Surgical Approach for Partial Nephrectomy in the Management of Small Renal Masses: A Systematic Review and Network Meta-Analysis.

Background: A variety of surgical and nonsurgical management options for small renal masses (SRMs) now exist. Surgery in the form of partial nephrectomy (PN) has three different approaches. It is unclear which PN approach, if any, offers superior clinical outcomes. Aim: The aim of this study is to compare outcomes in patients with SRMs <4 cm undergoing PN through the open partial nephrectomy (OPN), laparoscopic partial nephrectomy (LPN), or robotic partial nephrectomy (RPN) approach and to establish the advantages and disadvantages of the various approaches. Methods: A systematic literature search was conducted for studies comparing at least two of the above techniques. Eighteen studies and 17,013 patients were included in our study. A network meta-analysis with a frequentist framework was performed. OPN was used as the baseline comparator. The prespecified primary outcome was R0 resection rates. Secondary outcomes included operating time, ischemia time, blood loss, transfusion rates, urine leak rates, significant morbidity, length of stay, and recurrence. Results: There was no significant difference between the techniques in terms of R0 rates, tumor recurrence, urine leak rates, renal function, and >3a Clavien-Dindo complications. LPN had a longer ischemic time and operating time. OPN had a longer length of stay and higher average intraoperative blood loss. RPN had lower blood transfusion rates. Discussion: All approaches are acceptable from an oncological perspective. The minimally invasive approaches (i.e., RPN and LPN) offer advantages in terms of morbidity; however, LPN may increase ischemic time and operative duration. Variations between perioperative outcomes may influence the choice of approach on a case-by-case and institutional basis.

Alemtuzumab, Dual Graft-versus-Host Disease Prophylaxis, and Lower CD3+ T Cell Doses Equalize Rates of Acute and Chronic Graft-versus-Host Disease in Pediatric Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation with Matched Unrelated Donor Peripheral Blood Stem Cells or Bone Marrow Grafts.

Data comparing hematopoietic stem cell transplantation (HSCT) using bone marrow (BM) or peripheral blood stem cell (PBSC) grafts in children after alemtuzumab-based conditioning are lacking. We investigated whether in vivo T cell depletion using alemtuzumab could reduce the risk of severe acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) after HSCT with matched unrelated donor (MUD) BM or PBSCs. This retrospective multicenter study included 397 children (BM group, n = 202; PBSC group, n = 195) who underwent first MUD HSCT at 9 pediatric centers in the United Kingdom between 2015 and 2019. The median age at transplantation was 7.0 years (range, .1 to 19.3 years), and the median duration of follow-up was 3.1 years (range, .3 to 7.5 years). The 3-year overall survival was 81% for the entire cohort (BM group, 80%; PBSC group, 81%). The incidence of grade II-IV aGVHD was significantly higher in the PBSC group (31%) compared to the BM group (31% versus 19%; P = .003), with no difference in the incidence of grade III-IV aGVHD (BM, 7%; PBSC, 12%; P = .17). CD3+ T cell dose >5 × 108/kg and the use of PBSCs were independent predictors of grade II-IV aGVHD. When considering CD3+ T cell dose and GVHD prophylaxis, PBSC transplantation with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) and a CD3+ T cell dose ≤5 × 108/kg had a comparable grade II-IV aGVHD to BM transplantation plus a CNI (20% versus 18%; P = .52). PBSC transplantation was associated with a lower incidence of cGVHD compared to BM transplantation (6% versus 11%; P = .03). Within the limits of this study, we identified a potential strategy to reduce the risk of severe GVHD in pediatric PBSC recipients that includes a combination of in vivo T cell depletion using alemtuzumab and dual GVHD prophylaxis (with a CNI and MMF) and limiting the CD3+ T cell dose to ≤5 × 108/kg.

A Molecular Z-Scheme Artificial Photosynthetic System Under the Bias-Free Condition for CO2 Reduction Coupled with Two-electron Water Oxidation: Photocatalytic Production of CO/HCOOH and H2 O2.

Bio-inspired molecular-engineered systems have been extensively investigated for the half-reactions of H2 O oxidation or CO2 reduction with sacrificial electron donors/acceptors. However, there has yet to be reported a device for dye-sensitized molecular photoanodes coupled with molecular photocathodes in an aqueous solution without the use of sacrificial reagents. Herein, we will report the integration of SnIV - or AlIII -tetrapyridylporphyrin (SnTPyP or AlTPyP) decorated tin oxide particles (SnTPyP/SnO2 or AlTPyP/SnO2 ) photoanode with the dye-sensitized molecular photocathode on nickel oxide particles containing [Ru(diimine)3 ]2+ as the light-harvesting unit and [Ru(diimine)(CO)2 Cl2 ] as the catalyst unit covalently connected and fixed within poly-pyrrole layer (RuCAT-RuC2 -PolyPyr-PRu/NiO). The simultaneous irradiation of the two photoelectrodes with visible light resulted in H2 O2 on the anode and CO, HCOOH, and H2 on the cathode with high Faradaic efficiencies in purely aqueous conditions without any applied bias is the first example of artificial photosynthesis with only two-electron redox reactions.

Atypical mycobacterial infection masquerading as an endobronchial growth in an immunocompromised host.

Non-tuberculous mycobacteria (NTM) are ubiquitous organisms. Endobronchial growth as a presenting feature of NTM disease is uncommon. Here we present a case of a patient with retroviral disease on antiretroviral therapy, presenting with cough, wheezing and exertional dyspnoea. High-resolution CT showed a partial obstruction of the left main bronchus (LMB). Bronchoscopy showed an endobronchial growth in the distal LMB. An endobronchial biopsy showed non-necrotising granulomas; bronchial wash for acid-fast bacilli was positive and culture grew Mycobacterium avium complex. He was treated with a combination therapy of clarithromycin, rifampicin and ethambutol. Repeat bronchoscopy after 6 weeks of therapy showed complete resolution of the endobronchial growth.

An unusual case of metaphyseal osteonecrosis of humerus in a post covid patient: a case report.

Osteonecrosis of the metaphysis is often rare as it is a highly vascular region. Here we report an unusual case of non-traumatic osteonecrosis of the humerus predominantly involving the metaphysis in a post covid elderly female. The patient had a pathological fracture of humerus during the post-operative period of intertrochanteric femur fracture surgery. She was evaluated for the causes of pathological fracture and the fracture was managed with hemi replacement of the shoulder because of the extensive bone loss. The pathology here could only be explained as some sequelae of hyper inflammatory state associated with COVID-19 infection. The possible differentials are also discussed here. This case report will help clinicians to consider COVID-19 infection as a cause for non-traumatic osteonecrosis among other reported causes of osteonecrosis.

Urological service provision during the COVID-19 period: the experience from an Irish tertiary centre.

PURPOSE: Urological service provision has changed dramatically with the advent of the SARS-CoV-2, necessitating restructuring and reorganization. The aim of this study was to review the reorganization of our unit, map the change in volume of departmental activities and discuss potential solutions. METHODS: Departmental activities over the months of April and May 2020 and 2019 were analysed. Details of admissions, operations, diagnostic procedures, outpatient reviews, morbidities and mortalities were recorded. Operations were performed on two sites, with elective operation transferred to an offsite, COVID-free hospital. RESULTS: Seventy-four emergency operations were performed onsite, with 85 elective operations outsourced. A total of 159 operations were performed, compared with 280 in the same period in 2019. Five (5.0%) of 101 admitted patients to the COVID hospital contracted COVID-19. No patients outsourced to the COVID-free hospital were infected there. Outpatient referrals to urology service decreased from 928 to 481. There was a 66% decrease in new cancer diagnoses. A virtual review clinic was established, with remaining outpatients reviewed through a telephone clinic platform. CONCLUSION: Compared with 2019, we performed fewer operations and outpatient procedures, had fewer admissions and diagnosed fewer patients with new cancers. However, outsourcing elective operation to designated non-COVID hospitals prevented the infection of any patient with COVID-19 in the post-operative period. The use of virtual clinic and telephone clinic has had some success in replacing traditional outpatient visits. The overall significant decrease in operative volume will likely precipitate a mismatch between demand and service provision in the coming months, unless capacity is increased.

Predicting Adherent Perinephric Fat Using Preoperative Clinical and Radiological Factors in Patients Undergoing Partial Nephrectomy.

BACKGROUND: The decision to perform a partial nephrectomy (PN) relies largely upon the complexity of the renal mass and its surrounding anatomy. The presence of adherent perinephric fat (APF) can increase surgical complexity and extend operative times. The accurate prediction of APF may improve surgical planning and aid in decision making for the surgical approach. OBJECTIVE: We sought to develop and externally validate a score that predicts APF based on preoperative clinical and radiological prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed 495 consecutive patients who underwent open or minimally invasive PN. APF was defined as the presence of "dense," "adherent," or "sticky" perinephric fat at the time of dissection by the surgeon, and this did not require subcapsular dissection. Additionally, we analyzed an independent cohort of 285 patients for external validation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A score model was developed using multivariate logistic regression analysis. Calibration of the fitted model was assessed graphically with a plot of the predicted versus the actual probability of APF, and discrimination was assessed by calculating the area under the receiver operating characteristic curve. RESULTS AND LIMITATIONS: Of the 495 patients, 95 (19%) had APF. Patients with APF had longer operative (p=0.02) and arterial clamp (p=0.01) times than non-APF patients. On multivariate analyses, diabetes mellitus (p=0.009), posterior perinephric fat thickness (p<0.001), and perinephric stranding (p<0.001) were predictors of encountering APF in PN. A risk score ranging from 0 to 4 was developed based on these three variables to predict APF. The scoring system demonstrated good discrimination of 0.82 and 0.84 for the development and external validation cohorts, respectively. CONCLUSIONS: The APF score can accurately predict the presence of APF in patients with a small renal mass who are planning to undergo PN. This score could aid in pre- and intraoperative planning and impact the surgical approach. PATIENT SUMMARY: The presence of "sticky" fat surrounding the kidney in patients undergoing partial nephrectomy has previously been linked to longer operative times, intraoperative complications, and surgical conversion. In our study, we found that this feature is more often presented in patients with diabetes mellitus, and thicker and more inflammatory fat on renal imaging. Based on these findings, we developed a risk score that can accurately predict this feature before surgery, in order to improve surgical planning and better counsel the patients.

Comparative Evaluation of Genotoxicity in Tobacco Users versus Nontobacco Users.

BACKGROUND: Many of the contents of cigarette smoke are genotoxic in nature, and consequently, cytogenetic injury seems to be a trustworthy biomarker for deciding the influence of exposure to chromosome damaging agents in smoke. The cytokinesis-block micronucleus assay (CBMN assay) has been proven to be an effectual tool for the study of micronuclei (MN) that will help in estimating the genotoxicity in tobacco users alone which will further help in early cancer detection. OBJECTIVE: The objective is to find out whether there is pronounced contrast in genotoxicity between tobacco users and nonusers by determining MN number in peripheral blood lymphocytes using CBMN assay. METHODOLOGY: MN frequency in peripheral blood lymphocytes was estimated in 5 ml of fresh blood obtained from sixty individuals using tobacco either smoking, chewing, or combination of both and also from thirty individuals with no habit of tobacco use. All were in the age group of 20-40 years. RESULTS: There was a significant increase in genotoxicity in tobacco users when compared to that of nontobacco users. A positive correlation was also obtained between smoking index and MN frequency in the study. CONCLUSION: Approximation of frequency of MN by CBMN assay can be used to evaluate the genotoxicity present in blood and helps in identifying tobacco users who are at a high risk for the presence of cancer even before the appearance of clinical changes.

Implementation of a nurse-led lower urinary tract symptoms (LUTS) clinic reduces general urology clinic workload in a Model 4 Hospital: a pilot study in Tallaght University Hospital.

BACKGROUND: With among the lowest urologist per population ratios in Europe, the demand for urology specialist review in Ireland far exceeds supply. Lower urinary tract symptoms (LUTS) account for a significant number of referrals. The traditional paradigm of every patient being reviewed in a consultant-led clinic is unsustainable. New models of care with nurse-led clinics represent an opportunity to optimise limited resources. METHODS: Existing long-waiting male LUTS referrals were triaged to a specialist nurse-led LUTS clinic. After urology CNS assessment, charts were reviewed by a consultant urologist and a plan formulated. Relevant data were prospectively collected and analysed. RESULTS: Fifty-eight new male patients with LUTS were seen over a 6-month period with an average waiting time of 15.8 months. Patients were assessed with uroflowmetry, IPSS and DRE. Mean age was 64, IPSS 14.5, Qmax 18.3 ml/s and PVR 89 ml. Thirty patients (52%) were discharged directly with lifestyle modification and medical therapy. Twenty-eight patients (48%) required one or more further investigations and subsequent review; 11 had flexible cystoscopy, 4 had urodynamics, 5 had prostate MRI, and 2 patients were listed for surgery (TURP and circumcision). The remaining 10 patients were for review post trial of lifestyle modifications and/or medical treatment. After review/investigations, 4 more patients were discharged. A total of 32 patients (55%) were discharged or listed for surgery after initial assessment. This total increased to 62% after a second review/investigations. CONCLUSION: Introduction of a CNS-led LUTS clinic has significantly reduced the number of patients requiring follow-up in general urology clinics, representing a quality improvement in service provision.

Intraoperative and early postoperative complications in postchemotherapy retroperitoneal lymphadenectomy among patients with germ cell tumors using validated grading classifications.

BACKGROUND: Postchemotherapy retroperitoneal lymphadenectomy (PC-RPLND) is an essential, yet potentially morbid, therapy for the management of patients with advanced germ cell tumors. In the current study, the authors sought to define the complication profile of PC-RPLND using validated grading systems for intraoperative adverse events (iAEs) and early postoperative complications. METHODS: Between 2000 and 2018, all patients who underwent PC-RPLND were analyzed for iAEs and early postoperative complications using the Kaafarani and Clavien-Dindo classifications, respectively. Logistic regression models were conducted to assess patient and tumor factors associated with iAEs and postoperative complications. RESULTS: Of the 453 patients identified, 115 patients (25%) and 252 patients (56%), respectively, experienced an iAE and postoperative complication. Major iAEs (grade ≥3) were observed in 15 patients (3%) and major postoperative complications (grade ≥3) were noted in 80 patients (18%). The most common iAE was vascular injury (112 of 132 events; 85%), which occurred in 92 patients (20%), and the most frequent postoperative complication was ileus, which occurred in 121 patients (27%). Original and postchemotherapy retroperitoneal mass size, nonretroperitoneal metastases, intermediate and/or poor International Germ Cell Cancer Collaborative Group classification, previous RPLND, elevated tumor markers at the time of RPLND, and anticipated adjuvant surgical procedures increased the risk of both iAEs and postoperative complications. Patients who experienced an iAE were significantly more likely to experience a postoperative complication (odds ratio, 2.50; 95% confidence interval, 1.58-3.97 [P < .001]). CONCLUSIONS: In what to the authors' knowledge is the first analysis of PC-RPLND using validated classifications for both iAEs and postoperative complications, advanced disease and surgical complexity significantly increased the risks of major iAEs and postoperative complications. Standardized reporting of adverse perioperative events allows providers and patients to appreciate the consequences of PC-RPLND during counseling and decision making.

Access to internet, smartphone usage, and acceptability of mobile health technology among cancer patients.

PURPOSE: The use of mobile health (mHealth) technologies to augment patient care enables providers to communicate remotely with patients enhancing the quality of care and patient engagement. Few studies evaluated predictive factors of its acceptance and subsequent implementation, especially in medically underserved populations. METHODS: A cross-sectional study of 151 cancer patients was conducted at an academic medical center in the USA. A trained interviewer performed structured interviews regarding the barriers and facilitators of patients' current and desired use of mHealth technology for healthcare services. RESULTS: Of the 151 participants, 35.8% were male and ages ranged from 21 to 104 years. 73.5% of participants currently have daily access to internet, and 68.2% currently own a smartphone capable of displaying mobile applications. Among all participants, acceptability of a daily mHealth application was significantly higher in patients with a college-level degree (OR 2.78, CI95% 1.25-5.88) and lower in patients > 80 years of age (OR 0.05, CI95% 0.01-0.23). Differences in acceptability when adjusted for current smartphone use and daily access to internet were nonsignificant. Among smartphone users, the desire to increase cancer knowledge was associated with a higher likelihood of utilizing a mHealth application (OR 261.53, CI95% 10.13-6748.71). CONCLUSION: The study suggests that factors such as age, educational achievement, and access to internet are significant predictors of acceptability of a mHealth application among cancer patients. Healthcare organizations should consider these factors when launching patient engagement platforms.

Implications of faecal ESBL carriers undergoing TRUS-guided prostate biopsy (TRUSPB): role of screening prior to TRUSPB.

INTRODUCTION: Modification of antibiotic prophylaxis prior to transrectal ultrasound-guided prostate biopsy (TRUSPB) based on pre-procedure rectal culture results is effective for prevention of infection from fluoroquinolone (FQ)-resistant and extended-spectrum beta-lactamase (ESBL) Escherichia coli strains. This has several implications for service delivery and cost. Our aim was to audit sepsis rates after introduction of ESBL screening and to identify risk factors for FQ resistance in ESBL strains and factors for sepsis risk. METHODS: This was a prospective cohort study from 2013 to 2016. TRUSPB patients underwent pre-procedure rectal swabs. ESBL-positive patients received amikacin in addition to ciprofloxacin prophylaxis. Patients filled a formal risk assessment questionnaire prior to biopsy. RESULTS: Sepsis rate after introduction of targeted prophylaxis reduced from 3.1% (2009-2012) to 1.4% (2013-2016). Of 38 ESBL patients, n = 5 (13%) developed severe post-TRUSPB sepsis. Among the FQ-resistant ESBL producers, the sepsis rate was 24%. Predictive factor for FQ resistance in ESBL producers included-antibiotic use in the last 3 months (OR 15). The logistic regression analysis did not identify any significant factor for post-TRUSPB sepsis in ESBL-positive patients once they had received additional prophylaxis. CONCLUSION: In the face of rising TRUSPB sepsis and higher sepsis rates with ESBL carriers despite additional prophylaxis, introduction of a targeted antibiotic prophylaxis prior to TRUSPB sepsis prostate biopsies based on rectal swabs or urine cultures may reduce sepsis rates or clinicians may find themselves leaning towards increasingly performing transperineal biopsies with lower sepsis rates supporting the 'trexit' initiative.

The utility of stent on strings in clinical practice.

INTRODUCTION: Various types of ureteric stents are used in the management of ureteric stones. Stents on strings (SOS) are an attractive option as they may be removed without the need for instrumentation. There is some hesitation using SOS due to perceived complications and the risk of premature dislodgement. The aim of this study was to evaluate the utility of SOS compared with the conventional stent (CS). METHODS: A retrospective review was performed on all ureteric stents removed in the urology department over a 7-month period. Only stents inserted during the endoscopic management of ureteric stones were included in analysis. Patients were contacted to identify the incidence of those seeking medical attention while the stent was in situ or within 2 weeks of stent removal. A basic cost analysis was performed. RESULTS: One hundred and sixty cases were identified (98 CS, 62 SOS). No SOS was dislodged prematurely. One SOS was removed cystoscopically due to a broken string. There was no significant difference in the number of patients with SOS seeking medical attention following stent placement compared with those with CS (38.1% (12/51) vs 25.6% (22/86), p = 0.48). There was an estimated cost saving of €23,790 associated with the use of SOS during the study period (€390/case). The use of SOS created additional capacity which was utilised for diagnostic cystoscopy. CONCLUSION: The SOS appeared to be well tolerated and showed similar complication rates as the CS. The use of SOS resulted in a significant cost saving and increased the availability of cystoscopy for other indications.

Primitive neuroectodermal tumour with synchronous ipsilateral clear cell carcinoma of the kidney.

We report the first case of a synchronous ipsilateral primitive neuroectodermal tumour (PNET) and clear cell renal cell carcinoma of the kidney. A 37-year-old man presented to the emergency department with a 24-hour history of colicky abdominal pain and visible haematuria. He had no relevant surgical or medical history. Physical examination was unremarkable apart from mild left flank tenderness. Triphasic CT of the abdomen and pelvis showed two solid lesions in the left kidney. Further staging CT of the chest showed no evidence of local or distal metastasis. He subsequently underwent laparoscopic radical nephrectomy. Pathological analysis of the kidney showed two synchronous renal tumours, a clear cell carcinoma and PNET of the kidney. The patient received adjuvant chemotherapy according to Ewing's sarcoma chemotherapy protocol. Surveillance CT scans at 3, 6 and 12 months showed no evidence of disease recurrence or metastasis.

Paratesticular myositis ossificans of the spermatic cord.

A 56-year-old man presented with a painless scrotal lump, enlarging over the preceding 1 month. The lump was roughly 1 cm in size, and located in his left hemiscrotum and separate from the testis. An ultrasound revealed an echogenic focus with dystrophic tissue calcification. Subsequent surgical excision and histopathological analysis revealed it to be late-stage myositis ossificans, a benign, extraosseous formation of the bone or cartilage. We report of only the second described case of myositis ossificans of the spermatic cord in the literature to date.

Incidence of Visible Hematuria Among Antithrombotic Agents: A Systematic Review of Over 175,000 Patients.

OBJECTIVE: To determine the probability of visible hematuria with antithrombotic agents and to evaluate association of urologic etiology in antithrombotic-related hematuria. METHODS: Preferred Reporting Items in Systematic Reviews and Meta-Analyses guidelines were followed to conduct a systematic review using search engines PUBMED and SCOPUS with the terms "(hematuria) OR (haematuria) OR urinary bleeding)) AND ((anticoagulants) OR anticoagulation) OR noac) OR novel anticoagulants) OR antiplatelet) OR dabigatran) OR rivaroxaban) OR apixaban) OR warfarin) OR aspirin) OR heparin) OR dipyridamole)." Raw data were used to perform a pooled analysis. Chi-square and logistic regression analysis were used for statistical analyses. RESULTS: Twenty-two studies describing 175,114 patients met inclusion criteria. Odds ratio of hematuria with warfarin to rivoraxaban was 33 and warfarin to dabigatran was 16. The odds ratio of hematuria for oral anticoagulant (26.7%) to prophylactic parenteral anticoagulant (1.1%) agents was 9.6. Antiplatelet agents are 76 times less likely to cause hematuria compared to anticoagulants. Odds of hematuria with aspirin were 6.7 times the odds with clopidogrel and 3.5 times the odds with ticagrelor. Dabigatran was 198 times more likely to cause major hematuria compared to warfarin, whereas clopidogrel is 1.2 times more likely to cause major hematuria compared to aspirin. Urologic pathology was identified in 44% (234/532) of cases, malignancy in 24%. CONCLUSION: Warfarin use poses the greatest risk for hematuria but is unlikely to cause major hematuria, whereas novel antithrombotic agents are more commonly associated with major hematuria. This review further characterizes the risk profile of antithrombotic agents and associated hematuria to equip clinicians with knowledge to choose an appropriate antithrombotic agent in patients with high-risk hematuria.

Quantitative Analysis of Technological Innovation in Urology.

OBJECTIVE: To assess major areas of technological innovation in urology in the last 20 years using patent and publication data. METHODS: Patent and MEDLINE databases were searched between 1980 and 2012 electronically using the terms urology OR urological OR urologist AND "surgeon" OR "surgical" OR "surgery". The patent codes obtained were grouped in technology clusters, further analyzed with individual searches, and growth curves were plotted. Growth rates and patterns were analyzed, and patents were correlated with publications as a measure of scientific support and of clinical adoption. RESULTS: The initial search revealed 417 patents and 20,314 publications. The top 5 technology clusters in descending order were surgical instruments including urinary catheters, minimally invasive surgery (MIS), lasers, robotic surgery, and image guidance. MIS and robotic surgery were the most emergent clusters in the last 5 years. Publication and patent growth rates were closely correlated (Pearson coefficient 0.78, P <.01), but publication growth rate remained constantly higher than patent growth, suggesting validated scientific support for urologic innovation and adoption into clinical practice. CONCLUSION: Patent metrics identify emergent technological innovations and such trends are valuable to understand progress in the field of urology. New surgical technologies like robotic surgery and MIS showed exponential growth in the last decade with good scientific vigilance.

One Electron-Initiated Two-Electron Oxidation of Water by Aluminum Porphyrins with Earth's Most Abundant Metal.

We report herein a new molecular catalyst for efficient water splitting, aluminum porphyrins (tetra-methylpyridiniumylporphyrinatealuminum: AlTMPyP), containing earth's most abundant metal as the central ion. One-electron oxidation of the aluminum porphyrin initiates the two-electron oxidation of water to form hydrogen peroxide as the primary reaction product with the lowest known overpotential (97 mV). The aluminum-peroxo complex was detected by a cold-spray ionization mass-spectrometry in high-resolution MS (HRMS) mode and the structure of the intermediate species was further confirmed using laser Raman spectroscopy, indicating the hydroperoxy complex of AlTMPyP to be the key intermediate in the reaction. The two-electron oxidation of water to form hydrogen peroxide was essentially quantitative, with a Faradaic efficiency of 99 %. The catalytic reaction was found to be highly efficient, with a turnover frequency up to ∼2×104  s-1 . A reaction mechanism is proposed involving oxygen-oxygen bond formation by the attack of a hydroxide ion on the oxyl-radical-like axial ligand oxygen atom in the one-electron-oxidized form of AlTMPyP(O- )2 , followed by a second electron transfer to the electrode.

The Role of Metastasectomy in Patients with Renal Cell Carcinoma with Sarcomatoid Dedifferentiation: A Matched Controlled Analysis.

PURPOSE: Management of metastatic renal cell carcinoma with sarcomatoid dedifferentiation remains a therapeutic challenge with no standard treatment strategies. We evaluated whether metastasectomy has any survival benefit in patients with metastatic sarcomatoid dedifferentiation treated with radical nephrectomy. MATERIALS AND METHODS: From an institutional database of 273 patients with sarcomatoid dedifferentiation treated with nephrectomy we matched 80 with synchronous and asynchronous metastases for age, ECOG (Eastern Cooperative Oncology Group) performance status, histology and lymph node status. Matched pairs were then retained only if patients who did not undergo metastasectomy were alive at metastasectomy comparable to matched surgical patients to decrease the bias of survival outcomes. Overall survival from nephrectomy was studied using univariable and multivariable proportional hazards regression. RESULTS: Median overall survival was 8.3 (95% CI 6.5-10.5) and 18.5 months (95% CI 11.5-42.9) in patients with synchronous and asynchronous metastases, respectively. Overall survival in patients who underwent metastasectomy for synchronous metastasis compared to nonsurgical patients was 8.4 and 8.0 months (p = 0.35), respectively. Similarly, overall survival in patients with asynchronous metastases treated with metastasectomy compared to the nonsurgical group was 36.2 and 13.7 months, respectively (p = 0.29). On multivariable analysis positive lymph nodes at nephrectomy were associated with an increased risk of death in the synchronous and asynchronous patient subgroups (HR 2.1, 95% CI 1.1-4.0, p = 0.03 and HR 3.3, 95% CI 1.2-9.2, p = 0.02, respectively). CONCLUSIONS: In the current study there was no clear evidence of benefit in patients with sarcomatoid dedifferentiation who underwent metastasectomy after nephrectomy. Particularly, the group of patients with pathological lymph node positive disease at nephrectomy had considerably worse survival.

The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma.

In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC.