Skin thickening and subcutaneous air were detected at ultrasound (US) of the scrotum in a patient with normal-appearing testicles and signs and symptoms suggestive of an acute inflammatory process, such as epidydimitis or orchitis. The patient was found to have Fournier gangrene. In more advanced cases, US can demonstrate that this skin thickening and subcutaneous air extends posteriorly to include the perineum and buttocks. Because of the high mortality of this mixed anaerobic and aerobic infection, it is important to recognize Fournier gangrene early so that the correct surgical and medical treatment can be promptly instituted. To the authors' knowledge, this is the first description of the US characteristics of Fournier gangrene.
Background. Prolonged infusional 5‐fluorouracil (5‐FU) and bolus 5‐FU modulated by leucovorin are associated with higher response rates than bolus 5‐FU alone. Cisplatin enhances 5‐FU cytotoxicity in some preclinical models.
Methods. The authors tested the feasibility of combining concurrent infusional leucovorin (500 mg/m2/d) with protracted infusional 5‐FU (200 mg/m2/d) and weekly bolus cisplatin (20 mg/m2) in 22 patients with metastatic colorectal cancer.
Results. Four partial responses (PR) were noticed among 21 evaluable patients (19%). The median time to treatment failure and median survival were 6 months and 11 months, respectively. All but two patients required 5‐FU dose reduction after a median of 2 weeks because of mucositis. However, severe mucositis and diarrhea occurred in only 18% and 5% of the patients, respectively. Palmar‐plantar erythrodysesthesia of mild to moderate severity occurred in 55% of patients. Megaloblastic changes were evident in the peripheral blood during therapy, and may reflect prolonged DNA‐directed toxicity of 5‐FU. The median tolerated dose level of 5‐FU was 113 mg/m2/d (range, 64–150 mg/m2/d). Mean steadystate plasma concentrations (Cpss) of 5‐FU appeared to increase linearly from 0.19 μM to 0.39 μM over the dose range 64 to 200 mg/m2/d. Patients with grade 2 gastrointestinal toxicity had significantly higher 5‐FU Cpss than patients with grade 0 or 1 toxicity.
Conclusions. The early onset of toxicity with this regimen of protracted infusional 5‐FU/high‐dose leucovorin and weekly cisplatin required marked attenuation of the 5‐FU dose intensity, and the results were no better than that expected with infusional 5‐FU alone.
Regional delivery of iododeoxyuridine (IdUrd) to patients with colorectal liver metastases was examined in a phase I study. The maximum-tolerated intraarterial (IA) dose (MTD) was 1,333 mg/m2/d administered continuously for 14 days. The dose-limiting toxicity was thrombocytopenia. Thrombocytopenia and leukopenia were correlated with the amount of IdUrd incorporated into DNA of peripheral granulocytes. In contrast to our experience with 5-fluorodeoxyuridine, there was no evidence of hepatobiliary toxicity. In 11 patients who received IA IdUrd alone, seven had a greater than or equal to 50% decrease in carcinoembryonic antigen (CEA) levels, with five having tumor volume reductions of 65%, 48%, 46%, 44%, and 27%. Thus, IA IdUrd alone has antitumor efficacy. Patients subsequently received IdUrd in combination with external beam radiation to a total dose of 2,400 cGy without acute local toxicity. In addition to these favorable clinical findings, we have previously shown that IdUrd is selectively incorporated into tumor DNA compared with normal liver in these patients. Further phase II evaluations of this approach are warranted.
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