Nipple Sparing Mastectomy Technique to Reduce Ischemic Complications: Preserving Important Blood Flow Based on Breast MRI.

BACKGROUND: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction is commonly performed. However, nipple areolar complex (NAC) and mastectomy skin necrosis represent significant complications requiring reoperation and revision. Breast MRI, often obtained for oncologic assessment, can visualize the dominant breast and NAC vascular supply. This study describes the surgical technique utilizing breast MRI blood flow information to preserve important NAC blood supply, thereby, reducing ischemic complications. METHODS: After IRB approval, a prospectively maintained database of all NSM by a single breast surgeon from 2018 to 2020 formed the study group. Preoperative contrast enhanced Breast MRI analysis determined the dominant NAC blood supply. Intraoperatively, the dominant Internal Mammary Artery Perforator (IMP) to the NAC was preserved (IMP-NSM). The IMP-NSM surgical technique preserving the IMP blood flow, evaluation of breast MRI blood flow patterns, surgical findings, and ischemic complications were analyzed. RESULTS: 114 NSM were performed in 74 patients (mean age: 49 years [range, 22-73 years], BMI 25.8 kg/m2 [range, 19-41 kg/m2]). Breast MRI identified the dominant IMP to the NAC in 92%. IMP preservation was successful in 89% (101/114). Necrosis requiring NAC removal occurred in 0.9% (1/114), and skin necrosis reoperation in 1.8% (2/114). Including all post-operative necrosis occurred in 10.5% (12/114), statistically significantly lower compared to the literature for NSM assessing MRI blood flow data without surgical IMP preservation (necrosis 24.4%, p < 0.001) (Bahl et al. in J Am Coll Surg 223(2):279-285, 2016) utilizing Doppler for IMP preservation (necrosis 37%, p < 0.001) (Swistel et al. in Plast Reconstr Surg Glob Open 2(8):e198, 2014) and dividing the IMP in all (necrosis 31.4%, p < 0.001) (Ahn et al. in Eur J Surg Oncol 44(8):1170-1176, 2018). CONCLUSIONS: The IMP-NSM surgical technique preserves the dominant blood supply to the NAC, thereby, decreasing ischemic complications.

WheatQTLdb V2.0: a supplement to the database for wheat QTL.

We recently developed a database for hexaploid wheat QTL (WheatQTLdb; www.wheatqtldb.net), which included 11,552 QTL affecting various traits of economic importance. However, that database did not include valuable QTL from other wheat species and/or progenitors of hexaploid wheat. Therefore, an updated and improved version of wheat QTL database (WheatQTLdb V2.0) was developed, which now includes information on hexaploid wheat (Triticum aestivum) and the following seven other related species: T. durum, T. turgidum, T. dicoccoides, T. dicoccum, T. monococcum, T. boeoticum, and Aegilops tauschii. WheatQTLdb V2.0 includes a much-improved list of QTL, including 27,518 main effect QTL, 202 epistatic QTL, and 1321 metaQTL. This newly released WheatQTLdb V2.0 also has additional valuable options to search and choose the QTL, category-wise, and trait-wise data for their use in research or breeding programs.

WheatQTLdb: a QTL database for wheat.

During the last three decades, QTL analysis in wheat has been conducted for a variety of individual traits, so that thousands of QTL along with the linked markers, their genetic positions and contribution to phenotypic variation (PV) for concerned traits are now known. However, no exhaustive database for wheat QTL is currently available at a single platform. Therefore, the present database was prepared which is an exhaustive information resource for wheat QTL data from the published literature till May, 2020. QTL data from both interval mapping and genome-wide association studies (GWAS) have been included for the following classes of traits: (i) morphological traits, (ii) N and P use efficiency, (iii) traits for biofortification (Fe, K, Se, and Zn contents), (iv) tolerance to abiotic stresses including drought, water logging, heat stress, pre-harvest sprouting and salinity, (v) resistance to biotic stresses including those due to bacterial, fungal, nematode and insects, (vi) quality traits, and (vii) a variety of physiological traits, (viii) developmental traits, and (ix) yield and its related traits. For the preparation of the database, literature was searched for data on QTL/marker-trait associations (MTAs), curated and then assembled in the form of WheatQTLdb. The available information on metaQTL, epistatic QTL and candidate genes, wherever available, is also included in the database. Information on QTL in this WheatQTLdb includes QTL names, traits, associated markers, parental genotypes, crosses/mapping populations, association mapping panels and other useful information. To our knowledge, WheatQTLdb prepared by us is the largest collection of QTL (11,552), epistatic QTL (107) and metaQTL (330) data for hexaploid wheat to be used by geneticists and plant breeders for further studies involving fine mapping, cloning, and marker-assisted selection (MAS) during wheat breeding.

Pretreatment Tattoo Marking of Suspicious Axillary Lymph Nodes: Reliability and Correlation with Sentinel Lymph Node.

BACKGROUND: Tattooing is an alternative method for marking biopsied axillary lymph nodes (ALNs) before initiation of treatments for newly diagnosed breast cancer. Detection of black ink-stained nodes is performed under direct visualization at surgery and is combined with sentinel node (SLN) mapping procedures. METHODS: Women with newly diagnosed breast cancer who underwent fine or core-needle biopsy of suspicious ALNs were recruited. The nodal cortex and perinodal soft tissue was injected with 0.1-1.0 ml of Spot™ (GI Supply) black ink under ultrasound guidance. Intraoperatively, black stained nodes were removed along with SLNs, noting concordance between the two. RESULTS: Sixty-six evaluable patients were enrolled (2013-2017). Nineteen received surgery first (Group 1) and 47 neoadjuvant therapy (NAT, Group 2). The average number of nodes tattooed was 1.16 for Group 1 and 1.04 for Group 2. The average interval from tattoo to surgery was 21 days (range 1-62) for Group 1 and 148 days (range 71-257) for Group 2. The tattooed node(s) were visually identified at surgery and corresponded to the sentinel lymph node(s) in 98.5% of cases (18/19 in Group 1 and 47/47 in Group 2). Of the 14 patients in Group 2 whose nodes remained positive following NAT, the tattooed node was the SLN associated with carcinoma. CONCLUSIONS: Tattooing is an alternative method for marking biopsied ALNs. Tattooed nodes coincided with SLNs in 98.5% of cases. This technique is advantageous, because it allows for fewer procedures and lower costs compared with other methods.

Improving Performance of Mammographic Breast Positioning in an Academic Radiology Practice.

OBJECTIVE: The purpose of this project was to achieve sustained improvement in mammographic breast positioning in our department. MATERIALS AND METHODS: Between June 2013 and December 2016, we conducted a team-based performance improvement initiative with the goal of improving mammographic positioning. The team of technologists and radiologists established quantitative measures of positioning performance based on American College of Radiology (ACR) criteria, audited at least 35 mammograms per week for positioning quality, displayed performance in dashboards, provided technologists with positioning training, developed a supportive environment fostering technologist and radiologist communication surrounding mammographic positioning, and employed a mammography positioning coach to develop, improve, and maintain technologist positioning performance. Statistical significance in changes in the percentage of mammograms passing the ACR criteria were evaluated using a two-proportion z test. RESULTS: A baseline mammogram audit performed in June 2013 showed that 67% (82/122) met ACR passing criteria for positioning. Performance improved to 80% (588/739; p < 0.01) after positioning training and technologist and radiologist agreement on positioning criteria. With individual technologist feedback, positioning further improved, with 91% of mammograms passing ACR criteria (p < 0.01). Seven months later, performance temporarily decreased to 80% but improved to 89% with implementation of a positioning coach. The overall mean performance of 91% has been sustained for 23 months. The program cost approximately $30,000 to develop, $42,000 to launch, and $25,000 per year to maintain. Almost all costs were related to personnel time. CONCLUSION: Dedicated performance improvement methods may achieve significant and sustained improvement in mammographic breast positioning, which may better enable facilities to pass the recently instated Enhancing Quality Using the Inspection Program portion of a practice's annual Mammography Quality Standards Act inspections.

Initial results with preoperative tattooing of biopsied axillary lymph nodes and correlation to sentinel lymph nodes in breast cancer patients.

BACKGROUND: Pretreatment evaluation of axillary lymph nodes (ALNs) and marking of biopsied nodes in patients with newly diagnosed breast cancer is becoming routine practice. We sought to test tattooing of biopsied ALNs with a sterile black carbon suspension (Spot™). The intraoperative success of identifying tattooed ALNs and their concordance to sentinel nodes was determined. METHODS: Women with suspicious ALNs and newly diagnosed breast cancer underwent palpation and/or ultrasound-guided fine needle aspiration or core needle biopsy, followed by injection of 0.1 to 0.5 ml of Spot™ ink into the cortex of ALNs and adjacent soft tissue. Group I underwent surgery first, and group II underwent neoadjuvant therapy followed by surgery. Identification of black pigment and concordance between sentinel and tattooed nodes was evaluated. RESULTS: Twenty-eight patients were tattooed, 16 in group I and 12 in group II. Seventeen cases had evidence of atypia or metastases, 8 (50 %) in group I and 9 (75 %) in group II. Average number of days from tattooing to surgery was 22.9 (group I) and 130 (group II). Black tattoo ink was visualized intraoperatively in all cases, except one case with microscopic black pigment only. Fourteen group I and 10 group II patients had black pigment on histological examination of ALNs. Sentinel nodes corresponded to tattooed nodes in all except one group I patient with a tattooed non-sentinel node. CONCLUSION: Tattooed nodes are visible intraoperatively, even months later. This approach obviates the need for additional localization procedures during axillary staging.

Rim sign in breast lesions on diffusion-weighted magnetic resonance imaging: diagnostic accuracy and clinical usefulness.

PURPOSE: To investigate the diagnostic accuracy and clinical usefulness of the rim sign in breast lesions observed in diffusion-weighted magnetic resonance imaging (DWI). MATERIALS AND METHODS: The magnetic resonance imaging (MRI) findings of 98 pathologically confirmed lesions (62 malignant and 36 benign) in 84 patients were included. Five breast radiologists were asked to independently review the breast MRI results, to grade the degree of high peripheral signal, the "rim sign," in the DWI, and to confirm the mean apparent diffusion coefficient (ADCmean ) values. We analyzed the diagnostic accuracy and compared the consensus (when ≥ 4 of 5 independent reviewers agreed) results of the rim sign with the ADCmean values. Additionally, we evaluated the correlation between the dynamic contrast-enhanced (DCE)-MRI morphologic appearance and DWI rim sign. RESULTS: According to the consensus results, the rim sign in DWI was observed on 59.7% of malignant lesions and 19.4% of benign lesions. The sensitivity, specificity, and area under the curve (AUC) value for the rim sign in DWI were 59.7%, 80.6%, and 0.701, respectively. The sensitivity, specificity, and AUC value for the ADCmean value (criteria ≤ 1.46 × 10(-3) mm(2) /sec) were 82.3%, 63.9%, and 0.731, respectively. Based on consensus, no correlation was observed between the DCE-MRI and DWI rim signs. CONCLUSION: In DWI, a high-signal rim is a valuable morphological feature for improving specificity in DWI.

Why are patients noncompliant with follow-up recommendations after MRI-guided core needle biopsy of suspicious breast lesions?

OBJECTIVE: The objective of this study was to investigate patient and breast MRI characteristics associated with noncompliance with recommended follow-up after MRI-guided core needle biopsy of suspicious breast lesions. MATERIALS AND METHODS: A retrospective review was performed of 576 breast lesions biopsied under MRI guidance between 2007 and 2010. Patient follow-up was obtained from the medical record and from contact with referring physicians. RESULTS: Of 415 women who underwent 576 MRI-guided core needle biopsies for suspicious breast lesions, 123 (29.6%) patients representing 154 of 576 (26.7%) lesions were noncompliant with recommended excision or 6-month MRI follow-up. Referring physicians provided information for 63% (97/154) of lesions in noncompliant patients, of which 49.5% (48/97) were followed by mammography instead of excision or MRI. Noncompliance with MRI follow-up was significantly associated with referral for biopsy by outside hospital physicians (odds ratio [OR], 2.40; p = 0.0001) and with referral for screening MRI (1.46; p = 0.093) and biopsy of a focus or foci lesion (1.63; p = 0.088). Among 178 lesions in patients compliant with follow-up MRI after MRI-guided core needle biopsy, 7.9% (14/178) had abnormal follow-up MRI results, half of which (3.9%, 7/178) were found on repeat biopsy to be high-risk or malignant. CONCLUSION: Institutions performing MRI-guided core biopsies should be aware that patients referred from outside institutions are more likely to be noncompliant with recommended follow-up. Strategies to improve follow-up should include educating patients on the difference between mammography and MRI follow-up.

Sustaining Mammography Image Quality With a Technologist Coaching Program in the Era of the Enhancing Quality Using the Inspection Program (EQUIP).

OBJECTIVE: To evaluate the ability of a long-term technologist coaching program to sustain gains in mammography quality made by a previously implemented quality improvement (QI) initiative. METHODS: Mammography quality metrics from July 2014 to June 2020 were reviewed. Numbers of screening mammograms performed/audited, monthly average mammogram overall quality pass rates, changes in facilities/staffing, and technical recall rates were evaluated. Performance metrics at baseline (July 2013), during the improvement (July 2014 to January 2015), postimprovement (February 2015 to August 2015), and sustained coaching periods (after initiation of the technologist coaching model, from September 2015 to June 2020) were compared. RESULTS: During the postimprovement and sustained coaching periods, 93% (501/541) and 90% (8902/9929) of audited mammograms, respectively, met overall passing criteria, achieving or exceeding the QI goal of 90%, and results for both periods were significantly higher than that during the improvement period (74%, 1098/1489), at P < 0.0001 and P < 0.0001, respectively. The technical recall rates during the improvement and postimprovement periods were 2.6% (85/3321) and 1.7% (54/3236), respectively; the rate during the sustained coaching period was significantly lower than these, at 1.2% (489/40 440) (P < 0.0001 and P = 0.0232, respectively). Sustained quality passing rates and lower technical recall rates were observed despite statistically significantly increases in screening volumes. CONCLUSION: A technologist coaching program resulted in sustained high mammographic quality for almost 5 years.

Freehand MRI-guided preoperative needle localization of breast lesions after MRI-guided vacuum-assisted core needle biopsy without marker placement.

PURPOSE: To evaluate the feasibility of magnetic resonance imaging (MRI)-guided preoperative needle localization (PNL) of breast lesions previously sampled by MRI-guided vacuum-assisted core needle biopsy (VACNB) without marker placement. MATERIALS AND METHODS: We reviewed 15 women with 16 breast lesions undergoing MRI-guided VACNB without marker placement who subsequently underwent MRI-guided PNL, both on an open 0.5T magnet using freehand techniques. Mammograms and specimen radiographs were rated for lesion visibility; MRI images were rated for lesion visibility and hematoma formation. Imaging findings were correlated with pathology. RESULTS: The average prebiopsy lesion size was 16 mm (range 4-50 mm) with 13/16 lesions located in mammographically dense breasts. Eight hematomas formed during VACNB (average size 13 mm, range 8-19 mm). PNL was performed for VACNB pathologies of cancer (5), high-risk lesions (5), or benign but discordant findings (6) at 2-78 days following VACNB. PNL targeted the lesion (2), hematoma (4), or surrounding breast architecture (10). Wire placement was successful in all 16 lesions. Final pathology showed six cancers, five high-risk lesions, and five benign findings. CONCLUSION: MRI-guided PNL is successful in removing lesions that have previously undergone VACNB without marker placement by targeting the residual lesion, hematoma, or surrounding breast architecture, even in mammographically dense breasts.

Identification and characterization of SET domain family genes in bread wheat (Triticum aestivum L.).

SET domain genes (SDGs) that are involved in histone methylation have been examined in many plant species, but have never been examined in bread wheat; the histone methylation caused due to SDGs is associated with regulation of gene expression at the transcription level. We identified a total of 166 bread wheat TaSDGs, which carry some interesting features including the occurrence of tandem/interspersed duplications, SSRs (simple sequence repeats), transposable elements, lncRNAs and targets for miRNAs along their lengths and transcription factor binding sites (TFBS) in the promoter regions. Only 130 TaSDGs encoded proteins with complete SET domain, the remaining 36 proteins had truncated SET domain. The TaSDG encoded proteins were classified into six classes (I-V and VII). In silico expression analysis indicated relatively higher expression (FPKM > 20) of eight of the 130 TaSDGs in different tissues, and downregulation of 30 TaSDGs under heat and drought at the seedling stage. qRT-PCR was also conducted to validate the expression of seven genes at the seedling stage in pairs of contrasting genotypes in response to abiotic stresses (water and heat) and biotic stress (leaf rust). These genes were generally downregulated in response to the three stresses examined.

Estrogen receptor-negative invasive breast cancer: imaging features of tumors with and without human epidermal growth factor receptor type 2 overexpression.

PURPOSE: To prospectively determine if estrogen receptor (ER)-negative human epidermal growth factor receptor type 2 (HER2)-positive and ER-negative HER2-negative breast cancers have distinguishing clinical and imaging features with use of retrospectively identified patients and tissue samples. MATERIALS AND METHODS: This HIPAA-compliant study was institutional review board approved. Informed consent was obtained from living patients and waived for deceased patients. Mean patient age at diagnosis was 53 years (range, 31-84 years). Clinical history; histopathologic, mammographic, and breast sonographic findings; and HER2 status as determined with immunohistochemistry or fluorescent in situ hybridization were evaluated in 56 women with ER-negative breast cancer. Imaging appearances and clinicopathologic characteristics were correlated with tumor HER2 status. P < .05 indicated a significant difference. RESULTS: Lesion margins on mammograms (P = .028) and sonograms (P = .023), calcifications on mammograms (P = .003), and clinical cancer stage at diagnosis (P = .029) were significantly associated with HER2 status. In contrast to ER-negative HER2-negative tumors, ER-negative HER2-positive tumors were more likely to have spiculated margins (56% vs 15%), be associated with calcifications (65% vs 21%), and be detected at a higher cancer stage (74% vs 57%). CONCLUSION: Biologic diversity of cancers may manifest in imaging characteristics, and, conversely, studying the range of imaging features of cancers may help refine current molecular phenotypes.

Mammographic screening in women at increased risk of breast cancer after treatment of Hodgkin's disease.

Treatment regimens for Hodgkin's disease (HD) that have included radiation to lymph node regions in the thorax have contributed to high rates of long-term disease-free survival. However, incidental radiation exposure of breast tissue in young women has significantly increased the risk of breast cancer compared to expected rates in the general population. After informing patients about risks associated with previous treatment of HD, we studied screening mammograms and call-back rates in women at increased risk for developing breast cancer at a younger age. We contacted by mail a cohort of 291 women between 25 and 55 years of age who had received thoracic irradiation before 35 years of age for HD with or without chemotherapy. Subjects were offered information about risks identified after HD therapy with questionnaires to assess response to this information. Ten patients refused participation, 93 did not respond, and 21 were excluded after they reported a prior diagnosis of invasive (1) or in situ (2) breast cancer. One hundred and sixty seven women received information about secondary breast cancer risk and were advised to initiate or maintain mammographic screening. Available mammograms were reviewed by two radiologists and classified according to the ACR BI-RADS Mammography Lexicon. Abnormal findings were correlated to pathology results from biopsies. One hundred and fifteen subjects reported that they obtained new mammograms during the period of the study. Ninety-nine were available for secondary review. Patients were studied an average of 16.9 years after HD treatment (Range: 4.5-32.5 years) at an average of 41 years of age (range 25-55 years). High density breast tissue was identified in 60% (60/99). Seventeen of the women (17.2%) were recalled for further imaging. This was more common in women with heterogeneously dense breast tissue. Seven of those recalled (41%) were advised to undergo biopsies that identified ductal carcinoma in situ (DCIS) in one and benign findings in the others. Among 16 women whose mammograms were unavailable for review, three were diagnosed with DCIS; two of these had microscopic evidence of invasive breast cancer. The four in situ or microinvasive cancers were diagnosed in the study participants at 25-40 years of age and from 5 to 23 years after HD therapy. Biopsies were performed because mammograms detected microcalcifications without palpable abnormality in three of these cases. Women who have had thoracic nodal irradiation for Hodgkin's disease have an increased risk of developing secondary breast cancer at an unusually young age. As expected in younger women, high density breast tissue was common on mammography, and the recall and biopsy rates were unusually high. However, early mammographic screening facilitated diagnosis of in situ and early invasive cancer in 3.5% of our subjects.

Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays.

Retinoids have been found to be promising chemopreventive agents that play an important role in regulating cell growth, differentiation, and apoptosis. The action of retinoids is mediated by retinoid receptors (retinoic acid receptors and retinoid X receptors), which are nuclear transcription factors that, when bound to retinoids, regulate gene expression. LGD1069 is a highly selective RXR agonist that has reduced toxicity compared with retinoids. Our previous studies have shown that RXR-selective ligands (or "rexinoids"), including LGD1069, can inhibit the growth of normal and malignant breast cells and can suppress the development of breast cancer in transgenic mice. For the current study, we attempted to identify biomarkers of the chemopreventive effect of the RXR-selective retinoid LGD1069. In these experiments, we used Affymetrix microarrays to identify target genes that were modulated by LGD1069 in normal human breast cells. Affymetrix and dChip analysis identified more than 100 genes that were up-regulated or down-regulated by LGD1069 treatment. We then tested 16 of these genes in validation experiments using quantitative reverse transcription-PCR and Western blotting of independently prepared samples, and found that 15 of 16 genes were modulated in a similar manner in these validation experiments as in the microarray experiments. Genes found to be regulated include known retinoid-regulated genes, growth regulatory genes, transcription factors, and differentiation markers. We then showed that the expression of several of these rexinoid-regulated biomarkers is modulated in vivo in mammary glands from mice treated with LGD1069. These critical growth-regulating proteins will be promising targets of future agents for the prevention and treatment of breast cancer.

Subcutaneous infusion and capillary "finger stick" sampling of stable isotope tracer in metabolic studies.

Metabolic studies utilizing stable isotope tracer in humans have typically used intravenous tracer infusions and venous blood sampling. These studies explore subcutaneous infusion of isotope and "finger stick" capillary blood sampling to measure glucose turnover. Five subjects received simultaneous 8-h infusions of glucose labeled with isotope: [1-(13)C]glucose subcutaneously and [6,6-(2)H(2)]glucose intravenously. At regular intervals, venous and finger stick blood specimens were obtained. Finger stick blood was applied to filter paper. Substrate and isotopic steady state was reached after 7.0 h with both routes of infusion. The isotopic enrichments of finger stick and venous specimens did not differ significantly for the subcutaneously infused [1-(13)C]glucose (p = 0.33 and p = 0.23, respectively) but the finger stick [6,6-(2)H(2)]glucose enrichment was slightly higher (p < 0.03) than that of the venous sample. Using [6,6-(2)H(2)]glucose infusion and venous plasma sampling as the reference method, the [1-(13)C]glucose gave estimates of glucose R(a) that were 13% (plasma) and 17% (finger stick) lower (p < 0.001 and p < 0.02, respectively). This difference could be attributed to recycling of (13)C label. In conclusion, subcutaneous infusion and finger stick specimen collection onto filter paper represent a potential method of conducting in vivo studies of substrate metabolism outside of a hospital-based research unit.