MR Elastography of the Pancreas: Bowel Preparation and Repeatability Assessment in Pancreatic Cancer Patients and Healthy Controls.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) stromal viscoelasticity can be measured using MR elastography (MRE). Bowel preparation regimens could affect MRE quality and knowledge on repeatability is crucial for clinical implementation. PURPOSE: To assess effects of four bowel preparation regimens on MRE quality and to evaluate repeatability and differentiate patients from healthy controls. STUDY TYPE: Prospective. POPULATION: 15 controls (41 ± 16 years; 47% female), 16 PDAC patients (one excluded, 66 ± 12 years; 40% female) with 15 age-/sex-matched controls (65 ± 11 years; 40% female). Final sample size was 25 controls and 15 PDAC. FIELD STRENGTH/SEQUENCE: 3-T, spin-echo echo-planar-imaging, turbo spin-echo, and fast field echo gradient-echo. ASSESSMENT: Four different regimens were used: fasting; scopolaminebutyl; drinking 0.5 L water; combination of 0.5 L water and scopolaminebutyl. MRE signal-to-noise ratio (SNR) was compared between all regimens. MRE repeatability (test-retest) and differences in shear wave speed (SWS) and phase angle (ϕ) were assessed in PDAC and controls. Regions-of-interest were defined for tumor, nontumorous (n = 8) tissue in PDAC, and whole pancreas in controls. Two radiologists delineated tumors twice for evaluation of intraobserver and interobserver variability. STATISTICAL TESTS: Repeated measures analysis of variance, coefficients of variation (CoVs), Bland-Altman analysis, (un)paired t-test, Mann-Whitney U-test, and Wilcoxon signed-rank test. P-value<0.05 was considered statistically significant. RESULTS: Preparation regimens did not significantly influence MRE-SNR. Therefore, the least burdensome preparation (fasting only) was continued. CoVs for tumor SWS were: intrasession (12.8%) and intersession (21.7%), and intraobserver (7.9%) and interobserver (10.3%) comparisons. For controls, CoVs were intrasession (4.6%) and intersession (6.4%). Average SWS for tumor, nontumor, and healthy tissue were: 1.74 ± 0.58, 1.38 ± 0.27, and 1.18 ± 0.16 m/sec (ϕ: 1.02 ± 0.17, 0.91 ± 0.07, and 0.85 ± 0.08 rad), respectively. Significant differences were found between all groups, except for ϕ between healthy-nontumor (P = 0.094). DATA CONCLUSION: The proposed bowel preparation regimens may not influence MRE quality. MRE may be able to differentiate between healthy tissue-tumor and tumor-nontumor. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

The Value of Decision Analytical Modeling in Surgical Research: An Example of Laparoscopic Versus Open Distal Pancreatectomy.

OBJECTIVE: To illustrate how decision modeling may identify relevant uncertainty and can preclude or identify areas of future research in surgery. SUMMARY BACKGROUND DATA: To optimize use of research resources, a tool is needed that assists in identifying relevant uncertainties and the added value of reducing these uncertainties. METHODS: The clinical pathway for laparoscopic distal pancreatectomy (LDP) versus open (ODP) for nonmalignant lesions was modeled in a decision tree. Cost-effectiveness based on complications, hospital stay, costs, quality of life, and survival was analyzed. The effect of existing uncertainty on the cost-effectiveness was addressed, as well as the expected value of eliminating uncertainties. RESULTS: Based on 29 nonrandomized studies (3.701 patients) the model shows that LDP is more cost-effective compared with ODP. Scenarios in which LDP does not outperform ODP for cost-effectiveness seem unrealistic, e.g., a 30-day mortality rate of 1.79 times higher after LDP as compared with ODP, conversion in 62.2%, surgically repair of incisional hernias in 21% after LDP, or an average 2.3 days longer hospital stay after LDP than after ODP. Taking all uncertainty into account, LDP remained more cost-effective. Minimizing these uncertainties did not change the outcome. CONCLUSIONS: The results show how decision analytical modeling can help to identify relevant uncertainty and guide decisions for future research in surgery. Based on the current available evidence, a randomized clinical trial on complications, hospital stay, costs, quality of life, and survival is highly unlikely to change the conclusion that LDP is more cost-effective than ODP.

[Is there such a thing as 'fitting evidence'?]. / Bestaat 'passend' bewijs?

The 'levels of evidence' system, which dates back to the 1980s, ranks studies based on the strength of the corresponding study design. Level sets have been developed for studies of interventions, for test accuracy research, and many other forms of clinical research. For some authors, practicing evidence-based medicine has become identical to assigning levels of evidence. This is unfortunate, because more modern systems to come out of the evidence-based medicine movement, such as GRADE, distinguish between the credibility of evidence (which is not just affected by the selected design), the magnitude of the effect, and the applicability of the findings to the clinical question at hand. A new system - :fitting evidence" - has recently been developed by the Dutch Health Care Insurance Board, to evaluate evidence for reimbursement decisions. That system, with an 18-item checklist, looks at threats to the internal validity of studies as well as to the feasibility of randomized comparisons, to see whether it is "fitting" to design a randomized trial. It is unclear yet how these evaluations can and should be combined in the appraisal of the strength of the existing evidence.

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial).

BACKGROUND: For esophageal cancer patients, radical esophagolymphadenectomy is the cornerstone of multimodality treatment with curative intent. Transthoracic esophagectomy is the preferred surgical approach worldwide allowing for en-bloc resection of the tumor with the surrounding lymph nodes. However, the percentage of cardiopulmonary complications associated with the transthoracic approach is high (50 to 70%).Recent studies have shown that robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RATE) is at least equivalent to the open transthoracic approach for esophageal cancer in terms of short-term oncological outcomes. RATE was accompanied with reduced blood loss, shorter ICU stay and improved lymph node retrieval compared with open esophagectomy, and the pulmonary complication rate, hospital stay and perioperative mortality were comparable. The objective is to evaluate the efficacy, risks, quality of life and cost-effectiveness of RATE as an alternative to open transthoracic esophagectomy for treatment of esophageal cancer. METHODS/DESIGN: This is an investigator-initiated and investigator-driven monocenter randomized controlled parallel-group, superiority trial. All adult patients (age ≥ 18 and ≤ 80 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal carcinoma of the intrathoracic esophagus and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 112) with resectable esophageal cancer are randomized in the outpatient department to either RATE (n = 56) or open three-stage transthoracic esophageal resection (n = 56). The primary outcome of this study is the percentage of overall complications (grade 2 and higher) as stated by the modified Clavien-Dindo classification of surgical complications. DISCUSSION: This is the first randomized controlled trial designed to compare RATE with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer. If our hypothesis is proven correct, RATE will result in a lower percentage of postoperative complications, lower blood loss, and shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with open transthoracic esophagectomy. The study started in January 2012. Follow-up will be 5 years. Short-term results will be analyzed and published after discharge of the last randomized patient. TRIAL REGISTRATION: Dutch trial register: NTR3291 ClinicalTrial.gov: NCT01544790.

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): study protocol for a randomized controlled trial.

BACKGROUND: Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice. METHODS/DESIGN: The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs. DISCUSSION: The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2666.

Small gallstones are associated with increased risk of acute pancreatitis: potential benefits of prophylactic cholecystectomy?

OBJECTIVES: Pancreatitis is a severe complication of gallstone disease with considerable mortality. Small gallstones may increase the risk of pancreatitis. Our aims were to evaluate potential association of small stones with pancreatitis and potential beneficial effects of prophylactic cholecystectomy. METHODS: Stone characteristics were determined in patients with biliary pancreatitis (115), obstructive jaundice due to gallstones (103), acute cholecystitis (79), or uncomplicated gallstone disease (231). Sizes and numbers of gallbladder and bile duct stones were determined by ultrasonography and endoscopic retrograde cholangiopancreatography, respectively. Effects of prophylactic cholecystectomy were assessed by decision analyses with a Markov model and Monte Carlo simulations. RESULTS: Patients with pancreatitis or obstructive jaundice had more and smaller gallbladder stones than those with acute cholecystitis or uncomplicated disease (diameters of smallest stones: 3 +/- 1, 4 +/- 1, 8 +/- 1, and 9 +/- 1 mm, respectively, p < 0.01). Bile duct stones were smaller in case of pancreatitis than in obstructive jaundice (diameters of smallest stones: 4 +/- 1 vs 8 +/- 1, p < 0.01). Multivariate analysis identified old age and small stones as independent risk factors for pancreatitis. Decision analysis in a representative group of patients with small (