Diffusion-weighted MRI of peritoneal tumors: comparison with conventional MRI and surgical and histopathologic findings--a feasibility study.

OBJECTIVE: The purpose of our study was to evaluate the utility of single-shot spin-echo echo-planar diffusion-weighted imaging (DWI) using a b value of 400-500 s/mm(2) for depicting peritoneal tumors. MATERIALS AND METHODS: Thirty-four consecutive oncology patients underwent preoperative abdominal and pelvic MRI for tumor staging. MRI included breath-hold DWI with a b value of 400-500 s/mm(2), T1-weighted spoiled gradient-echo, T2-weighted fast spin-echo, and 0- and 5-minute delayed gadolinium-enhanced imaging. At three separate sessions, two observers independently reviewed images for peritoneal tumors at 16 anatomic sites. First DWI alone was reviewed, followed by conventional MRI alone, and then conventional MRI, including DWI, was reviewed. Results of laparotomy and histopathologic evaluation were compared with MRI results. Sensitivity, specificity, and accuracy were calculated for DWI, conventional MRI, and combined DWI and conventional MRI for peritoneal tumor depiction. RESULTS: Two-hundred fifty-five sites of peritoneal tumor were proven by surgical and histopathologic findings. The combination of DWI and conventional MRI was most sensitive and accurate for peritoneal tumors, depicting 230 and 214 tumor sites for the two observers (sensitivity, 0.90, 0.84; and accuracy, 0.91, 0.88) compared with DWI alone, which depicted 182 and 182 tumor sites with sensitivity (0.71, 0.71; and accuracy, 0.81, 0.81), and conventional MRI alone, which depicted 185 and 132 tumor sites (sensitivity, 0.73, 0.52; and accuracy, 0.81, 0.72). Peritoneal tumor showed restricted diffusion on DWI and ascites was of low signal intensity, increasing tumor conspicuity. CONCLUSION: Adding DWI to routine MRI improves the sensitivity and specificity for depicting peritoneal metastases. Breath-hold DWI is now routinely used in all oncology patients referred for abdominal MRI at our institution.

Mucinous appendiceal neoplasms: preoperative MR staging and classification compared with surgical and histopathologic findings.

OBJECTIVE: The objective of our study was to determine the accuracy of MRI in the preoperative staging and classification of mucinous appendiceal neoplasms and to describe the MRI features that are useful for selecting patients for surgical resection. MATERIALS AND METHODS: Twenty-two patients underwent preoperative MRI including T1-weighted, T2-weighted, immediate gadolinium-enhanced, and delayed gadolinium-enhanced imaging. Two observers reviewed the images for peritoneal tumor at 13 sites, tumor size and distribution, and degree of tumor enhancement. Peritoneal tumor sites were recorded at surgery. Cytoreduction was categorized as complete or suboptimal. Surgical specimens were classified as disseminated peritoneal adenomucinosis tumors, intermediate-grade tumors, or peritoneal mucinous carcinomatosis tumors. RESULTS: Surgery confirmed 232 tumor sites. Delayed gadolinium-enhanced MRI was the most accurate of the MR techniques, with a sensitivity, specificity, and accuracy of 89%, 87%, and 89%, respectively, for observer 1 and 82%, 87%, and 83% for observer 2 (p < 0.001). Surgical cytoreduction was complete in 14 patients and suboptimal in eight. MRI findings predicting suboptimal cytoreduction included a large (> 5 cm) mesenteric mass, which was present in 75% of the patients in the suboptimal cytoreduction group and 0% of those in the complete cytoreduction group; diffuse mesenteric tumor (88% and 0%, respectively); tumor encasement of mesenteric vessels (88% and 0%); or diffuse small-bowel serosal tumor (75% and 0%). Histopathology results showed six disseminated peritoneal adenomucinosis tumors, four intermediate tumors, and 11 peritoneal mucinous carcinomatosis tumors. The specimens for the remaining patient were not available for histopathologic analysis. Qualitatively, the 11 peritoneal mucinous carcinomatosis tumors showed greater enhancement than the liver, whereas six disseminated peritoneal adenomucinosis and the four intermediate tumors showed less enhancement than the liver. Quantitatively, the mean tumor-to-liver contrast for disseminated peritoneal adenomucinosis and intermediate tumors was 0.67 compared with 1.53 for peritoneal mucinous carcinomatosis tumors (p < 0.0001). CONCLUSION: Of the MR techniques evaluated, delayed gadolinium-enhanced MRI was the most accurate for the staging and classification of mucinous appendiceal neoplasms and provided prognostic information useful for patient selection.

Interleukin 4 receptor on human lung cancer: a molecular target for cytotoxin therapy.

Previous studies have demonstrated that human lung tumor cell lines express interleukin 4 (IL-4) receptors, and IL-4 can mediate modest to moderate antiproliferative activity in vitro and in vivo in animal models of human lung tumors. On the basis of these studies, IL-4 was tested in clinical trials; however, it showed little antitumor activity in lung cancer patients. In the present study, we examined the expression of IL-4 receptors (IL-4Rs) in lung tumor samples and normal lung tissues and tested whether an IL-4R targeted agent will have better antitumor activity in vitro and in vivo compared with IL-4. IL-4R expression was tested by immunohistochemistry in 54 lung tumor samples and normal lung tissues in a tissue array, by reverse-transcription PCR and Northern blot analyses in lung tumor cell lines. Cytotoxic activity of IL-4 cytotoxin [IL-4(38-37)-PE38KDEL], composed of a circular permuted IL-4 and a mutated form of Pseudomonas exotoxin (PE38KDEL) was tested by protein synthesis inhibition and clonogenic assays in seven lung tumor cell lines. Antitumor activity of IL-4 cytotoxin was tested in vitro and in immunodeficient animal models of human lung tumors. We observed that IL-4Rs are expressed at higher levels in situ in lung tumor samples compared with normal lung tissues and IL-4 cytotoxin is highly and specifically cytotoxic to lung tumor cell lines in vitro. Intratumoral and i.p. administration of IL-4 cytotoxin to immunodeficient mice with s.c. established human lung H358 non-small cell lung cancer tumors mediated considerable antitumor activity in a dose-dependent manner with the higher dose producing durable complete responses. On the other hand, H460 non-small cell lung cancer tumors expressing low levels of IL-4R did not respond to IL-4 cytotoxin therapy. Because IL-4 cytotoxin mediates its antitumor activity through IL-4R, and a variety of lung tumors expressed high levels of IL-4R, we propose testing the safety of this agent in patients with lung cancer.