National trends of perioperative outcomes and costs for open, laparoscopic and robotic pediatric pyeloplasty.

PURPOSE: We performed a population based study comparing trends in perioperative outcomes and costs for open, laparoscopic and robotic pediatric pyeloplasty. Specific billing items contributing to cost were also investigated. MATERIALS AND METHODS: Using the Perspective database (Premier, Inc., Charlotte, North Carolina), we identified 12,662 pediatric patients who underwent open, laparoscopic and robotic pyeloplasty (ICD-9 55.87) in the United States from 2003 to 2010. Univariate and multivariate statistics were used to evaluate perioperative outcomes, complications and costs for the competing surgical approaches. Propensity weighting was used to minimize selection bias. Sampling weights were used to yield a nationally representative sample. RESULTS: A decrease in open pyeloplasty and an increase in minimally invasive pyeloplasty were observed. All procedures had low complication rates. Compared to open pyeloplasty, laparoscopic and robotic pyeloplasty had longer median operative times (240 minutes, p <0.0001 and 270 minutes, p <0.0001, respectively). There was no difference in median length of stay. Median total cost was lower among patients undergoing open vs robotic pyeloplasty ($7,221 vs $10,780, p <0.001). This cost difference was largely attributable to robotic supply costs. CONCLUSIONS: During the study period open pyeloplasty made up a declining majority of cases. Use of laparoscopic pyeloplasty plateaued, while robotic pyeloplasty increased. Operative time was longer for minimally invasive pyeloplasty, while length of stay was equivalent across all procedures. A higher cost associated with robotic pyeloplasty was driven by operating room use and robotic equipment costs, which nullified low room and board cost. This study reflects an adoption period for robotic pyeloplasty. With time, perioperative outcomes and cost may improve.

Factor VIIa bound to endothelial cell protein C receptor activates protease activated receptor-1 and mediates cell signaling and barrier protection.

Recent studies have shown that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor (EPCR), a cellular receptor for protein C and activated protein C, but the physiologic significance of this interaction is unclear. In the present study, we show that FVIIa, upon binding to EPCR on endothelial cells, activates endogenous protease activated receptor-1 (PAR1) and induces PAR1-mediated p44/42 mitogen-activated protein kinase (MAPK) activation. Pretreatment of endothelial cells with FVIIa protected against thrombin-induced barrier disruption. This FVIIa-induced, barrier-protective effect was EPCR dependent and did not involve PAR2. Pretreatment of confluent endothelial monolayers with FVIIa before thrombin reduced the development of thrombin-induced transcellular actin stress fibers, cellular contractions, and paracellular gap formation. FVIIa-induced p44/42 MAPK activation and the barrier-protective effect are mediated via Rac1 activation. Consistent with in vitro findings, in vivo studies using mice showed that administration of FVIIa before lipopolysaccharide (LPS) treatment attenuated LPS-induced vascular leakage in the lung and kidney. Overall, our present data provide evidence that FVIIa bound to EPCR on endothelial cells activates PAR1-mediated cell signaling and provides a barrier-protective effect. These findings are novel and of great clinical significance, because FVIIa is used clinically for the prevention of bleeding in hemophilia and other bleeding disorders.

Therapeutic Targeting of DNA Damage Repair in the Era of Precision Oncology and Immune Checkpoint Inhibitors.

Cancer manifestation is a multistep process involving accumulation of various genetic and epigenetic changes that results in oncogenic "hallmarks of cancer" processes including genomic instability. Exploitation of aberrant DNA-damage response (DDR) mechanisms in cancer is in part a goal of many therapeutic strategies, and recent evidence supports the role of targeting DDR in modulating the tumor immune microenvironment to enhance immunotherapeutic response. Improved cancer profiling, including next-generation and whole-genome mutational sequencing of tumor tissue, as well as circulating nucleic acids, has enhanced our understanding of the genetic and epigenetic molecular mechanisms in tumorigenesis and will become fundamental to precisely target tumors and achieve cancer control. With the successes of poly(ADP-ribose) polymerase inhibitors (PARPi) and immunotherapies, the intersection of DDR molecular machinery and corresponding antitumor immune response has gained much interest with a focus on achieving therapeutic synergy using DNA damage-targeting agents and immunotherapy. In this review, we provide a bench-to-bedside overview of the fundamentals of DDR signaling and repair as they relate to cancer therapeutic strategies including novel DDR-targeting agents. We also discuss the underlying mechanisms that link DDR signaling to antitumor immunity and immunotherapy efficacy, and how this knowledge can be used to improve precision medicine approaches in the treatment of cancer.

Intra-operative Urodynamics: Is the Test an Accurate Representation of the Lower Urinary Tract in Children?

OBJECTIVE: To compare intraoperative UDS results with UDS in the postoperative care unit (PACU) to assess the accuracy and efficacy of intraoperative UDS in children who cannot tolerate ambulatory urodynamic evaluation. METHODS: Pediatric patients undergoing intraoperative UDS at a single institution were enrolled over a 5-year time period (1/2013-8/2018). Urodynamics were performed in the operating room under general anesthesia, then in the PACU after recovery from anesthesia. Electromyographic (EMG) activity during filling, bladder compliance, cystometric bladder capacity (CBC), detrusor overactivity, presence of urinary leak, leak point pressure (LPP), and pressure specific volumes (PSV) at 10, 20, 30, and 40 cm water were compared between studies. RESULTS: Nineteen patients underwent urodynamic evaluation under general anesthesia and met inclusion criteria. Ten patients (52.6%) underwent 2 filling cycles while awake in PACU, resulting in a total of 48 urodynamic studies available for subsequent analysis. Intraoperative urodynamic studies were more likely to have decreased EMG activity during filling (P=<.01), normal compliance (P <.01), and a lower detrusor LPP (P = .03) compared to UDS performed after recovery from anesthesia. Detrusor overactivity was less frequently observed intraoperatively (P <.001) and involuntary detrusor contractions were lower in magnitude than those observed in the PACU. Twelve of the 19 (63%) children had detrusor overactivity that was present only on the UDS in PACU and not intra-operatively. CONCLUSIONS: The results of urodynamic testing performed under general anesthesia should be interpreted with caution, as pediatric patients appear to have improved bladder compliance, lower detrusor LPP and decreased detrusor overactivity when under anesthesia. For this reason, it is preferable to utilize ambulatory urodynamic evaluation to guide patient management and treatment.

The leucine zipper putative tumor suppressor 2 protein LZTS2 regulates kidney development.

Members of the leucine zipper putative tumor suppressor (LZTS) family play crucial roles in transcription modulation and cell cycle control. We previously demonstrated that LZTS2 functions as a novel ß-catenin-interacting protein and represses ß-catenin-mediated transcription on T-cell factor/lymphoid enhancing factor. Here, we investigate the biological role of LZTS2 using newly established Lzts2 KO mice. Homozygosity for loss-of-function of the Lzts2-targeted allele resulted in severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis, which were visible prenatally. Altered ureteric bud outgrowth was identified in Lzts2 null embryos. Further analysis indicated that ß-catenin subcellular localization was altered in fibroblasts isolated from Lzts2 null embryos. In addition, Wnt growth factor-induced ß-catenin-mediated transcriptional activity was increased in Lzts2 null fibroblasts, suggesting a direct role for Lzts2 in the Wnt signaling pathway. These data demonstrate a critical role of LZTS2 in renal development and implicate LZTS2 as a critical regulator of ß-catenin-mediated nephrogenesis.

Inhibition of protein kinase C attenuates Pseudomonas aeruginosa elastase-induced epithelial barrier disruption.

Pseudomonas aeruginosa pulmonary infection compromises the human airway epithelium, and can be especially devastating to immunocompromised or debilitated individuals. We have reported earlier that P. aeruginosa elastase (PE) increases paracellular permeability in epithelial cell monolayers by mechanisms involving tight junction (TJ) disruption and cytoskeletal reorganization, leading to destruction of epithelial barrier function. The aim of this study was to investigate putative TJ targets and potential mechanisms by which PE induces barrier disruption. We found that PE decreased localization of TJ proteins, occludin and zonula occludens (ZO)-1, in membrane fractions, and induced reorganization of F-actin within 1 hour. Although inhibition of protein kinase (PK) C α/ß signaling modestly altered the extent of cytoskeletal disruption and ZO-1 translocation, we found PKC signaling to play a significant role in decreased occludin functionality during PE exposure. Furthermore, elevated PKC levels correlated with decreased levels of TJ proteins in membrane fractions, and increased paracellular permeability in a time-dependent manner. Therefore, we conclude that PKC signaling is involved during PE-induced epithelial barrier disruption via TJ translocation and cytoskeletal reorganization. Specifically, occludin, as well as associated ZO-1 and F-actin, may be early targets of PE pathogenesis occurring via a PKC-dependent pathway.

Radiation exposure during pediatric videourodynamics.

PURPOSE: Videourodynamics is useful for evaluating and treating neurological disorders in children. Traditional urodynamic parameters can be obtained while simultaneous visualization of the urinary system can reveal anatomical anomalies. This additional information comes at the cost of radiation exposure to the child. We characterized radiation exposure from videourodynamics. MATERIALS AND METHODS: We reviewed all recent videourodynamic studies and recorded patient demographics, urological diagnoses, physical attributes, total fluoroscopy time, total radiation exposure in mGy, bladder capacity and the number of filling cycles performed. Multivariate linear regression was used to identify patient factors that independently influenced total radiation exposure. RESULTS: A total of 64 videourodynamic studies were performed in 34 female and 28 male patients with a mean age of 8.6 years (95% CI 7.2-10.0). The most common diagnosis was neurogenic bladder in 40 patients, although 49 had multiple diagnoses. Mean total fluoroscopy time was 1.8 minutes (95% CI 1.4-2.1) and mean total radiation exposure was 10 mGy (95% CI 7.5-13.3). On multivariate linear regression patient weight and bladder capacity were the only independent predictors of total radiation exposure. CONCLUSIONS: Videourodynamics entail significant radiation exposure. Patient weight and bladder capacity were independent predictors of total radiation exposure. Physician awareness of radiation exposure may result in the judicious use of fluoroscopy and aid in counseling parents on the risk of videourodynamics. Further research is needed to quantify organ specific doses of radiation due to medical imaging in children and the associated cancer risks.

Sacral nerve stimulator revision due to somatic growth.

PURPOSE: Sacral nerve modulation is a Food and Drug Administration approved treatment for refractory urgency, frequency, urge incontinence and nonobstructive urinary retention in adults. The sparse literature on sacral nerve modulation in children focuses on its initial efficacy in patients with neurogenic bladder and dysfunctional elimination. We describe our initial experience with sacral nerve modulation and the phenomenon of growth spurts associated with lead malfunction that necessitates revision. MATERIALS AND METHODS: After receiving institutional review board approval we retrospectively reviewed the charts of pediatric patients who underwent sacral nerve modulation surgery at our institution. Charts were examined for patient demographics, subjective success, the need for further surgery and success after revision. RESULTS: Four patients underwent sacral nerve modulation at an average age of 12.1 years. All patients reported initial success, defined as greater than 50% symptom improvement. Subsequently 3 patients required a total of 5 revisions due to lead malfunction with an average of 1.5 years between surgeries. In those requiring revision the average somatic growth between revisions was 8.1 cm. Return of efficacy was reported after each revision. All patients had functioning nerve stimulators in place and continued to have a positive subjective response. CONCLUSIONS: The sparse data on sacral nerve modulation in children shows efficacy and safety similar to those in adults. Somatic growth may be associated with lead malfunction and require surgical revision. We report a small series showing that revision can be done successfully and safely. Informed consent for sacral nerve modulation in pediatric patients should include a discussion of somatic growth as a possible cause of lead malfunction necessitating revision.

A rare case of adult Wilms' tumor.

Although Wilms tumor is the most common primary renal malignancy in children, it is exceedingly rare in adults and has an estimated incidence of less than 0.2 cases per million. Little is known about the biology of this tumor in adults and clinicians have had to rely on pediatric treatment protocols. Overall, prognosis is worse in adults, though like in children, unfavorable histology and higher stage at presentation confer a worse prognosis.

Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) has poor prognosis with limited treatment options, with little therapeutic progress made during the past several decades. DNA damage response (DDR) associated therapies, including radiation and inhibitors of DDR, demonstrate potential efficacy against TNBC, especially under the guidance of genomic subtype-directed treatment. The tumor immune microenvironment also contributes greatly to TNBC malignancy and response to conventional and targeted therapies. Immunotherapy represents a developing trend in targeted therapies directed against TNBC and strategies combining immunotherapy and modulators of the DDR pathways are being pursued. There is increasing understanding of the potential interplay between DDR pathways and immune-associated signaling. As such, the question of how we treat TNBC regarding novel immuno-molecular strategies is continually evolving. In this review, we explore the current and upcoming treatment options of TNBC in the context of DNA repair mechanisms and immune-based therapies, with a focus on implications of recent genomic analyses and clinical trial findings.

Durable Metastatic Melanoma Remission Following Pembrolizumab and Radiotherapy: A Case Report of Prophylactic Immunosuppression in a Patient with Myasthenia Gravis and Immune-Mediated Colitis.

Immune checkpoint inhibitors (ICIs) and radiotherapy (RT) combinations for various metastatic cancers are increasingly utilized, yet the augmentation of anti-cancer immunity including distant tumor responses by RT remains ill-characterized. Immunosuppressive tumor microenvironments and defective anti-tumor immune activation including immune-related adverse events (irAEs) likely limit dramatic immuno-radiotherapy combinations, though it remains unclear which immune characteristics mediate dramatic systemic tumor regression in only a small subset of patients. Moreover, the efficacy of ICI treatment in patients receiving immunosuppressive therapies for autoimmune conditions or irAEs is convoluted, yet clinically valuable. Here, we report a case of a 75-year-old man with myasthenia gravis and metastatic melanoma who experienced complete and durable systemic regression after receiving pembrolizumab and single-lesion RT while on prednisone for myasthenia gravis prophylaxis and vedolizumab for immune-mediated colitis after previously experiencing mixed response on pembrolizumab monotherapy. We discuss the potential paradoxical effects and clinical considerations of immunosuppressive regimens in patients with underlying autoimmune disease or adverse immune reactions while receiving immuno-radiotherapy combinations.

Estrogen receptor beta signaling in CD8+ T cells boosts T cell receptor activation and antitumor immunity through a phosphotyrosine switch.

BackgroundThe non-overlapping functions of the two estrogen receptor subtypes, ERα (Estrogen Receptor α)and ERß (Estrogen Receptor ß), in tumor cells have been studied extensively. However, their counterparts in host cells is vastly underinterrogated. Even less is known about how ERα and ERß activities are regulated in a subtype-specific manner. We previously identified a phosphotyrosine residue (pY36) of human ERß that is important for tumor ERß to inhibit growth of breast cancer cells in vitro and in vivo. A role of this ERß phosphotyrosine switch in regulating host ERß remains unclear.Conventional gene editing was used to mutate the corresponding tyrosine residue of endogenous mouse ERß (Y55F) in mouse embryonic stem cells. The derived homozygous mutant Esr2Y55F/Y55F mouse strain and its wild-type (WT) counterpart were compared in various transplant tumor models for their ability to support tumor growth. In addition, flow cytometry-based immunophenotyping was carried out to assess antitumor immunity of WT and mutant hosts. Adoptive transfer of bone marrow and purified CD8+ T cells were performed to identify the host cell type that harbors ERß-dependent antitumor function. Furthermore, cell signaling assays were conducted to compare T cell receptor (TCR)-initiated signaling cascade in CD8+ T cells of WT and mutant mice. Lastly, the ERß-selective agonist S-equol was evaluated for its efficacy to boost immune checkpoint blockade (ICB)-based anticancer immunotherapy.Disabling the ERß-specific phosphotyrosine switch in tumor-bearing hosts exacerbates tumor growth. Further, a cell-autonomous ERß function was defined in CD8+ effector T cells. Mechanistically, TCR activation triggers ERß phosphorylation, which in turn augments the downstream TCR signaling cascade via a non-genomic action of ERß. S-equol facilitates TCR activation that stimulates the ERß phosphotyrosine switch and boosts anti-PD-1 (Programmed cell death protein 1) ICB immunotherapy.Our mouse genetic study clearly demonstrates a role of the ERß phosphotyrosine switch in regulating ERß-dependent antitumor immunity in CD8+ T cells. Our findings support the development of ERß agonists including S-equol in combination with ICB immunotherapy for cancer treatment.

CD122-targeted interleukin-2 and αPD-L1 treat bladder cancer and melanoma via distinct mechanisms, including CD122-driven natural killer cell maturation.

Bladder cancer (BC) and melanoma are amenable to immune checkpoint blockade (ICB) therapy, yet most patients with advanced/metastatic disease do not respond. CD122-targeted interleukin (IL)-2 can improve ICB efficacy, but mechanisms are unclear. We tested αPD-L1 and CD122-directed immunotherapy with IL-2/αIL-2 complexes (IL-2c) in primary and metastatic bladder and melanoma tumors. IL-2c treatment of orthotopic MB49 and MBT-2 BC generated NK cell antitumor immunity through enhanced activation, reduced exhaustion, and promotion of a mature, effector NK cell phenotype. By comparison, subcutaneous B16-F10 melanoma, which is IL-2c sensitive, requires CD8+ T and not NK cells, yet we found αPD-L1 efficacy requires both CD8+ T and NK cells. We then explored αPD-L1 and IL-2c mechanisms at distinct metastatic sites and found intraperitoneal B16-F10 metastases were sensitive to αPD-L1 and IL-2c, with IL-2c but not αPD-L1, increasing CD122+ mature NK cell function, confirming conserved IL-2c effects in distinct cancer types and anatomic compartments. αPD-L1 failed to control tumor growth and prolong survival in B16-F10 lung metastases, yet IL-2c treated B16-F10 lung metastases effectively even in T cell and adaptive immunity deficient mice, which was abrogated by NK cell depletion in wild-type mice. Flow cytometric analyses of NK cells in B16-F10 lung metastases suggest that IL-2c directly boosts NK cell activation and effector function. Thus, αPD-L1 and IL-2c mediate nonredundant, immune microenvironment-specific treatment mechanisms involving CD8+ T and NK cells in primary and metastatic BC and melanoma. Mechanistic differences suggest effective treatment combinations including in other tumors or sites, warranting further studies.

Efficacy of c-Met inhibitor for advanced prostate cancer.

BACKGROUND: Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. METHODS: We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. RESULTS: We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. CONCLUSIONS: The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer.

Chemoradiotherapy-induced Cytodifferentiation in Bladder/Prostate Rhabdomyosarcoma With Genetic Downregulation of Myogenin and MyoD1 Gene Expression: A Case Study and Review of the Literature.

Rhabdomyosarcoma is the most common sarcoma diagnosed in childhood and adolescence, arising from the bladder/prostate in only 5%-10% of cases. Treatment-induced cytodifferention of tumor cells into mature rhabdomyoblasts has been reported following chemoradiation and is thought to suggest a more favorable outcome. We report a case of embryonal rhabdomyosarcoma of the bladder/prostate that exhibited extensive cytodifferentiation with downregulation of myogenin and MyoD1 gene expression in rhabdomyoblasts following treatment with chemoradiation therapy. The downregulation of myogenin and MyoD1 expression in rhabdomyoblasts following chemoradiation treatment has not previously been described in the literature and its significant remains uncertain.

Intermediate Follow-up and Management of Previously Reported Malignant Peripheral Nerve Sheath Tumor of the Penis.

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from peripheral nerve fibers and primarily occur in the setting of neurofibromatosis (NF1). MPNST arising from the penis is very rare and may require mutilating surgery to achieve surgical cure. We previously reported a case of MPNST involving the penis in a 14-month-old boy treated with neoadjuvant chemotherapy, total penectomy, and adjuvant radiation. Here we report intermediate follow-up of the same patient, describe his subsequent genitourinary reconstruction, and discuss management dilemmas that arise following treatment of penile MPNST.

Bone mineral density in adolescent urinary stone formers: is sex important?

Urinary stone disease (USD) is affecting a greater number of children and low bone mineral density (BMD) and increased skeletal fractures have been demonstrated in stone patients; however, the mechanism(s) driving bone disease remain unclear. This pilot study was undertaken to assess an adolescent kidney stone cohort's BMD and evaluate for an inverse correlation between BMD and urine concentration of lithogenic minerals and/or inflammatory levels. Prospective case-control study was carried out at a large pediatric center. 15 participants with USD (12-18 years of age, 8 female) were matched by age, sex, and body mass index to 15 controls. Lumbar and total body BMD z-score did not differ between groups. When stone formers were separated by sex, there was a significant difference between male stone formers vs. controls total body BMD z-score (Fig. 1). BMD z-score did not significantly correlate with urine calcium, oxalate, citrate or magnesium. Higher urine IL-13 did significantly correlate with higher total body BMD z-score (r = 0.677, p = 0.018). Total body BMD z-score did significantly correlate with body mass index (BMI) as expected for the control group (r = 0.6321, p = 0.0133). However, this relationship was not present in the USD group (r = - 0.1629, p = 0.5619). This is a small but hypothesis-generating study which demonstrates novel evidence of male-specific low BMD in adolescent stone formers. Furthermore, we demonstrated a positive association between urine IL-13 and total body BMD z-score USD patients as well as a lack of a positive BMD and BMI correlations in stone formers.

CD122-Selective IL2 Complexes Reduce Immunosuppression, Promote Treg Fragility, and Sensitize Tumor Response to PD-L1 Blockade.

The IL2 receptor (IL2R) is an attractive cancer immunotherapy target that controls immunosuppressive T regulatory cells (Treg) and antitumor T cells. Here we used IL2Rß-selective IL2/anti-IL2 complexes (IL2c) to stimulate effector T cells preferentially in the orthotopic mouse ID8agg ovarian cancer model. Despite strong tumor rejection, IL2c unexpectedly lowered the tumor microenvironmental CD8+/Treg ratio. IL2c reduced tumor microenvironmental Treg suppression and induced a fragile Treg phenotype, helping explain improved efficacy despite numerically increased Tregs without affecting Treg in draining lymph nodes. IL2c also reduced Treg-mediated, high-affinity IL2R signaling needed for optimal Treg functions, a likely mechanism for reduced Treg suppression. Effector T-cell IL2R signaling was simultaneously improved, suggesting that IL2c inhibits Treg functions without hindering effector T cells, a limitation of most Treg depletion agents. Anti-PD-L1 antibody did not treat ID8agg, but adding IL2c generated complete tumor regressions and protective immune memory not achieved by either monotherapy. Similar anti-PD-L1 augmentation of IL2c and degradation of Treg functions were seen in subcutaneous B16 melanoma. Thus, IL2c is a multifunctional immunotherapy agent that stimulates immunity, reduces immunosuppression in a site-specific manner, and combines with other immunotherapies to treat distinct tumors in distinct anatomic compartments. SIGNIFICANCE: These findings present CD122-targeted IL2 complexes as an advancement in cancer immunotherapy, as they reduce Treg immunosuppression, improve anticancer immunity, and boost PD-L1 immune checkpoint blockade efficacy in distinct tumors and anatomic locations.

Quantitative ultrasound renal parenchymal area correlates with renal volume and identifies reflux nephropathy.

PURPOSE: Studies show that renal volume on magnetic resonance imaging correlates with differential function and is decreased in children with vesicoureteral reflux diagnosed after urinary tract infection. We examined the correlation between ultrasound renal parenchymal area and magnetic resonance imaging volume to determine whether quantitative ultrasound renal parenchymal area might be a reliable, less costly and less invasive substitute for renal magnetic resonance imaging volume. MATERIALS AND METHODS: To determine the correlation of ultrasound renal parenchymal area with magnetic resonance imaging, we identified 82 children with primary vesicoureteral reflux who underwent renal magnetic resonance imaging and ultrasound. Magnetic resonance imaging volume was compared with ultrasound renal parenchymal area, renal length and calculated ellipsoid volume. To determine the correlation of ultrasound renal parenchymal area with reflux grade, ultrasound renal parenchymal area was examined in 96 children with reflux and urinary tract infection, and in 52 with reflux without urinary tract infection. Linear regression and multivariate analysis were performed to find the relationship between ultrasound renal parenchymal area and reflux grade. RESULTS: The correlation of ultrasound renal parenchymal area with magnetic resonance imaging volume was superior to that of renal length and calculated ellipsoid volume (r(2) = 0.90 vs 0.83 and 0.84, respectively). Hydronephrosis did not affect the correlation. On multiple regression analysis in children with reflux and urinary tract infection higher reflux grade correlated with decreased ultrasound renal parenchymal area (p = 0.0016). In children with reflux without urinary tract infection reflux grade did not correlate with decreased ultrasound renal parenchymal area (p = 0.47). CONCLUSIONS: Ultrasound renal parenchymal area correlates closely with magnetic resonance imaging derived 3-dimensional renal volume and is capable of detecting progressive renal area loss in patients with reflux and urinary tract infection. More studies are necessary to verify whether data from more invasive tests, such as renal magnetic resonance imaging and dimercapto-succinic acid scan, may be attained from ultrasound renal parenchymal area alone.

Novel approach for removal of heavily encrusted ureteral stent.

OBJECTIVES AND BACKGROUND: We describe a novel approach for removal of a retained, heavily encrusted ureteral stent via combined laparoscopic cystolithotomy and pyelolithotomy. Due to noncompliance, our patient with a history of nephrolithiasis returned with large proximal and distal stones 2.5 years after placement of a left ureteral stent. METHODS: Laparoscopy was performed using three 12 mm ports and two 5 mm ports. The bladder was opened in the midline and the stent divided at the ureteral orifice. The bladder stone (4.7 cm x 4 cm) was placed in a retrieval bag and the cystotomy closed with vicryl suture. The proximal ureter and renal pelvis were dissected free and incised. The stent with 2.3 cm x 1.5 cm stone on the proximal curl was removed. The incision was closed transversely with vicryl suture. RESULTS: The patient's recovery was uneventful, including drain removal prior to discharge on postoperative day 3. The foley was removed after a negative cystogram 7 days later. Analysis revealed calcium phosphate and struvite stones. Left ureteroscopy 2 months later revealed a widely patent proximal ureter. No complications have been identified. CONCLUSIONS: Laparoscopic cystolithotomy with stent division combined with pyelolithotomy can be performed safely and successfully as a single procedure to remove the heavily encrusted ureteral stent.