The effect of the absence of an accompanying person at birth on the basic perinatal outcomes - a randomized study during the lockdown in the COVID epidemic.

OBJECTIVES: To investigate the impact of an accompanying person on the basic parameters of perinatal outcome [e.g. length of stages of labour, proportion of Caesarean sections (CS), vaginal surgical delivery, perineal injury, Abgar score, epidural analgesia] were analysed. MATERIAL AND METHODS: A retrospective single-institution study analysed data from 872 deliveries during three periods: March, 2020 ( COVID-19 government restriction on accompanying person), February, 2020 (control 1) and March, 2019 (control 2). RESULTS: In all, 872 deliveries were evaluated. There was no delivery with accompanying person in group 1 and 181 and 254 in groups 2 and 3. Groups were balanced in caesarean section rate. There were more acute CS in the group 1 than in the group 3 (36% vs 25%, p = 0.028), however there were no diferrence when compared with the group 2 (36% vs 33%, p = 0.602). No difference was found in the length of the labour between the groups. There was no difference in Apgar score in 5th or 10th minute either and also in the incidence of perineal tear IIIrd grade. CONCLUSIONS: The absence of accompanying person or father at the delivery does not affect the the basic parameters of perinatal outcome. This finding provides more freedom in the mother's decision about the presence of an accompanying person at the birth. And also may be an argument for reducing the remorse (bad feelings) of fathers who cannot or do not want to be present at birth.

Axillary reverse mapping in breast cancer surgery - functional study.

The aim of the study was to map the lymphatic drainage of the upper extremity that traverses the axilla and elucidate its relationship with the lymphatic drainage of the breast. In 79 breast cancer patients indicated to the axillary lymph node dissection for category cN1, cN2, Technetium-99m (particle size <80 nm) was applied prior to surgery at two injection sites between the second and third metacarpophalangeal joints to visualize upper extremity lymphatics. During the surgery, the axilla was anatomically divided into 6 quadrants. A C-Trak® device was used for the intraoperative detection of radioactivity. After verifying activity, the nodes were resected and their position was recorded. Active nodes were sent separately according to topographic localizations for microscopic examination. All affected nodes (both macro- and micrometastases) were recorded as positive. The location, involvement and radioactivity, and the number of lymph nodes obtained were analyzed. In total, 1,109 lymph nodes were removed and examined. Radioactive nodes were found in all 79 patients. A total of 230 radioactive nodes were found. 21 nodes were both radioactive and metastatically affected. Results show that part of the lymph from the upper extremity flows through the nodes in the central part of the axilla and mixes with the lymph from the breast. This suggests that lymphatic drainage of the upper limb cannot be functionally separated from lymphatic drainage of the breast. The results also explain the possible mechanical cause of arm lymphedema after sentinel lymph node biopsy.

Selective Extirpation of Tattooed Lymph Node in Combination with Sentinel Lymph Node Biopsy in the Management of Node-Positive Breast Cancer Patients after Neoadjuvant Systemic Therapy.

INTRODUCTION: Axillary dissection has little diagnostic and therapeutic benefit in node-positive breast cancer patients in whom axillary disease has been completely eradicated after neoadjuvant chemotherapy (ypN0). We sought to assess the efficacy of an algorithm used for the identification of the ypN0 patient consisting of intraoperative evaluation of sentinel and tattooed (initially positive) lymph nodes. METHODS: Included were T1 and T2 breast cancer patients with 1-3 positive axillary lymph nodes marked with carbon who were referred for neoadjuvant chemotherapy followed by a surgery. Axillary dissection was performed only in the patients with residual axillary disease after neoadjuvant chemotherapy on ultrasound or with metastases described in the sentinel or tattooed lymph nodes either intraoperatively or in the final histology. RESULTS: Out of 62 initially included node-positive patients, 15 (24%) were spared axillary dissection. The detection rate of tattooed lymph nodes after neoadjuvant chemotherapy was 81%. The ypN0 patients were identified with 91% sensitivity and 38% specificity using ultrasound and intraoperative assessment of both sentinel and tattooed lymph node according to the final histology. DISCUSSION/CONCLUSION: Lymph node marking with carbon dye is a useful and cost-effective method, which can be successfully implemented in order to reduce the number of patients undergoing axillary dissection. Low specificity of the presented algorithm was caused mostly by the overestimation of residual axillary disease on ultrasound.

Is It Possible to Personalize the Diagnosis and Treatment of Breast Cancer during Pregnancy?

The main goal of precision medicine in patients with breast cancer is to tailor the treatment according to the particular genetic makeup and the genetic changes in the cancer cells. Breast cancer occurring during pregnancy (BCP) is a complex and difficult clinical problem. Although it is not very common, both maternal and fetal outcome must be always considered when planning treatment. Pregnancy represents a significant barrier to the implementation of personalized treatment for breast cancer. Tailoring therapy mainly takes into account the stage of pregnancy, the subtype of cancer, the stage of cancer, and the patient's preference. Results of the treatment of breast cancer in pregnancy are as yet not very satisfactory because of often delayed diagnosis, and it usually has an unfavorable outcome. Treatment of patients with pregnancy-associated breast cancer should be centralized. Centralization may result in increased experience in diagnosis and treatment and accumulated data may help us to optimize the treatment approaches, modify general treatment recommendations, and improve the survival and quality of life of the patients.

Multiplex PCR and NGS-based identification of mRNA splicing variants: Analysis of BRCA1 splicing pattern as a model.

Alternative pre-mRNA splicing increases transcriptome plasticity by forming naturally-occurring alternative splicing variants (ASVs). Alterations of splicing processes, caused by DNA mutations, result in aberrant splicing and the formation of aberrant mRNA isoforms. Analyses of hereditary cancer predisposition genes reveal many DNA variants with unknown clinical significance (VUS) that potentially affect pre-mRNA splicing. Therefore, a comprehensive description of ASVs is an essential prerequisite for the interpretation of germline VUS in high-risk individuals. To identify ASVs in a gene of interest, we have proposed an approach based on multiplex PCR (mPCR) amplification of all theoretically possible exon-exon junctions and subsequent characterization of size-selected and pooled mPCR products by next-generation sequencing (NGS). The efficiency of this method is illustrated by a comprehensive analysis of BRCA1 ASVs in human leukocytes, normal mammary, and adipose tissues and stable cell lines. We revealed 94 BRCA1 ASVs, including 29 variants present in all tested samples. While differences in the qualitative expression of BRCA1 ASVs among the analyzed human tissues were minor, larger differences were detected between tissue and cell line samples. Compared with other ASV analysis methods, this approach represents a highly sensitive and rapid alternative for the identification of ASVs in any gene of interest.

Ultrasound-guided cryoablation of breast fibroadenoma: a pilot trial.

PURPOSE: The aim of the study was to evaluate cryoablation (CA) under ultrasound guidance in the office setting with liquid nitrogen system for patients with fibroadenoma (FA). METHODS: For this prospective multicenter trial, an office-based cryosurgical system was used to treat histological confirmed benign FA with a maximum dimension of 3 cm. Sixty CA procedures were performed under ultrasound guidance. A freeze-thaw-freeze treatment cycle was performed according to the size of the FA. During the CA procedure continuous ultrasound monitoring was performed, verifying engulfment of the FA. Patients attended four follow-up visits at 1 week, 3, 6 months and 1 year and underwent ultrasound, physical examination and photography. RESULTS: Data were collected and analyzed in 60 cases. 59 of 60 FA (98 %) were fully engulfed by the ice ball. No serious adverse events occurred related to the IceSense3 system. At the 1-year follow-up, the FAs were gone in 93% of the cases. Prior to CA procedure, 76% of the FAs were palpable. Afterwards in some cases (22%), a scar/cryo lesion was palpable. 28% of the patients reported pain, described as mild or moderate, compared to 2% after 1 year. Cosmetic results at 12 months follow-up were reported as good or excellent in 100% by physician and in 97% by patients. CONCLUSIONS: The cryodestruction of the FA using liquid nitrogen system proved functional and safe, while showing meaningful reduction in volume, palpability, pain and cosmetic satisfying outcomes.

Is the small size of a breast cancer tumor the crucial point for successful medical treatment?

The presented case displays a clinical study of a cancer phenotype with a poor clinical outcome. Prediction of cancer development and effects of treatment at the beginning of the clinical stage is difficult as the knowledge of cancer process and all necessary parameters of the host body are limited. Cancer is mainly studied on the basis of biochemical-genetic processes and their morphological manifestation. However, the malignant process is assumed to be of essential biophysical nature and develops after mitochondrial dysfunction, which is a direct result of oncogene mutation. Cancers based on the normal and the reverse Warburg effect should be distinguished. The cancer tumors with the reverse Warburg effect display aggressiveness associated with a high rate of recurrence and metastatic implantation. Besides the nature of the two basic types of breast cancer tumors the outcome depends not only on their type, size, and site but also on reactions and interaction with the surrounding tissue and the body aptitude for metastatic activity connected with individual blood or lymphatic vessels for metastatic transport. It is necessary to assess all favourable and adverse factors for cancer development. General reliable method of their specification for all cancers is not available. Nevertheless, the main factor seems to be aggressiveness of cancer cells as follows from interpretation. To reveal the aggressive reverse Warburg effect tumors, metabolic biomarkers of the fibroblast stress should be examined.

Relationship between the lymphatic drainage of the breast and the upper extremity: a postmortem study.

BACKGROUND: This anatomic study details the lymphatic drainage of the upper extremity (UE) and breast, as well as its course in the axilla and its relation to axillary reverse mapping. Two aspects important for breast cancer surgery were followed: connection between the lymphatics of the UE and breast, and the possible cause of lymphedema of the UE after sentinel node (SN) biopsy. METHODS: Patent blue dye was injected bilaterally in 23 cadavers with no history of breast carcinoma to simultaneously visualize the lymphatics of the UE and breast. After visualization and dissection of the lymphatic vessels and nodes, a record of their routes was made. A scheme of superficial UE and breast lymphatics was constructed. RESULTS: After application of color contrast to the UE, 2-4 main afferent collectors were shown. As opposed to cranial and medial collectors, caudal collectors diverged from the axillary vein and entered the caudal axilla. In five (10.8%) cases, the caudal collector entered a node, which was considered to be the SN of the breast. In six (13%) cases, the SN of the breast and SNs of the UE were found in close proximity (up to 1.5 cm). CONCLUSIONS: Lymphatic drainage of the UE and breast are closely related in the caudal part of the axilla. SN groups for the UE and breast share connections in 24% of cases, which could explain lymphedema after surgery if damaged. Additional studies are needed to further improve our understanding of the lymphatic drainage of the UE and breast.

Comparative analysis of loss of heterozygosity and expression profile in normal tissue, DCIS and invasive breast cancer.

INTRODUCTION: Ductal carcinoma in situ (DCIS) is considered to be related to the development of invasive breast cancer. The aim of molecular biological research of preinvasive breast lesion characteristics and comparison with normal tissues and tissue of invasive tumours is to identify patients at high risk of developing invasive tumour on the basis of already established preinvasive lesions, and thus influence clinical decision-making. The aim of our study was to analyse several key molecules involved in different cellular pathways important for cancer development and progression in different types of breast tissue and to describe similarities and differences between premalignant and malignant lesions. MATERIAL AND METHODS: Genetic material isolated from both the tumour and healthy tissue was examined by loss of heterozygosity (LOH) analysis and real-time PCR using collagen 2A as a house-keeping gene. RESULTS: We analysed 65 samples of healthy mammary gland, 25 DCIS and 42 invasive ductal breast cancer samples. We analysed the LOH in three genes: BRCA1, BRCA2 and p53; and the gene expression of the VEGF gene and Bcl-2 gene. LOH in the BRCA1 gene was present in 44.74% of invasive samples and in 8.69% of DCIS (p=0.026); LOH in the BRCA2 gene in 45.0% of invasive samples and in 9.52% of DCIS (p=0.036); LOH in the p53 gene in 32.5% of invasive samples and in 31.82% of DCIS (p=0.97). No LOH was observed in normal tissue samples. VEGF was overexpressed in 14.3% of invasive cancers and in 12.0% of DCIS. Overexpression of Bcl-2 was observed in 11.9% of invasive cancers and in 8.0% of DCIS. CONCLUSION: We have confirmed that some of the molecular characteristics of DCIS are identical to those of invasive carcinoma. This approach could lead to the identification of molecular markers as indicators for the potential development of DCIS into invasive carcinoma or identification of DCIS subgroups with latent invasion.

Abdominal radical trachelectomy in fertility-sparing treatment of early-stage cervical cancer.

BACKGROUND: Abdominal radical trachelectomy (ART) is one of the fertility-sparing procedures in women with early-stage cervical cancer. In comparison with vaginal radical trachelectomy, the published results of ART are so far limited. METHODS: Enrolled were women referred for ART either by laparoscopy or laparotomy. The main inclusion criterion was stage IA2 or IB1 with a cranial extent that allows for preservation of at least 1 cm of the endocervical canal. RESULTS: A total of 24 women were referred for the procedure, but fertility could not be preserved in 7 (29%) of them. Four women underwent immediate completion of radical hysterectomy because of a positive cranial surgical margin (n = 2) or sentinel node macrometastasis (n = 2) on frozen section. We found no correlation between tumor volume and inability to preserve fertility. A positive sentinel node was identified in 4 patients (17%); there were no false-negative results. Of the 9 women (53%) who have tried to conceive so far, 6 (67%) have conceived and 5 given birth, 2 of which were premature deliveries. CONCLUSIONS: Fertility cannot be preserved because of positive cranial margins or involved lymph nodes in almost one third of patients originally referred for radical trachelectomy. The main criterion for the selection of suitable patients should be the cranial extent of the tumor. Abdominal radical trachelectomy allows for achievement of satisfactory obstetrical outcomes.

High-risk human papillomavirus DNA in the primary tumor, sentinel, and nonsentinel pelvic lymph nodes in patients with early-stage cervical cancer: a correlation with histopathology.

INTRODUCTION: Metastatic involvement of pelvic lymph nodes is the most important prognostic parameter in early-stage cervical cancer. Still, approximately 15% of patients with negative pelvic nodes experience recurrence, most of them in the pelvis. The presence of human papillomavirus (HPV) DNA in histologically negative pelvic nodes is considered a subclinical metastatic spread. METHODS: Patients with early-stage cervical cancer referred for surgical treatment were enrolled in the study. Cytobrush technique was used for sample collection from the fresh tissue to avoid any loss of material for histology. RESULTS: Altogether, 49 patients were enrolled in the study. High-risk (HR) HPV DNA was identified in the tumor in 91.8% patients and in the sentinel node or other pelvic nodes in 49.9% patients. Among the 10 HR HPV genotypes detected, HPV 16 was the most frequently represented in both the tumor and the lymph nodes (66.7% and 71.4%, respectively). All metastatic lymph nodes were HR HPV positive. CONCLUSIONS: The presence of HR HPV DNA in a sentinel node had a 100% positive predictive value for metastatic involvement of pelvic lymph nodes in our study. This could be considered a sign of an early subclinical metastatic spread; however, the prognostic value has to be evaluated through a longer follow-up.

Localization of the sentinel node of the upper outer breast quadrant in the axillary quadrants.

BACKGROUND: Sentinel node (SN) biopsy is associated with much less morbidity than axillary dissection. In patients with early breast cancer, lymphatic mapping and SN biopsy accurately stage the axillary nodes. Both currently available lymphatic mapping agents, radiocolloid and blue dye, have some limitations that may make perioperative or preoperative SN identification difficult. In such cases, exact knowledge of the topography of the axilla and the most probable location of the SN may be crucial. METHODS: In 12 fresh female cadavers with no history of breast carcinoma, injections of patent blue dye were used to visualize the SNs in the axillary quadrants and their lymphatic collectors from the upper outer quadrant of the breast, which is the most common location of breast cancer. The axilla was divided into quadrants with regard to the intersection of the thoracoepigastric vein and the third intercostobrachial nerve. RESULTS: All SNs were located within a circle of 2-cm radius of this intersection in the fatty tissue at the clavipectoral fascia. In most cases, the SN was located in the fatty tissue near the clavipectoral fascia in the lower ventral quadrant of the axilla (n = 14, 58%). In seven cases (29%), the SN was located in the upper ventral quadrant, in two cases (8%) in the upper dorsal quadrant, and in one case in the lower dorsal quadrant. CONCLUSIONS: The results of this anatomical study may facilitate SN biopsy in patients with breast cancer.