of experimental outcomes will offer a novel approach in cancer detection and management.

A novel way of hook wire placement for surgical resection of suspicious breast lesions using the stereotactic vacuum assisted breast biopsy table.

Preoperative hook localization is a necessary procedure for targeting impalpable breast lesions. The aim of the current study is to introduce an alternative technique of wire placement by using the stereotactic biopsy device instead of the conventionally used mammography device. Fifty-one patients with impalpable mammographic lesions, graded BIRADS 4 or 5, were prospectively enrolled. Mean duration was 7 ± 1.5 minutes. Lesion-to-wire distance was <1 cm in 96% (51/53). Hook wire placement using the stereotactic biopsy device is considered as a safe, accurate, fast, and well-tolerable for the patient procedure.

Circulating miRNA Expression Profiling in Breast Cancer Molecular Subtypes: Applying Machine Learning Analysis in Bioinformatics.

BACKGROUND/AIM: Breast cancer is a leading worldwide cause of female cancer-related morbidity and mortality. Since molecular characteristics increasingly guide disease management, demystifying breast tumor miRNA signature emerges as an essential step toward personalized care. This study aimed to investigate the variations in circulating miRNA expression profiles between breast cancer subtypes and healthy controls and to identify relevant target genes and molecular functions. MATERIALS AND METHODS: MiRNA expression was tested by miScript™ miRNA PCR Array Human Cancer Pathway Finder kit, and subsequently, a machine learning approach was applied for miRNA profiling of the various breast cancer molecular subtypes. RESULTS: Serum samples from patients with primary breast cancer (n=66) and healthy controls (n=16) were analyzed. MiR-21 was the single common molecule among all breast cancer subtypes. Furthermore, several miRNAs were found to be differentially expressed explicitly in the different subtypes; luminal A (miR-23b, miR-142, miR-29a, miR-181d, miR-16, miR-29b, miR-155, miR-181c), luminal B (miR-148a, let-7d, miR-92a, miR-34c, let-7b, miR-15a), HER2+ (miR-125b, miR-134, miR-98, miR-143, miR-138, miR-135b) and triple negative breast cancer (miR-17, miR-150, miR-210, miR-372, let-7f, miR-191, miR-133b, miR-146b, miR-7). Finally, miRNA-associated target genes and molecular functions were identified. CONCLUSION: Applying a machine learning approach to delineate miRNA signatures of various breast cancer molecular subtypes allows further understanding of molecular disease characteristics that can prove clinically relevant.

Implant infections after breast reconstruction surgery following mastectomy: Experience from a Greek breast unit.

BACKGROUND: Despite the dominance of implant-based breast reconstruction after mastectomy, during recent years, it has been correlated to some complications. The aim of this study is to present the Greek experience about management of implant infections after breast reconstructions and to investigate the relationship between possible risk factors and breast pocket fluid cultures. METHODS: In total, 260 patients underwent implant-based breast reconstruction due to breast cancer in our center from 2016 until 2020. 46 patients, that underwent implant or expander replacement after breast reconstruction due to mastectomy were included in the present study. RESULTS: 260 patients underwent breast reconstruction in our center and in 46 (18%) of them an implant replacement was required. 21 patients (8%) presented clinically with an implant infection, but 12 of them (5%) had positive cultures from the breast pocket fluid. On the contrary, 25 patients (10%) presented no clinical signs of implant infection, but 5 of them (2%) had a positive culture. In addition, we demonstrated a correlation between implant infection and positive cultures (p = 0.009), along with an association between chemotherapy before implant placements and negative cultures (p = 0.035). Finally, the most common pathogen was Staphylococcus epidermidis (29%), followed by Escherichia coli (24%) and Staphylococcus aureus (18%). CONCLUSION: Implant infection still remains a very serious complication after breast reconstruction surgery. The establishment of a therapeutic protocol, with specific antimicrobial and surgical targets seems as an effective strategy against implant infections.

Type 2 diabetes mellitus status in obese patients following sleeve gastrectomy or one anastomosis gastric bypass.

This study aims to compare sleeve gastrectomy (SG) and one anastomosis gastric bypass (OAGB) in terms of remission of type 2 diabetes mellitus (T2DM) in obese patients. All T2DM patients were followed-up for at least 36 months. The primary outcome was remission of T2DM. Secondary endpoints included weight reduction and the procedure's impact on quality of life. In total, 53/1177 morbidly obese patients who underwent SG (Group A, n = 28) or OAGB (Group B, n = 25) had T2DM. Preoperatively, the mean Body Mass Index (BMI) values were 52.2 ± 8.5 kg/m2 and 52.9 ± 10.9 kg/m2 for Group A and Group B, respectively. Six patients in Group A were insulin dependent, while 8 were insulin dependent in Group B. After 36 months, diabetes remission was achieved by only 10 patients (35.7%) in Group A. However, in Group B, 22 patients (88%) remained off antidiabetic agents (p < 0.0001), with ΔHbA1c (%) reaching 1.4 ± 1.5% in Group A and 2.7 ± 2.1% in Group B (p = 0.02). Excess weight loss% (%EWL) was again significantly different between the two groups (MA = 79.8 ± 14.5%, MB = 93.3 ± 16.0%, p = 0.003). OAGB is more effective in improving glycaemic control and %EWL, with almost immediate resolution of diabetes, as well as long-term weight loss.

Severe anaphylactic reaction after blue dye injection for sentinel lymph node biopsy in breast surgery: Report of two cases and literature review.

Anaphylactic reactions, and especially the severe ones (types III and IV), should be kept in mind as considerable adverse effects while using blue dyes for SLNB.

Kounis syndrome after patent blue dye injection for sentinel lymph node biopsy.

BACKGROUND: Kounis syndrome (KS) has been described as an acute coronary syndrome (ACS) associated with an anaphylactic reaction. Several triggers have been identified and the diagnostic and treatment process can be challenging. CASE: A 58-year-old, female patient diagnosed with breast cancer and no history of allergies had subcutaneous injection of patent blue V dye for sentinel lymph node biopsy (SLNB). Intraoperatively, she developed anaphylactic shock and was transferred to the intensive care unit (ICU). A few hours later, electrocardiographic alterations and elevation of blood troponin were observed. Emergency coronary angiography revealed no occlusive lesions in coronary vessels. Further investigation in the allergy department set the diagnosis of KS. CONCLUSION: There are just ten cases of perioperative KS in the literature so far and here we present the first one triggered by patent blue V dye for sentinel node biopsy.

Impact of Deserosalization on Small Bowel Anastomosis Healing in Swine: A Pilot Study.

BACKGROUND: Healing is related to gastrointestinal anastomotic leak, which is a severe and common complication. This study aimed to investigate the feasibility and the impact of deserosalization on healing of jejuno-jejunal anastomoses in an animal model. MATERIALS AND METHODS: Seven swine underwent three types of side-to-side jejuno-jejunal anastomosis twice and survived seven days. Three different types of jejuno-jejunal side-to-side anastomoses were performed twice at 20-cm distance from each other in each animal: no serosa removal, one-sided, and two-sided serosa removal, respectively. Bursting pressure, tissue hydroxyproline concentration, and pathology scores were evaluated. RESULTS: Hydroxyproline tissue concentration was a mean±standard deviation of 0.37±0.09, 0.38±0.08, and 0.30±0.05 nmoI/ml respectively (p<0.05). Bursting pressure was a mean±standard deviation of 59.02±8.60, 73.20±11.09, and 100.01±7.49 mmHg, respectively (p<0.001). The histopathological assessment did not find any statistically significant differences. CONCLUSION: Deserosalization in jejuno-jejunal anastomosis was technically feasible and seemed to improve mechanical strength and collagen deposition in this experimental porcine model. Further investigation is warranted.

Evaluation of plasma and tissue expression levels of Endothelins (ET-1, Big ET-1) and VEGF in lobular neoplasia of the breast.

PURPOSE: The endothelin system is involved in the evolution of multiple malignancies, participating in cancer cell proliferation, tumor invasion and angiogenesis. Our purpose was to simultaneously assess endothelin expression in the systemic circulation of patients with lobular neoplasia (LN) of the breast and to investigate its correlation with vascular endothelial growth factor (VEGF) specimen expression levels as well as clinicopathologic findings. METHODS: This was a retrospective analysis of prospectively collected data regarding 60 women examined in a single breast unit. Thirty of these women underwent stereotactic biopsy and were diagnosed with LN and the remaining 30 were healthy controls. Circulating levels of endothelin (ET)-1 and Big ET-1 were measured using ELISA, while tissue expression of ET-1 and VEGF in biopsy specimens were assessed using qualitative immunohistochemical staining. RESULTS: The plasma levels of Big ET-1 were significantly increased in patients with LN compared to healthy controls. There was no significant difference in the plasma levels of ET-1 between the patient groups. In patients with LN, plasma expression of ET-1 and Big ET-1 did not correlate with ET-1 or VEGF tissue expression status, neither existed a relationship between tissue expressions of ET-1 and VEGF. CONCLUSIONS: Our results imply that Big ET-1 is a potential biomarker for LN. Further investigation of the endothelin system role in LN seems a promising research field.

Long-term outcome of myotomy and fundoplication based on intraoperative real-time high-resolution manometry in achalasia patients.

BACKGROUND: Current treatment options for achalasia of the esophagus predominantly consist of endoscopic myotomy or laparoscopic myotomy combined with a partial fundoplication. The intraoperative use of conventional manometry has previously been proposed with various results. The aim of the present study was to introduce the use of high-resolution manometry (HRM) during surgical treatment for achalasia and to assess the long-term outcome of this technique. METHODS: We enrolled achalasia patients within the time period November 2013 to July 2016 who underwent HRM and evaluation of Eckardt scores (ES) before and after tailored laparoscopic myotomy and fundoplication with intraoperative recording using HRM. RESULTS: Twenty patients were classified as having achalasia type I (20%), type II (55%), or type III (25%). During surgery, 9 myotomies were extended and 13 fundoplications were modified according to HRM findings. Mean resting (16.1 vs. 41.9 mmHg) and residual (9 vs. 28.7 mmHg) pressures of the lower esophageal sphincter and ES (0.7 vs. 6.9) were significantly eliminated postoperatively over a mean follow-up time of 17.7 months. CONCLUSIONS: The use of intraoperative HRM gives us the advantage of simultaneous real-time estimation of intraluminal pressures of the esophagus and the ability to identify the exact points that produce pressure during laparoscopy. Consequently, it may be the key to the tailoring of the Heller-Dor technique and improving the outcomes for achalasia patients.

Can the upper esophageal sphincter contractile integral help classify achalasia?

BACKGROUND: The use of high-resolution manometry (HRM) in achalasia patients has revealed abnormal findings concerning upper esophageal sphincter (UES) function. The introduction of the UES contractile integral (UES-CI), as with the distal contractile integral (DCI), may complement the interpretation of the manometric study of achalasia subtypes, defined by the Chicago Classification v3.0. METHODS: Patients were classified into achalasia subtypes based on HRM. UES length (cm), UES resting pressure (mmHg), and UES residual pressure (mmHg) were recorded. UES-CI (mmHg·sec·cm) was calculated in a manner similar to that used for the DCI measurement at rest (landmark CI), corrected for respiration, and its relation to achalasia subtypes was evaluated. RESULTS: Twenty-four achalasia patients with mean age 55.29 years were included. Of these, 16.6% (n=4) were diagnosed with achalasia type I, 58.3% (n=14) with type II, and 25% (n=6) with type III. The landmark UES-CI, mean UES-CI, UES-CI corrected for respiration, and UES resting pressure were found to be significantly higher among patients with achalasia type II compared to the other types (1768.9 vs. 677.1, P=0.03; 1827.1 vs. 3555.1, P=0.036; 174.2 vs. 72.8, P=0.027; and 108.1 vs. 55.8, P=0.009, respectively). CONCLUSIONS: We introduce the CI index as a tool for the manometric evaluation of the UES in achalasia. UES resting pressure, landmark UES-CI and mean UES-CI were significantly higher in achalasia patients with panesophageal pressurization compared to types I and III. This finding may reflect a protective reaction against the risk of aspiration in this group, but further studying and clinical correlation is required.