Proliferative activity in benign and neoplastic prostatic epithelium

The increasing availability of means for the early detection of prostatic cancer has brought under scrutiny the criteria used for prognosis and emphasized our limitations in understanding what determines the rate of progression in these cancers. The rate of cancer cell proliferation has been under intense investigation, which, however, has yielded conflicting results. In this study we evaluated the proliferative activity of benign and neoplastic prostatic epithelium, using various existing methodologies. We first analysed the variability introduced by the methodological approach and then attempted to demonstrate whether determination of the proliferative capacity had any clinical consequence that complemented the histological grading. Tissue samples from patients, 88 with cancer and 46 with benign prostatic pathology, were studied using in vitro bromodeoxyuridine (BrdU) incorporation as well as Ki67 and the proliferating cell nuclear antigen (PCNA) to estimate the proliferative activity. Increased proliferation was found consistently in inflammation and metaplasia, but not in hyperplasia. In contrast, cancers showed marked variability. Although average proliferation indices increased with grade, there was a wide scatter of values. Correlation was stronger with stage, but also depended on the methodology. Bromodeoxyuridine indices over 10 per mille had a positive predictive value of 79 per cent for cancers extending beyond the prostatic capsule and may prove particularly helpful for evaluating patients with grade 7 cancer. This observation is significant, since grade 7 cancers are the most frequent and the least predictable.     

An intrauterine progesterone contraceptive system (52 mg) used in pre- and peri-menopausal patients with endometrial hyperplasia

An intrauterine progesterone contraceptive system (IPCS) (52 mg) was inserted in 25 women with cystic endometrial hyperplasia. Among these women, 11 complained of heavy climacteric symptoms and also received an oestrogen replacement therapy consisting of conjugated oestrogens (0.625 mg/day) administered cyclically for 3 out of 4 wk. Prior to the therapy and after 6 mth of treatment, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oestrone (E1) and oestradiol (E2) plasma levels were measured and endometrial histology was evaluated. In the women receiving IPCS treatment alone, there were no significant changes in FSH, LH, PRL, E1 and E2 plasma levels. However, there were remarkable changes found in their endometrial histology. In the remaining women receiving both treatments there was a sharp decrease in FSH and LH plasma levels and an increase in E1 and E2 plasma levels, while the prolactin levels remained unchanged. With the exception of two of these women, the endometrial histology changed remarkably. The endometrial morphology of the two exceptions remained unchanged. All climacteric symptoms disappeared after the administration of both IPCS and the oestrogen replacement therapy. The remarkable changes which did occur in the endometrial histology resulted in a less active glandular epithelium and stromal decidual formation, thus proving a useful effect of treatment.     

Aromatization of androstenedione to estrogen by benign prostatic hyperplasia,prostate cancer and expressed prostatic secretions

Summary Human prostatic tissue and expressed prostatic secretions (EPS) efrom patients with benign prostatic hyperplasia (BPH) and prostate cancer were incubated with (1 ³H) androstenedione. The extent of aromatization was determined by measuring the transfer of ³H from the 1 position into water. The amount of ³H₂O recovered corresponds to the estrogens formed. Tissue from 5 patients with BPH yielded 2.13 (±1.05) pmol/mg protein/h while the EPS from the same patients yielded 727 fmol/mg protein/h. In patients with prostate cancer the mean formation of estrogens was 388 fmol/mg protein/h (±75). 4-hydroxyandrostenedione, an aromatase inhibitor, successfully inhibited aromatization in BPH and prostate cancer 53–98%.Part of this paper was presented at the 5th Congress of the European Society for Urological Oncology and Endocrinology, 18–20 August 1986, Edinburgh, UK     

Partial epilepsy in neurologically normal children: clinical syndromes and prognosis

A clinical and electroencephalographic study of 107 neurologically normal children with partial seizures was undertaken to verify the existence and determine the frequency of epileptic syndromes reported in selected populations. Sixty-three children had simple partial seizures, 39 had complex partial seizures, and 5 children were unclassifiable. The syndrome of benign partial epilepsy of children with rolandic spikes (BPEC, 38 cases) was clearly identified and its uniformly benign final prognosis was confirmed even if some of these children had at times severe or poorly controlled seizures. Among the children with simple partial seizures outside the BPEC (25 cases) and complex partial seizures (39 cases), no homogeneous clinical or electroclinical subgroup could be found. Two children with benign partial epilepsy and myoclonic-astatic seizures ("atypical benign partial epilepsy of childhood") and one child with "benign epilepsy with occipital spike-waves" were identified. 74% of children with epilepsy with complex partial seizures (ECP) had a 1-year seizure-free interval, and many children with epilepsy with simple partial seizures outside the BPEC group (ESP) had no more than two seizures. A benign course is thus not limited to the BPEC but is difficult to predict. Prospective studies are necessary to confirm the existence of well-defined benign syndromes among the idiopathic partial epilepsies of childhood, which appear quite rare outside the BPEC.     

Assessment of changes in penile sensation by electrophysiological study after radical prostatectomy: A pilot study

Background:To evaluate the changes in penile sensation by electrophysiological tests in patients who underwent radical prostatectomy (RP) and to demonstrate the role of dorsal penile nerve injury in postoperative erectile dysfunction.Materials and methods:Twenty-six volunteer patients who were eligible for RP were included in the study. Preoperative penile sensory electromyography and the International Index of Erectile Function-5 (IIEF-5) questionnaire were done for each patient. Erectile function assessment and electrophysiological evaluation of penile sensation were repeated at postoperative 3rd and 6th months.Results:Postoperative IIEF-5 scores and electromyography values were significantly lower than preoperative findings (p < 0.05). The IIEF-5 scores in the nerve sparing-RP (NS-RP) group were significantly higher than the non-nerve sparing-RP (NNS-RP) group in the postoperative period. Nerve conduction velocity values in the NS-RP group were also higher than the NNS-RP group at the postoperative 3rd and 6th months. However, these changes were not statistically significant (p > 0.05).Conclusions:Patients who underwent RP have decreased penile sensation due to cavernous nerve damage and a possible dorsal penile nerve injury. The decrease of penile sensation may be associated with postoperative erectile dysfunction.     

Case report of Brunner’s gland hyperplasia: A rare “mimic” of malignant pathology

IntroductionBrunner’s gland hyperplasia is a rare, benign lesion of the duodenum. The symptomology can range from asymptomatic (as an incidental finding on endoscopy) to gastrointestinal obstruction or haemorrhage.Case presentationWe report a case of a 60-year-old man presenting with post-prandial vomiting and weight loss. Inpatient evaluation led to the likely diagnosis of a duodenal malignancy for which the patient underwent a laparotomy and proximal duodenectomy.Clinical discussionBrunner’s gland hyperplasia is a rare, benign condition that can be overtreated due to the difficulty in obtaining an accurate pre-operative diagnosis. The literature has been reviewed to discuss the approach to diagnosis.ConclusionThis case highlights the potential for Brunner’s gland hyperplasia mimicking a malignancy.     

Narrative review of prostate cancer grading systems: will the Gleason scores be replaced by the Grade Groups?

The Gleason grading system, proposed by Dr. Donald F. Gleason in 1966, is one of the most important prognostic factors in men with prostate cancer (PCa). At consensus conferences held in 2005 and 2014, organized by the International Society of Urological Pathology (ISUP), the system was modified to reflect the current diagnostic and therapeutic approaches. In particular, in the 2014 Conference, it was recognized that there were weaknesses with the original and the 2005 ISUP modified Gleason systems. Based on the results of a research conducted by Prof. JI Epstein and his group, a new grading system was proposed by the ISUP in order to address some of such deficiencies: i.e., the five distinct Grade Groups (GGs). Since 2014, results of studies have been published by different groups and societies, including the Genitourinary Pathology Society (GUPS), giving additional support to the prognostic role of the architectural Gleason patterns and, in particular, of the GGs. A revised GG system, taking into account the percentage of Gleason pattern (GP) 4, cribriform and intraductal carcinoma, tertiary GP 5, and reactive stroma grade, has shown to have some advantages, however not ready for adoption in the current practice. The aim of this contribution was to review the major updates and recommendations regarding the GPs and GSs, as well as the GGs, trying to give an answer to the following questions: “How has the grade group system been used in the routine?” and “will the Gleason scoring system be replace by the grade groups?” We also discussed the potential implementation in the future of molecular pathology and artificial intelligence in grading to further define risk groups in patients with PCa.     

Pilot study of an HLA-A2 peptide vaccine using flt3 ligand as a systemic vaccine adjuvant

A pilot vaccine study was conducted to test the safety and immunological efficacy of four monthly immunizations of an MHC class I peptide vaccine, the E75 HLA-A2 epitope from HER-2/neu, using flt3 ligand as a systemic vaccine adjuvant. Twenty HLA-A2-expressing subjects with advanced stage prostate cancer were randomly assigned to one of four immunization or treatment schedules: (a) Flt3 ligand (20 g/kg per day) administered subcutaneously daily for 14 days on a 28-day cycle, monthly for four months; (b) flt3 ligand course as above with the E75 peptide vaccine administered on day 7 of each flt3 ligand cycle; (c) flt3 ligand course as above with the E75 peptide vaccine administered on day 14 of each flt3 ligand cycle; or (d) E75 peptide admixed with granulocyte–macrophage colony-stimulating factor and administered intradermally once every 28 days, as has previously been reported. The primary endpoints of the study were the determination of safety and immunological efficacy in generating E75-specific T cells as determined by peptide-specific interferon-gamma ELIspot. Adverse events included one grade 3 skin reaction and the development of grade 2 autoimmune hypothyroidism in two subjects with preexisting subclinical autoimmune hypothyroidism. Dendritic cells were markedly increased in the peripheral blood of subjects receiving flt3 ligand with each repetitive cycle, but augmentation of antigen-presenting cells within the dermis was not observed. Apart from a single subject, no significant peptide-specific T-cell responses were detected by ELIspot, whereas delayed-type hypersensitivity responses were detectable in control subjects and in subjects receiving peptide vaccine early in the course of flt3 ligand administration. The absence of robust peripheral immune responses in the current study may be attributable to the small numbers of subjects or differences in the subject population. In addition, the inability of flt3 ligand to augment the number of peripheral skin antigen-presenting cells may have contributed to the absence of robust peptide-specific immunity detectable in the peripheral blood of immunized subjects treated with flt3 ligand.