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Leydig and Sertoli cells are essential for the testicular homeostasis. Clinically, the testicular homeostasis is impaired in hypogonadal and subfertile men. Therapeutically, the selective oestrogen receptor modulator clomiphene citrate (CC) is frequently used to treat these patients. In men, the mechanism of action of CC has long been thought to be limited to inhibition of the retro-control by oestrogen on the pituitary gland. However, oestrogen receptors are also expressed in the testis. Therefore, we will explore in this review the systemic effects as well as its action on reproductive function. We will describe in particular the possible effects of CC on the secretory functions of Leydig and Sertoli cells and their implication on the testicular microenvironment. CC is a costeffective and relatively safe off-label treatment for young hypogonadal men actively trying for a child or subfertile men with low testosterone with a positive effect on sperm concentration. Nevertheless, its effects on the oestrogen receptors and other signalling pathways at the testicular level remain poorly investigated. Further research, including combined treatment, could allow improving sperm morphology and sperm motility which do not seem to be significantly enhanced by CC alone.

INTRODUCTION AND OBJECTIVE:There is increased interest in using testicular sperm in assisted reproduction technology (ART) to improve outcomes after previous failed cycles. Mehta et al. (2015) repo...

Study question Does Leukaemia affect spermatogenesis more adversely than Hodgkin’s lymphoma and is the effect consistent in sequential samples? Summary answer LLeukaemia is associated with a higher incidence of azoospermia, oligozoospermia and asthenozoospermia compared to Hodgkin’s lymphoma. These findings were consistent in sequential samples. What is known already Hodgkin’s lymphoma (HL) and leukaemias are common haematological malignancies that affect young men. Although not all treatments for these malignancies are gonadotoxic, there is evidence that malignancy affects sperm quality. Our own analysis in over 3000 men revealed that a diverse group of malignancies affected semen parameters adversely. There is concern that a single sample analysis may not reveal the true state due to varied period of abstinence and naturally occurring variation in semen quality. Leukaemia and lymphoma are systemic diseases; leukaemia usually runs a more torrid course whilst HL a more indolent course and therefore may variably affect spermatogenesis. Study design, size, duration A retrospective analysis was performed on 125 men with leukaemia and 303 men with HL. Only those men who had sequential semen analyses (1 and 2) within a month were included. Volume, sperm concentration and motility were the selected parameters in samples 1 and 2. Time period was April 1980 to January 2021. Participants/materials, setting, methods We included all post-pubertal men diagnosed with 2 most common haematological malignancies (Hodgkin’s lymphoma and leukaemia) in our database. Patient’s demographics, cancer diagnosis and semen parameters were extracted from a secure electronic database and analysed using MS Excel. Cancer diagnoses were obtained from referral letters from oncologists. Differences between samples 1 and 2 were tested using Fisher’s test, and odds ratios (OR) were calculated for the two malignancy groups. Main results and the role of chance We analysed 250 samples in 125 men with leukaemia and 606 samples in 303 men with HL. The mean intervals between the two semen samples were similar; 4.4 (1-30) and 3.8 (1-30) days. There were 95.7% of men Limitations, reasons for caution As we selected men with at least two semen samples on two separate occasions, we had to exclude men with single samples which substantially reduced the number of participants. Types of leukaemia and the stage of disease in HL were not analysed. Wider implications of the findings Our findings are pertinent when counselling men about fertility preservation even in the absence of planned gonadotoxic treatment. Awareness about increased azoospermia incidence may help plan oncoTESE procedures. Our findings could form a basis for studies examining spermatogenesis pathways in haematological malignancies. Trial registration number not applicable

Study question What live birth rate do we see when we use testicular sperm in ART for non-azoospermic couples after at least one previous failed cycle? Summary answer In our cohort of couples 24% had a live birth using testicular sperm and therefore was not higher than national average ART rates. What is known already There is increased interest in using testicular sperm in assisted reproduction technology (ART) to improve outcomes after previous failed cycles. Mehta et al. reported results of a 50% live birth rate using testicular sperm in the first cycle for couples with oligospermia and a history of failed cycles with ejaculated sperm. We aim to audit our results in a similar population of couples. Study design, size, duration St Peters Andrology Centre in London, United Kingdom completed 128 surgical testicular sperm retrievals reviewed between the two-year period of 2018–2019. We conducted a retrospective audit of their paper-based records to identify those couples with injectable sperm on their semen analysis and who had previous cycles attempts using ejaculated sperm. Participants/materials, setting, methods We identified 27 couples who underwent testicular sperm extraction despite having an ejaculated semen analysis with injectable sperm and at least one previous failed cycle. A systematic review of their paper and electronic medical record was conducted to assess live birth rates and fertilization rates from ART. Main results and the role of chance Couples had an average male age of 41 (range 31–60) and an average female age of 38 (range 30–45). The men had an average serum testosterone of 15 nmol/L (range 8–35 nmol/L) and an average serum FSH of 8.9 IU/L (range 1.7–30 IU/L). 59% (n = 17) of men had a DNA fragmentation index completed with an average score of 41% (range 31%–51[Y1]%). In the women the mean serum anti-Müllerian hormone (AMH) was 15.8 pmol/l (range 1–64 pmol/l). With ejaculated sperm the fertilization rate was 59% (95% CI [27%, 59%]) and blastocyst conversion rate was 43% (95% CI [50%, 69%]). There was no statistical significance with testicular sperm where the fertilization rate was 58% (95% CI [51%, 65%]) and blastocyst conversion rate was 54% (95% CI [40%, 67%]). Overall, there were 7 clinical pregnancies in this population of couples. Of these clinical pregnancies, 2 miscarried and 5 progressed to a live birth. This audit yielded a live birth rate per cycle of 15% and a live birth rate per couple of 24%. Limitations, reasons for caution Limitations of the study are low number of patients and absence of a control group. Wider implications of the findings: We recommend caution and further analysis going forward using testicular sperm in ART where ejaculated sperm in available. Trial registration number Not applicable

To describe the prevalence of Y-chromosome microdeletions in a multi-ethnic urban population in London, UK. To also determine predictive factors and a clinical threshold for genetic testing in men with Y chromosome microdeletions.A retrospective cohort study of 1473 men that were referred to a tertiary Andrology centre with male factor infertility between July 2004 and December 2016. All had a genetic evaluation, hormonal profile and 2 abnormal semen analyses. Those with abnormal examination findings also had targeted imaging performed.The prevalence of microdeletions was 4% (n = 58) in this study. These microdeletions were partitioned into the following regions: Azoospermia factors (AZF); AZFc (75%), AZFb+c (13.8%), AZFb (6.9%), AZFa (1.7%), and partial AZFa (1.7%). A high follicle-stimulating hormone level (P0.001) and a low sperm concentration (P0.05) were both found to be significant predictors for the identification of a microdeletion. Testosterone level, luteinising hormone level and testicular volume did not predict the presence of a microdeletion. None of the men with an AZF microdeletion had a sperm concentration of0.5 million/mL. Lowering the sperm concentration threshold to this level retained the high sensitivity (100%) and increased the specificity (31%). This would produce significant cost savings when compared to the European Academy of Andrology/European Molecular Genetics Quality Network and European Association of Urology guidelines. The surgical sperm retrieval (SSR) rate after microdissection testicular sperm extraction was 33.2% in men with AZFc microdeletion.The prevalence of Y-chromosome microdeletions in infertile men appears to vary between populations and countries. A low sperm concentration was a predictive factor (P0.05) for identifying microdeletions in infertile males. A threshold for genetic testing of 0.5 million/mL would increase the specificity and lower the relative cost without adversely affecting the sensitivity. The rate of SSR was lower than that previously described in the literature.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal malignancy with a poor 5-year survival rate. Accurate staging of PDAC is an important initial step in the development of a stage-specific treatment plan. Different staging systems/consensus statements convened by different societies and academic practices are currently used. The most recent version of the American Joint Committee on Cancer (AJCC) tumor/node/metastases (TNM) staging system for PDAC has shifted its focus from guiding management to assessing prognosis. In order to preoperatively define the resectability of PDAC and to guide management, additional classification systems have been developed. The National Comprehensive Cancer Network (NCCN) guidelines, one of the most commonly used systems, provide recommendations on the management and the determination of resectability for PDAC. The NCCN divides PDAC into three categories of resectability based on tumor-vessel relationship: 'resectable,' 'borderline resectable,' and 'unresectable'. Among these, the borderline disease category is of special interest given its evolution over time and the resulting variations in the definition and the associated recommendations for management between different societies. It is important to be familiar with the evolving criteria, and treatment and follow-up recommendations for PDAC. In this article, the most current AJCC staging (8th edition), NCCN guidelines (version 2.2019-April 9, 2019), and challenges and controversies in borderline resectable PDAC are reviewed.

Introduction and objectives Adult undescended testicles (UDTs) often present to fertility specialists with subfertility or azoospermia and with either an intra-abdominal or inguinal testicle(s). Performing an orchidopexy followed by a surgical sperm retrieval (SSR) is a potential option to retrieve spermatozoa. A microdissection TESE (mTESE) procedure is performed to retrieve mature spermatozoa for use in ICSI. This paper reviews the outcomes of mTESE in adults following an orchidopexy. Material and methods A cohort of azoospermic patients underwent adult orchidopexy over a 10-year period at a single specialist centre. Data were collected retrospectively from the patient records retrieved from an institutional database. All patients underwent pre-operative imaging to localize the testicles, serum testosterone levels and a semen analysis. Separate intraoperative testicular biopsies were performed to exclude intratubular germ cell neoplasia (ITGCN) and to analyse the Johnsen score. Results Twelve patients (age range 18-36 years) underwent orchidopexy procedures for either intra-abdominal or inguinal testicles. Mean follow-up was 34 months (range 13-58). Ninety per cent of patients had bilateral UDT with azoospermia. Pre-operative testosterone levels were within the normal range (mean 13.9 nmol/L; range 9.1-24.2). Five pelvic testicles (from four patients) were brought down and underwent a delayed mTESE. A total of nine inguinal orchidopexy procedures were carried out in eight men, and spermatozoa were found and preserved in three patients. None of the men with intra-abdominal testicles had mature spermatozoa present following a delayed mTESE. Overall, SSR was successful in 37.5% of the patients. Histological analysis showed no cases of ITGCN and the Johnsen scores ranged from 1 to 3.3. Conclusions Microdissection TESE following orchidopexy for inguinal testicles can result in a successful SSR in over 1/3rd of patients. Intra-abdominal testicles appear to lack spermatogonia although the testicles can still be preserved for endogenous hormone production. Adult orchidopexy allows preservation of endogenous testosterone, easier self-examination and an immediate or delayed mTESE in azoospermic patients.

Carcinoid tumors are the most common form of gut neuroendocrine tumors, however, they rarely present with small bowel obstruction. We present a case of a 65-year-old woman without prior abdominal operations who presented with symptoms of small bowel obstruction. Computed tomography (CT) showed multiple air fluid levels and a transition point in the left mesentery with two soft tissue densities at the same level. The patient was taken to the operating room for surgical exploration, which showed two intramural masses in the mid and distal jejunum, which surgical pathology showed to be stage IIIB carcinoid tumor.

OBJECTIVE To assess whether incomplete bladder emptying and the need for clean intermittent self-catheterization (CISC) is predictable, by analysing urodynamic and detrusor contractility variables in patients treated with botulinum toxin-A (BTX-A) for refractory idiopathic detrusor overactivity (IDO). PATIENTS AND METHODS Sixty-seven patients (mean age 50.3) with IDO, from two centres, had bladder injections of 200 U BTX-A. Patients with difficulty in emptying their bladder and/or persistent overactive bladder symptoms, with postvoid residual volumes (PVR) of >150 mL after treatment were started on CISC. Urodynamics were conducted at baseline, 4 and 12–16 weeks after injection with BTX-A. Detrusor contractility was assessed using the projected isovolumetric pressure (PIP1) in women and bladder contractility index (BCI) in men. RESULTS There were improvements in the mean maximum cystometric capacity, bladder compliance and maximum detrusor pressures during filling cystometry after BTX-A injections. The PVR was significantly increased at 4 but not at 12 weeks. Nineteen patients required CISC and when compared with those not needing CISC their pretreatment maximum flow rate (15 vs 22 mL/s, P = 0.003), PIP1 (43 vs 58, P = 0.02) and BCI (113 vs 180, P = 0.001) were lower. Receiver operator characteristic curve analysis suggested that a PIP1 of ≤50 in women (sensitivity 0.83; specificity 0.70; area under the curve 0.822) and BCI ≤120 (sensitivity 0.7; specificity 0.79; area 0.879) might predict the need for CISC. CONCLUSION The maximum flow rate, PIP1 and BCI were significantly lower in patients who required CISC after BTX-A treatment than in those who did not. A PIP1 of ≤50 in women and a BCI of ≤120 might be predictive of a need for CISC in this setting, and might help when counselling patients.

Ion suppression is a well-known phenomenon in electrospray ionization (ESI) mass spectrometry. These suppression effects have been shown to adversely affect the accuracy and precision of quantitative bioanalytical methods using ion spray. Such suppression effects have not been as well defined in atmospheric pressure chemical ionization (APCI) and there is some debate whether these effects actually occur in the ionization process using APCI. Here an example is described where clear ion suppression was observed during studies on a model compound and three metabolites using APCI liquid chromatography/tandem mass spectrometry (LC/MS/MS). Copyright © 2004 John Wiley & Sons, Ltd.

Health economic aspects are crucial in arguing the feasibility of setting up a new service using an unlicensed treatment. Overall, the costs of intradetrusor botulinum neurotoxin-A treatment appear to be modest relative to the improvement in quality of life. However, in managing the overactive bladder, there is a need for a widely accepted definition of ‘clinical improvement’ or a common outcome measure to direct future clinical and health economic research.

Sources of analytical variation in high-performance liquid chromatography/mass spectrometry (HPLC/MS), such as changes in retention, mass accuracy or signal intensity, have been investigated to assess their importance as a variable in the metabonomic analysis of human urine. In this study chromatographic retention and mass accuracy were found to be quite reproducible with the most significant source of analytical variation in the data sets obtained being the result of changes in detector response. Depending on the signal intensity threshold used to define the presence of a peak a sample component could be present in some replicate injections and absent in others within the same run. The implementation of a more sophisticated data software analysis package was found to greatly reduce the impact of detector response variability resulting in improved data analysis.