Pilot study of salvage laparoscopic prostatectomy for the treatment of recurrent prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? After primary radiation therapy or cryotherapy for prostate cancer, a biochemical‐only recurrence poses a diagnostic and therapeutic dilemma for clinicians and patients alike. Open radical prostatectomy (ORP) represents the most effective curative treatment option for these patients. Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy.

OBJECTIVE

? To evaluate feasibility, safety and oncological efficacy of salvage laparoscopic radical prostatectomy for pathology‐proven biochemical recurrence after primary radiation therapy or cryotherapy for prostate cancer.

MATERIALS AND METHODS

? This retrospective pilot study examined 15 patients from 2004 to 2010 with biochemical recurrence after external beam radiation therapy (N= 8), brachytherapy (N= 6) or cryotherapy (N= 1). ? Patients were treated with salvage laparoscopic radical prostatectomy (11 conventional, four robotic‐assisted) with bilateral pelvic dissection.

RESULTS

? Median duration of surgery was 235 min. None of the following occurred: conversion to open surgery, transfusion, urethrovesical stenosis or perioperative or postoperative mortality. One patient presented with a rectal injury, repaired using uninterrupted sutures and a colostomy. One patient had anastomotic leak treated with prolonged Foley catheterization. ? Pathological stage was pT2a in three, pT2b in three, pT3a in four, pT3b in three and pT4 in two patients; two patients had nodal metastasis. Within an 8‐month median follow‐up, 11 patients were disease‐free and three had persistent postoperative prostate‐specific antigen (PSA) elevation; the remaining patient experienced PSA recurrence after 21 months. ? Seven patients achieved continence (no pads) by 8.4 months (median), one patient manifested severe incontinence corrected by implanting an artificial sphincter, and seven patients with a 12.6‐month mean follow‐up continued to need one or two pads per day. ? Erectile dysfunction was present in five patients before surgery and in 14 patients after surgery.

CONCLUSION

? Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy. However, larger studies with longer‐term data are required.     

Prospective Analyses of Circulating B Cell Subsets in ABO‐Compatible and ABO‐Incompatible Kidney Transplant Recipients

Immunosuppressive strategies applied in renal transplantation traditionally focus on T cell inhibition. B cells were mainly examined in the context of antibody‐mediated rejection, whereas the impact of antibody‐independent B cell functions has only recently entered the field of transplantation. Similar to T cells, distinct B cell subsets can enhance or inhibit immune responses. In this study, we prospectively analyzed the evolution of B cell subsets in the peripheral blood of ABO‐compatible (n = 27) and ABO‐incompatible (n = 10) renal transplant recipients. Activated B cells were transiently decreased and plasmablasts were permanently decreased in patients without signs of rejection throughout the first year. In patients with histologically confirmed renal allograft rejection, activated B cells and plasmablasts were significantly elevated on day 365. Rituximab treatment in ABO‐incompatible patients resulted in long‐lasting B cell depletion and in a naïve phenotype of repopulating B cells 1 year following transplantation. Acute allograft rejection was correlated with an increase of activated B cells and plasmablasts and with a significant reduction of regulatory B cell subsets. Our study demonstrates the remarkable effects of standard immunosuppression on circulating B cell subsets. Furthermore, the B cell compartment was significantly altered in rejecting patients. A specific targeting of deleterious B cell subsets could be of clinical benefit in renal transplantation.     

Brain imaging in pregnant women with acute headache

Background

Brain imaging is one of the most important diagnostic methods for evaluating headache during pregnancy. In this study, we aimed to identify anamnestic and clinical predictors for pathological brain imaging findings in pregnant women suffering from acute headache.

Methods

We conducted a retrospective chart review of 151 pregnant women with acute headache between 2010 and 2016. We screened the medical records of these patients and analyzed radiological variables, including brain imaging frequency and modality, delay to imaging and imaging findings. In patients with brain imaging, we compared several anamnestic and clinical features between those with and without symptomatic pathological findings.

Results

Half of the patients (50.3%) underwent brain imaging, mainly magnetic resonance imaging (MRI) including venography (53.9%) or MRI including both venography and arteriography (31.6%). Symptomatic pathological results could be observed in 27.6% of the patients with a brain scan. Patients in the first trimester with acute headache had a statistically higher risk for a symptomatic pathological imaging finding (p?=?0.024). Strong pain intensity, a reduced level of consciousness and seizures were significantly associated with a symptomatic pathological imaging outcome across all stages of pregnancy.

Conclusion

Brain imaging may reveal a secondary headache etiology in more than 25% of pregnant women presenting with acute headache. In particular, when the acute headache is of severe intensity, and the headache is accompanied by seizures or a change in consciousness, brain imaging is required.

     

Interaction of the cholinergic system and the hypothalamic-pituitary-adrenal axis as a risk factor for depression: evidence from a genetic association study

Chronic stress and related disruption of hypothalamic-pituitary-adrenal axis reactivity is a known risk factor for depression. Besides its effects on glucocorticoids, stress also impacts the cholinergic system. Therefore, the interaction of two polymorphisms, one on the cholinergic CHRNA4 receptor gene and one on the glucocorticoid receptor gene (NR3C1), on depression was investigated. In a sample of 800 healthy participants, we genotyped for the BCL1 rs41423247 and the CHRNA4 rs1044396 single-nucleotide polymorphisms and assessed depressiveness by means of the Beck Depression Inventory. We identified a significant epistasis effect BCL1 by CHRNA4 showing that carriers of the CC genotype at the BCL1 locus who were also homozygous for the T allele at the CHRNA4 locus had the highest depression scores. This is the first evidence from molecular genetics to show that the hypothalamic-pituitary-adrenal axis and the cholinergic system--both involved in stress reactivity--represent a combined risk factor for depression.     

Pushing attention to one side: Force field adaptation alters neural correlates of orienting and disengagement of spatial attention

Sensorimotor adaptation to wedge prisms can alter the balance of attention between left and right space in healthy adults, and improve symptoms of spatial neglect after stroke. Here we asked whether the orienting of spatial attention to visual stimuli is affected by a different form of sensorimotor adaptation that involves physical perturbations of arm movement, rather than distortion of visual feedback. Healthy participants performed a cued discrimination task before and after they made reaching movements to a central target. A velocity‐dependent force field pushed the hand aside during each reach, and required participants to apply compensatory forces toward the opposite side. We used event‐related potentials (ERPs) to determine whether electroencephalography (EEG) responses reflecting orienting (cue‐locked N1) and disengagement (target‐locked P1) of spatial attention are affected by adaptation to force fields. After adaptation, the cue‐locked N1 was relatively larger for stimuli presented in the hemispace corresponding to the direction of compensatory hand force. P1 amplitudes evoked by invalidly cued targets presented on the opposite side were reduced. This suggests that force field adaptation boosted attentional orienting responses toward the side of hand forces, and impeded attentional disengagement from that side, mimicking previously reported effects of prism adaptation. Thus, remapping between motor commands and intended movement direction is sufficient to bias ERPs, reflecting changes in the orienting of spatial attention in the absence of visuo‐spatial distortion or visuo‐proprioceptive mismatch. Findings are relevant to theories of how sensorimotor adaptation can modulate attention, and may open new avenues for treatment of spatial neglect.     

Identification of first candidate genes for creativity: a pilot study

Nitric oxide (NO) can be neuroprotective or neurotoxic during cerebral ischemia, depending on the NO synthase (NOS) isoform involved. In addition to neurotoxic effect in ischemic brain, inducible NOS (iNOS) also adversely affect ischemic outcome by blocking neurogenesis. In the present study, therefore, we studied the chronological and spatial change of the distribution of iNOS and cell proliferation in subventricular zone (SVZ) after transient focal cerebral ischemia. After 90 min of transient middle cerebral artery occlusion (tMCAO), iNOS-positive cells decreased in the ischemic core at 1 to 21 days, and increased in the ipsilateral periischemic area at 1 and 3 days. 5-Bromodeoxyuridine (BrdU)-positive cells appeared in the ischemic core at 3 to 21 days, appeared in the periischemic area at 3 and 7 days, and increased in the ipsilateral SVZ at 7 days. ED-1-positive cells appeared in the ischemic core at 3 to 21 days, and some of them were double positive with BrdU or iNOS, but the majority were BrdU-negative. The present study suggests that astrocytes are born within the periischemic area at early stage after tMCAO and migrate from SVZ into periischemic area at later stage, and that time-dependent and spatial changes of iNOS expression may be involved in the proliferation and differentiation of adult neurogenesis after focal cerebral ischemia.     

Near-death experiences are associated with rapid eye movement (REM) sleep intrusions in migraine patients,independent of migraine aura

Background and purpose

Migraine aura, near-death experiences (NDEs), and rapid eye movement (REM) sleep intrusions might share common mechanisms. Here, we investigated the prevalence of NDEs and REM sleep intrusions in people with migraine. We hypothesized that NDEs and REM sleep intrusions are more prevalent in migraine patients with aura than in those without.

Methods

We conducted a prospective cross-sectional cohort study at a tertiary headache center, based on a prespecified sample size (n = 808). Migraine patients completed a series of questionnaires, including questions about demographic and headache characteristics, the 16-item Greyson NDE scale, four questions about REM sleep intrusions, and the Depression, Anxiety, and Stress Scale 21 (DASS-21).

Results

Of 808 migraine patients (mean age 44.4 ± 13.3 years, 87.0% women), 353 (43.7%) had a current or previous history of migraine aura. Prevalence of NDE was 2.7% and not different in patients with and without aura (2.8% vs. 2.6%; p > 0.999). REM sleep intrusions were reported by 5.4% of participants and in a similar proportion of patients with and without aura (6.3% vs. 4.9%; p = 0.43). However, participants with REM sleep intrusions had had an NDE more often than participants without REM sleep intrusions (n = 5/44, 11.4% vs. n = 17/754, 2.2%; p = 0.005). Higher DASS-21 scores were associated with REM sleep intrusions (p < 0.001).

Conclusions

In this tertiary center cohort study, the prevalence of NDE and REM sleep intrusions was not influenced by migraine aura status. However, we identified an association between NDE and REM sleep intrusions, which corroborates the notion that they might share pathophysiological mechanisms.