Noninvasive Diagnostic Criteria Research Articles

Cholangiocarcinoma in cirrhosis: Absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma # †

This study assesses the magnetic resonance (MR) features of intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis with specific analysis of the contrast enhancement pattern. Cholangiocarcinoma may show increased contrast uptake in the arterial phase, and, if washout in the delayed venous phase were to be detected, the noninvasive diagnostic criteria proposed in the American Association for the Study of Liver Diseases guidelines would be refuted. We reviewed the MR findings of 25 patients with cirrhosis with 31 histologically confirmed ICC nodules. Signal intensity on basal T1-weighted and T2-weighted images and characteristics of enhancement after contrast administration on arterial, portal, and delayed phase were registered. Enhancement pattern was defined according to the behavior of the lesions in each phase, and dynamic pattern was described according to the progression of enhancement throughout the different phases. The most frequent pattern displayed by ICC was a progressive contrast uptake (80.6%). Stable contrast enhancement was registered in 19.4%. None of the ICCs showed a washout pattern, a profile that is specific for hepatocellular carcinoma (HCC). The ICC dynamic behavior differed significantly according to tumor size: progressive enhancement pattern was the most frequent (20 of 25 cases) in lesions larger than 20 mm, whereas the stable pattern was mainly identified in nodules smaller than 20 mm. The most characteristic MR contrast pattern in ICC in cirrhosis is a progressive contrast uptake throughout the different phases, whereas contrast washout at delayed phases is not observed. Because stable enhancement pattern without washout also can be registered in small HCC nodules, the evaluation of delayed phase is mandatory for a proper nodule characterization. If washout is not registered, a biopsy should be mandatory for diagnosis.

Diagnostic Value of Endomyocardial Biopsy Guided by Electroanatomic Voltage Mapping in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Voltage Mapping-Guided Biopsy in ARVC/D. To improve the endomyocardial biopsy (EMB) diagnostic sensitivity for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), we hypothesized a biopsy sampling focused on selected right ventricle (RV) low-voltage areas identified by electroanatomic voltage mapping. The study population (22 patients, 10 men; mean age 34 +/- 10 years) included 11 patients with overt ARVC/D (group A) and 11 patients with suspected ARVC/D (group B), according to both arrhythmic profile and standardized noninvasive diagnostic criteria. In all 22 patients, an RV bipolar voltage mapping was performed with CARTO system sampling multiple endocardial sites (262 +/- 61), during sinus rhythm, with a 0.5-1.5 mV color range setting of voltage display. All 11 (100%) group A patients and 8 of the 11 (73%) group B patients (P = nonsignificant [NS]) presented RV low-voltage areas (<0.5 mV). In 8 group A patients and in all 8 group B patients with a pathological RV voltage map, an EMB focused on the low-voltage areas was performed. In 6 (75%) group A patients and in 7 (87%) group B patients (P = NS), voltage mapping-guided EMB was diagnostic for ARVC/D. In the remaining 3 patients, only nonspecific histological findings were observed. The results of our study (1) confirm the high diagnostic sensitivity of RV voltage mapping in patients with overt ARVC/D, (2) document a high prevalence of RV low-voltage areas even in patients with suspected ARVC/D, and (3) demonstrate that in patients with clinical evidence or suspicion for ARVC/D, presenting RV low-voltage areas, EMB guided by voltage mapping may provide ARVC/D diagnosis confirmation.

Evaluation of serum vascular endothelial growth factor (VEGF) and microvessel density (MVD) as prognostic indicators in carcinoma breast

Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide. A great deal of interest has been paid to the predictive value of neoangiogenesis represented by microvessel density (MVD), on clinical progression and prognosis of several types of tumors. Serum VEGF levels may therefore be clinically useful for the prediction of increase in tumor growth, metastasis or recurrence spread in individual patients. A total of 265 cases of breast lesions were studied to note the importance of Serum VEGF as a prognostic marker in cases of breast carcinoma. The expressed serum VEGF levels and microvessel density (MVD) were assessed quantitatively and were correlated with tumor grade, tumor necrosis, stromal reaction and nodal metastasis. Serum VEGF was increased in patients with lesions of breast and the levels of serum VEGF in malignant lesions were significantly increased when compared to benign lesions. It was also noted that the levels of serum VEGF increased with increasing grades of malignancy. MVD showed a significant correlation in the early stages of the malignant tumors, where there was no necrosis, but in tumors associated with necrosis and hemorrhage MVD failed to show significant correlation. Hence, serum vascular endothelial growth factor can be used as a more reliable, non-invasive adjunctive diagnostic criteria in the assessment of the grade and hence, the prognosis of malignant tumors of the breast.

Epidemiology of hepatocellular carcinoma in Finistère Prospective study from June 2002 to May 2003

The aims of this prospective study were to evaluate the incidence of hepatocellular carcinoma (HCC) in Finistère, an administrative district of western France, and to highlight epidemiological characteristics. From June 1st 2002 to May 31st 2003, all cases of HCC in Finistère were registered prospectively. Standardized incidence rates were calculated. One hundred and six cases of HCC were registered. Standardized incidence rates were 13.8/100000 among men and 0.8/100000 among women. Among the incident cases of HCC, 52% were discovered in patients consulting for symptoms, and 28% in patients undergoing screening. The new non-invasive diagnostic criteria of HCC were used in 60% of cases. HCC was associated with cirrhosis in 89 patients (84%). Excessive alcohol intake was the main cause of cirrhosis. In all, 27 patients (25.5%) received potentially curative treatment. Incidence of HCC is high in Finistère. The proportion of patients given potentially curative treatment is still low, illustrating how difficult screening can be when alcoholic cirrhosis predominates in the target population.

Usefulness of the MSG/IFICG/EORTC diagnostic criteria of invasive pulmonary aspergillosis in the clinical management of patients with acute leukaemia developing pulmonary infiltrates

Invasive pulmonary aspergillosis (IPA) is a frequently fatal complication in patients with acute leukaemia. Because diagnosis is still difficult, non-invasive diagnostic criteria were recently proposed by MSG/IFICG/EORTC for study purposes. We have analysed their usefulness in the clinical management of acute leukaemic patients with pulmonary infiltrates. Twenty-seven infiltrates developed during 174 chemotherapy cycles given to 50 consecutive patients. According to diagnostic criteria, IPA was diagnosed in 42% of patients and 77.8% of pulmonary infiltrates. AML diagnosis and the first induction cycle were significant risk factors. "Proven" IPA was rare, occurring in one patient (2%). The diagnosis of "probable" IPA was made in seven patients (14%) and was strongly supported by the significant association of characteristic radiological lesions ("major" clinical criterion) with the positivity of one microbiological criterion (P = 0.026). Conversely, "possible" IPA was frequent (26%) because its pertinent diagnostic criteria were fulfilled in 48.1% of pulmonary infiltrates. However, in 84.6% of cases, the diagnosis of "possible IPA" aspecifically derived from the association of two conditions, a new pulmonary infiltrate with symptoms of lower respiratory tract infection ("minor clinical criterion"), together with the definition of "susceptible" host, which applied to 100% of our leukaemic patients. We conclude that, according to MSG/IFICG/EORTC criteria, a high number of pulmonary infiltrates would be diagnosed as IPA, but only a diagnosis of "proven/probable" IPA should be considered reliable in the clinical management of suspected IPA.

Comparison of Liver Biopsy and Noninvasive Methods for Diagnosis of Hepatocellular Carcinoma

Current management guidelines for hepatocellular carcinoma (HCC) do not require biopsy to prove the diagnosis. We evaluated our experience of patients with liver disease and hepatic lesions suspicious for HCC who underwent both fine-needle aspiration and core biopsy and correlated the results with those from commonly used noninvasive approaches. We retrospectively reviewed the outcomes of a series of patients undergoing biopsy because of a suspicion of HCC and compared sensitivity, specificity, and predictive value of biopsy with existing noninvasive methods for diagnosing HCC. HCC was diagnosed by biopsy in 74 (63%) of 118 cases, and an additional 10 were found to have HCC on follow-up. Patients with positive biopsy results had significantly higher serum alpha-fetoprotein levels (median, 57 vs 12; P = .014) than those with negative biopsies, although these 2 groups were otherwise similar with regard to tests of liver function, lesion size on imaging, and Child-Pugh class. No patient developed evidence of tumor spread along the needle track after biopsy. We compared the diagnosis of HCC by biopsy with noninvasive diagnostic criteria advocated by the European Association for the Study of the Liver and those used by the United Network for Organ Sharing. Compared with criteria of the European Association for the Study of the Liver and the United Network for Organ Sharing, biopsy had greater sensitivity, specificity, and predictive value. We recommend a greater role for image-guided biopsy of lesions greater than 1 cm clinically suspicious for HCC to allow adequate treatment planning because the risks of biopsy appear small and the potential benefits significant. Obtaining material for both cytologic and histologic examination at biopsy maximizes the diagnostic yield.

Performance of IFIGC/MSG/EORTC Criteria for the Diagnosis of Invasive Pulmonary Aspergillosis in the Clinical Management of Unselected Patients with Acute Leukemia.

Invasive pulmonary aspergillosis (IPA) is a severe complication in patients (pts) treated for acute leukemia. Since its diagnosis is still difficult, sets of non-invasive diagnostic criteria were recently proposed by IFIGC/MSG/EORTC for study purposes. The performance of those criteria in the clinical management of unselected leukemic pts is still unknown. We have therefore applied IFIGC/MSG/EORTC criteria to the diagnosis of pulmonary infiltrates occurred in 83 consecutive pts, aged <65, with newly diagnosed acute leukemia (19 APL, 38 AML, 26 ALL) treated at a single Institution between 1/2000 and 12/2003. The frequency of the different categories of IPA as diagnosis of pulmonary infiltrates and the relative contribution of the specific sets of diagnostic criteria were analysed. Forty-one pulmonary infiltrates developed in 30/83 pts (36.1%), during 364 chemotherapy cycles. IPA was diagnosed in 22 pts (26.5%). “Proven” IPA occurred in 1 (1.2%), “probable” IPA in 7 (8.4%) and “possible” IPA in 14 pts (16.8%). IPA was significantly more frequent in AML (36,8%), than in APL (15,7%) or ALL (15,3%) (P=0.041), and during the first induction (21/83; 25.3%) than during subsequent cycles (20/281; 7.1%) (P< 0.001). Considering the episodes of pulmonary infiltrate, IPA criteria were met in 27/41 (65,8%) [1 “proven”, 7 “probable” (17%) and 19 “possible” (46,3%)]. Specifically, “host criteria” were met in 41/41 (100%), “microbiological criteria” in 8/41 (17%), and “clinical criteria” in 27/41 (65,8%). The presence of one “major clinical” criterion, i.e. a typical radiological image on chest Xray or CT, was significantly associated with the positivity of a “microbiological” criterion, hence with a diagnosis of “probable” IPA (P=0,012). On the other hand, since “host” criteria were not discriminant, being positive in 100% of cases, the presence of two aspecific “minor clinical” criteria (dyspnea, cough, pleural rub, chest pain, hemophtysis) was the sole responsible for the classification of any non-typical pulmonary infiltrate either as “possible” IPA (17/19 cases; 84.2 %) or as “no IPA”. The bacterial origin of the pulmonary infiltrate was documented on follow-up in 5/19 “possible” IPA, which responded to specific antibacterial treatment. All patients had received antifungal prophylaxis, in 88% with oral itraconazole. A clinical response to ampho/voriconazole was obtained in 6/8 (71,4%) “proven/probable” and 17/19 (89,4%) “possible” IPA. Four of 22 pts with IPA (2 “probable” and 2 “possible”) died early during aplasia (multiorgan failure (MOF) 3, cerebral hemorrhage 1) compared to 2/8 pts without IPA (MOF 1, leukemia 1). In conclusion, according to IFIGC/MSG/EORTC criteria, IPA was diagnosed in 26.5% of pts with acute leukemia and in 65,8% of pulmonary infiltrates. AML and the first induction cycle were significant risk factors. “Proven” IPA was rare. “Probable” IPA was more frequent (8,4% of pts), its diagnosis being strongly supported by the association of a “major” clinical criterion with one microbiological criterion. “Possible IPA” likely represents an overestimation (43,9% of pulmonary infiltrates) since its diagnosis derived in most cases from the combined presence of a “host” criterion with two “minor” aspecific clinical criteria. These data allow a critical analysis of IFIGC/MSG/EORTC criteria in the setting of acute leukemia.

Cerebral vasculitis: clinical features and diagnostic principles

Cerebral vasculitis (CV) is a severe, potentially disabling disease that usually develops in the presence of rheumatic, infectious, medicinal, or malignant diseases. In rare cases, isolated (primary) vasculitis of the central nervous system (CNS) is observed [17, 33]. The complex pathogenesis, polymorphism of clinical manifestations, and the absence in most cases of reliable non-invasive diagnostic criteria for CV complicate early diagnosis and treatment. In this regard, it seems relevant to analyze the features of clinical manifestations and diagnostic capabilities in cerebrovascular pathology caused by vasculitis.

Holter recording of ventricular arrhythmias during intravenous thrombolysis for acute myocardial infarction

Ventricular arrhythmias during thrombolysis for acute myocardial infarction and their relation to coronary artery patency were examined. Twenty-four-hour Holter monitoring was begun 3.1 ± 0.2 hours after onset of pain in 40 patients (age 54 ± 1.6 years; anterior infarction 42.5%) treated with streptokinase (42.5%) or recombinant tissue-type plasminogen activator (57.5%) (delay from pain 3.3 ± 0.2 hours). A Marquette 8000 computer was used for Holter analysis. The infarct-related artery was considered as patent (72.5%) or non-patent (27.5%) according to coronary angiography (delay from pain 26.7 ± 2.5 hours; 60% <24 hours). Ventricular arrhythmias were present in all patients. Tolerance was good (1 cardioversion for ventricular fibrillation). The incidence of accelerated idioventricular rhythm was not different between patients with a patent and nonpatent artery (90 vs 82%), nor for ventricular tachycardia (VT) (83 vs 73%). Coronary artery patency was associated with a 14-, 13- and 32-fold increase of ventricular premature complexes, VT and accelerated idioventricular rhythms, respectively. The increased incidence of sustained VT (patent 38%; nonpatent 0%; p <0.05) and early (before the first 6 hours) accelerated idioventricular rhythm (patent 76%; nonpatent 18%; p <0.01) associated with artery patency suggests that these arrhythmias may be noninvasive diagnostic criteria for reperfusion (sensitivity 38 vs 76%, and specificity 100 vs 82%). A positive correlation was found between the frequency of ventricular premature complexes and VT, and peak creatine kinase.