REVIEW


Record and Appraisal of Endophytic Tumor Localization Techniques in Minimally Invasive Kidney-Sparing Procedures. A Systematic Review

Spyridon Paparidis, Eleftherios Spartalis, Eleftheria Mavrigiannaki, Nikolaos Ferakis, Konstantinos Stravodimos, Gerasimos Tsourouflis, Dimitrios Dimitroulis, Nikolaos I. Nikiteas

Urology Journal, Vol. 19 No. 03 (2022), , Page 161-178
https://doi.org/10.22037/uj.v19i.7056

Purpose: Review and efficacy assessment of techniques used for intraprocedural endophytic renal mass localization.


Materials and Methods: Advanced search was carried out on PubMed, Cochrane Library, Web of Science and Google Scholar databases up to August 2020. Eligibility criteria were set, according to PRISMA statement. OR (95 % CI) for identification or technical success, positive margins and recurrence, were calculated for completely endophytic tumors. Risk of Bias was evaluated using ROBVIS tool.


Results: 77 studies used for result synthesis, including 1,317 endophytic tumors, with 758 of them completely endophytic. 356 endophytic tumors treated laparoscopically and 598 robotically, using ultrasound-based methods, transarterial embolization, dual-source CT, invasive signage, 3D printing, and augmented reality variations. Identification success was 97.8-100%, positive margins 0-12.5 %  (completely endophytic: 95 % CI; 0.255-1.971, OR 0.709 in laparoscopic, 95 % CI ; 0.379-3.109, OR 0.086 in robotic partial nephrectomy), recurrences 0-3.9 % (completely endophytic: 0 recurrences in laparoscopic, 95 % CI ; 0.0917-2.25, OR 0.454, in robotic partial nephrectomy), and complications 0-60 % . 363 were treated with ablation techniques using CT-based methods, thermal monitoring, transarterial embolization, ultrasound guidance and invasive signage. Technical success was 33.4-100 % (completely endophytic: 95 % CI ; 0.00157-2.060, OR 0.0569 for invasive and 95 % CI ; 0.598-13.152, OR 2.804 for non-invasive localization techniques) and recurrences were 0-20%.


Conclusion: Ultrasound-based techniques showed acceptable identification success and oncologic outcomes in laparoscopic or robotic setting. Augmented reality, showed no superiority over conventional techniques. Near infrared fluoroscopy with intravenous indocyanine green, was incapable of endophytic tumor tracking, although when administered angiographic, results were promising, along with other embolization techniques. Percutaneous hook-wire or embolization coil signage, aided in safe and successful tracking of parenchymal isoechoic masses, but data are inadequate to assess efficacy.  CT-guidance, combined with ultrasound or thermal monitoring, showed increased technical success during thermal ablation, unlike ultrasound guidance that showed poor outcomes.

ORIGINAL PAPER (ENDOUROLOGY AND STONE DISEASE)


Effect of a Probiotic Supplement Containing Lactobacillus Acidophilus and Bifidobacterium Animalis Lactis on Urine Oxalate in Calcium Stone Formers with Hyperoxaluria: A Randomized, Placebo-controlled, Double-blind and In-vitro Trial

Sanaz Tavasoli, Saba Jalali, Mohammad Naji, Nasrin Borumandnia, Ghazaleh Shakiba Majd, Abbas Basiri, Kianaoush Khosravi Darani, Dina Karamad, Maryam Tajabadi-Ebrahimi, Maryam Taheri

Urology Journal, Vol. 19 No. 03 (2022), , Page 179-188
https://doi.org/10.22037/uj.v18i.6789

Purpose: To determine the effect of a probiotic supplement containing native Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium animalis lactis (B. lactis) on 24-hour urine oxalate in recurrent calcium stone formers with hyperoxaluria. Moreover, the in-vitro oxalate degradation capacity and the intestinal colonization of consumed probiotics were evaluated.


Materials and Methods: The oxalate degrading activity of L. acidophilus and B. lactis were evaluated in-vitro. The presence of oxalyl-CoA decarboxylase (oxc) gene in the probiotic species was assessed. One hundred patients were randomized to receive the probiotic supplement or placebo for four weeks. The 24-hour urine oxalate and the colonization of consumed probiotics were assessed after weeks four and eight.


Results: Although the oxc gene was present in both species, only L. acidophilus had a good oxalate degrading activity, in-vitro. Thirty-four patients from the probiotic and thirty patients from the placebo group finished the study. The urine oxalate changes were not significantly different between groups (57.21 ± 11.71 to 49.44 ± 18.14 mg/day for probiotic, and 56.43 ± 9.89 to 50.47 ± 18.04 mg/day for placebo) (= .776). The probiotic consumption had no significant effect on urine oxalate, both in univariable (= .771) and multivariable analyses (P = .490). The consumed probiotics were not detected in the stool samples of most participants.


Conclusion: Our results showed that the consumption of a probiotic supplement containing L. acidophilus and B. lactis did not affect urine oxalate. The results may be due to a lack of bacterial colonization in the intestine.

ORIGINAL PAPER(UROLOGICAL ONCOLOGY)


The Association of Cell Surface Fibromodulin Expression and Bladder Carcinoma

Ali-Ahmad Bayat, Niloufar Sadeghi, Ali Salimi, Ghazaleh Fazli, Mohammad Reza Nowroozi, Solmaz Ohadian Moghadam, Amin Radmanesh, Mohsen Tabasi, Ali Reza Sarrafzadeh, Omid Zarei, Hodjattallah Rabbani

Urology Journal, Vol. 19 No. 03 (2022), , Page 189-195
https://doi.org/10.22037/uj.v18i.6461

Background: Fibromodulin (FMOD) is a secretory protein which is considered a major component of extracellular matrix. Its dysregulation in different types of cancer implies it as a promising target for cancer therapy. Within the scope of its rather wide expression in different tumors, we studied expression of FMOD and effect of anti-FMOD antibody in bladder cancer cells in order to identify new target for diagnostic and therapeutic interventions. We report here for the first time the expression of FMOD in bladder cancer cell lines in comparison to the normal cell line and tissues.


Methods: A peptide-based produced anti-FMOD murine monoclonal antibody (mAb) (clone 2C2-A1) was applied for evaluation of FMOD expression in bladder cancer and normal tissues by immunohistochemistry (IHC) staining. Furthermore, the expression of FMOD was examined in human bladder cell lines, 5637 and EJ138, as well as a non-cancerous human cell line, human fetal foreskin fibroblast (HFFF), by immunocytochemistry (ICC) and flow cytometry. The apoptosis induction of anti-FMOD mAb was also evaluated in bladder cancer cells.


Results: IHC and ICC analyses revealed that the qualitative expression of FMOD in bladder cancer tissues and cell lines is higher than in normal tissues and cell lines. Flow cytometry analyses revealed that 2C2-A1 mAb could recognize FMOD expression in 84.05 ± 1.85%, 46.1 ± .4% , and 2.56 ± 1.26% of 5637, EJ138, and HFFF cells, respectively. An effective apoptosis induction was detected in 5637 and EJ138 cells with no significant effect on HFFF cell.


Conclusion: To our knowledge, this is for the first time reporting surface expression of FMOD in bladder cancer. This significant surface expression of FMOD in bladder cancer with no expression in normal bladder tissues and the capacity of inducing apoptosis through directed targeting of FMOD with specific monoclonal antibody might candidates FMOD as a diagnostic marker as well as a potential immunotargeting with monoclonal antibody.

The Role of Pentraxin-3, Fetuin-A and Sirtuin-7 in the Diagnosis of Prostate Cancer

Özer Güzel, Arzu Kösem, Yılmaz Aslan, Ahmet Asfuroglu, Melih Balci, Cagdas Senel, Altug Tuncel

Urology Journal, Vol. 19 No. 03 (2022), , Page 196-201
https://doi.org/10.22037/uj.v18i.6626

Purpose: Prostate canceris the most commonly diagnosed type of cancer and one of the leading causes of cancer-related death in men.Numerous efforts have been made to improve existing diagnostic methods and develop a new biomarker to identify patients with prostate cancer. In line with current literature, we preferred new serum-based biochemical markers as Pentraxin-3, Fetuin-A and Sirtuin-7 in the present study.


Materials and Methods: A total of 174 patients aged 42-76 years were included in the study. Patients with prostate cancer (n=38) were enrolled as Group 1 and patients with benign prostatic hyperplasia (n=136) as Group 2. The serum levels of Pentraxin-3, Fetuin-A and Sirtuin-7 levels were compared between the groups.


Results: The mean age of the patients was 61.9±7.6 years (p= .001). The mean serum Prostate Specific Antigen levels 32.0±59.6 (2.6-336) ng/mL and 10.0±11.3 (2.5-77.4) ng/mL in Group 1 and 2, respectively (p= .029). The mean serum levels of Pentraxin-3 and Fetuin-Ain Group 1 were statistically significantlydifferent from Group 2(3.3±4.4 ng/mL vs 1.8±2.4 ng/mL, p= .002 and 466.8±11.0 µg/mL vs 513.3±11.0 µg/mL,p= .041,respectively). There was no significant difference between Group 1 and 2 according to serum levels of Sirtuin-7 (12.7±8.2 ng/mL vs 12.7±12.4 ng/mL respectively, p= .145).


Conclusion: Pentraxin-3, Fetuin-A and Sirtuin-7 may be effective in the diagnosis of prostate cancerin light of the current literature.In this study, it was found that Pentraxin-3 and Fetuin-A were significantly different in the diagnosis of prostate cancer.Larger-scale prospective studies are needed to determine the importance of Pentraxin-3 and Fetuin-A in the diagnosis of prostate cancer.

Favorable Response of Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma with Only Small Lesions to not be Considered Measurable by RECIST

Yoshifumi Kadono, Shohei Kawaguchi, Takahiro Nohara, Kazuyoshi Shigehara, Kouji Izumi, Taiki Kamijima, Chikashi Seto, Akinobu Takano, Satoshi Yotsuyanagi, Ryunosuke Nakagawa, Tohru Miyagi, Shuhei Aoyama, Hideki Asahi, Rie Fukuda, Atsushi Mizokami

Urology Journal, Vol. 19 No. 03 (2022), , Page 202-208
https://doi.org/10.22037/uj.v18i.6652

Purpose: Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.


Materials and Methods: The study included 97 patients with advanced UC whose lesions were classified according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median age was 73 years. Nineteen patients (20%) with performance status (PS) 2–4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The efficacy, safety, and risk factors for prognosis were evaluated for patients with and without measurable lesions.


Results: The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8–4.7) and 11.8 months (95% CI: 6.7–17.0), respectively. Twenty-one (22%) patients had no measurable lesions per RECIST. In univariate and multivariate analysis, PS 2–4 and lesions by RECIST were identified as factors associated with short overall survival (OS). The median OS of 18.3 months in patients without lesions by RECIST was significantly longer than the median OS of 6.7 months in patients with lesions by RECIST (p = .012).


Conclusion: We demonstrated that good PS 0–1 and no measurable lesions, especially small lesions, by RECIST were favorable prognostic factors in patients with advanced UC treated by pembrolizumab.


 

Predictors of Secondary Bladder Cancer in Patients with Prostate Cancer Treated with Brachytherapy: A Single-institution Study of a Japanese Cohort

Kiyoshi Takahara, Makoto Sumitomo, Masayuki Ito, Fumitaka Ito, Masashi Nishino, Takuhisa Nukaya, Masashi Takenaka, Kenji Zennami, Kosuke Fukaya, Manabu Ichino, Naohiko Fukami, Hitomi Sasaki, Mamoru Kusaka, Shinya Hayashi, Hiroshi Toyama, Ryoichi Shiroki

Urology Journal, Vol. 19 No. 03 (2022), , Page 209-2013
https://doi.org/10.22037/uj.v18i.6718

Purpose: The incidence of secondary bladder cancer after treatment for localized prostate cancer (PCa) remains unclear. In this study, PCa cases treated with brachytherapy (BT) were evaluated to assess the incidence of a second malignancy of bladder cancer in a Japanese cohort.


Materials and Methods: Overall, 969 patients treated with BT at our hospital between July 2006 and January 2019 were included in the study cohort. The incidence and predictors of secondary bladder cancer were also assessed.


Results: The incidence of secondary bladder cancer was 1.5% (n = 14). Of the seven factors (age, pretreatment PSA, Gleason score, cTNM stage, prostate volume, total activity, and combined external beam), prostate volume and total activity showed significant differences between the cohorts with and without secondary bladder cancer (P = .03 and P = .001, respectively). Upon comparison of the seven parameters for the 969 patients treated with BT, we found that only the total activity factor was affected by the incidence of secondary bladder cancer in the multivariate analysis (P = .007).


Conclusion: The incidence of secondary bladder cancer was evaluated after BT for PCa. Total activity was associated with the incidence of secondary bladder cancer in Japanese patients who received BT.

DNA Hypermethylation af a Panel Of Genes as an Urinary Biomarker For Bladder Cancer Diagnosis

Petros Georgopoulos, Maria Papaioannou, Soultana Markopoulou, Aikaterini Fragou, George Kouvatseas, Apostolos Apostolidis

Urology Journal, Vol. 19 No. 03 (2022), , Page 214-220
https://doi.org/10.22037/uj.v18i.6743

Purpose: Several studies have shown frequent changes in DNA methylation in bladder cancer (BCa), which vary among different geographical areas. The aim of this study is to examine the diagnostic accuracy of a panel of DNA methylation biomarkers in a Greek clinical setting contributing to the development of a universal panel of urine biomarkers.


Materials and Methods: Individuals with primary BCa and control individuals matching the gender, age and smoking status of the cancer patients were recruited. DNA methylation was assessed for the gene promoters of RASSF1, RARB, DAPK, TERT and APC in urine samples collected by spontaneous urination using quantitative Methylation Specific PCR (qMSP). All genes had been previously separately associated with BCa.


Results: Fifty patients and 35 healthy controls were recruited, with average age of 70.26 years and average smoking status of 44.78 pack-years. In the BCa group, DNA methylation was detected in 27 (61.4%) samples. RASSF1 was methylated in 52.2% of samples. Only 3 (13.6%) samples from the control group were methylated, all in the RASSF1 gene promoter. The specificity and sensitivity of this panel of genes to diagnose BCa was 86% and 61% respectively. The RASSF1 gene could diagnose BCa with specificity 86.4% and sensitivity 52.3%.


Conclusion: Promoter DNA methylation of this panel of five genes could be further investigated as urine biomarker for the diagnosis of BCa. The RASSF1 could be a single candidate biomarker for predicting BCa patients versus controls. Studies are required in order to develop a geographically adjusted diagnostic biomarker for BCa.

ORIGINAL PAPER (PEDIATRIC UROLOGY)


Purpose: This study aimed to examine the short and long-term complications of thermocautery-assisted circumcisions with local anesthesia done in a sterile environment in operating room conditions, accompanied by literature.


Materials and Methods: The participants who consecutively underwent thermocautery-assisted circumcision with local anesthesia from June 2018 to May 2019 included in the study. They were one month-17 years old, same ethnic origin, in same location. The age groups were compared in terms of complications.


Results: The participant age and surgical duration means were 4.89 ± 2.08 (30 days-17 years) years old and 7.484 ± 1.524 (5-20 minutes) minutes, respectively. Complications were observed in fifty-three participants or 2.9% of the whole observation set. The participants under intervals of one six months and over 6 years of age had significantly lowered complication rates when compared to the other participants, and this comparison was statistically significant (P = 0.001).


Conclusion: The study results demonstrated that circumcision with thermocautery after local anesthesia viable, reliable, and effective method. It can be assumed that circumcisions in males especially may be effective in 1-6 months, and over 6 years of age. Parents choose this method because it is more appropriate and eliminates the risk of general anesthesia.

ORIGINAL PAPER (KIDNEY TRANSPLANTATION)


Objective: In this study, we aimed to compare the frequency of lymphoceles that needed intervention in recipients who received kidneys from living versus deceased donors.


Materials and methods: The records of all patients who underwent kidney transplantation at the Labbafinejad Hospital from 2012 to 2021 were retrospectively reviewed to determine the incidence of lymphoceles that needed intervention for management.


Results: From March 2012 to April 2021, 1752 patients received kidney transplantation in Labbafinejad Hospital including 975 transplantations from living donors and 777 transplantations from deceased donors. Symptomatic lymphoceles were observed postoperatively in 23 patients. Symptoms included compressive effect on the ureter, hydroureteronephrosis of the transplanted kidney, frequency, urinary retention, infection,  abdominal discomfort, or rise in serum creatinine. Out of 23 patients who needed intervention for symptomatic lymphocele, 15 patients were recipients of living donors and 8 patients were recipients of deceased donors [1.53% versus 1.03%, P=.40]. Intervention consisted of open surgical drainage in 6 patients [4 recipients of living donors and 2 recipients of deceased donors], and nephrostomy insertion in 17 patients. Open operation was necessary in 5 (47%) patients in whom arterial anastomosis was made to the internal iliac artery versus 1 (9%) patient in whom the anastomosis was not made to the internal iliac artery (P=0.15).


Conclusion: Symptomatic lymphoceles which needed intervention were observed in low frequency (1.31%). Most cases can be managed by endoscopic drainage without relapse. Type of donation had no relationship with the need for open or endoscopic intervention in lymphoceles. A higher proportion of open surgeries to control lymphocele were observed in recipients in whom the internal iliac artery was used for arterial anastomosis however the difference was not statistically significant.

ORIGINAL PAPER (ANDROLOGY)


Evaluation of Sperm Parameters and DNA Integrity Following Different Incubation Times in PVP Medium

Ali Nabi, Farahnaz Entezari, Seyed Mohsen Miresmaeili, Serajoddin Vahidi, Keivan Lorian, Fatemeh Anbari, Leila Motamedzadeh

Urology Journal, Vol. 19 No. 03 (2022), , Page 232-237
https://doi.org/10.22037/uj.v18i.6936

Purpose: Polyvinylpyrrolidone (PVP) is a chemical material used in intracytoplasmic sperm injection (ICSI) program.  The aim of this study was to investigate the ideal time that sperm can be safely incubated in PVP with less structure and DNA damage.


Method: Thirty-one Oligoasthenoteratospermia (OAT) samples were used. Sperm samples were prepared by discontinuous density-gradients method and incubated in 10% PVP at different time intervals (0, 5, 10, 15, 20, and 30 min). The effect of PVP was assessed on sperm DNA fragmentation and viability via SCD assay and Eosin–nigrosin staining respectively.


Results: Data showed there was a significant increase in sperm DNA fragmentation at 10 min compared to 0 min. The viability rate also significantly reduced at 10 min  compared to 0 min.


Conclusion: As a result, sperm samples could be incubated with PVP for less than 10 min.  While prolonged incubation may significantly damage the sperm DNA integrity and viability.

UNCLASSIFIED


A Proposal for Data Registry system for Urologic Cancers in Iran

Fatemeh Simforoosh, Nasser Simforoosh, Mehdi Dadpour, Mohammad Hadi Radfar

Urology Journal, Vol. 19 No. 03 (2022), , Page 238-240
https://doi.org/10.22037/uj.v18i.6790

Purpose: Data registries are organized systems that facilitate collection, storage, and analysis of data related to a specific disease in a defined population. Here we introduce a data registry system which was designed to cover the four most common urologic cancers (prostate, bladder, renal and testis).


Materials and methods: All contributing centers can enter data into the system after logging in with their unique usernames and passwords. In this system, the information of each individual patient will be entered in several structured forms covering various steps of management of the patients.


Results: Our proposed registry is an interactive, web-based database designed to collect complete data of patients with common urological cancers. We devised a council that functions as the central committee that will initiate, supervise, and monitor all steps of the projects including data collection, data audit, as well as data analysis and publication. To facilitate manuscript publication, the system will provide assistance and support throughout all the steps of statistical analysis and manuscript preparation.


Conclusion: This proposed registry can have a national target and is designed to provide evidence-based information that could support strategic planning and national multi-centric studies.

LETTER


Implementation of Telemedicine in Indonesian Urology Practice During COVID-19 Pandemic: a National Survey

Faridz Albam Wiseso, Ahmad Zulfan Hendri, Sakti Ronggowardhana Brodjonegoro

Urology Journal, Vol. 19 No. 03 (2022), , Page 241-245
https://doi.org/10.22037/uj.v18i.6772

Background: The pandemic of COVID-19 is nowhere from over, which pushes us to adapt to it.  Social distancing rules were applied to restrict the people and prevent virus transmission. Despite these restrictions, the patient's care should not be compromised. Doctors are encouraged to technologically improve themselves to get used to the utilization of telemedicine.


Methods: We conducted an online survey of urology specialists and urology residents throughout the country. The survey was accompanied by the Indonesian Urological Association, and the survey was opened for one month and sent by email to all members of the association.


Results: A total of 50 urologists and 182 urology residents participated. Almost half (48%) currently do not have facilities to hold a telemedicine practice in their institution, and 14% reported inadequate facilities. The majority reveals that the barrier to conducting this method was due to insufficient facility. Other issues like insurance coverage and patient's interest in telemedicine, the risk of patient's data leak, and the urologist's lack of interest in telemedicine might also be challenging. Despite some doubts, in sum, more than half have thought that telemedicine would keep utilized although the pandemic is resolved.


Conclusions: We are currently learning the novel telemedicine implementation and some challenges still need to be resolved. Starting from the regulation and legal protection fundamentally, and the health insurance coverage needs to be determined. After all, the low interest in adopting this method has become the greatest barrier.