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Objective Previous research has indicated cognitive decline (CD) among testicular cancer patients (TCPs), even in the absence of chemotherapy, but little is known about the underlying pathophysiology. The present study assessed changes in cognitive functions and structural brain connectomes in TCPs and explored the associations between cognitive changes and endocrine status and hypothesized risk genotypes. Methods Thirty‐eight newly orchiectomized TCPs and 21 healthy controls (HCs) comparable to TCPs in terms of age and years of education underwent neuropsychological testing, structural MRI, and a biological assessment at baseline and 6 months later. Cognitive change was assessed with a neuropsychological test battery and determined using a standardized regression‐based approach, with substantial change defined as z‐scores ≤−1.64 or ≥1.64. MRI scans and graph theory were used to evaluate changes in structural brain connectomes. The associations of cognitive changes with testosterone levels, androgen receptor gene (AR) CAG repeat length, and genotypes (APOE, COMT, and BDNF) were explored. Results Compared with HCs, TCPs showed higher rates of substantial decline on processing speed and visuospatial ability and higher rates of substantial improvement on verbal recall and visuospatial learning (p < 0.05; OR = 8.15–15.84). Brain network analysis indicated bilateral thalamic changes in node degree in HCs, but not in TCPs (p < 0.01). In TCPs, higher baseline testosterone levels predicted decline in verbal memory (p < 0.05). No effects were found for AR CAG repeat length, APOE, COMT, or BDNF. Conclusions The present study confirms previous findings of domain‐specific CD in TCPs following orchiectomy, but also points to domain‐specific improvements. The results do not indicate changes in brain connectomes or endocrine status to be the main drivers of CD. Further studies evaluating the mechanisms underlying CD in TCPs, including the possible role of the dynamics of the hypothalamic–pituitary–gonadal axis, are warranted. The present study confirms previous findings of domain‐specific cognitive decline in testicular cancer patients following orchiectomy, but also points to domain‐specific improvements. The results do not indicate changes in brain connectomes or endocrine status to be the main drivers of cognitive changes.

Background Paratesticular leiomyosarcoma (LMS) is a rare tumor. Conventionally, tumor resection by high inguinal orchiectomy is performed as the preferred treatment approach for paratesticular sarcoma. On the other hand, testis-sparing surgery has recently attracted attention as a less-invasive treatment option for paratesticular sarcoma. However, the prognostic predictors and optimal treatment strategy for paratesticular LMS remain unclear because of its rarity. In this study, we systematically reviewed previously reported cases of paratesticular LMS to evaluate the prognostic factors and establish the optimal treatment strategy. Methods A systematic search of Medline, Web of Science, Embase, and Google was performed to find articles describing localized paratesticular LMS published between 1971 and 2020 in English. The final cohort included 217 patients in 167 articles. The starting point of this study was the time of definitive surgical treatment, and the end point was the time of local recurrence (LR), distant metastasis (DM), and disease-specific mortality. Results Patients with cutaneous LMS had a slightly better LR-free survival, DM-free survival, and disease-specific survival than those with subcutaneous LMS ( p  = 0.745, p  = 0.033, and p  = 0.126, respectively). Patients with higher grade tumors had a significantly higher risk of DM and disease-specific mortality (Grade 3 vs Grade 1 p  < 0.001, and Grade 3 vs Grade 1 p  < 0.001, respectively). In addition, those with a microscopic positive margin had a significantly higher risk of LR and DM than those with a negative margin (p < 0.001, and p  = 0.018, respectively). Patients who underwent simple tumorectomy had a slightly higher risk of LR than those who underwent high inguinal orchiectomy ( p  = 0.067). Subgroup analysis of cutaneous LMS demonstrated that the difference in LR between simple tumorectomy and high inguinal orchiectomy was limited ( p  = 0.212). On the other hand, subgroup analysis of subcutaneous LMS revealed a significant difference in LR ( p  = 0.039). Conclusions Our study demonstrated that subcutaneous LMS and high-grade tumors are prognostic factors for paratesticular LMS. For subcutaneous LMS, tumorectomy with high inguinal orchiectomy should be the optimal treatment strategy to achieve a negative surgical margin.

Background Testicular epidermoid cysts (TECs) are rare benign testicular neoplasms. As TECs are rarely associated with germ cell tumours (GCTs), the understanding of biological behaviour and clinical management of TEC is unresolved. Methods We retrospectively searched the files of patients treated for testicular neoplasms and germ cell cancer in the time from 2000 to 2017. Those with TEC were subjected to closer review looking to clinical and histological features, and to results from imaging with ultrasonography (US), contrast enhanced sonography (CEUS) and magnetic resonance imaging (MRI). Results Among 589 patients undergoing surgery for testicular tumour, nine simple TECs were identified (1.5, 95% confidence intervals 0.53–2.50%). Median age was 26 years. Imaging revealed sharply demarcated roundish lesions with avascular central areas. Eight patients underwent testis-sparing excision with no recurrence ensuing. One had orchiectomy because of large size of the mass. Histologically, TECs consisted of cornifying squamous cell epithelium and no accompanying germ cell neoplasia in situ. Two additional cases (0.3% of all) required orchiectomy because these TECs were associated with ipsilateral GCT. Conclusions TEC is usually a benign lesion that can safely be diagnosed with US, CEUS and MRI due to its roundish shape and its avascular centre. Histologically, this TEC corresponds to the prepubertal-type teratoma unrelated to germ cell neoplasia in situ of the 2016 WHO classification. The other subtype of TEC that is associated with invasive GCT represents a teratoma of postpubertal-type. From a clinical point of view it could be easier to differentiate between a “simple TEC” which is benign (prepubertal type) and a “complex TEC” which is malignant because of its association with invasive GCT.

Objective To perform a systematic review on the effects of testicular sparing surgery (TSS) on the oncological, functional, and hormonal outcomes of adults with testicular tumors. Methods A literature search was performed after PROSPERO registration (CRD42020200842) and reported in compliance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) methods. We conducted a systematic search of Medline (Ovid), Embase, Cochrane CENTRAL, CINAHL, Scopus, Web of Science, ClinicalTrials.gov, and the WHO/ICTRP from inception to November 20, 2020. Manuscripts and published s were included if they involved testis‐sparing surgery (TSS) and contained data on any outcomes related to fertility, hormonal parameters, or oncological control, or if they evaluated surgical technique. Results Our initial search yielded 3,370 manuscripts, with 269 of these screened for full‐text eligibility. After our exclusion criteria were applied, 32 studies were included in the final analysis. Oncological outcomes were obtained from 12 studies (average follow‐up 57.8 months), functional data from 26 studies (average follow‐up 49.6 months), fertility information from 10 studies (average follow‐up 55.8 months), and data on nonpalpable tumors from 11 studies (average follow‐up 32.1 months). Oncological control appears to be excellent in studies that reported these outcomes. Presence of germ cell neoplasia in situ was controlled with adjuvant radiation in nearly all cases. Functional outcomes are also promising, as development of primary and compensated hypogonadism was rare. Semen parameters are poor preoperatively among men with benign and malignant testis tumors, with occasional decline after TSS. Frozen section analysis at the time of surgery appears to be very reliable, and the majority of nonpalpable tumors appear to be benign. Conclusions TSS is a safe and efficacious technique with regards to oncological control and postoperative hormonal function based on retrospective, noncontrolled studies. TSS avoids unnecessary removal of benign testicular tissue, and should be given serious consideration in cases of nonpalpable, small tumors under 2 cm. In cases of malignancy, TSS can safely avoid anorchia in men with bilateral tumors and in men with solitary testicles. The use of the operating microscope, while theoretically promising, does not necessarily lead to better outcomes, however data are limited.

Background To investigate the correlation between testicular fat content (TFC) and sex hormone levels in patients with cryptorchidism and its value in assessing postsurgical testicular function. Methods Pelvic MRI with the mDIXON Quant sequence was performed on 23 cryptorchidism patients and 15 normal controls. The TFC before and after surgery was measured and compared. The correlations between cryptorchid TFC and testosterone (TSTO), follicle-stimulating hormone (FSH), and estradiol (E2) levels were analyzed, as was the specificity of TFC and each hormone for assessing testicular function after surgery. Results The preoperative cryptorchid TFC (3.06% ± 0.74) was higher than that of the normal controls (1.36% ± 0.49). TSTO was negatively correlated with the cryptorchid TFC (r = −0.698), while FSH and E2 were positively associated with the cryptorchid TFC (r = 0.658, 0.676). Cryptorchid TFC after surgery (2.01% ± 0.55) was lower than the preoperative TFC, but hormone levels were not significantly different. The TFC after surgery (0.864) had a larger AUC value than did TSTO (0.639), FSH (0.597), and E2 (0.586). Conclusion Noninvasive quantification of cryptorchid TFC using the mDIXON Quant sequence is more specific than hormone levels for assessing postsurgical changes in testicular function. Impact The cryptorchid testicular fat content is significantly higher than the normal testicular fat content. Cryptorchid testicular fat content is negatively correlated with presurgical serum TSTO levels and positively correlated with presurgical FSH and E2 levels. Pre- and postoperative changes in cryptorchid testicular fat content change are more sensitive than changes in TSTO, FSH, or E2 levels. Noninvasive cryptorchid testicular fat content quantified by the mDIXON Quant sequence is more specific than serum TSTO, FSH, and E2 levels for assessing changes in testicular function after cryptorchidism surgery.

Persistent Müllerian duct syndrome (PMDS) is a rare sexual development disorder. It is even more rarely associated with transverse testicular ectopia (TTE), a rare form of testicular ectopia, in which both testes descend through a single inguinal canal and are present in the same hemiscrotum. PMDS with TTE is associated with 18%–33% malignant transformation. Here we report the case of a 48-year-old man who presented with a large right inguinoscrotal swelling and on evaluation was found to have a large right testicular mass with complete right inguinal hernia, undescended left testis and a central abdominal mass. On evaluation with contrast-enhanced computed tomography abdomen and pelvis and image-guided biopsy he was diagnosed with mixed germ cell tumour of the right testis (predominantly a seminoma) with a retroperitoneal nodal mass and absent left testis, for which he received chemotherapy. Post-chemotherapy he underwent surgery and was diagnosed intraoperatively with PMDS along with TTE and testicular malignancy arising from the ectopic left testis. Postoperative recovery and follow-up were uneventful. Most cases of PMDS are diagnosed early in life. They present clinically with unilateral or bilateral undescended testis with inguinal hernia. In adults, PMDS is usually associated with male infertility. However, TTE is associated with an increased risk of testicular tumours if undiagnosed until adulthood. In adults PMDS with TTE is usually an intraoperative finding and is commonly associated with malignancy in the ectopic/undescended testis.

Cryptorchidism is a common cause of male infertility, often necessitating microdissection testicular sperm extraction (m-TESE) for sperm retrieval post-surgery. However, uncertainties persist regarding m-TESE outcomes and influencing factors following cryptorchidism surgery. A systematic review and meta-analysis were conducted to evaluate sperm retrieval rates (SRR) among patients undergoing m-TESE after cryptorchidism surgery. Factors including age at orchidopexy, age at m-TESE, type of cryptorchidism, serum hormone levels, testicular volume, and interval from surgery to m-TESE were analyzed for their impact on SRR.Nine studies encompassing 935 patients were included. The overall SRR was 57% (95% confidence interval [CI] 51% to 63%). Compared to patients with negative sperm retrieval (SR-), patients with positive sperm retrieval (SR+) underwent m-TESE at an older age (1.81 years; 95% CI 1.17 to 2.45) and orchidopexy at a younger age (-3.35 years; 95% CI -6.34 to -0.36). Different types of cryptorchidism (including high scrotal, inguinal canal, intra-abdominal) significantly influenced SRR (P<0.05). Serum testosterone, follicle-stimulating hormone, luteinizing hormone levels and testicular volume showed no significant correlation with SRR (P>0.05). Furthermore, SR- patients typically experienced shorter intervals from orchidopexy to m-TESE compared to SR+ patients (34.09 months; 95% CI 0.40 to 67.77). Earlier orchidopexy and much later m-TESE procedures, as well as undescended testis closer to the scrotum, increase the likelihood of successful sperm retrieval. Orchidopexy for cryptorchidism should be done as early as possible, whether it is performed before 18 months of age or detected at a much older age. In patients with undetected cryptorchidism and azoospermia after puberty, m-TESE should not be performed immediately after orchidopexy, the optimal interval from orchidopexy to m-TESE still requires further study.

Post-operative intra-abdominal adhesions, significantly affecting testicular tissue, are a prevalent and serious complication following laparoscopic surgery. This study investigated the efficacy of boric acid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, in preventing post-operative testicular adhesions. Forty rats, were divided into four groups: control, laparoscopy (LA), boric acid (BA), and LA + BA. Following laparoscopic surgery, BA treatment was administered for seven days. While the adhesion score was around 3 in the LA group, it was 1 or below in the LA + BA group. Testicular tissues were examined by histopathological and biochemical methods. In testis tissues, in the LA group, malondialdehyde (MDA) levels increased while superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels decreased; these parameters normalized with BA treatment. Additionally, the LA group exhibited reduced levels of IL-10, Bcl-2, Kisspeptin-1, and GnRH, alongside elevated levels of inflammatory markers IL-1β, IL-6, TNF-α, JNK, BAX, and Caspase 3. BA treatment significantly restored these levels to normal. In conclusion, oxidative stress, inflammation, and apoptosis in testicular tissues were associated with post-operative testicular adhesions. BA demonstrated potential as an anti-adhesive agent, reducing testicular adhesions and normalizing biochemical and histological parameters following laparoscopic surgery.

ObjectivesTo evaluate the biochemical milieu in testes with nonobstructive azoospermia (NOA) by using proton MR spectroscopy (1H-MRS) in detecting differences in testicular metabolites between histological stages of NOA and in assessing the possible presence of spermatozoa before microdissection testicular sperm extraction (mTESE).MethodsForty-nine NOA men and fifty age-matched controls were included in this prospective study. A single-voxel point-resolved spectroscopy sequence with TR/TE (2000/25 ms) was used. NOA testes were classified using the higher Johnsen score (hJS) (group 1, hJS ≥ 8; and group 2, hJS < 8). Nonparametric statistical tests were used to assess differences in normalized metabolite concentrations, defined as ratios of the metabolite concentrations versus creatine concentration between (a) NOA and controls, (b) NOA groups, and (c) NOA with positive and negative sperm retrieval.ResultsNormalized concentrations of total choline (median 0.396 vs 1.09 mmol/kg, p = 0.002), myo-inositol (median 1.985 vs 3.19 mmol/kg, p = 0.002), and total lipids and macromolecules (TLM) resonating at 0.9 ppm (median 0.962 vs 2.43 mmol/kg, p = 0.024), 1.3 ppm (median 4.88 vs 10.7 mmol/kg, p = 0.043), and 2.0 ppm (median 2.33 vs 5.96 mmol/kg, p = 0.007) were reduced in NOA testes compared with controls. Decreased concentrations of TLM 2.0 (median 3.755 vs 0.436 mmol/kg, p = 0.043) were found in group 2 compared with group 1. Increased normalized concentrations of glutamate were observed in NOA testes with failed sperm retrieval (median 0.321 vs 0.000 mmol/kg, p = 0.028).Conclusions1H-MRS provides metabolic information about the testis in NOA patients and assesses spermatogenic status before mTESE.Key Points• NOA testes differed from age-matched controls, in terms of reduced normalized concentrations of tChol, mI, and lipids.• TLM 2.0 peaks were found useful in the identification of NOA testes with the presence of foci of advanced spermatogenesis up to the haploid gamete stage.• Glu proved a reliable metabolic signature of spermatogenesis in NOA population by assessing the possible presence of sperm after mTESE.

This study assessed testicular function in children with cryptorchidism following different orchidopexy procedures by measuring serum anti-Müllerian hormone (AMH). The aim was to identify clinical factors associated with testicular function recovery by comparing pre- and post-operative levels of AMH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and testicular volume at various time points. This prospective observational cohort study included children aged 1 to 1.5 years diagnosed with cryptorchidism via physical examination and ultrasound. The study evaluated testicular function parameters before and after two different orchidopexy techniques, measured at five intervals. Serum AMH was the primary outcome, with FSH, LH, testosterone, and testicular volume as secondary measures. A control group of 57 healthy male infants aged 1 to 2 years was included for comparative analysis. A total of 138 patients were enrolled, with testicular function evaluated preoperatively and at 10 days, 1 month, 3 months, and 6 months post-surgery. Preoperative AMH levels were significantly higher in unilateral compared to bilateral cryptorchidism ( P  < 0.05). Postoperatively, AMH levels increased by 3 months in children with palpable testicles and by 6 months in those with non-palpable testicles ( P  < 0.05), with no significant difference between groups at 6 months. Cases with intraperitoneal release procedures also showed significant AMH increases at 3 and 6 months ( P  < 0.05), and testicular function improved similarly across surgical techniques. Conclusion : Orchidopexy can pose a risk of injury, emphasizing the need for careful treatment planning. While surgical technique did not significantly affect outcomes in children aged 1 to 1.5 years, serum AMH is a valuable tool for preoperative evaluation and prognosis in cryptorchidism. What is Known: • Cryptorchidism impairs testicular function. • Orchidopexy improves function but varies by technique and testicular position. What is New: • AMH is a sensitive postoperative marker for testicular recovery. • Function improvement is consistent across surgical techniques, with intraperitoneal release showing significant AMH gains by 3–6 months.