Surgical and minimally invasive treatment of ischaemic and non-ischaemic priapism: a systematic review by the EAU Sexual and Reproductive Health Guidelines panel.

Surgical treatments for ischemic priapism (IP) include shunts or penile implants. Non-ischemic priapism (NIP) is usually the result of penile/perineal trauma causing an arterial fistula and embolisation may be required. We conducted a systematic review on behalf of the EAU Sexual and Reproductive health Guidelines panel to analyse the available evidence on efficacy and safety of surgical modalities for IP and NIP. Outcomes were priapism resolution, sexual function and adverse events following surgery. Overall, 63 studies (n = 923) met inclusion criteria up to September 2021. For IP (n = 702), surgery comprised distal (n = 274), proximal shunts (n = 209) and penile prostheses (n = 194). Resolution occurred in 18.7-100% for distal, 5.7-100% for proximal shunts and 100% for penile prostheses. Potency rate was 20-100% for distal, 11.1-77.2% for proximal shunts, and 26.3-100% for penile prostheses, respectively. Patient satisfaction was 60-100% following penile prostheses implantation. Complications were 0-42.5% for shunts and 0-13.6% for IPP. For NIP (n = 221), embolisation success was 85.7-100% and potency 80-100%. The majority of studies were retrospective cohort studies. Risk of bias was high. Overall, surgical shunts have acceptable success rates in IP. Proximal/venous shunts should be abandoned due to morbidity/ED rates. In IP > 48 h, best outcomes are seen with penile prostheses implantation. Embolisation is the mainstay technique for NIP with high resolution rates and adequate erectile function.

What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Guidelines Panel.

Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by the occlusion of small blood vessels by sickle-shaped red blood cells. SCD is associated with a number of complications, including ischemic priapism. While SCD accounts for at least one-third of all priapism cases, no definitive treatment strategy has been established to specifically treat patients with SC priapism. The aim of this systematic review was to assess the efficacy and safety of contemporary treatment modalities for acute and stuttering ischemic priapism associated with SCD. The primary outcome measures were defined as resolution of acute priapism (detumescence) and complete response of stuttering priapism, while the primary harm outcome was as sexual dysfunction. The protocol for the review has been registered (PROSPERO Nr: CRD42020182001), and a systematic search of Medline, Embase, and Cochrane controlled trials databases was performed. Three trials with 41 observational studies met the criteria for inclusion in this review. None of the trials assessed detumescence, as a primary outcome. All of the trials reported a complete response of stuttering priapism; however, the certainty of the evidence was low. It is clear that assessing the effectiveness of specific interventions for priapism in SCD, well-designed, adequately-powered, multicenter trials are strongly required.

Andrological effects of SARS-Cov-2 infection: a systematic review and meta-analysis.

PURPOSE: The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated. METHODS: All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (n = 19), as well as those reporting data on semen analysis (n = 5) and hormonal parameters (n = 11) in infected/recovered patients without any arbitrary restriction were included. RESULTS: Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1 ± 12.6 years, and mean follow-up 24.3 ± 18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological effects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality. CONCLUSIONS: The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specific contribution of reduced T levels during the acute phase of the infection needs to be better clarified.

The management of penile intraepithelial neoplasia (PeIN): clinical and histological features and treatment of 345 patients and a review of the literature.

INTRODUCTION: Penile intraepithelial neoplasia (PeIN) is a histological term for precancerous penile lesions. PeIN is important due to the high morbidity and mortality associated with progression to penile squamous cell carcinoma (PSSC). But PeIN is rare, contributing to a limited evidence-base for the relative efficacy of available treatment options. OBJECTIVES & METHODS: To consolidate and expand knowledge about PeIN and its treatment, we describe the clinical and histological characteristics, treatments and outcomes of 345 patients with PeIN, managed by our multidisciplinary team. Our results are compared and contrasted with those in the literature, following comprehensive review. RESULTS: 8.7% of patients had concomitant, invasive PSCC, whilst 91.3% demonstrated PeIN alone. 84% had undifferentiated PeIN, and 10.7% differentiated PeIN (5.2%, not specified). Clinical or histological evidence of HPV alone was present in 58%; features of lichen sclerosus alone in 12%; features of both in 29.4%. Only 14.4% of patients could be treated solely with topical agents or cryotherapy, whereas the remaining 85.6% underwent some form of surgical intervention, circumcision being the mainstay. Just 2.6% progressed to PSCC. CONCLUSIONS: Clinical management of PeIN can be rationally optimized with excellent outcomes. Circumcision is important. Topical treatments alone are disappointing.

The role of artery-preserving varicocelectomy in subfertile men with severe oligozoospermia: a randomized controlled study.

BACKGROUND: There is wide agreement nowadays that a clinical varicocoele should be ligated to treat male factor infertility. However, the significance of testicular artery preservation in patients with severe oligozoospermia has not been addressed before. OBJECTIVES: To assess the outcome of varicocelectomy in infertile men with severe oligozoospermia and clinical varicocoeles and to compare internal spermatic artery preservation vs. artery ligation. MATERIALS AND METHODS: This prospective randomized study included 302 infertile patients with severe oligozoospermia and clinical (grade II/III) varicocoeles. Patients were randomized into two groups: group A (150 patients) underwent artery-preserving varicocelectomy (APV) and group B (152 patients) underwent artery-ligating varicocelectomy (ALV). The primary outcome was to assess the changes in sperm density and motility at 3 and 6 months postoperatively in both groups. The secondary outcome was to compare the natural pregnancy rate at 1-year of follow-up. Univariate and multivariate analyses were performed to determine factors affecting pregnancy rate. RESULTS: In both groups, there was a statistically significant improvement in sperm density and motility at 3 and 6 months postoperatively. In group A, there was a greater improvement in sperm density (p < 0.001) and motility (p < 0.001) compared to group B. At 1-year follow-up, overall 35.1% achieved a natural pregnancy. Group A achieved a significantly higher natural pregnancy rate (40% vs. 30%, p value = 0.03) compared to group B. Smaller testicular volume and ALV were the independent predictors of lower pregnancy rate ((HR = 3.2, 95% CI 1.2-8.3, p = 0.01) and (HR = 3.2, 95% CI 1.4-7.1, p = 0.003), respectively). CONCLUSION: In men with severe oligozoospermia and a clinical varicocoele, APV results in improved outcomes as compared to ALV with respect to semen parameters and natural pregnancy rates. Therefore, all attempts should be made to preserve internal spermatic arteries (ISA) during varicocelectomy in men with severe oligozoospermia.

Penile lymphoedema: approach to investigation and management.

BACKGROUND: Penile lymphoedema (with and without cellulitis) is a rare, often chronic, clinically heterogeneous entity with an uncertain pathogenesis and an important differential diagnosis. It creates significant physical and psychosexual morbidity, and presents considerable therapeutic challenges. The existing literature is limited. AIM: To describe and share our updated cumulative experience of a cohort of patients with penile lymphoedema. METHODS: This was a retrospective review of the case records of patients with chronic penile lymphoedema seen in two dedicated male genital dermatology clinics between January 2011 and July 2016. RESULTS: In total, 41 cases were identified. Over a third had Crohn disease (CD) (which was occult in one-third of these), and over a third had serological evidence of streptococcal infection. All patients responded to systemic antibiotics and specialized urological surgery circumcision and excision). CONCLUSIONS: Penile lymphoedema should be investigated to exclude underlying pathology especially CD and streptococcal infection. Treatment with antibiotics should be considered early and long term to try to preserve the foreskin: most patients are uncircumcised. Some patients may benefit from a course or courses of oral steroids. The development of gross dysfunction of the prepuce usually dictates circumcision and excision of lymphoedematous tissue once the situation is medically stabilized.

Endometriosis of the appendix presenting as acute appendicitis with unusual appearance.

INTRODUCTION: Endometriosis of the appendix is an uncommon mimicker of acute appendicitis which makes for a diagnostic dilemma. PRESENTATION OF CASE: We present a rare case of a menstruating woman presenting with classic symptoms of appendicitis, without the characteristic inflammatory changes seen on laparoscopy consistent with appendicitis. Instead, the appendix appeared unusually contracted on itself. Pathologic review of the appendix revealed microscopic findings of endometriosis. DISCUSSION: We theorize the growth and shedding of the endometrial tissue during menstruation caused compression of the neural plexi in the wall of the appendix leading to the presentation mimicking acute appendicitis. CONCLUSION: Given the potential for endometrial appendicitis, we propose appendectomy in reproductive age female patients with right lower quadrant pain, regardless of appendix appearance on laparoscopy.

Practical consensus recommendations on management of HR + ve early breast cancer with specific reference to genomic profiling.

Breast cancer is a heterogeneous disease and patients are managed clinically based on ER, PR, HER2 expression, and key risk factors. The use of gene expression assays for early stage disease is already common practice. These tests have found a place in risk stratifying the heterogeneous group of stage I-II breast cancers for recurrence, for predicting chemotherapy response, and for predicting breast cancer-related mortality. Most guidelines for hormone receptor (HR)-positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. Expert oncologist discussed about strategies of gene expression assays and aid in chemotherapy recommendations for treatment of HR + ve EBC and the expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Practical consensus recommendation on when to do BRCA testing.

BRCA-mutation associated breast cancer and to future cancer risks and sensitivity to systemic therapies. Now that rapid genetic testing for BRCA1 and BRCA2 mutations is available, BRCA mutation status can be considered when making treatment and prevention decisions for BRCA testing, BRCA mutation carriers with breast cancer. Expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

Practical consensus recommendations regarding the management of HER2 neu positive metastatic breast cancer.

Metastatic breast cancer (MBC) is cancer that has spread from the breast to another part of the body or has come back in another distant location. Treatment options for MBC depend on several factors, including where the cancer has spread, the patient's overall health, and the levels of hormone receptors and HER2 in the tumour. Over-expression of HER2 is generally considered to be a negative prognostic feature because it accompanies an increase in breast cancer mortality. However, the development of agents that specifically target HER2 has improved the management of patients with these tumours.[7],[8],[9],[10] This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations in regards with the use of these agents and the management of HER2 positive MBC for the benefit of community oncologists.

The diagnosis and management of male genital lichen sclerosus: a retrospective review of 301 patients.

INTRODUCTION: Male genital lichen sclerosus (MGLSc) is an acquired, chronic, inflammatory skin disease that is associated with significant morbidity and squamous cell carcinoma of the penis (PSCC). However, some clinical, diagnostic and management controversies endure, including the relationship with penile intraepithelial neoplasia (PeIN). OBJECTIVES: To clarify clinical presentations, diagnostic approaches, histological findings, response to treatment and the relationship with PeIN. METHODS: Retrospective review of patients with a diagnosis of MGLSc who attended a specialist male genital dermatoses clinic. RESULTS: 301 patients were identified: 260 had isolated MGLSc and 41 both MGLSc and PeIN. Referrals were made from the local Urology and Andrology departments (128), primary care (89), GUM (54), other dermatology departments (28) and other specialties (2). In isolated MGLSc, 94.6% were diagnosed clinically with 93.5% accuracy (based on data from subsequent circumcisions). In combined MGLSc/PeIN, 85.4% were diagnosed following diagnostic biopsy and 14.6% retrospectively after circumcision. In isolated MGLSc, 50% were treated topically, and 50% required surgery. In MGLSc/PeIN, 78% required surgical interventions. In isolated MGLSc, 92.2% achieved resolution of symptoms, 3.5% were awaiting procedures, and 4.8% were receiving ongoing topical therapy. In MGLSc/PeIN, 90.2% achieved clearance, 2.4% were waiting surgery, and 7.3% were treated topically. Only 2.7% reported ongoing symptoms, all in patients treated surgically. None progressed to PSCC. DISCUSSION: MGLSc is generally a disease of the uncircumcised; the majority of cases of MGLSc are accurately diagnosed clinically; suspected PeIN or PSCC requires histological confirmation; circumcision histology can be non-specific; most men are either cured by topical treatment with ultrapotent corticosteroid (53.1%) or by circumcision (46.9%); surgical intervention is required in most cases of concomitant MGLSc and PeIN; the majority of patients with MGLSc alone or with MGLSc and PeIN remit with this approach; effective management appears to negate the risk of malignant transformation to PSCC.

Pre-operative functional status as a predictor of morbidity and mortality after elective cervical spine surgery.

AIMS: Patients seeking cervical spine surgery are thought to be increasing in age, comorbidities and functional debilitation. The changing demographics of this population may significantly impact the outcomes of their care, specifically with regards to complications. In this study, our goals were to determine the rates of functionally dependent patients undergoing elective cervical spine procedures and to assess the effect of functional dependence on 30-day morbidity and mortality using a large, validated national cohort. PATIENTS AND METHODS: A retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program data files from 2006 to 2013 was conducted to identify patients undergoing common cervical spine procedures. Multivariate logistic regression models were generated to analyse the independent association of functional dependence with 30-day outcomes of interest. RESULTS: Patients with lower functional status had significantly higher rates of medical comorbidities. Even after accounting for these comorbidities, type of procedure and pre-operative diagnosis, analyses demonstrated that functional dependence was independently associated with significantly increased odds of sepsis (odds ratio (OR) 5.04), pulmonary (OR 4.61), renal (OR 3.33) and cardiac complications (OR 4.35) as well as mortality (OR 11.08). CONCLUSIONS: Spine surgeons should be aware of the inherent risks of these procedures with the functionally dependent patient population when deciding on whether to perform cervical spine surgery, delivering pre-operative patient counselling, and providing peri-operative management and surveillance. Cite this article: Bone Joint J 2017;99-B:824-8.

Mean velocity and peak systolic velocity can help determine ischaemic and non-ischaemic priapism.

AIM: To determine the threshold waveform characteristics at Doppler ultrasound (DUS) to differentiate between ischaemic and non-ischaemic priapism. MATERIALS AND METHODS: Fifty-two patients were categorised into "ischaemic" and "non-ischaemic" types based on clinical and blood-gas findings: 10 patients with non-ischaemic priapism; 20 with ischaemic priapism before surgical shunt placement and 22 with ischaemic priapism after surgical shunt placement. DUS traces were analysed: peak systolic velocity (PSV) and mean velocity (MV) were calculated. Histological samples were obtained at the time of surgery. Three clinical outcome groups were defined: (1) normal, (2) regular use of pharmacostimulation, and (3) refractory dysfunction/penile implant. RESULTS: All non-ischaemic priapism cases had a PSV >50 cm/s and all but one had an MV of >6.5 cm/s. In pre-surgery ischaemic cases, all men had a PSV <50 cm/s and MV <6.5 cm/s. Two flow patterns were observed in this group: PSV <25 cm/s in all men scanned before needle aspiration; and in 6/14 after needle aspiration, a high velocity/high resistance (low net inflow) pattern, with peak systolic flows >22 cm/s but diastolic reversal. In post-surgery ischaemic priapism, flow parameters overlapped with the non-ischaemic group. PSV/MV did not predict clinical outcome or histology. CONCLUSION: In the present cohort, PSV <50 cm/s and MV <6.5 cm/s were predictive of ischaemic priapism (pre-shunt; p<0.01). Patients with ischaemic priapism may show PSV >22 cm/s, but have diastolic reversal and therefore low net perfusion. Post-shunt, DUS findings were extremely variable and did not predict histology or clinical outcome.

Self injection of foreign materials into the penis.

Injection of the subcutaneous tissues of the penis for enlargement of penile girth has been practised for many years by laypeople and medical practitioners alike. However, with recognition of the complications, the practice has died out. We report a series of five patients who presented having injected foreign materials into the subcutaneous tissues of their penises, including paraffin and mineral oils. Our patients had a variable time course of presentation ranging from 1 day following injection to over 26 years. Self-injection of the subcutaneous tissues of the penis is an unusual presentation for a penile mass but should be considered as a differential diagnosis in patients with a long latent period to presentation or with characteristic magnetic resonance imaging and histological appearances.

Minimal Invasive Management of Lymph Nodes.

Penile cancer is a rare genitourinary malignancy. Lymph node involvement is the single most important factor determining survival in these patients, and those patients with occult disease are difficult to identify on conventional cross-sectional imaging. Until recently, lymph node sampling (eg, lymphadenectomy) has been the diagnostic modality of choice in the detection of micrometastasis. More recently, several novel molecular and minimally invasive diagnostic techniques have been developed, which have been demonstrated to decrease the false-negative and -positive results of conventional imaging and lymphadenectomy. This article focuses on the minimally invasive management of lymph nodes in men with penile cancer.

Prevalence of CYP2C8 polymorphisms in a North Indian population.

CYP2C8 is an important member of the cytochrome P450 family of enzymes; it affects the activity of various drugs used in routine clinical practice, including amiodarone, chloroquine, amodiaquine, and repaglinide, as well as endogenous compounds, such as arachidonic acid and retonic acid. It is also the main enzyme involved in the metabolism of the widely used anticancer drug Paclitaxel, which has a very narrow therapeutic index. There is evidence that single nucleotide polymorphisms in the CYP2C8 gene influence the adverse reactions and/or the efficacy of drugs metabolized by this enzyme. We examined the allele and genotype frequencies of widely studied functional polymorphisms of the CYP2C8 gene in a North Indian population. We assayed the genomic DNA of at least 251 healthy unrelated North Indians for CYP2C8*2, CYP2C8*3 (G416A, A1196G), and CYP2C8*4 genetic polymorphisms by RFLP technique. These results were compared to information on other populations. The allelic frequencies of CYP2C8*2, CYP2C8*3, and CYP2C8*4 were found to be 3, 4, and 4% respectively. The two CYP2C8*3 polymorphisms (G416A and A1196G) were found to be completely linked to each other. Allele frequencies of CYP2C8 genetic variants in northern Indians were found to have a distinct pattern that differs from that of southern Indian and other global populations. This is the first report from North India on CYP2C8 polymorphisms. Ethnic differences with respect to polymorphisms are the molecular basis of interethnic variability in pharmacokinetics. Our study may help in rational use of drugs that are substrates for CYP2C8 in this population.

Hypoxia-induced mixed-lineage leukemia 1 regulates glioma stem cell tumorigenic potential.

Normal stem cells reside in functional niches critical for self-renewal and maintenance. Neural and hematopoietic stem cell niches, in particular, are characterized by restricted availability of oxygen and the resulting regulation by hypoxia-inducible factors (HIFs). Glioblastoma multiforme (GBM) is the most common malignant brain tumor and also contains high degrees of hypoxia. Heterogeneity within the neoplastic compartment has been well characterized in GBM and may be derived from genetic and epigenetic sources that co-evolve during malignant progression. Recent experimental evidence has supported the importance of hypoxia in glioma stem cell (GSC) niches. We hypothesized that HIFs require epigenetic-modifying proteins to promote tumor malignancy in GBM. Here we demonstrate that in GBM the histone methyltransferase mixed-lineage leukemia 1 (MLL1) is induced by hypoxia and enhances hypoxic responses. Loss of MLL1 reduces the expression of HIF transcripts and HIF2α protein. Targeting MLL1 by RNA interference inhibited the expression of HIF2α and target genes, including vascular endothelial growth factor (VEGF). GSCs expressed higher levels of MLL1 than matched non-stem tumor cells and depletion of MLL1 reduced GSC self-renewal, growth, and tumorigenicity. These studies have uncovered a novel mechanism mediating tumor hypoxic responses linking microenvironmental regulation of epigenetic-modifying proteins to cellular heterogeneity and provide rationale for the design of more sophisticated clinical approaches targeting epigenetic regulation.