Luis Fernando Moreira

Kupffer cell function in chronic liver injury and after partial hepatectomy.

The reticuloendothelial system (RES) plays an important role in the biological defense system. In the liver, Kupffer cells are the main constituent of the RES, and when their function is impaired postoperative complications may more often occur. By using99mTc-labeled human serum albumin millimicrospheres (99mTc-HSA-MM) combined with assessment of single photon emission computed tomography (SPECT), we have attempted to determine the function of Kupffer cells independently of the hepatic blood flow. First, Kupffer cell function in rats with chronic liver injury caused by CCl4 was studied. The hepatic uptake rate in chronic liver injury was decreased, and a reduced phagocytic activity of the Kupffer cells was noted. The parameter concerning Kupffer cell degradation, the excretion rate (k), was markedly decreased in the early period of chronic liver injury. Changes in Kupffer cell function after 30% and 70% hepatectomy were also studied. After 30% hepatectomy, the excretion rate was decreased on the first postoperative day (POD), and it was increased beyond that found after sham operation on the 3rd POD. In contrast, slower recovery of uptake rate was demonstrated. After 70% hepatectomy, both uptake and excretion rates were markedly reduced, and recovery was prolonged beyond the 5th POD. The hepatic uptake was not parallel with the excretion rate in either experiment. These results suggest that the method that measures the hepatic excretion rate may provide a better assessment of Kupffer cell function than the current uptake measurement with radiolabeled colloid.

TNF-α, IFN-α and Tegafur Combination Therapy for Advanced Pancreatic Cancer

Eighteen patients with advanced adenocarcinoma of the pancreas were treated with a combination of natural human tumor-necrosis factor-α, natural human interferon-α, and tegafur. Complete and partial response was observed in one and two patients respectively(17% response rate). Seven patients (39%) showed stable disease. The median survival period for the overall population of patients treated is 209 days. Patients with evidence of tumor response or with apparent disease stabilization had a median survival of 313 days, while patients with progressive disease lived 154 days.