Robert M. Barone

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.

Infusional 5‐fluorouracil and x‐ray therapy for non‐resectable esophageal cancer

Six patients with unresectable carcinoma of the esophagus received a combined course of external radiation therapy (1000 rads in four fractions in four days commencing on day 2) combined with constant infusional 5‐fluorouracil (20 mg/kg every 24 hours for five days beginning on day 1). This program was repeated every other week to give a total x‐ray dose of 6000 rads. This regimen has been well‐tolerated by the majority of the patients and resulted in a complete response rate within the x‐ray treatment field of 83% (5/6). All patients who showed a demonstrable systemic response to 5‐fluorouracil reached complete response. The median survival has not yet been reached at six months with post‐treatment survivors alive and without disease (four patients) at one, six, nine, and 22 months. Our previous median survival by x‐ray therapy alone was 4 1/2 months. Toxicity consists primarily of hematologic suppression at a subclinical level. Although the length of therapy is substantial (11 weeks), the program appears tolerable and is capable of inducing long‐term remissions. The program is currently being studied for dose escalation because neither local nor systemic side effects of a doselimiting nature have been observed at 20 mg/kg 5‐FU. Cancer 45:703‐708, 1980.

Intra-arterial chemotherapy using an implantable infusion pump and liver irradiation for the treatment of hepatic metastases.

Liver metastases are a common cause of death in colon carcinoma. The dual blood supply of the liver permits regional perfusion while hepatic catabolism of 5‐fluorouracil (FU), floxuridine (FUdR) permit higher drug exposures than systemic (IV) administration. We have studied the effect of continuous intraarterial chemotherapy (FU: 5–10 mg/kg/day and FUdR: 0.2 mg/kg/day) and whole liver irradiation (1000 rad every 4 weeks, total dose of 3000 rad) for metastatic colon carcinoma to liver. Eighteen patients with metastases to liver only are reported using this combination therapy. Seven patients had percutaneous placement of a catheter via the brachial artery, two had operative placement of a catheter via the gastroduodenal artery, all of which were connected to the Cormed infusor system, nine had operative placement of the Infusaid implantable pump with catheter placement into the hepatic artery via the gastroduodenal artery. The median survival for the entire group was 241 days. In those patients whose liver function tests (bilirubin and alkaline phosphatase) were less than two times normal, the median survival was 770 days. The median survival of the patients with greater than two times normal LFTs was 178 days. Two patients died of complications of the treatment. One who developed irreversible radiation hepatitis but at autopsy had only two areas of microscopic tumor foci in the liver and another who had received only 15 days of infusion and 1000 rad to liver. This patient developed irreversible chemical enteritis secondary to chemotherapy infusion into the superior mesenteric artery. Three patients have undergone abdominal reexploration and one at autopsy, who were found to have no gross evidence of tumor in the liver despite previous pathologic confirmation. It appears that some patients with minimal tumor burdens can have sterilization of their tumors. There were three cases of reversible liver function abnormalities. Complications associated with conventional intra‐arterial chemotherapy (artery thrombosis, catheter sepsis and dislodgement, pump infusion variation and pump failure) were not seen with the Infusaid delivery system. The pump is refilled every 2–3 weeks via percutaneous puncture. All therapy was given on an outpatient basis. Pump acceptance and tolerance was 100%. Intra‐arterial chemotherapy can now be accomplished without the morbidity associated with it in the past. The combination of chemotherapy and liver irradiation may offer improved survival in selected patients.

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.

Surgical adjuvant therapy in colon carcinoma: a human tumor spheroid model for evaluating radiation sensitizing agents.

HT‐29 human colon tumor cells growing as spheroids have been evaluated as a model system for measuring the response of human colon tumor cell to antineoplastic agents. HT‐29 cells have the capacity to form spheroids up to 1 mm or more in diameter when grown in spinner culture. The multicellular HT‐29 spheroids develop hypoxic centers reflecting the cellular conditions found in human cancer treatment, i.e., nutritionally deficient hypoxic cells that are felt to be a significant source of both radiation and chemotherapy clinical treatment failures. Spheroids of increasing size were radiated and then dispersed into single cells for colony survival assay. Compared with irradiated single cell suspensions, the spheroid cells demonstrated a significant increase in radioresistance. Growing spheroids developed a complex radiation survival curve which was variable with respect to size of the spheroid. The drug 5‐FU was studied to examine in a preliminary fashion its interaction with these resistant cell fractions. In direct cytotoxicity assay, 5‐fluorouracil (5‐FU) exhibited both cytotoxic and cytostatic effects when the drug was present at a concentration greater than 0.4 μg/ml. The interaction of 5‐FU with x‐rays in the HT‐29 spheroids was complex and dependent on the type of assay employed (spheroid size versus clonogenicity). The effect of allopurinol, an agent that protects cells from 5‐FU toxicity was also examined. Allopurinol at a concentration of 100 μg/ml was found to protect these human colonic carcinoma cells from the cytotoxic effects of 5‐FU under conditions resembling those found in vivo. Overall, this HT‐29 spheroid system appears to be an interesting model for studying a variety of drug/x‐ray interactions in vitro and may prove capable of answering specific questions of preclinical and clinical relevance.