Frank Pilleul

Fatty infiltration of the liver. Detection and grading using dual T1 gradient echo sequences on clinical MR system.

AIM To evaluate the relationship between histopathology results and magnetic resonance imaging (MRI) on in and opposed-phase sequences grading of fat deposition within human liver. MATERIALS AND METHODS In and opposed-phase T1-weighted gradient-echo sequences (double echo time 2.3 ms and 4.6 ms) were performed in 25 patients, using a 1.5-T clinical MR imaging system. Fat/water ratio on in- and opposed-phase images of the liver was compared with pathologically defined degree of steatosis. The signal intensity in the images was acquired with operator-defined regions of interest at the same location in both fat and water images and the ratio was calculated by dividing signal intensity of liver in opposed phased sequence on signal intensity of liver in phased sequence. Fat/water ratio and the degree of steatosis were compared using linear regression. The sensitivity and specificity of opposed-phase for diagnosing steatosis were defined by ROC analysis. Furthermore, a correlation between visual signal intensity variation and the degree of steatosis was assessed using Pearson correlation coefficient. RESULTS Histology demonstrated fatty liver infiltrations in 81% of specimens. The percentage of fatty hepatocytes was 28 +/- 30%. Fat/water ratio was significantly correlated with the pathologic grading of steatosis (r = 0.816, P < 0.001). The opposed phase MR imaging sensibility and specificity for the diagnosis of hepatic steatosis were respectively 80% and 71%. We obtained a statistically significant correlation between visual SIV and fatty liver grading (P = 0.017). CONCLUSION We demonstrated a significant correlation between fat/water ratio and histological findings for the detection and grading of fatty liver.

Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: results from the PRECISION V randomized trial.

OBJECTIVE The purpose of our study was to evaluate hepatic, gastrointestinal, and cardiac toxicity after PRECISION transarterial chemoembolization (TACE) with drug-eluting beads (DEB) versus conventional TACE with doxorubicin in the treatment of intermediate-stage hepatocellular carcinoma (HCC). SUBJECTS AND METHODS Two hundred twelve patients (185 men and 27 women; mean age, 67 years) were randomized to TACE with DEB or conventional TACE. The majority of patients (67% in both groups) presented in a more advanced stage. Safety was measured by rate of adverse events (Southwest Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed with left ventricular ejection fraction (LVEF) mainly on MRI or echocardiography. RESULTS The mean maximum postchemoembolization alanine transaminase increase in the DEB group was 50% less than in the conventional TACE group (p < 0.001) and 41% less in respect to aspartate transaminase (p < 0.001). End-of-study values returned to approximately baseline levels but with greater variability in conventional TACE patients. Treatment-emergent adverse events in the hepatobiliary system organ class occurred in 16.1% of DEB group patients compared with 25% of conventional TACE patients. There were fewer liver toxicity events in the DEB group. There was a small but statistically significant difference in mean change from baseline in LVEF between the two groups of 4 percentage points for the conventional TACE group (95% CI, 0.71-7.3; p = 0.018). CONCLUSION PRECISION TACE with DEB loaded with doxorubicin offers a safe therapy option for intermediate-stage HCC, even in patients with more advanced liver disease.

Low Microvessel Density Is an Unfavorable Histoprognostic Factor in Pancreatic Endocrine Tumors

BACKGROUND AND AIMS In many malignant tumors, intratumoral microvascular density (MVD) has been suggested to be a prognostic parameter. We aimed to provide a quantitative evaluation of intratumoral microvascular density in a large series of resected endocrine tumors of the pancreas and to evaluate the potential prognostic significance of this parameter. METHODS Eighty-two tumors from 77 patients have been studied. MVD was evaluated by 2 observers after CD34 immunostaining and correlated with the following parameters: WHO classification, hormonal profile, tumor size, vascular endothelial growth factor expression, occurrence of metastasis, duration of survival. RESULTS MVD ranged from 5 to 92 vessels/field. MVD was significantly higher in well-differentiated benign endocrine tumors than in tumors of uncertain behavior and in carcinomas. No close correlation was found between MVD and the hormonal profile. MVD was significantly higher in tumors characterized by the following histoprognostic parameters: size <2 cm, proliferation index <2%, no evidence of metastasis. No close correlation was observed between MVD and VEGF expression. Finally, a MVD <30 vessels/field was associated with the occurrence of metastasis in tumors <2 cm and/or with a proliferation index <2% and with a significantly shorter survival after surgery. CONCLUSIONS The quantitative analysis of microvessel density in pancreatic endocrine tumors may identify patients who, despite favorable conventional histoprognostic factors, are at risk of unfavorable evolution.

Targeted deletion of liver glucose-6 phosphatase mimics glycogen storage disease type 1a including development of multiple adenomas

BACKGROUND AND AIMS Glycogen storage disease type 1a (GSD1a) is an inherited disease caused by a deficiency in the catalytic subunit of the glucose-6 phosphatase enzyme (G6Pase). GSD1a is characterized by hypoglycaemia, hyperlipidemia, and lactic acidosis with associated hepatic (including hepatocellular adenomas), renal, and intestinal disorders. A total G6pc (catalytic subunit of G6Pase) knock-out mouse model has been generated that mimics the human pathology. However, these mice rarely live longer than 3 months and long-term liver pathogenesis cannot be evaluated. Herein, we report the long-term characterization of a liver-specific G6pc knock-out mouse model (L-G6pc(-/-)). METHODS We generated L-G6pc(-/-) mice using an inducible CRE-lox strategy and followed up the development of hepatic tumours using magnetic resonance imaging. RESULTS L-G6pc(-/-) mice are viable and exhibit normoglycemia in the fed state. They develop hyperlipidemia, lactic acidosis, and uricemia during the first month after gene deletion. However, these plasmatic parameters improved after 6 months. L-G6pc(-/-) mice develop hepatomegaly with glycogen accumulation and hepatic steatosis. Using an MRI approach, we could detect hepatic nodules with diameters of less than 1 mm, 9 months after induction of deficiency. Hepatic nodules (1 mm) were detected in 30-40% of L-G6pc(-/-) mice at 12 months. After 18 months, all L-G6pc(-/-) mice developed multiple hepatocellular adenomas of 1-10 mm diameter. CONCLUSIONS This is the first report of a viable animal model of the hepatic pathology of GSD1a, including the late development of hepatocellular adenomas.

Value of CT enteroclysis in suspected small-bowel carcinoid tumors.

OBJECTIVE The purpose of this study was to evaluate the value of CT enteroclysis in depicting small-bowel carcinoid tumors in symptomatic patients with surgical, histologic, or clinical follow-up findings as a reference standard. SUBJECTS AND METHODS At our institution, 44 patients with symptoms of suspected gastrointestinal carcinoid tumors underwent CT enteroclysis. Clinical symptoms were as follows: carcinoid syndrome (n = 3), abdominal pain with diarrhea (n = 24), hypervascular liver metastases (n = 7), subileus condition (n = 1), hypervascular peritoneal lesion (n = 3), abnormal ileal stenosis on optical colonoscopy (n = 3), and follow-up extraintestinal carcinoid lesion (n = 3). Positive CT enteroclysis findings were compared with pathology results after surgical procedures (n = 19). Negative examinations were compared with surgery results (n = 3) or clinical follow-up (n = 22). RESULTS CT enteroclysis findings were positive in 19 patients and negative in 25 patients. The sizes of the carcinoid tumors identified were 5-30 mm in axial diameter. These tumors were depicted as focal nodular lesions located in the small-bowel wall or as intraluminal polypoid masses with marked enhancement. Twenty-two patients underwent only clinical follow-up, with a mean clinical follow-up time of 20 months. The overall sensitivity and specificity of CT enteroclysis in identifying patients with small-bowel carcinoid tumors were 100% and 96.2%, respectively. The negative predictive value of CT enteroclysis was 100% and the positive predictive value, 94.7%. Pathologic findings confirmed small-bowel carcinoid tumors in 18 patients. CONCLUSION CT enteroclysis should be considered an excellent tool for the diagnosis of the carcinoid tumor before any surgical procedures.

Preoperative evaluation of intraductal papillary mucinous tumors performed by pancreatic magnetic resonance imaging and correlated with surgical and histopathologic findings

To evaluate the effectiveness of magnetic resonance imaging (MRI) in predicting the location, type of ductal involvement, and malignant transformation of intraductal papillary mucinous (IPM) pancreatic tumors made in a preoperative routine exam.

Diagnosis of Splanchnic Artery Aneurysms and Pseudoaneurysms, with Special Reference to Contrast Enhanced 3D Magnetic Resonance Angiography: a Review

Splanchnic artery aneurysms are rare. In the past, conventional angiography was the only way to detect them, but today non-invasive techniques are available. Breath-hold contrast-enhanced 3D magnetic resonance angiography has become a routine examination for evaluation of the aorta and its visceral branches. In this article, we briefly discuss the technical aspects of 3D contrast-enhanced magnetic resonance angiography and illustrate various splanchnic artery aneurysms-pseudoaneurysms with their main characteristics.

Hepatic Arterial Embolization versus Chemoembolization in the Treatment of Liver Metastases from Well-Differentiated Midgut Endocrine Tumors: A Prospective Randomized Study

Background: Liver surgery is the best treatment for endocrine liver metastases, but it is often impossible due to diffuse disease. Systemic chemotherapy is poorly effective. Hepatic arterial embolization (HAE) and chemoembolization (HACE) have shown efficacy but have never been compared. Patients and Methods: Patients with progressive unresectable liver metastases from midgut endocrine tumors were randomly assigned to receive HAE or HACE (two procedures at 3-month interval). The primary end point was the 2-year progression-free survival (PFS) rate. Secondary end points were response rates, overall survival, and safety. Results: Twelve patients were assigned to receive HACE and 14 to receive HAE. The patient characteristics were well matched across the treatment arms. The 2-year PFS rates were 38 and 44% in the HACE and HAE arms, respectively (p = 0.90). Age, gender, previous resection of the primary tumor or liver metastases, extent of liver involvement, and concomitant treatment with somatostatin analogues were not associated with changes in PFS, whereas elevated baseline urinary 5-HIAA and serum chromogranin A levels were associated with shorter PFS. The 2-year overall survival rates were 80 and 100% in the HACE and HAE arms, respectively (p = 0.16). The disease control rate on CT scan was 95%. Grade 3 toxicity occurred in 19% of patients, with no treatment-related deaths and no differences in the treatment arms. Conclusion: HACE and HAE are safe and permit tumor control in 95% of patients with progressive liver metastases from midgut endocrine tumors. The 2-year PFS was not higher among patients receiving HACE, not favoring the hypothesis of an additive efficacy of arterial chemotherapy or embolization alone.

Liver steatosis quantification using magnetic resonance imaging: a prospective comparative study with liver biopsy.

Background and Aims: To prospectively determine the accuracy of liver fat quantification with magnetic resonance imaging (MRI). Patients and Methods: The population consisted of 40 patients (mean age, 52.5 years; range, 23-78 years). The same day, all patients underwent MRI and ultrasonography-guided liver biopsy. The histological evaluation of steatosis was performed by an experienced liver pathologist blinded to the MRI results. On T1-weighted in- and opposed-phase images, one radiologist, experienced in abdominal imaging, blinded to the clinical and pathological results, recorded signal intensity (SI) by mean regions of interest placed at same locations in both phases. Fat-water ratio was obtained by dividing SI of liver in opposed-phase sequence by SI of liver in in-phase sequence. The fat-water ratio and the histological grade of steatosis were compared by linear regression. Receiver operating characteristic curve was used to define the sensitivity and specificity of fat-water ratio as a diagnostic tool for evaluation of steatosis. Results: Diagnoses were nonalcoholic fatty liver disease (n = 25), alcoholic liver disease (n = 10), cholangiopathy (n = 2), and autoimmune hepatitis (n = 3). Fatty liver infiltration was present in 80% of patients. The mean (SD) percentage of fatty hepatocytes was 38.7% (29.2). Fat-water ratio and steatosis grade were highly correlated (r = 0.852, P < 0.0001). Sensitivity and specificity of fat-water ratio to detect fatty infiltration greater than 20% were 96% and 93%, respectively. Conclusions: This prospective study demonstrates that MRI can be proposed as a noninvasive method to screen and quantify liver steatosis.

Portal Venous Gas Detected on Computed Tomography in Emergency Situations: Surgery Is Still Necessary

BackgroundPortal venous gas (PVG) has been reported to be associated with lethal surgical diagnosis. Recent studies tend to confirm the clinical significance of gas in the portal vein; however, some patients are managed without surgical treatment. The aim of this study was to assess both the diagnoses and the treatment of patients with PVG in an emergency surgical setting.Materials and methodsWe performed a retrospective chart review of 15 patients with PVG in the emergency setting detected by computed tomography (CT) between July 1999 and July 2004. Characteristics assessed included age, sex, clinical presentation, first CT diagnosis of both PVG and the underlying pathology, American Society of Anesthesiologists (ASA) score, surgical findings, final clinical diagnosis, duration of hospitalization, and evolution of the illness/mortality. All patients were examined one month after operation.ResultsThis series of 5 women and 10 men ranged in age from 38 to 90 years at the time they underwent emergency surgical treatment. The mean preoperative ASA score was 4.20. Computed tomography diagnosed the underlying pathology in all cases: bowel obstruction (4 cases), bowel necrosis (9 cases), and diffuse peritonitis (2 cases). The mean length of hospital stay was 12.4 days. The mortality rate was 46.6%; (7 patients).ConclusionsA wide range of pathologies can generate PVG. Computed tomography can detect both the presence of gas and the underlying pathology. In emergency situations, all the diagnosed causal pathologies required a surgical procedure without delay. We report that the prognosis was related to the pathology itself and was not influenced by the presence of PVG.