Clarisse Eveno

Netrin-4 Delays Colorectal Cancer Carcinomatosis by Inhibiting Tumor Angiogenesis

A close relationship between tumor angiogenesis, growth, and carcinomatosis has been observed. Netrin-4 (NT-4) has been shown to regulate angiogenic responses. We aimed to examine the effects of NT-4 on colon tumor angiogenesis, growth, and carcinomatosis. We showed that NT-4 was expressed in human colon cancer cells (LS174). A 20-fold increase in NT-4 expression was stably induced by NT-4 pcDNA in LS174 cells. In vivo, a Matrigel angiogenesis assay showed that NT-4 overexpression altered vascular endothelial growth factor (VEGF)/basic fibroblast growth factor-induced angiogenesis. In nude mice with LS174 xenografts, NT-4 overexpression inhibited tumor angiogenesis and growth. In addition, these NT-4-involved inhibitory effects were associated with decreased tumor cell proliferation and increased tumor cell apoptosis. Using an orthotopic peritoneal carcinomatosis model, we demonstrated that NT-4 overexpression decreased colorectal cancer carcinomatosis. Moreover, carcinomatosis-related ascites formation was significantly decreased in mice transplanted with NT-4 LS174 cells versus control LS174 cells. The antiangiogenic activity of NT-4 was probably mediated by binding to its receptor neogenin. Netrin-4 had a direct effect on neither in vitro apoptosis and proliferation of cultured LS174 cells nor the VEGF-induced acute increase in vascular permeability in vivo. We propose that NT-4 overexpression decreases tumor growth and carcinomatosis, probably via an antiangiogenic effect, underlying the potential therapeutic interest in NT-4 in the treatment of colorectal cancer growth and carcinomatosis.

Pitfalls and mimickers at 64-section helical CT that cause negative appendectomy: an analysis from 1057 appendectomies

PURPOSE To determine the rate of negative appendectomy and clarify the causes of negative appendectomy in patients with clinically suspected acute appendicitis who had surgery after 64-section helical computed tomography (CT). MATERIAL AND METHODS A retrospective analysis of 1057 patients who had appendectomy after 64-section helical CT was performed to determine the rate of negative appendectomy. The 64-section helical CT examinations obtained with submillimeter and isotropic voxels in the patients with negative appendectomy were analyzed by two readers and compared to clinical, operative and histopathological reports, discharge summaries and original radiology reports. RESULTS The negative appendectomy rate was 1.7% (18/1057). Appendix enlargement (>6 mm) and fat stranding were present in 17 (17/18; 94%) and 6 patients (6/18; 33%), respectively. In 13 patients (13/18; 72%) 64-section helical CT findings were consistent with acute appendicitis. Interpretive errors in original imaging reports were identified in five patients (5/18; 28%). CONCLUSION The preoperative use of 64-section helical CT results in a very low rate of negative appendectomy. Patients with negative appendectomy have 64-section helical CT findings consistent with a diagnosis of acute appendicitis in the majority of cases. Interpretive errors are less frequent.

Carcinoid tumors of the small-bowel: Evaluation with 64-section CT-enteroclysis

PURPOSE To describe the imaging presentation of carcinoid tumors of the small-bowel at 64-section CT-enteroclysis and determine the sensitivity of this technique for tumor detection. PATIENTS AND METHODS The 64-section CT-enteroclysis examinations of 22 patients with histopathologically proven small-bowel carcinoid tumors and those of 6 patients with suspected recurrence after small-bowel resection for carcinoid tumor were reviewed. Images were analyzed with respect to imaging presentation. Sensitivity, specificity, and accuracy, of 64-section CT-enteroclysis for the diagnosis of carcinoid tumor of the small-bowel were estimated with 95% confidence intervals (CIs). RESULTS Twenty-five carcinoid tumors were confirmed in 22 patients (prevalence, 22/28; 79%). Overall sensitivity for carcinoid tumor detection was 76% (19/25; 95%CI: 55-91%) on a per-lesion basis. On a per-patient basis, 64-section CT-enteroclysis had a sensitivity of 86% (19/22; 95%CI: 65-97%), a specificity of 100% (6/6; 95%CI: 54-100%) and an accuracy of 89% (25/28; 95%CI: 72-98%) for the diagnosis of carcinoid tumor. Focal small-bowel wall thickening, mesenteric stranding, and mesenteric mass were found in 20/22 (91%), 18/22 (82%) and 15/22 (68%) patients with pathologically confirmed tumors. CONCLUSION 64-Section CT-enteroclysis shows highly suggestive features for the diagnosis of carcinoid tumor of the small-bowel and achieves high degrees of sensitivity for tumor detection.

Liver resection for colorectal liver metastases with peri-operative chemotherapy: oncological results of R1 resections

BACKGROUND Retrospective analysis of outcomes of R0 (negative margin) versus R1 (positive margin) liver resections for colorectal metastases (CLM) in the context of peri-operative chemotherapy. METHODS All CLM resections between 2000 and 2006 were reviewed. Exclusion criteria included: macroscopically incomplete (R2) resections, the use of local treatment modalities, the presence of extra-hepatic disease and no peri-operative chemotherapy. R0/R1 status was based on pathological examination. RESULTS Of 86 eligible patients, 63 (73%) had R0 and 23 (27%) had R1 resections. The two groups were comparable for the number, size of metastases and type of hepatectomy. The R1 group had more bilobar CLM (52% versus 24%, P = 0.018). The median follow-up was 3.1 years. Five-year overall and disease-free survival were 54% and 21% for the R0 group and 49% and 22% for the R1 group (P = 0.55 and P = 0.39, respectively). An intra-hepatic recurrence was more frequent in the R1 group (52% versus 27%, P = 0.02) and occurred more frequently at the surgical margin (22% versus 3%, P = 0.01). DISCUSSION R1 resections were associated with a higher risk of intra-hepatic and surgical margin recurrence but did not negatively impact survival suggesting that in the era of efficient chemotherapy, the risk of an R1 resection should not be considered as a contraindication to surgery.

Pitfalls and mimickers on (18)F-FDG-PET/CT in peritoneal carcinomatosis from colorectal cancer: An analysis from 37 patients.

BACKGROUND Optimal selection is critical in patients with peritoneal carcinomatosis (PC) in whom curative cytoreductive surgery can be anticipated. (18)F-FDG-PET/CT may result in false-positive findings that may eliminate patients for whom cytoreductive surgery would be beneficial. OBJECTIVES To determine the rate of false-positive findings on (18)F-FDG-PET/CT and clarify their causes in patients with suspected PC from colorectal cancer. METHODS A retrospective analysis of 37 patients with suspected PC from colorectal cancer who had (18)F-FDG-PET/CT before cytoreductive surgery was performed to determine the rate and the causes of false-positive findings. (18)F-FDG-PET/CT was considered falsely positive when no tumor was found at surgery, histopathological analysis and follow-up. RESULTS False-positive findings were observed in four patients, yielding a 11% (95%CI: 3-25%) false-positive rate on a per-patient basis. The causes of false-positives were elucidated in two patients (surgical mesh after umbilical hernia repair and one foreign body granuloma). CONCLUSION False-positive findings on (18)F-FDG-PET/CT are observed in 11% of patients with suspected PC from colorectal cancer. Familiarity with false-positive findings would result in more accurate selection of patients candidates to cytoreductive surgery.

Neuroendocrine tumors of the small bowel: evaluation with MR-enterography

PURPOSE To determine the sensitivity of magnetic resonance (MR)-enterography for the detection of neuroendocrine tumors of the small-bowel (NETSB) and analyze the imaging presentation of NETSB on MR-enterography. PATIENTS & METHODS The MR-enterography studies (including HASTE, TruFISP, and 3D VIBE MR sequences before and after intravenous administration of a gadolinium-chelate) of 19 patients with pathologically confirmed NETSB were blindly reviewed. Images were analyzed with respect to imaging presentation. Sensitivity of MR-enterography as well as that of each individual MR-enterography sequence for the diagnosis of NETSB was estimated with 95% confidence intervals (CIs). Comparisons between individual MR-enterography sequences were performed using the McNemar test. RESULTS Twenty-seven NETSBs were confirmed in 19 patients. Overall sensitivity of MR-enterography for NETSB detection was 74% (20/27; 95% CI: 54-89%) on a per-lesion basis. On a per-patient basis, MR-enterography had a sensitivity of 95% (18/19; 95% CI: 74-100%) for the detection of NETSB. Best degrees of sensitivity were achieved with 3D VIBE MR-enterography sequences after intravenous administration of a gadolinium-chelate (Se=95%; 18/19) by comparison with HASTE (Se=26%; 5/19) and TruFISP (Se=26%; 5/19) sequences (P=.00022). Visible focal small-bowel mass, mesenteric stranding, and mesenteric mass were found in 16/19 (84%), 17/19 (89%), and 15/19 (79%) patients, respectively. CONCLUSION MR-enterography shows highly suggestive features for the diagnosis of NETSB and has high degrees of sensitivity for the diagnosis of NETSB on a per-patient basis.

Acute cholecystitis: quantitative and qualitative evaluation with 64-section helical CT.

Background Because of an expanded role for CT in the evaluation of patients with acute abdominal pain, it is not rare that acute cholecystitis is depicted by CT. However, the sensitivity and the specificity of a given CT variable for the diagnosis of acute cholecystitis is not known. Purpose To quantitatively and qualitatively analyze acute cholecystitis at 64-section helical CT with submilimeter and isotropic voxels using a retrospective case-control study. Material and Methods The 64-section helical CT examinations obtained with submilimeter and isotropic voxels in 40 patients with acute cholecystitis (25 men; mean age, 62.2years) were quantitatively and qualitatively analyzed and compared to those of 40 control subjects matched for age and gender. Receiver-operating characteristic (ROC) curve analysis was used to determine the most discriminating cut-off values for quantitative variables. Comparisons of qualitative variables were made using univariate analysis. Results Pericholecystic fat stranding, mural stratification, pericholecystic hypervascularity, spontaneous hyperattenuation of gallbladder wall, short (≥32-mm) and long (≥74-mm) gallbladder axis enlargement, and gallbladder wall thickening (≥3.6-mm) were the most discriminating and independent variables for the diagnosis of acute cholecystitis (P < 0.0001). Using cut-off values found at ROC curve analysis, gallbladder wall thickening, and short and long gallbladder axis enlargement were the most sensitive findings (sensitivity = 92.5%; 95%CI: 79.6%–98.4%) for the diagnosis of acute cholecystitis. Conclusion Acute cholecystitis is associated with myriad suggestive findings on 64-section helical CT. It can be anticipated that familiarity with these findings would result in more confident diagnosis of acute cholecystitis at 64-section helical CT.

Bone marrow‐derived endothelial and hematopoietic precursors cells enhance the metastasis of colon cancer in an orthotopic murine model

In their study, they evaluated transplantation of theKM12SM human colon cancer cell line mixed with mesen-chymal stem cells (MSCs) into the spleen. They reported asignificantly greater number of liver metastases at 4 weekswith the cell mixture than with the transplantation ofKM12SM cells alone. Additionally, MSCs surrounding thetumour were functionally incorporated into the stroma of theorthotopic colon tumour and expressed carcinoma-associatedfibroblast markers.This manuscript prompted us to analyze the relevance ofthe murine model.To induce liver metastasis, a human colon cancer line(LS174) was injected into the spleen of nude mice. First, wecharacterized the bone marrow-derived cell (BMDC) popula-tion by fluorescence-activated cell sorting isolated on greenmice C57 BL/6-Tg obtained after a density gradient. Thepopulation contained 30% of BM-derived endothelial precur-sor cells and derived haematopoietic precursor cells thatexpressed CD 133. At day 0, we injected BMDCs or PBS intothe tail veins of tumor-bearing mice.At day 38, the injection of BMDCs enhanced the metastaticprocess in our model of liver metastasis with a number ofmicro or macrometastases in 56% of the BMDC group ( n ¼16) versus 20% in the PBS group (n ¼ 20), p < 0.05. Immuno-fluorescent staining of cut liver specimens has demonstratedthat BMDCs labelled with Green fluorescent protein (GFP)always localized to the tumour invasion front and colocalizedwith endothelial cells (Fig. 1).There is increasing evidence that BMDCs participate in thetumour microenvironment and metastatic progression,

One-month apparent diffusion coefficient correlates with response to radiofrequency ablation of hepatocellular carcinoma

To assess whether apparent diffusion coefficient (ADC) values at 1 and 3 months after radiofrequency ablation (RFA) may be associated with a favorable response to therapy for hepatocellular carcinoma (HCC) and liver metastases.

Primary neuroendocrine tumors of the gallbladder: Ultrasonographic and MDCT features with pathologic correlation

a Department of Abdominal Imaging, Hôpital Lariboisière, Assistance Publique—Hôpitaux de Paris, 2, rue Ambroise-Paré, 75010 Paris, France b Department of Digestive Surgery, Hôpital Lariboisière, Assistance Publique—Hôpitaux de Paris, 2, rue Ambroise-Paré, 75010 Paris, France c Université Paris-Diderot, Sorbonne Paris Cité, 10, avenue de Verdun, 75010 Paris, France d UMR Inserm 965-Paris 7 « Angiogenèse et recherche translationnelle », 2, rue Amboise-Paré, 75010 Paris, France e Department of Pathology, Hôpital Lariboisière, Assistance Publique—Hôpitaux de Paris, 2, rue Ambroise-Paré, 75010 Paris, France