The Association of Computed Tomography-Assessed Body Composition with Mortality in Patients with Necrotizing Pancreatitis

Background: Identification of patients with necrotizing pancreatitis at high risk for a complicated course could facilitate clinical decision-making. In multiple diseases, several parameters of body composition are associated with impaired outcome, but studies in necrotizing pancreatitis are lacking. Methods: A post hoc analysis was performed in a national prospective cohort of 639 patients with necrotizing pancreatitis. Skeletal muscle mass, skeletal muscle density, and visceral adipose tissue were measured at the third lumbar vertebra level (L3) on contrast-enhanced computed tomography (CT) within 10 days after initial admission and 1 month thereafter. Results: In total, 496 of 639 patients (78%) were included. Overall mortality rate was 14.5%. Skeletal muscle mass and density and visceral adipose tissue on first CT were not independently associated with in-hospital mortality. However, low skeletal muscle density was independently associated with increased mortality in patients ≥65 years (OR 2.54 (95%CI 1.12–5.84, P = 0.028). Skeletal muscle mass and density significantly decreased within 1 month, for both males and females, with a median relative loss of muscle mass of 12.9 and 10.2% (both P < 0.001), respectively. Skeletal muscle density decreased with 7.2 and 7.5% (both P < 0.001) for males and females, respectively. A skeletal muscle density decrease of ≥10% in 1 month was independently associated with in-hospital mortality: OR 5.87 (95%CI 2.09–16.50, P = 0.001). Conclusion: First CT-assessed body composition parameters do not correlate with in-hospital mortality in patients with necrotizing pancreatitis. Loss of skeletal muscle density ≥10% within the first month after initial admission, however, is significantly associated with increased mortality in these patients

Guest-Dependence on Spin Crossover and Thermal Expansion in Nanoporous Coordination Framework Materials

Coordination framework materials have attracted much interest in modern chemistry due to the plethora of properties that they may possess. The frameworks described in this thesis demonstrate the properties of spin crossover, anomalous thermal expansion, and nanoporosity, which enables guest-dependent studies into the material behaviour. The first frameworks described are the [Fe(bpac)M(CN)4]•x(bpac){guest} (M = Ni, Pd, Pt; bpac = 1,4-bis(4′-pyridyl)acetylene) family. The properties of the alcohol-solvated [Fe(bpac)Pd(CN)4]•x(bpac) (x = 0.4, 0.5) frameworks were studied, and the major guest influence on the resulting spin crossover behaviour was determined to be due to an internal pressure effect produced by the kinetic volume and compressibility of the guest. By obtaining a variety of EtOH adsorption isotherms and isobars, a Temperature-Pressure phase diagram of SCO was produced for the [Fe(bpac)Pd(CN)4]•0.4(bpac){EtOH} material. In addition to these frameworks, the behaviour of the [Fe(bpac)(Au(CN)2)2)]•{guest} framework material was also investigated. This framework demonstrated unprecedented multifunctional behaviour, with a synergistic interplay between the spin crossover, lattice structure and host–guest properties. The framework lattice was exceptionally flexible, and displayed a facile ‘scissor-type’ motion of the {Fe(Au(CN)2)2} (4,4) grids. Due to the extreme conformational flexibility of the {Fe(Au(CN)2)2} (4,4)-grids of this material, the [Fe(bpac)(Au(CN)2)2)]•{EtOH} sample displayed colossal uniaxial thermal expansion behaviour. Below the spin transition, the a parameter displayed a maximum thermal expansion coefficient of −1070 × 10−6 K−1, which is an order of magnitude greater than any yet reported for this quantity. Guest-dependent studies on this framework demonstrate the strong effect of guest properties on the conformation of the framework lattice and the spin transition behaviour

Age and prognosis in patients with pancreatic cancer:a population-based study

BACKGROUND: The diagnosis of pancreatic ductal adenocarcinoma (PDAC) has an enormous impact on patients, and even more so if they are of younger age. It is unclear how their treatment and outcome compare to older patients. This study compares clinicopathological characteristics and overall survival (OS) of PDAC patients aged <60 years to older PDAC patients. METHOD: This is a retrospective, population-based cohort study using Netherlands Cancer Registry data of patients diagnosed with PDAC (1 January 2015-31 December 2018). Kaplan-Meier curves and Cox proportional hazards models were used to assess OS. RESULTS: Overall, 10,298 patients were included, of whom 1551 (15%) were <60 years. Patients <60 years were more often male, had better performance status, less comorbidities and less stage I disease, and more often received anticancer treatment (67 vs. 33%, p < 0.001) than older patients. Patients <60 years underwent resection of the tumour more often (22 vs. 14%p < 0.001), more often received chemotherapy, and had a better median OS (6.9 vs. 3.3 months, p < 0.001) compared to older patients. No differences in median OS were demonstrated between both age groups of patients who underwent resection (19.7 vs. 19.4 months, p = 0.123), received chemotherapy alone (7.8 vs. 8.5 months, p = 0.191), or received no anticancer treatment (1.8 vs. 1.9 months, p = 0.600). Patients <60 years with stage-IV disease receiving chemotherapy had a somewhat better OS (7.5 vs. 6.3 months, p = 0.026). CONCLUSION: Patients with PDAC <60 years more often underwent resection despite less stage I disease and had superior OS. Stratified for treatment, however, survival was largely similar

Increased long-term mortality after open colorectal cancer surgery:A multicentre population-based study

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Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancer:Chemotherapy or Chemoradiotherapy?

Worldwide, there is a shifting paradigm from immediate surgery with adjuvant treatment to a neoadjuvant approach for patients with resectable or borderline resectable pancreatic cancer (RPC or BRPC). Comparison of neoadjuvant and adjuvant studies is extremely difficult because of a great difference in patient selection. The evidence from randomized studies shows that overall survival by intention-to-treat improves after neoadjuvant gemcitabine-based chemoradiotherapy or chemotherapy (various regimens), as compared to immediate surgery followed by adjuvant chemotherapy. Radiotherapy appears to play an important role in mediating locoregional effects. Yet, since more effective chemotherapy regimens are currently available, in particular FOLFIRINOX and Gemcitabine/Nab-paclitaxel, these chemotherapy regimens should be investigated in future randomized trials combined with (stereotactic) radiotherapy to further improve outcomes of RPC and BRPC

The effect of remote ischaemic preconditioning on postoperative cardiac and inflammatory biomarkers in pancreatic surgery: a randomized controlled trial

Background: Cardiac and inflammatory biomarkers have been associated with adverse outcome after major abdominal surgery. This study investigated the effect of remote ischaemic preconditioning (RIPC) on perioperative concentrations of high-sensitive cardiac troponin (hs-cTn) T and interleukin (IL) 6. Methods: Adult patients scheduled for elective pancreatic surgery between March 2017 and February 2019 were randomized to either three cycles of upper-limb ischaemia and reperfusion (each 5 min) or a sham procedure before surgery. The primary endpoint was the maximum postoperative hs-cTnT concentration within 48 h after surgery. Secondary endpoints were postoperative myocardial injury (PMI), defined as an absolute increase of hs-cTnT of at least 14 ng/l above baseline concentration, maximum concentration of IL-6 within 48 h after surgery and postoperative complications within 30 days of surgery. Results: Of 99 eligible patients, 46 underwent RIPC and 46 a sham procedure. RIPC did not reduce the maximum hs-cTnT concentration after surgery (12.6 ng/l RIPC, 16.6 ng/l controls, P=0.225), nor did it lessen the incidence of PMI (15/45 RIPC, 18/45 controls, P=0.375). The maximum postoperative IL-6 concentration was 265 pg/ml after RIPC versus 385 pg/ml in controls (P=0.108). Postoperative complications occurred in 23 RIPC and 24 control patients respectively. Conclusions: Remote ischaemic preconditioning did not reduce the maximum postoperative hs-cTnT concentration. Postoperative myocardial injury, IL-6 concentrations and postoperative complications were similar between RIPC patients and controls

Completion pancreatectomy or a pancreas-preserving procedure during relaparotomy for pancreatic fistula after pancreatoduodenectomy:a multicentre cohort study and meta-analysis

Background: Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy.Methods: This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005-2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines.Results: From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P=0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P=0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel-Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84).Conclusion: Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy.Surgical oncolog

Prophylactic abdominal drainage or no drainage after distal pancreatectomy (PANDORINA):a binational multicenter randomized controlled trial

Background: Prophylactic abdominal drainage is current standard practice after distal pancreatectomy (DP), with the aim to divert pancreatic fluid in case of a postoperative pancreatic fistula (POPF) aimed to prevent further complications as bleeding. Whereas POPF after pancreatoduodenectomy, by definition, involves infection due to anastomotic dehiscence, a POPF after DP is essentially sterile since the bowel is not opened and no anastomoses are created. Routine drainage after DP could potentially be omitted and this could even be beneficial because of the hypothetical prevention of drain-induced infections (Fisher, Surgery 52:205-22, 2018). Abdominal drainage, moreover, should only be performed if it provides additional safety or comfort to the patient. In clinical practice, drains cause clear discomfort. One multicenter randomized controlled trial confirmed the safety of omitting abdominal drainage but did not stratify patients according to their risk of POPF and did not describe a standardized strategy for pancreatic transection. Therefore, a large pragmatic multicenter randomized controlled trial is required, with prespecified POPF risk groups and a homogeneous method of stump closure. The objective of the PANDORINA trial is to evaluate the non-inferiority of omitting routine intra-abdominal drainage after DP on postoperative morbidity (Clavien-Dindo score >= 3), and, secondarily, POPF grade B/C. Methods/design: Binational multicenter randomized controlled non-inferiority trial, stratifying patients to high and low risk for POPF grade B/C and incorporating a standardized strategy for pancreatic transection. Two groups of 141 patients (282 in total) undergoing elective DP (either open or minimally invasive, with or without splenectomy). Primary outcome is postoperative rate of morbidity (Clavien-Dindo score >= 3), and the most relevant secondary outcome is grade B/C POPF. Other secondary outcomes include surgical reintervention, percutaneous catheter drainage, endoscopic catheter drainage, abdominal collections (not requiring drainage), wound infection, delayed gastric emptying, postpancreatectomy hemorrhage as defined by the international study group for pancreatic surgery (ISGPS) (Wente et al., Surgery 142:20-5, 2007), length of stay (LOS), readmission within 90 days, in-hospital mortality, and 90-day mortality. Discussion: PANDORINA is the first binational, multicenter, randomized controlled non-inferiority trial with the primary objective to evaluate the hypothesis that omitting prophylactic abdominal drainage after DP does not worsen the risk of postoperative severe complications (Wente etal., Surgery 142:20-5, 2007; Bassi et al., Surgery 161:584-91, 2017). Most of the published studies on drain placement after pancreatectomy focus on both pancreatoduodenectomy and DP, but these two entities present are associated with different complications and therefore deserve separate evaluation (McMillan et al., Surgery 159:1013-22, 2016; Pratt et al., J Gastrointest Surg 10:1264-78, 2006). The PANDORINA trial is innovative since it takes the preoperative risk on POPF into account based on the D-FRS and it warrants homogenous stump closing by using the same graded compression technique and same stapling device (de Pastena et al., Ann Surg 2022; Asbun and Stauffer, Surg Endosc 25:2643-9, 2011)