Pre-Incisional and Multiple Intradermal Injection of N-Acetylcysteine Slightly Improves Incisional Wound Healing in an Animal Model.

The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing.

Tumour-Induced Osteomalacia-A Long Way to the Diagnosis Facilitated by [68Ga]Ga-DOTATATE PET/CT.

Background: Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. Detecting the primary tumour in TIO is challenging using conventional imaging methods. This study assesses the efficacy of [68Ga]Ga-DOTATATE PET/CT in identifying the primary tumour. Methods: Six patients with suspected TIO underwent [68Ga]Ga-DOTATATE PET/CT. The patients' clinical history and biochemical parameters were analysed. Results: [68Ga]Ga-DOTATATE PET/CT successfully identified primary tumours in four patients (femoral bones for two, iliac bone for one, subcutaneous tissue of pubic region for one). Tumour removal led to clinical and laboratory improvement. In one patient, PET/CT showed rib uptake, but the biopsy was negative. One patient showed no tumour lesions on PET/CT despite clinical evidence. Two patients had focal recurrence at the primary tumour site, detected by follow-up PET/CT. Conclusions: [68Ga]Ga-DOTATATE PET/CT is a valuable tool for detecting primary tumours in TIO, aiding in accurate diagnosis and guiding surgery, leading to improved outcomes. Further research is needed to validate these findings and explore [68Ga]Ga-DOTATATE PET/CT in other paraneoplastic syndromes.

Comparison of Multiparametric MRI, [68Ga]Ga-PSMA-11 PET-CT, and Clinical Nomograms for Primary T and N Staging of Intermediate-to-High-Risk Prostate Cancer.

PURPOSE OF THE REPORT: Although multiparametric magnetic resonance imaging (mpMRI) is commonly used for the primary staging of prostate cancer, it may miss non-enlarged metastatic lymph nodes. Positron emission tomography-computed tomography targeting the prostate-specific membrane antigen (PSMA PET-CT) is a promising method to detect non-enlarged metastatic lymph nodes, but more data are needed. MATERIALS AND METHODS: In this single-center, prospective study, we enrolled patients with intermediate-to-high-risk prostate cancer scheduled for radical prostatectomy with pelvic node dissection. Before surgery, prostate imaging with mpMRI and PSMA PET-CT was used to assess lymph node involvement (LNI), extra-prostatic extension (EPE), and seminal vesicle involvement (SVI). Additionally, we used clinical nomograms to estimate the risk of these three outcomes. RESULTS: Of the 74 patients included, 61 (82%) had high-risk prostate cancer, and the rest had intermediate-risk cancer. Histopathology revealed LNI in 20 (27%) patients, SVI in 26 (35%), and EPE in 52 (70%). PSMA PET-CT performed better than mpMRI at detecting LNI (area under the curve (AUC, 95% confidence interval): 0.779 (0.665-0.893) vs. 0.655 (0.529-0.780)), but mpMRI was better at detecting SVI (AUC: 0.775 (0.672-0.878) vs. 0.585 (0.473-0.698)). The MSKCC nomogram performed well at detecting both LNI (AUC: 0.799 (0.680-0.918)) and SVI (0.772 (0.659-0.885)). However, when the nomogram was used to derive binary diagnoses, decision curve analyses showed that the MSKCC nomogram provided less net benefit than mpMRI and PSMA PET-CT for detecting SVI and LNI, respectively. CONCLUSIONS: mpMRI and [68Ga]Ga-PSMA-11 PET-CT are complementary techniques to be used in conjunction for the primary T and N staging of prostate cancer.

Prostate-specific membrane antigen expression in intracranial lesions - a review of the primary, metastatic, and nonneoplastic lesions.

Prostate-specific membrane antigen (PSMA) is a membrane protein originally discovered in prostate cancer cells. It is widely used at all stages of prostate cancer diagnosis. Several studies have highlighted its possible wide application in other cancers. This review discusses the potential use of positron emission tomography with labelled PSMA for the diagnosis or differentiation of intracranial lesions. Given the numerous reports on the usefulness of PSMA in the diagnosis of brain tumours of glial origin, the focus is on lesions of a different aetiology.

A case of a patient with biochemical recurrence and inadequate results of suspected bone metastases in imaging methods - will [68Ga]Ga-PSMA-11 PET/CT give us an answer?

We present a case of a 79-year-old asymptomatic patient with prostate adenocarcinoma, Gleason score 9 (4 + 5), with the initial prostate-specific antigen (PSA) level of 17 ng/mL, treated with radiotherapy and hormonotherapy, who was diagnosed with the rapid growth of PSA levels up to 78.8 ng/mL. Due to suspected bone metastases, first, bone scintigraphy was performed. However, it showed only one intense "hot" lesion in the Th7 projection. This image was not consistent with a high level of PSA, for which reason a computed tomography (CT) scan was performed. It revealed lytic metastasis in Th7 and one more suspicious change in L2, which still was inconsistent with the patient's clinical picture. The patient was referred for [68Ga]Ga-PSMA-11 PET/CT. It showed an uncountable number of foci of increased marker accumulation in bones, mostly without visible change in CT examination. This case showed that the clinical results and suspicions of the advancement of a patient's disease are still the most important data in care and therapy planning.

68 Ga-Prostate-Specific Membrane Antigen PET/CT in Ovarian Tumors : Potential to Differentiate Benign and Malignant Tumors Before Surgery: A Preliminary Report.

PURPOSE OF THE REPORT: Ovarian cancer is usually diagnosed in an advanced stage of disease due to the absence of specific symptoms and a lack of sensitive diagnostic methods. Prostate-specific membrane antigen (PSMA) is expressed on prostate cancer cells but can be found in other tumors such as ovarian cancer.The aim of this pilot study was to evaluate the feasibility of using 68 Ga-PSMA-11 PET/CT in detection of ovarian neoplasm before surgical treatment. PATIENTS AND METHODS: Eight women with mean age of 56.0 ± 16.2 years were included in the study. All patients underwent transvaginal ultrasound followed by CT scan of the chest and abdomen as qualification for surgery. Within a 1-week interval, PET/CT was performed on a Siemens Biograph scanner, 60 minutes after injection of 2 MBq/kg 68 Ga-PSMA-11. RESULTS: In 3 cases (37.5%), the 68 Ga-PSMA-11 PET/CT was positive, whereas histological examination confirmed 2 serous ovarian cancer cases and 1 ovarian borderline tumor. The SUV max in the serous ovarian cancer was 8.7 and 4.1, and in the borderline ovarian tumor, it was 13.8. No correlation was found between antigen CA-125 level and 68 Ga-PSMA expression. Range of tumor SUV max was not correlated with stage of disease. The remaining 62.5% (5/8) were negative in 68 Ga-PSMA-11 PET/CT, and histopathology confirmed benign pelvic tumor. CONCLUSIONS: The initial experience supports the potential to use 68 Ga-PSMA-11 in ovarian cancer to differentiate malignant and benign tumors before surgery.This study was approved by the Ethical Committee of the Medical University of Warsaw (KB/2/A/2018).

Ga-68-PSMA-11 PET/CT in Patients with Biochemical Recurrence of Prostate Cancer after Primary Treatment with Curative Intent-Impact of Delayed Imaging.

The presence of prostate-specific membrane antigen (PSMA) on prostate cancer cells and its metastases allows its use in diagnostics using PET/CT. The aim of this study was to evaluate the usefulness of delayed phase images in the Ga-68-PSMA-11 PET/CT. Methods: 108 patients with prostate cancer (median age: 68.5 years, range: 49−83) were referred for Ga-68-PSMA-11 PET/CT due to biochemical relapse (PSA (prostate-specific antigen) (3.2 ± 5.4 ng/mL). Examinations were performed at 60 min, with an additional delayed phase of the pelvis region at 120−180 min. Results: The Ga-68-PSMA-11 PET/CT showed lesions in 86/108 (80%) patients; detection rate depending on the PSA level: 0.2 < PSA < 0.5 ng/mL vs. 0.5 ≤ PSA < 1.0 ng/mL vs. 1.0 ≤ PSA < 2.0 ng/mL vs. PSA ≥ 2.0 ng/mL was 56% (standard vs. delay: 56 vs. 56%) vs. 60% (52 vs. 60%) vs. 87% (83 vs. 87%) vs. 82% (77 vs. 82%) of patients, respectively. The delayed phase had an impact on the treatment in 14/86 patients (16%) (p < 0.05): 7 pts increased uptake was seen only after 60 min, which was interpreted as physiological or inflammatory accumulation; the delayed image showed increased accumulation in 7 patients only: 4 in regional lymph nodes, 1 in local recurrence, and 2 patients with local recurrence showed additional foci. Conclusions: Delayed phase of Ga-68-PSMA-11 PET/CT has an impact on treatment management in 16% of patients.

Expression of glutamate carboxypeptidase II in the glial tumor recurrence evaluated in vivo using radionuclide imaging.

Glutamate carboxypeptidase II (GCP), also known as prostate specific membrane antigen (PSMA) has been found to be expressed in glioma vasculature in in-vitro studies. GCP expression can be traced with the use of [68Ga]Ga-PSMA-11 PET/CT used routinely for prostate cancer imaging. The aim of this paper was to analyze GCP expression in the recurrent glial tumors in vivo. 34 patients (pts.) aged 44.5 ± 10.3 years with suspicion of recurrence of histologically confirmed glioma grade III (6 pts.) and grade IV (28 pts.) were included in the study. All patients underwent contrast-enhanced MR and [68Ga]Ga-PSMA-11 PET/CT. No radiopharmaceutical-related adverse events were noted. PET/CT was positive in all the areas suspected for recurrence at MR in all the patients. The recurrence was confirmed by histopathological examinations or follow-up imaging in all cases. The images showed a very low background activity of the normal brain. Median maximal standard uptake value (SUVmax) of the tumors was 6.5 (range 0.9-15.6) and mean standard uptake value (SUVmean) was 3.5 (range 0.9-7.5). Target-to-background (TBR) ratios varied between 15 and 1400 with a median of 152. Target-to-liver background ratios (TLR) ranged from 0.2 to 2.6, the median TLR was 1.3. No significant difference of the measured parameters was found between the subgroups according to the glioma grade. High GCP expression in the recurrent glioma was demonstrated in-vivo with the use of [68Ga]Ga-PSMA-11 PET/CT. As the treatment options in recurrent glioma are limited, this observation may open new therapeutic perspectives with the use of radiolabeled agents targeting the GCP.

Myelofibrosis Pattern in 68Ga-PSMA PET/CT of a Patient With Recurrence Prostate Cancer.

ABSTRACT: We present the case of a 64-year-old man with prostate adenocarcinoma, Gleason score 7, after radical prostatectomy and adjuvant radiotherapy in 2015. Because of high risk and perineural invasion, hormonotherapy was indicated. PSA levels began to rise, and at PSA level of 0.9 ng/mL, he was referred for 68Ga-PSMAPET/CT. It showed focal uptake in the right femur and diffuse tracer accumulation in bone marrow. The patient was previously diagnosed with macrocytic anemia. He underwent bone marrow biopsy. Based on clinical, laboratory, and histopathology results, myelodysplastic fibrosis was diagnosed. Diffuse uptake of 68Ga-PSMA was the sign of the bone marrow stimulation.

Targeted alpha therapy for glioblastoma.

According to the 2021 World Health Organization Classification of Tumors of the Central Nervous System, glioblastoma (GB) is a primary brain tumor and presents with the worst prognosis. Due to its infiltrating characteristic, molecular heterogeneity, and only partly preserved function of the blood-brain barrier, the median overall survival time is short (9-15 months), regardless of comprehensive treatment including surgery, radiotherapy, and chemotherapy. Several novel treatment strategies are under investigation. Unfortunately, none of them produced successful results; 90% of patients have a recurrence of the disease within 6 months. Local administration of the drug could be a promising approach to delivering treatment with minimized side effects, due to the recurrence of 95% glioblastomas in a margin of 2 cm at the primary site. Several ligand-receptor systems have been evaluated, such as targeting tenascin, the extracellular matrix protein, or radiolabeled somatostatin analogs, as it is overexpressed with the SSTR-2 receptor system in around 80% of gliomas. Moreover, this study revealed that the NK-1 receptor is overexpressed in GB, suggesting that substance P (SP) may serve as a ligand. A variety of radioisotopes, beta- (131I, 90Y, or 177 Lu) and alpha emitters (213Bi, 225Ac, or 211At), with different physical properties were tested for treatment. Alpha particles have many advantages over beta radiation such as short range with higher linear energy transfer. According to that characteristic, it is extremely dose delivered to the targeted cells, while reducing harm to nearby healthy tissue. Additionally, the biological effect of alpha radiation is independent of the cell cycle phase, cell oxygenation and O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation status. In this article, we summarize the experience with local treatment of primary and secondary GBs with locally used radioisotopes such as [213Bi]Bi-DOTA-SP or [225Ac]Ac-DOTA-SP.

Single Dose of N-Acetylcysteine in Local Anesthesia Increases Expression of HIF1α, MAPK1, TGFß1 and Growth Factors in Rat Wound Healing.

In this study, we aimed to investigate the influence of N-acetylcysteine (NAC) on the gene expression profile, neoangiogenesis, neutrophils and macrophages in a rat model of incisional wounds. Before creating wounds on the backs of 24 Sprague-Dawley rats, intradermal injections were made. Lidocaine-epinephrin solutions were supplemented with 0.015%, 0.03% or 0.045% solutions of NAC, or nothing (control group). Scars were harvested on the 3rd, 7th, 14th and 60th day post-surgery. We performed immunohistochemical staining in order to visualize macrophages (anti-CD68), neutrophils (anti-MPO) and newly formed blood vessels (anti-CD31). Additionally, RT-qPCR was used to measure the relative expression of 88 genes involved in the wound healing process. On the 14th day, the number of cells stained with anti-CD68 and anti-CD31 antibodies was significantly larger in the tissues treated with 0.03% NAC compared with the control. Among the selected genes, 52 were upregulated and six were downregulated at different time points. Interestingly, NAC exerted a significant effect on the expression of 45 genes 60 days after its administration. In summation, a 0.03% NAC addition to the pre-incisional anesthetic solution improves neovasculature and increases the macrophages' concentration at the wound site on the 14th day, as well as altering the expression of numerous genes that are responsible for the regenerative processes.

N-Acetylcysteine Added to Local Anesthesia Reduces Scar Area and Width in Early Wound Healing-An Animal Model Study.

The aim of the study was to evaluate if a pre-incisional N-acetylcysteine (NAC) treatment altered the process of wound healing in a rat model. The dorsal skin of 24 Sprague-Dawley rats was incised in six locations. Before the incisions were made, skin was injected either with lidocaine and epinephrine (one side) or with these agents supplemented with 0.015%, 0.03%, or 0.045% NAC (contralaterally). Photographic documentation of the wound healing process was made at 11 time points. Rats were sacrificed 3, 7, 14, or 60 days after incision to excise scars for histological analysis. They included: Abramov scale scoring, histomorphometry analysis, and collagen fiber arrangement assessment. Skin pretreated with 0.03% NAC produced the shortest scars at all analyzed time points, though this result was statistically insignificant. At this NAC concentration the scars had smaller areas on the third day and were narrower on the day 4 compared with all the other groups (p < 0.05). On day 7, at the same concentration of NAC, the scars had a higher superficial concentration index (p = 0.03) and larger dermal proliferation area (p = 0.04). NAC addition to pre-incisional anesthetic solution decreased wound size and width at an early stage of scar formation at all concentrations; however, with optimal results at 0.03% concentration.

Epithelial Cells of Deep Infiltrating Endometriosis Harbor Mutations in Cancer Driver Genes.

Endometriosis is an inflammatory condition manifested by the presence of endometrial-like tissue outside of the uterine cavity. The most common clinical presentations of endometriosis are dysmenorrhea, infertility, and severe pelvic pain. Few hypotheses attempt to explain the pathogenesis of endometriosis; however, none of the theories have been fully confirmed or considered universal. We examined somatic mutations in eutopic endometrium samples, deep endometriotic nodules and peripheral blood from 13 women with deep endometriosis of the rectovaginal space. Somatic variants were identified in laser microdissected samples using next-generation sequencing. A custom panel of 1296 cancer-related genes was employed, and selected genes representing cancer drivers and non-drivers for endometrial and ovarian cancer were thoroughly investigated. All 59 detected somatic variants were of low mutated allele frequency (<10%). In deep ectopic lesions, detected variants were significantly more often located in cancer driver genes, whereas in eutopic endometrium, there was no such distribution. Our results converge with other reports, where cancer-related mutations were found in endometriosis without cancer, particularly recurrent KRAS mutations. Genetic alterations located in ectopic endometriotic nodules could contribute to their formation; nevertheless, to better understand the pathogenesis of this disease, more research in this area must be performed.

miR-96-5p, miR-134-5p, miR-181b-5p and miR-200b-3p heterogenous expression in sites of prostate cancer versus benign prostate hyperplasia-archival samples study.

MicroRNAs are involved in various pathologies including cancer. The aim of the study was to assess the level of expression of miR-96-5p, -134-5p, -181b-5p, -200b-3p in FFPE samples of prostate cancer, adjacent cancer-free tissue, and benign prostatic hyperplasia. Samples of 23 FFPE prostate cancer and 22 benign prostatic hyperplasias were dissected and HE stained. Compartments of tumor tissue and adjacent healthy glandular tissue were isolated from each sample using Laser Capture Microdissection. Total RNA was isolated from dissected tissues. Expression of miR-96-5p, miR-134-5p, 181b-5p, and miR-200b-3p was determined by real-time RT-qPCR method. The expression of miR-200b-3p was significantly higher in cancerous prostate: both in adenocarcinomatous glands and in the adjacent, apparently unaffected glands compared to BPH samples. The expression of miR-181b-5p was lower in in both prostate cancer tissues and adjacent tissue compared to BPH samples. Expression of miR-96-5p and miR-134-5p was lower in prostate cancer tissues compared to BPH. Levels of miR-96-5p, miR-134-5p, and 181b-5p negatively correlated with the Gleason score. Given further studies, miR-96-5p, miR-134-5p and especially miR-200b-3p and miR-181b-5p may differentiate BPH and PC.

The expression of MMP-14 and microRNA-410 in FFPE tissues of human endometrial adenocarcinoma.

Endometrial cancer (EC) is the most common gynecological malignancy in Europe and North America. It is classified into two types exhibiting different characteristics and prognosis. Type I is an estrogen-dependent tumor, histologically classified as low grade and low stage, usually with an excellent prognosis. Type II EC is unrelated to estrogen stimulation and is characterized by a poor prognosis. MicroRNAs (miRNAs, miRs) are small non-coding RNA polynucleotides that regulate gene expression post-transcriptionally. Various dysregulations in microRNA expression are often considered to have an impact on the diagnosis, prognosis and overall survival in patients diagnosed with different types of cancers. Recent data suggest that microRNAs play an important role in the pathogenesis of EC. The aim of the study was to evaluate the involvement of matrix metaloprotease 14 (MMP-14) and microRNA-410 in formation of the EC tumor. To this end expression of MMP-14 and microRNA-410 was assessed within the cancer, transient and healthy zones in the histological sections of tumours using immunohistochemical staining and laser capture microdissection (LCM) followed by a quantitative real-time PCR. The results revealed significantly higher expression of MMP-14 in the cancer tissue zone in comparison to the healthy tissue zone, as well as a lower expression of microRNA-410 in the cancer zone compared with the healthy zone. This reverse correlation may suggest a regulatory role of miRNA-410 in modulating levels of MMP-14 in EC. This is the first report on such regulation in human endometrial cancer.