Liver metastases of colorectal cancer: US, CT or MR?

Schima, Wolfgang; Kulinna, C.; Langenberger, Herbert; Ba‐Ssalamah, Ahmed

doi:10.1102/1470-7330.2005.0035

Cited by 89 publications

(57 citation statements)

References 27 publications

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“…MMPs have been implicated in cancer cell invasion and metastasis for over 35 years (38), and many of the hallmarks of cancer (39) are dependent on MMP activity. An ultrasensitive diagnostic for MMP9 activity may be used in clinical settings when the tumor type is known, such as after primary resection, when the surveillance protocol relies on CT or magnetic resonance imaging (MRI) despite their difficulties detecting metastasis 1-2 cm in diameter (35). MMP9 is expressed to activate VEGF ligands (40) during the angiogenic "switch" that occurs when nascent tumors are 1-2 mm in diameter; therefore, measuring MMP9 activity may allow detection of tumors smaller than the detection threshold of medical imaging.…”

Section: Discussionmentioning

confidence: 99%

“…We chose 5-mm tumors as a target sensitivity threshold to represent a detection limit that is below the current thresholds associated with computed tomography (CT) (∼1 cm) (35) or blood biomarkers (∼1-2 cm) (4, 5). To estimate protease production rates, we analyzed conditioned media collected from four human CRC lines and detected MMP9 secretion rates ranging from ∼1.9 pg/10 6 cells per day to 12.5 pg/10 6 cells per day by ELISA (Fig.…”

Section: Significancementioning

confidence: 99%

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Mathematical framework for activity-based cancer biomarkers

Kwong

Dudani

Carrodeguas

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Advances in nanomedicine are providing sophisticated functions to precisely control the behavior of nanoscale drugs and diagnostics. Strategies that coopt protease activity as molecular triggers are increasingly important in nanoparticle design, yet the pharmacokinetics of these systems are challenging to understand without a quantitative framework to reveal nonintuitive associations. We describe a multicompartment mathematical model to predict strategies for ultrasensitive detection of cancer using synthetic biomarkers, a class of activity-based probes that amplify cancerderived signals into urine as a noninvasive diagnostic. Using a model formulation made of a PEG core conjugated with protease-cleavable peptides, we explore a vast design space and identify guidelines for increasing sensitivity that depend on critical parameters such as enzyme kinetics, dosage, and probe stability. According to this model, synthetic biomarkers that circulate in stealth but then activate at sites of disease have the theoretical capacity to discriminate tumors as small as 5 mm in diameter-a threshold sensitivity that is otherwise challenging for medical imaging and blood biomarkers to achieve. This model may be adapted to describe the behavior of additional activity-based approaches to allow cross-platform comparisons, and to predict allometric scaling across species.compartmental modeling | activity-based probes | cancer diagnostics | urine biomarkers | nanomedicine T he clinical management of cancer is increasingly dependent on the discovery of new biomarkers and the development of ultrasensitive technologies to detect them at a stage when therapeutic interventions may be effective (1, 2). However, despite their growing importance, biomarkers lack predictive power to impact patient outcomes during the earliest stages of disease. The challenges are multifaceted: Biomarkers are shed from tumors at rates that vary by four orders in magnitude (3), are significantly diluted in blood, and circulate for short periods. Recent mathematical studies showed that tumors may remain undetectable with blood biomarkers for an entire decade following tumorigenesis, reaching 1-2.5 cm in diameter (4, 5). To increase sensitivity, major research areas include the development of ultrasensitive in vitro diagnostic platforms (6-11), as well as methods to increase biomarker production by solid tumors (12, 13). These approaches are designed to measure the quantity, or abundance, of a disease biomarker.In contrast to abundance-based methods, activity-based probes are a class of agents that are administered in prodiagnostic form but produce strong diagnostic signals after enzymatic activation (14, 15). These approaches rely on disease-associated enzymes as catalysts to produce a detection signal, of which proteases are particularly potent because the cleavage of peptide bonds is irreversible, and a single protease can cleave many substrates to amplify signals. However, activity-based probes operate within a narrow time window and are activated by offtarget...

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Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Mathematical framework for activity-based cancer biomarkers

Kwong

Dudani

Carrodeguas

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Surgical resection of hepatic metastases should be performed whenever a curative result is possible. This is based on recent studies, where patients with R0 resected liver metastases reveal a 5-year-survival of nearly 40% (versus 5% with irresectable metastases) and a 10-year-survival of 25% [4,[6][7][8].…”

Section: Discussionmentioning

confidence: 99%

Bronchogenic Cyst in the Liver Mimicking Metastasis of Colorectal Carcinoma: A Case Report and Review

Reichert¹,

Hecker²

2015

J Cell Sci Ther

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Introduction Colorectal adenocarcinomaColorectal carcinoma is the third most common malignant disease worldwide [1]. Based on the primary depth of tumor invasion, the occurence of loco-regional lymphnode metastases and of distant tumor metastases colorectal adenocarcinomas can be graduated according to TNM-or Union internationale contre le cancer (UICC-) classification system. The five-year-survival rate decreases with higher tumor classification ( Table 1).The liver is the most common site for metastatic spread. In approximately 25% of the cases metastases can be found synchronously [1], in nearly 50% liver metastases appear metachronously after primary tumor resection [4]. Despite pulmonary and hepatic spreading a radical surgical resection of the hepatic metastases can be performed in a curative manner in 10-25% of the patients [5]. Surgical treatment of liver metastases of colorectal carcinomas is complex and should be *Corresponding author: Martin Reichert, MD, Department of General and Thoracic Surgery, University Hospital of Giessen, Justus-Liebig-University, Giessen, Germany, Rudolf-Buchheim-Street 7, 35392 Giessen, Germany, E-mail: martin.reichert@chiru.med.uni-giessen.de AbstractIntroduction: Carcinomas of the colon and rectum are the third most common cancer entity in the world and bear a high risk of synchronous (25%) or metachronous (50%) hepatic tumor seeding. For therapeutic decisions the differential diagnosis between benign and malignant hepatic lesions in the computer tomography scan is of major importance. We herein discuss congenital hepatic cysts derived from the primitive foregut as potential differential diagnosis for hepatic metastases from a colorectal primary tumor.

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“…These tumors are best seen in the arterial phase and may become isodense and difficult to detect at the later phases of contrast enhancement. At MR, metastases are usually hypointense on T1-weighted and hyperintense on T2-weighted images [75]. Peritumoral edema makes lesions appear larger on T2-weighted images and is highly suggestive of a malignant mass [76].…”

Section: Hepatic Metastasesmentioning

confidence: 99%