BACKGROUND Considering recent findings that both urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitors (PAIs) are involved in tumor growth through an urokinase‐type plasminogen activator (uPA) activity‐independent mechanism, the relation between the presence of these factors in tumor tissue and the clinicopathologic variables in colorectal carcinoma was reevaluated. METHODS In 100 colorectal carcinoma patients, antigen levels of u‐PA, uPAR, and PAI‐1 and PAI‐2 were assayed in both tumor tissues and their normal counterparts. Plasma levels of soluble uPAR also were determined. RESULTS All uPAR, uPA, PAI‐1, and PAI‐2 antigen levels in tumor tissue were significantly higher than those in normal tissue. Levels of both uPAR and PAI‐1 were significantly higher (3.09 ± 1.37 and 6.63 ± 7.49, respectively) in large tumors (≥50 mm in greatest dimension) than those in smaller tumors (< 50 mm) (2.50 ± 1.07 and 2.72 ± 2.70, respectively) (P < 0.05). Significant positive correlation coefficients (r) were obtained between tumor size and the calculated ratios of PAI‐1/uPAR (r = 0.490; P < 0.0001) and PAI‐1/uPA (r = 0.469; P < 0.0001). In addition to liver metastases (P = 0.004) and lymph node involvement (P = 0.04), high levels of uPAR (P = 0.05) also were found to be of independent prognostic value by multivariate analysis. CONCLUSIONS Higher expression of uPAR was related to poor prognosis of patients with colorectal carcinoma and excess amounts of PAI‐1 over uPAR or uPAR‐bound uPA appeared to play an important role in tumor progression. Cancer 1999;86:2602–11. © 1999 American Cancer Society.

Background/Aims: In patients with active ulcerative colitis (UC), pharmacologics, although initially effective in most patients, are associated with refractoriness, loss of response or unfavourable side effects as additional morbidity factors. Depletion of myeloid lineage leucocytes like the CD14(+)CD16(+) monocyte phenotype, which is a major source of tumour necrosis factor-α, by granulocyte/monocyte apheresis (GMA) if effective, is also known to be free from side effects. Methods: In clinical practice setting, 77 consecutive patients with moderate to severe UC, who failed to respond to first-line medications received GMA with the Adacolumn as remission induction therapy. Patients who achieved remission were followed for 3 years. Results: Among the 77 patients, 46.8% were corticosteroids-naïve, 26% corticosteroid-dependent and 27.3% corticosteroid-refractory. The overall clinical remission rate was 79.2%, and the overall mucosal healing (MH) rate according to the Mayo endoscopic subscore ≤1 was 58.5%. MH rates incorticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 70.8, 56.3, and 38.5%, respectively. The 3-year sustained clinical remission rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 83.3, 68.8, and 23.1%, respectively. Conclusion: Corticosteroid-naïve patients appeared to benefit the most from the Adacolumn GMA, and attain a favourable long-term clinical course. Accordingly, GMA should be a first-line therapy in this clinical setting.

Autoimmune hepatitis (AIH) is a disorder of unknown etiology, which often progresses to cirrhosis and carries a high mortality, even though its treatment with corticosteroids has become common. Hepatocellular carcinoma (HCC) has been reported as a rare complication of AIH. We describe herein a patient with HCC associated with AIH, in whom microwave coagulation therapy provided a means of definitive management, and we also review the literature. Male sex and longstanding cirrhosis seem to be the risk factors for hepatocarcinogenesis in AIH. The prognosis of this disease is extremely poor because of the low resectability caused by poor hepatic reserve. It is important to pay attention to hepatic disorders and the possible development of HCC at the time of diagnosis of AIH. Surgeons should select suitable treatment, without undue surgical stress, whenever the diagnosis of HCC has been established. Microwave coagulation therapy is a preferred option for the treatment of high-risk patients with poor hepatic reserve or unresectable multiple HCCs.

Considering recent findings that the urokinase plasminogen activation (PA) system is involved in invasion and vascular endothelial growth factor (VEGF) is involved in angiogenesis of colorectal cancer, we evaluated these factors in the liver metastasis of primary colorectal cancer. Cancer tissues from 71 colorectal cancer patients were assayed quantitatively for antigen levels of urokinase type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1, PAI-2), and were also assayed immunohistochemically for expression of VEGF protein. Among the PA system factors, both the levels of uPAR and PAI-1 were significantly higher in larger tumors than in smaller ones, and were also significantly higher in tumors that invaded subserosa, serosa or adjacent organs than in mucosal, submucosal tumors or in tumors that invaded the muscle layer. The uPAR levels were significantly higher in tumors with liver metastasis than in those without. VEGF overexpression was significantly more frequent in tumors with lymph node involvement or liver metastasis than in those without. Among the PA system factors, the uPAR levels were significantly higher in tumors with VEGF overexpression and a multivariate analysis revealed that high uPA level and VEGF overexpression were independent risk factors for liver metastasis. The combination of high uPAR level and overexpression of VEGF was associated with the worst prognosis in patients with colorectal cancer. These results suggest that uPAR and VEGF might contribute synergistically to the liver metastasis of colorectal cancer.

CMV reactivation might be encouraged by immunosuppressive drugs, like corticosteroids, immunomodulators, and therefore, patients with UC are at a high risk of CMV reactivation, potentially exacerbating UC. However, this study of 187 patients, CMV(+) and CMV(-), could not find colonoscopic features unique to CMV, except that CMV might be one factor for steroid refractoriness, and UC exacerbation.