Evaluation of Botox treatment in patients with chronic scrotal pain: Protocol for a randomized double-blinded control trial.

Background: Chronic scrotal pain is a common condition with a prevalence of 2.5-4.8% in male outpatients. Up to 40% of these patients report depressive symptoms and many feel isolated. Minimal invasive treatment is lacking, while spermatic cord injections of Botox® (BTX) have been proposed to offer long-term pain relief. Study Design: This research protocol comprises a prospective multicentre, randomized, double-blinded clinical trial drawing patients from other urological departments in the region of Southern Denmark. End Points: The primary end point will be reduction in pain evaluated by visual analogue score for pain at 3 months. Secondary end point will be length of effect of BTX injections along with changes in quality of life. Patients and Methods: The study will include 50 patients for randomization to either spermatic cord block with 100 IE BTX or sterile saline. All patients will prior to randomization undergo physical examination and will be asked to fulfil multiple questionnaires regarding pain and impact in daily life, that is, (1) visual analogue score for pain, (2) quality of life (EQ-5D-5L), (3) Chronic Prostatitis Symptom Index (NIH-CPSI), (4) ICD-10 depression questionnaire (MDI), (5) Likert global assessment scale, and (6) International Index of Erectile Function questionnaire. Physical examination and fulfilment of the questionnaires will be repeated multiple times throughout the study period of 12 weeks. After this time point, patients will be unblinded, and the control arm will be given the opportunity of cross-over.

Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges.

It is well known that N-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these to retrospectively identified cases of post-HSE NMDARE in Denmark, using a national cohort database of autoimmune encephalitis (AE) and two regional databases of infectious encephalitis patients. We identified 80 post-HSE NMDARE cases in the literature, 66% being children, who more often presented movement disorders, decreased consciousness, and sleep disturbances compared to adults. Eight patients with post-HSE NMDARE were identified from the national cohort database of AE, none being children. Forty-four HSE patients were identified from the regional infectious encephalitis databases. Of these, 16 (36%) fulfilled the Graus criteria for probable/definite NMDARE, and eight (18%) presented a prolonged/relapsing disease course. Ten (23%) were tested for AE during hospitalization. Six (14%) had leftover cerebrospinal fluid available for retrospective autoantibody testing. One out of these six patients (17%) harbored NMDARE antibodies. Thus, in total, nine post-HSE NMDARE patients have been identified in Denmark from 2009 to 2021. Comparing the adult Danish patients to the literature, Danish patients were older, but the clinical phenotype and paraclinical findings were similar. Overall, the incidence of adult post-HSE NMDARE in the Region of Southern Denmark was 0.17 per million people per year and only 7% of adult HSE patients in the region were diagnosed with post-HSE NMDARE. Our findings suggest that adult patients are still underdiagnosed and the absence of pediatric cases diagnosed with post-HSE NMDARE in Denmark is highly concerning.

Gastrin-releasing peptide receptor as theranostic target in estrogen-receptor positive breast cancer: A preclinical study of the theranostic pair [55Co]Co- and [177Lu]Lu-DOTA-RM26.

BACKGROUND: Patients with advanced metastatic estrogen receptor-positive breast cancer often develop resistance to standard treatments, leading to uncontrolled progression. Thus, innovative therapies are urgently needed. The gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers, including breast cancer, making it an interesting theranostic target. RM26, a GRPR-targeting antagonist, has demonstrated promising in vivo kinetics in prostate cancer models. This study evaluated the theranostic capabilities of [55Co]Co-/[177Lu]Lu-DOTA-RM26 in vitro in estrogen receptor-positive breast cancer cells and assessed the diagnostic potential of [55Co]Co-DOTA-RM26 in vivo in a breast cancer mouse model. METHODS: We analyzed the binding specificity of [57Co]Co-/[177Lu]Lu-DOTA-RM26 in T47D breast cancer cells, using [57Co]Co-DOTA-RM26 as a surrogate for [55Co]Co-DOTA-RM26. The therapeutic efficacy of increasing [177Lu]Lu-DOTA-RM26 concentrations was determined via viability assay in vitro. Ex vivo biodistribution of [57Co]Co-DOTA-RM26 (17.2 ± 2.7 kBq, 33 ± 5.2 pmol/mouse) was investigated in 12 mice (n= 4/group) with orthotopic breast cancer tumors. The mice were sacrificed at 4 and 24 h post-injection (pi), including a blocking group (20 nmol of unlabeled [Tyr4]-Bombesin) at 4 h pi. For imaging, two tumor-bearing mice underwent [55Co]Co-DOTA-RM26 PET/CT, 4 and 24 h pi (2.8 ± 0.2 MBq, 167.5 ± 0.5 pmol/mouse), with or without GRPR blocking. RESULTS: In vitro studies revealed high, specific binding of [57Co]Co-DOTA-RM26 (43 ± 1 % of total added activity per 106 cells (%IA/106)) and [177Lu]Lu-DOTA-RM26 (37 ± 4 %IA/106). The activity was predominantly localized at the cell surface: 71 ± 3 % and 80 ± 6 % for [57Co]Co-DOTA-RM26 and [177Lu]Lu-DOTA-RM26, respectively. [177Lu]Lu-DOTA-RM26 significantly reduced cell viability at all activity concentrations >0.625 MBq/mL (p < 0.0001), with cell viability below 1 % at concentrations ≥5 MBq/mL. Biodistribution data (n = 12) indicated a high, specific tumor uptake of [57Co]Co-DOTA-RM26, surpassing all other tissues significantly at both time points, 3.7 ± 0.6 % of the injected activity per gram (%IA/g) 4 h pi and 0.98 ± 0.05 %IA/g 24 h pi. The kidneys showed the second-highest uptake (2.0 ± 0.1 %IA/g 4 h pi), followed by the pancreas (1.4 ± 0.4 %IA/g 4 h pi). PET/CT imaging with [55Co]Co-DOTA-RM26 supported the biodistribution data and, distinctly visualized the tumor 24 h pi and showed an improved tumor-to-background compared to the earlier time points. Effective GRPR blocking significantly reduced tumor uptake in the PET images 24 h pi. CONCLUSION: These findings suggest that the theranostic pair [55Co]Co-/[177Lu]Lu-DOTA-RM26 holds significant promise as a theranostic agent for estrogen receptor-positive breast cancer.

Paraneoplastic neurologic syndromes.

Diagnosis of paraneoplastic neurologic syndromes (PNS) requires an understanding of the clinical, immunologic and oncologic heterogeneity. The 2004 PNS criteria were partially outdated due to advances in the field, and updated consensus criteria for PNS have been proposed in 2021, including the PNS-Care score for assessment of PNS probability. Furthermore, knowledge on the limitations of autoantibody testing is crucial to ensure accurate interpretation. This review presents the updated diagnostic criteria for PNS, in a Danish context.

Introduction of salvage prostatectomy in Denmark: the initial experience.

OBJECTIVE: To introduce salvage prostatectomy in Denmark. Prior to this, no national curative treatment for recurrent prostate cancer following radiation therapy existed in Denmark. This pilot study represent our initial experiences and the feasibility of performing salvage robot-assisted radical prostatectomy for true local, high-risk recurrence after initial therapy with external beam radiation for high-risk prostate cancer. RESULTS: Five patients underwent sRARP between April 2020 and July 2021. All patients were discharged within 48 h and no major complications were observed within 3 months. All patients had unmeasurable PSA (< 0.1 ng/ml) at follow-up 6 months after surgery. One patient with longer follow-up than 6 months experienced biochemical recurrence. At 3-months follow-up all patients reported considerable incontinence, at 6-month follow-up, pad usage decreased to 1 or 2 pads daily. Based on our initial results, the idea to introduce sRARP as a nationwide option remains and further patients will be included to establish the true role of sRARP in patients with recurrence after primary radiotherapy for PCa.

A prospective study of a urine and plasma biomarker test for the prediction of gleason ≥3 + 4 prostate cancer in a mixed cohort.

Purpose: Definitive diagnosis of prostate cancer is based on biopsies, a procedure associated with side-effects. The use of biomarkers in blood and urine could potentially help clinicians select patients for whom biopsies are needed. The aim of the study was to test a new urine and plasma biomarker test in detecting medium and high grade prostate cancer.Materials and methods: Blood and urine samples were prospectively collected from 41 patients prior to prostate biopsy or TUR-P and again after 3 months. The cohort included patients with suspicion of prostate cancer and patients with prior prostate cancer diagnosis. The mRNA expression of ten selected genes measured by PCR were used together with clinical data in multiple algorithms for prediction of medium-high grade prostate cancer in prostate biopsies. The testing was originally developed and validated in the USA. The method was transferred to a local Danish laboratory. Medium and high grade cancer was defined as Gleason score ≥ 3 + 4.Results: Using the biomarker test, prior to any prostate procedures, the sensitivity for detecting medium-high grade prostate cancer was 100% and the specificity was 56% and 63%, depending on the cut-off point used. When using the biomarker test, following biopsy or TUR-P, the sensitivity and specificity were reduced to 89% and 28-34% respectively. When comparing results, there was a significant difference (p < 0.05), favoring the test performed prior to the procedures.Conclusions: We were able to predict the presence of medium-high grade prostate cancer, thereby confirming earlier findings of the biomarker test.