ABSTRACT
BACKGROUND: Survivors of testicular cancer may experience long-term morbidity following treatment. There is an unmet need to investigate techniques that can differentiate individuals who need additional therapy from those who do not. 2-18fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with computerised tomography (CT) may be helpful in select settings and may be used outside of current evidence-based recommendations in real-world practice. METHODS: A institutional FDG-PET/CT database of scans performed between 2000 and 2020 for adults with testicular seminoma was interrogated. Endpoints of interest included the positive (PPV) and negative (NPV) predictive value of FDG-PET/CT for identifying active seminoma (defined by progressive radiology, response to treatment or biopsy); or no active seminoma within 24-months for patients with stage 1 and advanced seminoma. An exploratory analysis examining predictive role of SUVmax was also performed. RESULTS: 249 patients met eligibility criteria for the analysis, including 184 patients with stage 1 and 77 patients with advanced testicular seminoma. Of 193 FDG-PET/CT performed in stage 1 seminoma with available follow-up data, 79 were performed during active surveillance. 18 (23%) of these were positive, all of which had confirmed recurrent seminoma (PPV 100%). Of 45 negative FDG-PET/CT during active surveillance, 4 recurrences developed corresponding to a NPV 91%. When clinical suspicion precipitated FDG-PET/CT (n = 36): PPV 100%, NPV 86%. Of 145 FDG-PET/CT in advanced seminoma with available follow-up data, 25 (17%) were performed at baseline (within 2 months of diagnosis), 70 (48%) post-treatment for evaluation of treatment response and 50 (34%) during follow-up following prior curative treatment. 10 (14%) post-treatment FDG-PET/CT were positive corresponding to a PPV 60%. Of 46 negative FDG-PET/CT, 5 recurrences occurred (NPV 89%). During follow-up after prior curative treatment, 24 (50%) FDG-PET/CT were positive corresponding to a PPV 83%; of 20 negative FDG-PET/CT, 1 recurrence occurred, NPV 95%. When clinical suspicion indicated FDG-PET/CT (n = 36): PPV 100%, NPV 94%. CONCLUSION: FDG-PET/CT offers high PPV for identifying seminoma and accurately predicts non-recurrence across a clinically relevant 24-months. Notably, FDG-PET/CT may prevent unnecessary treatment in 45% of patients undergoing investigation for clinical suspicion of recurrence during follow-up of advanced seminoma. The use of FDG-PET/CT in selected patients now, may help prevent unnecessary treatment of people with testicular seminoma.
Subject(s)
Seminoma , Testicular Neoplasms , Adult , Fluorodeoxyglucose F18/therapeutic use , Follow-Up Studies , Glucose/therapeutic use , Humans , Male , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography/methods , Radiopharmaceuticals/therapeutic use , Retrospective Studies , Seminoma/diagnostic imaging , Seminoma/therapy , Testicular Neoplasms/diagnostic imaging , Testicular Neoplasms/therapy , Tomography, X-Ray ComputedABSTRACT
Neuroendocrine neoplasms (NENs) are a very diverse group of tumors with a worldwide rise in incidence. Systemic therapy remains the mainstay treatment for unresectable and/or metastatic NENs. 177Lu-DOTATATE, a radiopharmaceutical which emits beta particles, has emerged as a promising therapy for metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, limited treatment options are available particularly after the failure of 177Lu-DOTATATE therapy. This review aims to identify and summarize the available evidence for, and potential adverse events of, targeted alpha-particle therapy (TAT) in the treatment of metastatic NENs, specifically GEP-NENs. The MEDLINE, EMBASE, SCOPUS, and Cochrane Library databases were searched. Two articles which met the inclusion criteria were identified and included in the review. Putative radiopharmaceuticals that can be considered for metastatic NEN treatment include 225Actinium (225Ac)-DOTATATE and 213Bismuth (213Bi)-DOTATOC. There was evidence of partial response using both radiopharmaceutical agents without significant hematological, renal, or hepatotoxicity. Future studies should consider longer term, randomized controlled trials investigating the role of TAT, in particular, 225Ac-DOTATATE, in the treatment of metastatic NENs.
ABSTRACT
Interleukin-6 (IL-6) family cytokines act via gp130 in the osteoblast lineage to stimulate the formation of osteoclasts (bone resorbing cells) and the activity of osteoblasts (bone forming cells), and to inhibit expression of the osteocyte protein, sclerostin. We report here that a profound reduction in trabecular bone mass occurs both when gp130 is deleted in the entire osteoblast lineage (Osx1Cre gp130 f/f) and when this deletion is restricted to osteocytes (DMP1Cre gp130 f/f). This was caused not by an alteration in osteoclastogenesis, but by a low level of bone formation specific to the trabecular compartment. In contrast, cortical diameter increased to maintain ultimate bone strength, despite a reduction in collagen type 1 production. We conclude that osteocytic gp130 signaling is required for normal trabecular bone mass and proper cortical bone composition.
Subject(s)
Cytokine Receptor gp130/metabolism , Osteoblasts/metabolism , Osteoclasts/metabolism , Osteogenesis , Signal Transduction , Adaptor Proteins, Signal Transducing , Animals , Bone and Bones/anatomy & histology , Bone and Bones/metabolism , Cell Count , Cell Lineage , Collagen Type I/genetics , Collagen Type I/metabolism , Collagen Type I, alpha 1 Chain , Female , Gene Deletion , Gene Knockdown Techniques , Glycoproteins/metabolism , Integrases/metabolism , Intercellular Signaling Peptides and Proteins , Male , Mice, Inbred C57BL , Mice, Knockout , Models, Biological , Organ Size , Osteoblasts/cytology , Osteocalcin/genetics , Osteocalcin/metabolism , Osteoclasts/cytology , Osteocytes/metabolism , Reproducibility of Results , Sp7 Transcription Factor , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
During a study on the quality of the indoor environment, Acanthamoeba spp. were detected in 20 out of 87 dust samples collected from air-conditioners installed in a four-story campus building located in Kuala Lumpur, Malaysia. Twenty-one cloned Acanthamoeba isolates designated as IMU1 to IMU21 were established from the positive primary cultures. Five species were identified from the 16 isolates according to the morphological criteria of Pussard and Pons; i.e. A. castellanii, A. culbertsoni, A. griffini, A. hatchetti and A. polyphaga. Species identities for the remaining five isolates (IMU4, IMU5, IMU15, IMU20 and IMU21), however, could not be determined morphologically. At genotypic characterization, these isolates were placed into T3 (IMU14); T5 (IMU16 and IMU17) and T4 (all the remaining isolates). To predict the potential pathogenicity of these Acanthamoeba isolates, thermo- and osmotolerance tests were employed; many isolates were predicted as potential human pathogens based on the outcome of these tests. This is the first time potentially pathogenic Acanthamoeba have been isolated from air-conditioners in Malaysia.
