Sustained delivery of celecoxib from nanoparticles embedded in hydrogel injected into the biopsy cavity to prevent biopsy-induced breast cancer metastasis.

PURPOSE: We have previously reported that protracted Cyclooxygenase-2 (COX-2) activity in bone marrow-derived cells (BMDCs) infiltrating into biopsy wounds adjacent to the biopsy cavity of breast tumors in mice promotes M2-shift of macrophages and pro-metastatic changes in cancer cells, effects which were suppressed by oral administration of COX-2 inhibitors. Thus, local control of COX-2 activity in the biopsy wound may mitigate biopsy-induced pro-metastatic changes. METHODS: A combinatorial delivery system-thermosensitive biodegradable poly(lactic acid) hydrogel (PLA-gel) incorporating celecoxib-encapsulated poly(lactic-co-glycolic acid) nanoparticles (Cx-NP/PLA-gel)-was injected into the biopsy cavity of Py230 murine breast tumors to achieve local control of COX-2 activity in the wound stroma. RESULTS: A single intra-biopsy cavity injection of PLA-gel loaded with rhodamine-encapsulated nanoparticles (NPs) showed sustained local delivery of rhodamine preferentially to infiltrating BMDCs with minimal to no rhodamine uptake by the reticuloendothelial organs in mice. Moreover, significant reductions in M2-like macrophage density, cancer cell epithelial-to-mesenchymal transition, and blood vessel density were observed in response to a single intra-biopsy cavity injection of Cx-NP/PLA-gel compared to PLA-gel loaded with NPs containing no payload. Accordingly, intra-biopsy cavity injection of Cx-NP/PLA-gel led to significantly fewer metastatic cells in the lungs than control-treated mice. CONCLUSION: This study provides evidence for the feasibility of sustained, local delivery of payload preferential to BMDCs in the wound stroma adjacent to the biopsy cavity using a combinatorial delivery system to reduce localized inflammation and effectively mitigate breast cancer cell dissemination.

Direct Immunofluorescence of Skin and Oral Mucosa: Guidelines for Selecting the Optimum Biopsy Site.

Direct immunofluorescence is a vital diagnostic test for assessing vesiculobullous disorders, vasculitides, and connective tissue diseases. It is a robust and valuable technique that offers essential diagnostic information for many critical dermatoses. Dermatopathologists depend heavily on the data obtained from direct immunofluorescence evaluation to confirm final diagnoses. Selecting the most appropriate biopsy site is necessary for maximizing diagnostic accuracy, and the best site may vary depending on the clinical differential diagnosis. Inaccurate biopsy site selection can significantly impact the accuracy of the results. To optimize the use of direct immunofluorescence studies, this review provides helpful guidelines and some practical tips for selecting the best biopsy site.

Impact of reactive changes on multigene testing: histopathologic analysis of low-grade breast cancers with high-risk 21-gene recurrence scores.

PURPOSE: The 21-gene recurrence score (RS) assay predicts the recurrence risk and magnitude of chemotherapy benefit in patients with invasive breast cancer (BC). This study examined low-grade tumors yielding a high-risk RS and their outcomes.Kindly check the edit made in the article titleOk  METHODS: We compared patients with grade 1 BC and a high-risk RS to those with low-risk RS. Histologic sections were reviewed and features reported to elevate the RS were noted, mainly biopsy cavity and reactive stromal changes (BXC). RESULTS: A total of 54 patients had high-risk RS (median RS of 28, range 26-36). On review, BXC were seen in all cases. Thirty BCs in this group also had low to negative PR. Treatment regimens included: chemoendocrine therapy (63%), endocrine therapy alone (31%) and no adjuvant therapy (6%). There were no additional breast cancer events over a median follow-up of 54.0 months (range 6.2 to 145.3). A total of 108 patients had low-risk RS (median RS of 7, range 0-9). BXC were seen in 47% of cases and none were PR negative. One patient had a recurrence at 64.8 months while the rest had no additional events over a median of 68.1 months (2.4 to 100). CONCLUSION: We provide further evidence that reactive stromal changes and/or low-PR scores enhance the elevation of the RS. A high-RS result in low grade, PR-positive BC may not reflect actual risk and any suspected discrepancies should be discussed with the management teams. Multigene testing results should be interpreted after correlation with pathologic findings to optimize patient care.

Retained Biopsy Site Markers After Breast Lesion Surgical Resection: Associations With Residual Malignancy.

BACKGROUND. Biopsy site markers (BSMs) placed during image-guided core needle biopsy (CNB) are typically targeted for surgical excision, along with the breast imaging abnormality. Retained BSMs raise concern of incomplete resection of the breast abnormality. OBJECTIVE. The purpose of our study was to assess the frequency of residual malignancy in patients with retained BSMs identified on the initial mammography performed after breast lesion surgical excision. METHODS. This retrospective study included 30 patients (median age, 59 years) who underwent surgical resection between August 2015 and April 2022 of a borderline, high-risk, or malignant breast lesion after CNB and technically adequate preoperative image-guided localization, in whom the initial postoperative mammography report described a retained nonmigrated BSM. EMR data were extracted. The index pathology from CNB and initial surgical resection was classified as malignant or nonmalignant. The presence of residual malignancy after initial surgical resection required pathologic confirmation from subsequent tissue sampling; the absence of residual malignancy required 2 years of benign imaging follow-up. RESULTS. Thirteen specimen radiographs were interpreted intraoperatively by a surgeon with later radiologist interpretation, and 17 underwent real-time radiologist interpretation. Eighteen patients had malignant index pathology from the initially resected lesion. The frequency of residual malignancy on subsequent follow-up after initial surgical resection was higher in patients with malignant than nonmalignant index pathology (39% [7/18] vs 0% [0/12], respectively; p = .02). Among patients with malignant index pathology, the frequency of residual malignancy was higher in those without, than with, malignancy in the initial surgical specimen (80% [4/5] vs 23% [3/13]; p = .047). Also in these patients, the frequency of a positive interpretation of the initial postoperative mammography (BI-RADS category 4 or 6) was not significantly different between those with and without residual malignancy (57% [4/7] vs 55% [6/11]; p > .99). CONCLUSION. Patients with retained BSMs associated with malignant index lesions are at substantial risk of having residual malignancy. Initial postoperative mammography is not sufficient for excluding residual malignancy. CLINICAL IMPACT. Retained BSMs associated with index malignancy should be considered suspicious for residual malignancy. In this scenario, timely additional tissue sampling targeting the retained BSM is warranted, given the greater-than-2% chance of malignancy. Active surveillance is a reasonable management strategy in patients with retained BSMs from nonmalignant index lesions.

Hemorrhagic Complications After Brain Tumor Biopsy: Risk-Reduction Strategies Based on Safer Biopsy Targets and Techniques.

OBJECTIVE: Brain tumor biopsies are essential for pathologic diagnosis. However, hemorrhagic complications after biopsies may occur, leading to suboptimal outcomes. This study aimed to evaluate the associated factors of hemorrhagic complications after brain tumor biopsies and propose countermeasures. METHODS: We retrospectively collected data on 208 consecutive patients with brain tumors (malignant lymphoma or glioma) who underwent a biopsy from 2011-2020. We evaluated factors and microbleeds (MBs) in the tumor plus relative cerebral/tumoral blood flow (rCBF) at the biopsy site on preoperative magnetic resonance imaging (MRI). RESULTS: Postoperative all and symptomatic hemorrhage occurred in 21.6% and 9.6% of patients. In univariate analysis, a needle biopsy was significantly associated with the risk of all and symptomatic hemorrhages compared to techniques that allow adequate hemostatic manipulation (i.e., open and endoscopic biopsies). Multivariate analyses revealed that a needle biopsy and gliomas of World Health Organization (WHO) grade III/IV were significantly associated with postoperative all and symptomatic hemorrhages. Multiple lesions were also an independent risk factor for symptomatic hemorrhages. On preoperative MRI, abundant MBs in the tumor and MBs at the biopsy sites, in addition to high rCBF, were significantly associated with postoperative all and symptomatic hemorrhages. CONCLUSIONS: We recommend the following measures to prevent hemorrhagic complications: consider biopsy techniques that allow adequate hemostatic manipulation preferentially; perform more careful hemostasis in cases of suspected gliomas of WHO grade III/IV, multiple lesions, and abundant MBs in the tumors; and, if there are multiple candidate biopsy sites, select areas with lower rCBF and no MBs as a biopsy target.

Identification of a localization wire tip in an occult breast lesion using a handheld magnetometer.

BACKGROUND: The Sentimag hand-held probe detects the magnetic response from iron oxide particles trapped in a sentinel node. OBJECTIVES: To investigate if an electromagnetic probe can be helpful in the identification of a hook wire tip located in an occult breast lesion. MATERIAL AND METHODS: Forty-two patients undergoing lumpectomy without axillary procedure were enrolled. In all cases, suspicious non-palpable microcalcifications without mass were found, and a vacuum-assisted stereotactic biopsy was performed. On the day of surgery, a traditional localization wire (LW) was placed under imaging guidance. The Sentimag magnetometer was used to precisely detect the wire tip through the skin. Then, the skin incision was made and Sentimag was used again to guide the surgeon to the lumpectomy bed. The accuracy of excision was assessed with intra-operative specimen 3D tomosynthesis. RESULTS: Median lesion size was 16 mm (range: 4-38 mm) and median depth was 33 mm (range: 14-78 mm). In all cases, the wire tip was successfully identified. Neither wire displacement nor transection occurred. Intraoperative radiography demonstrated doubtful margin requiring selective cavity shaving in 6 patients (14%). The need for cavity shaving was significantly influenced by the lesion size and histology: median size 30 mm (range: 24-38 mm) compared to 15 mm (range: 4-28 mm) and histology of ductal carcinoma in situ (DCIS) compared to atypical ductal hyperplasia (ADH) and lobular neoplasia (LN). Tumors requiring cavity shaving tended to be deeper - they had a median depth of 43 mm (range: 17-78 mm) compared to 32 mm (range: 14-76 mm) in patients who did not need cavity shaving, but this parameter was statistically significant. CONCLUSIONS: Intraoperative identification of the wire tip using Sentimag is a simple technique facilitating targeted excision without excessive removal of breast tissue. Since it is not associated with additional costs, it may be worth considering, particularly in developing countries.

A smartphone application to improve the precision of biopsy site identification: A proof-of-concept study.

Dermatologists rely on skin biopsies to diagnose cutaneous tumors and rashes. Skin biopsy sites should be accurately identified with conventional anatomical site descriptors in the pathology request form. Reliance upon free-text entries to describe these biopsy sites is prone to user error and can cause medical misadventures such as wrong-site follow-up surgery. We sought to determine whether a smartphone application (RightSite) could improve the precision of biopsy site labeling. We conducted a prospective proof-of-concept study of 100 smartphone-assisted skin biopsy site identifiers with matched comparison to 100 historical controls. Student's t-test was used to identify significant differences in the precision of anatomic descriptors before and after adoption of the application. We found a 69% improvement in precision of anatomic site labeling with the RightSite smartphone application (P < 0.0001). These data show smartphone-assisted biopsy site labeling improves the precision of anatomic site descriptors. Integrating graphical user interfaces into the electronic health records system could improve health care by standardizing anatomic site nomenclature and site-specific descriptors.

Surgical site identification with personal digital device: A prospective pilot study.

BACKGROUND: Various means to facilit ate accurate biopsy site identification have been proposed. OBJECTIVE: To determine the accuracy of biopsy site identification by using photographs taken with a patient's digital device by a dermatologist versus professional medical photography. METHODS: Photographs of circled biopsy sites were taken with personal digital devices by the principal investigator (PI). Another set of photographs was taken by a professional photographer. Secondary photographs were taken of the biopsy site location pointed to by the staff and PI on the basis of the personal digital device image and professional medical photography, respectively. On the basis of secondary photographs, 2 independent dermatologists determined whether the skin biopsy locations pointed out by the staff were consistent with the ones pointed out by PI. RESULTS: Per dermatologist A, the staff correctly identified all 53 biopsy sites. Per dermatologist B, the staff were correct on 51 of 53 observations. Dermatologist C, the final arbiter, concurred with dermatologist A on the 2 cases in which dermatologist B was not certain of the location of the biopsy site. LIMITATIONS: The mean interval from initial biopsy to reidentification of the site was 36.2 days. CONCLUSION: Utilizing patients' personal digital devices is a cost-effective, Health Insurance Portability and Accountability Act-compliant, and readily available means to identify skin biopsy sites.

An update on intraoral application of colposcopy.

Colposcopy is an established technique for diagnosis in gynecology. Many premalignant and malignant lesions in these areas have discernible characteristics which can be detected using a colposcope, providing an enlarged view of the areas, allowing the colposcopist to visually distinguish normal from abnormal appearing tissue and take directed biopsies for further pathological examination. The diagnosis of a dysplastic lesion of the oral mucosa cannot be based solely on clinical findings. Therefore, histological evaluation of a representative biopsy specimen is necessary. The site for the biopsy is a subjective choice that sometimes raises doubts about its representativeness. So far, no simple and reliable method is available for selecting the most appropriate area for biopsy. Intraoral microscopy (oral application of the colposcopy technique) of mucosal lesions seems to offer advantages in selecting more representative sites for biopsy than routine clinical examination alone. The biopsy sites identified by direct oral microscopy show more advanced histologic signs than those selected by routine clinical examination. This article enlightens the application of colposcopy in diagnosis of oral premalignant lesions and malignant lesions.

Relevance of tumor angiogenesis patterns as a diagnostic value and prognostic indicator in oral precancer and cancer.

Tumor angiogenesis occurs by recruitment of endothelial cell precursors or by sprouting of existing capillaries, which differ from the normal vasculature by having an altered morphology that can be exploited for diagnosis and as a prognostic indicator. Improved technologies have propelled diagnosis into a new era. These technologies have to be used with great precision. The diagnosis of a dysplastic premalignant lesion of the oral mucosa cannot be based solely on clinical findings. Therefore histologic evaluation of a representative biopsy specimen is necessary. Accurate judgment of the proper site for biopsy is essential for reaching a correct diagnosis. The aim of this report is to analyze the vascular patterns with the help of direct oral microscopy and the technique of stereo-optical microscopy in the oral cavity to select biopsy sites, and compare the outcome of a directed biopsy with that of biopsy specimens obtained from sites selected solely on the basis of clinical criteria. The study sample comprised 50 oral mucosal lesions. A statistically significant difference was noted between samples judged to be microscopically representative sites. We conclude that this method would aid in early and better diagnosis and treatment planning of oral premalignant and malignant lesions by assessing the various vascular patterns in the mucosa.