Detection Of Hepatic Metastases Research Articles

Detection of Hepatic Metastases from Cancers of the Gastrointestinal Tract by Using Noninvasive Imaging Methods (US, CT, MR Imaging, PET): A Meta-Analysis

To perform a meta-analysis to compare current noninvasive imaging methods (ultrasonography [US], computed tomography [CT], magnetic resonance [MR] imaging, and (18)F fluorodeoxyglucose [FDG] positron emission tomography [PET]) in the detection of hepatic metastases from colorectal, gastric, and esophageal cancers. A MEDLINE literature search and review of article bibliographies and our institutional charts of patients with colorectal cancer identified data with histopathologic correlation or at least 6 months of patient follow-up. Two authors independently abstracted data sets and excluded data without contingency tables or data published more than once. Summary-weighted estimates of sensitivity were obtained and stratified according to specificity of less than 85% or 85% and higher. A covariate analysis was used to evaluate the influence of patient- or study-related factors on sensitivity. Among 111 data sets, nine US (509 patients), 25 CT (1,747 patients), 11 MR imaging (401 patients), and nine PET (423 patients) data sets met the inclusion criteria. In studies with a specificity higher than 85%, the mean weighted sensitivity was 55% (95% CI: 41, 68) for US, 72% (95% CI: 63, 80) for CT, 76% (95% CI: 57, 91) for MR imaging, and 90% (95% CI: 80, 97) for FDG PET. Results of pairwise comparison between imaging modalities demonstrated a greater sensitivity of FDG PET than US (P =.001), CT (P =.017), and MR imaging (P =.055). At equivalent specificity, FDG PET is the most sensitive noninvasive imaging modality for the diagnosis of hepatic metastases from colorectal, gastric, and esophageal cancers.

Ferumoxide-enhanced MRI in patients with colorectal cancer and rising CEA: surgical correlation in early recurrence

The purpose of this study was to evaluate the value of Ferumoxide-enhanced magnetic resonance (MR) imaging in the detection of hepatic metastases in high-risk patients treated for colorectal cancer that have rising CEA. We used 19 patients treated previously for colorectal cancer with rising CEA levels underwent an unenhanced T 1-weighted (T1W), T 2-weighted (T2W), STIR, and Ferumoxide-enhanced hepatic MRI. Following these studies, a laparotomy was performed and the liver was evaluated by palpation and intraoperative ultrasound. Two observers who were blinded to surgical results evaluated each MR sequence separately. The number of lesions considered highly suspicious for metastatic lesions were determined for each sequence and were compared to the results of surgery. The McNemar test was used to compare the outcomes of the different sequences. MR Imaging was unable to detect small (<5 mm) metastases discovered at surgery. The best non-contrast sequences for detecting metastases were the STIR with 42% sensitivity, 83% specificity and an overall accuracy of 56% and the T1W sequence (sensitivity 38%, specificity 100%, accuracy 57%), which were not significantly different ( p > 0.4). The noncontrast T2W sequence had a sensitivity of 29% and a specificity of 77% with an overall accuracy of 46%. When all pre contrast scans were grouped together the common sensitivity was 42%, specificity was 77% and accuracy was 54%. The post-ferumoxide T 2W scans had a sensitivity of 42%, specificity of 85%, and accuracy of 57%, but did not detect any additional lesions. There was no statistical difference between the pre- and post-contrast studies with regard to identifying patients with metastatic disease ( p > 0.1). In conclusion, we found small hepatic metastases in patients with early signs of recurrent colorectal cancer are difficult to detect on MRI. Ferumoxide-enhanced MRI was unable to detect additional hepatic metastases and performed no better than unenhanced MRI in detecting small hepatic metastasis.

Hepatic metastases: the value of quantitative assessment of contrast enhancement on computed tomography

Objective: Occult and overt hepatic metastases have been the target of research in an effort to improve detection and characterisation of cancer spread and, consequently, guidance of treatment. This paper aims to illustrate the value of two quantitative techniques for assessing contrast enhancement during CT in the detection of hepatic metastases. It outlines the applications to which they can be put, and the ease of incorporation into current protocols. Methods and material: The first technique, perfusion CT, uses a single location dynamic CT sequence to obtain time–attenuation data whilst a short, high concentration IV bolus of contrast passes through the abdominal vasculature. Quantitative hepatic arterial and portal values are calculated, along with a perfusion image map. The second technique uses densitometric analysis during a modified contrast enhanced dual-phase liver CT examination. Semi-quantitative values are calculated from the images obtained at the 25 and 40 s times. Results: Both perfusion CT and densitometric analysis have been to shown to differentiate between normal and tumour-bearing liver as defined by structural CT. Hepatic metastases are associated with increased arterial perfusion and arterial phase enhancement. Increased arterial phase enhancement on densitometric analysis in the absence of overt lesions heralds the onset of visible metastases in the liver in the ensuing 18 months. Perfusion CT has also demonstrated a correlation between high arterial perfusion around a visible metastasis and increased survival. Conclusion: Both techniques can provide more information than is available from conventional enhanced CT scans alone. An algorithm for the clinical application of perfusion CT is proposed. The ease with which these quantitative techniques can be performed and the extra information they provide could lead to improved staging of cancer and more appropriate patient management.

Pelvic exenteration for advanced primary rectal cancer in male patients

Between November 1987 and January 1996 pelvic exenteration for primary rectal cancer was carried out in 11 male patients. Two underwent a primary resection with subtotal cystectomy. In the remaining nine patients, the treatment commenced with a staging laparotomy and the fashioning of an end colostomy of the descending colon, followed by preoperative radiotherapy (50–56 Gy in 5 weeks). Total exenteration with ureteroileo-cutaneostomy was carried out 4–6 weeks later. In two patients, the exenteration was performed despite the detection of hepatic metastases during the second laparotomy. The pathological staging was T4 in six and T3 in five patients. The immediate postoperative course was uneventful in eight patients and their hospital stay averaged 20 days. Serious postoperative complications prolonged the hospital stay of three patients. Three died during the first 6 months. Recurrent disease caused the death of three of the eight remaining patients: one locoregional (7.5 years after surgery) one from pre-existing hepatic metastases (18 months after surgery) and one from the combination of locoregional and distant recurrence (15 months after surgery). Four patients are on follow-up without evidence of disease, 96, 43, 23 and 22 months after surgery. One patient is alive 20 months after exenteration, with two pulmonary metastases having been recently excised.We conclude that, notwithstanding the morbidity rate, total pelvic exenteration is an acceptable option for advanced primary rectal cancer in male patients. Preoperative radiotherapy should be administered for cancers seated in the lower two-thirds of the rectum and perioperative chemotherapy should be considered seriously.

Laparoscopic ultrasound for the detection of hepatic metastases during laparoscopic surgery

SummaryWe report the use of a new flexible-tipped laparoscopic ultrasound transducer during laparoscopic colorectal surgery. The flexible tip, in combination with ‘picture on picture’ videomonitoring, facilitates efficient hepatic assessment. Our early experience suggests that this technique may identify metastases not detected by conventional imaging modalities.

Intraoperative ultrasonography in detection of hepatic metastases from colorectal cancer

This study was designed to compare diagnostic accuracies of measuring liver enzymes, preoperative ultrasonography, surgical examination, and intraoperative ultrasonography for detection of liver metastases from colorectal cancer. Blind, prospective comparisons of diagnostic examinations mentioned above were performed in 295 consecutive patients with colorectal cancer. An experienced ultrasonologist performed the preoperative examinations, and results were unknown to the other experienced ultrasonologist who performed the intraoperative examinations. The latter, also was unaware of the findings by the surgeon. The presence of metastases was further assessed by ultrasonography three months postoperatively, as well as additional surgery and liver biopsy in some of the patients. The sensitivity of intraoperative ultrasonography (62/64) was significantly superior to that of surgical exploration (54/64) and that of preoperative ultrasonography (45/64). The lowest sensitivity was presented by liver enzymes. Bilobar metastases were detected in 42 of 46 patients by intraoperative ultrasonography but in only 33 patients by the surgeon. Intraoperative ultrasonography demonstrated the highest specificity of all examinations. Intraoperative ultrasonography reduces the number of patients with liver metastases from being subjected to superfluous or even harmful liver surgery, and it may increase the number in whom liver surgery will prolong life.

A PHASE I STUDY OF SWAINSONINE IN PATIENTS WITH ADVANCED MALIGNANCIES

Abstract Swainsonine, an α-mannosidase inhibitor which blocks Golgi oligosaccharide processing, represents a new class of compounds that inhibit both rate of tumor growth, and metastasis, in murine experimental tumor models. In this first phase I study, the quantitative and qualitative toxicities of swainsonine have been studied in patients given a continuous i.v. infusion over 5 days, repeated at 28-day intervals. Dose levels were escalated in increments of 100 µg/kg/day from 50–550 µg/kg/day. Nineteen patients with both solid tumor and hematological malignancies were given a total of 31 courses. Hepatotoxicity, particularly in patients with liver metastases, was the dose-limiting toxicity. The maximum tolerated dose (MTD) and the recommended starting dose (MTD -1 level) were 550 and 450 µg/kg/day, respectively. Common side effects included edema, mild liver dysfunction, a rise in serum amylase, and decreased serum retinol. Acute respiratory distress syndrome possibly precipitated by swainsonine resulted in a treatment-related death in a patient with significant pretreatment hepatic dysfunction. One patient with head and neck cancer showed >50% shrinkage of tumor mass for 6 weeks after treatment. Two patients with lymphangitis carcinomatosis on chest X-ray noted improvement in cough and shortness of breath during the infusion of swainsonine and for 1 week thereafter. Clearance and serum half-life for swainsonine were determined to be approximately 2 ml/h/kg, and 0.5 day, respectively. Golgi oligosaccharide processing, a putative anticancer target for swainsonine was inhibited in peripheral blood lymphocytes as evidenced by a marked decrease in leukoagglutinin binding after 5 days of treatment. Oligomannosides in patient urine increased 5-to 10-fold over the 5 days of treatment, indicating that tissue lysosomal α-mannosidases were also blocked by swainsonine. Urine oligomannoside accumulation reached steady state at 3 days, approximately 1 day after serum drug levels reached steady state. The fraction of HLA-DR-positive cells in peripheral blood lymphocytes increased following 5 days of swainsonine treatment, an effect similar to that observed for peripheral blood lymphocytes from normal subjects cultured with swainsonine. No significant changes in CD3, CD4, CD8, CD16, and CD25 were observed. Swainsonine produces minimal toxicity when administered i.v. to cancer patients at dosages that inhibit both Golgi α-mannosidase II and lysosomal α-mannosidases. Detection of hepatic metastases or liver enzyme abnormalities prior to treatment predict for more significant toxicity.

New imaging modalities for follow-up of colorectal carcinoma

Recurrent disease after curative resection occurred in 37-44% of patients. The common sites of recurrent disease are at the anastomotic site, in the liver, in the lymph nodes, and in the peritoneal linings. Computed tomography (CT), barium enema, and endoscopy detected local recurrent disease in 61-88% of the patients, whereas magnetic resonance imaging (MRI) detected 80-88% of the cases reported in some Phase 1 studies. CT and MRI are equally effective in the detection of hepatic metastases when lesions are larger than 2 cm, with detectability rate of 95-100%. They are fair (50-60% detectability rate) when tumors are between 1 and 2 cm and poor (less than 40%) when tumors are smaller than 1 cm. For recurrent nodal metastases and peritoneal deposits, CT is the modality of choice.

Comparisons of dynamic infusion and delayed computed tomography, intraoperative ultrasound, and palpation in the diagnosis of liver metastases

The purpose of this study was to determine whether delayed computed tomography (DCT) of the liver would more accurately detect hepatic malignancy when compared with bolus contrast-enhanced dynamic computed tomography (BCDCT). Fifty-one patients who required operation for intra-abdominal malignancy (92% with colorectal cancers) underwent preoperative BCDCT followed by DCT. At operation, palpation and intraoperative ultrasound (IOUS) examination of the liver were performed for localization and biopsy of tumor nodules. The standard for diagnosis was defined for this study as the combined results of IOUS, palpation, and biopsy. The sensitivities of BCDCT and DCT for hepatic metastases were 50% and 54%, respectively, with a corresponding specificity of 72% for each. DCT demonstrated no significant improvement over BCDCT in the detection of individual hepatic lesions. The sensitivity of palpation for the detection of metastases was 82%, equal to that of IOUS. Both palpation and IOUS were significantly superior to BCDCT or DCT in excluding false-positive and false-negative results (p < 0.001). IOUS failed to identify surface lesions less than 1.0 cm in diameter (sensitivity: 40%). Conversely, palpation was limited in the detection of subsurface tumors less than 1.0 cm in diameter (sensitivity: 33%). Combined IOUS and palpation were significantly more accurate in the detection of hepatic metastases than any single modality that was evaluated (p < 0.001).

Pancreatic adenocarcinoma: designing the examination to evaluate the clinical questions.

The dynamic incremental bolus technique and modifications in slice thickness can be used to tailor current computed tomographic (CT) technology to evaluate the extent of pancreatic cancer. Contrast material administered intravenously allows visualization of small lesions, an assessment of vascular invasion versus patency, and maximal conspicuity and detectability of hepatic metastases. CT findings in 104 cases of pancreatic cancer studied during 1979-1982 (group A) were compared with findings in 107 cases of pancreatic cancer studied during 1984-1987 (group B). Masses in the body and tail of the pancreas were recognized in 96% (n = 103) of cases in group B and 89% (n = 93) in group A. Masses in the head of the gland were detectable in 94% (n = 101) of cases in group B and 76% (n = 79) of cases in group A. Hypoattenuating tumors were detectable in 78% (n = 83) of cases in group B, as opposed to 24% (n = 25) in group A. CT is the primary diagnostic technique in the evaluation of pancreatic adenocarcinoma.

Alternative techniques in the detection of hepatic metastases: HPI or DPI?

Alternative techniques in the detection of hepatic metastases: HPI or DPI?

Hepatic metastases: CT versus MR imaging at 1.5T

A prospective multi-institutional study was performed to compare the sensitivity of computed tomography (CT) and high-field magnetic resonance (MR) imaging (1.5T) in the detection of hepatic metastases. T1-weighted and 72-weighted spin-echo (SE) MR images were compared with noncontrast, dynamic, and delayed CT. Sixty-nine oncology patients were studied. Noncontrast CT showed an overall sensitivity of 57%, dynamic CT 71%, delayed CT 72%, T1-weighted SE MR 47%, and T2-weighted SE MR 78%. Although there was no statistically significant (p less than 0.05) difference among dynamic CT, delayed CT, and T2-weighted SE MR, these three methods were significantly more sensitive (p less than 0.005) than noncontrast CT or T1-weighted SE MR. T2-weighted SE MR was significantly more sensitive (p less than 0.006) than CT or T1-weighted SE MR in the detection of small (less than 1 cm) lesions. CT was more sensitive in the detection of extrahepatic disease. These data confirm the superiority of T2-weighted SE over T1-weighted SE pulse sequences at 1.5T.

Liposomes as MR contrast agents: Pros and cons

Liposomes are generally thought of as being useful for entrapping drugs within their internal aqueous space. When used with MR contrast agents, this has the drawback that water flux across the membrane bilayer is limiting to contrast enhancement. This can be partially overcome by making the liposomes very small, such that surface area is relatively great compared to internal volume, thereby facilitating water exchange. Alternatively the membranes can be designed to be permeable to water but this may render the vesicles unstable in serum. Another approach is to incorporate the contrast agents into the lipid bilayer. By designing novel complexes of manganese with the ligands incorporated onto dual acyl chains, we have achieved R1 and R2 values of over 20/mmol sec-1 or more than five times higher than Gd-DTPA. Hepatic metastasis detection is significantly improved in rats at doses of only 10 mumol/kg manganese. Membrane-bound manganese complexes function as highly effective liver imaging agents and merit further study for development as agents to undergo human clinical trials.

Comparison of high molecular weight alkaline phosphatase and glycylproline dipeptidylaminopeptidase for the detection of hepatic metastasis by liver function tests in lung cancer patients : Nishio H, Sakuma T, Nakamura S-I, Horai T, Ikegami H, Matsuda M. Department of Internal Medicine, Osaka Second Police Hospital. Osaka. Lung Cancer (Japan) 1990;30:51–57

Comparison of high molecular weight alkaline phosphatase and glycylproline dipeptidylaminopeptidase for the detection of hepatic metastasis by liver function tests in lung cancer patients : Nishio H, Sakuma T, Nakamura S-I, Horai T, Ikegami H, Matsuda M. Department of Internal Medicine, Osaka Second Police Hospital. Osaka. Lung Cancer (Japan) 1990;30:51–57

The use of duplex sonography in the detection of colorectal hepatic metastases

Conventional imaging techniques are of limited value in identifying small liver metastases. Indirect methods of measuring blood-flow have shown that metastases may be associated with subtle changes in liver blood-flow. Doppler ultrasonography has the ability to measure liver blood-flow directly. In this study, the role of duplex sonography in the detection of hepatic metastases was evaluated. Hepatic arterial and portal venous blood-flows were measured in 30 patients awaiting surgery for colorectal cancer and 16 controls. The ratio of hepatic arterial: portal venous blood-flow (Doppler flow ratio; DFR) and the ratio of hepatic arterial:hepatic arterial and portal venous blood-flow (Doppler perfusion index; DPI) were calculated. Clear separation of the DPI and DFR values of controls and patients with histologically confirmed liver metastases was observed (P less than 0.001). The data suggest that the measurement of liver blood-flow by duplex sonography may be of value in the diagnosis of colorectal liver metastases.

AN EVALUATION OF HEPATIC RESECTION AND PATHOLOGICAL FINDINGS FOR METASTASIS FROM THE COLORECTAL CANCER

Among 276 patients operated on for colorectal cancers at our department from March 1982 to September 1989, 37 with hepatic metastasis, especially 14 undergone hepatic resection were subjected to a study of therapeutic outcomes and clinicopatological features. 1) All resectable cases of heterochronical hepatic metastasis can survive, showing a favorable prognosis. 2) Resectable cases of isochronical hepatic metastasis had poorer prognosis compared with those of heterochronical metastasis. However, when compared with inresectable hepatic metastasis cases, the survival rate was higher and a life-prolonging effect due to hepatic resection could be expected. 3) In cases of which metastasized hepatic lesions locate only in a lateral lobe, we should select lobectomy or a resective procedure where a sufficient distance between the tumor and resected section of the liver is left if the residual hepatic function can permit. 4) For early detection of hepatic metastasis from colorectal cancer, regularized followup with CEA, US, and CT is essential. 5) Histological findings of the primary lesions revealed that significantly high rates of hepatic metastasis were noted in moderately differentiated adenocarcinomas, cancers with positive regional lymph nodes, and those with positive vascular invasion.

Detection of hepatic metastases: comparison of contrast-enhanced CT, unenhanced MR imaging, and iron oxide-enhanced MR imaging.

Diagnostic accuracy of contrast-enhanced CT, unenhanced MR imaging, and MR images enhanced with superparamagnetic iron oxide was evaluated in 10 patients with histologically proved hepatic metastases. First, diagnostic performance of the imaging technique with respect to the ability of radiologists to recognize the presence or absence of a metastasis was measured by using receiver-operating-characteristic (ROC) analysis of single images. Second, the total number of lesions (N = 108) detected by "complete" CT and MR examinations was counted. Finally, lesion-liver contrast-to-noise ratios (CNR) were measured in all MR sequences. The area under the ROC curve was .67 +/- .03 for contrast-enhanced CT, .81 +/- .07 for the unenhanced SE 260/14 sequence, and .92 +/- .01 for the iron oxide-enhanced SE 1500/40 sequence. The enhanced SE 1500/40 sequence yielded significantly (p less than .005) greater accuracy than did contrast-enhanced CT. The same sequence detected significantly (p less than .05) more lesions than all other imaging techniques (19% more than the best unenhanced MR sequence and 36% more than contrast-enhanced CT). The enhanced SE 1500/40 sequence also yielded the highest CNR value (19.5 +/- 10.2) of all MR sequences. These results indicate that iron oxide-enhanced MR imaging is a superior imaging technique for the detection of hepatic lesions.

Detection of Hepatic Metastases in Breast Cancer

Nonenhanced and enhanced CT was compared in 88 patients with breast cancer and hepatic metastasis. Twenty-five patients had bolus, sequential dynamic CT, and 63 patients were scanned more slowly after a bolus or during drip infusion. Metastatic lesions were more conspicuous on nonenhanced CT and became isodense or nearly isodense after contrast medium administration in 28% of the patients scanned dynamically and in 29% of those scanned more slowly. Although breast cancer has not generally been considered a common origin of hypervascular metastases, we recommend that it be treated as such and that both enhanced and nonenhanced CT of the liver be obtained when patients are screened for metastasis.

Immunoscintigraphy of colorectal cancer with an antibody to epithelial membrane antigen (EMA)

Immunoperoxidase staining of LICR-LON M8, a mouse monoclonal antibody reactive with epithelial membrane antigen, showed a strong reaction with colorectal cancer. This finding prompted an immunoscintigraphic study of colorectal cancer patients using this antibody. Sixteen patients had external gamma scintigraphy after intravenous injection of indium 111-labeled M8. Positive scans were obtained in 11 of the 13 patients with primary colorectal cancers, and 2 of the 3 patients with recurrent tumors. The high indium 111 background in the liver prevented the detection of hepatic metastases in 5 patients. Twelve patients had samples taken of tumor, normal colon, and venous blood at the time of surgery. The ratio of labeled antibody uptake in tumor to that of blood was 5.1 (+/- 3.6 S.D.), which was significantly different (P = 0.001) to that of the similar ratio for normal colon (2.0 +/- 1.6 S.D.). The tumor to normal colon uptake ratio was 2.6 (+/- 1.3 S.D.). These results suggest a specific uptake of indium 111-labeled M8 by colorectal cancer.

The Role of CEA and Liver Function Tests in the Detection of Hepatic Metastases From Colo‐Rectal Cancer

Carcinoembryonic antigen and some liver function tests (alkaline phosphatase, gamma-glutamyl-transpeptidase, lactic dehydrogenase and cholinesterase) were evaluated in patients with primary colorectal cancer in order to define their role in the pre-operative detection of liver metastases. The records of 278 consecutive patients admitted to the Istituto Nazionale Tumori of Milan between January 1982 and December 1983 who were suffering from primary invasive colo-rectal cancer and who underwent laparotomy were retrospectively analyzed. At laparotomy, liver metastases were found in 38 pts (13.7%). Considering single tests, CEA was the most sensitive (71%); no single test was found to be reliably predictive, when the result was abnormal. On the contrary, the normal value of each test was associated with a good prediction. When we considered all the five tests together in the single patient their predictive value, when abnormal, proved to be quite good only if four or five results were abnormal. On the other hand, liver metastases in the presence of all normal tests were found only in two patients, so giving a negative predictive value of about 97%. So we conclude that, in the lack of an infallable imaging technique for liver evaluation, in the presence of all normal tests any other investigation on the liver could be avoided. However, when liver tests are pathologic, some other imaging technique should be performed in order to supply the surgeon with information about the extent and the spread of the metastases.