Aktuelle medikamentöse Therapiekonzepte des metastasierten Prostatakarzinoms

Zusammenfassung

Hintergrund

Seit der Einführung der Androgendeprivationstherapie (ADT) vor mehr als 70 Jahren durch chirurgische Kastration hat sich die medikamentöse Therapie des metastasierten Prostatakarzinoms (PCa) erheblich diversifiziert. Durch neues Verständnis der Resistenzmechanismen gegenüber ADT sowie Chemotherapie stehen derzeit fünf zugelassene Medikamente zur Therapie zur Verfügung, die sich unterschiedlicher Wirkmechanismen bedienen.

Ergebnisse

Durch Verschiebung der Therapiezeitpunkte in Richtung frühen Einsatz beim metastasierten hormonsensitiven PCa (mHSPC) konnten weitere, signifikante Überlebensvorteile beobachtet werden. Neue Studien zu Sequenz und/oder Kombination der vorhandenen Präparate setzen weiteres Potenzial der Therapieoptimierung des metastasierten kastrationsresistenten PCa (mCRPC) frei. Diese Untersuchungen werden möglicherweise durch innovative Therapiekonzepte weiterhin verbessert und neue Zulassungen werden insbesondere beim M0 CRPC erwartet. Zudem laufen Studien, die den Stellenwert der Primariustherapie und/oder Metastasenbehandlung auf Symptome und Prognose untersuchen.

Schlussfolgerung

Aus Sicht der Autoren wird die Therapie des metastasierten PCa in Zukunft multimodal, interdisziplinär und individuell gestaltet werden müssen, um eine Chronifizierung der Tumorerkrankung bei guter Lebensqualität zu erreichen.

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Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes

Abstract

Purpose

Nivolumab is a monoclonal antibody that blocks the activation of programmed death-1 receptor, promoting T-cell activation against cancer cells. Thyroid dysfunction (TD) is a common immune-related adverse event (irAE) induced by nivolumab. We report the prevalence, patterns and outcomes of nivolumab-induced TD among cancer patients in our center.

Methods

All patients treated with nivolumab during 2016 were included. We assessed thyroid function tests, thyroid autoimmunity, thyroid imaging, and clinical outcome during nivolumab therapy as well as overall survival (OS).

Results

Seventy-three patients (55 with non-small-cell lung cancer [NSCLC], 9 with melanoma and 9 with Hodgkin lymphoma) were included. Median of follow up: 390.5 days. Seventeen patients (23.3%) developed TD during treatment. Thyrotoxicosis was reported in seven patients. Serum thyroid-stimulating hormone (TSH) nadir occurred after a median of 51 days (95% CI: 35–71). Thyroid antibodies were positive in three of the seven patients. Five of the seven hyperthyroid patients became hypothyroid later, and four of them required levothyroxine treatment. Primary hypothyroidism occurred in ten patients. Serum TSH peak occurred after a median of 110 days [95% CI: 85.2–197]. Thyroid autoimmunity was positive in one patient. In patients with NSCLC, TD was associated with better OS (HR = 0.4 [95% CI: 0.17–0.94]; p = 0.035).

Conclusions

TD induced by nivolumab is a common and heterogeneous irAE. Thyrotoxicosis develops earlier than hypothyroidism. A pattern consistent with a transient thyroiditis followed by hypothyroidism was observed in one-third of patients. Our results suggest that patients with NSCLC and nivolumab-induced TD might have better survival.

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Characterization and risk assessment of heavy metals in road dust from a developing city with good air quality and from Shanghai, China

Abstract

To investigate the differences in characteristics of heavy metals associated with different levels of ambient air quality, we collected road dust samples from Beihai (BH) and Shanghai (SH). The mean concentrations of Ni, Cr, Zn, and Cu in BH samples were one to four times the background concentrations in soil, whereas the concentrations of Cd, Cr, Mn, Zn, Cu, and Pb in SH were one to three times the background concentrations. The geo-accumulation index (I_geo) indicated widespread moderate contamination by Zn and high contamination near industrial areas by Ni and Cr in BH, whereas in SH was partly moderately contaminated by Pb, Cu, and Zn. The potential ecological risk index ( \( {E}_r^i \) ) indicated the low risk posed by all metals in both BH and SH. However, special attention should be given to the maximal \( {E}_r^i \) values, such as considerable risk for Hg ( \( {E}_r^i \)  = 148.7) and high risk for Ni (254.1) in BH, respectively. According to the health risk assessment results, there were no non-carcinogenic or carcinogenic risks (CR) posed by heavy metals in road dust collected from BH and SH. Non-carcinogenic risks due to Cr for children in both BH (0.36) and SH (0.24) were relatively high compared to other metals, and a maximal CR value for Cr (2.7 × 10⁻⁶) was found to pose a potential carcinogenic risk near the industrial area in BH. Compared with those in developed cities, the health risks in BH related to Cu, Pb, and Zn from motor vehicle emissions were relatively low, but those related to Ni and Cr from local industrial activity in road dust were relatively high.

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Transpedicular Endoscopic Surgery for Highly Downmigrated L5-S1 Disc Herniation

Endoscopic surgery for highly downmigrated disc herniation at level L5-S1 is a challenging technique. Most surgeons prefer the interlaminar access because of the special anatomy of the L5-S1 disc level, i.e., narrow neuroforamen and large interlaminar window. Transforaminal access to the neuroforamen L5-S1 is difficult in cases with high iliac crest. Here, the access to the highly downmigrated disc herniation with the recently reported technique of transpedicular endoscopic surgery by Krzok et al. was described. In 3 cases with highly downmigrated disc herniation of L5-S1, the sequester was removed successfully through the bone hole of S1 pedicle. This technique is demanding for experienced endoscopic surgeons.

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The effects of particulate matters on allergic rhinitis in Nanjing, China

Abstract

Particulate matter pollution is a serious environmental problem. Individuals exposed to particulate matters have an increased prevalence to diseases. In the present study, we performed an epidemiological study to investigate the effects of particulate matter less than 10 μm in aerodynamic diameter (PM₁₀) and particulate matter less than 2.5 μm in aerodynamic diameter (PM_2.5) on allergic rhinitis in Nanjing, China. Daily numbers of allergic rhinitis patients (33,063 patients), PM₁₀, PM_2.5, and weather data were collected from January 2014 to December 2016 in Nanjing, China. Generalized additive models (GAM) were used to evaluate the effects of PM₁₀ and PM_2.5 on allergic rhinitis. We found that the interquartile range (IQR) increases in PM₁₀ (difference of estimates, 5.86%; 95% CI, 3.00–8.81%; P = 4.72 × 10⁻⁵) and PM_2.5 (difference of estimates, 5.39%; 95% CI, 2.73–8.12%; P = 5.67 × 10⁻⁵) concentrations were associated with the higher increased numbers of allergic rhinitis patients with 3-day cumulative effects in single-pollutant model. In addition, we found that the IQR increase in PM₁₀ (age ≥ 18 years: 7.37%, 3.91–10.96%, 2.14 × 10⁻⁵; 0–17 years: 0.83%, − 4.00–5.91%, 0.740) and PM_2.5 (age ≥ 18 years: 7.00%, 3.78–10.32%, 1.40 × 10⁻⁵; 0–17 years: 0.40%, − 4.10–5.10%, 0.866) increased the number of allergic rhinitis patients in adults, but not in children. In summary, our findings suggested that exposure to PM₁₀ and PM_2.5 was associated with the risk of allergic rhinitis.

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Validation of web‐based thyroid imaging reporting and data system in atypia or follicular lesion of undetermined significance thyroid nodules

Abstract

Background

Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) show variable malignancy risk. We validated the web‐based predictive models and the scoring system by the American College of Radiology (ACR) for AUS/FLUS nodules to stratify the malignancy risk.

Methods

From January 2011 to November 2014, 275 consecutive nodules diagnosed as AUS/FLUS were enrolled. The discrimination and calibration ability of a web‐based scoring with inclusion of biopsy result and sonographic features, old web‐based scoring model without biopsy result, and ACR models were assessed.

Results

The areas under the receiver operating characteristic curve of the validation set were 0.670 for the new web‐based model, 0.710 for the old web‐based model, and 0.732 for the ACR scoring risk‐stratification model. All models were well calibrated.

Conclusion

The web‐based scoring risk‐stratification model using the combined information of ultrasonography features and biopsy result for AUS/FLUS nodules to stratify malignancy risk presents an acceptable predictive accuracy.

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Development of magnetic porous coordination polymer adsorbent for the removal and preconcentration of Pb(II) from environmental water samples

Abstract

A novel porous coordination polymer adsorbent (BTCA-P-Cu-CP) based on a piperazine(P) as a ligand and 1,2,4,5-benzenetetracarboxylic acid (BTCA) as a linker was synthesized and magnetized to form magnetic porous coordination polymer (BTCA-P-Cu-MCP). Fourier transform infrared (FTIR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), field emission scanning electron microscope(FESEM), energy-dispersive X-ray spectroscopy(EDS), CHN, and Brunauer–Emmett–Teller(BET) analysis were used to characterize the synthesized adsorbent. BTCA-P-Cu-MCP was used for removal and preconcentration of Pb(II) ions from environmental water samples prior to flame atomic absorption spectrometry(FAAS) analysis. The maximum adsorption capacity of BTCA-P-Cu-MCP was 582 mg g⁻¹. Adsorption isotherm, kinetic, and thermodynamic parameters were investigated for Pb(II) ions adsorption. Magnetic solid phase extraction (MSPE) method was used for preconcentration of Pb(II) ions and the parameters influencing the preconcentration process have been examined. The linearity range of proposed method was 0.1–100 μg L⁻¹ with a preconcentration factor of 100. The limits of detection and limits of quantification for lead were 0.03 μg L⁻¹ and 0.11 μg L⁻¹, respectively. The intra-day (n = 7) and inter-day (n = 3) relative standard deviations (RSDs) were 1.54 and 3.43% respectively. The recoveries from 94.75 ± 4 to 100.93 ± 1.9% were obtained for rapid extraction of trace levels of Pb(II) ions in different water samples. The results showed that the BTCA-P-Cu-MCP was steady and effective adsorbent for the decontamination and preconcentration of lead ions from the aqueous environment.

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