Prostate cancer : population-based screening and markers for long-term clinical outcome

In 1988 and 1989 a large screening study for prostate cancer was launched in Stockholm, Sweden. At the time approximately 27 000 men between 55 and 70 years of age resided within a defined area of southern Stockholm. 2400 men were randomly selected to participate in the trial and those accepting (n=1782), were examined with digital rectal exam (DRE), transrectal ultrasound (TRUS) and a PSA test. If DRE or TRUS indicated suspicious findings or if PSA levels were 10 ng/mL or greater quadrant core biopsies of the prostate were performed. Additionally, the screening algorithm employed stipulated reexamination with DRE and TRUS if PSA concentrations were between 7 ng/L and 10 ng/mL. The initial screening yielded 65 cases of prostate cancer. In this thesis the screening material have been assessed after 20 years (paper I) and 30 years (paper II-IV). In paper I the result of the one-time screening was evaluated after linking the background population, the participants of the study and the invited but not participating cohort to the Swedish cause of death registry and the Swedish cancer registry. Estimating the possible cancer-specific mortality reduction using the Poisson regression model resulted in no difference in prostate cancer-specific mortality between the screened population and the unscreened population, IRR= 0.97 (0.71-1.23; 95% CI). Paper II evaluated the association between the androgen DHT and prostate cancer incidence and mortality. High levels of DHT protected from lethal prostate cancer HR= 0.44 (0.25‐0.77; 95% CI), p=0.004 after 30 years of follow up. The association remained significant both for men seemingly heathy at time of inclusion HR=0.25 (0.07‐0.88; 95% CI), p= 0.032 and for those with a recently diagnosed cancer HR= 0.50 (0.26‐0.94; 95% CI), p=0.031. In paper III the threshold for PSA was examined and the proportions of its isoforms – free/bound PSA that is indicative for low, or negligible risk for prostate cancer death. The associations between both PSA and the ratio free/bound PSA and lethal prostate cancer were strong at long-term follow up. A baseline PSA of 2 ng/mL or less combined with ratio free/bound PSA of 0.25 or greater indicated a very low long-term risk for prostate cancer death and further screening in this cohort can be abstained or continued with lower frequency. In paper IV thawed serum from 330 men including 36 men with lethal prostate cancer was analysed. The aim was to estimate association between elevated levels of the enzyme Thymidine kinase (TK1), a phosphorylation enzyme important in DNA synthesis, and future risk for prostate cancer-specific mortality and overall mortality. The analyses were performed with a commercially available western blot kit. Preliminary estimates indicate that high levels of TK1 is associated with an increased risk for overall mortality irrespective of whether death occurred shortly after blood draw or after a period of follow up

Serum thymidine kinase 1 concentration as a predictive biomarker in prostate cancer

Background Thymidine kinase 1 (TK1) recycles DNA before cell division. We do not know if baseline blood concentrations of TK1 predict death in prostate cancer within 30 years. Our objective is to determine if there is an association between baseline levels of TK1 and future prostate cancer-specific mortality. Methods With a "proof of concept" approach, we performed a nested case-control study among 1782 individuals screened for prostate cancer between 1988 and 1989. The concentration of TK1 was measured in frozen serum from 330 men, 36 of whom have died of prostate cancer. The primary endpoint was prostate cancer-specific mortality and outcomes after 30 years were analyzed using logistic regression modeling odds ratios (Ors). Results The estimated OR (adjusted for age) for dying from prostate cancer among the men who had a TK1 value in the upper tertile was 2.39 (95% confidence interval 1.02-5.63). The corresponding OR, regardless of the cause of death, was 2.81 (1.24-6.34). Conclusions High levels of TK1 predicts death in prostate cancer within 30 years of follow-up

Segmental cerebral vasoconstriction: successful treatment of secondary cerebral ischaemia with intravenous prostacyclin.

We describe a 23-year-old male patient who presented with spontaneous intermittent and increasing attacks of severe, left-sided thunderclap headache combined with rapidly progressive muscle weakness and dysphasia, including gradual loss of consciousness. Subsequent CT, MRI and DSA showed progressive brain ischaemia and oedema within the left cerebral hemisphere with strict ipsilateral segmental arterial vasoconstriction. Despite extensive medical care, including steroids, the patient deteriorated rapidly. However, the clinical course changed dramatically within 15 h after the start of an intravenous infusion of prostacyclin at a dose of 0.9 ng/kg/min, with an almost complete recovery of consciousness and speech. In addition the pathophysiological alterations seen on magnetic resonance (imaging and digital) subtraction angiography including diffusion-weighted imaging and apparent diffusion coefficient maps shortly before prostacyclin treatment were clearly reduced when the patient was examined 3-4 days later and he continued to recover thereafter. Although not fully compatible, our case had several clinical characteristics and radiological findings reminiscent of those of the 'segmental reversible vasoconstriction syndrome', sometimes called the Call-Fleming syndrome

Ablative or Surgical Treatment for Small Renal Masses (T1a): A Single-Center Comparison of Perioperative Morbidity and Complications

The purpose of this study is to evaluate the treatment safety of thermal ablation compared to surgical treatment of T1a tumors (small renal masses) at a high-volume center. We conducted an observational single-center study based on data collected form the National Swedish Kidney Cancer Register (NSKCR) between 2015 and 2021. In total, 444 treatments of T1a tumors were included. Patients underwent surgery (partial or total nephrectomy) or ablative treatment—radiofrequency ablation (RFA) or microwave ablation (MWA). Patient characteristics were retrieved from patient records, and tumor complexity was estimated from pre-interventional CT scans. The odds ratio (OR) of suffering from a severe surgical complication following ablative treatment was estimated using a logistic regression model adjusted for age, BMI, ASA physical status classification, smoking status and RENAL nephrometry score. The frequency of severe surgical complications was 6.3% (16/256 treatments) after surgical intervention and 2.1% (4/188 treatments) following ablative treatment. Our primary hypothesis that ablative treatment is associated with a lower risk of severe surgical complications is supported by the results (OR 0.39; 0.19–0.79; p = 0.013). When adjusting for age, smoking status, ASA score, BMI score and RENAL nephrometry score, we see an even greater difference between the two groups (OR 0.34; 0.17–0.68; p = 0.002). Our study was limited by the differences in patient and tumor characteristics between the two compared groups and the study design. If oncological outcomes are found to be comparable, ablative treatment should be considered as a first-line treatment for all small renal masses

Transient Structures of PdO during CO Oxidation over Pd(100)

In situ high-energy surface X-ray diffraction was employed to determine the surface structure dynamics of a Pd(100) single crystal surface acting as a model catalyst to promote CO oxidation. The measurements were performed under semirealistic conditions, i.e., 100 mbar total gas pressure and 600 K sample temperature. The surface structure was studied in detail both in a steady gas flow and in a gradually changing gas composition with a time resolution of 0.5 s. The experimental technique allows for rapid reciprocal 1 space mapping providing the complete information on structural changes of a surface with unprecedented time resolution in harsh conditions. Our results show that the (root 5 x root 5)R27 degrees-PdO(101) surface oxide forms in a close to stoichiometric O-2 and CO gas mixture as the mass spectrometry indicates a transition to a highly active state with the reaction rate limited by the CO mass transfer to the Pd(100) surface. Using a low excess of O-2 in the gas stoichiometry, islands of bulk oxide grow epitaxially in the same (101) crystallographic orientation of the bulk PdO unit cell according to a Stranski Krastanov type of growth. The morphology of the islands is analyzed quantitatively. Upon further increase of the O-2 partial pressure a polycrystalline Pd oxide forms on the surface

Quantitative surface structure determination using in situ high-energy SXRD: Surface oxide formation on Pd(100) during catalytic CO oxidation

We have performed a quantitative structure determination of the (root 5 x root 5) R27 degrees surface oxide, formed on Pd(100) under semi-realistic conditions for catalytic CO oxidation, using in situ high-energy surface X-ray diffraction. We describe the experiment and the extraction of quantitative data in detail. The structural results are in agreement with previous reports of a system consisting of a single layer of PdO(101) formed in pure O-2 on top of Pd(100) and studied under ultra-high vacuum conditions. (C) 2014 The Authors. Published by Elsevier B.V

Combining synchrotron light with laser technology in catalysis research

High-energy surface X-ray diffraction (HESXRD) provides surface structural information with high temporal resolution, facilitating the understanding of the surface dynamics and structure of the active phase of catalytic surfaces. The surface structure detected during the reaction is sensitive to the composition of the gas phase close to the catalyst surface, and the catalytic activity of the sample itself may affect the surface structure, which in turn may complicate the assignment of the active phase. For this reason, planar laser-induced fluorescence (PLIF) and HESXRD have been combined during the oxidation of CO over a Pd(100) crystal. PLIF complements the structural studies with an instantaneous two-dimensional image of the CO2 gas phase in the vicinity of the active model catalyst. Here the combined HESXRD and PLIF operando measurements of CO oxidation over Pd(100) are presented, allowing for an improved assignment of the correlation between sample structure and the CO2 distribution above the sample surface with sub-second time resolution