Detection Of Occult Liver Metastases Research Articles

Potential use of Doppler perfusion index in detection of occult liver metastases from colorectal cancer.

Many clinical and preclinical studies demonstrated that measurements of liver hemodynamic [Doppler perfusion index (DPI)] may be used to accurately diagnose and predict liver metastases from primary colorectal cancer in a research setting. However, Doppler measurements have some serious limitations when applied to general population. Ultrasound is very operator-dependent, and requires skilled examiners. Also, many conditions may limit the use of Doppler ultrasound and ultrasound in general, such as the presence of air in digestive tract, cardiac arrhythmias, vascular anomalies, obesity and other conditions. Therefore, in spite of the results from clinical studies, its value may be limited in everyday practice. On the contrary, scientific research of the DPI in detection of liver metastases is of great importance, since current research speaks strongly for the presence of systemic vasoactive substance responsible for observed hemodynamic changes. Identification of such a systemic vasoactive substance may lead to the development of a simple and reproducible laboratory test that may reliably identify the presence of occult liver metastases and therefore increase the success of adjuvant chemotherapy through better selection of patients. Further research in this subject is therefore of great importance.

Hepatic Transit Time Analysis Using Contrast-Enhanced Ultrasound with BR1: A Prospective Study Comparing Patients with Liver Metastases from Colorectal Cancer with Healthy Volunteers

We prospectively compared hepatic transit time (HTT) measurements in subjects with liver metastases from colorectal cancer (group a) and healthy volunteers (group b) using contrast-enhanced ultrasound with BR1. The purpose of this study was to verify our hypothesis that the hemodynamic changes of the liver, which occur during metastasis seeding, would shorten the HTT, and we expect that such changes could be used for the detection of occult liver metastases from colorectal cancer in the future. The study had institutional review board approval and all subjects gave informed written consent. Group a and group b consisted of 22 subjects each. Baseline and post contrast images were acquired starting 10 s before and ending 40 s after administration of BR1, using nonlinear imaging at a frame rate of 5/s. The baseline images were used to determine the signal intensity without contrast enhancement as the reference signal. Arrival times (AT) of the contrast agent for the hepatic artery, the portal vein and one hepatic vein were determined using (i) quantitative analysis and (ii) subjective analysis by two blinded readers. HTT was calculated based on arrival time measurements. Quantitative and subjective analysis showed significantly shorter arterial to venous and portal to venous HTT in group a compared with group b ( p < 0.001). Arterial to venous HTT (quantitative analysis) was ≤9 s in 19 of 22 subjects of group a and >9 s in 18 of 22 subjects of group b (sensitivity 86%, specificity 82%, positive predictive value 83%, negative predictive value 86%, area under the curve [AUC] 0.87). Portal to venous HTT (quantitative analysis) was < 7 s in 21 of 22 subjects of group a and > 7s in 15 of 22 subjects of group b (sensitivity 95%, specificity 68%, PPV 75%, NPV 94%, AUC 0.85). There was an inverse relation with number of liver segments involved for arterial to venous and portal to venous HTT in group a ( p < 0.05), but no correlation between HTT and overall volume of metastases (group a) or subject age (group b). From the results of our study, we conclude that HTT measurements using contrast-enhanced ultrasound with BR1 can detect hemodynamic changes caused by metastatic liver disease from colorectal cancer. However, comparison with the literature suggests that the use of other contrast agents might provide better results. Comparison of different contrast agents for the purpose of transit time analysis would therefore be useful before embarking on a prospective trial looking at the detection of occult liver metastases in patients with colorectal cancer. (E-mail: jhohmann@uhbs.ch)

Epidemiology of colorectal liver metastases

In summary, the natural history of patients presenting with synchronous liver metastases has been well documented. However, the epidemiology and natural history of patients presenting with metachronous disease is scant. It is clear, therefore, that the accurate detection of occult liver metastases at the time of presentation underpins further improvements in the selection of appropriate treatment for patients presenting with colorectal cancer. This will facilitate early referral for investigation and treatment of their liver metastases.

PRL-3 Expression in Primary Colorectal Cancer

Purpose: Overexpression of the protein tyrosine phosphatase (PRL-3) is elevated in liver metastases derived from colorectal cancer. We examined PRL-3 expression in the primary lesion of colorectal cancer patients and investigated its relation to clinicopathological features. Methods: A total of 63 randomly selected patients who underwent surgical resection for colorectal cancer between May 2001 and June 2005 at our hospital were investigated. Formalin-fixed and paraffin-embedded specimens from colorectal cancer patients who underwent surgical resections for primary tumors were collected. The expression of PRL-3 was detected by immunohistochemistry and the relation with age, sex, primary tumor size, tumor cell differentiation, depth of invasion, microscopic lymph node metastases, vascular invasion, numbers of lymph node metastases, postoperative stage, and postoperative survival time were analyzed. Results: A total of 16 of the 63 colorectal cancer patients were detected with liver metastases during the follow-up periods. Liver resection was performed for those liver metastases patients. Five patients developed lung metastases after liver resection. PRL-3 expression was detected in 46 colorectal cancer patients. Fourteen patients with lymphatic invasion had positive expression of PRL-3 that was significant (P=0.042). The incidence of PRL-3 expression in the T stage was significant (P=0.019). Moreover, PRL-3 expression was closely associated with liver metastases (P=0.048). Conclusions: These results indicate that an investigation of PRL-3 expression in primary colorectal cancer lesions may contribute to the detection of occult liver metastases and to a differentiation between postoperative management strategies.

Detection of Unsuspected Left Hepatic Lobe Metastases During EUS Staging of Cancer of the Esophagus and Cardia

High resolution imaging of the left hepatic lobe can be obtained via endoscopic ultrasound (EUS), allowing for detection of unsuspected metastatic disease during cancer staging. The frequency at which occult liver metastases are detected during EUS staging of cancer of the esophagus and cardia is unknown. Over an 18-month period, 98 patients underwent EUS staging for a new diagnosis of cancer of the esophagus and cardia. Wire-guided dilation was performed if necessary. Standard radial examination was followed by curvilinear evaluation with attention to the left hepatic lobe. All suspicious liver lesions were aspirated under EUS guidance. The radial and curvilinear echoendoscope were successfully passed to the antrum in 86% and 81% of cases, respectively, without complication. Thirty-two percent of patients required dilation. Lesions suspicious for left hepatic lobe metastases were found in 7% of cases that could be completely evaluated by EUS, all of which underwent EUS-guided fine needle aspiration. All lesions were proven metastases: four true-positive and one false-negative cytologic result. Curvilinear EUS examination of the left hepatic lobe in addition to standard radial EUS examination can be performed safely when staging cancer of the esophagus and cardia. Dedicated left hepatic lobe examination should be performed as it avoids unnecessary surgery in a subset of these patients by detection of occult liver metastases.

Early detection of occult colorectal hepatic metastases using duplex colour Doppler sonography.

Previous studies have shown that overt intrahepatic tumours are associated with subtle changes in liver perfusion that can be measured directly using duplex colour Doppler sonography (DCDS). This study assessed the predictive value of DCDS in the early detection of occult colorectal hepatic metastases. Hepatic arterial and portal venous blood flow was measured in 50 control subjects and 135 patients with colorectal cancer, 67 with overt liver metastases and 68 with an apparently disease-free liver on the basis of computed tomography and laparotomy findings. The Doppler perfusion index (DPI), defined as the ratio of hepatic arterial to total liver blood flow, was calculated. Clear separation of the DPI values of controls and those of patients with overt metastases was observed (P < 0.0001). Thirty-eight of the 68 patients with a disease-free liver also had an abnormally high DPI value. After 1 year of follow-up, 21 patients with an abnormally high DPI at the time of apparently curative primary resection had developed liver metastases and a further four had died without post-mortem examination. The 30 patients with normal DPI remain disease-free. The data suggest that DPI is of value in the early detection of occult liver metastases.

Changes in the hepatic perfusion index during the development of experimental hepatic tumours.

A model of microscopic liver tumour has been developed in the Fisher rat by intraportal injection of 1.6 x 10(7) Walker 256 carcinosarcoma cells. Rats were studied at 2, 4 and 6 days after the inoculation of live Walker cells. A control group received dead Walker cells. No tumour was visible in control groups at 2, 4 and 6 days after inoculation. Similarly in rats injected with live cells no tumour was visible at 2 days after inoculation but at 4 and 6 days the percentage hepatic replacement was (mean +/- s.d.) 7.0 +/- 2.3 and 27.9 +/- 6.80 respectively. The hepatic perfusion index was significantly raised at 4 and 6 days after inoculation of live cells compared with control animals and those receiving viable cells after 2 days inoculation. Portal flow and portal venous inflow were significantly reduced when the hepatic perfusion index increased but hepatic arterial flow did not alter. Changes in the hepatic haemodynamics were accompanied by increases in the portal and splanchnic vascular resistance and an increase in the amount of arteriovenous shunting through the liver. These findings confirm studies that the hepatic perfusion index is useful in the detection of occult liver metastases but that the change is not a consequence of an increase in the hepatic arterial flow.

Tuech et al.: Detection of occult liver metastases in colorectal cancer by measurement of biliary carcinoembryonic antigen concentration: a prospective study

Tuech et al.: Detection of occult liver metastases in colorectal cancer by measurement of biliary carcinoembryonic antigen concentration: a prospective study

Detection of occult liver metastases during EUS for staging of malignancies

Background EUS is commonly used in the staging of GI, thoracic, and other malignancies. Studies suggest EUS can detect occult liver metastases, but the frequency with which this occurs is unknown. Methods Records were reviewed for all patients seen during a 3-year period who underwent EUS of the upper-GI tract for staging of known or suspected malignancy. Patients were included if there was histopathologic evidence of malignancy, they had undergone noninvasive liver imaging within 6 weeks of EUS, and liver surveillance was specifically mentioned in the report of the EUS procedure. Results A total of 222 patients were included. Liver lesions were seen in 27 patients, 17 of whom had an abnormal noninvasive liver imaging test. EUS-guided FNA of the liver was performed in 21 patients and was diagnostic of malignancy in 15 (6.8%), 5 of whom (2.3%) had normal noninvasive imaging. In 6 patients, the EUS-guided FNA result was benign. EUS missed liver lesions in 4 patients known to have abnormalities by other imaging modalities. Conclusions EUS can detect occult liver metastases in patients in whom noninvasive hepatic imaging studies are normal, although the frequency at which such lesions are detected is low. Liver surveillance during EUS is worthwhile for patients in whom there is another indication for the procedure; but, at present, EUS should not replace traditional imaging modalities.

The detection of occult liver metastases of colorectal carcinoma.

Despite undergoing an apparently curative surgery, over 50% of colorectal cancer patients will die within 5 years, the majority within the first 2 years from disseminated disease. Occult liver metastases are reported to be present in approximately 30% of patients and they predominantly determine the likelihood of dying from disseminated disease. The question is how to detect these occult hepatic metastases. This article reviews some of the alternative techniques, such as dynamic scintigraphy, functional computerized tomography, and duplex colour Doppler sonography (DCDS), which have been developed to predict which patients harbor these occult metastases. More recently, DCDS measurements of the Doppler perfusion index (DPI: ratio of hepatic arterial to total liver blood flow) have been shown to be highly accurate in the detection of these occult liver metastases. In addition, irrespective of Dukes stage, patients with abnormal DPI were shown to have a very poor outcome while for those with normal DPI, the prognosis was excellent. If the data are reproduced, the administration of adjuvant chemotherapy should be based on DPI status rather than Dukes stage.

Does intraoperative hepatic ultrasonography change surgical decision making during liver resection?

Intraoperative hepatic ultrasonography (IOUS) has been used to accurately identify and localize hepatic tumors as an adjunct to hepatic resection and for the detection of occult liver metastases during primary resection of other gastrointestinal carcinomas. The face validity of IOUS to identify more lesions than conventional diagnostic modalities and the content validity of IOUS to change the planned surgical management has been assessed in a blinded, prospective manner. Sixty-two patients were studied at two institutions by one surgeon. IOUS was compared with computed tomography (CT) angioportography in 30 patients undergoing planned hepatic resection (19 metastatic, 11 primary) and with conventional hepatic ultrasonography (+/- venous enhanced CT scan) in 32 patients undergoing primary excision of gastrointestinal carcinomas. Twenty of the 30 hepatic resections (67%) were changed or guided by IOUS as determined by the operating surgeon at the completion of the laparotomy. IOUS detected 26 more metastases (44%) in 10 of 19 patients (1 to 5 per patient). Two patients had preoperatively suspected metastases refuted by IOUS-guided biopsy. Eight of the 11 patients (73%) undergoing resection of primary carcinoma of the liver had the planned procedure changed or guided by IOUS. This included four hepatocellular carcinomas with more extensive involvement at the confluence of the hepatic veins and the inferior vena cava, necessitating resection with the aid of total vascular isolation. In 32 patients undergoing primary resection of gastrointestinal carcinomas, 5 patients (16%) had the stage of disease altered by IOUS when compared with conventional ultrasound (+/- venous enhanced CT scan). The validity of IOUS is good. IOUS guided the intraoperative surgical management of two thirds of the patients undergoing hepatic resection when compared with CT angioportography. Intraoperative hepatic ultrasonography using a reproducible systematic approach can change the clinical management of patients undergoing hepatic resection for malignancy.