Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases.

BACKGROUND: We developed models for tumor segmentation to automate the assessment of total tumor volume (TTV) in patients with colorectal liver metastases (CRLM). METHODS: In this prospective cohort study, pre- and post-systemic treatment computed tomography (CT) scans of 259 patients with initially unresectable CRLM of the CAIRO5 trial (NCT02162563) were included. In total, 595 CT scans comprising 8,959 CRLM were divided into training (73%), validation (6.5%), and test sets (21%). Deep learning models were trained with ground truth segmentations of the liver and CRLM. TTV was calculated based on the CRLM segmentations. An external validation cohort was included, comprising 72 preoperative CT scans of patients with 112 resectable CRLM. Image segmentation evaluation metrics and intraclass correlation coefficient (ICC) were calculated. RESULTS: In the test set (122 CT scans), the autosegmentation models showed a global Dice similarity coefficient (DSC) of 0.96 (liver) and 0.86 (CRLM). The corresponding median per-case DSC was 0.96 (interquartile range [IQR] 0.95-0.96) and 0.80 (IQR 0.67-0.87). For tumor segmentation, the intersection-over-union, precision, and recall were 0.75, 0.89, and 0.84, respectively. An excellent agreement was observed between the reference and automatically computed TTV for the test set (ICC 0.98) and external validation cohort (ICC 0.98). In the external validation, the global DSC was 0.82 and the median per-case DSC was 0.60 (IQR 0.29-0.76) for tumor segmentation. CONCLUSIONS: Deep learning autosegmentation models were able to segment the liver and CRLM automatically and accurately in patients with initially unresectable CRLM, enabling automatic TTV assessment in such patients. RELEVANCE STATEMENT: Automatic segmentation enables the assessment of total tumor volume in patients with colorectal liver metastases, with a high potential of decreasing radiologist's workload and increasing accuracy and consistency. KEY POINTS: • Tumor response evaluation is time-consuming, manually performed, and ignores total tumor volume. • Automatic models can accurately segment tumors in patients with colorectal liver metastases. • Total tumor volume can be accurately calculated based on automatic segmentations.

Cost of Follow Up After Endovascular Abdominal Aortic Aneurysm Repair in Patients With an Initial Post-Operative Computed Tomography Angiogram Without Abnormalities.

OBJECTIVE: The Observing a Decade of Yearly Standardised Surveillance in EVAR patients with Ultrasound or CT Scan (ODYSSEUS) study was conducted to assess differences in outcomes of patients with continued or discontinued yearly follow up after endovascular abdominal aortic aneurysm repair (EVAR). Earlier results of this study showed that discontinued follow up was not associated with poor outcomes. Therefore, an incremental cost analysis and budget impact analysis of de-implementation of yearly imaging following EVAR was performed. METHODS: In total, 1 596 patients from the ODYSSEUS study were included. The expected cost savings were assessed if yearly imaging was reduced in patients with a post-operative computed tomography angiogram without abnormalities made around 30 days after EVAR. Costs were derived from the Dutch costs manual, benchmark cost prices, and literature review. Costs were expressed in euros (€) and displayed at 2019 prices. Sensitivity analysis was performed by varying costs. RESULTS: A difference of 24% in cost was found between patients with continued and discontinued imaging follow up. The cost per patient was €1 935 in the continued group vs. €1 603 per patient in the discontinued group at five years post-EVAR, with a mean difference of €332 (95% bias corrected and accelerated bootstrap confidence interval -741 to 114). De-implementation of yearly imaging would result in an annual nationwide cost saving of €678 471. Sensitivity analysis with variation in adherence rates, imaging, or secondary intervention costs resulted in a saving of at least €271 388 per year. CONCLUSION: This study provided an in depth analysis of hospital costs for post-EVAR patients in the Netherlands with a modest impact on the Dutch healthcare budget.

Interobserver Variability in CT-based Morphologic Tumor Response Assessment of Colorectal Liver Metastases.

Purpose To evaluate interobserver variability in the morphologic tumor response assessment of colorectal liver metastases (CRLM) managed with systemic therapy and to assess the relation of morphologic response with gene mutation status, targeted therapy, and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 measurements. Materials and Methods Participants with initially unresectable CRLM receiving different systemic therapy regimens from the randomized, controlled CAIRO5 trial (NCT02162563) were included in this prospective imaging study. Three radiologists independently assessed morphologic tumor response on baseline and first follow-up CT scans according to previously published criteria. Two additional radiologists evaluated disagreement cases. Interobserver agreement was calculated by using Fleiss κ. On the basis of the majority of individual radiologic assessments, the final morphologic tumor response was determined. Finally, the relation of morphologic tumor response and clinical prognostic parameters was assessed. Results In total, 153 participants (median age, 63 years [IQR, 56-71]; 101 men) with 306 CT scans comprising 2192 CRLM were included. Morphologic assessment performed by the three radiologists yielded 86 (56%) agreement cases and 67 (44%) disagreement cases (including four major disagreement cases). Overall interobserver agreement between the panel radiologists on morphology groups and morphologic response categories was moderate (κ = 0.53, 95% CI: 0.48, 0.58 and κ = 0.54, 95% CI: 0.47, 0.60). Optimal morphologic response was particularly observed in patients treated with bevacizumab (P = .001) and in patients with RAS/BRAF mutation (P = .04). No evidence of a relationship between RECIST 1.1 and morphologic response was found (P = .61). Conclusion Morphologic tumor response assessment following systemic therapy in participants with CRLM demonstrated considerable interobserver variability. Keywords: Tumor Response, Observer Performance, CT, Liver, Metastases, Oncology, Abdomen/Gastrointestinal Clinical trial registration no. NCT02162563 Supplemental material is available for this article. © RSNA, 2022.

Cost Effectiveness of Endovascular Revascularisation vs. Exercise Therapy for Intermittent Claudication Due to Iliac Artery Obstruction.

OBJECTIVE: To compare cost effectiveness of endovascular revascularisation (ER) and supervised exercise therapy (SET) as primary treatment for patients with intermittent claudication (IC) due to iliac artery obstruction. METHODS: Cost utility analysis from a restricted societal perspective and time horizon of 12 months. Patients were included in a multicentre randomised controlled trial (SUPER study, NCT01385774, NTR2648) which compared effectiveness of ER and SET. Health status and health related quality of life (HRQOL) were measured using the Euroqol 5 dimensions 3 levels (EQ5D-3L) and VascuQol-25-NL. Incremental costs were determined per allocated treatment and use of healthcare during follow up. Effectiveness of treatment was determined in quality adjusted life years (QALYs). The difference between treatment groups was calculated by an incremental cost utility ratio (ICER). RESULTS: Some 240 patients were included, and complete follow up was available for 206 patients (ER 111 , SET 95). The mean costs for patients allocated to ER were €4 031 and €2 179 for SET, a mean difference of €1 852 (95% bias corrected and accelerated [bca] bootstrap confidence interval 1 185 - 2 646). The difference in QALYs during follow up was 0.09 (95% bcaCI 0.04 - 0.13) in favour of ER. The ICER per QALY was €20 805 (95% bcaCI 11 053 - 45 561). The difference in VascuQol sumscore was 0.64 (95% bcaCI 0.39 - 0.91), again in favour of ER. CONCLUSION: ER as a primary treatment, results in slightly better health outcome and higher QALYs and HRQOL during 12 months of follow up. Although these differences are statistically significant, clinical relevance must be discussed due to the small differences and relatively high cost of ER as primary treatment.

Wound infection following implant removal of foot, ankle, lower leg or patella; a protocol for a multicenter randomized controlled trial investigating the (cost-)effectiveness of 2 g of prophylactic cefazolin compared to placebo (WIFI-2 trial).

BACKGROUND: Elective implant removal (IR) after fracture fixation is one of the most common procedures within (orthopedic) trauma surgery. The rate of surgical site infections (SSIs) in this procedure is quite high, especially below the level of the knee. Antibiotic prophylaxis is not routinely prescribed, even though it has proved to lower SSI rates in other (orthopedic) trauma surgical procedures. The primary objective is to study the effectiveness of a single intravenous dose of 2 g of cefazolin on SSIs after IR following fixation of foot, ankle and/or lower leg fractures. METHODS: This is a multicenter, double-blind placebo controlled trial with a superiority design, including adult patients undergoing elective implant removal after fixation of a fracture of foot, ankle, lower leg or patella. Exclusion criteria are: an active infection, current antibiotic treatment, or a medical condition contraindicating prophylaxis with cefazolin including allergy. Patients are randomized to receive a single preoperative intravenous dose of either 2 g of cefazolin or a placebo (NaCl). The primary analysis will be an intention-to-treat comparison of the proportion of patients with a SSI at 90 days after IR in both groups. DISCUSSION: If 2 g of prophylactic cefazolin proves to be both effective and cost-effective in preventing SSI, this would have implications for current guidelines. Combined with the high infection rate of IR which previous studies have shown, it would be sufficiently substantiated for guidelines to suggest protocolled use of prophylactic antibiotics in IR of foot, ankle, lower leg or patella. Trial registration Nederlands Trial Register (NTR): NL8284, registered on 9th of January 2020, https://www.trialregister.nl/trial/8284.

Volar Plate Fixation in Adults with a Displaced Extra-Articular Distal Radial Fracture Is Cost-Effective.

BACKGROUND: To our knowledge, a health economic evaluation of volar plate fixation compared with plaster immobilization in patients with a displaced extra-articular distal radial fracture has not been previously conducted. METHODS: A cost-effectiveness analysis of a multicenter randomized controlled trial was performed. Ninety patients were randomly assigned to volar plate fixation or plaster immobilization. The use of resources per patient was documented prospectively for up to 12 months after randomization and included direct medical, direct non-medical, and indirect non-medical costs due to the distal radial fracture and the received treatment. RESULTS: The mean quality-adjusted life-years (QALYs) at 12 months were higher in patients treated with volar plate fixation (mean QALY difference, 0.16 [bias-corrected and accelerated 95% confidence interval (CI), 0.07 to 0.27]). (The 95% CIs throughout are bias-corrected and accelerated.) In addition, the mean total costs per patient were lower in patients treated with volar plate fixation (mean difference, -$299 [95% CI, -$1,880 to $1,024]). The difference in costs per QALY was -$1,838 (95% CI, -$12,604 to $9,787), in favor of volar plate fixation. In a subgroup analysis of patients who had paid employment, the difference in costs per QALY favored volar plate fixation by -$7,459 (95% CI, -$23,919 to $3,233). CONCLUSIONS: In adults with a displaced extra-articular distal radial fracture, volar plate fixation is a cost-effective intervention, especially in patients who had paid employment. Besides its better functional results, volar plate fixation is less expensive and provides a better quality of life than plaster immobilization. LEVEL OF EVIDENCE: Economic Level I. See Instructions for Authors for a complete description of levels of evidence.

The effect of on-demand vs deep neuromuscular relaxation on rating of surgical and anaesthesiologic conditions in patients undergoing thoracolaparoscopic esophagectomy (DEPTH trial): study protocol for a randomized controlled trial.

BACKGROUND: Deep muscle relaxation has been shown to facilitate operating conditions during laparoscopic surgery. Minimally invasive esophageal surgery is a high-risk procedure in which the use of deep neuromuscular block (NMB) may improve conditions in the thoracic phase as well. Neuromuscular antagonists can be given on demand or by continuous infusion (deep NMB). However, the positioning of the patient often hampers train-of-four (TOF) monitoring. A continuous infusion thus may result in a deep NMB at the end of surgery. The use of neostigmine not only is insufficient for reversing deep NMB but also may be contraindicated for this procedure because of its cholinergic effects. Sugammadex is an effective alternative but is rather expensive. This study aims to evaluate the use of deep versus on-demand NMB on operating, anaesthesiologic conditions, and costs in patients undergoing a two- or three-phase thoracolaparoscopic esophageal resection. METHODS/DESIGN: We will conduct a single-center randomized controlled double-blinded intervention study. Sixty-six patients undergoing a thoracolaparoscopic esophageal resection will be included. Patients will receive either continuous infusion of rocuronium 0.6 mg/kg per hour (group 1) or continuous infusion of NaCl 0.9 % 0.06 ml/kg per hour (group 2). In both groups, on-demand boluses of rocuronium can be given (open-label design). The primary aim of this study is to compare the surgical rating scale (SRS) during the abdominal phase. Main secondary aims are to evaluate SRS during the thoracic phase, to evaluate anesthesiologic conditions, and to compare costs (in euros) associated with use of rocuronium, sugammadex, and duration of surgery. DISCUSSION: This study is the first to evaluate the benefits of deep neuromuscular relaxation on surgical and anaesthesiologic conditions during thoracolaparoscopic esophageal surgery. This surgical procedure is unique because it consists of both an abdominal phase and a thoracic phase taking place in different order depending on the subtype of surgery (a two- or three-stage transthoracic esophagectomy). In addition, possible benefits associated with deep NMB, such as decrease in operating time, will be weighed against costs. TRIAL REGISTRATION: European Clinical Trials Database (EudraCT) number: 2014-002147-18 (obtained 19 May 2014) ClinicalTrials.gov: NCT02320734 (obtained 18 Dec. 2014).

The global burden of diabetes and its complications: an emerging pandemic.

The number of patients with type 2 diabetes is increasing rapidly in both developed and developing countries around the world. The emerging pandemic is driven by the combined effects of population ageing, rising levels of obesity and inactivity, and greater longevity among patients with diabetes that is attributable to improved management. The vascular complications of type 2 diabetes account for the majority of the social and economic burden among patients and society more broadly. This review summarizes the burden of type 2 diabetes, impaired glucose tolerance, and their vascular complications. It is projected that by 2025 there will be 380 million people with type 2 diabetes and 418 million people with impaired glucose tolerance. Diabetes is a major global cause of premature mortality that is widely underestimated, because only a minority of persons with diabetes dies from a cause uniquely related to the condition. Approximately one half of patients with type 2 diabetes die prematurely of a cardiovascular cause and approximately 10% die of renal failure. Global excess mortality attributable to diabetes in adults was estimated to be 3.8 million deaths.