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Introduction: Herein, we analyzed the histopathological, oncological and functional outcomes of testis-sparing surgery (TSS) in patients with distinct risk for testicular cancer. Methods: This is a multicenter retrospective study on consecutive patients who underwent TSS. Patients were categorized in high- or low-risk testicular germ cell tumor (TGCT) according to the presence/absence of features compatible with testicular dysgenesis syndrome. Histology was categorized per size and risk groups. Results: TSS was performed in 83 patients (86 tumors) of them, 27 in the high-risk group. Fifty-nine patients had a non-tumoral contralateral testis present. Sixty masses and 26 masses were benign and TGCTs, respectively. No statistical differences were observed in mean age (30.9 ± 10.32 years), pathological tumor size (14.67 ± 6.7 mm) between risk groups or between benign and malignant tumors (p = 0.608). When categorized per risk groups, 22 (73.3%) and 4 (7.1%) of the TSS specimens were malignant in the high- and low-risk patient groups, respectively. Univariate analysis showed that the only independent variable significantly related to malignant outcome was previous history of TGCT. During a mean follow-up of 25.5 ± 22.7 months, no patient developed systemic disease. Local recurrence was detected in 5 patients and received radical orchiectomy. Postoperative testosterone levels remained normal in 88% of those patients with normal preoperative level. No erectile dysfunction was reported in patients with benign lesions. Conclusion: TSS is a safe and feasible approach with adequate cancer control, and preservation of sexual function is possible in 2/3 of patients harboring malignancy. Incidence of TGCT varies extremely between patients at high and low risk for TGCT requiring a careful consideration and counseling. [ABSTRACT FROM AUTHOR]

IntroductionCurrent evidence shows that serum miR-371a-3p can identify disease recurrence in testicular germ cell tumour (TGCT) patients and correlates with tumour load. Despite convincing evidence showing the advantages of including miR-371a-3p testing to complement and overcome the classical serum tumour markers limitations, the successful introduction of a serum miRNA based test into clinical practice has been impeded by a lack of consensus regarding optimal methodologies and lack of a universal protocol and thresholds. Herein, we investigate two quantitative real-time PCR (qRT-PCR) based pipelines in detecting disease recurrence in stage I TGCT patients under active surveillance, and compare the sensitivity and specificity for each method.MethodsSequential serum samples collected from 33 stage I TGCT patients undergoing active surveillance were analysed for miR-371a-3p via qRT-PCR with and without an amplification step included.ResultsUsing a pre-amplified protocol, all known recurrences were detected via elevated miR-371a-3p expression, while without pre-amplification, we failed to detect recurrence in 3/10 known recurrence patients. For pre-amplified analysis, sensitivity and specificity was 90% and 94.4% respectively. Without amplification, sensitivity dropped to 60%, but exhibited 100% specificity.DiscussionWe conclude that incorporating pre-amplification increases sensitivity of miR-371a-3p detection, but produces more false positive results. The ideal protocol for quantification of miR-371a-3p still needs to be determined. TGCT patients undergoing active surveillance may benefit from serum miR-371a-3p quantification with earlier detection of recurrences compared to current standard methods. However, larger cross-institutional studies where samples are processed and data is analysed in a standardised manner are required prior to its routine clinical implementation.

Objective:Distant metastasis other than non-regional lymph nodes and lung (i.e., M1b stage) significantly contributes to the poor survival prognosis of patients with germ cell testicular cancer (GCTC). The aim of this study was to develop a machine learning (ML) algorithm model to predict the risk of patients with GCTC developing the M1b stage, which can be used to assist in early intervention of patients.MethodsThe clinical and pathological data of patients with GCTC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Combing the patient's characteristic variables, we applied six machine learning (ML) algorithms to develop the predictive models, including logistic regression(LR), eXtreme Gradient Boosting (XGBoost), light Gradient Boosting Machine (lightGBM), random forest (RF), multilayer perceptron (MLP), and k-nearest neighbor (kNN). Model performances were evaluated by 10-fold cross-receiver operating characteristic (ROC) curves, which calculated the area under the curve (AUC) of models for predictive accuracy. A total of 54 patients from our own center (October 2006 to June 2021) were collected as the external validation cohort.ResultsA total of 4,323 patients eligible for inclusion were screened for enrollment from the SEER database, of which 178 (4.12%) developing M1b stage. Multivariate logistic regression showed that lymph node dissection (LND), T stage, N stage, lung metastases, and distant lymph node metastases were the independent predictors of developing M1b stage risk. The models based on both the XGBoost and RF algorithms showed stable and efficient prediction performance in the training and external validation groups.ConclusionS-stage is not an independent factor for predicting the risk of developing the M1b stage of patients with GCTC. The ML models based on both XGBoost and RF algorithms have high predictive effectiveness and may be used to predict the risk of developing the M1b stage of patients with GCTC, which is of promising value in clinical decision-making. Models still need to be tested with a larger sample of real-world data.

Among males aged between 15 and 35 years, testicular cancer is the most commonly diagnosed cancer. Testicular germ cell tumours are generally considered curable and respond dramatically to adjuvant treatment. Cisplatin-based chemotherapy regimens are used ubiquitously, inevitably leading to iatrogenic morbidity. Herein, we represent a case of a patient diagnosed with a non-seminomatous germ cell tumour, who underwent adjuvant cisplatin-based chemotherapy treatment and subsequently developed an acute ischemic stroke. In cancer patients, a malignancy-induced hypercoagulability state can cause thromboembolic events. Nonetheless, anti-cancer therapy may dramatically increase the risk of thromboembolic events, by analogue mechanisms, such as the release of pro-coagulant mediators, direct endothelial injury or stimulation of tissue factor production by host cells. Among various chemotherapy agents correlated with thromboembolism, cisplatin is expected to carry a higher risk for thromboembolic complications. Acute cerebrovascular events secondary to anti-neoplastic agents require an interdisciplinary approach, including referral to more experienced centres when needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cisplatin-based chemotherapy regimens are the backbone of chemotherapy for germ cell testicular cancer. Cisplatin is administered for five days, causing an overlap of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Although CINV is widely researched, studies involving multiday chemotherapy regimens are limited. OBJECTIVES: This article synthesizes the research in antiemetics used in multiday cisplatin-based chemotherapy regimens and provides recommendations to optimize antiemetic therapy. METHODS: A literature review was conducted for articles examining antiemetics in multiday cisplatin-based chemotherapy regimens. Results were synthesized, and findings were applied to existing antiemetic strategies. FINDINGS: Although an optimal regimen has not been identified, patients receiving multiday cisplatin chemotherapy should have an antiemetic administered on each day of chemotherapy and two to three days after chemotherapy. Antiemetics should include an NK1 antagonist, 5-HT3 receptor antagonist, and dexamethasone. [ABSTRACT FROM AUTHOR]

Introduction: Current evidence shows that serum miR-371a-3p can identify disease recurrence in testicular germ cell tumour (TGCT) patients and correlates with tumour load. Despite convincing evidence showing the advantages of including miR-371a-3p testing to complement and overcome the classical serum tumour markers limitations, the successful introduction of a serum miRNA based test into clinical practice has been impeded by a lack of consensus regarding optimal methodologies and lack of a universal protocol and thresholds. Herein, we investigate two quantitative real-time PCR (qRT-PCR) based pipelines in detecting disease recurrence in stage I TGCT patients under active surveillance, and compare the sensitivity and specificity for each method., Methods: Sequential serum samples collected from 33 stage I TGCT patients undergoing active surveillance were analysed for miR-371a-3p via qRT-PCR with and without an amplification step included., Results: Using a pre-amplified protocol, all known recurrences were detected via elevated miR-371a-3p expression, while without pre-amplification, we failed to detect recurrence in 3/10 known recurrence patients. For pre-amplified analysis, sensitivity and specificity was 90% and 94.4% respectively. Without amplification, sensitivity dropped to 60%, but exhibited 100% specificity., Discussion: We conclude that incorporating pre-amplification increases sensitivity of miR-371a-3p detection, but produces more false positive results. The ideal protocol for quantification of miR-371a-3p still needs to be determined. TGCT patients undergoing active surveillance may benefit from serum miR-371a-3p quantification with earlier detection of recurrences compared to current standard methods. However, larger cross-institutional studies where samples are processed and data is analysed in a standardised manner are required prior to its routine clinical implementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Christiansen, Lobo, Fankhauser, Rothermundt, Cathomas, Batavia, Grogg, Templeton, Hirschi-Blickenstorfer, Lorch, Gillessen, Moch, Beyer and Hermanns.)

Objective: Distant metastasis other than non-regional lymph nodes and lung (i.e., M1b stage) significantly contributes to the poor survival prognosis of patients with germ cell testicular cancer (GCTC). The aim of this study was to develop a machine learning (ML) algorithm model to predict the risk of patients with GCTC developing the M1b stage, which can be used to assist in early intervention of patients., Methods: The clinical and pathological data of patients with GCTC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Combing the patient's characteristic variables, we applied six machine learning (ML) algorithms to develop the predictive models, including logistic regression(LR), eXtreme Gradient Boosting (XGBoost), light Gradient Boosting Machine (lightGBM), random forest (RF), multilayer perceptron (MLP), and k-nearest neighbor (kNN). Model performances were evaluated by 10-fold cross-receiver operating characteristic (ROC) curves, which calculated the area under the curve (AUC) of models for predictive accuracy. A total of 54 patients from our own center (October 2006 to June 2021) were collected as the external validation cohort., Results: A total of 4,323 patients eligible for inclusion were screened for enrollment from the SEER database, of which 178 (4.12%) developing M1b stage. Multivariate logistic regression showed that lymph node dissection (LND), T stage, N stage, lung metastases, and distant lymph node metastases were the independent predictors of developing M1b stage risk. The models based on both the XGBoost and RF algorithms showed stable and efficient prediction performance in the training and external validation groups., Conclusion: S-stage is not an independent factor for predicting the risk of developing the M1b stage of patients with GCTC. The ML models based on both XGBoost and RF algorithms have high predictive effectiveness and may be used to predict the risk of developing the M1b stage of patients with GCTC, which is of promising value in clinical decision-making. Models still need to be tested with a larger sample of real-world data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Wang, Zhang, Zhang, Wang, Li and Wang.)

OBJECTIVE To explore the efficacy and safety of testosterone undecanoate (TU) (Nebido®; Bayer Schering Pharma AG, Berlin, Germany) in patients with bilateral germ cell testicular cancer (GCTC) who have switched androgen substitution from testosterone enanthate (Primoteston Depot®, Bayer Schering Pharma AG). PATIENTS AND METHODS In total, 47 bilaterally orchidectomized GCTC patients were included in a prospective study to monitor serum gonadal hormones, biochemical safety and symptoms of hypogonadism based on the Aging Males' Symptoms scale during TU treatment for a 28-week period. RESULTS During treatment, serum levels of total (TT) and calculated free testosterone (CFT) increased with simultaneously decreasing levels of FSH and LH. However, considerable variations in median levels of TT and CFT were observed during the study. The highest levels of TT and CFT were observed 1-2 weeks after each injection and the lowest immediately before the second injection. Insufficient levels of TT ( < 8 nmol/L) were observed in 10 patients, with nine of these during the second half of the first treatment cycle. Supernormal levels of TT ( > 35 nmol/L) were measured in 28 patients of which 26 occurred at least once during the first 3 weeks of each treatment cycle. A follow-up review at median 39 months after study start showed a median steadystate injection interval of 10 weeks, with an individual variability of 6-14 weeks. Symptoms according to the Aging Males' Symptoms scale remained unchanged. No severe toxicity was encountered. Only one patient experienced transient elevation of serum alanine transaminase and aspartate transaminase with maximal Common Toxicity Criteria, grade 2. CONCLUSIONS TU is safe and highly efficient for the treatment of anorchid GCTC survivors. Androgen substitution with TU in bilateral GCTC survivors requires individuallyadjusted injection intervals. In most cases, 10-week intervals appear to be sufficient. [ABSTRACT FROM AUTHOR]

The purpose of our study was to establish a reliable and practical nomogram based on significant clinical factors to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with germ cell testicular cancer (GCTC). Patients diagnosed with GCTC between 2004 and 2015 were obtained from the SEER database. Nomograms were constructed using the R software to predict the OS and CSS probabilities and the constructed nomograms were validated and calibrated. A total of 22,165 GCTC patients were enrolled in the study, including the training cohort (15,515 patients) and the validation cohort (6,650 patients). In the training cohort, multivariate Cox regression showed that age, race, AJCC stage, SEER stage and surgery were independent prognostic factors for OS, while age, race, AJCC stage, TM stage, SEER stage and radiotherapy were independent prognostic factors for CSS. Based on the above Cox regression results, we constructed prognostic nomograms of OS and CSS in GCTC patients and found that the OS nomograms had higher C-index and AUC compared to TNM stage in the training and validation cohorts. In addition, in the training and external validation cohorts, the calibration curves showed a good consistency between the predicted and actual 3-, 5- and 10-year OS and CSS rates of the nomogram. The current prognostic nomogram can provide a personalized risk assessment for the survival of GCTC patients.

Objectives: Although it is a well known condition that presence of testicular microlithiasis (TM) with the co-occurrence of specific risk factors such as historyof previous germ cell testicular cancer (GCTC), infertility, undescended testes or atrophic testes have high risks for GCTC development, TM is still a controversial topic. Its effects on oncological outcomes have still not been investigated in detail. In this study, we aimed to evaluate whether the presence of TM has an effect on GCTC prognosis and oncological outcomes., Methods: Seventy five patients among 93 patients who underwent radical orchidectomy between January 2010 and February 2016 were selected and divided into two groups. Group I consisted of 51 patients without TM. Group II consisted of 24 patients with TM. Each groups were compared in terms of demographic datas, prognostic risk factors, complete blood count parameters and oncological outcomes., Results: During the median follow-up of 58 (1-106) months, a significantly higher local recurrence rate (54.2% vs. 3.9%, p<0.001) distant metastasis rate (58.3% vs. 5.9%, p<0.001) and lower cancer-specific survival rate (45.8% vs. 94.1%, p<0.001) were observed in patients with TM. In this group, the duration of recurrence-free survival (47.65±9.45 vs.101.96±2.80 months, p<0.001), metstais-free survival (49.50±8.88 vs. 100.00±3.36 months, p<0.001) and cancer-specific survival (54.37±8.76  vs. 100.19±3.25 months, p<0.001) were also statisticaly lower. In multivariate analysis, β-hCG, LDH, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio and the presence of undescended testis were found as independent predictive factors for local recurrence, distant metastasis and cancer-specific survival. Red blood cell distribution width and the presence of testicular microlithiasis were found to be independent predictive factors for local recurrence., Conclusion: According to our results, bilateral TM was associated with higher rates of local recurrence, distant metastasis and cancer spesific mortality in presenceof risk factors, regardless of classic or limited microlithiasis.

Aim: The aim of this study is to investigate the role of F-18 florodeoksiglukoz (FDG)- pozitron emisyon tomografi (PET/CT) in the restaging of germ cell testicular cancer with elevated tumor markers and treatment response assessment after chemotherapy. Method: FDG-PET/CT study was performed in 36 patients (mean age±SD: 35.8±7.3 years) with germ cell testicular tumor in this retrospective study. FDG uptake was interpreted visually correlated with CT and when pathological FDG uptake or lymph node detected, the standardized uptake value was measured. Twenty two patient's histopathology were nonseminomatous germ cell tumors (NSGCTs) and 14 patient had seminomatous germ cell tumor (SGCT). An FDG-PET/CT scan was taken for restaging in seven SGCT patients and 9 NSGCTs patients with elevated tumor marker levels (hCG, AFP, and LDH). 7 SGCT patients and 13 NSGCTs patients underwent FDG-PET/CT imaging for treatment response assessment. Results: In all patients who underwent FDG-PET/CT for restaging paraaortic metastatic lymph nodes were detected with high FDG uptake and SUVmax values were 5.1-34.1 (21.2±7.8). In NSGCTs group; SUVmax values of paraaortic lymph nodes were 5.1-34.1 (20.1±8.9) and 12.9-32.0 (22.7±1.4) in NSGCTs and SGCT group, respectively. The lymph node SUVmax values were higher in the patients as the tumor marker (hCG, AFP, and LDH) level increased and it was found to be statistically significant (p<0.05). Also, there was a significant correlation between the maximum diameter of the hypermetabolic lymph node and SUVmax values, tumor marker levels (p<0.05 and p=0.312, respectively). In the treatment response assessment patient group; neither SGCT nor NSGCTs patients had lymph nodes showing pathological FDG uptake. hCG, AFP, and LDH levels were significantly reduced compared to before treatment and were in normal levels. Conclusion: FDG-PET/CT is an efficient hybrid imaging modality in restaging both SGCT and NSGCTs especially in markedly high tumor marker levels also in treatment response assessment. [ABSTRACT FROM AUTHOR]