UMIN000001396.

Our findings suggested that PMX treatment appears to adsorb endotoxin and also modulates circulating cytokine during a 2-h interval of direct hemoperfusion in septic patients with such condition.

Acute cholangitis due to impacted bile duct stone is sometimes fatal and require prompt bile duct decompression. Particularly, AOSC (acute obstructive suppurative cholangitis) is the most serious form of bacterial cholangitis and its prognosis is ususally very poor when treated conservatively. We have been treated impacted bile duct stones by decompressing the duct endoscopically. Here, we report the characteristics of our elderly patients with impacted bile duct stones who received urgent decompression treatment mainly by endoscopic techniques. In the endoscopical traetment group, the number of patients with AOSC was 5 out of 46 AC (acute cholangitis) patients (11%) under 69 years old, 14 out of 52 (27%) from 70 to 79 years old, and 12 out of 28 (43%) over 80 years old. Obviously, the severity of acute cholangitis (ratio of AOSC to AC) was higher in the elderly. This tendency was similar to the patients who received urgent transhepatic decompression treatment, although they were small in number. In all the patients treated, 7 were classified into the most serious AOSC category with Reynolds'sign, and notably 6 out of 7 were over 70 years old. More strikingly, 5 of 7 patients were over 80, and their mortality rate was indeed high. Thus, in the elderly, bacterial cholangitis by impacted bile stones was a very serious condition. Especially, the outcome of AOSC over 80 years old with Reynolds' sign was very poor, in spite of emergency endoscopic treatment.

Although 5-fluorouracil (5-FU) is an important drug for colorectal cancer (CRC) treatment, no useful biomarker is currently available to predict treatment response. Since 5-FU is converted into active or inactive forms by orotate phosphoribosyltransferase (OPRT) or dihydropyrimidine dehydrogenase (DPD), a correlation between these enzymes and response to 5-FU has been suggested. However, such a correlation has not been investigated prospectively. Therefore, in the present study, we aimed to prospectively evaluate whether OPRT and DPD were predictive factors of the response to 5-FU treatment in patients with resectable CRC. The present investigation was designed as a multicenter prospective cohort study. OPRT and DPD activities were assessed in biopsy samples, obtained surgically from patients with resectable CRC. The OPRT/DPD ratio was calculated and the cut-off values for this ratio were determined for 5-year disease-free survival (DFS) and overall survival (OS). Patients were treated with 5-FU/leucovorin (LV) regimens and oral 5-FU. The endpoint of this study was the correlation between the OPRT/DPD ratio and 5-year DFS and OS. The cut-off value for the OPRT/DPD ratio was determined by using the maximum χ2 statistic method against 5-year DFS and OS. Sixty-eight patients were enrolled from July 2003 to May 2005. The median follow-up period was 1925 days. The OPRT/DPD ratio cut-off values for 5-year DFS and OS were 0.015 and 0.013, respectively. During the 5-year DFS and OS periods, patients with higher cut-off values had a better prognosis than those with lower ratios (P=0.03 and 0.02, respectively). In conclusion, our results suggest that the OPRT/DPD ratio could be a predictive factor for response to 5-FU/LV adjuvant chemotherapy.

Background: The efficacy of direct hemoperfusion with polymyxin B-immobilized fiber columns (PMX) has already been demonstrated in clinical studies for the treatment of septic shock. However, serum procalcitonin levels following PMX remain unknown. Methods: This prospective, multicenter, nonrandomized clinical study was performed at 12 institutions. Forty-five patients with severe sepsis or septic shock due to colorectal perforation underwent PMX. Patients’ outcome as well as circulating levels of endotoxin, procalcitonin and IL-6 were monitored. Results: Before surgery, procalcitonin level, but not endotoxin and IL-6 levels, was elevated according to patients’ septic conditions. Procalcitonin was significantly and positively correlated with sequential organ failure assessment score. Circulating levels of procalcitonin peaked 24 h after PMX treatment. Change in serum procalcitonin level was significantly higher in nonsurvivors than survivors. Nine mortalities were observed within 28 days. The best predictor for 28-day mortality was procalcitonin >85.7 ng/ml at 24 h after PMX (area under the receiver operating characteristic curve: 0.808 ± 0.105). Conclusions: Procalcitonin may be a good indicator of severity of sepsis secondary to colorectal perforation. Furthermore, procalcitonin level at 24 h after PMX appears to predict outcome after PMX. Therefore, procalcitonin may be a useful diagnostic marker to evaluate patients’ condition in candidates for PMX treatment.