Accurate staging of non-metastatic colon cancer with CT: the importance of training and practice for experienced radiologists and analysis of incorrectly staged cases.

PURPOSE: To investigate whether locoregional staging of colon cancer by experienced radiologists can be improved by training and feedback to minimize the risk of over-staging into the context of patient selection for neoadjuvant therapy and to identify potential pitfalls of CT staging by characterizing pathologic traits of tumors that remain challenging for radiologists. METHODS: Forty-five cases of stage I-III colon cancer were included in this retrospective study. Five experienced radiologists evaluated the CTs; 5 baseline scans followed by 4 sequential batches of 10 scans. All radiologists were trained after baseline scoring and 2 radiologists received feedback. The learning curve, diagnostic performance, reader confidence, and reading time were evaluated with pathologic staging as reference. Pathology reports and H&E slides of challenging cases were reviewed to identify potential pitfalls. RESULTS: Diagnostic performance in distinguishing T1-2 vs. T3-4 improved significantly after training and with increasing number of reviewed cases. Inaccurate staging was more frequently related to under-staging rather than over-staging. Risk of over-staging was minimized to 7% in batch 3-4. N-staging remained unreliable with an overall accuracy of 61%. Pathologic review identified two tumor characteristics causing under-staging for T-stage in 5/7 cases: (1) very limited invasive part beyond the muscularis propria and (2) mucinous composition of the invading part. CONCLUSION: The high accuracy and specificity of T-staging reached in our study indicate that sufficient training and practice of experienced radiologists can ensure high validity for CT staging in colon cancer to safely use neoadjuvant therapy without significant risk of over-treatment, while N-staging remained unreliable.

Interrater agreement of contouring of the neurovascular bundles and internal pudendal arteries in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.

BACKGROUND AND PURPOSE: Radiation damage to neural and vascular tissue, such as the neurovascular bundles (NVBs) and internal pudendal arteries (IPAs), during radiotherapy for prostate cancer (PCa) may cause erectile dysfunction. Neurovascular-sparing magnetic resonance-guided adaptive radiotherapy (MRgRT) aims to preserve erectile function after treatment. However, the NVBs and IPAs are not routinely contoured in current radiotherapy practice. Before neurovascular-sparing MRgRT for PCa can be implemented, the interrater agreement of the contouring of the NVBs and IPAs on pre-treatment MRI needs to be assessed. MATERIALS AND METHODS: Four radiation oncologists independently contoured the prostate, NVB, and IPA in an unselected consecutive series of 15 PCa patients, on pre-treatment MRI. Dice similarity coefficients (DSCs) for pairwise interrater agreement of contours were calculated. Additionally, the DCS of a subset of the inferior half of the NVB contours (i.e. approximately prostate midgland to apex level) was calculated. RESULTS: Median overall interrater DSC for the left and right NVB was 0.60 (IQR: 0.54 - 0.68) and 0.61 (IQR: 0.53 - 0.69) respectively and for the left and right IPA 0.59 (IQR: 0.53 - 0.64) and 0.59 (IQR: 0.52 - 0.64) respectively. Median overall interrater DSC for the inferior half of the left NVB was 0.67 (IQR: 0.58 - 0.74) and 0.67 (IQR: 0.61 - 0.71) for the right NVB. CONCLUSION: We found that the interrater agreement for the contouring of the NVB and IPA improved with enhancement of the MRI sequence as well as further training of the raters. The agreement was best in the subset of the inferior half of the NVB, where a good agreement is clinically most relevant for neurovascular-sparing MRgRT for PCa.

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial.

BACKGROUND: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. METHODS: The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. DISCUSSION: The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. TRIAL REGISTRATION: Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018.

The additive value of restaging-CT during neoadjuvant chemotherapy for gastric cancer.

INTRODUCTION: Computed tomography (CT) is used for restaging of gastric cancer patients during neoadjuvant chemotherapy (NAC). The treatment strategy could be altered after detection of distant interval metastases, possibly leading to a reduction in unnecessary chemotherapy cycles, its related toxicity, and surgical procedures. The aim of this study was to evaluate the additive value of restaging-CT during NAC in guiding clinical decision making in gastric cancer. MATERIALS AND METHODS: This retrospective, multicenter cohort study identified all patients with surgically resectable gastric adenocarcinoma (cT1-4a-x, N0-3-x, M0-x), who started NAC with curative intent. Restaging-CT was performed after 2 out of 3 cycles of NAC. The primary outcome was treatment alterations made based on restaging-CT by a multidisciplinary tumor board. Confirmation of metastases was obtained by surgery or biopsy. RESULTS: Between 2007 and 2015, CT-restaging was performed in 122 out of 152 included patients and timed after 2 cycles (n = 76) or after 3 cycles (n = 46) of NAC. Restaging-CT revealed a metastasis in 1 out of 122 restaged patients (1%) after which surgical resection was omitted, whereas 4 patients (3%) with distant interval metastases were not identified by restaging-CT and underwent a futile laparotomy. In 5 out of 76 patients (7%) disease progression was detected while undergoing NAC, leading to omission of the 3rd cycle of chemotherapy. CONCLUSION: The additive value of restaging-CT during NAC in gastric cancer is limited in guiding clinical decision making and therefore not recommended. Further studies may identify subgroups that may benefit of alternative diagnostic modalities.

Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study).

BACKGROUND: Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. METHODS: This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. DISCUSSION: In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. TRIAL REGISTRATION: NCT03208621 . This trial was registered prospectively on June 30, 2017.

Evaluation of motion correction for clinical dynamic contrast enhanced MRI of the liver.

Motion correction of 4D dynamic contrast enhanced MRI (DCE-MRI) series is required for diagnostic evaluation of liver lesions. The registration, however, is a challenging task, owing to rapid changes in image appearance. In this study, two different registration approaches are compared; a conventional pairwise method applying mutual information as metric and a groupwise method applying a principal component analysis based metric, introduced by Huizinga et al (2016). The pairwise method transforms the individual 3D images one by one to a reference image, whereas the groupwise registration method computes the metric on all the images simultaneously, exploiting the temporal information, and transforms all 3D images to a common space. The performance of the two registration methods was evaluated using 70 clinical 4D DCE-MRI series with the focus on the liver. The evaluation was based on the smoothness of the time intensity curves in lesions, lesion volume change after deformation and the smoothness of spatial deformation. Furthermore, the visual quality of subtraction images (pre-contrast image subtracted from the post contrast images) before and after registration was rated by two observers. Both registration methods improved the alignment of the DCE-MRI images in comparison to the non-corrected series. Furthermore, the groupwise method achieved better temporal alignment with smoother spatial deformations than the pairwise method. The quality of the subtraction images was graded satisfactory in 32% of the cases without registration and in 77% and 80% of the cases after pairwise and groupwise registration, respectively. In conclusion, the groupwise registration method outperforms the pairwise registration method and achieves clinically satisfying results. Registration leads to improved subtraction images.

The peri-esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging.

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri-esophageal fascias have not been described and it is unclear whether this layer can be visualized by non-invasive imaging. This study aimed to provide a comprehensive description of the peri-esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2-weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri-esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion-triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named 'aorto-esophageal ligament' and the layer connecting aorta to the right pleural reflection 'aorto-pleural ligament'. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named 'peri-esophageal compartment' and the posterior compartment 'para-aortic compartment'. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long-standing paradigm that no such structure exists. A comprehensive, detailed description of the peri-esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized in vivo by MRI.

Vasodilatory capacity of the cerebral vasculature in patients with carotid artery stenosis.

BACKGROUND AND PURPOSE: Impairment of the cerebral autoregulation is an important predictor of TIA and stroke in patients with an ICA stenosis. The autoregulative status can be assessed directly by measuring the vasodilatory capacity of the cerebral arteries. The aim of our study was to investigate the vasodilatory capacity of the proximal and distal cerebral vasculature in patients with an ICA stenosis and healthy control subjects by combining MRA with an acetazolamide provocation challenge. MATERIALS AND METHODS: Fourteen functionally independent patients (mean age, 67.2 ± 8.7 years) with a symptomatic ICA stenosis and 19 healthy controls (mean age, 63.1 ± 7.2 years) were included. MRA was performed before and 20 minutes after intravenous administration of acetazolamide. The vasodilatory capacity of 11 proximal and distal cerebral vessels was assessed by measuring the increase in vessel diameter after acetazolamide. RESULTS: In the hemisphere ipsilateral to the ICA stenosis, there was no increase in diameter after acetazolamide, whereas a significant increase was measured in the contralateral hemisphere for the A1 and A2 segments of the ACA, the pericallosal artery, and the BA. A significant diameter increase was measured in all except 1 vessel of the controls. The vasodilatory capacity was significantly lower ipsilateral to the ICA stenosis compared with the A1 segment of the ACA and the P2 segment of the PCA in the controls. CONCLUSIONS: MRA combined with an acetazolamide provocation challenge can measure normal and impaired vasodilatory capacity of the cerebral vasculature.

[Epidemic of methicillin-resistant Staphylococcus aureus due to the transfer of 2 Dutch burn patients from a hospital outside of the Netherlands; who suffers the consequences?]. / Epidemie van meticillineresistente Staphylococcus aureus door overname uit een buitenlands ziekenhuis van 2 Nederlandse brandwondpatiënten; wie draagt de gevolgen?

Two burns patients who were transferred to the Central Military Hospital Utrecht from a foreign hospital, were found to be colonised with MRSA. During their 5-week hospitalisation, 21 healthcare workers and one patient became colonised with the same MRSA strain, despite isolation precautions. The department was closed for 29 days; 96 admissions were cancelled and 1411 screening cultures for MRSA were performed. Colonised healthcare workers were temporarily unable to work and additional costs were incurred for disposables and cleaning procedures. The resultant bill for this outbreak was approximately [symbol: see text] 122,500. MRSA outbreaks occur in hospitals with some degree of regularity, but the strong dispersal during this epidemic was exceptional. The transfer of possible MRSA-colonised patients from hospitals outside of the Netherlands sometimes faces opposition due to the considerable demands it makes on a hospital's personnel, organisation and finances. If this were to be compensated, then the currently successful Dutch MRSA policy could be coupled with a willingness to accept patients from hospitals outside of the Netherlands.

Radiofrequency ablation treatment of refractory carcinoid hepatic metastases.

BACKGROUND: Our institution has experienced excellent success using hepatic artery embolization for treating symptoms and slowing tumor progression for patients with unresectable hepatic metastases for carcinoid tumors. Our previous treatment strategies used hepatic artery embolization alone, examining control of symptoms and dependence on octreotide therapy. However, some patients exhibit hepatic metastases that are unresponsive to embolization. This report describes the use of radiofrequency ablation (RFA) as salvage treatment for these refractory metastases. METHODS: Thirteen patients with unresectable bilobar hepatic metastases from biochemically confirmed carcinoid tumors were treated with selective hepatic artery embolization using Lipiodol/Gelfoam between 1994 and 2000. Three patients developed symptoms resistant to embolization treatment resulting from progression of existing metastases or development of new metastases. These patients underwent surgical exploration and intraoperative ultrasound of their refractory lesions, followed by treatment with RFA. Tumor size, symptoms of carcinoid syndrome, and octreotide requirements were monitored postoperatively. RESULTS: Median follow-up for the three patients treated with RFA was 6 months. During the first 3-month interval following RFA, all three patients demonstrated decrease in the size of treated lesions. Using our previously developed symptom scoring system, all three patients demonstrated decreased symptoms following treatment. One patient was able to discontinue octreotide treatment, and the other two patients required decrease octreotide dosages. CONCLUSIONS: This study demonstrates that utilization of RFA treatment for carcinoid metastases refractory to hepatic artery embolization may represent a useful adjunct for symptomatic control, decreased octreotide dependence, and slowing of disease progression.