Immune checkpoint inhibitors in high-grade upper tract urothelial carcinoma: Paradigm shift emphasizing organ preservation.

Objective: The aim was to evaluate the role of immune check point inhibitors (ICIs) in patients with high-grade upper tract urothelial carcinoma (UTUC) who are managed endoscopically when nephroureterectomy (NU) is not feasible, such as in patients who are either not candidates for NU or decline extirpative surgery. Methods: All patients diagnosed with high-grade UTUC and managed endoscopically between January 1996 and August 2022 were included in the study. Subsequently, patients were categorised based on their use of ICIs into group 1 (patients who did not receive ICIs) and group 2 (patients who received ICIs). Survival outcomes were assessed using Kaplan-Meier analysis, while a multivariable regression model was employed to analyse the impact of clinical characteristics on survival. Results: A total of 29 patients were enrolled, with 14 in group 1 and 15 in group 2. Both groups exhibited similar demographic and disease characteristics, including multifocality, laterality and initial tumour size. The median follow-up period was 29.2 months. Notably, group 2 demonstrated significantly enhanced overall and metastasis-free survival rates compared to group 1. At 47.8 months, the overall survival rate was 0% (all patients died) in group 1, whereas it was 85.7% in group 2. Similarly, the metastasis-free survival rate was 0% (all patients had metastatic disease) in group 1 at 40.6 months, whereas it reached 78.0% in group 2. The multivariable analysis indicated a correlation between ICI usage and improved survival outcomes, with a hazard ratio of 0.002. Conclusion: Utilisation of adjuvant ICIs in the setting of endoscopically treated patients with high-grade UTUC is associated with significantly improved survival rates. ICIs should be considered in this patient population, however, more studies with larger sample size are warranted.

Head and neck lipoblastoma in children: A case report and systematic review.

BACKGROUND: Lipoblastoma is a rare and benign tumor arising from embryonal fat cells. It develops primarily in infancy and early childhood. We present a case study of a 10-month-old child treated for an extensive tumor of the infratemporal fossa and parapharyngeal space. The systematic review of 60 reports in 80 children with lipoblastoma of the head and neck is also reported. MATERIAL AND METHODS: Systematic review of all articles included lipoblastomas of the head and neck area in children published from 1964 to 2022 in the PubMed database was conducted. Clinical presentation of extensive lipoblastoma of the head and neck in a child. RESULTS: On the basis of all inclusion criteria 83 articles were identified concerning pediatric lipoblastoma. There were 36 F (45%) and 39 M (48%), in 6 patients, (7%) gender was not specified. Ages ranged from 0mth (6h) to 15 yo (180mth). The tumor was located in the head in 22 (27%) cases, while the neck area accounted for 53 (65%) cases. General description without precise location was shown in 6 (7%) cases. All patients underwent complete surgical excision. Post surgical recurrence was noted in 6% clinical cases in the analyzed articles. CONCLUSIONS: Lipoblastoma is characterized by a rapidly growing predominantly adipose mass. The treatment of choice is complete surgical excision. In selected cases when the pathology is hard to reach, as a consequence of the extensive penetration of the mass, we recommend performing the procedure with an interdisciplinary team. Endoscopy assistance and microdebrider significantly facilitated the removal of pathology in the described advanced case of lipoblastoma. This is the only case reported in the pediatric literature of a head and neck lipoblastoma, where due to extensive involvement and location of the disease the cranial nerves V2 and inferior alveolar branch of V3 could not be spared. Long-term follow-up even to 10 years is required because there is a reported tendency for these tumors to recur.

Prostate Cancer: Under-representation of African American Men in Research Studies Used in the Latest NCCN Guidelines.

OBJECTIVE: To evaluate racial data in studies used in current NCCN prostate cancer guidelines. These guidelines represent the latest information that informs clinical practice. Prostate cancer disproportionately affects mortality in Black patients compared to White patients at a 2.1-fold higher death rate. However, this racial disparity is not accounted for when including patients in research. METHODS: The studies referenced in the latest NCCN guidelines were evaluated for inclusion of racial demographics, and whether they properly account for the higher mortality rate of prostate cancer seen in Black patients. We then analyzed topics within prostate cancer. RESULTS: After application of exclusion criteria, 547 of 878 studies were included for analysis; of those, only 32.4% included demographic data. Overall, Black patients accounted for 472,476 (12.8%) of total patients, while 3,023,007 (81.7%) patients were White. These findings were consistent with specific areas including risk stratification (12% vs 75%), imaging and staging (11% vs 80%), treatment (16% vs 81%), recurrence (15% vs 73%), castration-sensitive prostate cancer (9% vs 84%), castration-resistant prostate cancer (8% vs 73%), and metastatic bone disease (7% vs 84%). CONCLUSION: Our analysis showed consistently that although the guidelines utilize the best research, such studies often do not report racial demographics or have patient populations that do not reflect racial differences in mortality of prostate cancer. Our study questions the generalization of these studies to Black patients. Future research should emphasize inclusion of racial demographics and recruit appropriately representative study cohorts.

Application of "banana cochleostomy" and looped electrode insertion for cochlear implantation in children with common cavity malformation and cystic forms of cochlear hypoplasia.

OBJECTIVES: Patients with profound hearing loss due to inner ear malformations may benefit from cochlear implantation; however, the surgery may present a substantial problem for the cochlear implant surgeon due to anatomical variations. The authors describe a new surgical and technical advancement for implantation in patients with small inner ear cavities that make the surgery easier and safer. On the basis of experience involving five consecutive surgeries performed in four patients with inner ear malformations, we present the advantages and application possibilities of the technique. METHODS: The technique does not change the surgical approach in general; however, modification of the cochleostomy shape and looping of the cochlear implant electrode enables safe advancement of the electrode with optimal positioning in the cavity. Additionally, these modifications protect against the insertion of the electrode into the internal auditory canal minimizing the risk of gushing and extracochlear stimulation. RESULTS: The present technique has been used in five cases of cystic implantable inner ear spaces in three independent institutions by different surgeons. It has proven to be a reliable, relatively easy and safe procedure performed with very good anatomic and initially functional effects (positive intraoperative neural response telemetry measurements). CONCLUSIONS: We hope that utilization of the "banana cochleostomy" and insertion of the looped cochlear implant electrode in the implantable cystic spaces of children with malformed inner ears will facilitate and simplify the surgical technique in this difficult procedure and additionally, in revision surgical cases. To our knowledge, the looped insertion and banana-shaped cochleostomy have not been reported previously.

Percutaneous and Endoscopic Management of Nephrolithiasis in a Patient with Five Native Ureters (Trifid Right and Bifid Left Collecting System).

Triplication of the ureter is a rare urologic finding that has been well described in the literature. Patients can present with urinary tract infections, incontinence, and calculi. We present the case of a patient with extensive stone burden with right trifid and left bifid collecting systems. Stone management was performed with a multimodal approach using a combination of endoscopic and percutaneous approaches. Our systematic and staged approach highlights a method for efficacious stone treatment in a complex endourologic case.

The Petrosquamous Stalactite.

Objective To define the presence and relationship of the petrosquamous stalactite (PsS)-a condensation of the trabecular Korner's septum into a bony plate of the petrosquamous suture-to surrounding structures and understand its surgical implications. Study Design Series of cadaver dissections. Setting University of Missouri Alumni Temporal Bone and Microvascular Laboratory. Subjects and Methods Anatomic dissections were conducted on 15 consecutive formalin-preserved and frozen adult human temporal bones. A calibrated Dino-Lite Premier Digital Microscope was used to photograph dissections of each bone. Measurements were conducted with DinoCapture 2.0 software, with measurement agreement between 2 authors. Results The PsS was present in all specimens. A conserved vascular structure courses within the structure, and the superior malleolar ligament inserts on it. The mean ± SEM distances from the PsS to the tegmen tympani and incus buttress were 2 ± 0.24 mm and 4.23 ± 0.14 mm, respectively. The shortest distance from the PsS to the posterior body of the incus was 1.25 ± 0.13 mm, while the greatest distance from the posterior prominence of the PsS to the posterior body of the incus was 4.58 ± 0.25 mm. Conclusion The PsS is a consistently identifiable structure that may facilitate identification of the tegmen tympani and guide the otologic surgeon from the mastoid antrum to the incus. It is important to recognize the contribution of the PsS to the division of the epitympanic space when cholesteatoma involves the region, to avoid leaving a nidus for future disease.

Enhancement of the subtemporal approach by partial posterosuperior petrosectomy with hearing preservation.

BACKGROUND: The microsurgical management of aneurysms in the interpeduncular and ambient cisterns remains challenging. The classic subtemporal approach has several limitations. OBJECTIVE: To present a modification of this approach that allows for broader exposure with hearing preservation. METHODS: We retrospectively reviewed our clinical database between August 2007 and February 2012 for all patients who underwent a modified subtemporal partial posterosuperior petrosectomy. Clinical data, complications, and postoperative head computed tomography (CT) scans were analyzed. Improvement in the angle of view acquired by the new approach was measured using the OsiriX 3-D rendering software and was compared with that obtained from the subtemporal approach. Similar methods were used to study improvement in the angle of view in head CT scans of randomly selected control patients. RESULTS: Five patients underwent a modified subtemporal approach for posterior circulation aneurysm clipping. All patients were women with a mean age of 49.8 years. Mean aneurysm size was 5.75 mm. Mean improvement in the angle of view was 17.52° in the study group (n = 5) and 11.7° in the control group (n = 10). Hearing was completely preserved in 3 patients. One patient had a subclinical conductive hearing loss, and 1 patient was not assessed formally at follow-up, but had no hearing concerns. No neurological sequelae were recorded. CONCLUSION: Our modified subtemporal approach appears to be safe and provides an increased angle of view with minimal additional operative time and with low risk to hearing. This approach may expand this surgical corridor and reduce the need for temporal lobe retraction.

Preventive effect of specific antioxidant on oxidative renal cell injury associated with renal crystal formation.

OBJECTIVE: To investigate whether calcium oxalate monohydrate (COM), a key element of hyperoxaluria, would induce renal cell injury through oxidative stress and also whether certain antioxidants could prevent chemically induced renal crystal formation in rats. MATERIALS AND METHODS: COM-exerted oxidative stress on the kidney epithelial Madin-Darby canine kidney cells was assessed using the lipid peroxidation assay. Glyoxalase I (Gly-I) activity was also determined. Two antioxidants, vitamin C and N-acetylcysteine (NAC), were then tested to determine whether they could abolish such oxidative stress in Madin-Darby canine kidney cells. Both antioxidants were also tested to determine whether they might prevent or reduce renal crystal formation induced with ethylene glycol (EG) and vitamin D3 (VD3) in Wistar rats. RESULTS: COM (200 µg/mL) demonstrated ∼1.3-fold greater oxidative stress with a significant reduction in cell viability and Gly-I activity compared with controls. However, such adverse events were almost completely prevented with NAC but not with vitamin C. In the animal study, no renal crystals were seen in the sham group. However, numerous crystals, with reduced Gly-I activity and elevated oxidative stress, were found in the EG-VD3 group. However, markedly (>70%) fewer crystals, with full Gly-I activity and diminished oxidative stress, were detected in the EG-VD3+NAC group. CONCLUSION: COM exerted oxidative stress on Madin-Darby canine kidney cells, leading to cell viability reduction and Gly-I inactivation, with NAC fully preventing such adverse consequences. Similarly, numerous crystals with Gly-I inactivation and elevated oxidative stress seen in the rats (EG-VD3) were also significantly prevented with NAC supplement. Thus, NAC might have clinical implications in preventing oxidative renal cell injury and, ultimately, kidney stone formation.

Long term outcomes of lymphatic sparing laparoscopic varicocelectomy.

OBJECTIVE: To assess the long-term occurrence of hydroceles and varicocele recurrence in patients receiving lymphatic sparing laparoscopic varicocelectomy (LSLV) compared to those receiving plain laparoscopic varicocelectomy (PLV), and also to assess the growth of testicular volume postoperatively. METHODS: We employed a standard three-trocar configuration. The spermatic vessels were identified in the retroperitoneum above the internal inguinal ring. Lymphatics were dissected free from the spermatic artery and veins based on laparoscopic appearance. The spermatic artery and veins were divided between plastic locking clips. We performed a retrospective chart review of all pediatric patients who underwent laparoscopic varicocelectomy between June 2003 and January 2009. RESULTS: Of a total of 97 patients, 67 underwent LSLV with mean follow-up of 45.8 ± 20.7 months and 30 underwent PLV with mean follow-up of 40.8 ± 25.3 months (p = 15). There was a 4.5% hydrocele rate in the LSLV group compared to 43.3% in the PLV group. Of the patients who underwent a PLV and subsequently developed a hydrocele, 31% (n = 4) required a hydrocelectomy, vs none of those who developed a hydrocele after LSLV. Varicocele rate was 6% in the LSLV group vs 3.3% in the PLV group. However, when the artery was not preserved, the probability of recurrence in the LSLV group was 1.3%. Time to hydrocele formation was 16 months in the LSLV group vs 37 months in the PLV group. There was catch-up testicular growth in both groups. CONCLUSIONS: There appears to be increased risk of need for a hydrocelectomy after a PLV as compared to LSLV. Performing a lymphatic sparing, non-artery preserving, laparoscopic varicocelectomy has success and complication rates comparable with those of subinguinal microsurgical varicocelectomy. There appears to be excellent catch-up testicular growth with either laparoscopic varicocelectomy technique.

Induction of cell death in renal cell carcinoma with combination of D-fraction and vitamin C.

HYPOTHESIS: Although several conventional therapeutic options for advanced renal cell carcinoma (RCC) are currently available, the unsatisfactory outcomes demand establishing more effective interventions. D-fraction (PDF), a bioactive proteoglucan of Maitake mushroom, demonstrates anticancer and immunomodulatory activities, which are also shown to be potentiated by vitamin C (VC). We thus hypothesized that a combination of PDF and VC (PDF + VC) could be an alternative approach to more effectively inhibit the growth of RCC. STUDY DESIGN: We examined the dose-dependent effects of PDF + VC on RCC cell viability and also performed biochemical assays to explore the growth regulatory mechanism. METHODS: Human RCC, ACHN cell line, was employed and exposed to varying concentrations of PDF or VC and their combinations. Cell viability at specified times was determined by MTT assay. Lipid peroxidation assay, cell cycle analysis, and Western blot analysis were also performed. RESULTS: PDF or VC alone led to the significant reduction in cell viability at 72 hours with PDF >500 µg/mL and VC ≥300 µM. When various combinations of PDF and VC were tested, the combination of the ineffective concentrations of PDF (300 µg/mL) and VC (200 µM) resulted in ~90% cell death in 24 hours. Lipid peroxidation assay then indicated significantly (~2.5 fold) elevated oxidative stress with this PDF + VC. Cell cycle analysis also indicated a G1 cell cycle arrest following a 6-hour PDF + VC treatment. Western blots further revealed a downregulation of Bcl2, an upregulation of Bax, and proteolytic activation of PARP (poly[ADP-ribose] polymerase) in PDF + VC-treated cells, indicating induction of apoptosis. CONCLUSION: The present study demonstrates that the combination of PDF and VC can become highly cytotoxic, inducing severe cell death in ACHN cells. This cytotoxic mechanism appears to be primarily attributed to oxidative stress, accompanied by a G1 cell cycle arrest. Such cell death induced by PDF + VC could be more likely linked to apoptosis, as indicated by the modulation of apoptosis regulators (Bcl2, Bax, and PARP). Therefore, as PDF and VC may work synergistically to induce apoptotic cell death, they may have clinical implications in an alternative, improved therapeutic modality for advanced RCC.

Laparoscopic-assisted surgical reconstruction of a rare congenital abdominal wall defect in two children misdiagnosed with prune-belly syndrome.

PURPOSE: Abdominal wall laxity is typically associated with prune-belly syndrome (PBS). Incomplete forms of PBS have been rarely reported with only the abdominal wall laxity. Herein, we describe a rare congenital abdominal wall defect that has been confused with PBS and illustrate the laparoscopic-assisted surgical technique used for reconstruction. MATERIALS AND METHODS: Two boys with symmetrical, bilateral absence or hypoplasia of the internal and external oblique muscles and no genitourinary abnormalities underwent a laparoscopic-assisted abdominal wall reconstruction utilizing the technique previously described by Firlit. Each patient had a Ct scan which confirmed the absence of the oblique muscles. In one patient EMG data confirmed no electrical activity of the obliques. Radiologic evaluation of the urinary tracts revealed no abnormalities. The abdominal wall was plicated utilizing bilateral subcostal incisions. RESULTS: Both patients had excellent cosmetic and functional results with no weakness or bulging of the lateral abdominal wall and improvement of associated symptoms. CONCLUSIONS: We believe these two cases and their congenital abdominal wall defects are a rare and often misdiagnosed muscular deficiency separate from PBS. The novel laparoscopic-assisted surgical technique illustrated is feasible and highly successful for these and possible other patients with similar rare congenital abdominal wall defects.

Attenuation of androgenic regulation by brefeldin A in androgen-responsive prostate cancer cells.

OBJECTIVES: To investigate the effects of an antibiotic brefeldin A (BFA) on androgen-regulated cellular events in androgen-responsive prostate cancer cells, focusing on PSA (prostate-specific antigen) status, cell growth, and bioactivity of androgen receptor (AR). MATERIALS AND METHODS: Androgen-responsive human prostate cancer LNCaP cells were employed and 5α-dihydrotestosterone (DHT) was used as an androgenic mediator to induce androgen-modulated cellular events. Effects of BFA on synthesis and secretion of PSA, cell growth, and AR activity were assessed using Tandem PSA assay, trypan blue exclusion method, and AR binding assay, respectively. RESULTS: BFA (30 ng/ml) dramatically (90%) blocked secretion of PSA and also reduced cell growth by >75% under non-androgen-regulated condition. Under androgen-stimulated condition using DHT (1 nM), both the cellular and secreted PSA levels as well as cell growth was significantly elevated or stimulated by DHT (compared with controls); however, BFA was capable of completely inhibiting such DHT-stimulated cellular events. In addition, AR binding assay revealed that AR activity has been drastically (~90%) diminished by BFA, likely resulting in interruption of DHT-mediated events. CONCLUSIONS: BFA is capable of attenuating androgenic regulation in LNCaP cells such as androgen-stimulated PSA synthesis/secretion and cell growth. This BFA-blocked androgen action appears to be primarily attributed to severe inactivation of AR with BFA because AR is a crucial factor for relaying androgenic messages (to DNA). Therefore, BFA could be considered a promising agent for a more effective treatment of hormone-dependent prostate cancer.

Nephrotoxin-induced renal cell injury involving biochemical alterations and its prevention with antioxidant.

BACKGROUND: Although nephrotoxic agents or nephrotoxins are known to induce acute renal cell injury, their cytotoxic action is not fully elucidated. It is thus crucial to explore such a cytotoxic mechanism and the increasing volume of reports indicated a significant involvement of oxidative stress. To test this possibility, we investigated if a nephrotoxin would exert oxidative stress, leading to renal cell injury accompanied by certain biochemical alterations. We also examined if specific antioxidant might help prevent such oxidative cell injury. These studies may then help establish a prophylactic or preventive modality for renal cell injury induced by nephrotoxins. METHODS: As glycerol has been commonly used for studying acute renal failure in animals, whether it would induce cellular injury was tested in renal proximal tubular OK cells in vitro. Cells were exposed to the varying concentrations of glycerol and cell number/viability was determined in 24 hours. Severity of oxidative stress was assessed by lipid peroxidation assay. Possible effects of glycerol on biochemical parameters were also examined on glyoxalase I activity and heat shock protein 90 using spectrophotometric (enzymatic) assay and Western blot analysis. RESULTS: Glycerol (2.5%) was highly cytotoxic to OK cells, inducing 95% cell death in 24 hours. Lipid peroxidation assay indicated that nearly 3-fold greater oxidative stress was exerted by this glycerol. Concurrently, glyoxalase I activity was drastically lost by 75% and heat shock protein 90 was partially degraded following glycerol exposure. However, N-acetylcysteine, a potent glutathione-based antioxidant, was capable of almost completely preventing the glycerol-mediated adverse outcomes, such as cell death, glyoxalase I inactivation, and heat shock protein 90 degradation. CONCLUSIONS: Glycerol is cytotoxic, capable of inducing specific biochemical alterations such as inactivation of glyoxalase I and degradation of heat shock protein 90, which may reflect a breakdown of the cellular detoxification and defense systems, leading ultimately to OK cell death. Nevertheless, as N-acetylcysteine can provide full cytoprotection against such glycerol toxicity, it could be considered a prophylactic modality for nephrotoxin-induced oxidative renal cell injury and death. KEYWORDS: Glycerol; Glyoxalase I; Heat shock protein; N-acetylcysteine; Renal cell injury.

The zone-based approach for selection of tympanoplasty technique.

At the outset of surgery, the extent of a tympanic membrane defect is judged including any additional loss of area that may result from disease extirpation or removal of the mucocutaneous junction. There are, three tiers of complexity when deciding upon which technique should be used for repair. Limited central perforations are defects amenable to a standard underlay technique. The Zone Based Approach is applied for marginal perforations whereby the specific technique is selected based on the zone of the defect. The zones and specific techniques are detailed. There are however, still a significant number of patients who have scarce residual tympanic membrane, or keratin matrix adherently involving the undersurface requiring sacrifice. These situations prove poor for either standard underlay or the zone based techniques. The total tympanic membrane reconstruction (TT MR) technique was developed specifically to avoid these complications as well as facilitate extirpation of the more extensive inflammatory and neoplastic pathologies commonly encountered, yet still amenable to intact canal wall mastoidectomy approaches.

Additively enhanced antiproliferative effect of interferon combined with proanthocyanidin on bladder cancer cells.

Although interferon (IFN) has been often used as immunotherapy for bladder cancer, its efficacy is rather unsatisfactory, demanding further improvement. Combination therapy is one of viable options, and grape seed proanthocyanidin (GSP) could be such an agent to be used with IFN because it has been shown to have anticancer activity. We thus investigated whether combination of IFN and GSP might enhance the overall antiproliferative effect on bladder cancer cells in vitro. Human bladder cancer T24 cells were employed and treated with the varying concentrations of recombinant IFN-α(2b) (0-100,000 IU/ml), GSP (0-100 µg/ml), or their combinations. IFN-α(2b) alone led to a ~50% growth reduction at 20,000 (20K) IU/ml, which further declined to ~67% at ≥50K IU/ml. Similarly, GSP alone induced a ~35% and ~100% growth reduction at 25 and ≥50 µg/ml, respectively. When IFN-α(2b) and GSP were then combined, combination of 50K IU/ml IFN-α(2b) and 25 µg/ml GSP resulted in a drastic >95% growth reduction. Cell cycle analysis indicated that such an enhanced growth inhibition was accompanied by a G(1) cell cycle arrest. This was further confirmed by Western blot analysis revealing that expressions of G(1)-specific cell cycle regulators (CDK2, CDK4, cyclin E and p27/Kip1) were distinctly modulated with such IFN-α(2b)/GSP treatment. Therefore, these findings support the notion that combination of IFN-α(2b) and GSP is capable of additively enhancing antiproliferative effect on T24 cells with a G(1) cell cycle arrest, implying an adjuvant therapeutic modality for superficial bladder cancer.

Ureteroscopic and extirpative treatment of upper urinary tract urothelial carcinoma: a 15-year comprehensive review of 160 consecutive patients.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UTUC) have historically been treated with radical, extirpative surgery, primarily nephroureterectomy with bladder-cuff excision. In general, there has been growing interest in renal preservation, as evidenced by the broadening application of nephron-sparing surgery for renal parenchymal tumours. Beyond imperative reasons such as tumour in a solitary kidney, bilateral disease, or comorbidities preventing radical surgery, there is a growing role for endoscopic management of upper tract tumours. The aim has been to obtain similar oncological results to those of extirpative surgery, while preserving long-term renal function. Properly selecting patients for these therapies, designing specific treatments based on a complex presentation, and general information with regard to outcomes and risks for patient counselling have been based historically on results from relatively small series without long-term follow-up. This study reflects all patients with UTUC treated by a single tertiary referral surgeon, accrued prospectively over 15 years using the same surgical techniques and treatment algorithms throughout the entire study period, with 10-year survival data. The consecutively accrued nature and size of the study groups, uniformity in treatments, statistical review and long-term follow-up provide baseline oncological data that could help frame future study. OBJECTIVE: • To present long-term oncological outcomes of all patients treated surgically for upper urinary tract urothelial carcinoma (UTUC) over a 15-year period. PATIENTS AND METHODS: • All patients (N = 160) treated from January 1996 to August 2011 were prospectively studied and placed into three distinct groups after initial diagnostic ureteroscopy (URS): Group 1: low grade lesions treated with URS (n = 66); Group 2: high grade lesions palliatively treated with URS (n = 16); and Group 3: extirpative surgery (nephroureterectomy [NU]; n = 80). • Statistical analysis was performed using Kaplan-Meier methodology to calculate overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS). RESULTS: • The median patient age at presentation was 73 years, and the mean (range) follow-up time was 38.2 (1-185) months. At initial diagnostic URS, 71 (44.4%) patients presented with high grade and 89 (55.6%) patients presented with low grade disease. • The 2-, 5- and 10-year CSS rates were 98, 87 and 81% for patients with low grade disease, and 97, 87 and 78% for patients treated with URS (Group 1), not significantly different from those patients with low grade disease treated with NU (Group 3), (P = 0.54). • Of the patients treated with URS for low grade disease, 10 (15.2%) progressed to high grade disease at a mean time of 38.5 months. • Patients with high grade disease treated with NU had a 2-, 5-, and 10-year CSS of 70, 53 and 38%, with a MFS of 55, 45 and 35%. • Median survival of patients with high grade disease treated with palliative URS was 29.2 months with a 2-year OS of 54%. • On multivariate analysis only high grade lesion on initial presentation was found to be a significant factor (P < 0.001; hazard ratio = 7.27). CONCLUSIONS: • Grade is the most significant predictor of OS and CSS in those with UTUC, regardless of treatment method. • Ureteroscopic and extirpative therapy are acceptable options for those with low grade disease showing excellent long-term CSS. • Extirpative therapy was found to result in relatively poor long-term CSS in patients with high grade disease, underscoring the need for adjuvant or neoadjuvant therapies.

Imaging and anatomy for cochlear implants.

At a minimum, successful cochlear implantation requires that electrical impulses be delivered to a surviving spiral ganglion cell population, and that these impulses be transmitted to a functioning auditory cortex by an existent neural connection. Accordingly, imaging the auditory pathway of the implant candidate is necessary to screen for morphologic conditions that will preclude or complicate the implantation process. In addition to radiography, increasing resolution of computed tomography and magnetic resonance imaging technology has provided the clinician with more detailed information about the integrity of the auditory pathway.

Amelioration of renal ischemia-reperfusion injury with a novel protective cocktail.

PURPOSE: Extended warm ischemia during partial nephrectomy can lead to considerable renal injury. Using a rat model of renal ischemia we examined the ability of a unique renoprotective cocktail to ameliorate warm ischemia-reperfusion injury. MATERIALS AND METHODS: A warm renal ischemia model was developed using 60 Sprague-Dawley® rats. The left renal artery was clamped for 40 minutes, followed by 48 hours of reperfusion. A renoprotective cocktail of a mixture of specific growth factors, mitochondria protecting biochemicals and Manganese-Porphyrin (MnTnHex-2-PyP(5+)) was given intramuscularly at -24, 0 and 24 hours after surgery. At 48 hours the 2 kidneys were harvested and examined with hematoxylin and eosin, and periodic acid-Schiff stains. Protein and gene expression were also analyzed to determine ischemia markers and the antioxidant response. RESULTS: Compared to ischemic controls, kidneys treated with the renoprotective cocktail showed significant reversal of morphological changes and a significant decrease in the specific ischemic markers lipocalin-2, mucin-1 and galectin-3. Quantitative reverse transcriptase-polymerase chain reaction revealed up-regulation of several antioxidant genes in treated animals. CONCLUSIONS: According to histopathological and several molecular measures our unique renoprotective cocktail mitigated ischemia-reperfusion injury.