Interobserver agreement of transvaginal ultrasound and magnetic resonance imaging in local staging of cervical cancer.

OBJECTIVE: To evaluate interobserver agreement for the assessment of local tumor extension in women with cervical cancer, among experienced and less experienced observers, using transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI). METHODS: The TVS observers were all gynecologists and consultant ultrasound specialists, six with and seven without previous experience in cervical cancer imaging. The MRI observers were five radiologists experienced in pelvic MRI and four less experienced radiology residents without previous experience in MRI of the pelvis. The less experienced TVS observers and all MRI observers underwent a short basic training session in the assessment of cervical tumor extension, while the experienced TVS observers received only a written directive. All observers were assigned the same images from cervical cancer patients at all stages (n = 60) and performed offline evaluation to answer the following three questions: (1) Is there a visible primary tumor? (2) Does the tumor infiltrate > ⅓ of the cervical stroma? and (3) Is there parametrial invasion? Interobserver agreement within the four groups of observers was assessed using Fleiss kappa (κ) with 95% CI. RESULTS: Experienced and less experienced TVS observers, respectively, had moderate interobserver agreement with respect to tumor detection (κ (95% CI), 0.46 (0.40-0.53) and 0.46 (0.41-0.52)), stromal invasion > ⅓ (κ (95% CI), 0.45 (0.38-0.51) and 0.53 (0.40-0.58)) and parametrial invasion (κ (95% CI), 0.57 (0.51-0.64) and 0.44 (0.39-0.50)). Experienced MRI observers had good interobserver agreement with respect to tumor detection (κ (95% CI), 0.70 (0.62-0.78)), while less experienced MRI observers had moderate agreement (κ (95% CI), 0.51 (0.41-0.62)), and both experienced and less experienced MRI observers, respectively, had good interobserver agreement regarding stromal invasion (κ (95% CI), 0.80 (0.72-0.88) and 0.71 (0.61-0.81)) and parametrial invasion (κ (95% CI), 0.69 (0.61-0.77) and 0.71 (0.61-0.81)). CONCLUSIONS: We found interobserver agreement for the assessment of local tumor extension in patients with cervical cancer to be moderate for TVS and moderate-to-good for MRI. The level of interobserver agreement was associated with experience among TVS observers only for parametrial invasion. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Designing interactions by control of protein-ligand complex conformation: tuning arginine-arene interaction geometry for enhanced electrostatic protein-ligand interactions.

We investigated galectin-3 binding to 3-benzamido-2-O-sulfo-galactoside and -thiodigalactoside ligands using a combination of site-specific mutagenesis, X-ray crystallography, computational approaches, and binding thermodynamics measurements. The results reveal a conformational variability in a surface-exposed arginine (R144) side chain in response to different aromatic C3-substituents of bound galactoside-based ligands. Fluorinated C3-benzamido substituents induced a shift in the side-chain conformation of R144 to allow for an entropically favored electrostatic interaction between its guanidine group and the 2-O-sulfate of the ligand. By contrast, binding of ligands with non-fluorinated substituents did not trigger a conformational change of R144. Hence, a sulfate-arginine electrostatic interaction can be tuned by the choice of ligand C3-benzamido structures to favor specific interaction modes and geometries. These results have important general implications for ligand design, as the proper choice of arginine-aromatic interacting partners opens up for ligand-controlled protein conformation that in turn may be systematically exploited in ligand design.

Multidetector CT of pancreatic ductal adenocarcinoma: Effect of tube voltage and iodine load on tumour conspicuity and image quality.

OBJECTIVES: To compare a low-tube-voltage with or without high-iodine-load multidetector CT (MDCT) protocol with a normal-tube-voltage, normal-iodine-load (standard) protocol in patients with pancreatic ductal adenocarcinoma (PDAC) with respect to tumour conspicuity and image quality. METHODS: Thirty consecutive patients (mean age: 66 years, men/women: 14/16) preoperatively underwent triple-phase 64-channel MDCT examinations twice according to: (i) 120-kV standard protocol (PS; 0.75 g iodine (I)/kg body weight, n = 30) and (ii) 80-kV protocol A (PA; 0.75 g I/kg, n = 14) or protocol B (PB; 1 g I/kg, n = 16). Two independent readers evaluated tumour delineation and image quality blindly for all protocols. A third reader estimated the pancreas-to-tumour contrast-to-noise ratio (CNR). Statistical analysis was performed with the Chi-square test. RESULTS: Tumour delineation was significantly better in PB and PA compared with PS (P = 0.02). The evaluation of image quality was similar for the three protocols (all, P > 0.05). The highest CNR was observed with PB and was significantly better compared to PA (P = 0.02) and PS (P = 0.0002). CONCLUSION: In patients with PDAC, a low-tube-voltage, high-iodine-load protocol improves tumour delineation and CNR leading to higher tumour conspicuity compared to standard protocol MDCT. KEY POINTS: • Low-tube-voltage high-iodine-load MDCT improves pancreatic cancer conspicuity compared to a standard protocol. • The pancreas-to-tumour attenuation difference increases significantly by reducing the tube voltage. • The radiation exposure dose decreases by reducing the tube voltage.

Evaluation of a new system for chest tomosynthesis: aspects of image quality of different protocols determined using an anthropomorphic phantom.

OBJECTIVE: To compare the image quality obtained with the different protocols in a new chest digital tomosynthesis (DTS) system. METHODS: A chest phantom was imaged with chest X-ray equipment with DTS. 10 protocols were used, and for each protocol, nine acquisitions were performed. Four observers visually rated the quality of the reconstructed section images according to pre-defined quality criteria in four different classes. The data were analysed with visual grading characteristics (VGC) analysis, using the vendor-recommended protocol [12-s acquisition time, source-to-image distance (SID) 180 cm] as reference, and the area under the VGC curve (AUCVGC) was determined for each protocol and class of criteria. RESULTS: Protocols with a smaller swing angle resulted in a lower image quality for the classes of criteria "disturbance" and "homogeneity in nodule" but a higher image quality for the class "structure". The class "demarcation" showed little dependency on the swing angle. All protocols but one (6.3 s, SID 130 cm) obtained an AUCVGC significantly <0.5 (indicating lower quality than reference) for at least one class of criteria. CONCLUSION: The study indicates that the DTS protocol with 6.3 s yields image quality similar to that obtained with the vendor-recommended protocol (12 s) but with the clinically important advantage for patients with respiratory impairment of a shorter acquisition time. ADVANCES IN KNOWLEDGE: The study demonstrates that the image quality may be strongly affected by the choice of protocol and that the vendor-recommended protocol may not be optimal.

Gastrointestinal neuroendocrine tumors (NETs): new diagnostic and therapeutic challenges.

This paper summarizes the current understanding of the biology of somatostatin receptor (sst), role of immunotherapy in neuroendocrine tumor (NET), new agents for PPRT, and methods to assess response and clinical benefit in NET. One of the most interesting aspects of sst biology is the recent discovery of truncated variants of the sst5 receptor subtype with unique tissue distribution and response to somatostatin (SST). These truncated receptors are associated with bad patient prognosis, decreased response to SST analogs, and may be new targets for diagnoses and treatment. IFN remains a cost-effective agent, particularly in classic mid gut carcinoids, and there is interest to continue examining immunotherapy's in this disease. PRRT remains a key strategy for treatment and imaging. In addition to the classic agents, there are a series of new agents targeting other receptors such as the incretin receptors (GLP-1R; GIPR) and other G-protein coupled receptors with great potential. With regards to therapy monitoring, the most commonly used criteria are Response Criteria Evaluation in Solid Tumors (RECIST). However, for different reasons, these criteria are not very useful in NET. Incorporation of other criteria such as Choi as well as functional imaging assessment with PET would be of great interest in this area.

Computed tomography staging of pancreatic cancer: a validation study addressing interobserver agreement.

BACKGROUND/OBJECTIVES: Ductal adenocarcinoma in the head of the pancreas (PDAC) is usually unresectable at the time of diagnosis due to the involvement of the peripancreatic vessels. Various preoperative classification algorithms have been developed to describe the relationship of the tumor to these vessels, but most of them lack a surgically based approach. We present a CT-based classification algorithm for PDAC based on surgical resectability principles with a focus on interobserver variability. METHODS: Thirty patients with PDAC undergoing pancreaticoduodenectomy were examined by using a standard CT protocol. Nine radiologists, representing three different levels of expertise, evaluated the CT examinations and the tumors were classified into four categories (A-D) according to the proposed system. For the interobserver agreement, the Intraclass Correlation Coefficient (ICC) was estimated. RESULTS: The overall ICC was 0.94 and the ICCs among the trainees, experienced radiologists, and experts were 0.85, 0.76, and 0.92, respectively. All tumors classified as category A1 showed no signs of vascular invasion at surgery. In category A2, 40% of the tumors had corresponding infiltration and required resection of the superior mesenteric vein/portal vein (SMV/PV). One of two tumors in category B2 and two of three in category C required SMV/PV resection. All six patients in category D had both arterial and venous involvement. CONCLUSION: There is almost perfect agreement among radiologists with different levels of expertise in regards to the local staging of PDAC. For tumors in a more advanced preoperative category, an increased risk for vascular involvement was noticed at surgery.

Methodical aspects of text testing in a driving simulator.

A test with 30 test persons was conducted in a driving simulator. The test was a concept exploration and comparison of existing user interaction technologies for text message handling with focus on traffic safety and experience (technology familiarity and learning effects). Focus was put on methodical aspects how to measure and how to analyze the data. Results show difficulties with the eye tracking system (calibration etc.) per se, and also include the subsequent raw data preparation. The physical setup in the car where found important for the test completion.

The initial change in tumor size predicts response and survival in patients with metastatic colorectal cancer treated with combination chemotherapy.

BACKGROUND: To determine whether the change in tumor diameters at the first follow-up computed tomography (CT) examination after baseline examination (first change) correlates with outcome in patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy. PATIENTS AND METHODS: The first change was analyzed in a multicenter randomized phase III trial (Nordic VI, N = 567) comparing first-line irinotecan with either bolus or infused 5-fluorouracil. Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses after correction for guarantee-time bias were carried out to evaluate correlations between first change, objective response according to RECIST 1.0, progression-free survival (PFS), and overall survival (OS). RESULTS: The hazard ratios for PFS and OS decreased along with first change. A decrease between 10% and <30%, albeit RECIST does not regard this as a partial response, was a positive prognostic factor for PFS and OS. Patients who had new lesions or unequivocal progression of nonmeasurable lesions had a worse prognosis than those with only an increase in size of >20%. CONCLUSIONS: The change in tumor size at the first follow-up CT is strongly prognostic for PFS and OS in mCRC.

Metomidate-based imaging of adrenal masses.

Due to broader use of conventional imaging techniques, adrenal tumors are detected with increasing frequency comprising a wide variety of different tumor entities. Despite improved conventional imaging techniques, a significant number of adrenal lesions remain that cannot be easily determined. A particular diagnostic challenge are lesions in patients with known extra-adrenal malignancy because these patients frequently harbor adrenal metastases. Furthermore, adrenal masses with low fat content and no detectable hormone excess are difficult to diagnose properly. Fine needle biopsy is invasive, often unsuccessful, and puts patients at risk, e. g., in cases of pheochromocytoma or adrenal cancer. Noninvasive characterization using radiotracers has therefore been established in recent years. (18)F-FDG PET helps to differentiate benign from malignant lesions. However, it does not distinguish between adrenocortical or nonadrenocortical lesions (e.g., metastases or adrenocortical carcinoma). More recently, enzyme inhibitors have been developed as tracers for adrenal imaging. Metomidate is most widely used. It binds with high specificity and affinity to CYP11B enzymes of the adrenal cortex. As these enzymes are exclusively expressed in adrenocortical cells, uptake of labeled metomidate tracers has been shown to be highly specific for adrenocortical neoplasia. (11)C-metomidate PET and (123)I-iodometomidate SPECT imaging has been introduced into clinical use. Both tracers not only distinguish between adrenocortical and nonadrenocortical lesions but are also able to visualize metastases of adrenocortical carcinoma. The very specific uptake has recently led to first application of (131)I-iodometomidate for radiotherapy in ACC. In conclusion, metomidate-based imaging is an important complementary tool to diagnose adrenal lesions that cannot be determined by other methods.

11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism.

PURPOSE: To evaluate whether dexamethasone suppression treatment can improve (11) C-metomidate positron emission tomography (MTO-PET) detection of small adrenocortical adenomas in primary aldosteronism (PA). MATERIALS AND METHODS: Eleven patients with proven PA and two patients with non-hyperfunctioning adrenocortical incidentalomas and small adrenocortical tumours observed on CT underwent MTO-PET before and 3 days after administration of oral dexamethasone suppression treatment. Small "hot-spot" regions of interest comprising 4 pixels (SUVhs) and 1 pixel (SUVmax) were placed in the tumour area with the highest radioactivity concentration and their respective standardised uptake values (SUV) were recorded. RESULTS: All tumours were detected and categorised as adrenocortical by MTO-PET. SUVhs as well as SUVmax were higher in PA compared to nonfunctional adenomas. Normal adrenal cortex was suppressed after dexamethasone (p < 0.05), but tumour SUV was not significantly decreased after suppression in either PA or nonfunctional tumours (p > 0.05). However, these changes caused no significant increase in the tumour-to-normal adrenal ratio (p > 0.05). CONCLUSION: MTO-PET is a highly sensitive method for detecting and categorising even small adrenocortical tumours in PA. In this series, dexamethasone-suppressed MTO-PET was unable to increase the tumour-to-normal adrenal ratio to further facilitate detection of small adenomas in PA as an alternative to adrenal venous sampling.

The value of 11C-5-hydroxy-tryptophan positron emission tomography in neuroendocrine tumor diagnosis and management: experience from one center.

Many neuroendocrine tumors (NET) are small and may escape localization by conventional imaging techniques. In such cases, 11C-5-hydroxy-tryptophan (11C-5-HTP) positron emission tomography (PET) has been tested as an additional diagnostic tool. Nine patients with clinically, biochemically and/or histologically confirmed NET and negative computerized tomography (CT) or magnetic resonance imaging (MRI), and 111In-pentetreotide (Octreoscan) scintigraphy underwent imaging with 11C-5-HTP-PET/CT in order to: 1) detect the primary tumor lesion in three patients; 2) detect residual disease in two patients with appendiceal carcinoid, one with rectal carcinoid, one with midgut carcinoid, and one with ectopic ACTH secretion (EAS) due to residual pulmonary carcinoid; and 3) restage a patient with medullary thyroid carcinoma (MTC) and hepatic metastases. 11C-5-HTP-PET/CT detected lesions in the mediastinum in a patient with EAS due to a pulmonary carcinoid, further hepatic metastases in a patient with carcinoid syndrome (CS) from a NET of unknown primary, further hepatic metastases in the patient with MTC, and hepatic metastases in the patient with midgut carcinoid. The 11C-5-HTP-PET/CT findings contributed to radical cure of the patient with recurrent EAS, and pointed towards bilateral adrenalectomy in the patient with EAS without evident primary tumor. In addition, 11C-5- HTP-PET/CT directed towards combined surgical and medical treatment in the patient with CS and multiple rather than single hepatic metastases and in the patient with midgut carcinoid, and towards continuation of medical treatment in the patient with MTC. 11C-5-HTP-PET/CT is a useful imaging technique, providing additional information for the diagnosis, staging and decision-making regarding management of patients with NET.

Long-term effects of surgical correction of adrenal hyperplasia and adenoma causing primary aldosteronism.

PURPOSE: The purpose of this is to study long-time results of surgery for primary aldosteronism. MATERIALS AND METHODS: Thirty patients operated on for primary aldosteronism were followed for an average of 7 years. All but five required potassium substitution. Systolic as well as diastolic hypertension (mean 157/93 mmHg) was present necessitating one to five antihypertensive drugs daily (mean 2.33). Preoperative indications for surgery included presumed adenoma (aldosterone-producing adenoma (APA)) or in one case unilateral dominance of hyperplasia. RESULTS: Histopathology was classified into adenoma (n = 9), dominant nodule (n = 16), and general hyperplasia without dominating nodules (n = 5), demonstrating a higher frequency of hyperplasia than anticipated. Long-term results revealed well-controlled blood pressure (BP; mean 134/80 mmHg). Antihypertensive medication was reduced (average of 1.78 per day), but only 36% of the patients were taken off these drugs completely. S-Aldosterone was normalized. All but one (a recurrence) were normokalemic without potassium substitution at follow-up. The APA group needed less medication (median 0.5 vs. 1.5 and 2 per day) and more patients in this group were totally medication free (50%). Two recurrences occurred in the group with general hyperplasia without dominating nodules. CONCLUSION: Nodular hyperplasia is more common than anticipated. Hypersecretion of aldosterone may be released from a large nodule identified as an adenoma, as well as from a generally hyperplastic gland that has not been identified as such. Nevertheless, surgery for lateralized disease results in good long-term control of BP with less antihypertensive medication. However, patients with dominant nodule or general hyperplasia without dominating nodules need more postoperative treatment than patients with APA. The majority of patients do not achieve normotension without medications, but they do become normokalemic.

Positron emission tomography in clinical islet transplantation.

The fate of islets in clinical transplantation is unclear. To elude on this positron emission tomography combined with computed tomography (PET/CT) was performed for 60 min during islet transplantation in five patients receiving six transplants. A fraction of the islets (23%) were labeled with 18F-fluorodeoxyglucose ([(18)F]FDG) and carefully mixed with unlabeled islets just prior to intraportal transplantation. The peak radioactivity concentration in the liver was found at 19 min after start of islet infusion and corresponded to only 75% of what was expected, indicating that islets are lost during the transplantation procedure. No accumulation of radioactivity was found in the lungs. A nonphysiological peak of C-peptide was found in plasma during and immediately after transplantation in all subjects. Distribution in the liver was heterogeneous with wide variations in location and concentration. Islets found in areas with concentrations of >400 IEQ/cc liver tissue varied between 1% and 32% of the graft in different subjects. No side effects attributed to the PET/CT procedure were found. Clinical outcome in all patients was comparable to that previously observed indicating that the [(18)F]FDG labeling procedure did not harm the islets. The technique has potential to be used to assess approaches to enhance islet survival and engraftment in clinical transplantation.

Early prediction of response to first-line chemotherapy by sequential [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with advanced colorectal cancer.

BACKGROUND: To evaluate [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), for early evaluation of response to palliative chemotherapy and for prediction of long-term outcome, in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: In a randomized trial, patients with mCRC received irinotecan-based combination chemotherapy. FDG-PET was carried out before treatment and after two cycles in 51 patients at two centers. Visual changes in tumor FDG uptake and changes measured semi-automatically, as standard uptake values (SUVs), were compared with radiological response after four and eight cycles. RESULTS: The mean baseline SUV for all tumor lesions per patient was higher in nonresponders than in responders (mean 7.4 versus 5.6, P = 0.02). There was a strong correlation between metabolic response (changes in SUV) and objective response (r = 0.57, P = 0.00001), with a sensitivity of 77% and a specificity of 76%. There was no significant correlation between metabolic response and time to progression (P = 0.5) or overall survival (P = 0.1). CONCLUSIONS: Although metabolic response assessed by FDG-PET reflects radiological tumor volume changes, the sensitivity and specificity are too low to support the routine use of PET in mCRC. Furthermore, PET failed to reflect long-term outcome and can, thus, not be used as surrogate end point for hard endpoint benefit.