Histopathological Assessment Research Articles

Stimulated Raman Histology and Artificial Intelligence Provide Near Real-Time Interpretation of Radical Prostatectomy Surgical Margins.

Balancing surgical margins and functional outcomes is crucial during radical prostatectomy for prostate cancer. Stimulated Raman Histology (SRH) is a novel, real-time imaging technique that provides histologic images of fresh, unprocessed, and unstained tissue within minutes, which can be interpreted by either humans or artificial intelligence. Twenty-two participants underwent robotic-assisted laparoscopic radical prostatectomy (RALP) with intraoperative SRH surgical bed assessment. Surgeons resected and imaged surgical bed tissue using SRH and adjusted treatment accordingly. An SRH convolutional neural network (CNN) was developed and tested on 10 consecutive participants. The accuracy, sensitivity, and specificity of the surgical team's interpretation were compared to final histopathological assessment. A total of 121 SRH periprostatic surgical bed tissue (PSBT) assessments were conducted, an average of 5.5 per participant. The accuracy of the surgical team's SRH interpretation of resected PSBT samples was 98%, with 83% sensitivity, and 99% specificity. Intraoperative SRH assessment identified 43% of participants with a pathologic positive surgical margin intraoperatively. PSBT assessment using the CNN demonstrated no overlap in tumor probability prediction between benign and tumor infiltrated samples, mean 0.30% (IQR 0.10-0.43%) and 26% (IQR 18-34%, p<0.005), respectively. SRH demonstrates potential as a valuable tool for real-time intraoperative assessment of surgical margins during RALP. This technique may improve nerve-sparing surgery and facilitate decision-making for further resection, reducing the risk of positive surgical margins and minimizing the risk of recurrence. Further studies with larger cohorts and longer follow-up periods are warranted to confirm the benefits of SRH in RALP.

Targeted thoracic ultrasonography shows high diagnostic potential for interstitial pneumonia in feedyard cattle.

To use a novel approach of targeted thoracic point-of-care ultrasound (TT-POCUS) of the caudodorsal right lung to determine potential associations between TT-POCUS measurements and the presence of interstitial pneumonia (IP) in feedyard cattle. Cross-sectional study evaluated feedyard animals (n = 62; 358.4 ± 10.5 kg; heifer, n = 38; steer, n = 24) using TT-POCUS at time of respiratory disease treatment and microscopic assessment of lesions at subsequent mortality. Evaluations took place from July through December 2023. Pulmonary samples were collected at necropsy for histopathologic assessment, and lesions were used to diagnose IP or non-IP. Statistical models determined potential associations between IP, cattle demographic, and TT-POCUS measured variables. Evaluations of animals enrolled (n = 62) displayed significant associations with IP, including ultrasound lung score (ULS), B-line count, A-line count, and days on feed at treatment. Cattle with a ULS of 5 had the lowest probability of IP (0.12 ± 0.16) compared to cattle with a ULS of 2, 3, or 4 (0.72 ± 0.18, 0.93 ± 0.06, and 0.85 ± 0.08, respectively). Cattle with B-line counts > 5 had a higher probability of IP (0.86 ± 0.11) compared to cattle with 3 to 5 B-lines (0.38 ± 0.14). The probability of IP was higher in cattle with A-line counts < 3 (0.83 ± 0.10) compared to cattle with ≥ 3 A-lines (0.51 ± 0.15). Strategic targeted thoracic ultrasonography has potential a value of timely IP diagnosis in feedyard cattle, thereby offering important insights into therapeutic and management decisions. Targeted thoracic ultrasonography can be utilized as a method for IP diagnosis in feedyard cattle.

Basal cell carcinoma: A report of a case in the upper lip

Basal cell carcinoma (BCC) is a malignant epithelial tumor that develops from the basal cell layer of the epidermis. It is predominantly found in older adults, with a high incidence in people aged 40 to 80. This form of cancer rarely metastasizes but is known to be locally invasive. In this report, we present a case of a 43-year-old male with a swelling on his upper lip. After thorough clinical, histopathological, and imaging assessments, a BCC was confirmed. He underwent full excision of the lesion with the surrounding tissue to ensure clear margins.

Clinical and Histopathological Effects of Isotretinoin on Neuroregeneration in Experimental Spinal Cord Injury

Aim: Spinal cord injury is an important problem, and a fully effective treatment for it has not yet been developed. Isotretinoin is a retinoid known for its anti-inflammatory effect. The present study aimed to evaluate whether isotretinoin has a positive impact on neural tissue in post-injury damage. Material and Methods: A total of 36 rats were randomly divided into 6 groups as control, sham, and injury with 14-day 7.5 mg/kg/day, 28-day 7.5 mg/kg/day, 14-day 15 mg/kg/day, and 28-day 15 mg/kg/day isotretinoin groups. Laminectomy was performed and spinal cord injury was produced by using the clip compression technique. Neurological examination was performed on days 1, 7, 14, and 28. After the treatment period, all rats were sacrificed, and their spinal cord samples were collected for histopathological assessment. Results: Groups receiving 7.5 mg/kg/day (p=0.048) and 15 mg/kg/day (p

Pneumonitis with amivantamab in squamous cell lung cancer with EGFR exon 20 insertion mutation: a case report

Abstract Background Amivantamab is a human antibody targeting epidermal growth factor receptor (EGFR) and c-MET. It is approved in patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion after progression with platinum-based chemotherapy. The most frequent adverse effects (AEs) are rash, infusion-related reactions, paronychia, and peripheral edema. Pneumonitis is a rare side effect, and there is no evidence about the possibility of reintroducing amivantamab after pulmonary toxicity. Clinical case A 56-year-old male was diagnosed with squamous cell lung cancer in 2021, with brain metastasis at diagnosis. The brain lesion was resected, and histopathologic assessment revealed metastasis from squamous cell lung cancer, and an exon 20 insertion mutation was identified. Chemotherapy with immunotherapy (carboplatin + paclitaxel + pembrolizumab) was initiated in October 2021, and progression was observed after three maintenance cycles. Amivantamab was started in May 2022, and partial response was observed after 2 months of treatment. In September 2022, the patient complained of dyspnea on exertion and dry cough. Computed tomography (CT) scan showed scattered ground-glass opacities. A pneumonitis grade 2 CTCAE was assumed, and corticosteroid therapy was started, with improvement in both symptoms and imaging abnormalities. After discussion with a multidisciplinary team, it was decided to restart treatment with amivantamab in January 2023 and there is no evidence of pulmonary toxicity to this date. Conclusion Amivantamab-related pneumonitis is a rare side effect and usually predicts drug discontinuation. In this clinical case, it was possible to reintroduce the drug without reoccurrence of the toxicity successfully. This possibility of reintroducing treatment after non-life-threatening toxicity occurs can be of great importance as therapeutic options for these patients are limited.

Assessing liver fibrosis in chronic liver disease: Comparison of diffusion-weighted MR elastography and two-dimensional shear-wave elastography using histopathologic assessment as the reference standard

Assessing liver fibrosis in chronic liver disease: Comparison of diffusion-weighted MR elastography and two-dimensional shear-wave elastography using histopathologic assessment as the reference standard

Protective Effects of NRF2 Activator Sulforaphane in Polyinosinic:Polycytidylic Acid-Induced In Vitro and In Vivo Model.

NRF2 is a nuclear transcription factor involved in the cellular protection against oxidative stress and inflammatory signaling. Sulforaphane is a known NRF2 activator used for its strong antioxidant and anti-inflammatory activity through regulation of Keap-1-HO-1 pathway. However, there is a limited exploration about the role of NRF2 activator, sulforaphane in regulation of poly(I:C)-induced oxidative stress, inflammation and injury in lung. Therefore, we aimed to evaluate the therapeutic effect of sulforaphane in poly(I:C)-induced responses using in vitro as well as in vivo model. We evaluated oxidative stress and inflammatory cytokines in poly(I:C)-induced RAW264.7 cells. We also employed in vivo animal study to evaluate tissue oxidative-antioxidative balance along with expression of NRF2, Keap-1, histopathological assessment by hematoxylin-eosin staining and picrosirius red staining to explore the protective mechanisms of sulforaphane in poly(I:C)-induced mouse model. Our results indicated that sulforaphane increased the expression of NRF2 and its downstream proteins. In addition, sulforaphane alleviated poly(I:C)-induced activation of the oxidative and pro-inflammatory pathways, histopathological changes, depleted expression of GSH and superoxide dismutase in lung tissue. This study suggested that sulforaphane may be one of the useful therapeutic alternatives for poly(I:C) induced lung injury and inflammation.

Endoscopic Endonasal Approach for Calcified Sellar/Parasellar Region Pathologies: Report of 11 Pituitary Adenoma Cases

Calcification in pituitary adenomas is a rare occurence and its differential diagnosis typically includes other sellar masses.Common calcifications in pituitary adenomas are classified into two morphological forms: capsular(eggshell-like)and multiple small nodular calcifications located within the adenoma.Also,there is a pituitary stone term.This study aims to present the results of calcified pituitary adenoma case series who underwent endoscopic endonasal approach(EEA)and the clinical,histopathological characteristics and surgical outcomes of these cases. This study conducted a retrospective cohort analysis of patients with calcified pituitary adenoma operated on by EEA between August 1997 and February 2024.The inclusion criteria were as follows:proven radiological calcification on pre-operative neuroimaging,intraoperative findings of calcification and definitive histopathological diagnosis of calcification.Among these patients,11 cases were included. The mean follow-up duration was 51.45±37.24 (6-118)months.Based on the pre-operative paranasal sinus computed tomography(CT)scans of patients,nine patients(81.8%)had intratumoral calcification,one(9.1%)had capsular(eggshell like)calcification and one(9.1%)had both intratumoral and capsular calcification.Moreover,stone-like calcifications were observed in four patients(36.4%),soft type calcifications in three(27.3%),hard-type calcifications in three(27.3%)and soft and hard-type calcifications in one(9%).Gross total resection(GTR)was achieved in nine patients(81.8%).Pathologic subtypes included non-functioning(n = 4),prolactin secreting(n = 3),growth hormone secreting adenoma(n = 2)and pituitary apoplexy(n = 2).Ten patients had psammomatous type calcifications and one had extensive ossification and osteoid metaplasia. Pre-operative radiological evaluation,intraoperative classification of calcification,and post-operative histopathological assessments are crucial in the treatment of calcified adenomas.Bases on these findings,the EEA,with its advantages,is an approach that can be effectively used in the management of these calcified adenomas.

Local Single-Dose Teriparatide Administration for BRONJ Prevention: Insights from a Rat Model Study.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) presents significant clinical challenges with uncertain treatment outcomes. Teriparatide, a fragment of human parathyroid hormone, shows potential in prevention strategies for BRONJ. This study investigates the impact of a single local dose of teriparatide on BRONJ prevention in an animal model. BRONJ was induced on 26 male Wistar rats via intraperitoneal injections of 0.06mg/kg Zoledronic acid weekly for four weeks. Following tooth extraction under general anesthesia, rats were divided into two groups: one received teriparatide via Gelatamp in the tooth socket and the other as a local injection in the vestibule. Control groups received the treatment without teriparatide. Histopathological assessments for bone remodeling, osteoclast number, inflammation, angiogenesis, and necrosis were performed after four weeks. Histopathological analysis indicated a significant improvement in bone remodeling and new bone formation in both treatment groups compared to controls, with notably better outcomes in the injection group (p = 0.01). Necrosis in the Gelatamp group was significantly higher in the control group than in the treatment group (p = 0.01), and bone formation was significantly higher in the injection group compared to the Gelatamp group (p = 0.03). Local administration of teriparatide significantly enhances bone remodeling and reduces necrosis, suggesting a potential role in the prevention of BRONJ. These findings support further clinical investigation into teriparatide as a preventive strategy against BRONJ.

Attenuating Cartilage Degeneration in a Low Mechanical Compression Rat Model Through Intra-Articular Injections of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells.

Mechanical stimulation significantly contributes to posttraumatic osteoarthritis (PTOA), a condition that impedes patient recovery following intra-articular injury. Effective treatment options for compression-induced injuries are limited. Bone marrow-derived mesenchymal stem cell (BMSC) implantation has emerged as a potential therapeutic breakthrough for joint diseases. The aim of this study was to attenuate the progression of PTOA induced by cyclic loading and demonstrate the potential effectiveness of BMSCs in a rat model of low mechanical compression. Using a rat model of compression-induced articular cartilage injury, assessments were conducted 2, 4, and 8 weeks after cyclic compressive loading. The expression of matrix metallopeptidase 13, transforming growth factor-beta 3 (TGF-β3), insulin-like growth factor 1 (IGF-1), and cleaved caspase-3 was evaluated through immunohistochemistry to investigate the mechanistic aspects underlying the prevention of compression-induced injury following BMSCs treatment. Intra-articular injections of BMSCs significantly improved scores in the OARSI (Osteoarthritis Research Society International) Osteoarthritis Cartilage Histopathology Assessment System and Histological-Histochemical Grading System. This treatment showed positive outcomes in maintaining high relative cell density and reducing proteoglycan loss after cyclic compression-induced injury. The expression patterns of IGF-1 and TGF-β3 provide valuable insights into the presence and distribution of these growth factors in healthy and injured cartilage. These findings highlight the efficacy of BMSCs treatment in attenuating the advancement of compression-induced injuries, albeit within a limited timeframe.

A Quantitative Method for Assessing Treatment-Related Changes within the Airway Mucosa in Patients with Chronic Bronchitis

No standardized method has yet been established for evaluating airway mucosal aberrancies associated with chronic obstructive pulmonary disease (COPD) or chronic bronchitis (CB). While goblet cell hyperplasia (GCH) is an established pathognomonic hallmark of the CB disease process, no standardized method exists for acquiring mucosal biopsies and assessing morphologic airway mucosa alterations. Additionally, the impacts from interventions targeting the airway mucosa are not well defined. In this context, a reliable and robust measure for assessing airway mucosa at baseline and subsequent to an intervention is critical for characterizing treatment-related changes. Can standardizing airway biopsy tissue collection and histopathological assessment methods generate a robust and repeatable measure to assess airway mucosa tissue characteristics in the setting of COPD/CB? Initial tissue collection and histological assessment methods were designed by integrating various aspects from previously published evaluations, applied to an initial tissue sample cohort, and then iteratively refined by independent pathologists. A standardized metric for histologic airway mucosa assessments was developed that specified tissue collection methods, including re-sampling airways at multiple time points to enable evaluation of treatment-related effects by incorporating scores for GCH, eosinophilia, and chronic inflammation, and the degree of GCH heterogeneity present within each sample. This multi-center study generated a robust, reproducible approach for assessing airway mucosa aberrancies in the setting of COPD/CB. The iterative approach established consistent tissue specimen recovery and a granular scoring matrix that enabled quantitative scoring of the various tissue findings with substantial histopathologic interrater reliability. ClinicalTrials.gov; NCT03107494, NCT04677465; URL: www. gov Australian New Zealand Clinical Trials Registry (ANZCTR); ACTRN12617000330347; URL: anzctr.org.au.

Preparation of gallic acid-loaded chitosan nanoparticles and their chemoprotective effects on N-ethyl-N-nitrosourea-induced hepatotoxicity and mortality in rats.

N-ethyl-N-nitrosourea (ENU) as n-nitrosamine and alkylating agent, ubiquitous within living cells and in the environment can act as a full carcinogen and induce tumor formation in various tissues such as liver. In this study, gallic acid-loaded chitosan nanoparticles (GANPs) were synthesized and evaluated for their chemopreventive effect against ENU-induced hepatotoxicity and mortality in rats. Twenty-four male Wistar rats were divided into four groups including: control, ENU (single doses of 50mg/kg via intraperitoneal injection), GA + ENU and GANPs + ENU. Animals were orally pretreated with GA (50 mg/kg) and GANPs (50 mg/kg) for 30 days, and liver injuries induced by ENU on the 31st day of study. After ENU administration, weight changes and mortality were monitored during 30 days, and then the animals were sacrificed and alpha-fetoprotein (AFP) as a tumor marker, liver function tests (ALT, AST and ALP), oxidative stress markers (GSH and MDA), mitochondrial toxicity parameters, and histopathological assessment were evaluated. Except for AFP and MDA, ENU caused significant elevation of liver enzymes, mitochondrial ROS formation, collapse of mitochondrial membrane potential depletion of GSH, histopathological abnormalities and mortality in rats. Our data showed that GANPs significantly increased the survival of rats by up to 66%, delayed in death time and prevented weight changes after exposure to ENU. Moreover, GANPs restored liver enzyme levels, ROS formation, mitochondrial dysfunction, GSH levels, and histopathological abnormalities towards normal. Our findings suggest that GANPs revealed a significant protective effect against deadly toxicity induced by ENU as an alkylating full carcinogen agent in liver tissue.

Comparative Effects of Monascin and Monascinol Produced by Monascus pilosus SWM-008 on Pro-Inflammatory Factors and Histopathological Alterations in Liver and Kidney Tissues in a Streptozotocin–Nicotinamide-Induced Rat Model

Monascinol (Msol), an analog of monascin (MS) produced by Monascus pilosus, possesses potential anti-inflammatory properties. This study compares the effects of M. pilosus SWM-008 fermented red mold rice, which contains the functional components MS and Msol, on liver and kidney damage related to diabetic complications in rats. An animal model of liver and kidney injury was induced by an intraperitoneal injection of streptozotocin (STZ) at 65 mg/kg body weight combined with nicotinamide (NA) at 150 mg/kg body weight. Our findings indicate that Msol significantly reduces STZ-NA induced pro-inflammatory markers, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) in both liver and kidney tissues. Significant improvements were noted in the histopathological assessments. Msol was more effective than MS in suppressing renal IL-1β and COX-2 expressions. In summary, the findings indicate that Msol shows potential as a novel therapeutic agent for treating liver and kidney injuries associated with diabetic complications.

A Rare Presentation of IgG4-Related Disease with Gastric Outlet Obstruction and Lymphadenopathy: A Case Report.

Background. IgG4-related disease (IgG4-RD) is a systemic immune-mediated condition characterized by fibro-inflammatory infiltration. It is a rare disease that can affect any organ, with the involvement of the stomach being particularly uncommon. The clinical manifestations of IgG4-RD are highly variable depending on the type and number of organs involved and mirror the symptoms of other conditions. Case presentation. We report a 61-year-old man who presented with symptoms of gastric outlet obstruction and was subsequently diagnosed with IgG4-RD. The patient experienced recurrent vomiting, early satiety, and substantial weight loss. Imaging studies revealed luminal narrowing in the pyloric region, prompting further endoscopic evaluation. Initial endoscopic biopsies were nondiagnostic. Because the patient's clinical symptoms and previous investigations were highly indicative of malignancy, he underwent distal gastrectomy with Roux en Y anastomosis. However, final histopathology revealed lymphoplasmacytic infiltration and dense fibrosis, confirming the diagnosis of IgG4-RD; no malignant cells were noted. The surgery resulted in symptom improvement. Conclusion. This presentation highlights the diagnostic challenges of IgG4-RD with gastric outlet obstruction, emphasizing the significance of a multidisciplinary approach involving clinical, radiological, and histopathological assessments to achieve an accurate diagnosis and develop tailored management strategies.

Surface-modified liposomal in-situ nasal gel enhances brain targeting of berberine hydrochloride for Alzheimer's therapy: optimization and in vivo studies.

This work aimed to formulate surface-modified berberine hydrochloride (BER)-loaded liposomes containing in-situ nasal gel for bran targeting. The liposomes were prepared by ethanol-injection method and optimized following a 32 full-factorial design. Size, morphology, zeta potential, ex-vivo permeation, and in-vitro release were estimated. The surface of optimized liposome was modified with ascorbic acid. The size of surface-modified liposomes was bigger (191.4 nm) than the unmodified liposomes (171 nm). Surface-modified liposomes were embedded in in-situ gel using poloxamer and Carbopol 934P. Liposomal in-situ gel showed higher permeation (71.94%) in contrast to the plain gel (46.64%). In-vivo pharmacokinetic examination of payload from liposomal in-situ gel displayed higher concentration in brain (Cmax of 93.50 ng/mL). The liposomal in-situ nasal gel had a higher drug targeting efficiency (138.43%) and a higher drug targeting potential (27.77%) confirming improved brain targeting. In male Wistar rats, the pharmacodynamic parameters (path length and escape latency) were evaluated with trimethyl tin-induced neurodegeneration. Animals treated with BER-loaded in-situ gel significantly decreased escape latency and path length in comparison to the control group. Histopathological assessment showed that the formulated gel was safe for intranasal administration. The developed formulation has the potential to effectively enhance the efficacy of BER in Alzheimer's disease management.

Classification of pediatric soft and bone sarcomas using DNA methylation-based profiling

Pediatric sarcomas present heterogeneous morphology, genetics and clinical behavior posing a challenge for an accurate diagnosis. DNA methylation is an epigenetic modification that coordinates chromatin structure and regulates gene expression, determining cell type and function. DNA methylation-based tumor profiling classifier for sarcomas (known as sarcoma classifier) from the German Cancer Research Center (Deutsches Krebsforschungszentrum) was applied to 122 pediatric sarcomas referred to a reference pediatric oncology hospital. The classifiers reported 88.5% of agreement between histopathological and molecular classification confirming the initial diagnosis of all osteosarcomas and Ewing sarcomas. The Ewing-like sarcomas were reclassified into sarcomas with BCOR or CIC alterations, later confirmed by orthogonal diagnostic techniques. Regarding the CNAs profile, osteosarcomas had several chromosomal gains and losses as well as chromothripsis, whereas Ewing sarcomas had few large events, such as amplifications of chromosomes 8 and 12. The molecular classification together with clinical and histopathological assessment could improve the diagnosis of pediatric sarcomas although there are limitations to deal with more rare classes. This study provides an increase in the number of sarcomas evaluated for DNA methylation profiling in the pediatric population.

Label-Free Prediction of Tumor Metastatic Potential via Ramanome.

Assessing metastatic potential is crucial for cancer treatment strategies. However, current methods are time-consuming, labor-intensive, and have limited sample accessibility. Therefore, this study aims to investigate the urgent need for rapid and accurate approaches by proposing a Ramanome-based metastasis index (RMI) using machine learning of single-cell Raman spectra to rapidly and accurately assess tumor cell metastatic potential. Validation with various cultured tumor cells and a mouse orthotopic model of pancreatic ductal adenocarcinoma show a Kendall rank correlation coefficient of 1 compared to Transwell experiments and histopathological assessments. Significantly, lipid-related Raman peaks are most influential in determining RMI. The lipidomic analysis confirmed strong correlations between metastatic potential and phosphatidylcholine, phosphatidylethanolamine, cholesteryl ester, ceramide, and bis(monoacylglycero)phosphate, crucial in cell membrane composition or signal transduction. Therefore, RMI is a valuable tool for predicting tumor metastatic potential and providing insights into metastasis mechanisms.

Comparative Evaluation of Wound Healing Efficacy of Bombyx mori L. Body Extracts, Gland Extracts, and Cocoon for the Treatment of Second-Degree Burns: A Pilot Study

Background: The silkworm (Bombyx mori L.) and its cocoon are rich in bioactive proteins like sericin and fibroin, as well as enzymes such as serrapeptase, which possess anti-inflammatory and skin-healing properties. This study aimed to evaluate the in vivo effects of various silkworm products, including cocoon patches and extracts from the silkworm body and glands, on the healing of second-degree burns. Methods: Hairless, female SKH-2 mice were used to model second-degree burns. The study tested formulations containing 1%, 10%, or 20% silkworm body or gland extracts, as well as cocoon-derived patches. In addition to histopathological and clinical assessments, the study measured parameters including burn size, hydration, transepidermal water loss and thickness. Results: The results of this study demonstrated that, in terms of primary outcomes (complete healing), both the silkworm cocoon and the 20% body extract significantly promoted wound healing, with similar efficacy. All body extracts showed statistical significance in wound area reduction, while the gland extracts had no significant effect. Histopathological evaluation confirmed the superior healing potential of the body extracts increasing by increased concentration and cocoon. This novel insight into the therapeutic properties of silkworm body extracts opens new opportunities for the development of cost-effective, renewable second-degree burn healing treatments.

Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by blue light in the treatment of facial cutaneous squamous cell carcinoma in situ

Background: Cutaneous squamous cell carcinoma in situ (isSCC) is a common skin cancer occurring from sun exposure and often appears on the face. Treatment is primarily surgical but less invasive treatments are desirable. Currently, aminolevulinic acid for photodynamic therapy (ALA-PDT) is approved in the US and Canada for the treatment of single and multiple non-hyperkeratotic actinic keratoses of the face and scalp. This study evaluated the safety, tolerability, and efficacy of ALA-PDT for treatment of facial isSCC.Methods: Thirty-two patients with biopsy-confirmed isSCC on the face were recruited. Lesions 0.4–1.3 cm in diameter were included. Per the actinic keratosis treatment protocol, the lesion was debrided with a 4 x 4 gauze and ALA 20% topical solution was applied to the lesion and adjacent skin and incubated for 18–24 hours, followed by blue light therapy 16 minutes 40 seconds at 10 J/cm2. Patients underwent two treatments with ALA-PDT spaced 28 +/- 3 days apart. The area of the original lesion was excised eight weeks following the second treatment for histopathological assessment. The primary efficacy endpoint was the complete absence histologically of the isSCC at end of treatment. The secondary efficacy endpoint was the achievement of clinical clearance of the skin lesion. Safety assessment was done through adverse events and local skin reactions (LSRs; erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) and site pain within 15 minutes of each treatment session.Results: Of the 32 patients enrolled, two did not complete the study. No residual SCCis was detected in 30/30 (100%) patients. Clinical clearance was achieved in 30/30 (100%) of the patients by the end of treatment. None of the patients experienced related adverse events and only 2/30 (5%) experienced an AE of hypertension and was considered to be unrelated. The most common LSRs were erythema and scaling and were primarily mild, seen to occur immediately after both treatments and diminished over time. The average median ± SD immediate post-treatment pain score was 2.56 ± 2.15 on the VAS scale.Conclusion: The ALA-PDT protocol outlined in this study appears to be a very effective, safe and well-tolerated treatment option for isSCC on the face.

The challenge to identify sensitive safety biomarkers of peripheral neurotoxicity in the rat: A collaborative effort across industry and academia (IMI NeuroDeRisk project)

Peripheral nervous system (PNS) toxicity assessment in non-clinical safety studies is challenging and relies mostly on histopathological assessment. The present work aims to identify blood-based biomarkers that could detect peripheral neuropathy in rats upon exposure to neurotoxic compounds. Three anticancer agents (oxaliplatin, cisplatin, paclitaxel) and a developmental compound (NVS-1) were assessed in male rats (Wistar Han). Clinical and/or functional endpoints (i.e., electronic Von Frey, Cold Plate, and Paw Pressure tests) and blood biomarkers (i.e., neurofilament light chain (NfL), neurofilament heavy chain (NF-H), microtubule-associated protein Tau (Tau), neuron specific enolase (NSE), vascular endothelial growth factor A (VEGFA), and glial fibrillary acidic protein (GFAP)) were assessed. Drug exposure and histopathological evaluations were conducted on selected nervous tissues. Oxaliplatin, cisplatin and paclitaxel treatment resulted in a significant decrease of nociceptive thresholds. Clinical signs suggestive of PNS toxicity were observed with NVS-1. NfL was consistently increased in the NVS-1 study and correlated with moderate microscopic findings in dorsal root ganglia (DRG). Only minimal microscopic findings were observed in oxaliplatin-treated animals, whereas no treatment-related microscopic findings were observed in animals treated with cisplatin and paclitaxel. For all compounds, exposure was confirmed in the PNS tissues. Clinical and functional changes were observed with all the compounds evaluated. NfL levels in plasma proved to be the most sensitive indicator of PNS toxicities, capturing moderate nervous degeneration in DRG. A combined approach that includes both functional assessments and biomarker measurements offers a more comprehensive evaluation than histopathological analysis alone when monitoring drug-induced neurotoxicity in rat models.