Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression.

Tumor angiogenesis is closely associated with clinical staging and has been proposed to correlate with clinical response in terms of subsequent metastases following primary resection. Netrin-4 (NT-4) regulates angiogenic responses. Therefore, we sought to examine the effects of NT-4 on the primary tumor growth of colon cancer cells, liver and lung metastases of colon cancer cells, and responses following primary tumor resection. We used 3 different mouse models of orthotopic primary tumor and liver and lung metastases, comparing 2 human colon cancer cells lines: wild-type (low expression of NT-4) and NT-4 (overexpression of NT-4) LS174 cells. NT-4 overexpression inhibited the primary tumor growth of colorectal LS174 xenografts in nude mice (144.3±12.9 vs. 62.4±4.5 mm3; p<0.0001) as well as its related local and systemic recurrence (38 vs. 0%; p<0.01). NT-4 overexpression also markedly decreased colorectal cancer progression in terms of tumor number and volume of liver metastases in the NT-4 group of the orthotopic liver metastasis model (25 vs. 90% and 4±1 vs. 709±190 mm3, p<0.001 and p<0.05). Collectively, our findings indicate that NT-4 overexpression decreases colorectal lung metastasis and its associated lymph node involvement. NT-4 overexpression decreases tumor recurrence and metastasis after surgical resection, likely via an anti-angiogenic effect. These observations suggest that NT-4 may hold therapeutic potential in the treatment of colorectal cancer growth and major metastatic sites.

Tumor and non-tumor liver angiogenesis is traced and evaluated by hepatic arterial ultrasound in murine models.

We studied the relationships between hepatic and mesenteric mean blood-flow velocities (mBFVs) measured by ultrasound imaging and (1) downstream tumor angiogenesis during liver metastasis induced by spleen injection of LS174 human colon cells overexpressing the antiangiogenic Netrin4 (LS174-NT4) or not (LS174-WT) and (2) downstream normal angiogenesis during hepatic regeneration after 50% hepatectomy. Liver volume and mBFVs were measured before and after surgery, at day 30 in the first model and at days 2, 7 and 16 in the second model. LS174-NT-4 vs. LS174-WT mice presented fewer metastases (25% vs. 90%, p < 0.001) and decreased hepatic mBFVs (16.5 ± 0.8 vs. 21.8 ± 1.4 cm s(-1), p < 0.01), without difference in mesenteric mBFVs. After partial hepatectomy, hepatic and mesenteric mBFVs increased at day 7, from 12.4 ± 1.7 and 11.8 ± 2.6 to 19.1 ± 1.8 and 17.5 ± 2.4 cm s(-1), respectively, (p < 0.01) then returned to baseline as liver volume. Duplex Doppler ultrasonography reliably assesses normal or tumor angiogenesis and may provide follow-up functional evaluation.

Small bowel tumors: spectrum of findings on 64-section CT enteroclysis with pathologic correlation.

Improvements in helical technology have made detection of benign and malignant small bowel tumors easier so that they are now frequently detected at an early stage. Sixty-four-section CT enteroclysis provides suggestive features that help determine the actual nature of a small bowel tumor in a large number of cases. Specific diagnosis of small bowel tumor is based on a combination of findings that are depicted owing to the use of the multiple capabilities of 64-section CT enteroclysis, allowing optimal planning prior to endoscopic or surgical resection.

Association between a high number of isolated lymph nodes in T1 to T4 N0M0 colorectal cancer and the microsatellite instability phenotype.

HYPOTHESIS: Stage I or II colorectal carcinomas with microsatellite instability (MSI) are characterized by more isolated lymph nodes in the resected specimen than their counterparts with microsatellite stability (MSS). DESIGN: Prospective study. SETTING: Academic research. PATIENTS: Using a pentaplex polymerase chain reaction assay, MSI status was determined prospectively for 135 operative patients. MAIN OUTCOME MEASURES: Mismatch repair defects were investigated by immunohistochemistry on tumors demonstrating MSI. RESULTS: Among 82 stage I or II colorectal carcinomas, 11 had MSI, and 71 had MSS, with a mean (SD) number of 23.6 (3.1) and 13.7 (1.0) negative lymph nodes, respectively (P = .001). The mean number of lymph nodes for all resected stage I or II colorectal carcinomas analyzed at our hospital was 15. The prevalence of MSI among tumors with more than 15 lymph nodes in the specimen was 25% (9 of 36), and 82% (9 of 11) of MSI tumors belonged to this group. CONCLUSIONS: A high number of isolated lymph nodes in stage I or II colorectal carcinomas was associated with the MSI phenotype. Good prognosis that is usually associated with tumors having a high number of uninvolved lymph nodes might reflect the high prevalence of MSI among these tumors. The number of examined lymph nodes as a quality criterion should be used with caution. For stage I or stage II colorectal carcinomas, restricting MSI phenotyping to tumors with more than the mean number of lymph nodes identifies almost all MSI tumors.

Poisoning-related bowel infarction: characteristics and outcomes.

BACKGROUND: Bowel infarction (BI) is a rare complication of poisoning. We aimed to describe the characteristics of BI in poisoned patients compared to nonpoisoned patients. METHODS: A retrospective review over a 4-year period of patients hospitalized in an intensive care unit who were diagnosed with BI; Mann-Whitney and Fischer's exact tests were used for comparisons. RESULTS: Seventeen patients with BI [11 F/6 M, 66-year olds (55-72), median (25-75% percentiles)], including five out of around 1,800 poisoned patients, were identified (toxicants: nicardipine + venlafaxine, amlodipine, propranolol + hydroxyzine, dextropropoxyphene + clomipramine, and turpentine). Clinical presentation and severity were comparable between both groups. However, poisoned patients were significantly younger (p = 0.03) with less cardiovascular disease (p = 0.04) and fewer risk factors (p = 0.008). Delayed BI occurred 48 h (36-60) after the start of vasopressor administration [15.5 mg/h (4.5-30.0) norepinephrine and 6.0 mg/h (4.9-6.3) epinephrine]. Typical poisoning-related injury was jejunal ischemia without ileal localization. The predominant mechanism was nonocclusive mesenteric ischemia. Mortality was lower in poisoned patients (20 vs. 90%, p = 0.009). CONCLUSION: Physicians should be aware that, despite patient age and the lack of cardiovascular risk factors, BI may rarely complicate severe poisonings requiring elevated doses of vasopressors and may present in a delayed fashion.

Multidetector row helical computed tomography enteroclysis findings in ileal endometriosis.

Ileal endometriosis is a rare condition, which, most of the time, is found incidentally in women who have had abdominal or pelvic surgery. In general, ileal endometriosis is asymptomatic and is responsible for small bowel obstruction in only 0.5% of the cases. In addition, in most published cases, the diagnosis was established postoperatively. We report herein two cases of ileal endometriosis, which were responsible for small bowel occlusion. The diagnosis was considered preoperatively owing to the presence of a constellation of findings, including those obtained on multidetector row helical CT enteroclysis images. Multidetector row helical CT enteroclysis demonstrated dilated small bowel up to a stenosis due to circumferential parietal thickening in the distal ileum in one case and an ileal parietal solid nodule in the other one. Although multidetector row helical CT enteroclysis does not show specific findings, it may help to suggest the diagnosis of ileal endometriosis in the proper clinical setting.