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1.
NMR Biomed ; 37(10): e5180, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38775032

ABSTRACT

Ultrahigh field magnetic resonance imaging (MRI) (≥ 7 T) has the potential to provide superior spatial resolution and unique image contrast. Apart from radiofrequency transmit inhomogeneities in the body at this field strength, imaging of the upper abdomen faces additional challenges associated with motion-induced ghosting artifacts. To address these challenges, the goal of this work was to develop a technique for high-resolution free-breathing upper abdominal MRI at 7 T with a large field of view. Free-breathing 3D gradient-recalled echo (GRE) water-excited radial stack-of-stars data were acquired in seven healthy volunteers (five males/two females, body mass index: 19.6-24.8 kg/m2) at 7 T using an eight-channel transceive array coil. Two volunteers were also examined at 3 T. In each volunteer, the liver and kidney regions were scanned in two separate acquisitions. To homogenize signal excitation, the time-interleaved acquisition of modes (TIAMO) method was used with personalized pairs of B1 shims, based on a 23-s Cartesian fast low angle shot (FLASH) acquisition. Utilizing free-induction decay navigator signals, respiratory-gated images were reconstructed at a spatial resolution of 0.8 × 0.8 × 1.0 mm3. Two experienced radiologists rated the image quality and the impact of B1 inhomogeneity and motion-related artifacts on multipoint scales. The images of all volunteers showcased effective water excitation and were accurately corrected for respiratory motion. The impact of B1 inhomogeneity on image quality was minimal, underscoring the efficacy of the multitransmit TIAMO shim. The high spatial resolution allowed excellent depiction of small structures such as the adrenal glands, the proximal ureter, the diaphragm, and small blood vessels, although some streaking artifacts persisted in liver image data. In direct comparisons with 3 T performed for two volunteers, 7-T acquisitions demonstrated increases in signal-to-noise ratio of 77% and 58%. Overall, this work demonstrates the feasibility of free-breathing MRI in the upper abdomen at submillimeter spatial resolution at a magnetic field strength of 7 T.


Subject(s)
Abdomen , Magnetic Resonance Imaging , Respiration , Humans , Female , Male , Abdomen/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Respiratory-Gated Imaging Techniques/methods , Artifacts
2.
Eur Radiol ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38907886

ABSTRACT

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.

3.
HPB (Oxford) ; 26(3): 389-399, 2024 03.
Article in English | MEDLINE | ID: mdl-38114400

ABSTRACT

BACKGROUND: Retrospective analysis to investigate the relationship between the flow-metabolic phenotype and overall survival (OS) of pancreatic ductal adenocarcinoma (PDAC) and its potential clinical utility. METHODS: Patients with histopathologically proven PDAC between 2005 and 2014 using tumor attenuation on routine pre-operative CECT as a surrogate for the vascularity and [18F]FDG-uptake as a surrogate for metabolic activity on [18F]FDG-PET. RESULTS: In total, 93 patients (50 male, 43 female, median age 63) were included. Hypoattenuating PDAC with high [18F]FDG-uptake has the poorest prognosis (median OS 7 ± 1 months), compared to hypoattenuating PDAC with low [18F]FDG-uptake (median OS 11 ± 3 months; p = 0.176), iso- or hyperattenuating PDAC with high [18F]FDG-uptake (median OS 15 ± 5 months; p = 0.004) and iso- or hyperattenuating PDAC with low [18F]FDG-uptake (median OS 23 ± 4 months; p = 0.035). In multivariate analysis, surgery combined with tumor differentiation, tumor stage, systemic therapy and flow metabolic phenotype remained independent predictors for overall survival. DISCUSSION: The novel qualitative flow-metabolic phenotype of PDAC using a combination of CECT and [18F]FDG-PET features, predicted significantly worse survival for hypoattenuating-high uptake pancreatic cancers compared to the other phenotypes.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Male , Female , Middle Aged , Fluorodeoxyglucose F18 , Prognosis , Retrospective Studies , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/surgery , Biomarkers , Phenotype , Positron Emission Tomography Computed Tomography
4.
Radiology ; 308(3): e230275, 2023 09.
Article in English | MEDLINE | ID: mdl-37724961

ABSTRACT

Background A priori identification of patients at risk of artificial intelligence (AI) failure in diagnosing cancer would contribute to the safer clinical integration of diagnostic algorithms. Purpose To evaluate AI prediction variability as an uncertainty quantification (UQ) metric for identifying cases at risk of AI failure in diagnosing cancer at MRI and CT across different cancer types, data sets, and algorithms. Materials and Methods Multicenter data sets and publicly available AI algorithms from three previous studies that evaluated detection of pancreatic cancer on contrast-enhanced CT images, detection of prostate cancer on MRI scans, and prediction of pulmonary nodule malignancy on low-dose CT images were analyzed retrospectively. Each task's algorithm was extended to generate an uncertainty score based on ensemble prediction variability. AI accuracy percentage and partial area under the receiver operating characteristic curve (pAUC) were compared between certain and uncertain patient groups in a range of percentile thresholds (10%-90%) for the uncertainty score using permutation tests for statistical significance. The pulmonary nodule malignancy prediction algorithm was compared with 11 clinical readers for the certain group (CG) and uncertain group (UG). Results In total, 18 022 images were used for training and 838 images were used for testing. AI diagnostic accuracy was higher for the cases in the CG across all tasks (P < .001). At an 80% threshold of certain predictions, accuracy in the CG was 21%-29% higher than in the UG and 4%-6% higher than in the overall test data sets. The lesion-level pAUC in the CG was 0.25-0.39 higher than in the UG and 0.05-0.08 higher than in the overall test data sets (P < .001). For pulmonary nodule malignancy prediction, accuracy of AI was on par with clinicians for cases in the CG (AI results vs clinician results, 80% [95% CI: 76, 85] vs 78% [95% CI: 70, 87]; P = .07) but worse for cases in the UG (AI results vs clinician results, 50% [95% CI: 37, 64] vs 68% [95% CI: 60, 76]; P < .001). Conclusion An AI-prediction UQ metric consistently identified reduced performance of AI in cancer diagnosis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Babyn in this issue.


Subject(s)
Lung Neoplasms , Mental Disorders , Male , Humans , Artificial Intelligence , Retrospective Studies , Magnetic Resonance Imaging , Lung Neoplasms/diagnostic imaging , Tomography, X-Ray Computed
5.
Magn Reson Med ; 89(5): 1931-1944, 2023 05.
Article in English | MEDLINE | ID: mdl-36594436

ABSTRACT

PURPOSE: To increase the effectiveness of respiratory gating in radial stack-of-stars MRI, particularly when imaging at high spatial resolutions or with multiple echoes. METHODS: Free induction decay (FID) navigators were integrated into a three-dimensional gradient echo radial stack-of-stars pulse sequence. These navigators provided a motion signal with a high temporal resolution, which allowed single-spoke binning (SSB): each spoke at each phase encode step was sorted individually to the corresponding motion state of the respiratory signal. SSB was compared with spoke-angle binning (SAB), in which all phase encode steps of one projection angle were sorted without the use of additional navigator data. To illustrate the benefit of SSB over SAB, images of a motion phantom and of six free-breathing volunteers were reconstructed after motion-gating using either method. Image sharpness was quantitatively compared using image gradient entropies. RESULTS: The proposed method resulted in sharper images of the motion phantom and free-breathing volunteers. Differences in gradient entropy were statistically significant (p = 0.03) in favor of SSB. The increased accuracy of motion-gating led to a decrease of streaking artifacts in motion-gated four-dimensional reconstructions. To consistently estimate respiratory signals from the FID-navigator data, specific types of gradient spoiler waveforms were required. CONCLUSION: SSB allowed high-resolution motion-corrected MR imaging, even when acquiring multiple gradient echo signals or large acquisition matrices, without sacrificing accuracy of motion-gating. SSB thus relieves restrictions on the choice of pulse sequence parameters, enabling the use of motion-gated radial stack-of-stars MRI in a broader domain of clinical applications.


Subject(s)
Artifacts , Image Interpretation, Computer-Assisted , Humans , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Abdomen/diagnostic imaging , Motion , Respiration , Imaging, Three-Dimensional/methods
6.
Ann Surg Oncol ; 30(9): 5376-5385, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37118612

ABSTRACT

BACKGROUND: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study. METHODS: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons. RESULTS: A total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0-12% and 27-62%, and for permanently unresectable CRLM between 3-40% and 6-47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients. CONCLUSION: Considerable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-based decisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Colorectal Neoplasms/pathology , Liver Neoplasms/surgery , Liver Neoplasms/drug therapy , Hepatectomy/methods
7.
HPB (Oxford) ; 25(12): 1513-1522, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37580180

ABSTRACT

BACKGROUND: Due to centralization of pancreatic surgery, patients with pancreatic cancer are treated in pancreatic cancer networks, composed of referring hospitals (Spokes) and an expert center (Hub). This study aimed to investigate I) how pancreatic cancer networks are organized and II) evaluated by involved clinicians. METHODS: Two online surveys were sent out between January-May 2022. Part I was sent out to the surgical network directors of all hospitals of the Dutch Pancreatic Cancer Group (DPCG). Part II was sent out to all involved clinicians in the Hubs-and-Spokes networks. RESULTS: There was a large variety between the 15 networks concerning number of affiliated Spokes (1-7), annual pancreatoduodenectomies (20-129), and use of a service level agreement (SLA) (40%). More Spoke clinicians considered the Spoke the best location for diagnostic workup (74% vs 36%, P < 0.001). Only 30% of Spoke clinicians attended the Hubs multidisciplinary team meeting frequently. More Hub clinicians thought that exchange of patient information should be improved (37% vs 51%, P = 0.005). CONCLUSION: A large variety in Dutch pancreatic cancer networks was observed concerning number of affiliated Spokes, use of SLAs, and logistic aspects of network care. Improvement of network care concern agreements on diagnostic workup, use of SLA, Spoke participation in the MDT, and patient information exchange.


Subject(s)
Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/adverse effects , Pancreatic Neoplasms
8.
Dig Surg ; : 1-7, 2020 Dec 10.
Article in English | MEDLINE | ID: mdl-33302266

ABSTRACT

BACKGROUND: The primary aim was to assess the diagnostic accuracy of routine ultrasound assessment for gallbladder polyps. The secondary aim was to identify the characteristics that differentiate neoplastic polyps from nonneoplastic polyps. METHODS: A total of 156 patients with histopathologically proven gallbladder polyps in 4 Dutch hospitals between 2003 and 2013 were included. Sensitivity and specificity of ultrasound for polyp size, number of polyps, and polyp type were assessed using histopathological findings as a reference standard. In addition, diagnostic accuracy of sonographic size ≥1 cm for neoplasia was assessed. Subgroup analysis for patients with polyps as primary indication for cholecystectomy was performed. The sonographic polyp characteristics on preoperative routine ultrasound were described. RESULTS: Fifty-six percent of gallbladder polyps were preoperatively identified on ultrasound, of which 31% were neoplastic. Sensitivity and specificity of ultrasound to estimate polyp size were 93 and 43% (subgroup; 92 and 33%). Sensitivity and specificity of sonographic polyp size ≥1 cm for neoplasia were 86 and 32% (subgroup; 94 and 26%). No specific sonographic characteristics for neoplastic polyps could be established due to lack of reporting. CONCLUSION: Routine ultrasound assessment of polyps is associated with overestimation of polyp size and low specificity of sonographic size ≥1 cm for neoplasia, which contributes to surgical overtreatment of nonneoplastic polyps.

12.
Nature ; 478(7369): 412-6, 2011 Oct 19.
Article in English | MEDLINE | ID: mdl-22012399

ABSTRACT

Extremophilic organisms require specialized enzymes for their exotic metabolisms. Acid-loving thermophilic Archaea that live in the mudpots of volcanic solfataras obtain their energy from reduced sulphur compounds such as hydrogen sulphide (H(2)S) and carbon disulphide (CS(2)). The oxidation of these compounds into sulphuric acid creates the extremely acidic environment that characterizes solfataras. The hyperthermophilic Acidianus strain A1-3, which was isolated from the fumarolic, ancient sauna building at the Solfatara volcano (Naples, Italy), was shown to rapidly convert CS(2) into H(2)S and carbon dioxide (CO(2)), but nothing has been known about the modes of action and the evolution of the enzyme(s) involved. Here we describe the structure, the proposed mechanism and evolution of a CS(2) hydrolase from Acidianus A1-3. The enzyme monomer displays a typical ß-carbonic anhydrase fold and active site, yet CO(2) is not one of its substrates. Owing to large carboxy- and amino-terminal arms, an unusual hexadecameric catenane oligomer has evolved. This structure results in the blocking of the entrance to the active site that is found in canonical ß-carbonic anhydrases and the formation of a single 15-Å-long, highly hydrophobic tunnel that functions as a specificity filter. The tunnel determines the enzyme's substrate specificity for CS(2), which is hydrophobic. The transposon sequences that surround the gene encoding this CS(2) hydrolase point to horizontal gene transfer as a mechanism for its acquisition during evolution. Our results show how the ancient ß-carbonic anhydrase, which is central to global carbon metabolism, was transformed by divergent evolution into a crucial enzyme in CS(2) metabolism.


Subject(s)
Acidianus/enzymology , Carbon Disulfide/metabolism , Evolution, Molecular , Hydrolases/genetics , Acidianus/classification , Acidianus/genetics , Catalytic Domain , Crystallography, X-Ray , Hydrolases/chemistry , Models, Molecular , Molecular Sequence Data , Mutation , Phylogeny , Protein Structure, Tertiary
13.
Eur J Haematol ; 94(2): 182-5, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24766347

ABSTRACT

Four patients diagnosed with haematological malignancies developed an isolated hyperbilirubinaemia following cytarabine- and anthracycline-based chemotherapy. The clinical picture was consistent with acalculous cholecystitis, but ultrasonography did not show the typical gallbladder wall thickening. All patients suffered from severe mucositis with neutropenic enterocolitis. We hypothesise that damage of the mucosa of the gallbladder induced by chemotherapy results in hyperpermeability of the mucosal barrier with bile leakage and isolated hyperbilirubinaemia.


Subject(s)
Acalculous Cholecystitis/diagnosis , Acalculous Cholecystitis/etiology , Hematologic Neoplasms/complications , Hyperbilirubinemia/etiology , Acalculous Cholecystitis/drug therapy , Anti-Infective Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Hematologic Neoplasms/drug therapy , Humans , Liver Function Tests , Male , Middle Aged , Treatment Outcome
14.
Scand J Gastroenterol ; 49(4): 449-57, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24467299

ABSTRACT

OBJECTIVE: There is strong evidence for an association between obesity and esophageal adenocarcinoma (EAC). This study investigated the association between directly measured visceral adipose tissue and the risk of EAC. METHODS: In a case-control setting, we measured visceral adipose tissue in patients with EAC and healthy controls. Visceral adipose tissue was determined by abdominal CT. Exclusion criteria were uninterpretable CT scans and severe comorbidity. Controls were healthy volunteers undergoing screening CT colonography. Cross-sectional areas of visceral and subcutaneous adipose tissues were measured in cm(2) at L3/L4. Values of adipose tissue of EAC patients were extrapolated to stage 0 and compared to controls. The association between visceral adipose tissue and EAC was calculated with least-squares regression, adjusted for age, sex and TNM stage. RESULTS: We included 175 EAC patients and 251 controls. While body mass index was similar in EAC patients (26.1 kg/m(2)) and controls (26.2 kg/m(2)), visceral adipose tissue was significantly higher in EAC patients at stage 0 than in controls (276 vs. 231 cm(2); p = 0.015). Regarding subcutaneous adipose tissue, there was no difference. CONCLUSIONS: Patients with EAC have significantly higher visceral adipose tissue than healthy controls. Visceral adipose tissue is a risk factor in the development of EAC and seems to be more important than obesity alone.


Subject(s)
Adenocarcinoma/etiology , Esophageal Neoplasms/etiology , Intra-Abdominal Fat/diagnostic imaging , Case-Control Studies , Female , Humans , Male , Middle Aged , Neoplasm Staging , Radiography, Abdominal , Risk Factors , Tomography, X-Ray Computed
15.
Cancers (Basel) ; 16(3)2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38339328

ABSTRACT

CT perfusion (CTP) analysis is difficult to implement in clinical practice. Therefore, we investigated a novel semi-automated CTP AI biomarker and applied it to identify vascular phenotypes of pancreatic ductal adenocarcinoma (PDAC) and evaluate their association with overall survival (OS). METHODS: From January 2018 to November 2022, 107 PDAC patients were prospectively included, who needed to undergo CTP and a diagnostic contrast-enhanced CT (CECT). We developed a semi-automated CTP AI biomarker, through a process that involved deformable image registration, a deep learning segmentation model of tumor and pancreas parenchyma volume, and a trilinear non-parametric CTP curve model to extract the enhancement slope and peak enhancement in segmented tumors and pancreas. The biomarker was validated in terms of its use to predict vascular phenotypes and their association with OS. A receiver operating characteristic (ROC) analysis with five-fold cross-validation was performed. OS was assessed with Kaplan-Meier curves. Differences between phenotypes were tested using the Mann-Whitney U test. RESULTS: The final analysis included 92 patients, in whom 20 tumors (21%) were visually isovascular. The AI biomarker effectively discriminated tumor types, and isovascular tumors showed higher enhancement slopes (2.9 Hounsfield unit HU/s vs. 2.0 HU/s, p < 0.001) and peak enhancement (70 HU vs. 47 HU, p < 0.001); the AUC was 0.86. The AI biomarker's vascular phenotype significantly differed in OS (p < 0.01). CONCLUSIONS: The AI biomarker offers a promising tool for robust CTP analysis. In PDAC, it can distinguish vascular phenotypes with significant OS prognostication.

16.
Diagnostics (Basel) ; 14(6)2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38534994

ABSTRACT

This study evaluated the relationship between apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and tumor grades based on WHO, Adsay, and Kalimuthu classifications, using whole-mount pancreatectomy specimens. If glandular formation plays a key role in the degree of diffusion restriction, diffusion-weighted imaging could facilitate non-invasive grading of PDAC. A freehand region of interest (ROI) was drawn along tumor borders on the preoperative ADC map in each tumor-containing slice. Resection specimens were retrospectively graded according to WHO, Adsay, and Kalimuthu classifications and correlated with overall survival and the 10th percentile of whole-volume ADC values. Findings from 40 patients (23 male, median age 67) showed no correlation between ADC p10 values and WHO differentiation (p = 0.050), Adsay grade (p = 0.955), or Kalimuthu patterns (p = 0.117). There was no association between ADC p10 and overall survival (p = 0.082) and other clinicopathological variables. Survival was significantly lower for poor tumor differentiation (p = 0.046) and non-glandular Kalimuthu patterns (p = 0.016) and there was a trend towards inferior survival for Adsay G3 (p = 0.090) after correction for age, tumor location, and stage. Preoperative ADC measurements for determining PDAC aggressiveness had limited clinical utility, as there was no correlation with histological parameters or overall survival in resectable PDAC.

17.
J Nucl Med ; 2024 Oct 17.
Article in English | MEDLINE | ID: mdl-39419553

ABSTRACT

Precise anatomic localization of insulinomas is crucial for surgical treatment. Current routine noninvasive imaging techniques, including CT, MRI, and 68Ga-DOTA-somatostatin analog (DOTA-SSA) PET/CT, have limited sensitivity. Endoscopic ultrasound is highly sensitive but invasive. In this prospective multicenter study, we compared the diagnostic accuracy of 68Ga-NODAGA-exendin-4 (exendin) PET/CT with all routine imaging procedures for the localization of insulinomas. Methods: Sixty-nine adults with biochemically proven adult endogenous hyperinsulinemic hypoglycemia underwent exendin PET/CT and current routine imaging. Images were evaluated in a clinical reading and in an expert reading. Image quality was determined by quantitative analysis. Results: Based on clinical readings, the accuracy of exendin PET/CT (94.4%; 95% CI, 84.6%-98.8%) was greater than that of DOTA-SSA PET/CT (64.8%; 95% CI, 50.6%-77.3%), contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (83.3%; 95% CI, 70.7%-92.1%), and endoscopic ultrasound (82.8%; 95% CI, 64.1%-94.1%). In 13% of patients, a correct diagnosis was only reached after exendin PET/CT. Interobserver agreement between readings was higher for exendin PET/CT than for DOTA-SSA PET/CT and contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (Cohen κ, 1.0 vs. 0.5 and 0.55). Exendin PET/CT provided a higher insulinoma-to-background ratio (15.3 ± 6.7 vs. 5.2 ± 3.0) and contrast-to-noise ratio (22.6 ± 11.1 vs. 5.1 ± 3.7) than did DOTA-SSA PET/CT. Conclusion: This study demonstrates the superiority of exendin PET/CT in a unique prospective comparison to all current routine imaging modalities for preoperative localization of benign insulinomas, providing the level of evidence needed for clinical implementation.

18.
Eur J Cancer ; 207: 114185, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38924855

ABSTRACT

BACKGROUND: This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment. METHODS: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center. RESULTS: In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P < 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008). CONCLUSION: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Neoplasm Recurrence, Local , Tumor Burden , Humans , Liver Neoplasms/secondary , Liver Neoplasms/drug therapy , Liver Neoplasms/diagnostic imaging , Male , Female , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Middle Aged , Prognosis , Aged , Neoplasm Recurrence, Local/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adult
19.
J Bacteriol ; 195(18): 4046-56, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23836868

ABSTRACT

Carbon disulfide (CS(2)) and carbonyl sulfide (COS) are important in the global sulfur cycle, and CS(2) is used as a solvent in the viscose industry. These compounds can be converted by sulfur-oxidizing bacteria, such as Acidithiobacillus thiooxidans species, to carbon dioxide (CO(2)) and hydrogen sulfide (H2S), a property used in industrial biofiltration of CS(2)-polluted airstreams. We report on the mechanism of bacterial CS(2) conversion in the extremely acidophilic A. thiooxidans strains S1p and G8. The bacterial CS(2) hydrolases were highly abundant. They were purified and found to be homologous to the only other described (archaeal) CS(2) hydrolase from Acidianus strain A1-3, which forms a catenane of two interlocked rings. The enzymes cluster in a group of ß-carbonic anhydrase (ß-CA) homologues that may comprise a subclass of CS(2) hydrolases within the ß-CA family. Unlike CAs, the CS(2) hydrolases did not hydrate CO(2) but converted CS(2) and COS with H(2)O to H(2)S and CO(2). The CS(2) hydrolases of A. thiooxidans strains G8, 2Bp, Sts 4-3, and BBW1, like the CS(2) hydrolase of Acidianus strain A1-3, exist as both octamers and hexadecamers in solution. The CS(2) hydrolase of A. thiooxidans strain S1p forms only octamers. Structure models of the A. thiooxidans CS(2) hydrolases based on the structure of Acidianus strain A1-3 CS(2) hydrolase suggest that the A. thiooxidans strain G8 CS(2) hydrolase may also form a catenane. In the A. thiooxidans strain S1p enzyme, two insertions (positions 26 and 27 [PD] and positions 56 to 61 [TPAGGG]) and a nine-amino-acid-longer C-terminal tail may prevent catenane formation.


Subject(s)
Acidianus/enzymology , Acidithiobacillus thiooxidans/enzymology , Archaeal Proteins/chemistry , Bacterial Proteins/chemistry , Carbon Disulfide/metabolism , Hydrolases/chemistry , Sequence Homology, Amino Acid , Acidianus/genetics , Acidithiobacillus thiooxidans/genetics , Amino Acid Sequence , Anthracenes/chemistry , Anthracenes/metabolism , Archaeal Proteins/genetics , Archaeal Proteins/isolation & purification , Archaeal Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Bacterial Proteins/metabolism , Carbon Disulfide/chemistry , DNA, Bacterial/analysis , Hydrolases/genetics , Hydrolases/isolation & purification , Hydrolases/metabolism , Models, Molecular , Molecular Sequence Data , Phylogeny , Sequence Alignment , Sequence Analysis, DNA , Substrate Specificity
20.
World J Surg ; 37(1): 147-55, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23015224

ABSTRACT

BACKGROUND: In esophageal cancer patients preoperative staging will determine the type of surgical procedure and use of neoadjuvant therapy. Tumor location and lymph node status play a pivotal role in this tailored strategy. The aim of the present study was to prospectively evaluate the accuracy of preoperative assessment of tumor location according to the Siewert classification and lymph node status per station with endoscopy/endoscopic ultrasound (EUS) and computed tomography (CT). METHODS: In 50 esophagectomy patients with adenocarcinoma of the gastroesophageal junction (GEJ), tumor location according to Siewert and N-stage per nodal station as determined preoperatively by endoscopy/EUS and CT were compared with the histopathologic findings in the resection specimen. RESULTS: Overall accuracy in predicting tumor location according to the Siewert classification was 70 % for endoscopy/EUS and 72 % for CT. Preoperative data could not be compared with the pathologic assessment in 11 patients (22 %), as large tumors obscured the landmark of the gastric folds. The overall accuracy for predicting the N-stage in 250 lymph node stations was 66 % for EUS and 68 % for CT. The accuracy was good for those stations located high in the thorax, but poor for celiac trunk nodes. CONCLUSIONS: Given the frequent discrepancy between the endoscopic and pathologic location of the GEJ and the common problem of advanced tumors obscuring the landmarks used in the assessment of the Siewert classification, its usefulness is limited. The overall accuracy for EUS and CT in predicting the N-stage per station was moderate.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/secondary , Esophageal Neoplasms/pathology , Esophagogastric Junction/pathology , Stomach Neoplasms/pathology , Adenocarcinoma/surgery , Aged , Aged, 80 and over , Esophageal Neoplasms/surgery , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Preoperative Care , Prospective Studies , Stomach Neoplasms/surgery
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