Distance of Biopsy-Confirmed High-Risk Breast Lesion from Concurrently Identified Breast Malignancy Associated with Risk of Carcinoma at the High-Risk Lesion Site.

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series.

Omitting axillary staging in selected patients: Rationale of Choosing Wisely in breast cancer treatment.

Axillary surgery for breast cancer has continually evolved, with sentinel lymph node biopsy for clinically node-negative women with invasive breast cancer having long replaced axillary lymph node dissection. The information obtained from axillary staging has been important in providing prognostic information and guiding adjuvant treatment recommendations. However, recent studies suggest that sentinel lymph node biopsy should be omitted in select low-risk patients whose axillary surgery provides minimal prognostic value. This was highlighted by the Society of Surgical Oncology Choosing Wisely Guidelines, advocating against routine axillary staging in older women with early-stage hormone receptor-positive breast cancer. Since the guideline release, ongoing research has continued to identify the subset of low-risk patients who would benefit from the omission of axillary staging and improve adherence to Choosing Wisely to prevent overtreatment in older people.

New Technology for the Breast Surgeon.

New innovations aid the breast surgeon with better ability to localize tumors using wireless techniques, reduce re-excision rates by intraoperative margin evaluation and perform aesthetically; pleasing, and safe surgeries. In addition to improving oncological outcomes, we can continue to improve the quality of life for our patients through evolving surgeries including nerve-sparing mastectomies, robotic mastectomies, and lymphovascular surgeries (LYMPHA). Our article reviews current and evolving techniques and technology that all breast surgeons should add to his or her armamentarium to provide optimal surgical care.

Machine Learning-Based Epigenetic Classifiers for Axillary Staging of Patients with ER-Positive Early-Stage Breast Cancer.

BACKGROUND: In the era of molecular stratification and effective multimodality therapies, surgical staging of the axilla is becoming less relevant for patients with estrogen receptor (ER)-positive early-stage breast cancer (EBC). Therefore, a nonsurgical method for accurately predicting lymph node disease is the next step in the de-escalation of axillary surgery. This study sought to identify epigenetic signatures in the primary tumor that accurately predict lymph node status. PATIENTS AND METHODS: We selected a cohort of patients in The Cancer Genome Atlas (TCGA) with ER-positive, HER2-negative invasive ductal carcinomas, and clinically-negative axillae (n = 127). Clinicopathological nomograms from the Memorial Sloan Kettering Cancer Center (MSKCC) and the MD Anderson Cancer Center (MDACC) were calculated. DNA methylation (DNAm) patterns from primary tumor specimens were compared between patients with pN0 and those with > pN0. The cohort was divided into training (n = 85) and validation (n = 42) sets. Random forest was employed to obtain the combinations of DNAm features with the highest accuracy for stratifying patients with > pN0. The most efficient combinations were selected according to the area under the curve (AUC). RESULTS: Clinicopathological models displayed a modest predictive potential for identifying > pN0 disease (MSKCC AUC 0.76, MDACC AUC 0.69, p = 0.15). Differentially methylated sites (DMS) between patients with pN0 and those with > pN0 were identified (n = 1656). DMS showed a similar performance to the MSKCC model (AUC = 0.76, p = 0.83). Machine learning approaches generated five epigenetic classifiers, which showed higher discriminative potential than the clinicopathological variables tested (AUC > 0.88, p < 0.05). CONCLUSIONS: Epigenetic classifiers based on primary tumor characteristics can efficiently stratify patients with no lymph node involvement from those with axillary lymph node disease, thereby providing an accurate method of staging the axilla.

Epigenetic Signatures Predict Pathologic Nodal Stage in Breast Cancer Patients with Estrogen Receptor-Positive, Clinically Node-Positive Disease.

BACKGROUND: Breast cancer patients with clinically positive nodes who undergo upfront surgery are often recommended for axillary lymph node dissection (ALND), yet more than half are found to have limited nodal disease (≤ 3 positive nodes, pN1) at surgery. In this study, we examined the efficiency of molecular classifiers in stratifying patients with clinically positive nodes to pN1 versus > pN1 disease. METHODS: We evaluated the clinical and epigenetic data of patients in The Cancer Genome Atlas with estrogen receptor-positive, human epidermal growth factor receptor 2-negative invasive ductal carcinoma who underwent ALND for node-positive disease. Patients were divided into control (pN1, ≤ 3 positive nodes) and case (> pN1, > 3 positive nodes) groups. Machine learning algorithms were trained on 50% of the cohort and validated on the remaining 50% to identify DNA methylation signatures that predict > pN1 disease. Clinical variables and epigenetic signatures were compared. RESULTS: Controls (n = 34) and case (n = 24) cohorts showed similar mean age (56.4 ± 12.2 vs. 57.6 ± 16.7 years; p = 0.77), number of nodes removed (16.1 ± 7.3 vs. 17.5 ± 6.2; p = 0.45), tumor grade (p = 0.76), presence of lymphovascular invasion (p = 0.18), extranodal extension (p = 0.17), tumor laterality (p = 0.89), and tumor location (p = 0.42). The mean number of positive nodes was significantly different (1.76 ± 0.82, pN1; 8.83 ± 5.36, > pN1; p < 0.001). Three epigenetic signatures (EpiSig14, EpiSig13, EpiSig10) based on DNA methylation patterns of the primary tumors demonstrated high accuracy in predicting > pN1 disease (area under the curve 0.98). CONCLUSIONS: Epigenetic signatures have an excellent diagnostic accuracy for stratifying nodal disease in patients with clinically positive nodes. Validation of this tool is warranted and may provide an accurate and cost-effective method of identifying patients with predicted low nodal burden who could be spared the morbidity of ALND.

Impact of Choosing Wisely Recommendations on Sentinel Lymph Node Biopsy and Postoperative Radiation Rates in Women Over Age 70 Years with Hormone-Positive Breast Cancer.

BACKGROUND: In 2016, the Society of Surgical Oncology released a Choosing Wisely guideline recommending sentinel lymph node biopsy (SLNB) omission in females ≥70 years of age with early-stage, hormone-positive, clinically node-negative invasive breast cancer. This study investigated the impact of this guideline on SLNB and radiotherapy rates, in addition to assessing temporal trends of nodal biopsy and factors associated with recurrence. METHODS: The study involved a retrospective review of women who met the guideline criteria and underwent partial mastectomy at a single institution between 2009 and 2018. Using the same inclusion criteria, the National Cancer Database was queried to obtain a separate dataset. Statistical analyses included univariate comparisons, and multivariate logistic regression modeling to predict radiotherapy delivery. RESULTS: In our institutional series, 487 patients were included, 274 (56.3%) of whom received radiotherapy. There were 414 patients (85.0%) who underwent SLNB, with a nodal positivity rate of 11%. SLNB correlated with higher rates of radiotherapy (63.5% vs. 15.1%, p < 0.001). Age <80 years was an independent predictor of radiotherapy receipt (odds ratio 3.0, 95% confidence interval 0.22-0.52). SLNB performance decreased after 2016 (88.4% vs. 78.4%, p = 0.003). Median follow-up was 4.8 years, with 19 (3.9%) documented recurrences. SLNB performance was not associated with recurrence (2.9% vs. 5.5%, p = 0.279), whereas radiotherapy resulted in reduced recurrence (1.1% vs. 6.1%, p = 0.002). One (0.2%) disease-related mortality was observed. CONCLUSION: Recurrence rates and disease-related mortality remain low in this demographic regardless of treatment rendered. Omission of SLNB and radiotherapy should remain a consideration, and efforts in both patient and physician education should continue.

An immunoblot assay for cysteine oxidation by reactive oxygen species allows detection of novel thioprotective efficacy of black tea extracts.

INTRODUCTION: While cysteine thiol groups help to maintain the redox status of many proteins, they can be very susceptible to damaging oxidants. Despite broad interest in their antioxidant properties, whether tea polyphenols protect against protein thiol damage of this kind is unclear. This study sought to develop a simple immunoassay for use in screening tea extracts and other antioxidants for thioprotective efficacy at protein thiol groups. METHODS: Fresh aqueous extracts were prepared from commercially sourced green, white, black and red teas. Traut's reagent (2-iminothiolane) was used to prepare surface-thiolated bovine serum albumin for use as assay substrate in the protein oxidation assay. Oxidative damage was induced during a 15 min incubation with hydrogen peroxide (H2O2) in the presence of tea extracts and reference antioxidants. The substrate protein was then derivatised with dimedone before samples were loaded onto a nitrocellulose membrane housed within a Slot-Blot apparatus. After blocking nonspecific protein binding a commercially available antibody was used to detect dimedone-labelled groups. RESULTS: While the total phenol content of tea extracts typically correlated with their activity in lipid peroxidation and galvinoxyl radical-trapping assays, the former did not fully predict their abilities to suppress H2O2-induced cysteine oxidation, with black tea extracts displaying greater activity than the other teas and an apparent ability to reverse pre-existing cysteine oxidation. Among the model antioxidants tested, quercetin displayed a heightened ability to suppress cysteine oxidation. DISCUSSION: This slot-blot immunoassay is a convenient method that facilitates standardised comparisons between the thioprotective properties of structurally- and constitutively-diverse antioxidants.

Halitosis and Pain Post Electrocautery Adenoidectomy.

Background and Objectives: Electrocautery adenoidectomy (ECA) is a common procedure performed in paediatric otolaryngology. ECA has been preferred over curettage adenoidectomy due to its lower intraoperative bleeding rates, decreased procedure time, and higher subjective success. However, post-ECA symptoms of pain and halitosis have never been studied. The objective of our study was to identify the pattern of post-ECA halitosis and pain in the paediatric population. Materials and Methods: This is a single centre, prospective observational study that uses visual analogue scales (VAS) by parent proxy to assess post-ECA pain and halitosis in paediatric patients (age < 18) in South Australia. A total of 19 patients were enrolled in the study and followed for seven days. Results: Postoperative pain and halitosis reaches a peak 3 days post-ECA (median = 2 for pain; median = 6 for halitosis) but resolves 7 days post-ECA (median = 0 for both). Conclusions: Our study demonstrates that halitosis and pain occur over a seven-day period in patients undergoing ECA and will resolve post-operatively with simple analgesia and without antibiotics.

A Novel Treatment of Nasal Stenosis Using Steel Gauging Earrings.

Nasal stenosis is an uncommon and challenging deformity. Most common etiologies for nasal stenosis include congenital, iatrogenic, trauma, and infection. Repair techniques typically include tissue replacement with grafts or flaps with subsequent stent placement. These procedures often require general anesthesia and carry high rates of restenosis. We describe a case of a 10-year-old girl with Teebi syndrome and iatrogenic nasal stenosis who underwent successful nasal dilation with inexpensive, minimally invasive steel gauge earrings.

A case of hypermucoviscous Klebsiella pneumoniae liver abscess syndrome in an Iraqi male.

A 53-year-old man presented with fevers, productive cough and decreased appetite. He emigrated from Iraq 4 years ago. Chest x-ray revealed a left lung consolidation. Respiratory cultures and two sets of blood cultures grew out pan-susceptible Klebsiella pneumoniae Liver ultrasound revealed a 6.4-cm complex lesion in the left hepatic lobe. A biopsy of the liver lesion produced bloody purulent aspirate; abscess cultures yielded a highly viscous pan-susceptible K. pneumoniae Klebsiella pneumoniae liver abscess syndrome is a newly described invasive syndrome due to a hypermucoviscous phenotype associated with serotypes K1 and K2 of Klebsiella. Although it is more commonly endemic to the Asian-Pacific region, it has been increasingly reported as an emerging global disease. We present the first case of this syndrome in a patient of middle-eastern descent. We also present pictorial evidence of the microbe's unique viscous, muculent texture grown on agar.

A rare case of giant cell tumor involving the clivus resected through Le Fort I Osteotomy and median maxillotomy.

BACKGROUND: Giant cell tumors (GCTs) are bone tumors that seldom involve the skull. Skull GCTs preferentially occur in the sphenoid and temporal bones with few reported cases involving the clivus. Due to the rarity and complex location, surgical management is not well established for clival GCTs. CASE DESCRIPTION: A 49-year-old male presented with headaches and blurred vision in the right eye for 2 weeks. Computed tomography (CT) with contrast revealed a sellar mass eroding through the sphenoid sinuses with compression of optic chiasm. Biopsy was consistent with GCT. Patient underwent tumor resection by Le Fort I Osteotomy and median maxillotomy for an extended transsphenoidal approach. Upon discharge, patient showed no neurological deficits and intact cranial nerves. CONCLUSION: This case contributes to the limited amount of skull-based GCT cases worldwide. Additionally, the extended transoral approach can be performed safely in the context of a GCT within the clivus with acceptable morbidity and cosmesis.

Genetic ablation of Pals1 in retinal progenitor cells models the retinal pathology of Leber congenital amaurosis.

Mutation of the polarity gene Crumbs homolog 1 (CRB1) is responsible for >10% of Leber congenital amaurosis (LCA) cases worldwide; LCA is characterized by early-onset degenerative retinal dystrophy. The role of CRB1 in LCA8 pathogenesis remains elusive since Crb1 mouse mutants, including a null allele, have failed to mimic the early-onset of LCA, most likely due to functional compensation by closely related genes encoding Crb2 and Crb3. Crb proteins form an evolutionarily conserved, apical polarity complex with the scaffolding protein associated with lin-seven 1 (Pals1), also known as MAGUK p55 subfamily member 5 (MPP5). Pals1 and Crbs are functionally inter-dependent in establishing and maintaining epithelial polarity. Pals1 is a single gene in the mouse and human genomes; therefore, we ablated Pals1 to establish a mouse genetic model mimicking human LCA. In our study, the deletion of Pals1 leads to the disruption of the apical localization of Crb proteins in retinal progenitors and the adult retina, validating their mutual interaction. Remarkably, the Pals1 mutant mouse exhibits the critical features of LCA such as early visual impairment as assessed by electroretinogram, disorganization of lamination and apical junctions and retinal degeneration. Our data uncover the indispensible role of Pals1 in retinal development, likely involving the maintenance of retinal polarity and survival of retinal neurons, thus providing the basis for the pathologic mechanisms of LCA8.