Exploiting Residue Curve Maps to Assess Thermodynamic Feasibility Boundaries under Uncertain Operating Conditions

The very first step of almost any separation process design procedure is the thermodynamic feasibility analysis. In the case of distillation, residue curve maps (RCMs) represent an essential tool to assess whether the separation is feasible or not. However, the analysis is generally carried out by referring to nominal operating conditions and product purities as specification. This means that, when process parameters are likely to undergo fluctuations, the prediction of the system response is not that obvious. An ABE/W (acetone−butanol−ethanol/water) mixture was then selected as a case study since it allows us to discuss several non-ideal thermodynamic behaviors and because of the renewed interest in biorefinery and sustainable processes during recent years. Residue curve mapping was then exploited to determine the thermodynamic feasibility range for multicomponent distillation processes as well as for distillation trains and process-intensified solutions taking into account both product purity and product recovery specifications. The final product of this study is a thorough procedure to determine the flexibility boundaries of feed and product compositions as well as an immediate and intuitive graphical representation from a binary standard distillation column to a complex multicomponent dividing wall column applicatio

Impact of complications after resection of pancreatic cancer on disease recurrence and survival, and mediation effect of adjuvant chemotherapy:nationwide, observational cohort study

Background: The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator.Methods: This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014-2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated.Results: In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P &lt; 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P &lt; 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (-1.71 (95 per cent c.i. -2.27 to -1.05) and -3.05 (95 per cent c.i. -4.03 to -1.80) respectively) and overall survival (-1.92 (95 per cent c.i. -2.60 to -1.16) and -3.49 (95 per cent c.i. -4.84 to -2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (-5.38 (95 per cent c.i. -9.27 to -1.94)) and overall survival (-6.32 (95 per cent c.i. -10.43 to -1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy.Conclusion: Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adequate treatment of complications and use of neoadjuvant treatment may improve oncological outcomes.</p

Treatment of post-traumatic degenerative changes of the radio-carpal and distal radio-ulnar joints by combining radius, scaphoid, and lunate (RSL) fusion with ulnar head replacement

Distal radial fractures are a common type of fracture. In the case of intra-articular fractures, they often result in post-traumatic arthrosis. The objective of this study is to describe a novel alternative to the established salvage techniques for the treatment of post-traumatic arthrosis of the radio-carpal and distal radio-ulnar joints (DRUJ). Six patients with radio-carpal and DRUJ arthrosis were treated with a combined radius, scaphoid, and lunate (RSL) arthrodesis and as a Herbert ulnar head prosthesis. Follow-up consisted of both radiographic and functional assessments. Functional measurements were noted both pre- and postoperatively. No non-union or pseudoarthrosis was seen; neither did any of the ulnar head prostheses show loosening. Clinical examination showed an improvement in strength, pain, and range of movement, as well as a decrease in disability. Combining RSL arthrodesis with a Herbert ulnar head prosthesis, which deals with pain while retaining partial wrist movement, can be an alternative to established salvage procedures

Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial):design and rationale of a nationwide stepped-wedge cluster-randomized trial

Background: Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection. Methods: This is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide daily multilevel advice on the management of patients after pancreatic resection (i.e. indication for abdominal imaging, antibiotic treatment, percutaneous drainage and removal of abdominal drains). The algorithm is designed to aid early detection and minimally invasive step-up management of postoperative pancreatic fistula. Outcomes of current practice will be compared with outcomes after implementation of the algorithm. The primary outcome is a composite of major complications (i.e. post-pancreatectomy bleeding, new-onset organ failure and death) and will be measured in a sample size of at least 1600 patients undergoing pancreatic resection. Secondary endpoints include the individual components of the primary endpoint and other clinical outcomes, healthcare resource utilization and costs analysis. Follow up will be up to 90 days after pancreatic resection. Discussion: It is hypothesized that a structured nationwide implementation of a dedicated algorithm for early detection and minimally invasive step-up management of postoperative pancreatic fistula will reduce the risk of major complications and death after pancreatic resection, as compared to current practice. Trial registration: Netherlands Trial Register: NL 6671. Registered on 16 December 2017

Impact of Complications After Pancreatoduodenectomy on Mortality, Organ Failure, Hospital Stay, and Readmission Analysis of a Nationwide Audit:Analysis of a Nationwide Audit

OBJECTIVE: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy. SUMMARY OF BACKGROUND DATA: An initial complication may provoke a sequence of adverse events potentially leading to mortality after pancreatoduodenectomy. This study was conducted to aid prioritization of quality improvement initiatives. METHODS: Data from consecutive patients undergoing pancreatoduodenectomy (2014-2017) were extracted from the Dutch Pancreatic Cancer Audit. Population attributable fractions (PAF) were calculated for the association of each complication (ie, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, wound infection, and pneumonia) with each unfavorable outcome [ie, in-hospital mortality, organ failure, prolonged hospital stay (>75th percentile), and unplanned readmission), whereas adjusting for confounders and other complications. The PAF represents the proportion of an outcome that could be prevented if a complication would be eliminated completely. RESULTS: Overall, 2620 patients were analyzed. In-hospital mortality occurred in 95 patients (3.6%), organ failure in 198 patients (7.6%), and readmission in 427 patients (16.2%). Postoperative pancreatic fistula and postpancreatectomy hemorrhage had the greatest independent impact on mortality [PAF 25.7% (95% CI 13.4-37.9) and 32.8% (21.9-43.8), respectively] and organ failure [PAF 21.8% (95% CI 12.9-30.6) and 22.1% (15.0-29.1), respectively]. Delayed gastric emptying had the greatest independent impact on prolonged hospital stay [PAF 27.6% (95% CI 23.5-31.8)]. The impact of individual complications on unplanned readmission was smaller than 11%. CONCLUSION: Interventions focusing on postoperative pancreatic fistula and postpancreatectomy hemorrhage may have the greatest impact on in-hospital mortality and organ failure. To prevent prolonged hospital stay, initiatives should in addition focus on delayed gastric emptying

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): A multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1):a multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

The Feasibility, Proficiency, and Mastery Learning Curves in 635 Robotic Pancreatoduodenectomies Following a Multicenter Training Program: "standing on the Shoulders of Giants"

Objective: To assess the feasibility, proficiency, and mastery learning curves for robotic pancreatoduodenectomy (RPD) in "second-generation" RPD centers following a multicenter training program adhering to the IDEAL framework. Background: The long learning curves for RPD reported from "pioneering" expert centers may discourage centers interested in starting an RPD program. However, the feasibility, proficiency, and mastery learning curves may be shorter in "second-generation" centers that participated in dedicated RPD training programs, although data are lacking. We report on the learning curves for RPD in "second-generation" centers trained in a dedicated nationwide program. Methods: Post hoc analysis of all consecutive patients undergoing RPD in 7 centers that participated in the LAELAPS-3 training program, each with a minimum annual volume of 50 pancreatoduodenectomies, using the mandatory Dutch Pancreatic Cancer Audit (March 2016-December 2021). Cumulative sum analysis determined cutoffs for the 3 learning curves: operative time for the feasibility (1) risk-adjusted major complication (Clavien-Dindo grade ≥III) for the proficiency, (2) and textbook outcome for the mastery, (3) learning curve. Outcomes before and after the cutoffs were compared for the proficiency and mastery learning curves. A survey was used to assess changes in practice and the most valued "lessons learned." Results: Overall, 635 RPD were performed by 17 trained surgeons, with a conversion rate of 6.6% (n=42). The median annual volume of RPD per center was 22.5±6.8. From 2016 to 2021, the nationwide annual use of RPD increased from 0% to 23% whereas the use of laparoscopic pancreatoduodenectomy decreased from 15% to 0%. The rate of major complications was 36.9% (n=234), surgical site infection 6.3% (n=40), postoperative pancreatic fistula (grade B/C) 26.9% (n=171), and 30-day/in-hospital mortality 3.5% (n=22). Cutoffs for the feasibility, proficiency, and mastery learning curves were reached at 15, 62, and 84 RPD. Major morbidity and 30-day/in-hospital mortality did not differ significantly before and after the cutoffs for the proficiency and mastery learning curves. Previous experience in laparoscopic pancreatoduodenectomy shortened the feasibility (-12 RPDs, -44%), proficiency (-32 RPDs, -34%), and mastery phase learning curve (-34 RPDs, -23%), but did not improve clinical outcome. Conclusions: The feasibility, proficiency, and mastery learning curves for RPD at 15, 62, and 84 procedures in "second-generation" centers after a multicenter training program were considerably shorter than previously reported from "pioneering" expert centers. The learning curve cutoffs and prior laparoscopic experience did not impact major morbidity and mortality. These findings demonstrate the safety and value of a nationwide training program for RPD in centers with sufficient volume