Abstract(R-)miniCHOP therapy, which delivers approximately half-doses of the (R-)CHOP regimen, has shown efficacy and safety in patients who are more than 80 years old. This study aimed to compare the area under the plasma concentration–time curves (AUCs) of vincristine (VCR), doxorubicin (DXR), and cyclophosphamide (CPA) between (R-)CHOP and (R-)miniCHOP regimens. The AUCs were compared between patients aged 65–79 years receiving (R-)CHOP therapy and those aged 80 years and older receiving (R-)miniCHOP therapy. Age was not an independent variable for predicting the dose-adjusted AUCs (AUC/Ds) of cytotoxic anticancer drugs. The median AUCs of DXR and CPA were significantly smaller in the (R-)miniCHOP group than in the (R-)CHOP group (168.7 vs. 257.9 ng h/mL, P = 0.003, and 219.9 vs. 301.7 µg h/mL, P = 0.020, respectively). The median AUCs of VCR showed the same trend but the difference was not significant (24.83 vs. 34.85 ng h/mL, P = 0.135). It is possible that the AUCs of VCR, DXR, and CPA in patients aged 80 years and older receiving (R-)miniCHOP therapy may be lower than those in patients 65–79 years old receiving (R-)CHOP therapy.

In order to find out the sensitive tests to differentiate intravascular coagula tion from intravascular proteolysis, the changes in factors of coagulation fibrinolysis were studied on experimentally produced fibrinolysis, fibrinogenolysis and intravascular coagulation.Fibrinogen, and factors V and VIII were decreased; the prothrombin time, thrombin time and partial thromboplastin time were prolonged in both intravascular proteolysis and coagulation.The reliable factors to be tested for the differentiation were the prothrombin determined by the two stage method or by employing prothrombin-free plasma, plasminogen, platelets and the split products derived from either fibrinogen or fibrin. Namely, the platelets and prothrombin were decreased in intravascular coagulation, whereas these factors were normal in proteolytic stage. Plasminogen was low in both fibrinolytic and fibrinogenolytic states, but normal in intravascular coagulation. Basing on the facts that the split products from fibrinogenolysis were heat labile at 56°C for 15 minutes, while those from fibrinolysis were heat-stable, the differentiation between the split products from fibrinogen and fibrin was possible by measuring the thrombin clotting on a mixture of control plasma and heated or non-heated test sample, and by employing the simple radial immune diffusion technique.

In ordor to clarify the controversial findings concerned with the effect of estrogens on coagulation and plasmin systems, various preparations of estrogen having different chemical structures, i.e., desoxyestrone, estradiol and Premarin R, were administered to human subjects and the factors of blood coagulation and the plasmin systems were determined.There was no significant change in the factors of the coagulation system excepting a slight decrease in the recalcification time with the administration of estriol or Premarin R, slight elevation of Factor VII with Premarin R, and a slight prolongation of the thrombin time with estradiol, estriol and Premarin R. On the other hand, a marked change was noted in the plasmin system, namely, a decreases in the total plasmin and antiplasmin, and a marked elevation of the spontaneous caseinolytic activity of the euglobulin fraction.A hypercoagulemic state is observed during pregnancy characterized by a decrease in the clotting time of whole blood, a decrease in r (reaction time) and K (coagulation time) and an increase of ma (maximal amplitude) in the thrombel astogram as well as increases in fibrinogen, prothrombin, Factor V and Factor VII.1-5 At the same time, increases in the plasmin system including increases in the total plasmin (caseinolytic activity of the SK-euglobulin), and spontaneous proteolytic activities of the euglobulin fraction are also found in pregnant women, 6-8 as if they play a role in buffering the hypercoagulemic state . These changes seem to be under neurohormonal control especially by the sex hormones. It was reported that Premarin R, a mixture of sodium salts of estrone sulfate and equilin sulfate from the urine of pregnant mares, can produce increases of fibrino gen, Factor V and Factor VII.9 It was also noted that estrogens have a depress ing effect on the blood cholesterol level."," If it is true, as is generally accepted, that hyperlipemia can produce a hypercoagulemic state, the above actions of * The 16th report on Pathophysiology of Plasmin System 219

Purpose: Malnutrition increases chemotherapy toxicity and impairs quality of life. Previous studies have shown an association between nutrition assessment tools, such as the Geriatric Nutrition Risk Index (GNRI), and adverse events of chemotherapy. However, none are specific to colorectal cancer (CRC). Therefore, we evaluated this association by investigating adverse events needing treatment (AENT) in patients with CRC.Methods: We retrospectively classified 147 patients with CRC into the risk group (GNRI<98, 85 patients) and the no-risk group (GNRI≥98, 62 patients). We defined AENT as infection requiring antibiotics administration, grade ≥2 leukocytopenia, feasible neutropenia, anemia and thrombocytopenia requiring transfusion, grade≥3 diarrhea, and acute organ failure. Results: We compared the two groups regarding AENT, antibiotic use, admission treatment for AENT, and mortality. Fifty-two (61.2%) and twenty-eight (45.1%) patients in the risk group and no-risk group, respectively, experienced AENT (odds ratio [OR], 0.948; [95% confidence interval, 0.919–0.978]; area under the curve of the receiver-operating characteristic curve, 0.694; [0.608–0.780]). Those in the risk group had increased antibiotic use (OR, 0.945; [0.912–0.979]) and mortality (OR, 0.845; [0.765–0.932]). AENT and performance status were not associated, while GNRI score and chemotherapy toxicity were inversely associated.Conclusion: GNRI can predict a patient’s tolerability for cytotoxic chemotherapy. Prospective studies should validate GNRI and nutrition support benefits.

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