Epithelial-mesenchymal transition dysregulation in prostate cancer: Insights from molecular unraveling and epidemiological analyses in Tunisia, North Africa.

INTRODUCTION: The progression of prostate cancer (PCa) has been linked worldwide, including in African populations, to the dysregulation of the epithelial-mesenchymal transition (EMT). METHODS: To clarify the connection among EMT markers, clinicopathological parameters, and epidemiological factors, we analyzed 35 PCa specimens from patients in Tunisia, a country in North Africa, arranged by stages. We also carried out extensive molecular and epidemiological analyses. RESULTS: Significant dysregulation of EMT genes was found, with an overexpression of ZEB-1, Twist, Snail-1, and Vimentin (p < 0.05) and underexpression of E-cadherin and ß-catenin (p < 0.05). Positive correlations were observed between transcription factors and the mesenchymal marker Vimentin (p < 0.001, r = 0.574; p = 0.029, r = 0.411; and p < 0.001; r = 0.506) according to Spearman correlation analyses, whereas negative correlations were found between epithelial markers (E-cadherin, ß-catenin) and Vimentin (p < 0.05; r < 0). Higher PSA, Gleason scores, and metastasis were all correlated with the dysregulation of EMT (p < 0.05). Notably, there was a positive correlation between higher consumption of tobacco (≥20 Packets per year) and Vimentin expression (p < 0.001, r = 0.854), suggesting a relationship between smoking and EMT activation in the Tunisian population. Moreover, Twist showed a positive correlation with diabetes (p < 0.001, r = 0.385), whereas no significant correlations were found between EMT markers and comorbidities such as hypertension and coronary insufficiency. These results demonstrate the intricate connection between molecular changes, epidemiological factors, and disease progression, and they emphasize the crucial role that EMT plays in promoting PCa aggressiveness in African populations, particularly in Tunisia. CONCLUSION: In summary, understanding these correlations could help develop focused treatment plans and enhance patient outcomes for PCa management in African settings.

An insight into the diagnostic, prognostic, and taxanes resistance of double zinc finger and homeodomain factor's expression in naïve prostate cancer.

Currently, clinical biomarkers are urgently needed to improve patient management to guide personal therapy for cancer. In this study, we investigate the deregulation of Zeb-1 in prostate cancer (PC) Tunisian patients. Expression patterns of the Zeb-1 were investigated in prostate adenocarcinoma and benign prostate biopsies using quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) and 2-ΔΔCt method. Statistical analysis was used to identify differences across groups depending on gene expression level. Furthermore, we exploited a follow-up over 15 years to correlate Zeb-1 deregulation and clinical outcomes in PC patients. Based on ROC curve analyses, the AUC was found in discriminating PC patients from controls (AUC = 0.757; p < 0.001). In addition, the higher expression level was significantly associated with PSA, Digital Rectal Examination, Gleason score, tumor stage, and distant lymph node metastases. Moreover, Zeb-1 overexpression was correlated with shorter overall survival (OS) (p = 0.042), poor progression-free survival (PFS) (p = 0.007), and with resistance to taxanes (p = 0.012). Our data provide the aberrant expression of Zeb-1 in PC patients suggesting its potential diagnostic, prognostic, and theranostic role. Further functional studies are mandatory to strengthen these results and to uncover the molecular mechanism of this neoplasm. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03941-8.

Co-expression of Twist and Snai1: predictor of poor prognosis and biomarker of treatment resistance in untreated prostate cancer.

BACKGROUND: Prostate cancer (PCa) remains one of the most complex tumors in men. The assessment of gene expression is expected to have a profound impact on cancer diagnosis, prognosis, and treatment decisions. The aim of this study was to determine the utility of the epithelial-mesenchymal transition (EMT) transcription factors Twist and Snai1 in the treatment of naïve prostate cancer. METHODS AND RESULTS: We analyzed formalin-fixed paraffin-embedded (FFPE) prostate tissues from 108 PCa patients and 20 control biopsies using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and 2-ΔΔCt methods for Twist and Snail gene expression. The expression of Twist and Snai1 mRNA was significantly overexpressed in primary tissues of PCa patients compared with controls using ROC curve. Statistical analysis showed that the mRNAs of these two genes expression Snai1 and Twist were positively correlated with tumor development and prognostic parameters as Gleason score (p < 0.001; r = 0.707) and (p < 0.001; r = 0.627) respectively. The results of Kaplan-Meier analysis showed that mRNA expression of Snai1 and Twist genes expression were significant predictors of poor overall survival (OS) (Log rank p < 0.001) and progression-free survival (PFS) of patients (Log rank p < 0.001). Furthermore, our results showed that the expression of Snai1 and Twist genes expression in primary tissues of PCa patients could predict resistance to androgen deprivation therapy (p < 0.001) and resistance to the acidic drugs abiraterone or enzalutamide (p < 0.001). However, these two transcription factors failed to predict taxanes resistance at the time of diagnosis (p > 0.05). CONCLUSION: These results suggest that Snai1 and Twist are overexpressed during the onset and progression of PCa malignancies and may be theranostic markers of resistance to ADT, abiraterone, or enzalutamide therapy.

Correlation between E-cadherin/ß-catenin, Vimentin expression, clinicopathologic features and drug resistance prediction in naïve prostate cancer: A molecular and clinical study.

Although epithelial-mesenchymal markers play an important role in prostate cancer (PC), further research is needed to better understand their utility in diagnosis, cancer progression prevention, and treatment resistance prediction. Our study included 111 PC patients who underwent transurethral resection, as well as 16 healthy controls. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of E-cadherin, ß-catenin, and Vimentin. We found that E-cadherin and ß-catenin were underexpressed in primary PC tissues. E-cadherin expression was found to be inversely associated with prostate-specific antigen progression (PSA-P; serum marker of progression; p = 0.01; |r| = 0.262). Furthermore, the underexpression of two markers, E-cadherin and ß-catenin, was found to be associated with advanced tumor stage and grade (p < 0.05). On the other hand, Vimentin was overexpressed in PC patients with a fold change of 2.141, and it was associated with the diagnosis, prognosis, and prediction of treatment resistance to androgen deprivation therapy (p = 0.002), abiraterone-acid (p = 0.001), and taxanes (p = 0.029). Moreover, the current study highlighted that poor survival could be significantly found in patients who progressed after primary surgery, did not use drugs, and expressed these genes aberrantly. In Cox regression multivariate analysis (p < 0.05), a positive correlation between the Vimentin marker and coronary heart disease in PC patients was identified (p = 0.034). In summary, the present study highlights the diagnostic (p < 0.001), prognostic (p < 0.001), and therapeutic potential of Vimentin in primary PC (p < 0.05), as well as its implications for cardiovascular disease. Furthermore, we confirm the potential prognostic value of E-cadherin and ß-catenin.

The "Cut-to-the-Light" Technique Laser Endoureterotomy for Complete Ureteral Obstruction Resurfaces! A New Application of an Old Technique.

Objective: To describe our new endoscopic approach in treating iatrogenic ureteral stenosis using the "cut-to-The-light" technique. Methods: Case of a 54 year-old female patient who underwent a right percutaneous nephrolithotomy to treat a staghorn calculus with two subsequent complimentary ureteroscopies complicated by a severe proximal ureteral obstruction. An antegrade flexible uretereroscope and a retrograde rigid ureteroscope were used to locate the stenosis. With the aid of a 365-µm Ho: YAG laser fiber (settings 0.4 J, 12 Hz), we managed to successfully create a small incision in the stenotic lesion, the rigid ureterscopy light was clearly seen by the antegrade flexible ureteroscope and a through-and-through guidewire was then placed, securing the ureter. Ureteral dilatation was then performed followed by a full thickness incision of the ureteral stenosis. A single 8Fr, 28 cm double J ureteral stent was finally placed after stone fragmentation. Results: The operating time was 200 mins. No blood loss. No fever or signs of UTI were seen shortly after the operation. The Foley catheter was successfully removed at day one post-op. The hospital stay was short of only 2 days. Conclusion: The "cut-to-the-light" technique is a new application in the arsenal of ureteral stricture treatment that has been scarcely described in the literature before. The use of this method seems to offer excellent outcomes thus demonstrating the importance of this minimally invasive technique as an alternative to conventional invasive methods used. We believe that studies with larger samples and longer follow up are needed in order to fully determine the benefits of this method and to assess and reveal its suitable application and its drawbacks.

Association of a common genetic variant (insertion/deletion) in ACE gene with prostate cancer susceptibility in a Tunisian population.

BACKGROUND: Angiotensin-converting enzyme (ACE) plays a pivotal role in several pathologies including cancers. The association of insertion/deletion (I/D) polymorphism of the ACE gene with prostate cancer (PC) risk remains controversial. We aimed to investigate for the first time, to our Knowledge, in North Africa the potential relationship between ACE I/D polymorphism with PC susceptibility and clinical outcomes of PC patients. METHODS: This case-control study included 143 healthy individuals and 124 patients diagnosed with PC. Using genomic DNA, the samples were genotyped for ACE I/D polymorphism by polymerase chain reaction (PCR). RESULTS: We found that The D allele is significantly associated with an increased risk of PC and D/D + D/I genotypes were at 3 times increased risk of PC ([p = 0.005], OR = 2.95, IC 95% = 1.26-7.09) compared with I/I genotype (p = 0.003, OR = 0.3, IC 95% = 0.12-0.74). We observed an association between D/D and D/I genotypes with advanced age (≥70 years) (p = 0.014; r2  = 0.22). Furthermore, there is a significant prediction of advanced Gleason score ≥8 based on epidemiological parameters and ACE genotype (p = 0.000; R2  = 0.349), although no significant association was observed with stage and metastasis. CONCLUSION: The ACE I/D polymorphism is likely to predispose to PC and could play a role in PC progression and aggressiveness.

Polymorphisms in NQO1 and MPO genes and risk for bladder cancer in Tunisian population.

BACKGROUND: NAD (P) H: quinone oxidoreductase (1) (NQO1-HGNC: 2874) and myeloperoxidase (MPO-HGNC: 7218) are two enzymes involved in phase II of the xenobiotic metabolism pathway. METHODS: In this study, a case-control analysis was conducted to investigate the relationship between genetic variations in the NQO1 (C609T, rs1800566; IVS1-27 C >G, rs689452) and MPO (G463A, rs2333227) genes and the risk for bladder cancer among Tunisian population. RESULTS: We have found that the MPO 463GA genotype was associated with a decreased risk of developing bladder cancer (p = 0.049; OR = 0.696; 95% CI 0.484-0.999). In contrast, we have found that the NQO1 609CT genotype could increase the risk of bladder cancer patients (p = 0.0039; OR = 1.454; 95% CI = 1.017-2.078). Moreover, patients with "NQO1 609 CT/IVS1-27 CG" genotype show a 2.180-fold increasing risk for developing bladder cancer in comparison to the control group with wild genotype. This OR is estimated at 5.6-fold in smokers patients with "NQO1 609 CT/IVS1-27 CG" genotype. Lastly, study findings suggest that the NQO1 IVS-27 *CG genotype (rs689452) is associated with a risk of progression to muscle invasive bladder cancer. CONCLUSION: Our study suggests that environmental risk factors in association to NQO1 genotypes (NQO1 609 CT/IVS1-27 CG) play an important role in the development of bladder cancer in Tunisian population.

The diagnostic applicability of A-type Lamin in non-muscle invasive bladder cancer.

PURPOSE: Lamin A is a major component of the nuclear lamina maintaining nuclear integrity, regulation of gene expression, cell proliferation, and apoptosis. Its deregulation in cancer has been recently reported to be associated with its prognosis. However, its clinical significance in non-muscle invasive bladder cancer (NMIBC) remains to be defined. MATERIAL/METHODS: Immunohistochemical staining and RT-qPCR were performed to screen the expression patterns of Lamin A/C protein and Lamin A mRNA respectively in 58 high and low grade NMIBC specimens. RESULTS: Lamin A/C protein was expressed only in the nucleus and less exhibited in NMIBC tissues compared to non-tumoral ones. On the other side, Lamin A mRNA was up-regulated in NMIBC compared to controls. Nevertheless, both expression patterns (protein and mRNA) were not correlated to clinical prognosis factors and were not able to predict the overall survival of patients with high-grade NMIBC. CONCLUSIONS: The deregulation of A-type Lamin is not associated with the prognosis of NMIBC, but it could serve as a diagnostic biomarker distinguishing NMIBC patients from healthy subjects suggesting its involvement as an initiator event of tumorigenesis in our cohort.

Global Survey of the Roles and Attitudes Toward Social Media Platforms Amongst Urology Trainees.

OBJECTIVES: To perform a global survey assessing the role of and the attitudes toward media platforms amongst training Urologists METHODS: We distributed a 21-item online survey on social medial (SoMe) and other media platforms to current Urology trainees by email via individual institutions and multiple Urological associations. The survey acquired data including baseline characteristics, the role of and attitudes toward SoMe and other media platforms in training and assessed the prevalence of Social Media Disorder (SMD) based on the validated 9-item SMD Scale. Stata IC was used for statistical analysis. RESULTS: Three hundred and seventy-two urology trainees in 6 continents participated in the survey. Overall, 99.4% used SoMe and 27.3% listened to healthcare-focused podcasts. Most trainees (85.5%) are using guideline apps for education purposes, with the top 3 most utilized apps being the EAU, AUA, and UpToDate applications. There was mixed sentiment regarding the impact of SoMe on the patient-physician relationship, wherein most felt it challenges the doctor's authority (56.7%) but also empowers the patient (62.7%) and encourages shared-care (57.3%). Unfortunately, 11.3% of urology trainees met criteria for SMD while 65.4% had not reviewed professional guidelines on appropriate SoMe use. CONCLUSION: Despite practically all urology trainees using SoMe and guideline applications, the majority of trainees have not reviewed or have been educated on professional guidelines for SoMe usage. There is a small but significant number of trainees who are at risk for SMD which may be contributing to higher rates of physician burnout amongst urologists.

Telemedicine Usage Among Urologists During the COVID-19 Pandemic: Cross-Sectional Study.

BACKGROUND: Prior to the COVID-19 pandemic, urology was one of the specialties with the lowest rates of telemedicine and videoconferencing use. Common barriers to the implementation of telemedicine included a lack of technological literacy, concerns with reimbursement, and resistance to changes in the workplace. In response to the COVID-19 pandemic declared in March 2020, the delivery of urological services globally has quickly shifted to telemedicine to account for the mass clinical, procedural, and operative cancellations, inadequate personal protective equipment, and shortage of personnel. OBJECTIVE: The aim of this study was to investigate current telemedicine usage by urologists, urologists' perceptions on the necessity of in-person clinic appointments, the usability of telemedicine, and the current barriers to its implementation. METHODS: We conducted a global, cross-sectional, web-based survey to investigate the use of telemedicine before and after the COVID-19 pandemic. Urologists' perceived usability of telemedicine was assessed using a modified Delphi approach to create questions based on a modified version of the validated Telehealth Usability Questionnaire (TUQ). For the purposes of this study, telemedicine was defined as video calls only. RESULTS: A total of 620 urologists from 58 different countries and 6 continents participated in the survey. Prior to COVID-19, 15.8% (n=98) of urologists surveyed were using telemedicine in their clinical practices; during the pandemic, that proportion increased to 46.1% (n=283). Of the urologists without telemedicine experience, interest in telemedicine usage increased from 43.7% (n=139) to 80.8% (n=257) during the COVID-19 pandemic. Among urologists that used telemedicine during the pandemic, 80.9% (n=244) were interested in continuing to use it in their practice. The three most commonly used platforms were Zoom, Doxy.me, and Epic, and the top three barriers to implementing telemedicine were patients' lack of technological comprehension, patients' lack of access to the required technology, and reimbursement concerns. CONCLUSIONS: This is the first study to quantify the use, usability, and pervading interest in telemedicine among urologists during the COVID-19 pandemic. In the face of this pandemic, urologists' usage of telemedicine nearly tripled, demonstrating their ability to adopt and adapt telemedicine into their practices, but barriers involving the technology itself are still preventing many from utilizing it despite increasing interest.

Intratesticular leiomyoma: A case report and a literature review.

INTRODUCTION: Leiomyomas are benign tumors that originate from smooth muscles cells. Intratesticular leiomyoma is a very rare type of benign testicular masses. Through the literature, only 11 cases were reported. PRESENTATION OF CASE: A 36 years old man presented with painless right scrotal mass. Clinical examination showed right upper polar testicular mass, well circumscribed and highly vascularized on sonography. Serum tumor markers were normal. Patient was explained the possibility of an organ sparing surgery if frozen section shows no sign of malignancy. Midline incision with frozen section was performed, with wide local excision. Pathological examination of the specimen confirmed intratesticular leiomyoma. Two years after the surgery, patient showed no sign of recurrence. DISCUSSION: Intratesticular Leiomyoma is usually revealed as a non-tender firm scrotal mass that increases in size. Sonography is the imaging modality of choice for assessing intrascrotal pathology, and cannot distinguish benign from malignant tumor. Surgical management is subject of debate. While some authors recommend radical orchiectomy, others suggest the use of frozen section intraoperatively, and perform conservative treatment by mass excision in the absence of signs of malignancy. CONCLUSION: Intratesticular leiomyoma is a very rare finding. When suspected, conservative management using frozen section followed by mass excision can be done, but final diagnosis remains on pathological examination and immunohistochemistry of the specimen.

Primary Hydatid Cyst of the adrenal gland: A case report and a review of the literature.

INTRODUCTION: In North Africa which is an endemic region for Hydatid Cyst, Tunisia is considered as an endemic country. The liver and lungs are common locations for Hydatid Cysts, whereas the Adrenal Glands are unusual and rare locations. PRESENTATION OF CASE: Here is a report of primary Hydatid Cyst in a 55-year old patient, with left hypochondrium pain as chief complain. No remarkable findings were revealed by physical examination and blood analysis showed normal range. Hydatid serology was negative. The diagnosis of Hydatid Cyst was suspected based on CT Scan results which showed a well-circumscribed, non-enhanced, multi-cystic, 12 cm mass with scattered calcifications located in the left adrenal gland. Therefore, the patient underwent an open surgery with resection of the protruding dome of the cyst as it was attached to the renal pedicle, the pancreatic tail, the spleen and the jejunum. The final pathological examination of the specimen led to a Hydatid Cyst. DISCUSSION: Throughout an extensive literature review that we have made, we have analyzed 54 reported cases, with their clinical presentations, biological exams, radiological features and surgical managements. The treatment should be surgical and has to be as conservative as possible. The prevention of the parasite transmission has to be the cornerstone of the disease management. CONCLUSION: The hydatid cyst of the adrenal gland remains a rare diagnosis that has to be evoked in case of an adrenal gland cyst, especially in an endemic country.

Urological activity at the time of COVID-19 pandemic: is there any difference between public and private field?

INTRODUCTION: as COVID-19 pandemic is rapidly evolving, there is a whole reorganization in hospitals to concentrate more resources to face the crisis. The purpose of this study is to evaluate the impact of COVID-19 disease on urological activity in Tunisia. To assess the differences in the management of urological conditions between the private and the public field. METHODS: a survey was addressed to all certified urologists working in Tunisia in both the public and private sectors (n=194) using the national database of active urologists available and updated. We either called them or looked them up through email or social media. The form was open from March the 28th to April the 3rd. Results were obtained via spreadsheet and analysed using SPSS 23.0. RESULTS: one hundred and twenty urologists have filled in the form. Consultations at the outpatient office were restricted to urgent cases in 66% (n=79). Telemedicine was more used by urologists in private than in public fields p=0.03. Urologists in private sector followed more the sterilization protocol of the hospital/clinic and used more disposable materials whenever possible p=0.011. Elective surgical activity has completely stopped in 85% of the responders (n=102). Elective surgery requiring transfusion or intensive care unit was performed in 38% (n=46) and 26% (n=31) if there was a risk of disease progression. Benign Prostate Hyperplasia (BPH) surgery was more performed as usual in private sector than in public sector p=0.012. It was the only condition managed differently between both sectors. CONCLUSION: the drop of the urological activity is essential in order to give relevant stakeholders room to act efficiently against the spread of the virus. The context of the pandemic and the hospital´s condition must be taken into consideration without compromising the patient´s outcome.

State of the art: Open prostatectomy for benign prostate hyperplasia: Should we avoid it in all cases?

Surgical procedures for benign prostate hyperplasia (BPH) had considerably evolved during last decades. New techniques can nowadays treat prostate big in size, which are classically treated by open prostatectomy (OP). Therefore, the place of this procedure that has been used for over 150 years is nowadays questioned. Is it outdated? Is there emerging techniques that are more efficient, safer and cost effective? This state of the art based on literature review will assess the place of OP in BPH surgery from efficacy on functional outcomes, security, competitiveness with modern and minimally invasive techniques and socio-economic perspectives. Currently, OP has excellent functional outcomes, with low rate of retreatment after surgery, low morbidity and affordable cost in our country. It remains competitive with new surgery techniques for BPH, even if the latter offer the advantages of a minimally invasive surgery, especially in hospitalization length. Taking in consideration the social and economic context in Tunisia, it remains the most accessible and affordable surgical technique. Besides, OP is a procedure that has to be handled by every urologist given the theoretical risk of conversion during endoscopic surgery of BPH, and its use under certain circumstances (In case of bladder lithiasis ou diverticle or impossibility of lithotomy position).

Metastatic renal clear cell carcinoma mimicking a gallbladder polyp: Case report and literature review.

INTRODUCTION: Metastatic tumors to the gallbladder are uncommon. Metastases from renal cell carcinoma (RCC) to the gallbladder are exceptional. Frequencies of less than 0.6% reported in large autopsy reviews and few cases have been reported in the literature. PRESENTATION OF CASE: Herein we present a case of a 50-year-old man that developed four years after radical nephrectomy for RCC, a gallbladder metastasis, discovered incidentally on Computed Tomography (CT) scan. It was described as an intraluminal gallbladder polyp. Radiological features were very suggestive of primary gallbladder carcinoma, thus the patient had a laparoscopic cholecystectomy. The pathological examination of the surgical specimen concluded to a RCC metastasis. Immunochemistry with vimentin and pancytokeratin were supportive of this diagnosis. The clinical course was uneventful after 18 months period of follow up. DISCUSSION: At the time of presentation, almost one-third of the patients with RCC are metastatic. Metastases to the gallbladder are extremely rare. Clinical presentation and physical examination are unspecific. Radiological findings can raise information and orient the diagnosis although the difference between both diagnoses remains difficult. Usually, it is a pedunculated and not associated with gallstones with enhancement on CT scan. The treatment remains surgical with R0 cholecystectomy, and prognosis is mainly related to disease free interval and single site metastasis. CONCLUSION: We highlight here the challenge to make the difference between a primary gallbladder carcinoma and metastasis from RCC. Diagnosis is made on pathological examination and immunochemistry.

Acute urinary retention due to benign prostatic hyperplasia associated with cystitis glandularis in a 22-year-old patient.

A 22-year-old man has consulted in emergency for acute urinary retention and left renal colic. Bladder catheterization was performed. Symptomatic treatment was provided with no improvement. MRI showed a pseudotumoral bladder wall thickening associated with vesical floor budding with prostate median lobe infiltration. The patient got an endoscopy that concluded to an inflammatory aspect of the bladder mycosa and a solid mass in the bladder neck arising. The biopsy during examination concluded to a glandular cystitis. Ultrasonography performed six months later still showed an enlarged prostate of 60g volume, post void residue of 280ml and bilateral hydronephrosis. A second cystoscopy showed an obstructive prostate with a median lobe. A transurethral resection of this lobe was performed. The pathological examination concluded to a benign prostate hyperplasia. This case is likely to be the first reported so far about a BPH in a young male associated with Cystitis Glandularis. Neither etiology nor evidence of the cause behind this case has been identified so far. Although Benign Prostate Hypertrophia is rare among young males, its ethiopathogenesis is not well known, its relation with cystitis glanduralis in young patients has never been described before. Both medical and surgical approaches remain similar to the adults.