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Alotaibi MF, Al-Joufi F, Abou Seif HS, et al. Drug Des Devel Ther. 2020;14:4003-4019 The Editor and Publisher of Drug Design, Development and Therapy are retracting the published article. Concerns were raised regarding the duplication of images in Figure 2 and an investigation found overlap in the images for Figures 2D and 2E, despite both images representing results of different treatments. The authors cooperated with the investigation and provided data associated with the reported study. However, despite the authors’ assistance, a satisfactory explanation for how the images came to be duplicated could not be provided, and the validity of the published work could not be verified. The decision was made to retract the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Over the past three decades, minimally invasive robotic technology has evolved substantially in urological practice, replacing many open procedures and becoming part of routine clinical practice. The Health Sector Transformation Program for the Kingdom's Vision 2030 aims to restructure the health sector and optimize its status and prospects as an effective and integrated ecosystem centered on the patient's health. Therefore, this consensus seeks to endorse the clinical practice guidelines for robotic surgery (RS) in the KSA, highlighting its effectiveness, safety, and favorable outcomes compared to open and laparoscopic surgeries in certain procedures when used by trained surgeons in well-structured RS programs.

Olive leaf extract (OLE) has potential health benefits and protects against cytotoxicity in different organs. However, nothing has yet been reported on its potential to prevent cyclophosphamide (CP)-induced nephrotoxicity. This study investigated the possible protective effect of OLE on CP-induced kidney injury in rats, focusing on oxidative stress, inflammation, apoptosis and Nrf2/ARE/HO-1 signaling. Rats received 100 or 200 mg/kg body weight OLE for 15 days and a single injection of 150 mg/kg CP at day 16. CP induced kidney injury evidenced by the significantly increased serum creatinine and urea, and histopathological alterations, including glomerular atrophy, interstitial hemorrhage, dilated urinary space and necrosis. CP-induced rats exhibited increased kidney lipid peroxidation, protein carbonyl, nitric oxide (NO) and pro-inflammatory cytokines, and up-regulated NF-κB, Bax, cytochrome c and caspase-3. OLE ameliorated kidney function markers and prevented CP-induced tissue damage. In addition, OLE significantly prevented oxidative stress, inflammation and apoptosis by enhancing the antioxidant defenses and Bcl-2 expression, and suppressing the pro-inflammatory and pro-apoptotic markers NF-κB, Bax, cytochrome c and caspase-3. OLE up-regulated Nrf2, HO-1 and NQO-1 expression in the kidney of CP-induced rats. In conclusion, OLE has a substantial protective role against CP-induced nephrotoxicity in rats by up-regulating the Nrf2/ARE/HO-1 signaling, enhancing the antioxidant activity and attenuating inflammation and apoptosis.

Purpose: To present multinational experience in robot-assisted radical prostatectomy (RARP) by fellowship-trained expertise in low-volume regions in Gulf Cooperation Council (GCC) countries and to ...

Mohammed F Alotaibi,1 Fakhria Al-Joufi,2 Howida S Abou Seif,3 Mohammed A Alzoghaibi,1 Laiche Djouhri,4 Ahmad F Ahmeda,5 Ayman M Mahmoud6 1Physiology Department, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia; 2Department of Pharmacology, Faculty of Pharmacy, Jouf University, Sakaka 2014, Saudi Arabia; 3Medical Physiology Department, Medical Research Branch, National Research Centre, Giza 12622, Egypt; 4Department of Basic Medical Sciences, College of Medicine, Qatar University, Doha 2713, Qatar; 5College of Medicine, Ajman University, Ajman 346, United Arab Emirates; 6Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, EgyptCorrespondence: Ayman M MahmoudPhysiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, EgyptTel +201278355478Email ayman.mahmoud@science.bsu.edu.egIntroduction: Lead (Pb) is an environmental toxic metal that threatens human health. Umbelliferone (UMB) is a coumarin with known medicinal and protective properties against cytotoxicity. This study explored the ameliorative effect of UMB against Pb-induced testicular toxicity in rats, focusing on steroidogenesis, oxidative stress and inflammation.Materials and Methods: Rats received lead acetate (50 mg/kg) and UMB (25, 50 or 100 mg/kg) via oral gavage for 4 weeks.Results: Pb-intoxicated rats exhibited testicular tissue injury and decreased serum levels of LH, FSH and testosterone. The count, viability, motility and normal morphology of the sperms were decreased accompanied with downregulated steroidogenesis markers in Pb-induced group. UMB prevented testicular injury, increased serum levels of LH, FSH and testosterone, upregulated steroidogenesis markers and improved the semen quality. In addition, UMB attenuated oxidative stress and oxidative DNA damage, downregulated the expression of pro-inflammatory mediators and Bax, boosted antioxidant defenses and Bcl-2, and upregulated Nrf2/HO-1 signaling in Pb-intoxicated rats.Conclusion: UMB prevents Pb-induced testicular injury by suppressing oxidative damage, inflammation and cell death, and boosting antioxidant defenses, Nrf2/HO-1 signaling and pituitary-gonadal axis. Thus, UMB may represent a protective and cost-effective agent against Pb testicular toxicity, pending further investigations to elucidate other underlying mechanisms.Keywords: umbelliferone, StAR, oxidative stress, Nrf2, inflammation, pituitary-gonadal axis

Objectives: To report robotic partial nephrectomy (RPN) outcomes from a single tertiary hospital in Saudi Arabia. Methods : We retrospectively reviewed consecutive cases of patients undergoing RPN at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, between January 2008 and January 2018. The study reports patient’s demographics, tumor characteristics, operative details, and perioperative outcomes, using descriptive statistics of median and range values. Results : One hundred and one patients underwent RPN during the study period. Average tumor size was 3 (1.3-6.4) cm and average radius exophytic nearness anterior/posterior location (RENAL) score was 6 (4-10). Perioperative parameters were blood loss 200 (5-1500) ml and warm ischemia time 17 (8-40) minutes, excluding off-clamp surgery in 12 (11.9%); operative time was 166 (66-381) minutes. Conversion to open partial nephrectomy occurred in 9 (8.9%) patients, major complications in 3 (3%) patients, positive surgical margins in 5 (5%) patients, and the hospital stay was 4 (2-14) days. A total of 73 (73%) patients achieved a trifecta of freedom from any complication, negative surgical margins, and ischemia time ≤25 minutes. Study limitations included the retrospective design and small cohort size. Conclusions : The initial experience of robotic partial nephrectomy was associated with a surgical outcome comparable to that reported by higher-volume centers. Saudi Med J 2019; 40 (1): 33-40 doi: 10.15537/smj.2019.1.22782 How to cite this article: Seyam RM, Alalawi MM, Alkhudair WK, Alzahrani HM, Azhar RA, Alothman KI, Al-Hussain TO, Alotaibi MF. Operative outcomes of robotic partial nephrectomy: A report of the first 101 cases from a single center in Saudi Arabia. Saudi Med J 2019; 40; 33-40.

Normal repeated uterine contractions are associated with uterine hypoxic stresses and uterine transplantation and severe bleeding during hysterectomy may lead to hypoxia and irreversible cellular damage. This study investigated the effects of short repeated hypoxic episodes on the structure and function of uterine tissues following sustained prolonged hypoxia. Small segments of uterine tissue were dissected from three groups of nonpregnant rats and mounted in a tissue bath system. Prolonged hypoxia markedly increased the infiltration of eosinophils into the myometrium and caused fibrotic stroma and degeneration of endometrial glands with marked infiltration of eosinophils into the endometrium compared to the control group. In addition, the mean myometrial contractile function significantly decreased to 69 ± 1% compared to 100% control with irregular and uncoordinated contractile activity (p < 0.01). Intriguingly, preconditioning with brief hypoxic episodes prevented the endometrial and myometrial degenerative changes. Although the mean myometrial contractile function decreased to 80 ± 3% during reoxygenation compared to the 100% control, the entire force was greater than the force in the non-preconditioned group (p < 0.01). These results provide compelling evidence that prolonged hypoxia exacerbates the degree of cellular damage and that preconditioning with repeated cycles of short hypoxia/reoxygenation can ameliorate cellular damage.

During labour, the uterus itself is vulnerable to hypoxia/ischemia that can occur with each strong contraction and this may ultimately cause dysfunctional labour in some women. Periods of Intermittent re-oxygenations are beneficial to tissues subjected to hypoxia to wash out metabolic by-products that have been accumulated during hypoxic stresses which may affect the tissue viability. We proposed that short intermittent hypoxic episodes may protect the uterus from subsequent sustained long hypoxia. To investigate this, two sets of experiments were performed on term-pregnant and nonpregnant rat uterine tissues. In one set of experiment the uterus was subjected to sustained long hypoxia for 40 min and then allowed to recover in 100% O2. In the other set of experiment the uterus was subjected to 3 cycles of 2 min hypoxia each separated by 20 min reoxygenation and followed by a sustained long hypoxia for 40 min and then allowed to recover. We found that challenging the uterine tissues with intermittent short hypoxic episodes improved the uterine contractility significantly after the sustained long hypoxia in term-pregnant but not in non-pregnant tissues. These results suggest that a mechanism of uterine tolerance (preconditioning) is confined to uterine tissues very close to labour and it is a protective phenomenon to improve the uterine activity despite the long-lasting paradoxical metabolic challenges that occur during the repeated strong labour contractions.

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication that occurs as a result of liver failure. Umbelliferone (UMB; 7-hydroxycoumarin) is a natural product with proven hepatoprotective activity; however, nothing has yet been reported on its protective effect against hyperammonemia, the main culprit behind the symptoms of HE. Here, we evaluated the effect of UMB against ammonium chloride (NH4Cl)-induced hyperammonemia, oxidative stress, inflammation and hematological alterations in rats. We demonstrated the modulatory role of UMB on the glutamate-nitric oxide (NO)-cGMP pathways in the cerebrum of rats. Rats received intraperitoneal injections of NH4Cl (3 times/week) for 8 weeks and concomitantly received 50 mg/kg UMB. NH4Cl-induced rats showed significantly elevated blood ammonia and liver function markers. Lipid peroxidation and NO were increased in the liver and cerebrum of rats while the antioxidant defenses were declined. UMB significantly reduced blood ammonia, liver function markers, lipid peroxidation and NO, and enhanced the antioxidant defenses in NH4Cl-induced rats. UMB significantly prevented anemia, leukocytosis, thrombocytopenia and prolongation of PT and aPTT. Hyperammonemic rats showed elevated levels of cerebral TNF-α, IL-1β and glutamine as well as increased activity and expression of Na+/K+-ATPase, effects that were significantly reversed by UMB. In addition, UMB down-regulated nitric oxide synthase and soluble guanylate cyclase in the cerebrum of hyperammonemic rats. In conclusion, this study provides evidence that UMB protects against hyperammonemia via attenuation of oxidative stress and inflammation. UMB prevents hyperammonemia associated hematological alterations and therefore represents a promising protective agent against the deleterious effects of excess ammonia.

Aim To assess the in vitro effect of hydrogen peroxide (H 2 O 2 ) on uterine contractions in pregnant and non-pregnant rats. Methods The study was performed at the Department of Physiology, College of Medicine, King Saud University from December 2016 to October 2017. Intact uterine samples were obtained from non-pregnant (n = 7-8) and term-pregnant (n = 6-7) rats. Small longitudinal uterine strips were dissected and mounted in an organ bath. Isometric force measurements were used to assess the effect of 400, 800, and 1000 ?M H 2 O 2 on spontaneous uterine contractions and contractions induced by oxytocin (5 nM), high calcium (Ca +2 ) solution (6 mmol/L), and high potassium chloride (KCl) solution (60 mmol/L). Results In both term-pregnant and non-pregnant uterine strips, H 2 O 2 elicited a biphasic response, consisting of a transient contraction followed by a persistent decrease in spontaneously generated contractions, contractions induced by oxytocin, and contractions induced by high Ca +2 (all P< 0.01, compared with controls) in a concentration-dependent manner. The effect of H 2 O 2 was more pronounced in non-pregnant than in pregnant rats (P< 0.05). In both groups, H 2 O 2 failed to relax uterine strips pre-contracted with high-KCl solution (P> 0.05 compared with controls). Conclusion H 2 O 2 was shown to be a potent uterine relaxant in pregnant and non-pregnant states. The pregnant uterus better withstood the inhibitory effect of H 2 O 2 than non-pregnant uterus. FundingThestudywasfundedbyKingAbdulazizCityforScienceandTechnology(KACST)(projectnumberGSP-37-1118).ethicalapprovalTheexperimentalprotocolandstudieswereapprovedandcarriedoutaccordingtotheInstitutionalAnimalCareCommittee(IACC)ofKingSaudUniversityrecommendations(September2016). Scopus

The uterus is a myogenic organ that is able to produce discrete spontaneous action potentials and contractions without any stimuli. Myometrial excitability is governed by ion channels including Ca+2 and K+ channels, but whether or not other channels such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which play an important role in regulating cellular excitability, are also involved has not been reported in uterine smooth muscles. The aim of the present study was to examine whether blocking HCN channels with a specific blocker ZD7288 would modulate the uterine contractility in a rat model. Using longitudinal uterine strips from term-pregnant rats, the effects of varying concentrations of ZD7288 (50 μM, 100 μM, and 200 μM) were examined on uterine contractions generated spontaneously or by oxytocin (5 nmol/L) and on uterine strips depolarized by high-KCl (60 mM/L), or activated by L-type Ca2+ channels agonist (Bay K8644; 1 μM). Application of ZD7288 at concentrations of 200 μM and 100 μM, but not 50 μM, significantly decreased the amplitude of spontaneous uterine contractions. In addition, 200 μM of ZD7288 significantly reduced the force of contractions induced by oxytocin with a pronounced reduction while the tissues were depolarized by high-KCl solution, or activated by Bay K8644. The present study provides pharmacological evidence suggesting that pregnant uterine contractility is modulated by HCN channels and that these channels might represent a therapeutic target for controlling premature activation of uterine activity associated with preterm labor.

Objectives: We determined the surgical and oncological outcomes of laparoscopic nephroureterectomy (LNU) in comparison to open nephroureterectomy (ONU) and factors predicting bladder recurrence after nephroureterectomy. Methods : We retrospectively reviewed and compared the data of patients who underwent ONU or LNU for non-metastatic, upper-tract urothelial carcinoma from 2000 to 2016. The primary endpoint was to determine bladder cancer recurrence-free survival (BCRFS), cancer-specific survival (CSS), and overall survival (OS). The data were analysed using Student’s t-test, Chi-square test, and Kaplan-Meier curve. Results : Total of 50 patients, of which 24 had LNU and 26 had ONU, met the inclusion criteria. Median durations of follow-up were 4.2 and 6.5 years ( p =0.1070) in LNU and ONU, respectively. Operative time, blood loss and hospital stay were significantly lower in the LNU group than in the ONU group ( p =0.0001, p =0.0001, p =0.0018). Cancer-specific survival rate in the LNU was 75% and ONU was 73.3% ( p =0.1902), whereas BCRFS and CSS were not significantly different in both groups (log-rank test; BCRFS: p =0.809 and CSS: p =0.802). Patients who underwent ureteroscopy with biopsy ( p =0.001), had multifocality ( p =0.001) and previous history of (H/O) bladder cancer ( p =0.020) were at significant risk for developing bladder cancer recurrence after nephroureterectomy. Conclusion : Laparoscopic nephroureterectomy can benefit patients because of its minimal invasiveness, and oncologic outcomes are comparable to ONU. Preoperative ureteroscopy with biopsy, multifocality and previous H/O bladder cancer might be risk factors for bladder cancer recurrence. Saudi Med J 2020; Vol. 41 (1): 25-33 doi: 10.15537/smj.2020.1.24780 How to cite this article: Alothman KI, Mehmood S, Alzahrani HM, Alotaibi MF, Alkhudair WK, Eldali AM. Surgical and oncological outcome after laparoscopic versus open nephroureterectomy for non-metastatic, upper-tract urothelial carcinoma. A single-centre experience. Saudi Med J . 2020 Jan;41(1):25-33. doi: 10.15537/smj.2020.1.24780.

Ethnopharmacology relevance Pimpinella anisum is a well-known traditional medicinal herb which has been used in folk medicine as an antiulcer, anticancer, antibacterial and as a muscle relaxant. Aim of the study This study was performed to explore the modulatory effects of Pimpinella anisum on term-pregnant rat uterine contractility and to investigate its possible underlying mechanisms. Material and methods Intact uterine strips without endometrial layer were isolated from female term-pregnant Wistar rats (22 days of gestation) and mounted in a tissue bath apparatus for in vitro isometric force recording. The effects of different concentrations of Pimpinella anisum extract (PAE) (1, 3, 5, and 7 mg/mL) were examined on uterine contractions generated spontaneously or induced with oxytocin (5 nmol/L), Bay K8644 (1 μmol/L), and carbachol (10 μmol/L). In some experiments, PAE was applied on depolarized myometrium in the presence of high-KCl solution (60 mmol/L). The effect on Ca2+ release was also examined. Results Application of PAE significantly reduced uterine contractions generated spontaneously or induced with oxytocin, Bay K8644, and carbachol in a concentration-dependent manner (n = 7; P Conclusion The present findings demonstrate the potentials of PAE to relax pregnant uterine contractions possibly by blocking Ca2+ entry via L-type calcium channels and inhibiting Ca2+ release from the internal store. The tocolytic effects of PAE may be a potential adjuvant against strong premature uterine contractions which threaten early pregnancy although clinical studies are required.

Continuous oxytocin exposure to augment labor contractions may cause receptor desensitization and further reduce the uterine response to oxytocin, resulting in an increased risk of uterine atony. This study aimed to investigate and compare the uterine response to continuous and intermittent oxytocin stimulation. We hypothesized that intermittent brief episodes of oxytocin separated by recovery periods rather than continuous oxytocin application improves subsequent uterine contractions. Myometrial strips were isolated from term-pregnant rats (22 days of gestation; n = 11), mounted in tissue bath chambers, and exposed to continuous oxytocin (5 nM) for 2 h or 6 repeated episodes of 10-min oxytocin exposure (5 nM) separated by 10 min of recovery period in Krebs solution. Contractile parameters (force amplitude, frequency, and integral force) significantly decreased during continuous oxytocin exposure compared with control (n = 11; P

Oxytocin (OT) and oxytocin receptors (OTRs) play essential roles in parturition and the effect of OT on uterine contractility is greatly influenced by the expression of OTRs in myometrium. We investigated the effect of OT on uterine strips isolated from non-pregnant, late-pregnant, term-pregnant, and labouring rats and from labouring and non-labouring women. Longitudinal uterine strips (from each gestational stage) were dissected and mounted vertically in an organ bath setup system and challenged with 5 nM OT and the effect was investigated on uterine contractility. In other experiments, phospholipase C (PLC), prostaglandin H synthase-2 (PGHS-2), and calcium-activated chloride channels (CaCCs) were blocked and the effect of OT was tested in labouring rats. OT stimulated the labouring uterus with greater force compared to other gestations in rats and also augmented the uterine force in labouring women compared to the non-labouring. However, blocking the PLC, PGHS-2, and CaCCs significantly reduced the OT-induced force increase in labouring rats. These data suggest that as labour approaches, the sensitivity of the uterine tissues to OT is greatly enhanced concomitant with the increased expression of OTR to ensure strong and adequate uterine contractions essential for the normal delivery and to prevent the postpartum haemorrhage.

Renal artery pseudoaneurysm is an uncommonly recognized complication following partial nephrectomy. It is more common with trauma and percutaneous renal intervention. Furthermore, it is rarely reported with minimally invasive laparoscopic partial nephrectomy. Herein, we report the first case to our knowledge of renal artery pseudoaneurysm following a robotic-assisted partial nephrectomy.

Background: In the last three eras, the incidence of renal cell carcinoma (RCC) has increased, due to increased radiological studies. The expected 5-year survival rate has become better, associated with the identification of small size renal masses. However, this survival improvement may be secondary to improved surgical techniques and medical therapies for these malignancies. Objectives: The objective was to report the trends of clinical presentation, peri-operative, oncological outcomes, and surgical management trends for RCCs over the period. Methods: After Institutional Review Board approval, a retrospective study for adult patients was conducted, who presented with renal mass and were managed between 2008 and 2019. Variables, including demographics, perioperative and pathological outcomes analyzed using descriptive statistics for continuous variables reported as mean ± standard deviation and categorical variables values compared by Chi-square test. Survival Analysis calculated using the Kaplan-Meier method. The level of significance is set at P-value < 0.05. Results: A total of 588 patients underwent surgical treatment for kidney cancer from January 2008 to January 2019. 237 (40.30%) were females and 351 (59.69%) males. The clinical presentation was higher as an incidental diagnosis of 58.67%. 71.25% of patients were from outside Riyadh city. Pathology was mostly clear cell RCC 61.22% and grade 2 (57.48%). Tumor size, surgery time, and length of hospital stay showed a significant difference between the three periods (both P > 0.05). Robotic surgery performed more than open (P < 0.0001). There was no significant difference in the survival time, when compared to patients by the regions and when compared by the primary tumors (Log-Rank P = 0.4821). Patients from the Riyadh region (median = 54.0) had a significantly higher recurrence time (Log-Rank P < 0.0001). Conclusion: There was a rising trend in the incidence of RCC associated with comorbidities and incidental diagnosis. In our study period we found increase in the trend of minimal invasive approach. The size of the tumor, blood loss and operative time decreases over the period of time. The Robotic assisted nephrectomy approach has become increased over the period of time duration in present study.

Background: Cutaneous squamous cell carcinomas (cSCCs) are the second highest nonmelanoma skin cancer, commonly targeting the head and neck region. Owing to its rising annual incidence, the actual rate of metastasis from the primary cSCC is needed to be investigated separately to develop more efficient management plans, hence nobly decreasing the incidence rate of metastasis overall. Materials and Methods: We conducted a literature review about the incidence rate of metastasis from the primary (or de novo) cSCC, based on two popular databases (PubMed and Cochrane), excluding different-purpose serving articles, for example, unrelated outcomes, case series, and case reports. Results: The mean incidence rate of metastasis from the primary cSCC is 10% (1.2–16.5). The least mean tumor size reportedly associated with regional and distant metastasis was 1.11 cm, and the least median thickness was 3 mm deep. Most of the metastatic tumors were of T1 stage before metastasis, and all metastases reported in the literature had more than one risk factor at a time. The mean follow-up duration was 4 years. Discussion: About half of the included literature carried a suspicion of selection bias, which threatens both their internal validity by overestimating the actual rate of metastasis and their external validity by seizing the reproducibility of the current evidence. Almost 85% of the metastasis was reported in the regional lymph nodes, while only a few cases involved distant anatomies at the time of diagnosis. This was consistent with other separate literatures. Conclusion: The mean incidence rate of metastasis from the primary cSCC tumors in our literature review is 10%, which is relatively higher than what was reported before in similar reviews. However, a large prospective study needs to be conducted to control and follow the involved prognostic factors, stratify them according to their risk factors, and minimize the risk of the previously reported bias in other reviews.

Puberty is a physiological event involving the attainment of reproductive capability and complete development of sexual and physical organs. Changing from childhood to adulthood is a complex process and is tightly controlled by interconnection pathways at the level of the hypothalamus which can be influenced by environmental, psychosocial, and endocrine factors. Although various mechanisms underlying the onset of normal puberty have been investigated in humans and animals, the exact molecular mechanisms thereof remain unclear. The aim of this review is to summarize the current state of knowledge and provide a synoptic overview about the physiology of puberty in adolescent boys and girls, and describe pathological disorders affecting its onset.

Background: Intravesical Bacillus Calmette–Guerin (BCG) has been the standard of care for the prevention of nonmuscle invasive bladder cancer (NMIBC) recurrence following resection. Attempts to improve on the result by combining it with other agents have largely failed. This study addresses the result of BCG therapy in our patient population and compares the result with our combination BCG and interferon therapy published earlier. Materials and Methods: The medical records of patients diagnosed with NMIBC and treated with transurethral resection and intravesical BCG were reviewed. Univariate analysis was performed on most known prognostic factors. Results were compared to published data on the use of BCG and interferon from the same institution. Results: Thirty-one patients were identified. Median age was 66 (range 33–109), 80.6% were males. Fourteen patients (45%) had ≤ 3 tumors and 18 (58.1%) had T1 lesions. Four patients (12.9%) had Grade 3 tumors and 25 (80.6%) had Grade 2 tumors. One patient (3.2) had concurrent carcinoma in situ and 11 (35.5%) were treated upon initial diagnosis. At 5 years, the relapse-free survival was 61.3% (95% confidence interval (CI) 44.2–78.4%), progression-free survival was 85.6% (95% CI 73.3–97.9%), and overall survival was 93% (95% CI 84.1–100%). Comparison with the BCG and interferon data showed no significant difference. Conclusion: The result of BCG therapy in our patient population is similar to western reported data. Efficacy of BCG alone is equal to BCG and interferon within our institution.

Aims Given the importance of ATP in the control of uterine activity for successful labor and involution, this study was performed to measure the level of P2X7 receptors (P2X7Rs) in rat myometrium at different gestational stages and to investigate the mechanisms of ATP-induced uterine contraction. Materials and methods Myometrial tissues were obtained from rats at different gestational stages and the level of P2X7Rs was measured by ELISA. In other experiments, the effect of 1 mM ATP was tested on spontaneous contraction and the underlying mechanisms were investigated. Key findings P2X7Rs were expressed in nonpregnant uterine tissues, progressively increased throughout pregnancy, and markedly peaked during postpartum involution. ATP significantly increased the force of spontaneous contraction in all uterine strips from different gestational stages with marked increase during labor and postpartum. ATP could not maintain the force when external Ca2+ was removed. In addition, ATP was able to cause tonic transient contraction in the absence of external Ca2+. Significance P2X7Rs are functionally regulated and contributed to ATP-induced uterine contraction. The sensitivity of the myometrium to ATP increases as pregnancy progresses and it involves Ca2+ influx and Ca2+ release pathways. The clear effects of ATP on contractility suggest its physiological requirement for successful labor and postpartum involution.

Background Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a serious dose-limiting neurotoxic effect of cancer drug treatment. The underlying mechanism(s) of this debilitating condition, which lacks effective drug treatment, is incompletely understood. However, neural-immune interactions, involving increased expression and release of cytokines, are believed to be involved. Here, we examined, in the paclitaxel rat model of CIPNP, whether plasma levels of 24 cytokines/chemokines change after paclitaxel treatment, and whether blocking of signalling of some of those cytokines would reverse/attenuate behavioural signs of CIPNP. Methods To achieve these objectives luminex, pharmacological and behavioural experiments were performed on male Wistar rats (250-300 g) 31 days after the last injection of paclitaxel (1 mg/kg, i.p. on four alternate days) as well as on control (vehicle-treated) rats. Results Compared with control rats, plasma levels of IL-1α, IL-1β, IL-6, TNF-α, INF-γ and MCP-1 were significantly upregulated in paclitaxel-treated rats. Blocking of TNF-α signalling with etanercept (2 mg/kg, i.p.) or IL-1β with IL-1 receptor antagonist (IL-1ra; 3 mg/kg, i.p.), significantly attenuated established mechanical and cold hypersensitivity as well as spontaneous pain behaviour (spontaneous foot lifting) 24 and 48 h postdrug treatment. Pharmacological blockade of MCP-1/CCL2 signalling with a highly selective CCR2 receptor antagonist (S504393, 5 mg/kg, i.p.) also significantly reduced evoked, but not spontaneous, pain behaviours of CIPNP in paclitaxel-treated rats at the same time points. Conclusions The findings support the notion that cytokines/chemokines, particularly TNF-α, IL-1 and MCP-1, are involved in the pathophysiology of CIPNP and suggest that strategies that target their inhibition may be effective in treating CIPNP. Significance This study demonstrates that paclitaxel-treated rats exhibit, in addition to indices of mechanical and cold hypersensitivity, a behavioural sign of spontaneous pain, the principal compliant of patients with neuropathic pain. This was accompanied by upregulation in plasma levels of key cytokines/chemokines (IL-1α, IL-1β, IL-6, TNF-α, INF-γ and MCP-1) 31 days post-treatment. However, it is noteworthy that cytokine release, rather than nerve injury per se, may be causative of NP in this model of CIPNP. Nevertheless, our findings that pharmacological blockade of TNF-α, IL-1β and MCP-1 attenuated both evoked and spontaneous pain suggest that strategies that target inhibition of these cytokines may be effective in treating CIPNP.

In this report, updated guidelines for the evaluation, medical, and surgical management of transitional cell carcinoma of the urinary bladder are resented. They are categorized according the stage of the disease using the TNM staging system 7(th) edition. The recommendations are presented with supporting level of evidence.

Umbelliferone (UMB) is a coumarin derivative with promising hepatoprotective effects. In this study, we examined the possible protective effects of UMB against cyclophosphamide (CP)-induced hepatotoxicity, addressing the question of the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator activated receptor gamma (PPARγ). Wistar rats were orally administered UMB at doses 50 and 100mg/kg two weeks prior to CP injection. Five days after CP administration, the rats were sacrificed and samples were collected for analyses. CP induced a significant increase in circulating liver marker enzymes and pro-inflammatory cytokines. Hepatic lipid peroxidation and nitric oxide levels, and nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) expression were significantly increased following CP administration. UMB supplementation attenuated CP-induced inflammation and oxidative stress as assessed by restoration of the activity and expression of the antioxidant defenses, and suppression of pro-inflammatory cytokines. Histological examination also showed that UMB could significantly reduce CP-induced alterations. CP-induced rats showed significant down-regulation of Nrf2, HO-1 and PPARγ, an effect that was markedly reversed by UMB. In conclusion, the hepatoprotective effects of UMB appear to depend on co-activation of PPARγ and Nrf2, and subsequent suppression of oxidative stress and inflammation.

Background The mechanisms underlying the onset of labor are not fully understood. Extracellular adenosine 5'-triphosphate (ATP) is known to cause uterine contractions in different species but the exact underlying mechanisms are poorly investigated to date. The aims of this study were to investigate the effect of extracellular ATP on spontaneous uterine contractions from different gestational stages and to elucidate its possible underlying mechanisms. Methods Longitudinal uterine strips were obtained from rats in different gestational stages (nonpregnant, late-pregnant, and term-pregnant). The effects of 1 mM ATP were examined on uterine contractions generated spontaneously, depolarized by high-KCl (60 mM), induced by oxytocin (5 nM), in the presence of high external Ca2+, or in the absence of external Ca2+. Results Application of 1 mM extracellular ATP significantly increased the force of spontaneous contraction in uterine strips obtained from all gestational stages with prominent increase in term-pregnant rats compared to other gestations. ATP significantly increased the force induced by depolarization (122%, p=0.010, n=6), oxytocin (129%, p=0.001, n=7), high-Ca2+ (145%, p=0.005, n=6) and it was able to cause transient contraction in the absence of external Ca2+ (33%, p Conclusions Extracellular ATP is able to increase the force and frequency of uterine contractions and its effect increases with the progression of pregnancy and it involves Ca2+ influx and release. These findings open a new window for clinicians to consider ATP as a therapeutic target to control the uterine activity during difficult labors.

Gossypiboma or textiloma are terms commonly used to describe a retained sponge in the body that is composed of sponge invested within a layer of foreign body reaction in the form of an abscess or an aseptic fibrotic reaction. These cases are rarely reported despite an incidence of 1:1,000-1,500 of abdominal or pelvic surgery. We report a patient who presented with an incidental supravesical mass discovered upon work up for frequency and suprapubic pain. He had appendectomy 35 years ago. The mass was excised by robotic-assisted laparoscopic technique. The pathologic evaluation came as gossypiboma.

We report a case of extragonadal seminoma presenting as a polypoid mass in the urinary bladder. The patient presented with two months history of hematuria. Evaluation by CT scan and cystoscopic examination revealed a polypoid mass in the base of the bladder. Biopsy of the mass revealed a classical type of seminoma. The diagnosis of seminoma was supported by strong immunostaining of the tumor cells for C-Kit and placental alkaline phosphatase. Thorough physical examination and radiologic imaging of other organ systems failed to reveal any other tumor. Both testes were found to be normal on examination and on ultrasound imaging. Patient responded well to chemotherapy. This case is unique because to the best of our knowledge there are no previously reported cases in the literature with seminoma presenting as a bladder mass.

Although most patients with prostate cancer respond to initial androgen-deprivation therapy, progression to castration-resistant prostate cancer (CRPC) is almost inevitable. In 2004, the docetaxel/prednisone regimen was approved for the management of patients with metastatic CRPC, becoming the standard first-line therapy. Recent advances have also led to an unprecedented number of approved new drugs; thus, providing several treatment options for patients with metastatic CRPC. Five new drugs have received US Food and Drug Administration-approval between 2010 and 2012: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; enzalutamide, a novel androgen receptor inhibitor; and denosumab, a bone-targeting agent. Such drugs are either already marketed or about to be marketed in the Middle East. Data supporting the approval of each of these agents are described in this review, as are recent approaches to the treatment of metastatic CRPC.

Introduction The purpose of this video is to demonstrate the use of the robot to perform a transmesocolonic pyelolithotomy of a horseshoe kidney. Materials and Methods A 35-year old female presented with vague abdominal pain. CT scan imaging revealed the presence of a left horseshoe kidney with multiple pelvicalyceal stones. The patient was positioned in the supine position. A total of 4 ports were introduced. A 3-arm da Vinci robotic surgical system was docked, and the arms were connected. First, the dilated renal pelvis was identified behind the thin mesocolon. The mesocolon was entered and renal pelvis was dissected completely from the surrounding fat. Then, the renal pelvis was opened after adequate dissection and stones were visualized inside the calyces. By Prograsp forceps, stones were removed from all the calyces under vision and were extracted from the assistant trocar. Finally, the pylotomy incision was closed using 4 0 Maxon in a continuous fashion and the mesocolon was closed using 3 0 PDS interrupted sutures. A JP drain was placed. Result Operative time was forty-five minutes, blood loss was 100 ml. The patient was discharged after 48 hours with no immediate complications. Conclusion The utilization of minimal invasive surgery using the robot to extract multiple pelvicalyceal stones from a horseshoe kidney without reflecting the mesocolon proved to be a feasible and novel way in the management of complex stone disease improving the outcome with minimal morbidity.

This is an update to the previously published Saudi guidelines for the evaluation and medical/surgical management of patients diagnosed with urothelial cell carcinoma of the urinary bladder. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7th edition. The guidelines are presented with their accompanying supporting evidence level, which is based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health-care policymakers in the management of patients diagnosed with urothelial cell carcinoma of the urinary bladder.

Introduction: Multiple case reports and reviews have been described in the literature for bladder wall leiomyoma resection via different approaches. The minimally invasive partial cystectomy remains the most widely accepted technique; however, case reports for enucleation of bladder wall leiomyoma have also been described. The purpose of this video is to demonstrate the robotic extramucosal excision of a bladder wall leiomyoma, without cystotomy, but with complete removal of the muscular layer. Materials and Methods: A 35-year old male present with lower urinary tract symptoms and imaging showed bladder wall mass with histopathology showed leiomyoma. The patient consented for mass excision with the possibility of a partial cystectomy. The patient was placed in the supine, 30-degree Trendelenburg position during the procedure. A total of 4 ports were inserted. A 3-arm da Vinci robotic surgical system was docked, and the arms were connected. Extramucosal excision was accomplished without cystotomy and muscle approximation was achieved by 2 0 Vicryle. Result: The operative time was 90 minutes, blood loss of approximately 50mL and the patient was discharged after 72 hours with no immediate complications and a 6 months follow-up showed no recurrence. Conclusion: Such a technique results in complete excision of the tumor, without cystotomy, and also maintains an intact mucosa. These steps, in addition to decreasing the risk of local recurrence, also shorten the period of postoperative catheterization and hospitalization.

This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with testicular germ cell tumors. It is categorized according to the stage of the disease using the tumor-node-metastasis staging system 7(th) edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health care policy makers in the management of patients diagnosed with testicular germ cell tumors.

Lymphangioma of the urinary bladder is a very rare tumour inadulthood. Robotic partial cystectomy is evolving for treatmentof a limited number of bladder tumours. We describe a case ofan adult woman with a bladder dome lymphangioma for whichrobotic partial cystectomy was carried out.