Does the type of cryoprobe affect oncological and functional outcomes in men with clinically localized prostate cancer treated with primary whole gland prostate cryoablation?

Background:This study aimed to compare the oncological and functional outcomes of primary whole gland cryoablation of the prostate using the variable ice cryoprobe (V-Probe^®) and the conventional fixed-size ice probe.Materials and methods:We reviewed the Cryo On-Line Data Registry for men who were treated with primary whole gland prostate cryoablation from 2000 through 2017. A multivariate Cox proportional hazards model was used to compare timing to biochemical recurrence between the V-Probe^® and fixed-size ice probe after adjusting for preoperative prostate-specific antigen (PSA), neoadjuvant androgen deprivation therapy, preoperative Gleason score, and preoperative T stage.Results:A total of 1124 men were included. Median age, Gleason score, and pretreatment PSA were 70 years (interquartile range [IQR]: 65–74 years), 7 (IQR: 6–7) and 5.9 ng/mL (IQR: 4.6–8.1 ng/mL), respectively. The median follow-up time was 25.0 months (IQR: 11.2–48.6 months). V-Probes^® were used in 269 (23.9%) cases and fixed-size ice probes in 858 (76.1%) cases. After adjusting for clinical T stage, PSA, neoadjuvant androgen deprivation therapy and preoperative Gleason score, on the multivariate Cox regression model, we found that there was no significant difference between the type of probe and timing to biochemical recurrence (p = 0.35). On multivariate logistic regression, using the V-Probe^® was associated with a 91% increase in postoperative urinary retention compared to the fixed-size ice probe (p = 0.003).Conclusions:The use of the V-Probe^® versus conventional fixed-size ice probe was not associated with a difference in biochemical recurrence in patients undergoing primary cryoablation of the prostate.     

Attitudes and experience of urology trainees in interpreting prostate magnetic resonance imaging

IntroductionMultiparametric magnetic resonance imaging (mpMRI) has resulted in accurate prostate cancer localization and image-guided targeted sampling for biopsy. Despite its more recent uptake, knowledge gaps in interpretation and reporting exist. Our objective was to determine the need for an educational intervention among urology residents working with mpMRIs.MethodsWe administered an anonymous, cross-sectional, self-report questionnaire to a convenience sample of urology residents in U.S. and Canadian training programs. The survey included both open- and closed-ended questions employing a five-point Likert scale. It was designed to assess familiarity, exposure, experience, and comfort with interpretation of mpMRI.ResultsFifty-three surveys were completed by residents in postgraduate years (PGY) 1–5 and of these, only 12 (23%) reported any formal training in mpMRI interpretation. Most residents’ responses demonstrated significant experience with prostate biopsies, as well as familiarity with reviewing mpMRI for these patients. However, mean (± standard deviation [SD]) Likert responses suggested a relatively poor understanding of the components of Prostate Imaging-Reporting and Data System (PI-RADS) v2 scoring for T2-weighted films (2.45±1.01), diffusion-weighted imaging (DWI) films (2.26±0.90), and dynamic contrast-enhanced (DCE) films (2.21±0.99). Similar disagreement scores were observed for questions around interpretation of the different functional techniques of MRI images. Residents reported strong interest (4.21±0.91) in learning opportunities to enhance their ability to interpret mpMRI.ConclusionsWhile mpMRI of the prostate is a tool frequently used by care teams in teaching centers to identify suspicious prostate cancer lesions, there remain knowledge gaps in the ability of trainees to interpret images and understand PI-RADS v2 scoring. Online modules were suggested to balance the needs of trainee education with the residency workflow.     

Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells

Recent studies have demonstrated that following estrogen ablation, estrogen responsive breast cancer cells undergo apoptosis. In addition, estrogen receptor (ER) expression has been strongly correlated with the expression of the bcl-2 gene product, p26Bcl-2 protein, which is known to inhibit apoptosis. In the present studies, we investigated whether estrogen affects the intracellular levels of p26Bcl-2 and thereby modulates taxol-induced apoptosis of estrogen responsive human breast cancer MCF-7 cells. Transfer of MCF-7 cells to a culture-medium without estrogens reduced their intracellular p26Bcl-2 levels by 50%. Inclusion of 0.1 M estradiol in the medium produced approximately a four-fold increase in p26Bcl-2, but not p29Bcl-xL or p21Bax levels; the expression of the c-myc and mdr-1 genes remained unchanged. Estradiol-induced four-fold increase in the ratio of the p26Bcl-2 to p21Bax levels caused a significant decline in the lethal, kilobase size DNA fragments of apoptosis, which had resulted when MCF-7 cells were cultured in a medium without estrogen. In addition, in MCF-7 cells, estradiol-induced increase in the intracellular p26Bcl-2 to p21Bax ratios was associated with a significant reduction in the large-sized DNA fragmentation induced by treatment with taxol. The increased ratios also protected MCF-7 cells against taxol-mediated cytotoxicity as assessed by the MTT assay. These results suggest that by modulating p26Bcl-2 levels, estrogens may affect the antitumor activity of taxol and potentially of other anti-breast cancer drugs against estrogen responsive human breast cancer cells.     

The problem of missing clinical data for research in psychopathology: some solution guidelines

There are no guidelines to help psychiatric researchers statistically adjust for missing data. We discuss the problems resulting from missing values, and illustrate some of them with examples from our work. Using structured instruments, we obtained clinical information from 241 patients. Some instrument items were not rated, and these did not occur randomly: hallucinations and delusions were most frequently unrated, especially in chronic schizophrenics, and patients with high scores for other psychopathology. Systematically assigning an intermediate value between present and absent to nonrated items was a satisfactory solution, unaffected by nonrandom missing values. This simple solution was equivalent to a complicated one (vectoring) in discriminating patients. When relationships between variables are linear, we recommend the intermediate value method as a practical solution to missing values. We stress that missing values do not mean missing information, and the most common response to missing values (dropping subjects) is least informative.     

Lymphedema as a presenting sign of toxocariasis

Summary Toxocariasis in children is usually an asymptomatic infection and those with clinical illness have non-specific systemic or local manifestations. We present a 24-month-old boy with bilateral lymphedema of the feet as the main clinical manifestation of toxocariasis. The child presented with limping and nonpitting edema of both feet. Laboratory investigation revealed leucocytosis of <20,000/mm³ with a differential count of <50% eosinophils. No other cause of edema was found. The ELISA for toxocariasis revealed a high titer of 1:4,096. The limping and the lymphedema disappeared during the third week of his illness. We suggest that toxocariasis should be considered as a possible cause of lymphedema and eosinophilia in young children.Zusammenfassung Die Toxocariasis nimmt bei Kindern in der Regel einen asymptomatischen Verlauf. Wenn Krankheitszeichen auftreten, handelt es sich um unspezifische Allgemeinsymptome oder lokale Symptome. Wir berichten über einen 24 Monate alten Jungen, bei dem ein bilaterales Lymphödem der Füße die Hauptmanifestation der Toxocariasis war. Das Kind hinkte und hatte an beiden Füßen ein nicht dellenbildendes Ödem. Dabei bestand eine Leukozytose von >20 000/mm³ mit >50% Eosinophilen im Differentialblutbild. Andere Ursachen für das Ödem waren nicht zu finden. Der ELISA für Toxocariasis ergab einen hohen Titer von >1:4 096. Hinken und Lymphödem verschwanden im Verlauf von drei Wochen. Wir verweisen auf die Möglichkeit einer Toxocariasis als mögliche Ursache für Lymphödem und Eosinophilie bei kleinen Kindern.

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Lymphödem als Primärsymptom einer Toxocariasis

     

Antidepressant effects of nicotine in an animal model of depression

Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an attempt at self-medication with nicotine by these individuals. Although some animal and human studies suggest that nicotine may act as an antidepressant, further verification of this hypothesis and involvement of nicotinic cholinergic system in depressive symptoms is required. Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression. These rats, selectively bred for their hyperresponsiveness to cholinergic stimulation, show an exaggerated immobility in the forced swim test compared to their control Flinders Resistant Line (FRL) rats. Acute or chronic (14 days) administration of nicotine (0.4 mg/kg SC) significantly improved the performance of the FSL but not the FRL rats in the swim test. The effects of nicotine on swim test were dissociable from its effects on locomotor activity. Moreover, the FSL rats had significantly higher [³H]cytisine binding (selective for the α₄β₂ nicotinic receptor subtype) but not [¹²⁵I]alpha-bungarotoxin binding (selective for the α₇ subtype) in the frontal cortex, striatum, midbrain and colliculi compared to FRL rats. These data strongly implicate the involvement of central nicotinic receptors in the depressive characteristics of the FSL rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders. Received: 9 June 1998/Final version: 6 August 1998     

Laparoscopic management of suspicious adnexal masses

OBJECTIVE: Our aim was to evaluate the feasibility and applicability of operative laparoscopy in the management of adnexal masses that do not meet the standard serum CA 125 and ultrasonographic criteria for benignity. STUDY DESIGN: One hundred thirty-eight patients underwent operative laparoscopy for removal of suspicious adnexal masses. The CA 125 level was >35 mIU/ml in 39 of 138 (28%) patients; ultrasonographic findings were abnormal in 127 of 138 (92%); masses were >10 cm in 43 of 138 (32%) of patients. RESULTS: Malignancies were discovered in 14% (19/138) of patients. Eight percent (11/138) of the procedures were converted to laparotomy, six because of inability to dissect the mass laparoscopically and five for staging or debulking of carcinoma. Operative times ranged from 25 to 210 minutes, with a mean of 86. Three major complications were encountered-an enterotomy and a lacerated vena cava, both of which were repaired laparoscopically, and a small bowel herniation through a lateral port site that required reoperation. Hospital stays ranged from 0 to 11 days, with a mean of 1.5. In two patients with "apparent" stage I adnexal carcinomas recurrence was diagnosed 6 and 38 months after surgery. CONCLUSIONS: Laparoscopic management of suspicious adnexal masses is technically feasible, with a low rate of morbidity and a short hospital stay. Adnexal carcinomas can be identified and managed appropriately with staging and complete resection as indicated. (Am J Obstet Gynecol 1996;175:1451-9.)     

Breast cancer angiogenesis — new approaches to therapy via antiangiogenesis,hypoxic activated drugs,and vascular targeting

Summary Several groups have shown that quantitation of tumor angiogenesis by counting blood vessels in primary breast cancer gives an independent assessment of prognosis. Poor prognosis is associated with high blood vessel counts. We have shown that the rate of cell division in endothelial cells is much higher in breast tumours than in normal breast. Breast cancer cell lines and primary human breast tumours express a wide range of vascular growth factors, including VEGF, placenta growth factor, pleiotrophin, TGF1, acidic and basic FGF, and platelet-derived endothelial cell growth factor. Inhibiting angiogenesis by blocking vascular growth factors would be difficult with highly specific agents, but drugs with a broader spectrum of antagonism may be effective. We have developed several suramin analogues which are less toxic than suraminin vivo but more potent in inhibiting angiogenesis, and these have been developed for Phase I. A combination of anti-angiogenesis agents with drugs activated by hypoxia may also be useful, because anti-angiogenesis alone may not kill cells, whereas activation of hypoxic drugs could synergize.New endpoints may be necessary because inhibition of new blood vessel formation may not cause tumour regression. Thus, the endpoint of stable disease and biochemical assessment of inhibition of angiogenesis may be much more important in therapeutic studies and for drug development in the future. The prognostic importance of angiogenesis suggests that this should be a major new therapeutic target.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

The 24-Hour Sleep Propensity Function: Experimental Bases for Somnotypology

The present study investigated the temporal structure of sleep propensity during 48 hours using an ultrashort 7-min sleep/13-min wake cycle. Eight subjects were tested under two experimental conditions of either attempting sleep, or resisting sleep after a monitored night in the laboratory. Electrophysiological recordings were carried out during the 7-min trials. The temporal structure and the overall level of sleepiness of the 48-hour sleep propensity functions calculated from the amount of total sleep in each trial revealed a high within-subjects stability. This was found both across the two days of the study within conditions, and across conditions. Also, diurnal levels of sleepiness were systematically related to nocturnal sleep parameters. Subjects having short nocturnal sleep latencies and higher sleep efficiencies slept more during the day. It is proposed that the structure and level of the sleep propensity function can be used to characterize individuals along two dimensions of somnotypology: "morningness-eveningness" and "sleepy-alert."