Occult Lesions Research Articles

Non-Palpable Breast Cancer: A Targeting Challenge–Comparison of Radio-Guided vs. Wire-Guided Localization Techniques

Background: The incidence of non-palpable breast cancer is increasing due to widespread screening and neo-adjuvant therapies. Among the available tumor localization techniques, radio-guided occult lesion localization (ROLL) has largely replaced wire-guided localization (WGL). The aim of this study was to compare the ROLL and WGL techniques in terms of the effectiveness of isotopic marking of axillary sentinel lymph nodes and to assess patient perspectives along with surgeon and radiologist preferences. Methods: A single-center, prospective, randomized study enrolled 110 patients with non-palpable breast lesions (56 ROLL, 54 WGL). Breast type, tumor volume, location, histological and radiological features, and localization/surgical duration were evaluated in the context of sentinel lymph node marking using isotope (technetium-99m-labeled human serum albumin) and blue dye. Statistical analysis was performed with significance set at p < 0.05 and strong significance at p < 0.01. Results: A single-center, prospective, randomized study enrolled 110 patients with non-palpable breast lesions (56 ROLL, 54 WGL). Breast type, tumor volume, location, histological and radiological features, and localization/surgical duration were evaluated in the context of sentinel lymph node marking using isotope (technetium-99m-labeled human serum albumin) and blue dye. Statistical analysis was performed with significance set at p < 0.05 and strong significance at p < 0.01. Conclusions: While ROLL provided advantages in terms of patient comfort and logistical simplicity, WGL was superior for axillary sentinel lymph node marking, particularly in inner quadrant tumors, suggesting that WGL may be preferred in these cases.

Advanced ultrasound diagnosis of extrahepatic bile duct lesions.

Ultrasound (US) has high specificity and sensitivity, and it should be performed first for patients with suspicion of biliary tract cancer. However, the complicated anatomy in addition to the gas images makes it difficult to delineate the entire extrahepatic bile duct (EHBD). The keys to depiction of EHBD are the "J" shape manipulation in the left lateral decubitus position and the use of magnified images with high-frequency transducers. Furthermore, indirect findings such as gallbladder (GB) distension, BD dilatation, and debris echo in the GB and BD are also important for detecting occult lesions, particularly in the ampullary region of Vater. For the differential diagnosis of BD wall thickening, the spreading pattern in the long and short axial directions should be assessed first. Then, the characteristics of the innermost hyperechoic layer (IHL) and outermost hyperechoic layer (OHL) should be evaluated. Asymmetrical wall thickening, absence of IHL, and presence of irregularity or discontinuity in OHL are characteristic patterns of cholangiocarcinoma (CCA). Because CCA is the most common BD polypoid lesion, it is important to diagnose tumor extension and depth invasion in addition to differential diagnosis. Nodular-type CCA is usually hypoechoic and more likely to invade vertically. In contrast, papillary-type CCA is often hyperechoic and extends laterally. Contrast‑enhanced US may be useful for evaluating these findings. However, if the possibility of CCA cannot be ruled out or a definitive diagnosis is needed, a transpapillary biopsy or endoscopic US-guided tissue acquisition should be considered.

Intraoperative Molecular Imaging with Pafolacianine in Resection of Occult Pulmonary Malignancy in the ELUCIDATE trial

Clinical studies have demonstrated that intraoperative molecular imaging (IMI) with pafolacianine identifies occult pulmonary lesions that are not identified by preoperative CT or by intraoperative inspection techniques in ∼20% of patients. In this study we provide a description of occult lesion clinical data and evaluate characteristics so that surgeons can better incorporate this emerging technology into clinical decision making. Participants (n=100) enrolled in a Phase 3 trial of IMI with pafolacianine during pulmonary resection (ELUCIDATE, NCT04241315) were identified. Participants underwent preoperative computed tomography (CT)with 1.25mm slices. Variables and lesion characteristics were analyzed. Positive predictive value and false positive rates were tabulated for IMI fluorescent lesions with predictors of malignant versus benign occult lesions described. IMI identified 29 occult lesions in 23 (23%) participants. Seventeen of 29 (58%) lesions were identified within the same lobe as known lesions; 12 of 29 (42%) identified in a different lobe from the suspicious nodule known by preoperative assessment. Twenty-three of 29 (79%) of occult lesions found by IMI were resected with an additional wedge resection. Ten of 29 (34%) lesions identified by IMI were malignant. There was no additional morbidity in participants with lesions resected. With pafolacianine, 7 participants had a synchronous primary stage I lung cancer identified and one subject had additional metastases identified. . IMI with pafolacianine identifies occult malignant lesions during pulmonary resection despite thorough preoperative imaging and intraoperative assessment by experienced surgeons.

Bovine papillomavirus gene expression and inflammatory pathway activation vary between equine sarcoid tumour subtypes

Equine sarcoids are common non-metastasising skin tumours in horses, associated with bovine papillomavirus (BPV) infection. Six subtypes are recognised (occult, verrucose, nodular, fibroblastic, mixed and malevolent lesions), with variable clinical behaviour. The pathophysiology underlying varying tumour phenotype is poorly understood, and previous data on associations with viral load have been conflicting. To better understand this clinical variation, we investigated associations between tumour subtype and viral load, viral early protein gene expression, and expression of 10 host genes by quantitative polymerase chain reaction in 27 sarcoids and 5 normal skin samples. Viral DNA copy number did not differ between subtypes but was significantly higher in animals with fewer tumours. Expression of BPV E2 and E6 was higher in occult lesions compared to fibroblastic or nodular lesions, while E5 expression was higher in previously-treated lesions. Of the host genes, only IL6 and IL1B differed between subtypes, with higher expression in fibroblastic lesions, while IL10 and CCL5 were elevated compared to skin in all lesion types, and elevations in TNF and TGFB1 were significant for occult lesions only. Expression of TLR9, ATR, VEGFA and PTGS2 in sarcoids was not significantly different from normal skin, suggesting differences between BPV and human papillomavirus tumorigenesis. Results for BPV viral load and gene expression differed from previous reports and are insufficient to explain the spectrum of tumour phenotypes. Activation of both pro-inflammatory and anti-inflammatory immune pathways in sarcoids could influence tumour growth and effective immune responses, and the contribution of specific infiltrating immune cells requires further investigation.

What do we know About the Usefulness of 18F-FDG PET-CT for the Management of Invasive Fungal Infection? An International Survey.

Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.

Acute Macular Neuroretinopathy Associated with COVID-19 Pandemic: A Real-world Observation Study

PurposeTo evaluate the clinical and retinal imaging features of Chinese patients with acute macular neuroretinopathy (AMN) associated with COVID-19. DesignA prospective observational study. MethodsRetinal imaging, including color fundus photography, near-infrared imaging (NIR), swept-source optical coherence tomography (SS-OCT), optical coherence tomography angiography (OCTA), and Humphrey perimetry, were conducted for each case. ResultsAll cases were included within the first three months following the pandemic outbreak. A total of 12 male patients (36.36 %) and 21 female patients (63.64 %) were prospectively recruited, and 29 cases (87.88 %) were bilaterally affected. The median interval between the onset of fever and the appearance of ocular symptoms was two days (range, 0.5–5.0 days). Apart from the outer retinal changes typical of AMN, changes in the inner retinal layers were observed, including intraretinal hemorrhage (8.06 %), cotton wool spots (9.68 %), and paracentral acute middle maculopathy (PAMM) (8.06 %). Smaller retinal inner nuclear layer hyperreflective speckles (RIHS) (41.94 %) were identified as a distinguishing feature from typical PAMM. Voids of vessel signals were found in the superficial (11.54 %), intermediate (82.69 %), and deep capillary plexus (98.08 %), and in the choriocapillaris (19.23 %) on OCTA. Humphrey perimetry illustrated central, paracentral, and peripheral scotomas. The occult lesions associated with AMN, PAMM, and some of the RIHS illustrated by OCT were visualized topographically and further confirmed by OCTA as perfusion defects. ConclusionAn increase in AMN cases correlated with the SARS-CoV-2 outbreak. Additional features, including widespread inner retinal perfusion deficits, were observed and may serve as potential biomarkers for systemic microcirculation dysregulation in COVID-19.

A systematic review on artificial intelligence evaluating PSMA PET scan for intraprostatic cancer.

To assess artificial intelligence (AI) ability to evaluate intraprostatic prostate cancer (PCa) on prostate-specific membrane antigen positron emission tomography (PSMA PET) scans prior to active treatment (radiotherapy or prostatectomy). This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO identifier: CRD42023438706). A search was performed on Medline, Embase, Web of Science, and Engineering Village with the following terms: 'artificial intelligence', 'prostate cancer', and 'PSMA PET'. All articles published up to February 2024 were considered. Studies were included if patients underwent PSMA PET scan to evaluate intraprostatic lesions prior to active treatment. The two authors independently evaluated titles, abstracts, and full text. The Prediction model Risk Of Bias Assessment Tool (PROBAST) was used. Our search yield 948 articles, of which 14 were eligible for inclusion. Eight studies met the primary endpoint of differentiating high-grade PCa. Differentiating between International Society of Urological Pathology (ISUP) Grade Group (GG) ≥3 PCa had an accuracy between 0.671 to 0.992, sensitivity of 0.91, specificity of 0.35. Differentiating ISUP GG ≥4 PCa had an accuracy between 0.83 and 0.88, sensitivity was 0.89, specificity was 0.87. AI could identify non-PSMA-avid lesions with an accuracy of 0.87, specificity of 0.85, and specificity of 0.89. Three studies demonstrated ability of AI to detect extraprostatic extensions with an area under curve between 0.70 and 0.77. Lastly, AI can automate segmentation of intraprostatic lesion and measurement of gross tumour volume. Although the current state of AI differentiating high-grade PCa is promising, it remains experimental and not ready for routine clinical application. Benefits of using AI to assess intraprostatic lesions on PSMA PET scans include: local staging, identifying otherwise radiologically occult lesions, standardisation and expedite reporting of PSMA PET scans. Larger, prospective, multicentre studies are needed.

O-309 Safety and fertility potential of residual ovarian cortex surrounding borderline tumors in women of reproductive age

Abstract Study question How do borderline ovarian tumors (BOTs) at different oncological stages affect safety (presence of occult lesions) and quality of the ovarian reserve? Summary answer The ovarian follicle pool is decreased in women with BOTS, especially at younger age, and oncological safety is compromised in more advanced oncological stages. What is known already The clinical decision-making balancing the type of surgical treatment (radical or fertility-sparing) with the the risk of recurrence is still controversial for women diagnosed with BOTs at different oncological stages. The same is for the use of adjuvant techniques like oocyte or ovarian tissue cryopreservation to optimize the likelihood of fertility recovery. The prevalence of occult lesions in healthy-looking ovarian cortex, which may be managed by surgery or cryopreservation, has not been analyzed in all tumor types. Moreover, the status of the ovarian follicle pool may be affected by tumoral masses, making fertility preservation even more challenging in these patients. Study design, size, duration Multicentric retrospective study involving Cliniques Universitaires Saint Luc in Brussels (Belgium) and Macedonio Melloni hospital in Milan (Italy). Forty-two women at reproductive age (15-45 years) diagnosed with borderline ovarian tumors (BOTs), including 24 serous, 14 mucinous and 4 endometrioid BOTs were included. Participants/materials, setting, methods Histological samples of ovarian cortex surrounding tumors were analyzed to characterize the follicle pool (follicle density, classification and atresia rates) and results were compared with an aged-matched population of 45 subjects with non-ovarian pathologies. Any occult malignant lesions in healthy-looking cortex were investigated using tumor-specific markers (cytokeratin 7 and mucin 1), while immune system infiltration was quantified by CD3 for tumor-infiltrating lymphocytes (TILs) and CD68 for tumor associated macrophages (TAMs). Main results and the role of chance Occult ovarian lesions were observed in 5 out of 39 cases (12.8%). These included one mucinous stage-I BOT (1/13), one serous stage-I BOT (1/13), and 3 advanced-stage serous BOTs (3/11). Three 3 cases were excluded from the analysis because no cortex was available. Notably, follicle density was significantly lower in subjects diagnosed with ovarian tumors than in controls (p < 0.001) at a younger age, while no difference was detected in older patients. Significantly greater follicle atresia was encountered in the ovarian tumor group than in controls (20.1 ± 8.8% vs 9.2 ± 9.4%, p < 0.001) at all ages, but no difference was detected in follicle classification parameters (primordial and growing follicle rates). Mucinous BOTs exhibited lower follicle density than serous BOTs (98.8 ± 152.8 vs 225.8 ± 220.7, p < 0.01), although no age difference was evidenced. Although mucinous BOTS had also significantly bigger volume than serous BOTs, no significant correlation between follicle density and tumoral volume was found. Other factors like tumor microenvironment may play a role in ovarian follicle pool damage. Both TILs and TAMs were found in ovarian tumors irrespective of histotype, but no link was established with the status of the ovarian reserve. Limitations, reasons for caution Although this study helped to elucidate the risk profile of different types of epithelial ovarian tumors, observing that late-stage BOTs ran a 27% (3/11) risk of occult ovarian lesions, further research is needed to identify predictive markers. Wider implications of the findings Personalized counseling for fertility preservation is required in case of BOTs. Fertility-sparing surgery and adjuvant gamete preservation should be considered, balancing any oncological risks against tumor stage and histotype and fertility potential, especially at a younger age. Trial registration number NA

Contrast-enhanced mammography versus conventional imaging in women recalled from breast cancer screening (RACER trial): a multicentre, open-label, randomised controlled clinical trial

Women recalled from breast cancer screening receive post-screening work-up in the hospital with conventional breast imaging. The RACER trial aimed to study whether contrast-enhanced mammography (CEM) as primary imaging instead of conventional imaging resulted in more accurate and efficient diagnostic work-up in recalled women. In this randomised, controlled trial (registered under NL6413/NTR6589) participants were allocated using deterministic minimisation to CEM or conventional imaging as a primary work-up tool in two general and two academic hospitals. Predefined patients' factors were reason for recall, BI-RADS score, and study centre. Primary outcomes were sensitivity and specificity. Secondary outcomes were the proportion of women needing supplemental examinations, and number of days until diagnosis. Between April, 2018, and September, 2021, 529 patients recalled from the Dutch screening program were randomised, 265 to conventional imaging and 264 to CEM. Three patients in the control arm had to be excluded from analysis due to a protocol breach. After the entire work-up, sensitivity was 98.0% (95% CI; 92.2-99.7%) in the intervention arm and 97.7% (91.8-99.6%) in the control arm (p=1.0), and specificity was 75.6% (72.5-76.6%) and 75.4% (72.5-76.4%, p=1.0), respectively. Based on only primary full-field digital mammography/digital breast tomosynthesis or CEM, final diagnosis was reached in 27.7% (73/264) in the intervention arm and 1.1% (3/262) in the control arm. The frequency of supplemental imaging was significantly higher in the control arm (p<0.0001). Median time needed to reach final diagnosis was comparable: 1 day (control arm: IQR 0-4; intervention arm: IQR 0-3). Thirteen malignant occult lesions were detected using CEM, versus three using conventional imaging. No serious adverse events occurred. Diagnostic accuracy of CEM in the work-up of recalled women is comparable with conventional imaging. However, work-up with CEM as primary imaging is a more efficient pathway. ZonMw (grant number 843001801) and GE Healthcare.

Clear cell renal cell carcinoma metastasizing to the oral cavity: A diagnostic challenge of a case revealing an unusual clinical presentation

AbstractObjectiveDiagnosing lesions with unusual clinical presentation can be challenging, mostly for cases in which the inclusion of oral metastasis in the differential diagnosis is necessary.Materials and MethodsA 55‐year‐old man complaining of a large mass in the oral cavity was referred to the Hospital Dentistry Service. The patient reported bleeding episodes and pain, with a 5‐month evolution. Intraoral examination revealed a 5 cm tumour with purplish‐red and ulcerated focal areas at the right buccal mucosa. Differential diagnosis included malignant mesenchymal tumours, lymphoproliferative lesions, and metastasis of an occult primary lesion. Two biopsies were conducted, with the first one presenting an intense haemorrhage, and the second performed under general anaesthesia and difficult bleeding control.ResultsHistologic and immunohistochemical analysis diagnosed a clear cell carcinoma infiltration. A whole‐body CT scan reveals a renal tumour with multiple metastasis sites in the abdomen and bones. Metastatic clear cell renal cell carcinoma was finally confirmed, and the patient was followed with palliative care for 4 months.ConclusionA challenging diagnosis of a rare metastatic lesion in the oral cavity was conducted after two procedures under difficult bleeding conditions.

Non-palpable breast lesions localization techniques - A new priority: Results of a Senonetwork survey among breast centers in Italy

IntroductionNon palpable breast tumors are increasingly diagnosed because of screening programs, and their localization during surgery is essential to ensure an adequate resection. Little is known regarding which techniques are used in “real world”. Materials and methodsA national web-based survey, with a 21-items questionnaire, was conducted among Breast Centers (BCs) in Italy in 2023. ResultsAmong 153 BCs, 110 (72 %) participated. Wire-guided localization was reported to be the most used technique, regardless of the volume of malignant tumors treated by each Center (N = 36, 33 %). However, newer techniques such as Radioactive occult lesion localization and magnetic seeds, were reported to be employed in 34 (31 %) BCs, and more often among high-volume BCs (>300 cases/year) (N = 32, 29 % vs. N = 13, 12 %; p = 0.02). Logistic problems of localization were reported to cause delays to the scheduled surgery at least once or in multiple occasions in 26 (24 %) and in 4 (3.5 %) BCs, respectively. Although the majority of BCs declared they were satisfied (N = 48, 44 %) or somewhat satisfied (N = 41, 37 %) with the procedure used in their center, responders stated that they would change their technique, or that they were strongly considering this possibility in 24 (22 %) and in 38 (35 %) cases, respectively. The main barrier to introducing a new technique was associated with procedure costs (90 BCs, 82 %). ConclusionsThere are several critical issues regarding localization techniques at a national level. This should be recognized as a priority because of its impact on both patients and clinical practices.

Abstract PO4-07-09: CONTRAST-ENHANCED MAMMOGRAPHY IN LOCAL STAGING OF SCREEN-DETECTED BREAST CANCER: ADDITIONAL LESIONS AND CHANGES TO CLINICAL MANAGEMENT

Abstract Background BreastScreen Australia, a mammographic population screening program, provides assessment of suspected breast cancer to the point of diagnosis using a combination of conventional imaging and percutaneous biopsy. Comprehensive local staging, not performed at BreastScreen, determines the extent of disease and may identify additional clinically significant breast abnormalities. Local staging options include completion of bilateral mammographic work-up, ultrasound, and/or contrast-based imaging (CBI) (magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM)), with biopsy as required. We introduced CBI for local staging after diagnosis of screen-detected cancer at our academic hospital breast service in Melbourne, Australia. We report diagnostic findings for otherwise occult disease and their impact on treatment decisions in women who underwent CEM for local staging. Material and methods Women with screen-detected breast cancer who underwent CEM for local staging between November 2018 to April 2022 were identified retrospectively. The reporting breast-specialised radiologist compared BreastScreen and CEM images to identify additional enhancing abnormalities. Additional abnormalities were further investigated with preoperative percutaneous biopsy, surgical biopsy, or problem-solving CBI. Additional CEM-detected abnormalities were documented, with invasive cancer or DCIS recorded as true positive (TP) and any other findings as false positive (FP). Impact on surgical decisions was assessed. Results 204 patients underwent CEM. 62/204 (30%) patients had 76 additional abnormalities, of which 36 (47%) were TP and 40 (53%) FP. CEM identified otherwise occult malignant lesions in 30/204 (15%) patients. TPs comprised 75% invasive cancers and 25% DCIS. 83% (30/36) of malignant abnormalities were ipsilateral to the index lesion, while 17% (6/36) were contralateral. The majority of additional invasive cancers were Grade 2 (20/27, 74.1%), followed by Grade 1 (4/27, 14.8%) then Grade 3 (3/27, 11.1%). All additional invasive cancers had the same phenotype as the patient’s index cancer (ER+/HER2-), except for one abnormality which was ER+/HER2+ where the index cancer was ER+/HER2-. The FP abnormalities consisted of normal breast tissue (20/40, 50%), benign lesions (16/40, 40%) and atypical proliferative lesions (4/40, 10%). Occult malignancies were more common for patients with higher background parenchymal enhancement (20% for moderate/marked vs 4% for minimal/mild, p=0.0023), with no statistically significant differences found by breast density (BIRADS A or B = 12%, vs BIRADS C or D = 20%, p=0.23) or by age (40-49=38%, 50-59=13%, 60-69=13%, ³70=19%, p=0.88). Additional abnormalities found on CEM resulted in surgical management change in 45/204 (22%) patients, including wider resection (24/45), conversion to mastectomy (8/45), contralateral breast surgery (6/45), additional ipsilateral excision (5/45), and bracketing (2/45). Conclusions The use of CEM for local staging of screen-detected breast cancers identified otherwise occult malignancy in 15% of patients. Age and mammographic density did not identify groups at minimal risk of additional findings. Pathology of additional malignancy suggests it is clinically significant. CEM may improve local staging and direct appropriate management of screen-detected breast cancers. Citation Format: Caroline MacCallum, Kenneth Elder, Carolyn Nickson, Kelly Ruecker, Allan Park, Bruce Mann. CONTRAST-ENHANCED MAMMOGRAPHY IN LOCAL STAGING OF SCREEN-DETECTED BREAST CANCER: ADDITIONAL LESIONS AND CHANGES TO CLINICAL MANAGEMENT [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-09.

NIR-II light in clinical oncology: opportunities and challenges.

Novel strategies utilizing light in the second near-infrared region (NIR-II; 900-1,880 nm wavelengths) offer the potential to visualize and treat solid tumours with enhanced precision. Over the past few decades, numerous techniques leveraging NIR-II light have been developed with the aim of precisely eliminating tumours while maximally preserving organ function. During cancer surgery, NIR-II optical imaging enables the visualization of clinically occult lesions and surrounding vital structures with increased sensitivity and resolution, thereby enhancing surgical quality and improving patient prognosis. Furthermore, the use of NIR-II light promises to improve cancer phototherapy by enabling the selective delivery of increased therapeutic energy to tissues at greater depths. Initial clinical studies of NIR-II-based imaging and phototherapy have indicated impressive potential to decrease cancer recurrence, reduce complications and prolong survival. Despite the encouraging results achieved, clinical translation of innovative NIR-II techniques remains challenging and inefficient; multidisciplinary cooperation is necessary to bridge the gap between preclinical research and clinical practice, and thus accelerate the translation of technical advances into clinical benefits. In this Review, we summarize the available clinical data on NIR-II-based imaging and phototherapy, demonstrating the feasibility and utility of integrating these technologies into the treatment of cancer. We also introduce emerging NIR-II-based approaches with substantial potential to further enhance patient outcomes, while also highlighting the challenges associated with imminent clinical studies of these modalities.

Phase 2 Clinical Trial of VGT-309 for Intraoperative Molecular Imaging During Pulmonary Resection

BackgroundAdvances in intraoperative molecular imaging (IMI) may improve surgical outcomes when resecting tumors in the lung. A single-center trial was conducted using VGT-309, a cathepsin-targeted near-infrared imaging agent that causes lung nodules to fluoresce during surgical resection. The end point of this phase 2 study was to evaluate the frequency that IMI with VGT-309 resulted in a clinically significant event (CSE): localization of pulmonary nodules, discovery of unsuspected additional cancers, or identification of positive margins. MethodsPatients undergoing surgical resection for known or suspected cancer in the lung received VGT-309 (0.32 mg/kg) preoperatively. During the surgical procedure, localization and resection of the nodules were performed using standard surgical techniques. Near-infrared imaging was then used to localize nodules, seek occult lesions, and assess resection margins. Efficacy was measured by the frequency of CSEs. ResultsOf the 40 patients who underwent pulmonary resection with VGT-309, 17 (42.5%) had at least 1 CSE. Near-infrared imaging identified lesions not found by standard surgical methods in 16 patients, additional cancers not found by preoperative imaging in 1 patient, and margins within 5 mm of the closest staple line in 2 patients. VGT-309 performance was tested across a broad range of tumor types and commercial near-infrared imaging systems. VGT-309 appeared safe, well-tolerated, with no infusion reactions, and no drug-related serious adverse events. ConclusionsThis phase 2 study demonstrated the utility of IMI with VGT-309 in localizing pulmonary nodules, recognizing synchronous lesions, and identifying positive margins. A multi-institutional study will further evaluate the efficacy of VGT-309.

Histological Patterns and Mammographic Presentation of Invasive Lobular Carcinoma Show No Obvious Associations.

Invasive lobular carcinoma of the breast has different mammographic appearances, including spiculated or lobulated masses, architectural distortion, increased breast density, and the possibility of also being occult. Histologically, the morphology is also variable, as several patterns have been described beside the classical one, including the solid, the alveolar, the trabecular, the one with tubular elements, and others. Of 146 ILC cases, 141 were reviewed for mammographic appearance and 136 for histological patterns by two radiologist and two pathologists, respectively; 132 common cases were analyzed for possible associations between mammographic presentation and the histological patterns. Interobserver agreement on the presence or absence of a given mammographic morphology ranged from 45% (increased density) to 95% (occult lesion); the most common radiomorphology was that of a spiculated mass. Interobserver agreement on the presence or absence of a given histological pattern ranged between 79% (solid) and 99% (classical) but was worse when semi-quantification was also included. The mammography-pathology correlation was less than optimal. Multifocality was more commonly detected by histology. The identification of a mammographic mass lesion often coincided with a mass-like lesion on the histological slides and vice versa, but nearly half of the mammographically occult lesions were felt to have masses on histological slides assessed grossly. Histological patterns showed no obvious associations with one or the other mammographic appearance.

Evolution of localization methods for non-palpable breast lesions: a literature review from a translational medicine perspective.

With an increasing number of non-palpable breast lesions detected due to improved screening, accurate localization of these lesions for surgery is crucial. This literature review explores the evolution of localization methods for non-palpable breast lesions, highlighting the translational journey from concept to clinical practice. A comprehensive search of PubMed, Embase, and Scopus databases until September 2023 was conducted. Multiple methods have been developed throughout the past few decades. (I) Wire-guided localization (WGL) introduced in 1966, has become a reliable method for localization. Its simplicity and cost-effectiveness are its key advantages, but challenges include logistical constraints, patient discomfort, and potential wire migration. (II) Intraoperative ultrasound localization (IOUS) has shown promise in ensuring complete lesion removal with higher negative margin rates. However, its utility is limited to lesions visible on ultrasound (US) imaging. (III) Breast biopsy marker localization: the use of markers has improved the precision of localization without the need for wire. However, marker visibility remains a challenge despite improvements in their design. (IV) Radioactive techniques: radio-guided occult lesion localization (ROLL) and radioactive seed localization (RSL) offer flexibility in scheduling and improved patient comfort. However, they require close multidisciplinary collaboration and specific equipment due to radioactive concerns. (V) Other wireless non-radioactive techniques: wireless non-radioactive techniques have been developed in recent three decades to provide flexible and patient-friendly alternatives. It includes magnetic seed localization, radar techniques, and radiofrequency techniques. Their usage has been gaining popularity due to their safety profile and allowance of more flexible scheduling. However, their high cost and need for additional training remain a barrier to a wider adoption. The evolution of breast lesion localization methods has progressed to more patient-friendly techniques, each with its unique advantages and limitations. Future research on patient-reported outcomes, cosmetic outcomes, breast biopsy markers and integration of augmented reality with breast lesion localization are needed.

Development of a diagnostic support system for distal humerus fracture using artificial intelligence.

AI has shown promise in automating and improving various tasks, including medical image analysis. Distal humerus fractures are a critical clinical concern that requires early diagnosis and treatment to avoid complications. The standard diagnostic method involves X-ray imaging, but subtle fractures can be missed, leading to delayed or incorrect diagnoses. Deep learning, a subset of artificial intelligence, has demonstrated the ability to automate medical image analysis tasks, potentially improving fracture identification accuracy and reducing the need for additional and cost-intensive imaging modalities (Schwarz et al. 2023). This study aims to develop a deep learning-based diagnostic support system for distal humerus fractures using conventional X-ray images. The primary objective of this study is to determine whether deep learning can provide reliable image-based fracture detection recommendations for distal humerus fractures. Between March 2017 and March 2022, our tertiary hospital's PACS data were evaluated for conventional radiography images of the anteroposterior (AP) and lateral elbow for suspected traumatic distal humerus fractures. The data set consisted of 4931 images of patients sevenyears and older, after excluding paediatric images below sevenyears due to the absence of ossification centres. Two senior orthopaedic surgeons with 12 + years of experience reviewed and labelled the images as fractured or normal. The data set was split into training sets (79.88%) and validation tests (20.1%). Image pre-processing was performed by cropping the images to 224 × 224 pixels around the capitellum, and the deep learning algorithm architecture used was ResNet18. The deep learning model demonstrated an accuracy of 69.14% in the validation test set, with a specificity of 95.89% and a positive predictive value (PPV) of 99.47%. However, the sensitivity was 61.49%, indicating that the model had a relatively high false negative rate. ROC analysis showed an AUC of 0.787 when deep learning AI was the reference and an AUC of 0.580 when the most senior orthopaedic surgeon was the reference. The performance of the model was compared with that of other orthopaedic surgeons of varying experience levels, showing varying levels of diagnostic precision. The developed deep learning-based diagnostic support system shows potential for accurately diagnosing distal humerus fractures using AP and lateral elbow radiographs. The model's specificity and PPV indicate its ability to mark out occult lesions and has a high false positive rate. Further research and validation are necessary to improve the sensitivity and diagnostic accuracy of the model for practical clinical implementation.

Radioactive Seed Localization for Nonpalpable Breast Lesions: Systematic Review and Meta-Analysis.

This study is a systematic review with meta-analysis comparing radioactive seed localization (RSL) versus radio-guided occult lesion localization (ROLL) and wire-guided localization (WGL) for patients with impalpable breast cancer undergoing breast-conserving surgery and evaluating efficacy, safety, and logistical outcomes. The protocol is registered in PROSPERO with the number CRD42022299726. A search was conducted in the Embase, Lilacs, Pubmed, Scielo, Web of Science, and clinicaltrials.gov databases, in addition to a manual search in the reference list of relevant articles, for randomized clinical trials and cohort studies. Studies selected were submitted to their own data extraction forms and risk of bias analysis according to the ROB 2 and ROBINS 1 tools. A meta-analysis was performed, considering the random effect model, calculating the relative risk or the mean difference for dichotomous or continuous data, respectively. The quality of the evidence generated was analyzed by outcome according to the GRADE tool. Overall, 46 articles met the inclusion criteria and were included in this systematic review; of these, 4 studies compared RSL and ROLL with a population of 1550 women, and 43 compared RSL and WGL with a population of 19,820 women. The results showed that RSL is a superior method to WGL in terms of surgical efficiency in the impalpable breast lesions' intraoperative localization, and it is at least equivalent to ROLL. Regarding security, RSL obtained results equivalent to the already established technique, the WGL. In addition to presenting promising results, RSL has been proven to be superior to WGL and ROLL technologies.

The Sentinel Node and Occult Lesion Localization (SNOLL) Technique Using a Single Radiopharmaceutical in Non-palpable Breast Lesions.

In order to perform a full surgical resection on non-palpable breast lesions, a current method necessitates correct intraoperative localization. Additionally, because it is an important prognostic factor for these patients, the examination of the lymph node status is crucial. The aim of this study was to evaluate the efficiency of the sentinel node and occult lesion localization (SNOLL) technique in localizing nonpalpable breast lesions together with sentinel lymph node (SLN) using a single radiotracer, that is, nanocolloid particles of human serum albumin (NC) labeled with technetium-99m (99mTc). 39 patients were included, each having a single non-palpable breast lesion and clinically no evidence of axillary disease. Patients received 99mTc- NC intratumorally on the same day as surgery under the guidance of ultrasound. Planar and single-photon emission computed tomography/computed tomography lymphoscintigraphy were performed to localize the breast lesion and the SLN. The occult breast lesion and SLN were both localized using a hand-held gamma-probe, which was also utilized to determine the optimal access pathway for surgery. In order to ensure a radical treatment in a single surgical session and reduce the amount of normal tissue that would need to be removed, the surgical field was checked with the gamma probe after the specimen was removed to confirm the lack of residual sources of considerable radioactivity. Breast lesions were successfully localized and removed in all patients. Pathological findings revealed breast carcinoma in 11/39 patients (28%) and benign lesions in 28 (72%). Axillary SLNs were detected in 31/39 (79.5%) patients. The metastatic involvement of SLN was only seen in two cases. While the identification rate of the SNOLL technique performed with an intratumoral injection of 99mTc-NC as the sole radiotracer in non-palpable breast lesions was great, it was not fully satisfactory in SLNs.

A Systematic Review on Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA PET) Evaluating Localized Low- to Intermediate-Risk Prostate Cancer: A Tool to Improve Risk Stratification for Active Surveillance?

Active surveillance remains a treatment option for low- to intermediate-risk prostate cancer (PCa) patients. Prostate-specific membrane antigen positron emission tomography and computed tomography (PSMA PET/CT) has emerged as a useful modality to assess intraprostatic lesions. This systematic review aims to evaluate PSMA PET/CT in localized low- to intermediate-risk PCa to determine its role in active surveillance. Following PRISMA guidelines, a search was performed on Medline, Embase, and Scopus. Only studies evaluating PSMA PET/CT in localized low- to intermediate-risk PCa were included. Studies were excluded if patients received previous treatment, or if they included high-risk PCa. The search yielded 335 articles, of which only four publications were suitable for inclusion. One prospective study demonstrated that PSMA PET/CT-targeted biopsy has superior diagnostic accuracy when compared to mpMRI. One prospective and one retrospective study demonstrated MRI occult lesions in 12.3-29% of patients, of which up to 10% may harbor underlying unfavorable pathology. The last retrospective study demonstrated the ability of PSMA PET/CT to predict the volume of Gleason pattern 4 disease. Early evidence demonstrated the utility of PSMA PET/CT as a tool in making AS safer by detecting MRI occult lesions and patients at risk of upgrading of disease.