Correlation between ADC, ADC ratio, and Gleason Grade group in prostate cancer patients undergoing radical prostatectomy: Retrospective multicenter study with different MRI scanners.

Background: MRI is an important tool in the prostate cancer work-up, with special emphasis on the ADC sequence. This study aimed to investigate the correlation between ADC and ADC ratio compared to tumor aggressiveness determined by a histopathological examination after radical prostatectomy. Methods: Ninety-eight patients with prostate cancer underwent MRI at five different hospitals prior to radical prostatectomy. Images were retrospectively analyzed individually by two radiologists. The ADC of the index lesion and reference tissues (contralateral normal prostatic, normal peripheral zone, and urine) was recorded. Absolute ADC and different ADC ratios were compared to tumor aggressivity according to the ISUP Gleason Grade Groups extracted from the pathology report using Spearman's rank correlation coefficient (ρ). ROC curves were used to evaluate the ability to discriminate between ISUP 1-2 and ISUP 3-5 and intra class correlation and Bland-Altman plots for interrater reliability. Results: All patients had prostate cancer classified as ISUP grade ≥ 2. No correlation was found between ADC and ISUP grade. We found no benefit of using the ADC ratio over absolute ADC. The AUC for all metrics was close to 0.5, and no threshold could be extracted for prediction of tumor aggressivity. The interrater reliability was substantial to almost perfect for all variables analyzed. Conclusions: ADC and ADC ratio did not correlate with tumor aggressiveness defined by ISUP grade in this multicenter MRI study. The result of this study is opposite to previous research in the field.

A rare case of complete male genital self-amputation posing challenges in the psychiatric diagnosis and management.

Genital self-mutilation (GSM) is a rare phenomenon encountered mostly within the context of severe mental illness. The following case report highlights a rare case of self-inflicted total penile self-amputation in a patient with a psychiatric history of polydrug abuse and attention deficit disorder (ADD). The patient engaged in penile self-amputation under the influence of command hallucinations and religious delusions. He was operated on with microsurgical penile replantation but the penis had to be amputated after two weeks because of postoperative complications. The patient was admitted for compulsory psychiatric treatment. During the prolonged hospitalization course, he was arrested for stabbing two other patients and was transferred to a forensic psychiatric unit. The case fits the description for Klingsor Syndrome and involved multiple interacting risk factors that complicated the initial presentation and the ensuing management of the condition in the hospital setting.

Circulating Tumor Cells as a Marker for Progression-free Survival in Metastatic Castration-naïve Prostate Cancer.

BACKGROUND: Analysis of circulating tumor cells (CTC) is a promising prognostic marker in castration-resistant prostate cancer (CRPC). The aim of this study was to investigate CTC detection and phenotyping as prognostic biomarkers for response to primary androgen deprivation therapy (ADT) of metastatic prostate cancer (PC). METHODS: PC patients presenting with a prostate specific antigen (PSA) >80 ng/ml and/or metastatic disease, intended for ADT were enrolled in the study. CTCs were analysed for expression of PSA prostate specific membrane antigen (PSMA) and epidermal growth factor receptor (EGFR) before and three months after ADT and related to progression. RESULTS: At inclusion, 46 out of 53 patients (87%) were CTC-positive with a sensitivity and specificity for distant metastases (M1) of 98% and 75%, respectively. In patients with M1-disease, EGFR-detection in CTC was an independent prognostic marker for progression-free survival, whereas PSA and alkaline phosphatase serum levels, Gleason score, or T-stage were not. EGFR-positive patients had significantly shorter time to progression (5 months) compared to EGFR-negative patients (11 months) (P < 0.05). CONCLUSIONS: In this explorative study, CTCs were detected in 98% of M1 patients and detection of EGFR in CTCs was strongly associated with poor outcome, which indicated that phenotypical analysis of CTC could be a promising prognostic marker of ADT-response in castration-naïve metastatic PC patients. Prostate 77:849-858, 2017. © 2017 Wiley Periodicals, Inc.

Markers of proteolysis, fibrinolysis, and coagulation in relation to size and growth rate of abdominal aortic aneurysms.

UNLABELLED: We evaluated whether matrix metalloproteinases (MMPs) 2 and 9, their inhibitors, markers for fibrinolysis, and thrombin activation are associated with diameter and growth of abdominal aortic aneurysms (AAAs). MATERIAL AND METHODS: Matrix metalloproteinases 2 and 9, tissue inhibitor of MMPs (TIMP-1), serpine-1, tPa-serpine-1, and activated protein C- protein C inhibitor (APC-PCI) complex were analyzed in 353 patients with AAA grouped according to AAA size, and 219 gender- and age-matched healthy individuals. Follow-up of AAA growth for up to 7 years was possible in 178 of 353 patients. RESULTS: At baseline, all groups of patients with AAA showed lower levels of MMP-2 and -9, and higher levels of TIMP-1, serpine-1, and t-Pa-serpine-1 than controls. Matrix metalloproteinase 2 correlated inversely and APC-PCI complex correlated directly with AAA diameter. We found no correlations between markers for proteolysis, fibrinolysis, coagulation, and yearly AAA growth. CONCLUSION: Matrix metalloproteinase 2 is lower and APC-PCI higher in patients with larger AAA, but the relevance of the markers for AAA growth is far from clarified.

High levels of endothelin (ET)-1 and aneurysm diameter independently predict growth of stable abdominal aortic aneurysms.

The etiology of abdominal aortic aneurysm (AAA) includes inflammation and endothelial dysfunction. To evaluate relations between these mechanisms and AAA growth, endothelin (ET)-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and CD40 ligand were related to yearly AAA growth for 2.9 +/- 1.6 years (mean +/- SD) in 178 patients with conservatively followed AAA. Total number of follow-up years was 491. Abdominal aortic aneurysm diameter increased by 3.3 +/- 4.0 mm during the first year and by 4.9 +/- 4.4 mm during the first 2 years. Median (range) growth was 2.5 (-1.0 to 30.6) mm/year. When patients with AAA growth above or below median were compared, initial AAA diameter (46.1 +/- 5.8 vs 42.0 +/- 8.3 mm; P < .0001), age (75 +/- 7 vs 72 +/- 8 years; P < .029), and initial ET-1 levels (1.31 +/- 0.50 vs 1.13 +/- 0.49 pg/mL; P < .0177) were higher in patients with growth above median. Endothelin 1 (P = .0230) and initial AAA diameter (P = .0019) predicted AAA growth above median in logistic regression. In conclusion, higher initial levels of ET-1 and initial AAA diameter independently predict AAA growth.

Is increased thrombin activation in patients with abdominal aortic aneurysms dependent on area or volume of aneurysm thrombus mass?

OBJECTIVES: Does thrombin activation seen in patients with abdominal aortic aneurysms (AAA) relate to the thrombus surface area or volume within the aneurysm? PATIENTS AND METHODS: A total of 130 patients with AAA were analyzed regarding levels of the complex between activated protein C-protein C inhibitor (APC-PCI) and AAA morphology. Analysis of APC-PCI complex was made using a sandwich immunofluorometric method. RESULTS: Increased APC-PCI concentrations were seen in patients with AAA (0.44 microg/L; P < .001 compared with controls). The correlations of APC-PCI values were r = .13, P = .13 for aneurysm size, r = .08, P = .35 for thrombus surface area, and r = .13, P = .14 for thrombus volume. APC-PCI values elevated to 0.45 microg/L in 10 patients with AAA having no or very little thrombus mass. CONCLUSION: Disappointingly, no correlation was found between thrombus surface area or volume and levels of the APC-PCI complex. Mechanisms other than the AAA-sac thrombus must be evaluated as cause of thrombin activation in patients with AAA.

Cytokines and systemic biomarkers are related to the size of abdominal aortic aneurysms.

OBJECTIVE: The etiology of abdominal aortic aneurysm (AAA) includes atherosclerotic, inflammatory, immunological and coagulatory mechanisms. The aim of this study was to evaluate associations between markers for some of these mechanisms and AAA-size, in order to identify markers which might later be evaluated in relation to aneurysm growth. MATERIAL AND METHODS: Prospectively 360 AAA-patients and an age and sex-matched healthy control group (n=219) were analyzed. AAA-patients were divided in three groups according to AAA-diameter (small <45 mm, n=122, medium 45-55 mm, n=108, and large >55 mm, n=130). Associated diseases, blood pressures and routine laboratory markers were analyzed. Additionally we evaluated endothelin (ET)-1, tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, activated protein C-protein C inhibitor (APC-PCI) complex, and CD40 ligand. Groups were compared with the Kruskall-Wallis test and the Mann-Whitney U test. RESULTS: Of routine markers platelet count was lower (p=0.0006) and creatinine level was higher (p=0.028) in patients with large AAA. Almost all non-routine markers analyzed were highly elevated in AAA-patients compared to the control group. IL-6 (p=0.0002) and thrombin activation measured as APC-PCI (p<0.0001) increased depending on the size of AAA. CONCLUSION: Many of the analyzed biomarkers were markedly increased in AAA-patients and some were also related to aneurysm size. Whether any of the markers is also associated with aneurysm growth rate should be further evaluated.

Associations between statin treatment and markers of inflammation, vasoconstriction, and coagulation in patients with abdominal aortic aneurysm.

The association of statins with markers of inflammation, vasoconstriction, and coagulation was evaluated in 325 patients with abdominal aortic aneurysm with respect to statin treatment or not. Variables evaluated included routine laboratory markers, lipids, homocysteine, endothelin-1, matrix metalloproteinases (MMP)-2 and -9, and activated protein C-protein C inhibitor (APC-PCI) complex. Statin-treated patients were more often male (85% vs 75%; P = .024) and had ischemic heart disease (57% vs 19%; P < .0001). They showed lower levels of cholesterol (P < .0001), homocysteine (P = .027), MMP-9 (P = .038), and endothelin-1 (P = .005), and higher levels of APC-PCI complex (P = .042). Differences persisted in logistic regression for cholesterol (P < .0001), APC-PCI complex (P = .034), and homocysteine (P = .021). Statin-treated patients with abdominal aortic aneurysm show higher APC-PCI complex and lower homocysteine levels. Whether this translates into lower risk for aneurysm expansion or rupture will be evident from further follow-up.