Computational pathology definitions,best practices,and recommendations for regulatory guidance: a white paper from the Digital Pathology Association

In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.      

A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy

Maternal serum concentrations of inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC-related inhibin forms, total follistatin, steroids and gonadotrophins were measured longitudinally in six normal singleton pregnancies. Maternal venous blood was collected randomly during a spontaneous follicular phase prior to donor insemination, at 5, 7, 9, 11, 16, 20, 24, 28, 32 and 36 weeks after the first missed menses and in the early puerperium. Steroid and gonadotrophin profiles conformed to previous reports. While at week 5 of gestation inhibin-A, activin-A and follistatin concentrations were similar to those at the follicular phase, all three increased progressively (P < 0.001) to maximal concentrations in week 36: approximately 48-fold (3740 +/- 1349 ng inhibin-A/ml), approximately 22-fold (6109 +/- 1443 ng activin-A/ml) and approximately 10-fold (3563 +/- 418 ng follistatin/ml) higher. Pro- alphaC concentrations reached a maximum in weeks 5 (approximately 5- fold, P < 0.001) and 36 (1027 +/- 174 pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnancy) was undetectable (<12 pg/ml) between week 5-16 of gestation but increased slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB was undetectable throughout pregnancy. Post-partum concentrations of inhibin-A (41 +/- 12 ng/ml), inhibin-B (<12 pg/ml), activin-A (950 +/- 149 pg/ml), pro-alphaC (128 +/- 22 pg/ml) and follistatin (990 +/- 79 ng/ml) were substantially lower than at week 36 of gestation. The activin-A:follistatin ratio increased from 0.5 in week 5 to 1.8 in week 36, suggesting that more free activin-A is available in the maternal circulation during late pregnancy.      

Outcome in congenital stridor (laryngomalacia)

Twenty-one children who had been diagnosed as having laryngomalacia by direct laryngoscopy in infancy were reviewed 7 to 12 years later. The natural history of the disease is documented. A wide variation in the time of onset and duration of the stridor was found and there was a high incidence of feeding difficulties. A previously reported association with mental retardation or cerebral palsy is not confirmed. 4 out of the 21 children had early speech problems.     

18F‐fluorodeoxyglucose positron emission tomography imaging in brain tumours: The Western Australia positron emission tomography/cyclotron service experience

¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scans in the first 49 patients referred with either possible brain tumour or brain tumour recurrence were reviewed. FDG‐PET imaging was reported with reference to anatomical imaging. Based on the report the FDG study was classified as either positive or negative for the presence of tumour. Thirty‐eight cases were included in the analysis, 21 having pathological data and 17 with diagnostic clinical follow up. Eleven were excluded, as they had inadequate follow‐up data. Of the 21 cases with pathology, 18 were shown to have tumour. In this group there were five false‐negative scans and two false‐positive PET scans. Seventeen cases were assessed by clinical follow up, nine were considered to have been tumour. There were two false negatives with one false positive. The overall sensitivity, specificity and positive and negative predictive values were 74, 73, 87 and 53% respectively. This is similar to figures previously quoted in published work. Despite relatively limited numbers, the utility of FDG PET imaging in our hands is similar to published reports. With a positive predictive value of 87%, a positive FDG study indicates a high likelihood that there is brain tumour present. A negative study does not exclude the presence of tumour.     

Flashlamp-excited dye laser therapy of idiopathic vulvodynia is safe and efficacious

Objective: The management of chronic vulvovaginal pain, not explicable on specific histologic grounds, presents a major problem in referral centers for lower genital tract diseases.Study design: This article reports on a two-step protocol in a sample of 175 medical nonresponders, drawn from a 2-year cohort of 725 women with vulvovaginal pain. The first maneuver was the use of a flashlamp-excited dye laser to selectively photocoagulate symptomatic subepithelial blood vessels in 168 women; the second was the microsurgical removal of chronically painful Bartholin's glands in 52 women not responsive or not suited to flashlamp-excited dye laser photothermolysis.Results: Dye laser response rates werer independent of whether patients manifested macroscopic focl of painful erythema (“vestibular adenitis”) or just colposcopically apparent hyperemia-ectasia of the individual blood vessels (“pruritic papillomatosis”) (55% vs 45% after a single surgical procedure; 76% vs 65% after serial retreatment; p not significant). Conversely, response rates were much lower among women in whom pressure on the Bartholin's glands produced sharp, lancinating pain (15% vs 66% after a single surgical procedure; 22% vs 93% after serial retreatment; p < 0.001). Forty-two (85%) of 50 patients with flashlamp-excited dye laser failure had deep pain; however, the impasse to progress was broken by gland removal. Final response rates were 92.5% (complete response 62%; partial response 30%) in the “surface-only” group and 80.3% in the “surface-plus-deep” group (χ² = 14.9; p < 0.001). The major complication was acute bacterial cellulitis, occurring in the first postoperative week. Modification of the treatment protocol to include topical antibiotics with an occlusive dressing reduced the cellulitis rate from 17.2% to 2.5%. In four women (1.8%) Koebner-like exophytic condylomas also developed within 1 month of flashlamp-excited dye laser surgery.Conclusion: The availability of a safe, efficacious, and relatively noninvasive treatment should reduce the need for resective surgery in most patients with idiopathic vulvodynia. 1995; 172; 1684–1701.)     

Colour duplex Doppler ultrasonography evaluation of non‐vasculogenic male erectile dysfunction: An Indian perspective

We present the study of colour duplex Doppler ultrasonography on Indian patients with non‐vasculogenic erectile dysfunction. Patients with a history suggestive of psychogenic impotence along with a normal clinical response to intracavernosal papaverine were presumed to have non‐vasculogenic erectile dysfunction. In our patients, the incidence of psychogenic impotence was much higher and the mean age of patients presenting with erectile dysfunction was lower as compared to patients from developed countries reported in research. The Doppler flowmetry showed much higher mean peak systolic velocities (PSVs) with a negative correlation between age and PSV. End diastolic velocity, resistive index and acceleration time values conformed to the literature.     

Frequency, urgency, and pelvic pain: Treating the pelvic floor versus the epithelium

For years the bladder epithelium has been the focus for diagnosing and treating the frequency, urgency, and pelvic pain of interstitial cystitis. However, many patients have not found symptom relief with these therapies. Pelvic floor dysfunction is often present in these patients, yet it is often untreated. Pelvic floor dysfunction may be related to abuse, past surgeries, or other causes. It is important to look outside of the bladder and explore other causes and treatments for this condition. Pelvic floor therapies should be a first line of treatment for those women with chronic pelvic pain related to pelvic floor dysfunction.