Innovative Sonographie beim Prostatakarzinom

Zusammenfassung Zur Früherkennung und Stadieneinteilung des Prostatakarzinoms wird heutzutage fast ausschließlich die sog. systematische Mehrfachbiopsie eingesetzt. Hierbei tritt das bildgebende Verfahren – der transrektale Ultraschall – als Diagnostikum mehr und mehr in den Hintergrund und dient fast ausschließlich zur Führung der Biopsienadel in spezifische anatomische Regionen. Doch selbst bei multiplen systematischen Biopsien wird eine hohe Zahl klinisch signifikanter Karzinome übersehen. Diese Tatsache hat zu einer drastischen Steigerung der Anzahl von Gewebeproben geführt. So finden sich Zentren, in denen 6, 10, 12, ja bis zu 143 Gewebeproben in einer Sitzung entnommen werden. Diese immer invasivere heterogene Vorgehensweise bestätigt den Bedarf an Verbesserung in der Ultraschalldiagnostik. Neue und innovative bildgebende Verfahren in der Prostatasonographie werden vorgestellt mit dem Ziel, die diagnostische Aussagekraft bei Erstdiagnose sowie in der Stadienvorhersage zu verbessern. Eine verbesserte Bildgebung bei Diagnosestellung und in der Stadieneinteilung würde zu einer erheblichen Verbesserung bei den Therapieentscheidungen führen.Dieser Beitrag ist dem kürzlich verstorbenen Pathologen J. E. McNeal gewidmet, der die zonale Anatomie der Prostata erstbeschrieben hat.     

Neurologic Autoimmunity in the Era of Checkpoint Inhibitor Cancer Immunotherapy

Neurologic autoimmune disorders in the context of systemic cancer reflect antitumor immune responses against onconeural proteins that are autoantigens in the nervous system. These responses observe basic principles of cancer immunity and are highly pertinent to oncological practice since the introduction of immune checkpoint inhibitor cancer therapy. The patient’s autoantibody profile is consistent with the antigenic composition of the underlying malignancy. A major determinant of the pathogenic outcome is the anatomic and subcellular location of the autoantigen. IgGs targeting plasma membrane proteins (eg, muscle acetylcholine receptor -IgG in patients with paraneoplastic myasthenia gravis) have pathogenic potential. However, IgGs specific for intracellular antigens (eg, antineuronal nuclear antibody 1 [anti-Hu] associated with sensory neuronopathy and small cell lung cancer) are surrogate markers for CD8⁺ T lymphocytes targeting peptides derived from nuclear or cytoplasmic proteins. In an inflammatory milieu, those peptides translocate to neural plasma membranes as major histocompatibility complex class I protein complexes. Paraneoplastic neurologic autoimmunity can affect any level of the neuraxis and may be mistaken for cancer progression. Importantly, these disorders generally respond favorably to early-initiated immunotherapy and cancer treatment. Small cell lung cancer and thymoma are commonly associated with neurologic autoimmunity, but in the context of checkpoint inhibitor therapy, other malignancy associations are increasingly recognized.     

Autoimmune/Paraneoplastic Encephalitis Antibody Biomarkers: Frequency,Age, and Sex Associations

ObjectiveTo determine the frequency of detection and the age and sex associations of autoimmune/paraneoplastic encephalitis antibody biomarkers (AE-Abs).MethodsThere were 42,032 patients tested in the Mayo Clinic Neuroimmunology Laboratory between January 2018 and December 2019 for AE-Abs in serum or cerebrospinal fluid (CSF), including NMDA-R-IgG, AMPA-R-IgG, GABA_B-R-IgG, CASPR2-IgG, LGI1-IgG, GAD65-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1/2/Tr-IgGs, ANNA1/2/3-IgGs, GFAP-IgG, mGluR1-IgG, DPPX-IgG, and MOG-IgG1. Results were examined to determine frequency of antibody positivity. Age and sex associations were examined by multivariable logistic regression.ResultsAdult serum analysis (22,472 patients; 56% female) revealed that 814 (3.6%) were positive: NMDA-R-IgG (24.6%) > GAD65-IgG (21.5%) > LGI1-IgG (20.5%) > others. Of children (5649; 50% female), 251 (4.4%) were positive: NMDA-R-IgG (53.1%) > MOG-IgG1 (32%) > GAD65-IgG (7.1%) > others. Adult CSF analysis (18,745 patients; 54% female) revealed that 796 (4.2%) were positive: NMDA-R-IgG (39.7%) > GAD65-IgG (28.5%) > LGI1-IgG (11.4%) > others. Of children (5136; 50% female), 282 (5.5%) were positive: NMDA-R-IgG (88.1%) > GAD65-IgG (8.7%) > others. Age younger than 20 years was associated with NMDA-R-IgG and MOG-IgG1 (odds ratio [OR], 8.11 and 7.84, respectively; P<.001). Age older than 65 years was associated with GABA_B-R-IgG, LGI1-IgG, CASPR2-IgG, and ANNA1-IgG (OR, 7.33, 14.98, 3.67, and 14.53; P<.001). Women accounted for 60% of NMDA-R-IgG (CSF) and 78% of GAD65-IgG (CSF and serum) cohorts (OR, 1.32 [P=.002] and 2.23 [P<.001], respectively). Men accounted for 62% of the LGI1-IgG cohort (OR, 1.87; P<.001). Age and sex interacted for NMDA-R-IgG, particularly in female patients younger than 20 years (OR, 7.72; P<.001).ConclusionThe most frequent AE-Abs detected were NMDA-R-IgG, GAD65-IgG, LGI1-IgG, and MOG-IgG1. Age and sex associations may suggest paraneoplastic, or aging influences on neurologic autoimmunity.     

Paraneoplastic antibody during follow-up of a patient with anti-Ri-associated paraneoplastic neurological syndrome

Background – The role of classical antineuronal antibody determinations to confirm the paraneoplastic aetiology of a neurological syndrome is well established. However, the value of antineuronal antibody estimation during follow‐up of paraneoplastic neurological syndromes (PNS) is not known. Aims of the study – Prospective analysis of antibody concentrations in follow‐up serum samples from a patient with anti‐Ri‐associated PNS. Methods – Semiquantitative estimation of antibody concentrations with an ELISA using recombinant Ri antigen. Results – Semiquantitative estimation of circulating anti‐Ri antibodies demonstrated a renewed increase in antibody levels preceding relapse of the cancer, as confirmed using F‐fluorodeoxyglucose positron emission tomography (FDG‐PET). Conclusions – This is the first prospective report on serial anti‐Ri antibody determinations. As a large increase in antineuronal antibody concentrations in follow‐up serum samples preceded relapse of the cancer, paraneoplastic antineuronal antibodies may represent a marker for tumour activity in this case. These results warrant further multicentre studies to investigate the ability of serial quantification of classical antineuronal antibodies in monitoring PNS and in predicting relapse of cancers.