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Context Although percutaneous nephrolithotomy (PCNL) has been performed for decades and has gone through many refinements, there are still concerns regarding its more widespread utilization because of the long learning curve and the potential risk of severe complications. Many technical details are not included in the guidelines because of their nature and research protocol. Objective To achieve an expert consensus viewpoint on PCNL indications, preoperative patient preparation, surgical strategy, management and prevention of severe complications, postoperative management, and follow-up. Evidence acquisition An international panel of experts from the Urolithiasis Section of the European Association of Urology, International Alliance of Urolithiasis, and other urology associations was enrolled, and a prospectively conducted study, incorporating literature review, discussion on research gaps (RGs), and questionnaires and following data analysis, was performed to reach a consensus on PCNL. Evidence synthesis The expert panel consisted of 36 specialists in PCNL from 20 countries all around the world. A consensus on PCNL was developed. The expert panel was not as large as expected, and the discussion on RGs did not bring in more supportive evidence in the present consensus. Conclusions Adequate preoperative preparation, especially elimination of urinary tract infection prior to PCNL, accurate puncture with guidance of fluoroscopy and/or ultrasonography or a combination, keeping a low intrarenal pressure, and shortening of operation time during PCNL are important technical requirements to ensure safety and efficiency in PCNL. Patient summary Percutaneous nephrolithotomy (PCNL) has been a well-established procedure for the management of upper urinary tract stones. However, according to an expert panel consensus, core technical aspects, as well as the urologist’s experience, are critical to the safety and effectiveness of PCNL.

BACKGROUND: Color mismatch between tooth structure and restoration is a common reason for restoration replacement. This is due, in part, to the diverse chemical structure of both substrates, which display a different staining potential resulting in a significant color mismatch. AIM: The aim of the study was to evaluates the color change of single shade resin composite and compare it to fibrous-filled resin composite (FRc) after storage in coloring beverages. METHODS: Trapezoidal Class V cavities were prepared on the buccal and lingual surfaces of 30 premolars. Cavities on the buccal surface were restored with Omnichroma (ON) and palatal surface with FRc. Specimens were stored on water, tea, and coffee solutions for 24 h and 72 h. The color change was measured after each immersion time and statistically analyzed using three-way analysis of variance (ANOVA) (α = 0.05). RESULTS: Three-way ANOVA showed that different materials had a significant effect on both ΔL and Δa (p < 0.001). For both materials, ON in coffee showed the highest Δb values when compared to FRc for the same period. No difference between ON and FRc when stored in tea for 24 h and 72 h. CONCLUSION: Structural color property of ON can enhance the color perception of restoration to compensate for any color change after consuming coloring food and beverages.

T helper 17 (Th17) cells have a prominent role in autoimmune diseases. In contrast, the nature of these cells in cancer is controversial, with either pro- or antitumorigenic activities depending on various cancer settings. Chronic lymphocytic leukemia (CLL), a B-cell malignancy, is characterized by an imbalance in T-cell immune responses that contributes to disease progression and increased mortality. Many clinical reports indicate an increase in Th17 cells and/or interleukin 17 serum cytokine levels in patients with CLL compared with healthy individuals, which correlates with various prognostic markers and significant changes in the tumor microenvironment. The exact mechanisms by which Th17 cells might contribute to CLL progression remain poorly investigated. In this review, we provide an updated presentation of the clinical information related to the significance of Th17 cells in CLL and their interaction with the complex leukemic microenvironment, including various mediators, immune cells, and nonimmune cells. We also address the available data regarding the effects of CLL-targeted therapies on Th17 cells and the potential of using these cells in adoptive cell therapies. Having a sound understanding of the role played by Th17 cells in CLL is crucial for designing novel therapies that can achieve immune homeostasis and maximize clinical benefits.

The in-clinic phosphatidylinositol 3-kinase (PI3K) inhibitors idelalisib (CAL-101) and duvelisib (IPI-145) have demonstrated high rates of response and progression-free survival in clinical trials of B-cell malignancies, such as chronic lymphocytic leukemia (CLL). However, a high incidence of adverse events has led to frequent discontinuations, limiting the clinical development of these inhibitors. By contrast, the dual PI3Kδ/casein kinase-1-ε (CK1ε) inhibitor umbralisib (TGR-1202) also shows high rates of response in clinical trials but has an improved safety profile with fewer severe adverse events. Toxicities typical of this class of PI3K inhibitors are largely thought to be immune mediated, but they are poorly characterized. Here, we report the effects of idelalisib, duvelisib, and umbralisib on regulatory T cells (Tregs) on normal human T cells, T cells from CLL patients, and T cells in an Eμ-TCL1 adoptive transfer mouse CLL model. Ex vivo studies revealed differential effects of these PI3K inhibitors; only umbralisib treatment sustained normal and CLL-associated FoxP3+ human Tregs. Further, although all 3 inhibitors exhibit antitumor efficacy in the Eμ-TCL1 CLL model, idelalisib- or duvelisib-treated mice displayed increased immune-mediated toxicities, impaired function, and reduced numbers of Tregs, whereas Treg number and function were preserved in umbralisib-treated CLL-bearing mice. Finally, our studies demonstrate that inhibition of CK1ε can improve CLL Treg number and function. Interestingly, CK1ε inhibition mitigated impairment of CLL Tregs by PI3K inhibitors in combination treatment. These results suggest that the improved safety profile of umbralisib is due to its role as a dual PI3Kδ/CK1ε inhibitor that preserves Treg number and function.

Purpose: To evaluate the safety of one-day length of hospital stay (LOS) after pediatric percutaneous nephrolithotomy (PNL), and to study the predictors of LOS. Methods: A retrospective study included pediatric patients who PNL for renal calculi more than 1 cm between January 2016 and October 2019. PNL was performed in prone position. The nephrostomy tubes and ureteric catheters were removed on the second day and patients were discharged if there was no perforation or significant residual stones. The stone free rate, LOS and the surgical complications were reported. Bivariate and multivariate analysis were used to predict the LOS. Results: 220 patients were identified. The median age (range) was eight (Range: 3–17) years. Stone free rate was achieved in 200 patients (91%) of patients, while residual fragments were detected in 20 patients (9%). Complications, they were reported in 50 (22.7%) patients. 184 (83.6%) of patients stayed at the hospital for only 1 day, while 36 (16. 4%) stayed more than 1 day. Of 36 patients who stayed more than one-day, 34 had complications ( p value Conclusion: Early nephrostomy tube removal and 1-day length of hospital stay could be a safe option after pediatric PNL. Surgical complications is a statistically significant predictor of longer LOS.

Phosphatidylinositol-3 kinase (PI3K) delta signaling is essential for CLL B cell survival and proliferation. Several PI3K inhibitors are approved for treatment of CLL, but PI3K inhibitor-induced alterations in T cell function have been correlated with immune-related adverse events (irAEs). Zandelisib is a novel selective PI3Kδ inhibitor in clinical development with an intermittent dosing schedule for treatment of B cell malignancies. Here, we investigated the dynamic immunomodulatory properties of zandelisib alone or in combination with BTK inhibitor ibrutinib in normal human T cells, as well as the impact of continuous dosing of zandelisib on effector and regulatory immune cells, irAEs, and survival in a preclinical CLL murine model. Normal human T cells treated ex vivo with zandelisib, ibrutinib, or both were assessed for phenotype and function. A CLL model was initiated by transferring leukemic EμTCL1 splenocytes into syngeneic wildtype recipients. CLL-bearing mice were treated with vehicle or zandelisib (50 mpk bid or 100 mpk qd) for 3 weeks (n=5 per group). Antitumor efficacy, T cell and myeloid subsets in blood, bone marrow and spleen were analyzed. Survival was also observed in a separate cohort of mice treated with zandelisib (100 mpk qd). T cell proliferation was impaired by zandelisib (250nM) and ibrutinib (100 nM) alone, with the combination further reducing T cell proliferation. Zandelisib decreased expression of suppressive markers PD-1, CTLA-4, GITR and CD39 on iTregs; however, no further decrease was observed when zandelisib was combined with ibrutinib. Zandelisib also reduced normal T cell activation and expression of immune checkpoints PD-1 and CTLA-4 on CD4+ T cells and dose dependently inhibited T cell memory differentiation ex vivo, increasing the naïve/central to effector memory ratio. Combination with ibrutinib did not further affect T cell activation, checkpoint expression or memory differentiation. In the CLL murine model, no meaningful difference was seen between bid or qd administration of zandelisib in the reduction of tumor burden (CD19+ CD5+ CLL cells). Zandelisib treatment reduced activated T cells, antigen-experienced T cells, and Tregs. Increased naïve/central to effector memory ratio was observed in treated mice, and PD-1 was downregulated on memory T cells, indicating less T cell exhaustion. Zandelisib decreased macrophages in the spleen but did not impact myeloid-derived suppressor cells. Zandelisib treatment improved survival of CLL-bearing mice significantly when compared to vehicle group (median survival of zandelisib group 140 days vs. 105 days vehicle). In conclusion, zandelisib treatment reduced Tregs, prevented terminal memory differentiation, and T-cell exhaustion—features that have been shown to permit CLL immune evasion—demonstrated antitumor efficacy, and improved overall survival in a preclinical CLL model. Citation Format: Kamira Maharaj, Melanie Mediavilla-Varela, John J. Powers, Sandra Wiley, Angimar Uriepero, Wael Gamal, Kun Jiang, Eva Sahakian, Javier Pinilla-Ibarz. Efficacy and immune profiling of PI3K delta inhibitor zandelisib (ME-401) in a preclinical chronic lymphocytic leukemia (CLL) model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5496.

A painless skin delivery of vaccine for disease prevention is of great advantage in improving compliance in patients. To test this idea as a proof of concept, we utilized a pDNA vaccine construct, pDNAg333-2GnRH that has a dual function of controlling rabies and inducing immunocontraception in animals. The pDNA was administered to mice in a nanoparticulate form delivered through the skin using the P.L.E.A.S.E.® (Precise Laser Epidermal System) microporation laser device. Laser application was well tolerated, and mild skin reaction was healed completely in 8 days. We demonstrated that adjuvanted nanoparticulate pDNA vaccine significantly upregulated the expression of co-stimulatory molecules in dendritic cells. After topical administration of the adjuvanted nano-vaccine in mice, the high avidity serum for GnRH antibodies were induced and maintained up to 9 weeks. The induced immune response was of a mixed Th1/Th2 profile as measured by IgG subclasses (IgG2a and IgG1) and cytokine levels (IFN-γ and IL-4). Using flow cytometry, we revealed an increase of CD8+ T-cells and CD45R B cells upon the administration of the adjuvanted vaccine. Our previous study used the same pDNA nanoparticulate vaccine through an IM route, and a comparable immune response was induced using P.L.E.A.S.E. However, the vaccine dose in the current study was four-fold less than what was applied through the IM route.We concluded that laser-assisted skin vaccination has a potential of becoming a safe and reliable vaccination tool for rabies vaccination in animals or even in humans for pre- or post-exposure prophylaxis.

Introduction. Chronic graft-versus-host disease (cGVHD) can manifest as a complication in patients following allogeneic hematopoietic stem cell transplant resulting in morbidity and mortality. Effective treatment strategies for cGVHD are currently lacking. Ibrutinib, an irreversible BTK inhibitor with activity against several other Tec-family kinases, has been clinically developed for cGVHD treatment due to regulation of pathogenetic B cells and T-cell subsets. Vecabrutinib is a more selective, reversible inhibitor of BTK with a distinct kinase domain interaction, which could result in differentiated safety and activity profiles compared to ibrutinib. Vecabrutinib has the capacity to overcome the C481S mutation that mediates resistance to ibrutinib. Vecabrutinib also also demonstrates activity against ITK, which is expressed in T cells. In this study, we investigated the activity and immune modulation of vecabrutinib treatment in a murine model of sclerodermatous cGVHD. Ibrutinib was utilized for comparison. Methods. A murine model of sclerodermatous cGVHD was initiated by adoptive transfer of T-cell depleted bone marrow plus whole splenocytes from B10.D2 donors into BALB/c recipients that were previously subjected to sub-lethal irradiation. Total bone marrow and irradiation only groups were included as controls. Mice with established cGVHD characterized by weight loss and skin irritation symptoms were treated with vecabrutinib once daily at 50mg/kg by oral gavage or ibrutinib at 30mg/kg in drinking water 5 days per week for approximately 3 weeks beginning on day 27 post-adoptive transfer and ending on day 45 (n=10 mice per group). Body weight and clinical symptoms (appearance, activity, skin symptoms, diarrhea, conjunctivitis) were measured throughout the study. Immunophenotyping for B cells and T cells was performed on spleens collected from euthanized mice by flow cytometry at two timepoints (day 40 during treatment and on day 76 post-treatment). Levels of circulating immunoglobulins were measured by multiplex cytokine assay at both timepoints. Results. Clinical symptoms, including appearance, activity, skin irritation, redness, alopecia and diarrhea were significantly reduced in vecabrutinib- and ibrutinib-treated groups. Furthermore, there was a trend toward a more favorable clinical score overall for the vecabrutinib-treated group, however no statistical difference was observed compared to ibrutinib possibly due to small sample size. Weight loss was slightly elevated during vecabrutinib and ibrutinib treatment compared to vehicle (trend), however mice recovered body weight post-treatment and continued to maintain benefit. On day 40 (during treatment) and day 76 (post-treatment) groups of mice were euthanized for immunophenotyping analysis utilizing a 22-color flow cytometry panel. During treatment, both vecabrutinib and ibrutinib-treated mice retained total B cell numbers but exhibited reduced B-cell activation, proliferation, and number of B220+ CD138+ plasma cells. In addition, B cells secreted less IL-10, and IL-4/5. Expression of antigen-presentation molecules CD80 and CD86 on B cells were unchanged. Total CD3+ T cells, activated and proliferating CD4+ and CD8+ T cells, and cytotoxic granzyme-B+ CD8+ T cells were reduced in treated mice. Interestingly, CD4+ CD25+ FoxP3+ Treg number, expression of PD-1 on Tregs and CD4+ CXCR5+ PD-1+ T follicular helper cells were also reduced in both treatment groups. In addition, there were globally reduced numbers of cytokine-secreting CD4+ cells but no differences in Th1/Th2 or Th17/Treg ratios were observed. Post-treatment, proliferation and cytokine secretion of B cells and T cells were still lowered but less impaired than during treatment. Tregs and PD-1 expression were still reduced post-treatment. Finally, circulating levels of IgA were reduced during and post treatment in vecabrutinib-treated mice compared to vehicle, while IgG1, IgG2b were reduced in both treated groups. No changes in IgM levels were observed in either treatment group. In conclusion, vecabrutinib treatment demonstrated efficacy and beneficially regulated B cell and T cell immune subsets in a preclinical murine model of sclerodermatous cGVHD. Studies to further evaluate differences between vecabrutinib and ibrutinib treatment are ongoing. Figure 1 Figure 1. Disclosures Fox: Sunesis Pharmaceuticals: Current Employment. Taverna: Sunesis Pharmaceuticals: Current Employment. Pinilla Ibarz: Sellas: Other: ), patents/royalties/other intellectual property; MEI, Sunesis: Research Funding; AbbVie, Janssen, AstraZeneca, Takeda: Speakers Bureau; AbbVie, Janssen, AstraZeneca, Novartis, TG Therapeutics, Takeda: Consultancy, Other: Advisory.

Objectives: a prospective study of our experience and midterm results of laparoscopic pyeloplasty (LP) for patients who have failed open or Laparoscopic pyeloplasty in adults. Patients and methods: Thirty two patients with failed open pyeloplasty were reviewed; all of them had transperitoneal dismembered LP. All procedures were performed by experienced laparoscopist during a period of two years. Results: The study group consisted of 14 men and 18 women with the mean age of 29± 6 years. Mean operative time was 123± 22 minutes. Mean hospital stay was 4.7 ± 2.3 days. Mean follow-up was 5.6 ± 2.15 months (range 3-9 months). The overall success rate for secondary LP was 90.6%. There was no conversion to open surgery. Intraoperative and postoperative complications were 9.4 and 12.5% respectively. Conclusions:LP is a safe and viable treatment option for secondary pelviureteric junction obstruction with high success rate but with long operative time. A good experience in laparoscopic reconstructive procedures is a prerequisite for optimal results.

Background and study aim: Glypican-3 (GPC3) is common kind and new type of the Glypicans group. These groups were connected to the epithelial cell membrane by a glycosyl-phosphatidylinositol bond. These proteins control the signaling action of various growth factors, especially Wnts. This reaction is predicated on the power of glypican to initiate, promote or suppress the reaction of these growth agents with their interactive signaling receptors. It is obviously proven and documented that GPC3 is secreted and released by most malignant liver cells, this glypican is not isolated from healthy hepatocyte, cirrhotic liver cells , or in even in benign liver masses. GPC3 accelerates the development of malignant liver lesions especially HCC by stimulating canonical Wnt impulses. The study aimed to characterize and assess the diagnostic accuracy of serum glypican-3 (GPC3) in early detection of HCC in cirrhotic patients and could be used as good screening marker for HCC in cirrhotic patients instead of AFP. Patients and Methods: We enrolled 60 patients which divided into 2 groups, group1 which included 30 patients diagnosed to have HCC and group 2 which included 30 patients diagnosed to have liver cirrhosis. Results: Our results revealed increased levels of Glypican-3 in hepatoma group and liver cirrhosis group with no significant difference (p=0.3). Conclusion: Serum GPC3 is not an efficient immune-marker for HCC that can be used alone to differentiate HCC from benign hepatic focal lesions, particularly hepatocellular adenoma.

Objective To evaluate surgical outcome, complications, and patients satisfaction with the Tube® (Promedon, Cordoba, Argentina) malleable penile prosthesis in diabetic and non-diabetic patients with refractory erectile dysfunction (ED). Patients and methods The records of 128 eligible patients who received Tube malleable penile prostheses at our institute between September 2008 and October 2015 were reviewed. Results Of the 128 patients, who received Tube penile prostheses at our institute, 53 were diabetics and 75 were non-diabetics. Both groups of patients were comparable for mean age, education level, marital status, hospital stay, time to commencing sexual intercourse, and median follow-up. Complications included: inter-corporeal septal perforation (2.3%), glanular urethral injury (1.5%), acute urinary retention (3.9%), superficial wound infection (7%), penile discomfort (9.4%), and penile prostheses infection (5.5%). Moreover, 3.9% developed atrophy of the cavernosal tissue, 5.5% experienced bad cosmesis, 6.3% experienced ejaculatory disorders, and 2.3% developed bladder calculi. In all, 13 prostheses (9.4%) were removed, seven of them due to infection, three on the patients’ demand and three due to mechanical failure. The satisfaction rates with the prostheses were 77.3% and 79.4% in the diabetic and non-diabetic patients, respectively; with an overall satisfaction rate of 78.5%. There was no significant difference in the complication rate or prostheses infection between diabetic and non-diabetic patients. Conclusion Tube malleable penile prostheses are associated with low complication and high satisfaction rates. There was no significant difference in the complication rate or prostheses infection between diabetic and non-diabetic patients. A prospective comparative study with a large number of patients is recommended.

To investigate the surgical outcomes of dorsal onlay urethroplasty (DOU) using buccal mucosa graft (BMG) or penile skin graft (PSG) and to assess the effect of stricture length in men with anterior urethral strictures.A prospective cohort included men with anterior urethral strictures between 2008 and 2015. Patients underwent DOU using PSG or BMG. Patients had urethrography and uroflowmetry at 0, 3, 6, 12 months, and urethroscopy when needed. Student's t test, Mann-Whitney U tests, and Pearson's Chi-square test were used for analysis.Sixty-nine patients (43 ± 14 year) were included, 31 received BMG, and 38 received PSG. Mean stricture length was 8 ± 3 cm, mean operative time was 145 ± 31 min, and mean follow-up was 56 ± 10 mo. Success rate was 87 % (90 % BMG vs. 84 % PSG, p = 0.4). Mean operative time was significantly shorter in PSG group (136 ± 29 min vs. 256 ± 58 min, p = 0.0005). Complications of grade I developed in 36 % (wound infection = 10 %, postvoiding dribbling = 18.8 %). Thirty of 69 patients (43 %) had strictures ≥8 cm, and 39 (57 %) had strictures8 cm-success rate was equal for both subgroups (87 %). Mean blood loss, mean operative time, and incidence of postvoid dribbling were significantly lower in strictures8 cm.BMG and PSG have comparable success rates in treatment of long anterior urethral strictures. Operative time is significantly longer in BMG. Long-segment strictures are associated with longer operative time, more blood loss, and more occurrence of postvoid dribbling. However, the length of the stricture has no influence on the success rate and functional outcomes of DOU.

Resumen Objetivo Evaluar los resultados esteticos y funcionales de glanuloplastia con desepitelizacion aproximada en diferente grado de hipospadias. Material y metodos Este estudio se realizo en 96 pacientes varones (DPH = 68 y MPH = 28). Los pacientes seleccionados para la reparacion con la glanuloplastia de aproximacion deben tener placa uretral amplia y glande ranurados. Todos los casos fueron reparados con la tecnica clasica y la de aproximacion glandar. El seguimiento fue de un ano, mediante un examen clinico de la forma del meato, tamano y sitio, forma del glande, cubierta de piel, linea de sutura, sonda uretral, aparicion de edema y fistula, ademas de la satisfaccion de los padres. Resultados El tiempo operatorio promedio fue de 49 ± 9 min. En cuanto a los resultados funcionales y cosmeticos el exito se informo en el 95,8%, mientras que el fracaso fue de 4,16% en forma de interrupcion glandar en 2 pacientes y fistula uretrocutanea subcoronal en otros 2 pacientes. Conclusion La tecnica de aproximacion glandar tiene muchas ventajas, buenos resultados cosmeticos y funcionales, tiempo operatorio corto y menos perdida de sangre, no habiendo necesidad de torniquete.

Further evaluation of the cosmetic and functional results of approximated de-epithelized glanuloplasty in different degree of hypospadias.This study included 96 male patients (DPH=68MPH=28). Patients selected for repair with glans approximation should have wide urethral plategrooved glans. All cases were repaired with the classic TIP and glans approximation technique. Follow up was for one year by clinical examination of the meatal shape, sizesite, glans shape, skin covering, suture line, urethral catheter, edemafistula in addition to parent satisfaction.Mean operative time was 49±9minutes. As regards the functional and cosmetic outcomes, success was reported in 95.8%, while failure was in 4.16% in the form of glanular disruption in two patients and subcoronal urethrocutaneous fistula in another two patients.Glans approximation has many advantages, good cosmetic and functional results, short operative time, less blood loss, no need for tourniquet. Study of a large number of cases and comparing glans approximation with the classic TIP technique.

Introduction: Management of renal stones in children with a solitary kidney is a challenge. In the current study, the efficacy and safety of retrograde intrarenal surgery (RIRS) in these children were determined. Patients and Methods: Records of children with renal stones who were treated at our institute between August 2011 and August 2014 were retrospectively assessed. Inclusion criteria were: Children with single renal stone

Introduction: Invasive cancer bladder is a life-threatening disease that is best treated with radical cystectomy and a suitable urinary diversion. The aim of this study was to evaluate the oncological outcome, voiding and sexual functions after genital sparing radical cystectomy with orthotopic bladder reconstruction in pre-menopausal women with bladder cancer. Materials and Methods: 18 pre-menopausal women who underwent radical cystectomy and orthotopic urinary diversion with preservation of genital organs were included for this study. The patients were followed-up clinically and radiologically to assess their oncological outcome in addition to their voiding and sexual function. Results: Mean age of the patients was 37.8 years, and the median follow-up after surgery was 70 months. One patient was lost to follow-up at 12 months post-operatively. The surgery was completed as planned in all patients, with a mean operative time of 290 min and an average blood loss of 750 mL. 14 patients were able to void satisfactorily, being continent day and night, while four patients needed clean intermittent catheterization. Sexual life remained unchanged in 15 cases, while three patients reported dysparunea. Till the last follow-up, there was no local recurrence while distant metastases were detected in three cases, two of whom died. Conclusions: Genital sparing cystectomy is a valid option for managing carefully selected women with muscle-invasive bladder cancer with good functional and sexual outcomes.

Objective To develop a technique that helps avoid colonic injury during percutaneous nephrolithotomy (PCNL) in these patients. Patients and Methods PCNL was prospectively performed in a cohort of adults with renal stones in a horseshoe kidney (HSK). PCNLs were done using a standardized technique in prone position in all patients. The colon was radiologically delineated by injecting air—through a catheter in the anal canal—to help localize its position in relation to the pelvicalyceal system (PCS). Patients were observed in hospital for 48 hours postoperatively to detect any potential complications related to the PCNL or to the colon insufflation modification. Results Thirteen adult patients (11 men and 2 women) with renal stones in a HSK were included in the study. The colon was well radiologically delineated with air in all cases. The PCS was successfully accessed, subcostally, with a single access at the upper calyx in 11 cases and multiple accesses in 2 cases. The colon was in the way of the puncture in 2 cases in which we used a more medial access and the colon was successfully avoided. Stones were completely removed during the PCNL in 11 of the 13 cases (84.6%). One case necessitated intraoperative blood transfusion. No other complications were reported by any of the patients who were discharged home after 48 hours. Conclusion Colonic radiological delineation technique is helpful in accessing the PCS quickly, saving the colon, and causing no discomfort to patients with renal stones in a HSK.

The aim of this study was to retrospectively review the experience and midterm results of laparoscopic pyeloplasty (LP) in patients with previous failed open pyeloplasty in comparison to primary LP.Thirty-two patients who had undergone previous failed open surgery for management of ureteropelvic junction obstruction (UPJO) were reviewed. The patients underwent transperitoneal dismembered LP. All operations were performed by the same laparoscopist from March 2009 to June 2013. Surgical results were compared to 72 patients who underwent primary LP carried out by the same surgeon during the same period.The laparoscopic repyeloplasty group consisted of 14 men and 18 women. The mean age was 29 ± 6 years. The mean operative period was 133 ± 42 and 110 ± 57 min; the mean length of stay in hospital was 2.7 ± 2.3 and 1.3 ± 2.1 days; and the mean follow-up period was 32.4 ± 14 and 29.3 ± 11.2 months in the secondary and primary LP groups, respectively. The success rate was 90.6% for secondary LP and 94.4% for primary LP. There was no conversion in either group. The percentage of intraoperative and postoperative complications in secondary LP was 9.4% and 12.5%, respectively, compared with 0% and 5.6% in the primary LP group.Laparoscopic repyeloplasty is a safe and viable treatment option for secondary UPJO, with a success rate similar to that of primary repair but with longer operative time. Considerable experience in laparoscopic reconstructive procedures is a prerequisite for optimal results.

OBJECTIVE To evaluate the stone hardness in predicting the need for single or two sessions of retrograde intrarenal surgery (RIRS) for renal pelvis stones of 2-3 cm in size. MATERIAL AND METHODS Ninety-six patients (64 male and 32 female) with only renal stones (2.5±0.3 cm) underwent RIRS using flexible 7.5 Fr ureteroscope (FURS). The stone hardness was evaluated by preoperative non-contrast computed tomography (NCCT). The patients were divided into two groups based on stone hardness: Group I (n=54) (hard stones - Hounsfield Unit (HU) >1000) and group II (n=42) (not hard stone - HU

Objective: The current investigation is focused on the formulation and in vivo evaluation of optimized solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of amisulpride (AMS) for improving its oral dissolution and bioavailability.Methods: Liquid SNEDDS (L-SNEDDS) composed of Capryol™ 90 (oil), Cremophor® RH40 (surfactant), and Transcutol® HP (co-surfactant) were transformed to solid systems via physical adsorption onto magnesium aluminometasilicate (Neusilin US2). Micromeretic studies and solid-state characterization of formulated S-SNEDDS were carried out, followed by tableting, tablet evaluation, and pharmacokinetic studies in rabbits.Results: Micromeretic properties and solid-state characterization proved satisfactory flow properties with AMS present in a completely amorphous state. Formulated self-nanoemulsifying tablets revealed significant improvement in AMS dissolution compared with either directly compressed or commercial AMS tablets. In vivo pharmacokinetic study in rabbits empha...

It is well established that CD4+FOXP3+ T regulatory cells (Tregs) contribute to dampening anti-tumor responses. Despite our improved understanding of their role in cancer, there remains a knowledge gap with respect to the clonal composition and heterogeneity of tumor-infiltrating Tregs in solid cancers. We addressed this outstanding issue by conducting comprehensive phenotypic profiling of Tregs present in lung adenocarcinomas of a genetically engineered mouse model of non-small cell lung cancer (NSCLC) as well as those in resected tumors of NSCLC patients. Multi-parameter flow cytometric analysis revealed that unlike the peripheral tissues, the tumor harbors a distinct sub-population of Tregs that express the co-inhibitory receptor, KLRG1. Compared to their negative counterparts, the KLRG1+ Treg subset exhibited heightened expression of a number of Treg signature proteins as well as higher levels of activation and memory molecular markers suggesting that they are a highly activated and differentiated Treg pool that is recruited to, or induced in the tumor microenvironment. Consistent with this phenotype, these KLRG1+ Tregs were superior in their capacity to suppress T cell proliferation relative to the KLRG1-cells. Collectively, these findings demonstrate that the tumor microenvironment in non-small cell lung cancer harbors a unique Treg sub-population that is characterized by dominant expression of KLRG1, and which represents a clonal pool with the most potent inhibition of T cell responses. These studies highlight the installment of distinct Treg subsets in NSCLC that have implications for regulation of anti-tumor responses.

The management of renal calculi following previous open surgery represents a challenge for urologists. The aim of this study is to evaluate the outcomes and safety of ureteroscopic laser retrograde intrarenal surgery (RIRS) for renal calculi following prior open renal surgery. The charts of 53 patients who underwent RIRS for renal calculi following prior open surgery for urolithiasis were reviewed. Both flexible and semi-rigid ureteroscopes were utilized together with holmium: YAG laser for stone disintegration. Intravenous urography, computed tomography (CT) and ultrasound were used to evaluate the patient, perioperatively. Stone size ranged from 5 to 32 mm (mean 14.3 mm). The mean operative time was 86 min (20-130). The overall stone-free rate was 92.4%. The overall stone-free rates after one and two-procedures were 79.2% (42 cases) and 92.4% (49 cases), respectively. Four patients (7.5%) had larger residual fragments, 2 (3.8%) of them underwent SWL, and 2 (3.8%) cases were followed up conservatively. Major complications were reported in two patients (3.8%). Stone analysis revealed calcium oxalate in 39 patients, uric acid in 5, calcium phosphate in 4, struvite in 3, and cystine in 2 cases. Ureteroscopic retrograde intrarenal surgery for renal calculi following prior open renal surgery was a minimally invasive, safe procedure with a high success rate. It is a viable alternative for PNL in managing recurrent renal calculi efficiently.

To determine the necessity of ureteral stent placement after retroperitoneal laparoscopic ureterolithotomy (RLU) for upper ureteral stones more than 1 cm.Between May 2006 and May 2009, 104 RLUs were performed as primary management of large upper ureteral stones. The patients were randomly divided into two groups: In group 1 (52 patients), RLU was performed without stent placement afterward, and in group 2 (52 patients), the stent was placed after RLU. The mean stone size was 16.8 cm in group 1 and 18.2 cm in group 2. The stent in group 2 was placed cystoscopically.All procedures were performed successfully. The mean operative time was 48 minutes in group 1 vs. 65 minutes in group 2. The mean drainage time was 4.1 days in group 1 vs. 2.3 days in group 2. All the patients were followed up for a period of 6 months with no recorded cases of residual stone or ureteral stricture.RLU for large upper ureteral stones could be considered as a primary line for treatment as regards the economic status in developing countries. Laparoscopic ureterolithotomy (LU) without stent placement for upper ureteral stones is safe, cost effective, has less operative time, and needs no auxiliary procedures when compared with the use of stent placement after LU, which adds costs and discomfort for the patient.

Objective To assess the outcome of laparoscopic orchiopexy and the two-stage Fowler Stephens technique for managing patients with impalpable testis in terms of safety, feasibility and efficacy. Patients and methods This study included 78 patients who presented with 88 non-palpable testes to the outpatient clinic of Sohag university hospital in 2005–2009, and underwent laparoscopy by the same surgeon. Intra-abdominal testes were managed by laparoscopic orchiopexy if low, two-stage Fowler–Stephens technique if high, and orchiectomy if atrophic. Children were evaluated postoperatively to check the location and size of the testicle and to exclude any other complication. Results Median age at presentation was 16 months (range 11–42 months). Four testes were absent while inguinal exploration was necessary for six testes with the vas entering the internal ring. Of the 78 intra-abdominal testes, 45 were identified as high (Fowler–Stephens in 43; orchiectomy in two atrophic testes) and 33 as low (orchiopexy). Follow up was 3–55 months (mean 34 months). Twelve patients (12 testes) were lost to follow up (7 Fowler–Stephens; 5 orchiopexy). On follow up, the testes were normal sized and well positioned in the scrotum in 28/28 and 32/36 testes in the orchiopexy and Fowler–Stephens groups with an overall success rate of 100% and 88.8%, respectively. Two testes showed testicular displacement and two showed testicular atrophy in patients of the Fowler–Stephens group. Conclusion Laparoscopy provides a safe and accurate modality for diagnosing and managing patients with non-palpable testes, with excellent outcomes.

Summary Introduction/background Many authors reported their experience with supine PCNL in adult population comparing the outcome with prone PCNL and they found that the stone free rate and the operative time were in favor of prone PCNL with a lower patient morbidity among patients with supine PCNL. This encouraged us to perform supine PCNL in pediatric population. An objective In this study we evaluated the safety and efficacy of supine PCNL in pediatric population. Study design (subjects/patients/materials/methods) Between April 2011 and February 2014 a total of 27 children (6 girls and 21 boys) presented with renal calculi. The stones were single pelvic stone in 14 cases, pelvic stone with lower calyceal stones in 7 cases and pelvic stone with upper calyceal stones in 6 cases. The mean stone size was 32 mm (range 20–47 mm). All patients were managed with supine PCNL performed by a single surgeon. Marking the posterior axillary line in standing position before the operation is a mandatory initial step. The patients were placed in supine position with elevation of the ipsilateral shoulder and hip by means of two bags one underneath the shoulder and the other underneath the hip to widen the operative field. The technique was performed using a sheathless 19 fr. Richard wolf rigid nephroscope after acute tract dilation by amplatz dilators. Complications (intraoperative and postoperative) and stone free rate rates were reported. Results A single lower calyceal access was used in all cases through which we could successfully remove even the upper calyceal stones. Kinking of the guide wire during tract dilatation were encountered in 4 cases and the guide wire was successfully exchanged using a small Teflon dilator in 2 cases while ultrasonographic guided lower calyceal repuncture was done in 2 cases. The average operative time (from the beginning of the puncture trial to nephrostomy tube insertion) was (41 ± 15) min. The operation was successfully completed as planned in all cases with two cases of intraoperative complications (one case of pelvicalyceal system perforation and another case of intraoperative bleeding and blood transfusion). The initial stone free rate was (92.5%). Postoperative complications was reported in the form of 2 cases of fever that respond to medical treatment for 72 h. Discussion The main advantages of supine pediatric PCNL is that it is comfortable for the surgeon, the anesthetist and the child. The main disadvantages of supine pediatric PCNL is that it is not familiar for most urologists and small field of operation. The short outcome of our study is the small number of cases and the lack of comparative study with prone pediatric PCNL. Conclusions Pediatric supine PCNL is a safe and effective method for management of pediatric renal stones. It carries the advantages of easily upper calyx access through the lower calyceal tract, low incidence of fluid absorption or hypothermia and easy anesthesia monitoring. However a larger number of cases are needed to be evaluated. Download : Download high-res image (114KB) Download : Download full-size image Figure . Supine positioning with marked posterior axillary line and the needle puncture is horizontal.

To evaluate the safety and efficacy of endoscopically guided percutaneous suprapubic artery forceps litholapaxy for pediatric vesical and posterior urethral stone1 cm in diameter.A retrospective series study of 73 children (68 boys and 5 girls) with vesical and urethral stones less than 1 cm in diameter with an average age of 3.5 years (range 1-9 years) were included in this study. Cases with previous suprapubic surgery, stones of more than 1 cm in diameter, multiple bladder or urethral stone, anterior urethral stones and cases with neurological or anatomical abnormalities were excluded from our study. The bladder was filled and punctured suprapubically by an artery forceps under the vision of the pediatric cystoscopy then the stone is completely crushed. All intraoperative and postoperative complications were recorded. The stone-free rate status was evaluated 2 weeks postoperatively using plain X-ray/ultrasonography.All cases were successful, and the stones were completely crushed to smaller insignificant fragments in a single session. No intraoperative bladder perforation or bleeding was recorded. The mean operative time was 12.5 min (ranging from 9 to 17 min). There were no postoperative complications apart from 2 cases of persistent suprapubic leakage postoperatively for 24 h and the leakage stopped after 48 h with the insertion of 8 Fr Foley catheter. In all cases, no significant stone fragments were found 2 weeks postoperatively.Our technique for management of pediatric vesical and posterior urethral stone less than 1 cm is an easy and safe with no intraoperative or postoperative significant complications.

To present and evaluate our initial results with a modified double face onlay preputial flap (DOPF) for repair of different degrees of hypospadias.From April 2004 to April 2009, 182 patients with different degrees of hypospadias (distal penile hypospadias = 122, mid penile hypospadias = 38, proximal penile hypospadias = 22) were included in our study. All patients were treated with a modified DOPF. Their age ranged from 6 months to 10 years (mean 3.03 years). Selection criteria were those cases with urethral plate8 mm with either flat or conical glans, and non-circumcised patients. The technique of repair was to use the distally tapered inner preputial mucosa as onlay to augment the narrow urethral plate, while the outer face was tapered distally to augment the closed proximal part of the glanular wings and as skin cover. Suitable urethral catheter was inserted for 3-5 days. Follow-up duration was 27-30 months (mean 24 months).Functional and cosmetic success was reported in 176 patients (96.6%). Six patients (3.29%) had developed complications that affected the success rate: 1 (0.5%) glanular disruption, 2 (1.09%) fistula, 1 (0.5%) urethral diverticulum and 2 (1.09%) lateral penile torsion. Three (1.6%) patients had developed minor complications with no effect on functional and cosmetic success in form of superficial epidermal loss.Modified DOPF is a suitable technique for repair of different types of hypospadias as it results in satisfactory functioning and an acceptable cosmetic appearance.

J Trauma 2011; 71: 491–493. Background: Penile fracture usually results from direct trauma to the erected penis. We evaluate the outcomes of surgical and conservative treatment. Methods: Between February 2000 and February 2007, 77 patients with mean age 29 2.5 years (range, 20‐57 years) with penile fracture were evaluated retrospectively. A total of 56 patients (group A) were treated with immediate surgical repair and 21 patients (group B) were treated conservatively as they refused surgical intervention. Data on erectile function and any penile sequel were obtained during follow-up using the International Index of Erectile Function (IIEF-15) questionnaire, local examination, and color Doppler ultrasonography reports. Results: Only 69 patients were available for median follow-up period of 20.8 months (range, 17‐30 months), 51 patients of the group A and 18 of the group B. Injury involved unilateral and bilateral corporeal rupture in 50 and 6 cases, respectively. Concomitant urethral injury was detected in three cases. During follow-up, 49 cases (96%) of the surgical group (A) and 9 cases (50%) of the conservative group (B) reported erection adequate for intercourse, with no voiding dysfunction and no penile curvature. However, the remaining nine patients (50%) from the conservative group (B) reported erectile dysfunction and penile deviation. Conclusions: Immediate surgical repair of the penile fracture gave good results and is superior to conservative treatment; however, we cannot distinguish false from true penile fracture accurately to determine on whom we can use the conservative treatment. Editorial Comment: This series of 77 penile fracture cases from Egypt amplifies the message that prompt corporeal repair is associated with far fewer complications (erectile dysfunction and penile deformity). This article appears to be the 12th published series supporting this conclusion. The authors should be congratulated for the rigorous followup provided. Also highlighted is the difficulty in diagnosing this condition (true vs false fracture). Magnetic resonance imaging is mentioned but not advocated due to cost and practical constraints. Penile ultrasound (not used in this study) has recently been shown to be effective in documenting tunical defects, and we have found penile ultrasound to be useful in equivocal cases.

To evaluate the safety and efficacy of stentless pediatric ureteroscopic holmium laser stone disintegration without gravels retrieval. From Feb 2007 to Feb 2010, 21 children (12 boys and 9 girls) with unilateral single stone ureter, with an average age of 8.5 years (range 4–12 years), were treated with 6.9 Fr semirigid ureteroscope for a stone size ranged from 5 to 10 mm (mean 6.5 mm). All the stones were radioopaque, located in the upper ureter in 2 cases (9.5%), in the middle ureter in 5 cases (24%), and in the lower ureter in 14 cases (66.5%). Complete holmium laser stone disintegration was applied in all cases without gravels removal. No postoperative ureteral stent was inserted in any case. The stones were successfully approached and completely disintegrated in a single session in 20 cases (95.2%). All the procedures were done without ureteral orifice dilatation apart from 3 cases where another working guide wire was applied. No intraoperative complications were recorded in the form of mucosal injury, ureteral perforation, or urinary extravasation. There is no early postoperative complication in the form of urinary tract infection or colic apart from single case of hematuria which was successfully treated conservatively. Two weeks postoperatively, KUB (kidney, ureter, and bladder) films were completely free from any significant gravel (>3 mm) and US showed no hydronephrosis. Stentless ureteroscopic holmium laser disintegration without gravels removal is a safe and effective method for pediatric ureteral stone less than 10 mm in diameter.

Steinstrasse is a well-known complication following extracorporeal shockwave lithotripsy (ESWL). The objective of this study was to evaluate the efficacy of tamsulosin as a management of steinstrasse.88 patients with unilateral steinstrasse were treated between January 2005 and December 2008. The patients were randomly allocated into two equal groups. There were no significant differences between groups for age, gender, stone location, stone length or stone fragment size (p0.05). Patients in group 1 (study group) received a single daily morning dose of tamsulosin (0.4 mg) for a maximum of 4 weeks, in addition to pain-relieving therapy. Patients in group 2 (control group) received only the pain-relieving therapy. All patients were checked weekly with a plain X-ray of the urinary tract, urinary ultrasonography, urine analysis and serum creatinine. Pain episodes, day of spontaneous stone expulsion, total analgesic dosage and drug side-effects were recorded.Stone expulsion occurred in 32 of the 44 patients (72.7%) receiving tamsulosin and in 25 of the 44 patients (56.8%) in the control group. Patients receiving tamsulosin had a significantly higher stone expulsion rate (p = 0.017). There were no significant differences between groups for mean stone expulsion time or number of analgesics used. Twelve patients (27.3%) in the group receiving tamsulosin and 19 patients (43.3%) in the control group needed hospitalization; the group difference was statistically significant (p = 0.017).When compared with no treatment, tamsulosin can significantly facilitate expulsion of retained ureteral stone fragments following ESWL.