Ferumoxtran-10-enhanced MRI for pre-operative metastatic lymph node detection in pancreatic, duodenal, or periampullary adenocarcinoma.

OBJECTIVES: To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the pancreas, duodenum, or periampullary region in a node-to-node validation against histopathology. METHODS: Twenty-seven consecutive patients with a resectable pancreatic, duodenal, or periampullary adenocarcinoma were enrolled in this prospective single expert centre study. Ferumoxtran-10-enhanced 3-T MRI was performed pre-surgery. LNs found on MRI were scored for suspicion of metastasis by two expert radiologists using a dedicated scoring system. Node-to-node matching from in vivo MRI to histopathology was performed using a post-operative ex vivo 7-T MRI of the resection specimen. Sensitivity and specificity were calculated using crosstabs. RESULTS: Eighteen out of 27 patients (median age 65 years, 11 men) were included in the final analysis (pre-surgery withdrawal n = 4, not resected because of unexpected metastases peroperatively n = 2, and excluded because of inadequate contrast-agent uptake n = 3). On MRI 453 LNs with a median size of 4.0 mm were detected, of which 58 (13%) were classified as suspicious. At histopathology 385 LNs with a median size of 5.0 mm were found, of which 45 (12%) were metastatic. For 55 LNs node-to-node matching was possible. Analysis of these 55 matched LNs, resulted in a sensitivity and specificity of 83% (95% CI: 36-100%) and 92% (95% CI: 80-98%), respectively. CONCLUSION: USPIO-enhanced MRI is a promising technique to preoperatively detect and localise LN metastases in patients with pancreatic, duodenal, or periampullary adenocarcinoma. CLINICAL RELEVANCE STATEMENT: Detection of (distant) LN metastases with USPIO-enhanced MRI could be used to determine a personalised treatment strategy that could involve neoadjuvant or palliative chemotherapy, guided resection of distant LNs, or targeted radiotherapy. REGISTRATION: The study was registered on clinicaltrials.gov NCT04311047. https://clinicaltrials.gov/ct2/show/NCT04311047?term=lymph+node&cond=Pancreatic+Cancer&cntry=NL&draw=2&rank=1 . KEY POINTS: LN metastases of pancreatic, duodenal, or periampullary adenocarcinoma cannot be reliably detected with current imaging. This technique detected LN metastases with a sensitivity and specificity of 83% and 92%, respectively. MRI with ferumoxtran-10 is a promising technique to improve preoperative staging in these cancers.

Impact of network treatment in patients with resected pancreatic cancer on use and timing of chemotherapy and survival.

BACKGROUND: Centralization of pancreatic cancer surgery aims to improve postoperative outcomes. Consequently, patients with pancreatic cancer may undergo pancreatic surgery in an expert centre and adjuvant chemotherapy in a local hospital (network treatment). The aim of this study was to assess whether network treatment has an impact on time to chemotherapy, failure to complete adjuvant chemotherapy, and survival. Second, whether these parameters varied between pancreatic networks was studied. METHODS: This retrospective study included all patients diagnosed with non-metastatic pancreatic ductal adenocarcinoma who underwent pancreatic surgery and adjuvant chemotherapy, registered in the Netherlands Cancer Registry (2015-2020). Time to chemotherapy was defined as the time between surgery and the start of adjuvant chemotherapy. Completion of adjuvant chemotherapy was defined as the receipt of 12 cycles of FOLFIRINOX or six cycles of gemcitabine. Analysis was performed with linear mixed models and multilevel logistic regression models. Cox regression analyses were performed for survival. RESULTS: In total, 1074 patients were included. Network treatment was observed in 468 patients (43.6 per cent) and was not associated with longer time to chemotherapy (0.77 days, standard error (s.e.) 1.14, P = 0.501), failure to complete adjuvant chemotherapy (odds ratio (OR) = 1.140, 95 per cent c.i. 0.86 to 1.52, P = 0.349), and overall survival (hazards ratio (HR) = 1.04, 95 per cent c.i. 0.88 to 1.22, P = 0.640). Significant variation between the networks was observed for time to chemotherapy (range 40.5-63 days, P < 0.0001) and completion of adjuvant chemotherapy (range 19-52 per cent, P = 0.030). Adjusted for case mix, time to chemotherapy significantly differed between networks. CONCLUSION: In this nationwide analysis, network treatment in patients with resected pancreatic cancer was not associated with longer time to chemotherapy, failure to complete adjuvant chemotherapy, and worse survival. Significant variation between pancreatic cancer networks was found for time to chemotherapy.

Multimodal Prehabilitation in Patients Undergoing Complex Colorectal Surgery, Liver Resection, and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Pilot Study on Feasibility and Potential Efficacy.

BACKGROUND: Surgery for complex primary and metastatic colorectal cancer (CRC), such as liver resection and hyperthermic intraperitoneal chemotherapy (HIPEC), in academic settings has led to improved survival but is associated with complications up to 75%. Prehabilitation has been shown to prevent complications in non-academic hospitals. This pilot study aimed to determine the feasibility and potential efficacy of a multimodal prehabilitation program in patients undergoing surgery in an academic hospital for complex primary and metastatic CRC. METHODS: All patients awaiting complex colorectal surgery, liver resection, or HIPEC from July 2019 until January 2020 were considered potentially eligible. Feasibility was measured by accrual rate, completion rate, adherence to the program, satisfaction, and safety. To determine potential efficacy, postoperative outcomes were compared with a historical control group. RESULTS: Sixteen out of twenty-five eligible patients (64%) commenced prehabilitation, and fourteen patients fully completed the intervention (88%). The adherence rate was 69%, as 11 patients completed >80% of prescribed supervised trainings. No adverse events occurred, and all patients expressed satisfaction with the program. The complication rate was significantly lower in the prehabilitation group (37.5%) than the control group (70.2%, p = 0.020). There was no difference in the type of complications. CONCLUSION: This pilot study illustrates that multimodal prehabilitation is feasible in the majority of patients undergoing complex colorectal cancer, liver resection, and HIPEC in an academic setting.

Self-efficacy and application of skills in the workplace after multidisciplinary trauma masterclass participation: a mixed methods survey and interview study.

PURPOSE: The most complex injuries are usually least often encountered by trauma team members, limiting learning opportunities at work. Identifying teaching formats that enhance trauma skills can guide future curricula. This study evaluates self-assessed technical and nontechnical trauma skills and their integration into novel work situations for multidisciplinary trauma masterclass participants. METHODS: This mixed methods study included participants of a multidisciplinary 3-day trauma masterclass. Ratings of trauma skills were collected through pre- and postcourse questionnaires with 1-year follow-up. Qualitative semi-structured interviews 9 months postcourse focused on the course format and self-perceived association with technical and nontechnical skills applied at work. RESULTS: Response rates of pre- and postcourse questionnaires after 1 day, 3 months, and 1 year were respectively 72% (51/71), 85% (60/71), 34% (24/71), and 14% (10/71). Respondents were surgeons (58%), anesthesiologists (31%), and scrub nurses (11%). Self-efficacy in nontechnical (mean 3.4, SD 0.6 vs. mean 3.8, SD 0.5) and technical (mean 2.9, SD 0.6 vs. mean 3.6, SD 0.6) skills significantly increased postcourse (n = 40, p < 0.001). Qualitative interviews (n = 11) demonstrated that increased self-efficacy in trauma skills was the greatest benefit experienced at work. Innovative application of skills and enhanced reflection demonstrate adaptive expertise. Small-group case discussions and the operative porcine laboratory were considered the most educational working formats. The experienced faculty and unique focus on multidisciplinary teamwork were highly valued. CONCLUSION: Course participants' self-assessed work performance mostly benefited from greater self-efficacy and nontechnical skills. Future trauma curricula should consider aligning the teaching strategies accordingly.

Impact of multicentre diagnostic workup in patients with pancreatic cancer on repeated diagnostic investigations, time-to-diagnosis and time-to-treatment: A nationwide analysis.

BACKGROUND: Due to the centralization of pancreatic surgery, patients with suspected pancreatic cancer may undergo diagnostic workup in both a non-pancreatic centre and a pancreatic centre, i.e. multicentre workup. This retrospective study assessed whether multicentre diagnostic workup is associated with repeated diagnostics, delayed time-to-diagnosis, delayed time-to-treatment, survival and whether variation existed among pancreatic cancer networks. METHODS: This nationwide study included all patients diagnosed with non-metastatic pancreatic ductal adenocarcinoma (PDAC) in 2015, registered by the Netherlands Cancer Registry. A delayed time-to-diagnosis was defined as ≥3 weeks from initial hospital visit to final diagnosis. A delayed time-to-treatment was defined as ≥6 weeks from the first hospital visit to start of first tumour treatment. Multilevel logistic regression analyses and survival analyses were performed. RESULTS: In total, 931 patients with non-metastatic PDAC were included. Overall, 175 patients (19%) underwent a multicentre diagnostic workup, which was significantly associated with repeated diagnostic investigations (OR = 6.31, 95% CI 4.13-9.64, P < 0.0001), a delayed time-to-diagnosis (OR = 2.66 95% CI 1.74-4.06, P < 0.001), and a delayed time-to-treatment (OR = 1.93 95% CI 1.12-3.31, P = 0.02), but not with decreased survival (HR = 1.09 95% CI 0.83-1.44; P = 0.532). Variation in outcomes per network was observed, especially for time-to-treatment, though the ICC was not statistically significant (P = 0.065). CONCLUSION: Multicentre diagnostic workup for patients with PDAC is associated with repeated diagnostic investigations, a delayed time-to-diagnosis and delayed time-to-treatment compared to patients with monocentre workup. To reduce costs and improve treatment times, efforts should be made to improve network coordination, for example via network care pathways.

Comparison of the effectiveness of low pressure pneumoperitoneum with profound muscle relaxation during laparoscopic donor nephrectomy to optimize the quality of recovery during the early post-operative phase: study protocol for a randomized controlled clinical trial.

BACKGROUND: Since technique modifications of laparoscopic donor nephrectomy, e.g. retroperitoneoscopic donor nephrectomy or hand-assistance, have not shown significant benefit regarding safety or improvement of recovery, further research should focus on improving postoperative recovery. The use of low pressure pneumoperitoneum has shown to significantly reduce postoperative pain after laparoscopy. To facilitate the use of low pressure pneumoperitoneum, deep neuromuscular block will be used. METHODS/DESIGN: This trial is a phase IV, single center, double-blind, randomized controlled clinical trial in which 64 patients will be randomized to: low pressure pneumoperitoneum (6 mmHg) and deep neuromuscular block or normal pressure pneumoperitoneum (12 mmHg) and deep neuromuscular block. Deep neuromuscular block is defined as post tetanic count < 5. Primary outcome measurement will be Quality of Recovery-40 questionnaire (overall score) on day 1. DISCUSSION: This study is the first randomized study to assess the combination of low pressure pneumoperitoneum in combination with deep neuromuscular block from a patients' perspective. The study findings may also be applicable for other laparoscopic procedures. TRIAL REGISTRATION: The trial was registered at trials.gov (NCT02146417) in July 2014.

Diclofenac causes anastomotic leakage in the proximal colon but not in the distal colon of the rat.

BACKGROUND: Nonsteroidal anti-inflammatory drugs have been associated with anastomotic leakage. It was studied if diclofenac affects anastomoses differently depending on the location in the gut. METHODS: Ninety-five rats were randomized to 6 groups with an anastomosis in either ileum (IL), proximal colon (PC), or distal colon (DC). Groups IL+ (n = 10), PC+ (n = 30), and DC+ (n = 10) received diclofenac (3 mg/kg/day) from day 0 until sacrifice on day 3. Group PC- (n = 15) did not receive diclofenac. Groups PC1+ and PC2+ (n = 15 each) were given diclofenac from day 1 to 4 and from day 2 to 5. RESULTS: Leak rates were 10/10 in group IL+, 22/30 in PC+, 1/10 in DC+, and 1/15 in PC-. Delayed administration of diclofenac by 1 or 2 days (6/15, P = .05) resulted in reduced leakage rates. Mechanical strength results corresponded with leak rates. CONCLUSIONS: Diclofenac causes leakage of anastomoses in rat IL and PC, but not in the DC. This suggests a role for the ileal and proximal colonic content in diclofenac-induced leakage.

Secondary surgery after sleeve gastrectomy: Roux-en-Y gastric bypass or biliopancreatic diversion with duodenal switch.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has gained popularity as a stand-alone procedure with good short-term results for weight loss. However, in the long-term, weight regain and other complications are reported. Demand for secondary surgery is rising, partly for these reasons. OBJECTIVES: To review the indications and effects of secondary surgery, biliopancreatic diversion with duodenal switch (BPD/DS) versus laparoscopic Roux-en-Y gastric bypass (LRYGB), after LSG. METHODS: Data from all patients who underwent revision of LSG was retrospectively analyzed, concerning data on indications for secondary surgery, weight loss, and complications. RESULTS: 43 Patients underwent secondary surgery after LSG; 25 BPD/DS and 18 LRYGB, respectively. Main indications for secondary surgery were inadequate weight loss (n = 17 [40%]) and weight regain (n = 8 [19%]). For these indications, the median excess weight loss was greater for BPD/DS (59% [range 15-113]) compared to LRYGB (23% [range -49-84]) (P = .008) after 34 months (range 14-79). In case of dysphagia or gastroesophageal reflux disease the complaints resolved after converting to LRYGB. BPD/DS patients were more likely to develop a short-term complication and vitamin deficiencies compared to LRYGB. CONCLUSIONS: Secondary surgery of LSG to BPD/DS or LRYGB is feasible with slightly more complications after BPD/DS. Conversion to LRYGB is preferred in cases of dysphagia or gastroesophageal reflux disease. In cases of weight regain or insufficient weight loss after LSG, patients had better weight loss with a BPD/DS; however, this procedure has the risk of complications, such as severe vitamin deficiencies.

Vitamin and Mineral Deficiencies After Biliopancreatic Diversion and Biliopancreatic Diversion with Duodenal Switch--the Rule Rather than the Exception.

INTRODUCTION: Malabsorptive bariatric procedures, like the biliopancreatic diversion (BPD) and BPD with duodenal switch (BPD/DS), have excellent results in terms of weight loss. However, these malabsorptive techniques are associated with severe malnutrition and vitamin deficiencies. The aim of this study was to evaluate the vitamin and mineral status after BPD and BPD/DS in the long term. METHODS: All patients who underwent BPD or BPD/DS were selected and invited for an additional follow-up (FU) visit, including blood sampling for vitamin and mineral levels. RESULTS: Forty patients completed the blood sampling with a median FU of 42 (range 12-90) months. At that time, all patients used some kind of supplementation. However, 93 % of all patients were diagnosed with a deficiency. There were no significant differences in mean serum level vitamins and minerals between BPD and BPD/DS. Forty-three per cent of the patients were anaemic, and 40 % had an iron deficiency (ID). High deficiency rates for fat-soluble vitamins were present: vitamin A in 28 %, vitamin D in 60 %, vitamin E in 10 % and vitamin K in 60 % of the patients. Hypervitaminosis was found in 43 % of the patients for vitamin B1 and in 50 % for vitamin B6. CONCLUSION: High numbers of vitamin and mineral deficiencies were found after BPD and BPD/DS despite vitamin supplementation. Anaemia, ID and deficiencies for fat-soluble vitamins are frequently diagnosed. Repeated monitoring is necessary to detect deficiencies at an early stage. Taking all of this into consideration, a stringent multivitamin supplementation regimen should be implemented after malabsorptive procedures.

Optimization of vitamin suppletion after Roux-en-Y gastric bypass surgery can lower postoperative deficiencies: a randomized controlled trial.

Iron, vitamin B12, and folic acid deficiencies are among the most common deficiencies occurring after laparoscopic Roux-en-Y gastric bypass (LRYGB). The present study evaluates the effectiveness of a specially designed multivitamin supplement (WLS Forte, FitForMe, Rotterdam, the Netherlands) specifically developed for LRYGB patients.A triple-blind, randomized, 12-month study was conducted comparing WLS forte with a standard multivitamin supplement (sMVS) containing approximately 100% of the recommended daily allowance (RDA) for iron, vitamin B12, and folic acid. WLS Forte contains vitamin B12 14000% RDA, iron 500% RDA, and folic acid 300% RDA.In total, 148 patients (74 in each group) underwent a LRYGB procedure. Baseline characteristics were similar for both groups. Per protocol analysis demonstrated that sMVS treatment was associated with a decline in ferritin (-24.4 ±â€Š70.1 µg/L) and vitamin B12 (-45.9 ±â€Š150.3 pmol/L) over 12 months, whereas in WLS Forte patients, ferritin remained stable (+3.2 ±â€Š93.2 µg/L) and vitamin B12 increased significantly (+55.1 ±â€Š144.2 pmol/L). The number of patients developing ferritin or vitamin B12 deficiency was significantly lower with WLS Forte compared with sMVS (P < 0.05). Iron deficiency (ID) was reduced by 88% after WLS Forte compared with sMVS. Adverse events related to supplement use did not occur.An optimized multivitamin supplement is safe and reduces the development of iron and vitamin B12 deficiencies after LRYGB.