Surgical Management and Considerations for Patients with Localized High-Risk Prostate Cancer.

OPINION STATEMENT: Localized high-risk (HR) prostate cancer (PCa) is a heterogenous disease state with a wide range of presentations and outcomes. Historically, non-surgical management with radiotherapy and androgen deprivation therapy was the treatment option of choice. However, surgical resection with radical prostatectomy (RP) and pelvic lymph node dissection (PLND) is increasingly utilized as a primary treatment modality for patients with HRPCa. Recent studies have demonstrated that surgery is an equivalent treatment option in select patients with the potential to avoid the side effects from androgen deprivation therapy and radiotherapy combined. Advances in imaging techniques and biomarkers have also improved staging and patient selection for surgical resection. Advances in robotic surgical technology grant surgeons various techniques to perform RP, even in patients with HR disease, which can reduce the morbidity of the procedure without sacrificing oncologic outcomes. Clinical trials are not only being performed to assess the safety and oncologic outcomes of these surgical techniques, but to also evaluate the role of surgical resection as a part of a multimodal treatment plan. Further research is needed to determine the ideal role of surgery to potentially provide a more personalized and tailored treatment plan for patients with localized HR PCa.

The ultrastructure of infectious L-type bovine spongiform encephalopathy prions constrains molecular models.

Bovine spongiform encephalopathy (BSE) is a prion disease of cattle that is caused by the misfolding of the cellular prion protein (PrPC) into an infectious conformation (PrPSc). PrPC is a predominantly α-helical membrane protein that misfolds into a ß-sheet rich, infectious state, which has a high propensity to self-assemble into amyloid fibrils. Three strains of BSE prions can cause prion disease in cattle, including classical BSE (C-type) and two atypical strains, named L-type and H-type BSE. To date, there is no detailed information available about the structure of any of the infectious BSE prion strains. In this study, we purified L-type BSE prions from transgenic mouse brains and investigated their biochemical and ultrastructural characteristics using electron microscopy, image processing, and immunogold labeling techniques. By using phosphotungstate anions (PTA) to precipitate PrPSc combined with sucrose gradient centrifugation, a high yield of proteinase K-resistant BSE amyloid fibrils was obtained. A morphological examination using electron microscopy, two-dimensional class averages, and three-dimensional reconstructions revealed two structural classes of L-type BSE amyloid fibrils; fibrils that consisted of two protofilaments with a central gap and an average width of 22.5 nm and one-protofilament fibrils that were 10.6 nm wide. The one-protofilament fibrils were found to be more abundant compared to the thicker two-protofilament fibrils. Both fibrillar assemblies were successfully decorated with monoclonal antibodies against N- and C-terminal epitopes of PrP using immunogold-labeling techniques, confirming the presence of polypeptides that span residues 100-110 to 227-237. The fact that the one-protofilament fibrils contain both N- and C-terminal PrP epitopes constrains molecular models for the structure of the infectious conformer in favour of a compact four-rung ß-solenoid fold.

A prostate biopsy risk calculator based on MRI: development and comparison of the Prospective Loyola University multiparametric MRI (PLUM) and Prostate Biopsy Collaborative Group (PBCG) risk calculators.

OBJECTIVES: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC. PATIENTS AND METHODS: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts. RESULTS: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05). CONCLUSIONS: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa.

Improved functional status in patients undergoing cement and rebar reconstruction with total hip arthroplasty for uncontained metastatic tumors of the acetabulum.

BACKGROUND AND OBJECTIVE: Metastatic cancer of the acetabulum can produce marked pain and disability for patients. Several reconstruction techniques for such lesions have been described, with variable outcomes. The purpose of this study was to determine functional outcomes and complication rate for patients undergoing cement rebar reconstruction using posterior column screws with total hip arthroplasty for large, uncontained lesions of the acetabulum. METHODS: Twenty-two consecutive patients who underwent cement rebar reconstruction with posterior column screws and total hip arthroplasty for metastatic tumors of the acetabulum between 2014 and 2017 were identified. All cases were reviewed for patient demographics, surgical parameters, implant survival, complications, and functional status following these procedures. RESULTS: There was a significant increase in the proportion of patients able to ambulate post-surgery (95.5%) compared with presurgery (22.7%) (p < 0.001). Mean musculoskeletal tumor society score postoperatively was 17.9 (60%). Average operative time was 174 min and average estimated blood loss was 689 mL. Seven patients required an intraoperative or postoperative blood transfusion. Three patients had postoperative complications (14%), two of whom required revision (9%). CONCLUSION: Reconstruction using cement rebar with posterior column screws and total hip arthroplasty is a safe, reproducible approach that may greatly improve functional outcomes with a low rate of intraoperative or postoperative complications.

Survival and failure modes of the Compress® spindle and expandable distal femur endoprosthesis among pediatric patients: A multi-institutional study.

BACKGROUND: Expandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage System expandable distal femur endoprosthesis have not been reported. METHODS: We conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis. RESULTS: Thirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI, 5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvage failures requiring 63 unplanned surgeries. Periprosthetic joint infection occurred in six patients (16.7%). Limb preservation rate was 91% at 10 years. CONCLUSIONS: There is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Development of a real-world database for asthma and COPD: The SingHealth-Duke-NUS-GSK COPD and Asthma Real-World Evidence (SDG-CARE) collaboration.

PURPOSE: The SingHealth-Duke-GlaxoSmithKline COPD and Asthma Real-world Evidence (SDG-CARE) collaboration was formed to accelerate the use of Singaporean real-world evidence in research and clinical care. A centerpiece of the collaboration was to develop a near real-time database from clinical and operational data sources to inform healthcare decision making and research studies on asthma and chronic obstructive pulmonary disease (COPD). METHODS: Our multidisciplinary team, including clinicians, epidemiologists, data scientists, medical informaticians and IT engineers, adopted the hybrid waterfall-agile project management methodology to develop the SingHealth COPD and Asthma Data Mart (SCDM). The SCDM was developed within the organizational data warehouse. It pulls and maps data from various information systems using extract, transform and load (ETL) pipelines. Robust user testing and data verification was also performed to ensure that the business requirements were met and that the ETL pipelines were valid. RESULTS: The SCDM includes 199 data elements relevant to asthma and COPD. Data verification was performed and found the SCDM to be reliable. As of December 31, 2019, the SCDM contained 36,407 unique patients with asthma and COPD across the spectrum from primary to tertiary care in our healthcare system. The database updates weekly to add new data of existing patients and to include new patients who fulfil the inclusion criteria. CONCLUSIONS: The SCDM was systematically developed and tested to support the use RWD for clinical and health services research in asthma and COPD. This can serve as a platform to provide research and operational insights to improve the care delivered to our patients.

Incorporating artificial intelligence in urology: Supervised machine learning algorithms demonstrate comparative advantage over nomograms in predicting biochemical recurrence after prostatectomy.

OBJECTIVE: After radical prostatectomy (RP), one-third of patients will experience biochemical recurrence (BCR), which is associated with subsequent metastasis and cancer-specific mortality. We employed machine learning (ML) algorithms to predict BCR after RP, and compare them with traditional regression models and nomograms. METHODS: Utilizing a prospective Uro-oncology registry, 18 clinicopathological parameters of 1130 consecutive patients who underwent RP (2009-2018) were recorded, yielding over 20,000 data points for analysis. The data set was split into a 70:30 ratio for training and validation. Three ML models: Naïve Bayes (NB), random forest (RF), and support vector machine (SVM) were studied, and compared with traditional regression models and nomograms (Kattan, CAPSURE, John Hopkins [JHH]) to predict BCR at 1, 3, and 5 years. RESULTS: Over a median follow-up of 70.0 months, 176 (15.6%) developed BCR, at a median time of 16.0 months (interquartile range [IQR]: 11.0-26.0). Multivariate analyses demonstrated strongest association of BCR with prostate-specific antigen (PSA) (p: 0.015), positive surgical margins (p < 0.001), extraprostatic extension (p: 0.002), seminal vesicle invasion (p: 0.004), and grade group (p < 0.001). The 3 ML models demonstrated good prediction of BCR at 1, 3, and 5 years, with the area under curves (AUC) of NB at 0.894, 0.876, and 0.894, RF at 0.846, 0.875, and 0.888, and SVM at 0.835, 0.850, and 0.855, respectively. All models demonstrated (1) robust accuracy (>0.82), (2) good calibration with minimal overfitting, (3) longitudinal consistency across the three time points, and (4) inter-model validity. The ML models were comparable to traditional regression analyses (AUC: 0.797, 0.848, and 0.862) and outperformed the three nomograms: Kattan (AUC: 0.815, 0.798, and 0.799), JHH (AUC: 0.820, 0.757, and 0.750) and CAPSURE nomograms (AUC: 0.706, 0.720, and 0.749) (p < 0.001). CONCLUSION: Supervised ML algorithms can deliver accurate performances and outperform nomograms in predicting BCR after RP. This may facilitate tailored care provisions by identifying high-risk patients who will benefit from multimodal therapy.

Multi-institutional analysis of clinical and imaging risk factors for detecting clinically significant prostate cancer in men with PI-RADS 3 lesions.

BACKGROUND: Most Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions do not contain clinically significant prostate cancer (CSPCa; grade group ≥2). This study was aimed at identifying clinical and magnetic resonance imaging (MRI)-derived risk fac- tors that predict CSPCa in men with PI-RADS 3 lesions. METHODS: This study analyzed the detection of CSPCa in men who underwent MRI-targeted biopsy for PI-RADS 3 lesions. Multivariable logistic regression models with goodness-of-fit testing were used to identify variables associated with CSPCa. Receiver operating curves and decision curve analyses were used to estimate the clinical utility of a predictive model. RESULTS: Of the 1784 men reviewed, 1537 were included in the training cohort, and 247 were included in the validation cohort. The 309 men with CSPCa (17.3%) were older, had a higher prostate-specific antigen (PSA) density, and had a greater likelihood of an anteriorly located lesion than men without CSPCa (p < .01). Multivariable analysis revealed that PSA density (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.85; p < .01), age (OR, 1.05; 95% CI, 1.02-1.07; p < .01), and a biopsy-naive status (OR, 1.83; 95% CI, 1.38-2.44) were independently associated with CSPCa. A prior negative biopsy was negatively associated (OR, 0.35; 95% CI, 0.24-0.50; p < .01). The application of the model to the validation cohort resulted in an area under the curve of 0.78. A predicted risk threshold of 12% could have prevented 25% of biopsies while detecting almost 95% of CSPCas with a sensitivity of 94% and a specificity of 34%. CONCLUSIONS: For PI-RADS 3 lesions, an elevated PSA density, older age, and a biopsy-naive status were associated with CSPCa, whereas a prior negative biopsy was negatively associated. A predictive model could prevent PI-RADS 3 biopsies while missing few CSPCas. LAY SUMMARY: Among men with an equivocal lesion (Prostate Imaging-Reporting and Data System 3) on multiparametric magnetic resonance imaging (mpMRI), those who are older, those who have a higher prostate-specific antigen density, and those who have never had a biopsy before are at higher risk for having clinically significant prostate cancer (CSPCa) on subsequent biopsy. However, men with at least one negative biopsy have a lower risk of CSPCa. A new predictive model can greatly reduce the need to biopsy equivocal lesions noted on mpMRI while missing only a few cases of CSPCa.

Systematic versus Targeted Magnetic Resonance Imaging/Ultrasound Fusion Prostate Biopsy among Men with Visible Lesions.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion-guided biopsy may improve prostate cancer (PCa) detection and reduce grade misclassification. We compared PCa detection rates on systematic, magnetic resonance imaging-targeted, and combined biopsy with evaluation of important subgroups. MATERIALS AND METHODS: Men with clinical suspicion of harboring PCa from 2 institutions with visible Prostate Imaging-Reporting and Data System (PI-RADSTMv2) lesions receiving mpMRI-US fusion-guided prostate biopsy were included (2015-2020). Detection of PCa was categorized by grade group (GG). Clinically-significant PCa (csPCa) was defined as ≥GG2. Patients were stratified by biopsy setting and PI-RADS. RESULTS: Of 1,236 patients (647 biopsy-naïve) included, 626 (50.6%) harbored PCa and 412 (33.3%) had csPCa on combined biopsy. Detection of csPCa was 27.9% vs 23.3% (+4.6%) and GG1 PCa was 11.3% vs 17.8% (-6.5%) for targeted vs systematic cores. Benefit in csPCa detection was higher in the prior negative than biopsy-naïve setting (+7.8% [p <0.0001] vs +1.7% [p=0.3]) while reduction in GG1 PCa detection remained similar (-5.6% [p=0.0002] vs -7.3% [p=0.0001]). Targeted biopsy showed increased csPCa detection for PI-RADS 5, decrease in GG1 for PI-RADS 3, and both for PI-RADS 4 relative to systematic biopsy. Combined biopsy detected more csPCa (+10.0%) and slightly fewer GG1 PCa (-0.5%) compared to systematic alone. Upgrading to ≥GG2 by targeted biopsy occurred in 9.8% with no cancer and 23.6% with GG1 on systematic biopsy. CONCLUSIONS: Combined biopsy doubled the benefit of targeted biopsy alone in detection of csPCa without increasing GG1 PCa diagnoses relative to systematic biopsy. Utility of targeted biopsy was higher in the prior negative biopsy cohort, but advantages of combined biopsy were maintained regardless of biopsy history.

Impact of Circular, Waste-Heat Reuse Pathways on PM2.5-Air Quality, CO2 Emissions, and Human Health in India: Comparison with Material Exchange Potential.

India is home to 1.3 billion people who are exposed to some of the highest levels of ambient air pollution in the world. In addition, India is one of the fastest-growing carbon-emitting countries. Here, we assess how two strategies to reuse waste-heat from coal-fired power plants and other large sources would impact PM2.5-air quality, human health, and CO2 emissions in 2015 and a future year, 2050, using varying levels of policy adoption (current regulations, proposed single-sector policies, and ambitious single-sector strategies). We find that power plant and industrial waste-heat reuse as input to district heating systems (DHSs), a novel, multisector strategy to reduce local biomass burning for heating emissions, can offset 71.3-85.2% of residential heating demand in communities near a power plant (9.3-12.4% of the nationwide heating demand) with the highest benefits observed during winter months in areas with collocated industrial activity and higher residential heating demands (e.g., New Delhi). Utilizing waste-heat to generate electricity via organic Rankine cycles (ORCs) can generate an additional 22 (11% of total coal-fired generating capacity), 41 (8%), 32 (13%), and 6 (5%) GW of electricity capacity in the 2015, 2050-current regulations, 2050-single-sector, and 2050-ambitious-single-sector scenarios, respectively. Emission estimates utilizing these strategies were input to the GEOS-Chem model, and population-weighted, simulated PM2.5 showed small improvements in the DHS (0.2-0.4%) and ORC (0.3-3.4%) scenarios, where the minimal DHS PM2.5-benefit is attributed to the small contribution of biomass burning for heating to nationwide PM2.5 emissions (much of the biomass burning activity is for cooking). The PM2.5 reductions lead to ∼130-36,000 mortalities per year avoided among the scenarios, with the largest health benefits observed in the ORC scenarios. Nationwide CO2 emissions reduced <0.04% by DHSs but showed larger reductions using ORCs (1.9-7.4%). Coal fly-ash as material exchange in cement and brick production was assessed, and capacity exists to completely reutilize unused fly-ash toward cement and brick production in each of the scenarios.

Intravascular Ultrasound for the Evaluation and Management of Retroperitoneal, Genitourinary Malignancies.

PURPOSE OF REVIEW: Herein we provide a review of intravascular ultrasound (IVUS) and its ability to assist in the evaluation and surgical management of advanced retroperitoneal, genitourinary tumors. RECENT FINDINGS: Advanced retroperitoneal tumors such as advanced renal cell carcinoma, bulky retroperitoneal lymphadenopathy associated with advanced testicular carcinoma, large adrenal tumors, and retroperitoneal sarcomas can invade, compress, or distort vascular anatomy making surgical resection challenging and high risk. Intravascular ultrasonography is commonly used by vascular and cardiothoracic surgery to provide a real time assessment of vascular invasion, compression, and aberrant anatomy to assist with pre-operative and/or intraoperative decision-making. However, the application of this technology to assist with cancer surgery has been limited. The use of intravascular ultrasound prior to radical, extirpative, retroperitoneal surgery involving large vessels can aid in the planning and execution of such challenging operations.

Stereotactic body radiation therapy with simultaneous integrated boost for prostate cancer: does MRI-targeted biopsy alter the boost field?

INTRODUCTION: We aim to investigate if the addition of MRI-US fusion biopsy (FB) can aid in radiation planning and alter the boost field in cases of stereotactic body radiation therapy (SBRT) for prostate cancer with a simultaneous integrated boost (SIB) to a magnetic resonance imaging (MRI)-defined intraprostatic lesion. MATERIALS AND METHODS: Patients undergoing SBRT with SIB for biopsy-proven prostatic adenocarcinoma and a pre-radiation MRI were retrospectively reviewed. 36.25 Gy in 5 fractions was delivered to entire prostate along with SIB of 40 Gy to an MRI-defined intraprostatic lesion. Demographic, radiation planning details, and post-procedural outcomes were compared between patients undergoing systematic transrectal ultrasound (TRUS) biopsy followed by MRI to those undergoing an MRI followed by a FB prior to radiation planning. RESULTS: Forty-three patients underwent systematic TRUS biopsy followed by MRI and 46 patients underwent FB prior to radiation planning. Patients undergoing systematic TRUS biopsy had a smaller prostate volume when compared to the FB cohort (37.58 ± 13.78 versus 50.28 ± 26.76 cc, p = 0.007). No differences in prostate planning target volume (PTVprostate) and boost volume (PTVboost) were noted, but those undergoing TRUS biopsy prior to MRI had a higher integrated boost volume density (IBVD = PTVboost/total prostate volume) (0.16 ± 0.09 versus 0.13 ± 0.06, p = 0.045). No differences were observed in genitourinary or gastrointestinal toxicity rates. CONCLUSIONS: Compared to systematic TRUS biopsy, implementation of prebiopsy prostate MRI and FB allows for safe and feasible SBRT in patients with significantly larger prostate volumes without increasing SIB cancer-directed treatment volumes, oncologic outcomes, quality of life measures, or treatment-related toxicities.

Perioperative Outcomes of Single vs Multi-Port Robotic Assisted Radical Prostatectomy: A Single Institutional Experience.

PURPOSE: Surgical approach to radical prostatectomy has evolved due to advances in minimally invasive surgery, with most contemporary approaches involving the Si or Xi multi-port robotic systems. U.S. Food and Drug Administration approval of the single-port da Vinci® SP robotic platform has led to a few case series suggesting its safety and feasibility for robotic assisted radical prostatectomy in patients with prostate cancer. However, there are no established data on perioperative outcomes comparing single-port to multi-port robotic approaches to robot-assisted radical prostatectomy. MATERIALS AND METHODS: All patients who underwent robot-assisted radical prostatectomy by 2 urological surgeons at our institution between October 2018 and June 2019 were retrospectively reviewed. The available preoperative clinical and demographic data, operative parameters and postoperative outcomes were collected and analyzed using the t-test, chi-square and Fisher exact statistical measures. RESULTS: Overall 95 patients who underwent robot-assisted radical prostatectomy at our institution were included in our study, with 47 single-port and 48 multi-port. Preoperative clinical parameters including age, body mass index, prior abdominal surgery and biopsy grade group were similar across the 2 groups. No differences in estimated blood loss (169.2±114.2 vs 157.7±125.4 ml, p=0.64), operative time (255.9±44.1 vs 274.7±50.4 minutes, p=0.06), length of hospitalization (1.1±0.5 vs 1.4±1.1 days, p=0.17), rate of perioperative inpatient Clavien-Dindo complications 2 or greater (4.3% vs 6.3% p=0.66) and rate of positive pathological margin (21.3% vs 27.1%, p=0.51) were noted comparing the single-port and multi-port approaches, respectively. CONCLUSIONS: The single-port robotic system allows a feasible approach to robot-assisted radical prostatectomy and has operative and perioperative outcomes comparable to those of the well accepted multi-port robotic approach.

Early warning score validation methodologies and performance metrics: a systematic review.

BACKGROUND: Early warning scores (EWS) have been developed as clinical prognostication tools to identify acutely deteriorating patients. In the past few years, there has been a proliferation of studies that describe the development and validation of novel machine learning-based EWS. Systematic reviews of published studies which focus on evaluating performance of both well-established and novel EWS have shown conflicting conclusions. A possible reason is the heterogeneity in validation methods applied. In this review, we aim to examine the methodologies and metrics used in studies which perform EWS validation. METHODS: A systematic review of all eligible studies from the MEDLINE database and other sources, was performed. Studies were eligible if they performed validation on at least one EWS and reported associations between EWS scores and inpatient mortality, intensive care unit (ICU) transfers, or cardiac arrest (CA) of adults. Two reviewers independently did a full-text review and performed data abstraction by using standardized data-worksheet based on the TRIPOD (Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) checklist. Meta-analysis was not performed due to heterogeneity. RESULTS: The key differences in validation methodologies identified were (1) validation dataset used, (2) outcomes of interest, (3) case definition, time of EWS use and aggregation methods, and (4) handling of missing values. In terms of case definition, among the 48 eligible studies, 34 used the patient episode case definition while 12 used the observation set case definition, and 2 did the validation using both case definitions. Of those that used the patient episode case definition, 18 studies validated the EWS at a single point of time, mostly using the first recorded observation. The review also found more than 10 different performance metrics reported among the studies. CONCLUSIONS: Methodologies and performance metrics used in studies performing validation on EWS were heterogeneous hence making it difficult to interpret and compare EWS performance. Standardizing EWS validation methodology and reporting can potentially address this issue.

Evidence Versus Practice in Early Drain Removal After Pancreatectomy.

BACKGROUND: Early drain removal when postoperative day (POD) one drain fluid amylase (DFA) was ≤5000 U/L reduced complications in a previous randomized controlled trial. We hypothesized that most surgeons continue to remove drains late and this is associated with inferior outcomes. METHODS: We assessed the practice of surgeons in a prospectively maintained pancreas surgery registry to determine the association between timing of drain removal with demographics, comorbidities, and complications. We selected patients with POD1 DFA ≤5000 U/L and excluded those without drains, and subjects without data on POD1 DFA or timing of drain removal. Early drain removal was defined as ≤ POD5. RESULTS: Two hundred and forty four patients met inclusion criteria. Only 90 (37%) had drains removed early. Estimated blood loss was greater in the late removal group (190 mL versus 100 mL, P = 0.005) and pathological findings associated with soft gland texture were more frequent (97 [63%] versus 35 [39%], P < 0.0001). Patients in the late drain removal group had more complications (84 [55%] versus 30 [33%], P = 0.001) including pancreatic fistula (55 [36%] versus 4 [4%], P < 0.0001), delayed gastric emptying (27 [18%] versus 3 [3%], P = 0.002), and longer length of stay (7 d versus 5 d, P < 0.0001). In subset analysis for procedure type, complications and pancreatic fistula remained significant for both pancreatoduodenectomy and distal pancreatectomy. CONCLUSIONS: Despite level one data suggesting improved outcomes with early removal when POD1 DFA is ≤ 5000 U/L, experienced pancreas surgeons more frequently removed drains late. This practice was associated with known risk factors (estimated blood loss, soft pancreas) and may be associated with inferior outcomes suggesting potential for improvement.

A Prospective Randomized Multicenter Trial of Distal Pancreatectomy With and Without Routine Intraperitoneal Drainage.

OBJECTIVE: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications. BACKGROUND: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported. METHODS: Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy. RESULTS: A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores. CONCLUSIONS: This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.