PADUA and R.E.N.A.L. nephrometry scores correlate with perioperative outcomes of robot-assisted partial nephrectomy: analysis of the Vattikuti Global Quality Initiative in Robotic Urologic Surgery (GQI-RUS) database

Objectives: To evaluate and compare the correlations between Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) and R.E.N.A.L. [Radius (tumour size as maximal diameter), Exophytic/endophytic properties of the tumour, Nearness of tumour deepest portion to the collecting system or sinus, Anterior (a)/posterior (p) descriptor and the Location relative to the polar line] nephrometry scores and perioperative outcomes and postoperative complications in a multicentre, international series of patients undergoing robot-assisted partial nephrectomy (RAPN) for masses suspicious for renal cell carcinoma (RCC). Patients and Methods: We retrospectively evaluated the clinical records of patients who underwent RAPN between 2010 and 2013 for clinical N0M0 renal tumours in four international centres that completed all the data required for the Vattikuti Global Quality Initiative in Robotic Urologic Surgery (GQI-RUS) database. All patients underwent preoperative computed tomography or magnetic resonance imaging to define the clinical stage and anatomical characteristics of the tumours. PADUA and R.E.N.A.L. scores were retrospectively assessed in each centre. Univariate and multivariate analyses were used to evaluate the correlations between age, gender, Charlson comorbidity index, clinical tumour size, PADUA and R.E.N.A.L. complexity group categories and warm ischaemia time (WIT) of >20 min, urinary calyceal system closure, and grade of postoperative complications. Results: Overall, 277 patients were evaluated. The median (interquartile range) tumour size was 33.0 (22.0\u201343.0) mm. The median PADUA and R.E.N.A.L. scores were eight and seven, respectively; 112 (40.4%), 86 (31.0%) and 79 (28.5%) patients were classified in the low-, intermediate- or high-complexity group according to PADUA score, while 118 (42.5%), 139 (50.1%) and 20 (7.2%) were classified in the low-, intermediate- or high-complexity group according to R.E.N.A.L. score, respectively. Both nephrometry tools significantly correlated with perioperative outcomes at univariate and multivariate analyses. Conclusion: A precise stratification of patients before PN is recommended to consider both the potential threats and benefits of nephron-sparing surgery. In our present analysis, both PADUA and R.E.N.A.L. were significantly associated with predicting prolonged WIT and high-grade postoperative complications after RAP

The SCARE Statement: Consensus-based surgical case report guidelines

AbstractIntroductionCase reports have been a long held tradition within the surgical literature. Reporting guidelines can improve transparency and reporting quality. However, recent consensus-based guidelines for case reports (CARE) are not surgically focused. Our objective was to develop surgical case report guidelines.MethodsThe CARE statement was used as the basis for a Delphi consensus. The Delphi questionnaire was administered via Google Forms and conducted using standard Delphi methodology. A multidisciplinary group of surgeons and others with expertise in the reporting of case reports were invited to participate. In round one, participants stated how each item of the CARE statement should be changed and what additional items were needed. Revised and additional items from round one were put forward into a further round, where participants voted on the extent of their agreement with each item, using a nine-point Likert scale, as proposed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) working group.ResultsIn round one, there was a 64% (38/59) response rate. Following adjustment of the guideline with the incorporation of recommended changes, round two commenced and there was an 83% (49/59) response rate. All but one of the items were approved by the participants, with Likert scores 7–9 awarded by >70% of respondents. The final guideline consists of a 14-item checklist.ConclusionWe present the SCARE Guideline, consisting of a 14-item checklist that will improve the reporting quality of surgical case reports

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

The SCARE Statement: Consensus-based surgical case report guidelines

Introduction: Case reports have been a long held tradition within the surgical literature. Reporting guidelines can improve transparency and reporting quality. However, recent consensus-based guidelines for case reports (CARE) are not surgically focused. Our objective was to develop surgical case report guidelines.Methods: The CARE statement was used as the basis for a Delphi consensus. The Delphi questionnaire was administered via Google Forms and conducted using standard Delphi methodology. A multidisciplinary group of surgeons and others with expertise in the reporting of case reports were invited to participate. In round one, participants stated how each item of the CARE statement should be changed and what additional items were needed. Revised and additional items from round one were put forward into a further round, where participants voted on the extent of their agreement with each item, using a nine-point Likert scale, as proposed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) working group.Results: In round one, there was a 64% (38/59) response rate. Following adjustment of the guideline with the incorporation of recommended changes, round two commenced and there was an 83% (49/59) response rate. All but one of the items were approved by the participants, with Likert scores 7–9 awarded by >70% of respondents. The final guideline consists of a 14-item checklist.Conclusion: We present the SCARE Guideline, consisting of a 14-item checklist that will improve the reporting quality of surgical case reports.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Setting standards for cystectomy using the British Association of Urological Surgeons Complex Operations Reports, 2016–2018

Objective:To produce comprehensive standards for cystectomy using contemporary data collected across a nation.Patients and methods:Surgical departments upload cystectomy data to the British Association of Urological Surgeons (BAUS) Complex Operations Database. Analysis of 2016–2018 data was performed for all recorded 5288 patients undergoing cystectomy in England. Logistic regression with general linear models was used to assess differences in patient selection between operative modalities. Analysis involved assessment of case selection, operative decisions and outcomes, case volume and pathological outcomes.Results:Using national Hospital Episode Statistics, the BAUS cystectomy dataset was estimated 93% complete. Median age was 70 years (interquartile range 63–75) and 75% were male. Charlson comorbidity index ⩽2 was reported in 87%. Primary treatment of muscle-invasive bladder cancer accounted for 46% of cases. Commonest preoperative disease stages were T2N0 and T1N0 (35% and 25% respectively). Robotic-assisted (RAC), laparoscopic (LC) and open cystectomy (OC) were performed in 41%, 5.5% and 54% of cases respectively. T-stage distribution differed by operative modality. Transfusion rates were 3.7% for RAC, 6.0% for LC and 18% for OC. Increasing positive surgical margin rates were observed with increasing T-stage, up to T3. The conversion-to-open rate for minimally-invasive surgery was 1.7%. Median annual centre and surgeon case volumes were highest for RAC. Median length of stay was 7, 10 and 10 days for RAC, LC and OC respectively. Postoperative histological upstaging was common (33% of cT1, 50% of cT2 cases). Lymph node positive rates were 28% for muscle-invasive bladder cancer.Conclusion:Analysis of this data provides understanding of ‘real-world’ cystectomy practice. Presentation of data specific to operative modality allows surgeons and centres to benchmark their respective practices. These findings offer to enhance patient and public understanding beyond that currently facilitated by publicly-facing information sources. They carry relevance by describing a near-complete and large volume of modern practice in a publicly funded healthcare system.Level of evidence:2bThe article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted versio

A ‘real-world’ standard for radical prostatectomy: Analysis of the British Association of Urological Surgeons Complex Operations Reports, 2016–2018

Objective:To produce comprehensive and detailed benchmarking data allowing surgeons and patients to compare practice against, by using all recorded radical prostatectomies across a 3-year period in England.Patients and methods:The British Association of Urological Surgeons (BAUS) manages the radical prostatectomy (RP) Complex Operations Database. Surgical departments upload data which they can review and amend before lockdown and data cleansing. Analysis of 2016–2018 data held on the BAUS Complex Operations Database was performed for 21,973 patients undergoing RP in England, producing procedure-specific benchmarking data. General linear models were used to assess differences in patient selection between different operative modalities. Analysis involved assessment of case selection, operative decisions and outcomes, case volume and pathological outcomes.Results:Using national Hospital Episode Statistics, the BAUS RP dataset was estimated 91% complete. Median age was 65 and 96% were American Society of Anesthesiologists (ASA) Grades 1–2. Over 80% had RP performed in a high-volume centre (>100 annual RPs) and 88% had Gleason grade group (GGG) ⩾2 disease on biopsy. Robotic-assisted RP (RARP), laparoscopic RP (LRP) and open RP (ORP) were performed in 85%, 7.2% and 7.7% of cases, respectively. Patient and disease characteristics differed across surgical modalities. Transfusion rates were 0.14% in RARP, 0.38% in LRP and 1.8% in ORP. Increased positive surgical margin (PSM) rates were observed with increasing prostate-specific antigen (PSA), GGG and T-stage, with comparable PSM rates across surgical modalities. Lymph node dissection was performed more commonly in high-risk cases (cT3, PSA > 20, GGG ⩾ 4). Pathological upstaging was common. Median length of stay was 1, 2 and 3 days for RARP, LRP and ORP, respectively. ORP had Clavien–Dindo complications ⩾3 and unplanned hospital readmissions.Conclusion:This analysis has enabled the first set of UK national RP standards to be produced allowing procedure, patient and disease-specific national, centre and individual comparisons. The present degree of service centralisation, operative modalities, and specific aspects of surgical practice can be observed.Level of evidence:2bThe article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted versio

Retroperitoneal Robotic Partial Nephrectomy: Systematic Review and Cumulative Analysis of Comparative Outcomes.

OBJECTIVES: To compare the outcomes of retroperitoneal vs transperitoneal approach for robot-assisted partial nephrectomy (RAPN). MATERIALS AND METHODS: A systematic review of the literature was performed through January 2018 using PubMed, Scopus, and Ovid databases. Article selection proceeded according to the search strategy based on PRISMA criteria. Only studies comparing retroperitoneal to transperitoneal approach for RAPN were deemed eligible for inclusion. RESULTS: Seven retrospective case-control studies were identified and included in the analysis, with a total number of 1379 patients (866 for transperitoneal group; 513 for retroperitoneal group). In the retroperitoneal group, tumors were slightly larger [weighted mean difference (WMD): 0.29 cm; 95% confidence interval (CI): 0.04-0.54; p = 0.02], and more frequently located posterior/lateral (odds ratio: 0.61; 95% CI: 0.41-0.90; p = 0.01). In two of the studies only posterior tumors had been included. Both operating time (WMD 20.17 min; 95% CI 6.46-33.88; p = 0.004) and estimated blood loss (WMD 54.57 mL; 95% CI 6.73-102.4; p = 0.03) were significantly lower in the retroperitoneal group. In addition, length of stay was significantly shorter in the retroperitoneal group (WMD 0.46 days; CI 95% 0.15-0.76; p = 0.003). No differences were found regarding overall (p = 0.67) and major (p = 0.82) postoperative complications, warm ischemia time (p = 0.96), and positive surgical margins (p = 0.95). CONCLUSIONS: Retroperitoneal RAPN can offer in select patients similar outcomes to those of the most common transperitoneal RAPN. Furthermore, it may be particularly advantageous for posterior upper pole and perihilar tumors and associated with reduction in operative time and hospital stay. Robotic surgeons should be ideally familiar with both approaches to adapt their surgical strategy to confront renal neoplasms from a position of technical advantage and ultimately optimize outcomes