1.Prognostic Indicators and Comparative Treatment Outcomes in High-Risk Thyroid Cancer with Laryngotracheal Invasion
Eman A. TORAIH ; Jessan A. JISHU ; Mohammad H. HUSSEIN ; Aly A. M. SHAALAN ; Manal S. FAWZY ; Emad KANDIL
Endocrinology and Metabolism 2025;40(2):201-215
Background:
Laryngotracheal invasion occurs in a subset of patients with well-differentiated thyroid cancer (WDTC) and is associated with a poor prognosis. We aimed to analyze patterns and predictors/outcomes related to this high-risk manifestation.
Methods:
This population-based analysis utilized the Surveillance, Epidemiology, and End Results (SEER) registry (2000 to 2015) to identify WDTC patients. Temporal trends and geographic variation in invasion rates were assessed. Logistic regression and propensity score matching were employed to identify predictors of secondary malignancy, mortality, and treatment impact on overall and thyroid cancer (TC)-specific survival.
Results:
Of 131,721 WDTC patients, 1,662 (1.3%) had tracheal invasion and 976 (0.7%) had laryngeal invasion at diagnosis. Tracheal and laryngeal invasion rates declined from 3.7%–0.7% and 1.5%–0.6%, respectively, from 2000 to 2015. Compared to 98,835 noninvasive cases, patients with laryngotracheal invasion were older and more often male, Asian, and Hispanic (all P<0.001). This group had larger tumors with higher rates of nodal (N1: 61.8% vs. 15.1%) and distant metastases (M1: 9.3% vs. 0.4%). Age ≥55 years (hazard ratio [HR], 1.19; P=0.004) and metastases (HR, 1.75; P<0.001) increased TC-specific mortality, whereas the converse pattern was found for Asian race (HR, 0.63; P=0.002) and surgery (HR, 0.35; P<0.001). In rigorously matched groups to control confounding, adding radioactive iodine to surgery reduced mortality by 30% (P<0.001). However, external beam radiation and systemic therapy did not improve survival over surgery alone.
Conclusion
Laryngotracheal invasion is present in 0.7% to 1.3% of cases, conferring over double the mortality risk. Radioactive iodine with surgery improves outcomes in this aggressive WDTC subset.
2.Prognostic Indicators and Comparative Treatment Outcomes in High-Risk Thyroid Cancer with Laryngotracheal Invasion
Eman A. TORAIH ; Jessan A. JISHU ; Mohammad H. HUSSEIN ; Aly A. M. SHAALAN ; Manal S. FAWZY ; Emad KANDIL
Endocrinology and Metabolism 2025;40(2):201-215
Background:
Laryngotracheal invasion occurs in a subset of patients with well-differentiated thyroid cancer (WDTC) and is associated with a poor prognosis. We aimed to analyze patterns and predictors/outcomes related to this high-risk manifestation.
Methods:
This population-based analysis utilized the Surveillance, Epidemiology, and End Results (SEER) registry (2000 to 2015) to identify WDTC patients. Temporal trends and geographic variation in invasion rates were assessed. Logistic regression and propensity score matching were employed to identify predictors of secondary malignancy, mortality, and treatment impact on overall and thyroid cancer (TC)-specific survival.
Results:
Of 131,721 WDTC patients, 1,662 (1.3%) had tracheal invasion and 976 (0.7%) had laryngeal invasion at diagnosis. Tracheal and laryngeal invasion rates declined from 3.7%–0.7% and 1.5%–0.6%, respectively, from 2000 to 2015. Compared to 98,835 noninvasive cases, patients with laryngotracheal invasion were older and more often male, Asian, and Hispanic (all P<0.001). This group had larger tumors with higher rates of nodal (N1: 61.8% vs. 15.1%) and distant metastases (M1: 9.3% vs. 0.4%). Age ≥55 years (hazard ratio [HR], 1.19; P=0.004) and metastases (HR, 1.75; P<0.001) increased TC-specific mortality, whereas the converse pattern was found for Asian race (HR, 0.63; P=0.002) and surgery (HR, 0.35; P<0.001). In rigorously matched groups to control confounding, adding radioactive iodine to surgery reduced mortality by 30% (P<0.001). However, external beam radiation and systemic therapy did not improve survival over surgery alone.
Conclusion
Laryngotracheal invasion is present in 0.7% to 1.3% of cases, conferring over double the mortality risk. Radioactive iodine with surgery improves outcomes in this aggressive WDTC subset.
3.Prognostic Indicators and Comparative Treatment Outcomes in High-Risk Thyroid Cancer with Laryngotracheal Invasion
Eman A. TORAIH ; Jessan A. JISHU ; Mohammad H. HUSSEIN ; Aly A. M. SHAALAN ; Manal S. FAWZY ; Emad KANDIL
Endocrinology and Metabolism 2025;40(2):201-215
Background:
Laryngotracheal invasion occurs in a subset of patients with well-differentiated thyroid cancer (WDTC) and is associated with a poor prognosis. We aimed to analyze patterns and predictors/outcomes related to this high-risk manifestation.
Methods:
This population-based analysis utilized the Surveillance, Epidemiology, and End Results (SEER) registry (2000 to 2015) to identify WDTC patients. Temporal trends and geographic variation in invasion rates were assessed. Logistic regression and propensity score matching were employed to identify predictors of secondary malignancy, mortality, and treatment impact on overall and thyroid cancer (TC)-specific survival.
Results:
Of 131,721 WDTC patients, 1,662 (1.3%) had tracheal invasion and 976 (0.7%) had laryngeal invasion at diagnosis. Tracheal and laryngeal invasion rates declined from 3.7%–0.7% and 1.5%–0.6%, respectively, from 2000 to 2015. Compared to 98,835 noninvasive cases, patients with laryngotracheal invasion were older and more often male, Asian, and Hispanic (all P<0.001). This group had larger tumors with higher rates of nodal (N1: 61.8% vs. 15.1%) and distant metastases (M1: 9.3% vs. 0.4%). Age ≥55 years (hazard ratio [HR], 1.19; P=0.004) and metastases (HR, 1.75; P<0.001) increased TC-specific mortality, whereas the converse pattern was found for Asian race (HR, 0.63; P=0.002) and surgery (HR, 0.35; P<0.001). In rigorously matched groups to control confounding, adding radioactive iodine to surgery reduced mortality by 30% (P<0.001). However, external beam radiation and systemic therapy did not improve survival over surgery alone.
Conclusion
Laryngotracheal invasion is present in 0.7% to 1.3% of cases, conferring over double the mortality risk. Radioactive iodine with surgery improves outcomes in this aggressive WDTC subset.
4.Prognostic Indicators and Comparative Treatment Outcomes in High-Risk Thyroid Cancer with Laryngotracheal Invasion
Eman A. TORAIH ; Jessan A. JISHU ; Mohammad H. HUSSEIN ; Aly A. M. SHAALAN ; Manal S. FAWZY ; Emad KANDIL
Endocrinology and Metabolism 2025;40(2):201-215
Background:
Laryngotracheal invasion occurs in a subset of patients with well-differentiated thyroid cancer (WDTC) and is associated with a poor prognosis. We aimed to analyze patterns and predictors/outcomes related to this high-risk manifestation.
Methods:
This population-based analysis utilized the Surveillance, Epidemiology, and End Results (SEER) registry (2000 to 2015) to identify WDTC patients. Temporal trends and geographic variation in invasion rates were assessed. Logistic regression and propensity score matching were employed to identify predictors of secondary malignancy, mortality, and treatment impact on overall and thyroid cancer (TC)-specific survival.
Results:
Of 131,721 WDTC patients, 1,662 (1.3%) had tracheal invasion and 976 (0.7%) had laryngeal invasion at diagnosis. Tracheal and laryngeal invasion rates declined from 3.7%–0.7% and 1.5%–0.6%, respectively, from 2000 to 2015. Compared to 98,835 noninvasive cases, patients with laryngotracheal invasion were older and more often male, Asian, and Hispanic (all P<0.001). This group had larger tumors with higher rates of nodal (N1: 61.8% vs. 15.1%) and distant metastases (M1: 9.3% vs. 0.4%). Age ≥55 years (hazard ratio [HR], 1.19; P=0.004) and metastases (HR, 1.75; P<0.001) increased TC-specific mortality, whereas the converse pattern was found for Asian race (HR, 0.63; P=0.002) and surgery (HR, 0.35; P<0.001). In rigorously matched groups to control confounding, adding radioactive iodine to surgery reduced mortality by 30% (P<0.001). However, external beam radiation and systemic therapy did not improve survival over surgery alone.
Conclusion
Laryngotracheal invasion is present in 0.7% to 1.3% of cases, conferring over double the mortality risk. Radioactive iodine with surgery improves outcomes in this aggressive WDTC subset.
5.Male Infertility: New Developments, Current Challenges, and Future Directions
Murat GÜL ; Giorgio Ivan RUSSO ; Hussein KANDIL ; Florence BOITRELLE ; Ramadan SALEH ; Eric CHUNG ; Parviz KAVOUSSI ; Taymour MOSTAFA ; Rupin SHAH ; Ashok AGARWAL
The World Journal of Men's Health 2024;42(3):502-517
There have been many significant scientific advances in the diagnostics and treatment modalities in the field of male infertility in recent decades. Examples of these include assisted reproductive technologies, sperm selection techniques for intracytoplasmic sperm injection, surgical procedures for sperm retrieval, and novel tests of sperm function. However, there is certainly a need for new developments in this field. In this review, we discuss advances in the management of male infertility, such as seminal oxidative stress testing, sperm DNA fragmentation testing, genetic and epigenetic tests, genetic manipulations, artificial intelligence, personalized medicine, and telemedicine. The role of the reproductive urologist will continue to expand in future years to address different topzics related to diverse questions and controversies of pathophysiology, diagnosis, and therapy of male infertility, training researchers and physicians in medical and scientific research in reproductive urology/ andrology, and further development of andrology as an independent specialty.
6. Flavonoid chemical composition and antidiabetic potential of Brachychiton acerifolius leaves extract
Aisha Hussein ABOU ZEID ; Radwa Hassan EL-AKAD ; Hanaa Mohamed EL-RAFIE ; Mohamed Ali FARAG ; Zeinab Abdel Aziz KANDIL ; Manal Abdel Aziz HAMED
Asian Pacific Journal of Tropical Biomedicine 2017;7(5):389-396
Objective To evaluate Brachychiton acerifolius leaf extracts as antidiabetic potential agent and to identify the main active constituents using bioactivity guided fractionation. Methods In vitro antioxidant activity was evaluated for B. acerifolius different extracts using DPPH assay and vitamin C as control. Antidiabetic activity was then determined using STZ-induced rats treated daily with ethyl acetate and 70% ethanol leaf extracts for 4 weeks at a dose of 200 g/kg body weight against gliclazide reference drug. Blood glucose, α-amylase, lipid profile, liver function enzymes and oxidative stress markers were assessed along with histopathological study for liver and pancreatic tissues. Isolation and structural elucidation of active compounds were made using Diaion and Sephadex followed by spectral analyses. Results The results indicated that ethyl acetate and ethanol leaf extracts exhibited the strongest antioxidant activity compared to that of vitamin C (IC
7.The Renaissance of Male Infertility Management in the Golden Age of Andrology
Aldo E. CALOGERO ; Rossella CANNARELLA ; Ashok AGARWAL ; Taha Abo-Almagd ABDEL-MEGUID HAMODA ; Amarnath RAMBHATLA ; Ramadan SALEH ; Florence BOITRELLE ; Imad ZIOUZIOU ; Tuncay TOPRAK ; Murat GUL ; Tomer AVIDOR-REISS ; Parviz KAVOUSSI ; Eric CHUNG ; Ponco BIROWO ; Ramy Abou GHAYDA ; Edmund KO ; Giovanni COLPI ; Fotios DIMITRIADIS ; Giorgio Ivan RUSSO ; Marlon MARTINEZ ; Gokhan CALIK ; Hussein KANDIL ; Gianmaria SALVIO ; Taymour MOSTAFA ; Haocheng LIN ; Hyun Jun PARK ; Nazim GHERABI ; Nguyen Ho VINH PHUOC ; Nguyen QUANG ; Ricky ADRIANSJAH ; Sandro La VIGNERA ; Sava MICIC ; Damayanthi DURAIRAJANAYAGAM ; Ege Can SEREFOGLU ; Vilvapathy Senguttuvan KARTHIKEYAN ; Priyank KOTHARI ; Widi ATMOKO ; Rupin SHAH
The World Journal of Men's Health 2023;41(2):237-254
Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several “omics” technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its “Middle Ages” to its “Renaissance”, a golden age of andrology.
8.Impact of Antioxidant Therapy on Natural Pregnancy Outcomes and Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Ashok AGARWAL ; Rossella CANNARELLA ; Ramadan SALEH ; Ahmed M. HARRAZ ; Hussein KANDIL ; Gianmaria SALVIO ; Florence BOITRELLE ; Shinnosuke KURODA ; Ala’a FARKOUH ; Amarnath RAMBHATLA ; Armand ZINI ; Giovanni COLPI ; Murat GÜL ; Parviz KAVOUSSI ; Taha Abo-Almagd Abdel-Meguid HAMODA ; Edmund KO ; Gokhan CALIK ; Tuncay TOPRAK ; Germar-Michael PINGGERA ; Hyun Jun PARK ; Ramy Abou GHAYDA ; Suks MINHAS ; Gian Maria BUSETTO ; Mustafa Emre BAKIRCIOĞLU ; Ates KADIOGLU ; Eric CHUNG ; Giorgio Ivan RUSSO ; Aldo E. CALOGERO ; Rafael F. AMBAR ; Channa N. JAYASENA ; Rupin SHAH
The World Journal of Men's Health 2023;41(1):14-48
Purpose:
Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS.
Materials and Methods:
Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases.Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines.
Results:
We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients.We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies.A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair.
Conclusions
The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.
9.Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele:A Systematic Review and Meta-Analysis
Rossella CANNARELLA ; Rupin SHAH ; Ramadan SALEH ; Florence BOITRELLE ; Taha Abo-Almagd Abdel-Meguid HAMODA ; Rajender SINGH ; Gianmaria SALVIO ; Tuncay TOPRAK ; Marco FALCONE ; Murat GUL ; Fotios DIMITRIADIS ; Amarnath RAMBHATLA ; Giorgio I. RUSSO ; Edmund KO ; Armand ZINI ; Parviz KAVOUSSI ; Nguyen Ho Vinh PHUOC ; Hussein KANDIL ; Ramy Abou GHAYDA ; Ponco BIROWO ; Nazim GHERABI ; Erman CEYHAN ; Jie DONG ; Vineet MALHOTRA ; Damayanthi DURAIRAJANAYAGAM ; Bircan KOLBASI ; Fahmi BAHAR ; Gokhan CALIK ; Selahittin ÇAYAN ; Germar-Michael PINGGERA ; Aldo E. CALOGERO ; Osvaldo RAJMIL ; Taymour MOSTAFA ; Widi ATMOKO ; Ahmed M. HARRAZ ; Tan V. LE ; Jean de la ROSETTE ; Lukman HAKIM ; Edoardo PESCATORI ; Oleg SERGEYEV ; Ayman RASHED ; Pallavi SAINI ; Ashok AGARWAL
The World Journal of Men's Health 2024;42(2):321-337
Purpose:
Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA).
Materials and Methods:
A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD).
Results:
Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD −1.125, 95% confidence interval [CI] −1.410, −0.840; p<0.0001) with high inter-study heterogeneity (I2=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD −1.014, 95% CI −1.263, −0.765; p<0.0001, and SMD −1.495, 95% CI −2.116, −0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD −2.197, 95% CI −3.187, −1.207; p<0.0001), sperm chromatin structure assay (SMD −0.857, 95% CI −1.156, −0.559; p<0.0001) or TUNEL (SMD −1.599, 95% CI −2.478, −0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD −2.450, 95% CI −3.903 to −0.997, p=0.001) with high inter-study heterogeneity (I2=93.7%).
Conclusions
Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.
10.The new 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen: is it a step toward better standard operating procedure?
Eric CHUNG ; Mohamed ARAFA ; Florence BOITRELLE ; Hussein KANDIL ; Ralf HENKEL ; Ramadan SALEH ; Rupin SHAH ; Paraskevi VOGIATZI ; Armand ZINI ; Ashok AGARWAL
Asian Journal of Andrology 2022;24(2):123-124