Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA) : study protocol for a randomized controlled trial

Background: Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. Methods/design: DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin >= 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (alpha), 80% power (1-beta), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively. Discussion: The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting.Peer reviewe

Benchmarking of robotic and laparoscopic spleen-preserving distal pancreatectomy by using two different methods

Background: Benchmarking is an important tool for quality comparison and improvement. However, no benchmark values are available for minimally invasive spleen-preserving distal pancreatectomy, either laparoscopically or robotically assisted. The aim of this study was to establish benchmarks for these techniques using two different methods. Methods: Data from patients undergoing laparoscopically or robotically assisted spleen-preserving distal pancreatectomy were extracted from a multicentre database (2006-2019). Benchmarks for 10 outcomes were calculated using the Achievable Benchmark of Care (ABC) and best-patient-in-best-centre methods. Results: Overall, 951 laparoscopically assisted (77.3 per cent) and 279 robotically assisted (22.7 per cent) procedures were included. Using the ABC method, the benchmarks for laparoscopically assisted and robotically assisted spleen-preserving distal pancreatectomy respectively were: 150 and 207 min for duration of operation, 55 and 100 ml for blood loss, 3.5 and 1.7 per cent for conversion, 0 and 1.7 per cent for failure to preserve the spleen, 27.3 and 34.0 per cent for overall morbidity, 5.1 and 3.3 per cent for major morbidity, 3.6 and 7.1 per cent for pancreatic fistula grade B/C, 5 and 6 days for duration of hospital stay, 2.9 and 5.4 per cent for readmissions, and 0 and 0 per cent for 90-day mortality. Best-patient-in-best-centre methodology revealed milder benchmark cut-offs for laparoscopically and robotically assisted procedures, with operating times of 254 and 262.5 min, blood loss of 150 and 195 ml, conversion rates of 5.8 and 8.2 per cent, rates of failure to salvage spleen of 29.9 and 27.3 per cent, overall morbidity rates of 62.7 and 55.7 per cent, major morbidity rates of 20.4 and 14 per cent, POPF B/C rates of 23.8 and 24.2 per cent, duration of hospital stay of 8 and 8 days, readmission rates of 20 and 15.1 per cent, and 90-day mortality rates of 0 and 0 per cent respectively. Conclusion: Two benchmark methods for minimally invasive distal pancreatectomy produced different values, and should be interpreted and applied differently

Robot-assisted versus laparoscopic pancreatoduodenectomy: a pan-European multicenter propensity-matched study

Background: The use of robot-assisted and laparoscopic pancreatoduodenectomy is increasing, yet large adjusted analyses that can be generalized internationally are lacking. This study aimed to compare outcomes after robot-assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy in a pan-European cohort. Methods: An international multicenter retrospective study including patients after robot-assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy from 50 centers in 12 European countries (2009–2020). Propensity score matching was performed in a 1:1 ratio. The primary outcome was major morbidity (Clavien–Dindo ≥III). Results: Among 2,082 patients undergoing minimally invasive pancreatoduodenectomy, 1,006 underwent robot-assisted pancreatoduodenectomy and 1,076 laparoscopic pancreatoduodenectomy. After matching 812 versus 812 patients, the rates of major morbidity (31.9% vs 29.6%; P = .347) and 30-day/in-hospital mortality (4.3% vs 4.6%; P = .904) did not differ significantly between robot-assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy, respectively. Robot-assisted pancreatoduodenectomy was associated with a lower conversion rate (6.7% vs 18.0%; P < .001) and higher lymph node retrieval (16 vs 14; P = .003). Laparoscopic pancreatoduodenectomy was associated with shorter operation time (446 minutes versus 400 minutes; P < .001), and lower rates of postoperative pancreatic fistula grade B/C (19.0% vs 11.7%; P < .001), delayed gastric emptying grade B/C (21.4% vs 7.4%; P < .001), and a higher R0-resection rate (73.2% vs 84.4%; P < .001). Conclusion: This European multicenter study found no differences in overall major morbidity and 30-day/in-hospital mortality after robot-assisted pancreatoduodenectomy compared with laparoscopic pancreatoduodenectomy. Further, laparoscopic pancreatoduodenectomy was associated with a lower rate of postoperative pancreatic fistula, delayed gastric emptying, wound infection, shorter length of stay, and a higher R0 resection rate than robot-assisted pancreatoduodenectomy. In contrast, robot-assisted pancreatoduodenectomy was associated with a lower conversion rate and a higher number of retrieved lymph nodes as compared with laparoscopic pancreatoduodenectomy

Implementation and outcome of minimally invasive pancreatoduodenectomy in Europe: a registry-based retrospective study - a critical appraisal of the first 3 years of the E-MIPS registry

BACKGROUND: International multicenter audit-based studies focusing on the outcome of minimally invasive pancreatoduodenectomy (MIPD) are lacking. The European Registry for Minimally Invasive Pancreatic Surgery (E-MIPS) is the E-AHPBA endorsed registry aimed to monitor and safeguard the introduction of MIPD in Europe. MATERIALS AND METHODS: A planned analysis of outcomes among consecutive patients after MIPD from 45 centers in 14 European countries in the E-MIPS registry (2019-2021). The main outcomes of interest were major morbidity (Clavien-Dindo grade ≥3) and 30-day/in-hospital mortality. RESULTS: Overall, 1336 patients after MIPD were included [835 robot-assisted (R-MIPD) and 501 laparoscopic MIPD (L-MIPD)]. Overall, 20 centers performed R-MIPD, 15 centers L-MIPD, and 10 centers both. Between 2019 and 2021, the rate of centers performing L-MIPD decreased from 46.9 to 25%, whereas for R-MIPD this increased from 46.9 to 65.6%. Overall, the rate of major morbidity was 41.2%, 30-day/in-hospital mortality 4.5%, conversion rate 9.7%, postoperative pancreatic fistula grade B/C 22.7%, and postpancreatectomy hemorrhage grade B/C 10.8%. Median length of hospital stay was 12 days (IQR 8-21). A lower rate of major morbidity, postoperative pancreatic fistula grade B/C, postpancreatectomy hemorrhage grade B/C, delayed gastric emptying grade B/C, percutaneous drainage, and readmission was found after L-MIPD. The number of centers meeting the Miami Guidelines volume cut-off of ≥20 MIPDs annually increased from 9 (28.1%) in 2019 to 12 (37.5%) in 2021 ( P =0.424). Rates of conversion (7.4 vs. 14.8% P <0.001) and reoperation (8.9 vs. 15.1% P <0.001) were lower in centers, which fulfilled the Miami volume cut-off. CONCLUSION: During the first 3 years of the pan-European E-MIPS registry, morbidity and mortality rates after MIPD were acceptable. A shift is ongoing from L-MIPD to R-MIPD. Variations in outcomes between the two minimally invasive approaches and the impact of the volume cut-off should be further evaluated over a longer time period

Robot-Assisted Versus Laparoscopic Distal Pancreatectomy in Patients with Resectable Pancreatic Cancer: An International, Retrospective, Cohort Study

Background: Robot-assisted distal pancreatectomy (RDP) is increasingly used as an alternative to laparoscopic distal pancreatectomy (LDP) in patients with resectable pancreatic cancer but comparative multicenter studies confirming the safety and efficacy of RDP are lacking. Methods: An international, multicenter, retrospective, cohort study, including consecutive patients undergoing RDP and LDP for resectable pancreatic cancer in 33 experienced centers from 11 countries (2010–2019). The primary outcome was R0-resection. Secondary outcomes included lymph node yield, major complications, conversion rate, and overall survival. Results: In total, 542 patients after minimally invasive distal pancreatectomy were included: 103 RDP (19%) and 439 LDP (81%). The R0-resection rate was comparable (75.7% RDP vs. 69.3% LDP, p = 0.404). RDP was associated with longer operative time (290 vs. 240 min, p < 0.001), more vascular resections (7.6% vs. 2.7%, p = 0.030), lower conversion rate (4.9% vs. 17.3%, p = 0.001), more major complications (26.2% vs. 16.3%, p = 0.019), improved lymph node yield (18 vs. 16, p = 0.021), and longer hospital stay (10 vs. 8 days, p = 0.001). The 90-day mortality (1.9% vs. 0.7%, p = 0.268) and overall survival (median 28 vs. 31 months, p = 0.599) did not differ significantly between RDP and LDP, respectively. Conclusions: In selected patients with resectable pancreatic cancer, RDP and LDP provide a comparable R0-resection rate and overall survival in experienced centers. Although the lymph node yield and conversion rate appeared favorable after RDP, LDP was associated with shorter operating time, less major complications, and shorter hospital stay. The specific benefits associated with each approach should be confirmed by multicenter, randomized trials

Qualitative systematic reviews of treatment burden in stroke, heart failure and diabetes - methodological challenges and solutions.

BACKGROUND: Treatment burden can be defined as the self-care practices that patients with chronic illness must perform to respond to the requirements of their healthcare providers, as well as the impact that these practices have on patient functioning and well being. Increasing levels of treatment burden may lead to suboptimal adherence and negative outcomes. Systematic review of the qualitative literature is a useful method for exploring the patient experience of care, in this case the experience of treatment burden. There is no consensus on methods for qualitative systematic review. This paper describes the methodology used for qualitative systematic reviews of the treatment burdens identified in three different common chronic conditions, using stroke as our exemplar. METHODS: Qualitative studies in peer reviewed journals seeking to understand the patient experience of stroke management were sought. Limitations of English language and year of publication 2000 onwards were set. An exhaustive search strategy was employed, consisting of a scoping search, database searches (Scopus, CINAHL, Embase, Medline & PsycINFO) and reference, footnote and citation searching. Papers were screened, data extracted, quality appraised and analysed by two individuals, with a third party for disagreements. Data analysis was carried out using a coding framework underpinned by Normalization Process Theory (NPT). RESULTS: A total of 4364 papers were identified, 54 were included in the review. Of these, 51 (94%) were retrieved from our database search. Methodological issues included: creating an appropriate search strategy; investigating a topic not previously conceptualised; sorting through irrelevant data within papers; the quality appraisal of qualitative research; and the use of NPT as a novel method of data analysis, shown to be a useful method for the purposes of this review. CONCLUSION: The creation of our search strategy may be of particular interest to other researchers carrying out synthesis of qualitative studies. Importantly, the successful use of NPT to inform a coding frame for data analysis involving qualitative data that describes processes relating to self management highlights the potential of a new method for analyses of qualitative data within systematic reviews

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Minimally invasive robot-assisted and laparoscopic distal pancreatectomy in a pan-European registry a retrospective cohort study

BACKGROUND: International guidelines recommend monitoring the use and outcome of minimally invasive pancreatic surgery (MIPS). However, data from prospective international audits on minimally invasive distal pancreatectomy (MIDP) are lacking. This study examined the use and outcome of robot-assisted (RDP) and laparoscopic (LDP) distal pancreatectomy in the E-MIPS registry. PATIENTS AND METHODS: Post-hoc analysis in a prospective audit on MIPS, including consecutive patients undergoing MIDP in 83 centers from 19 European countries (01-01-2019/31-12-2021). Primary outcomes included intraoperative events (grade 1: excessive blood loss, grade 2: conversion/change in operation, grade 3: intraoperative death), major morbidity, and in-hospital/30-day mortality. Multivariable logistic regression analyses identified high-risk groups for intraoperative events. RDP and LDP were compared in the total cohort and high-risk groups. RESULTS: Overall, 1672 patients undergoing MIDP were included; 606 (36.2%) RDP and 1066 (63.8%) LDP. The annual use of RDP increased from 30.5% to 42.6% ( P <0.001). RDP was associated with fewer grade 2 intraoperative events compared with LDP (9.6% vs. 16.8%, P <0.001), with longer operating time (238 vs. 201 min, P <0.001). No significant differences were observed between RDP and LDP regarding major morbidity (23.4% vs. 25.9%, P =0.264) and in-hospital/30-day mortality (0.3% vs. 0.8%, P =0.344). Three high-risk groups were identified; BMI greater than 25 kg/m 2 , previous abdominal surgery, and vascular involvement. In each group, RDP was associated with fewer conversions and longer operative times. CONCLUSION: This European registry-based study demonstrated favorable outcomes for MIDP, with mortality rates below 1%. LDP remains the predominant approach, whereas the use of RDP is increasing. RDP was associated with fewer conversions and longer operative time, including in high-risk subgroups. Future randomized trials should confirm these findings and assess cost differences

Measurements Using Synthetic Packet-Pairs

Abstract- In this paper we describe a passive technique for round trip time (RTT) estimation called Synthetic Packet-Pairs (SPP). Regular and frequent measurement of round trip time (RTT) between points on the Internet is becoming increasingly important for a range of highly interactive real-time applications. Active probing techniques are possible but problematic. The extra packet traffic imposed by active probes along a network path can modify the behaviour of the network under test. In addition, estimated RTT results may be misleading if the network handles active probe packets differently to regular IP packets. In contrast, SPP provides frequently updated RTT estimates using IP traffic already present in the network. SPP estimates the RTT between two measurement points without requiring precise time synchronisation between each point. SPP accurately estimates the RTT experienced by any application’s traffic without needing modifications to the application itself or the routers along the path. In addition, SPP works with applications that do not exhibit symmetric client-server packet exchanges (such as many online multiplayer games) and applications generating IP multicast traffic. Given the popularity of 802.11 Wireless LANs, and their sensitivity to the load imposed by active probing schemes, we experimentally demonstrate the advantages of SPP in a small 802.11b test bed