The C-reactive protein/albumin ratio (CAR), an inflammatory marker, is a useful biomarker for pancreatic cancer. Although disease status is not constant, many inflammatory markers are only classified at the start of treatment. Therefore, biomarker analysis that considers the changes in inflammatory markers during treatment is desirable. We aimed to investigate whether time-dependent changes in the CAR during nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) administration can predict the prognosis of patients with unresectable or recurrent pancreatic cancer (urPC). CAR was measured in 150 participants of the NAPOLEON-2 study, an observational study involving patients with pancreatic cancer receiving NFF, and the patients were stratified by CAR. The CAR at NFF initiation was defined as CAR(1), while the minimum CAR before/throughout NFF administration was defined as CAR(min). Overall survival (OS) of patients in all groups was analyzed. Significant differences in OS between the CAR(1) < 0.54 and ≥ 0.54 groups and between the CAR(min) < 0.54 and ≥ 0.54 groups were observed. The OS was significantly better in the group with CAR(min)/CAR(1) < 0.5 than in the group with CAR(min)/CAR(1) ≥ 0.5. Dynamic changes in CAR were a clinically significant biomarker that considers not only the disease status at the start of treatment but also the response to treatment. CAR monitoring would help understand the disease status and thereby aid patients and physicians alike.
Textbook outcome (TO) reflects ideal surgical and postoperative quality measures from the patient’s perspective. Non-achievement of a TO has been linked to a poor prognosis after colorectal cancer surgery. Minimally invasive colectomy (MIC), being considerably less invasive than open colectomy (OC) may improve prognosis; however, its effect on the long-term prognosis of patients with non-achievement of a TO remains unclear. This study investigated the impact of TO achievement on prognosis after OC and MIC. The subjects of this retrospective analysis were 256 patients who underwent OC and 472 patients who underwent MIC for colorectal cancer at Miyazaki Prefectural Nobeoka Hospital or Kumamoto University. TO was defined by five criteria: surgery within 6 weeks of diagnosis, radical resection, lymph node (LN) yield ≥ 12, no stoma, and no adverse outcomes. TO was achieved when all criteria were met; otherwise, the result was defined as non-TO (nTO). Both OC and MIC groups were stratified by TO status. TO achievement was significantly higher after MIC than after OC (39.0
All-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) has become the international standard of care for newly diagnosed acute promyelocytic leukemia (APL), demonstrating superior efficacy and safety over ATRA-chemotherapy regimens. However, in Japan, ATO has been approved only for relapsed/refractory APL, and prospective data on its frontline use are lacking. We conducted FBMTG-APL2017, a prospective multicenter phase II trial in Japan, to evaluate ATRA-ATO in newly diagnosed APL patients, including both low-intermediate-risk and high-risk groups. Eighty-one patients were enrolled between 2017 and 2021 and treated with ATRA plus delayed ATO during induction, followed by four cycles of ATRA-ATO consolidation. Complete remission was achieved in 95.1% of patients. With a median follow-up of 55 months, 3-year disease-free survival (DFS) and overall survival (OS) were 93.6% and 95.0%, respectively, consistent with international ATRA-ATO trials. DFS was 96.9% in low-intermediate-risk and 80.0% in high-risk patients, with no significant difference. Molecular remission was achieved in 99% after consolidation, and only two molecular relapses occurred. Differentiation syndrome developed in 56.8% but was generally manageable, with only one fatal case; early death occurred in 4.9%, comparable to international data. These results provide the first prospective evidence in Japan that frontline chemo-free ATRA-ATO is highly effective and safe across all risk groups. They support its adoption as a new standard therapy and bridge the gap with established global practice. Trial Registration: Japan Registry of Clinical Trials: jRCTs071180040.
INTRODUCTION:The internal thoracic artery is commonly used as a graft in coronary artery bypass grafting. In this study, we aimed to investigate whether papaverine prevents vasoconstriction caused by various vasospasm inducers, including 5-hydroxytriptamine or serotonin, in endothelium-denuded internal thoracic artery at concentrations as low as 1.25 mM used for radial arteries. METHODS:Human internal thoracic artery tissue was obtained from patients (n=6) undergoing coronary artery bypass grafting. The organ bath technique was used to determine the inhibitory effects of papaverine on vasoconstriction induced by ergonovine, adenosine diphosphate, 5-hydroxytriptamine, noradrenaline, and angiotensin II in isolated endothelium-denuded internal thoracic artery. Moreover, the inhibitory effect of papaverine on collagen-stimulated human platelet aggregation was examined at the same concentration. RESULTS:Papaverine inhibited ergonovine-induced vasoconstriction in a concentration-dependent manner. Papaverine at concentrations > 30 μM not only blocked ergonovine-induced vasoconstriction but also induced vasodilation. Papaverine at 30 μM significantly suppressed the vasoconstriction induced by 5-hydroxytriptamine or noradrenaline and completely blocked that induced by adenosine diphosphate or angiotensin II. However, 100 μM papaverine completely blocked the vasoconstriction induced by adenosine diphosphate, 5-hydroxytriptamine, noradrenaline, and angiotensin II. Additionally, papaverine significantly inhibited collagen-stimulated human platelet aggregation in a concentration-dependent manner. CONCLUSION:Overall, 100 μM papaverine prevented vasoconstriction by various vasospasm inducers, such as 5-hydroxytriptamine, and significantly suppressed collagen-stimulated platelet aggregation. These results suggest that papaverine at 100 μM, which is 1/10th the concentration used for radial artery, is sufficient to prevent vasospasm in internal thoracic artery during coronary artery bypass grafting.
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy with a poor prognosis. We conducted a retrospective study across six institutions in Miyazaki Prefecture, Japan, to assess the efficacy of tucidinostat in patients with relapsed/refractory ATL who had not undergone transplantation. Between October 2021 and July 2023, 24 patients aged 41 to 88 years (median, 73.4 years) who had undergone prior therapies, including intensive chemotherapy (79.2%) and mogamulizumab immunotherapy (79.2%), received tucidinostat. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated as key outcomes. ORR and DCR reached 54.2% and 91.7%, respectively. The median PFS was 3.95 months, and OS was 8.04 months, which were not inferior to the results of a phase IIb study. The influential factors for PFS were age ≥ 75 years and high soluble IL-2 receptor (sIL-2R) levels above 5000 U/mL at the start of treatment. Favorable patients without these factors achieved a PFS of 11.4 months. Treatment-related adverse events were mainly hematologic but were managed over the course of treatment. Our findings indicate that tucidinostat provides survival benefits in patients with relapsed/refractory ATL in clinical practice and highlight key clinical factors for better outcomes.
