Antithrombotic drugs and non-variceal bleeding outcomes and risk scoring systems: comparison of Glasgow Blatchford, Rockall and Charlson scores.

OBJECTIVES: Antithrombotic drugs (ATDs) cause non-variceal upper gastrointestinal bleeding (NVUGIB). Risk scoring systems have not been validated in ATD users. We compared Blatchford, Rockall and Charlson scores in predicting outcomes of NVUGIB in ATD users and controls. METHODS: A total of 2071 patients with NVUGIB were grouped into ATD users (n=851) and controls (n=1220) in a single-centre retrospective analysis. Outcomes included duration of hospital admission, the need for blood transfusion, rebleeding requiring surgery and 30-day mortality. RESULTS: Duration of admission correlated with all scores in controls, but correlations were significantly weaker in ATD users. Rank correlation coefficients in control versus ATD: 0.45 vs 0.20 for Blatchford; 0.48 vs 0.32 for Rockall and 0.42 vs 0.26 for Charlson (all p<0.001). The need for transfusion was best predicted by Blatchford (p<0.001 vs Rockall and Charlson in both ATD users and controls), but all scores performed less well in ATD users. Area under the receiver operation characteristic curve (AUC) in control versus ATD: 0.90 vs 0.85 for Blatchford; 0.77 vs 0.61 for Rockall and 0.69 vs 0.56 for Charlson (all p<0.005). In predicting surgery, Rockall performed best; while mortality was best predicted by Charlson with lower AUCs in ATD patients than controls (p<0.05). Stratification showed the scores' performance to be age-dependent. CONCLUSIONS: Blatchford score was the strongest predictor of transfusion, Rockall's had the strongest correlation with duration of admission and with rebleeding requiring surgery and Charlson was best in predicting 30-day mortality. Modifications of these systems should be explored to improve their efficiency in ATD users.

Upper gastrointestinal bleeding in hospital inpatients: the role of antithrombotic drugs.

BACKGROUND: Critically ill patients are considered to be most at risk from developing non-variceal upper gastrointestinal bleeding (NVGIB) while in hospital. The increasing prescription of low-dose aspirin and other antithrombotic drugs for protection against thromboembolism to many patients admitted to hospital may increase the vulnerability of a wider group to NVGIB. OBJECTIVE: This study compares two groups of patients with NVGIB: group I, inpatients cared for outside the intensive care unit; and group II, patients admitted with this condition, while considering the use of antithrombotic drugs. METHODS: We identified all patients who developed NVGIB in the two calendar years between 2008 and 2009 and compared group I with group II while taking into account their clinical details including Rockall scores and drug usage. RESULTS: Compared with group II (n=274), group I (n=96) were older (median age of 77 years vs 68; p<0.001), had fewer males (45.8% vs 60.6%; p=0.016), higher prevalence of cardiovascular disease (52.1% vs 29.2%; p<0.001), more patients with complete Rockall score ≥ 3 (84.4% vs 66.7%; p=0.001) and more patients treated with aspirin or other antithrombotic drugs (64.6% vs 44.5%; p=0.001). After adjustment for age and sex, group I were still significantly more likely to be taking antithrombotic drugs than group II (OR (95% CIs), 2.15 (1.25 to 3.68); p=0.006). The endoscopic abnormalities in more than 80% of patients included erosive oesophagitis, gastric or duodenal ulcers or erosions. CONCLUSIONS: Subjects who develop NVGIB as inpatients have higher Rockall scores are mainly older females with cardiovascular disease and using antithrombotic drugs. Secondary care clinicians should be mindful of this at-risk group of patients and consider giving them prophylactic antiulcer therapy.

Falling mortality when adjusted for comorbidity in upper gastrointestinal bleeding: relevance of multi-disciplinary care.

OBJECTIVES: The understanding of changes in comorbidity might improve the management of upper gastrointestinal bleeding (UGIB); such changes might not be detectable in short-term studies. We aimed to study UGIB mortality as adjusted for comorbidity and the trends in risk scores over a 14-year period. METHODS: Patients presenting with UGIB to a single institution, 1996-2010, were assessed. Those with multiple comorbidities were managed in a multi-disciplinary care unit since 2000. Trends with time were assessed using logistic regression, including those for Charlson comorbidity score, the complete Rockall score and 30-day mortality. RESULTS: 2669 patients were included. The Charlson comorbidity score increased significantly with time: the odds of a high (3+) score increasing at a relative rate of 4.4% a year (OR 1.044; p<0.001). The overall 30-day mortality was 4.9% and inpatient mortality was 7.1%; these showed no relationship with time. When adjusted for the increasing comorbidity, the odds of death decreased significantly at a relative rate of 4.5% per year (p=0.038). After the introduction of multi-disciplinary care, the raw mortality OR was 0.680 (p=0.08), and adjusted for comorbidity it was 0.566 (p=0.013). CONCLUSIONS: 30-day mortality decreased when adjusted for the rising comorbidity in UGIB; whether this is related to the introduction of multi-disciplinary care needs to be considered.

Gastro-protective policy and the incidence of upper gastrointestinal bleeding.

OBJECTIVES: In recent years, policies have been proposed in order to guide the safer use of non-steroidal anti-inflammatory drugs (NSAIDs) and antiulcer therapy. We aimed to investigate the incidence of upper gastrointestinal bleeding (UGIB) before and after the introduction of these policies, 2007-2009, in a well-defined population in southwest Scotland. METHODS: All patients with non-variceal upper gastrointestinal bleeding (NV-UGIB), diagnosed at a single regional unit, were included. Total drugs prescribed in our population were noted, including antiulcer drugs, antithrombotic drugs and both cyclo-oxygenase-2 enzyme-selective and non-selective inhibiting NSAIDs. RESULTS: The incidence, the number of cases per 100 000 population per annum, of NV-UGIB fell from 134.7 in 2007 to 125.1 in 2008, and to 90.3 cases in 2009 (p<0.001). There was also a significant rise in the use of non-selective NSAIDs, proton pump inhibitors and antithrombotic drugs. CONCLUSIONS: Although a cause-and-effect relationship cannot be fully proven, physician education through drug-use policies is associated with a drop in the incidence of NV-UGIB. This is relevant to the prevention of this common condition.

Mortality following blood transfusion for non-variceal upper gastrointestinal bleeding.

OBJECTIVE: Blood transfusion remains an integral step in the management of acute non-variceal upper gastrointestinal bleeding (NV-UGIB), but its safety is being increasingly questioned in less severe cases. The authors aimed to measure 30-day and 2-year mortalities after blood transfusion for NV-UGIB. METHODS: Cox proportional hazards models were used to estimate the association of blood transfusion with mortality while adjusting for age, Charlson comorbidity score, the complete Rockall score for acute UGIB, admission status and medication intake prior to bleeding. MAIN OUTCOME MEASURES: Death from any cause at 30 days and 2 years after NV-UGIB. RESULTS: 1340 patients presented with NV-UGIB< (808 men (60.3%), median age 67 years) of whom 564 (42.1%) were transfused. The overall mortality was 5.3% at 30 days and 26.0% at 2 years in all patients. Comparing subjects with a haemoglobin concentration greater than 10.0 g/dl who were transfused with those who were not, 30-day mortalities (95% CIs) were 11.5% (6.7 to 18.0) versus 3.6% (2.3 to 5.3), respectively, p<0.001, and 2-year mortalities (95% CIs) were 40% (32 to 49) versus 20% (17 to 23), p<0.001. After adjusting for age, Charlson score, Rockall score and haemoglobin, the HRs (95% CIs) for death after transfusion were 1.88 (1.00 to 3.55) (p=0.051) at 30 days and 1.71 (1.28 to 2.28), (p<0.001) at 2 years. CONCLUSION: In patients with moderately severe NV-UGIB, mortality is higher following blood transfusion. Whether this reflects selection bias, an effect of comorbidity or an effect of transfusion requires urgent prospective study.

Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer.

Previous studies suggest that disease recurrence peaks at around 2 years in patients with early stage breast cancer (EBC), but provide no data regarding recurrence type. This retrospective analysis aimed to identify early recurrence types and risk factors in estrogen receptor-positive (ER+) EBC patients treated with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women diagnosed with ER+ EBC from 1995 to 2004 were evaluated. Annual hazard ratios (HR) for recurrence at different sites were calculated. Time-dependent Cox regression analysis was used to identify predictors of recurrence within 2.5 years of diagnosis, including factors that were more strongly predictive of early than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95% confidence interval) were: overall 6.3% (5.5-7.1), locoregional 1.1% (0.7-1.5), contralateral 0.5% (0.3-0.7), and distant 4.8% (4.0-5.6). The annual HR of overall recurrence peaked at 2 years (4.3% per annum). The majority of this peak represented distant recurrence (3.4% per annum). In Cox regression analysis, tumor size and grade, lymph node involvement, lymphovascular invasion, and symptomatic presentation were significant independent predictors of early recurrence. Age at diagnosis was independently predictive of recurrence within 2.5 years of diagnosis but not later recurrence. This study identified an early recurrence peak at 2 years, most of which were distant recurrences. Implementing an aromatase inhibitor after an initial 2-3 years of tamoxifen fails to address this early peak of distant recurrence and the potential breast cancer-associated mortality.

Tumor size is associated with the systemic inflammatory response but not survival in patients with primary operable colorectal cancer.

AIM: To examine the relationship between tumor diameter, C-reactive protein concentrations and survival in patients undergoing surgery for colorectal cancer. METHOD: Tumor diameter and pathological characteristics of the resected specimen were assessed in 227 patients. Circulating concentrations of C-reactive protein were measured prior to surgery. RESULTS: Ninety-six patients had an elevated C-reactive protein concentration (>10 mg/L) prior to surgery. Tumor size was associated with an elevated C-reactive protein concentration (P < 0.001). C-reactive protein concentrations (P < 0.001) were associated with poorer cancer-specific survival. CONCLUSION: Prior to surgery, the maximal tumor diameter is associated with an elevated preoperative C-reactive protein concentration but not survival in patients with primary operable colorectal cancer.

Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer.

BACKGROUND/AIMS: The aim of the study was to examine the value of the combination of an elevated C-reactive protein and hypoalbuminaemia (GPS) in predicting cancer-specific survival after resection for colon and rectal cancer. MATERIALS AND METHODS: The GPS was constructed as follows: Patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminaemia (<35 g/l) were allocated a score of 2. Patients in whom only one or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. RESULTS: A GPS of 1 (n = 109) was mainly due to an elevated C-reactive protein concentration and the remainder due to hypoalbuminaemia. In those patients with a GPS of 1 due to hypoalbuminaemia (n = 16), the 3-year overall survival rate was 94% compared with 62% in those patients with a GPS of 1 due to an elevated C-reactive protein concentration (n = 93, p = 0.0094). Therefore, the GPS was modified such that patients with hypoalbuminaemia were assigned a score of 0 in the absence of an elevated C-reactive protein. On univariate analysis of those patients with colon and rectal cancer, the modified GPS (p < 0.0001) was significantly associated with overall and cancer specific survival. On univariate survival analysis of those patients with Dukes B colon and rectal cancer, the modified GPS (p < 0.01) was significantly associated with overall and cancer specific survival. CONCLUSION: The results of the present study indicate that the GPS, before surgery, predicts overall and cancer-specific survival after resection of colon and rectal cancer.

Microsatellite analysis for determination of the mutagenicity of extremely low-frequency electromagnetic fields and ionising radiation in vitro.

Extremely low-frequency electromagnetic fields (ELF-EMF) have been reported to induce lesions in DNA and to enhance the mutagenicity of ionising radiation. However, the significance of these findings is uncertain because the determination of the carcinogenic potential of EMFs has largely been based on investigations of large chromosomal aberrations. Using a more sensitive method of detecting DNA damage involving microsatellite sequences, we observed that exposure of UVW human glioma cells to ELF-EMF alone at a field strength of 1 mT (50 Hz) for 12 h gave rise to 0.011 mutations/locus/cell. This was equivalent to a 3.75-fold increase in mutation induction compared with unexposed controls. Furthermore, ELF-EMF increased the mutagenic capacity of 0.3 and 3 Gy gamma-irradiation by factors of 2.6 and 2.75, respectively. These results suggest not only that ELF-EMF is mutagenic as a single agent but also that it can potentiate the mutagenicity of ionising radiation. Treatment with 0.3 Gy induced more than 10 times more mutations per unit dose than irradiation with 3 Gy, indicating hypermutability at low dose.

Prospective multicenter trial evaluating a novel method of characterizing focal liver lesions using contrast-enhanced sonography.

OBJECTIVE: The purpose of this study was to assess the clinical value and potential impact of SonoVue-enhanced sonography in the characterization of focal liver lesions. SUBJECTS AND METHODS: This study included 127 patients with 82 malignant and 52 benign lesions in the liver. Contrast-enhanced sonography was performed using nonlinear imaging modes at low mechanical index (0.1-0.3) to enable real-time visualization of arterial, portal, and late-phase enhancement. Digital recordings of unenhanced sonography and contrast-enhanced sonography were reviewed by on-site investigators and two off-site blinded interpreters. The final diagnosis was based on consensus interpreting of all examinations by another two expert observers with access to CT, MRI, and histologic data; the diagnostic accuracy of contrast-enhanced sonography in identifying the lesion as benign, malignant, or indeterminate and as actual tumor type was compared with baseline sonography. RESULTS: For on-site investigators, contrast-enhanced sonography reduced the number of indeterminate diagnoses by 67% and improved the sensitivity and specificity to 90.2% and 80.8%, respectively (p < 0.001). For off-site interpreters, contrast-enhanced sonography reduced the number of indeterminate diagnoses by 51-56% (p < 0.001); significantly improved sensitivity and specificity to 90.8-95.4% and 83.7-89.8%, respectively (p < 0.001); eliminated observers' variability (kappa coefficient: 0.66-0.77); and showed no significant difference in all comparisons in the analysis of lesions measuring less than 1.5 cm, 1.5-2.5 cm, and all sizes combined. Contrast-enhanced sonography did not rely on availability of clinical history to enable the diagnoses, and it reduced the need for further imaging investigations 23.7% to 90.4%. CONCLUSION: Contrast-enhanced sonography improves the characterization of focal liver lesions and may limit the need for further investigations.

Potential value of contrast-enhanced intraoperative ultrasonography during partial hepatectomy for metastases: an essential investigation before resection?

OBJECTIVE: The aim of the study was to assess the clinical value of contrast-enhanced intraoperative ultrasound (CE-IOUS) as a novel tool in the hepatic staging of patients undergoing liver resection. METHODS: Sixty patients scheduled to undergo liver resection for metastatic disease were studied. Preoperative staging with contrast-enhanced CT and/or MR scans was performed within 2 to 6 weeks of operation. Following exploration, intraoperative ultrasound (IOUS) was performed using an HDI-5000 scanner (Philips) and a finger-probe with pulse inversion harmonic (PIH) capability. CE-IOUS in the PIH mode was performed in a standardized protocol (low MI: 0.02-0.04) after intravenous injection of 3-4 mL of SonoVue (Bracco spa, Milan); all detected lesions on precontrast and postcontrast scans were counted and mapped. Any alteration in surgical management was documented following CE-IOUS compared with IOUS. RESULTS: Three patients were excluded due to disseminated disease on exploration. CE-IOUS was significantly more sensitive than CT/MR and IOUS in detecting liver metastases (96.1% versus 76.7% and 81.5%, respectively) (P<0.05); it altered surgical management in 29.8% (17 of 57) of cases, due to 1) additional metastases in 19.3% (11 of 57), 2) less metastases in 3.5% (2 of 57), 3) benign lesions wrongly diagnosed as metastasis on IOUS/CT in 5.3% (3 of 57), and 4) vascular proximity in 1.8% (1 of 57). Management was unchanged in 70.2% (40 of 57) despite additional lesions detected in 3.5% (2 of 57) and benign lesion wrongly diagnosed on IOUS and CT as metastasis in 1.8% (1 of 57). CE-IOUS altered combined IOUS/CT/MR staging in 35.1%. CONCLUSION: These preliminary results suggest CE-IOUS is an essential tool prior to liver resection for metastases.

[131I]meta-iodobenzylguanidine and topotecan combination treatment of tumors expressing the noradrenaline transporter.

PURPOSE: Both [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG) and the topoisomerase I inhibitor topotecan are effective as single-agent treatments of neuroblastoma. The aim of this study was to investigate the efficacy of [(131)I]MIBG in combination with topotecan in vitro and in vivo. EXPERIMENTAL DESIGN: The cell lines used were SK-N-BE(2c) (human neuroblastoma) and UVW/NAT (glioma cell line transfected with the noradrenaline transporter gene). Three different treatment schedules were assessed: topotecan given before (schedule 1), after (schedule 2), or simultaneously (schedule 3) with [(131)I]MIBG. DNA strand breakage was evaluated by comet assay, and cytotoxicity was determined by clonogenic survival. Efficacy was also measured by growth delay of tumor xenografts in nude mice. RESULTS: Combination schedules 2 and 3 caused more cytotoxicity than schedule 1. Similarly, significant DNA damage was observed following treatment schedules 2 and 3 (P < 0.005) but not schedule 1. The mean number of days for a doubling in volume of SK-N-BE(2c) tumors and a 10-fold increase in volume of UVW/NAT tumors were 10.4 and 18.6 (untreated), 19.7 and 25.3 (topotecan alone), 22.8 and 31.9 ([(131)I]MIBG alone), 26.3 and 37.1 (combination schedule 1), 34.3 and 49.7 (combination schedule 2), and 53.2 and >71 (combination schedule 3), respectively. The highest rate of cure of both xenografts was observed following treatment with combination schedule 3. CONCLUSIONS: The combination of topotecan and [(131)I]MIBG compared with either treatment alone gave rise to greater than additive DNA damage, clonogenic cell kill, and tumor growth delay. These effects were dependent on the scheduling of the two agents.

Natural antibiotic expression in celiac disease--correlation with villous atrophy and response to a gluten-free diet.

As infection influences the pathogenesis and presentation of celiac disease, we investigated the expression of natural antibiotics in this condition. Twenty-three adults were prospectively studied: 10 controls and 13 subjects with untreated celiac disease. Distal duodenal biopsies were taken at baseline and after 6 months of a gluten-free diet and assessed for the expression of natural antibiotics. Epithelial human beta-defensin 1 in subjects with celiac disease had a median of 0.02 unit at baseline, compared with 0.34 unit in controls (P < 0.001). It correlated negatively with the degree of villous atrophy (r = -0.64, P = 0.019) and rose to 0.04 unit on the gluten-free diet (P = 0.035 vs. baseline, P < 0.001 vs. controls). The expression of other antibiotics was unchanged. The expression of epithelial natural antibiotics is limited in celiac disease.

The systemic inflammatory response predicts overall and cancer specific survival in patients with malignant lymphoma.

BACKGROUND: The value of C-reactive protein concentrations in the assessment of prognosis in patients with advanced lymphoma has not been clearly defined. MATERIAL/METHODS: Patients with a diagnosis of non-Hodgkin's lymphoma (n = 108) and Hodgkin's lymphoma, (n = 39) and who had measurements of C-reactive protein were studied retrospectively and the data was reviewed over 8 years. RESULTS: Median survival, from the time of sampling, was 7.4 months. On univariate analysis there was a significant relationship between the duration of cancer specific survival and tumour type (p < 0.05), circulating concentrations of albumin (p < 0.001) and C-reactive protein (p < 0.001). In contrast, only C-reactive protein concentration was a predictor of death from intercurrent disease (p < 0.05). On multivariate analysis, C-reactive protein concentration remained a strong independent predictor of both death from cancer and intercurrent disease (p < 0.001). The hazard ratio associated with a unit increase in stratified C-reactive protein concentration was 8.18 (95% CI 4.80 - 13.95) for cancer specific death and 2.11 (95% CI 1.22 - 3.64) for intercurrent death. CONCLUSIONS: The results of the present study demonstrate that patients with advanced lymphoma have evidence of a systemic inflammatory response and the magnitude of the C-reactive protein response predicts the duration of overall and cancer specific survival.

Score based on hypoalbuminemia and elevated C-reactive protein predicts survival in patients with advanced gastrointestinal cancer.

The presence of a systemic inflammatory response (as evidenced by elevated C-reactive protein concentrations) has been shown to be associated with loss of lean body mass and poor survival in cancer patients. The aim of this study is to assess the value of the combination of hypoalbuminemia and an elevated circulating concentration of C-reactive protein as a prognostic score in patients with advanced gastrointestinal cancer. Patients with advanced colorectal (n = 99) and gastric (n = 66) cancer and who had measurements of albumin and C-reactive protein were identified. Hypoalbuminemia (< 35 g/l/ > or = 35 g/l) and an elevated C-reactive protein (< or = 10 mg/l/ > 10 mg/l) were combined to form a prognostic score (0, 1, and 2). In patients with colorectal cancer, median survival was 12.1, 6.1, and 1.7 m (P < 0.001) for scores of 0, 1, and 2, respectively. In patients with gastric cancer the corresponding median survival was 6.1, 3.1, and 1.6 m, respectively (P < 0.01). The results of the present study suggest that, in patients with advanced gastrointestinal cancer, a cumulative score based on hypoalbuminemia and an elevated C-reactive protein may be useful. It has the advantage that it is based on routinely available well-standardized measurements and is simple to use.

Correlation between erosive oesophageal and gastro-duodenal diseases. the influence of aspirin, simple analgesics, and Helicobacter pylori.

OBJECTIVE: Previous erosive oesophagitis studies have excluded patients with peptic ulcers or taking aspirin, and conflicting results have been reported concerning the influence of. We aimed to study the possible correlation between erosive oesophageal and gastro-duodenal diseases in patients with or without erosive oesophagitis who are taking low-dose aspirin, or simple analgesics, or those infected with. METHODS: Endoscopic oesophageal and gastro-duodenal lesions were graded in 287 patients with reflux oesophagitis, median age 57 years, including 168 with oesophageal erosions, 131 infected with, 45 patients taking aspirin 75 mg daily, and 65 patients taking simple analgesics containing paracetamol/codeine. RESULTS: The grades of oesophageal erosions correlated positively with the duodenal scores (r = 0.15; P = 0.01) in the study group as a whole (n = 287), and in patients (n = 131) with (r = 0.169; P = 0.05). Eighty of 168 patients with erosive oesophagitis had (48%), compared with 51 of 119 patients (43%) with non-erosive oesophageal disease (P = 0.47). Oesophageal scores were highest in the aspirin group (P = 0.04; Kruskal-Wallis test), with grades > or =3 being found in 36% of patients on aspirin, 22% on simple analgesics, and in 18% of other patients. CONCLUSIONS: The degree of oesophageal damage correlates positively with that in the duodenal mucosa, although the overall prevalence of erosive oesophagitis is not influenced by. Also, patients taking aspirin have a greater degree of oesophageal damage. These indicate the presence of a common process mediating both oesophageal and duodenal diseases in at least some patients with these disorders.

Performance status of male and female advanced cancer patients is independently predicted by mid-upper arm circumference measurement.

In the advanced cancer patient, performance status has considerable prognostic power. Karnofsky performance status, together with variables reported to influence its score, was measured in advanced gastrointestinal cancer patients (n = 148). For male and female patients, age, body mass index, weight loss, triceps skinfold thickness, mid-upper arm circumference, albumin, C-reactive protein, and tumor type and stage were regressed against Karnofsky performance status. On multiple regression analysis, only mid-upper arm circumference and log10 C-reactive protein in men (r2 = 0.462, P < 0.0001) and only mid-upper arm circumference and weight loss in women (r2 = 0.485, P < 0.01) were independent predictors of Karnofsky performance status. There was a significant partial correlation, with gender as a covariable, between log10 C-reactive protein and albumin (r = -0.530, P < 0.0001) and mid-upper arm circumference (r = -0.269, P = 0.035) and weight loss (r = 0.286, P = 0.024). The results of the present study indicate that mid-upper arm circumference is a major factor that influences performance status in male and female patients with advanced gastrointestinal cancer.

Contrast-enhanced Doppler perfusion index: clinical and experimental evaluation.

OBJECTIVE: To assess the potential of the power Doppler signal intensity rate of enhancement due to contrast agent wash-in for assessment of hepatic hemodynamics. METHODS: With the use of standardized settings, power Doppler sonography was performed before and after administration of a contrast agent. Video-recorded examinations were digitized for offline analysis on a personal computer. The temporal changes of the power Doppler signal intensity were quantified to provide contrast agent wash-in curves. The contrast-enhanced Doppler perfusion index was defined by the ratio of the wash-in gradient of the hepatic artery and portal vein as contrast-enhanced Doppler perfusion index = hepatic artery gradient/(hepatic artery gradient + portal vein gradient). The contrast-enhanced Doppler perfusion index was evaluated at 4 contrast agent doses in each of 14 patients with liver metastases and 3 patients with hemangiomas. An in vitro flow model was used to determine the relationships between the power Doppler rate of enhancement and flow in vessels of 4, 8, and 12 mm in diameter. RESULTS: In vivo, there was a significantly higher (P < .0001) mean contrast enhanced Doppler perfusion index in patients with liver metastases (mean, 0.59; 95% confidence interval, 0.54-0.63), compared with patients with hemangiomas (mean, 0.33; 95% confidence interval, 0.24-0.41). The corresponding coefficients of variations were 25% for patients with liver metastases and 31% for patients with hemangiomas. In vitro, the power Doppler rate of enhancement was proportional to flow speed and independent of vessel diameter. CONCLUSIONS: Measurement of the contrast-enhanced Doppler perfusion index may have potential in assessment of hepatic hemodynamics and focal liver disease.