Usefulness of serum lipase for early diagnosis of post-endoscopic retrograde cholangiopancreatography pancreatitis

BACKGROUND Post-endoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP)is new onset acute pancreatitis after ERCP.This complication is sometimes fatal.As such,PEP should be diagnosed early so that therapeutic interventions can be carried out.Serum lipase(s-Lip)is useful for diagnosing acute pancreatitis.However,its usefulness for diagnosing PEP has not been sufficiently investigated.AIM This study aimed to retrospectively examine the usefulness of s-Lip for the early diagnosis of PEP.METHODS We retrospectively examined 4192 patients who underwent ERCP at our two hospitals over the last 5 years.The primary outcomes were a comparison of the areas under the receiver operating characteristic(ROC)curves(AUCs)of s-Lip and serum amylase(s-Amy),s-Lip and s-Amy cutoff values based on the presence or absence of PEP in the early stage after ERCP via ROC curves,and the diagnostic properties[sensitivities,specificities,positive predictive values(PPV),and negative predictive value(NPV)]of these cutoff values for PEP diagnosis.RESULTS Based on the eligibility and exclusion criteria,804 cases were registered.Over the entire course,PEP occurred in 78 patients(9.7%).It occurred in the early stage after ERCP in 40 patients(51.3%)and in the late stage after ERCP in 38 patients(48.7%).The AUCs were 0.908 for s-Lip[95%confidence interval(CI):0.880-0.940,P<0.001]and 0.880 for s-Amy(95%CI:0.846-0.915,P<0.001),indicating both are useful for early diagnosis.By comparing the AUCs,s-Lip was found to be significantly more useful for the early diagnosis of PEP than s-Amy(P=0.023).The optimal cutoff values calculated from the ROC curves were 342 U/L for s-Lip(sensitivity,0.859;specificity,0.867;PPV,0.405;NPV,0.981)and 171 U/L for s-Amy(sensitivity,0.859;specificity,0.763;PPV,0.277;NPV,0.979).CONCLUSION S-Lip was significantly more useful for the early diagnosis of PEP.Measuring s-Lip after ERCP could help diagnose PEP earlier;hence,therapeutic interventions can be provided earlier.

Is the CD4/CD8 Ratio an Effective Indicator for Clinical Estimation of Adoptive Immunotherapy for Cancer Treatment?

Background: The importance of immunotherapy in cancer treatment has been increased owing to its non-toxicity and application to personalized medicine. However, precise estimation indices of immunotherapy have yet to be established. To determine effective evaluation indices of immunotherapy for cancer treatment, we analyzed the CD4/CD8 ratio under various conditions in clinical patients with advanced cancer. Patients and Methods: Thirty-four patients who underwent one course of adoptive activated immunotherapy with or without additional conventional chemotherapy were enrolled. Before and after one course of immunotherapy, changes in the CD4/CD8 ratio were estimated by flow cytometry. Results: All patients showed a tendency toward a decrease in the CD4/CD8 ratio during a 3-month period after one course of adoptive activated T lymphocyte immunotherapy. Patients who had undergone prior surgery showed a remarkable increase in CD8 T cell number. Thus, adoptive activated T lymphocyte immunotherapy improves immunological ability against cancer invasion. The Eastern Cooperative Oncology Group’s performance status during one course of immunotherapy was significantly improved in the antecedent surgery group, with no evidence of improved PS in the non-antecedent surgery group. Patients with an increased CD4/CD8 ratio (n = 6) may have a worse outcome during adoptive activated T lymphocyte immunotherapy even with an additional course of immunotherapy. Improved actuarial survival rate of patients in the antecedent surgery group showed significant long-term benefit compared to those in the non-antecedent surgery group (p = 0.0298), as previously reported. Conclusion: The CD4/CD8 ratio is a significant indicator of outcome of adoptive activated T lymphocyte immunotherapy.

Phase Ⅰ trial of combination chemotherapy with gemcitabine, cisplatin, and S-1 in patients with advanced biliary tract cancer

AIM: To evaluate the dose-limiting toxicities(DLTs)and determine the maximum-tolerated dose(MTD) and recommended dose(RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer.METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine(mg/m2), cisplatin(mg/m2), and S-1(mg/m2 per day) were as follows: level-1, 800/20/60;level 0, 800/25/60; level 1, 1000/25/60; and level 2,1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15,and S-1 was administered orally twice daily on days 1to 7 and days 15 to 21, every 4 wk.RESULTS: Twelve patients were enrolled, and level0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs(grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1.We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase Ⅱ study.CONCLUSION: The RD was defined as gemcitabine1000 mg/m2(days 1, 15), cisplatin 25 mg/m2(days1, 15), and S-1 80 mg/m2 per day(days 1-7, 15-21),every 4 weeks. A phase Ⅱ study is planned to evaluate the effectiveness of combination chemotherapy withgemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.