N2 Lymph Node Metastasis Is a Useful Predictor of Recurrence in Patients With Stage III Rectal Cancer Undergoing Adjuvant Chemotherapy Using Tegafur-uracil/leucovorin.

BACKGROUND/AIM: Fluoropyrimidine therapy or oxaliplatin combination therapy is recommended for patients with stage III colorectal cancer as adjuvant chemotherapy (AC). However, the criterion for selecting these regimens is still unclear in patients with stage III rectal cancer (RC). In order to select an appropriate regimen of AC for such patients, it is needed to identify characteristics associated with tumor recurrence. PATIENTS AND METHODS: The records of 45 patients with stage III RC undergoing AC using tegafur-uracil/leucovorin (UFT/LV) were retrospectively reviewed. The cut-off value of characteristics was determined using a receiver operating characteristic curve for recurrence. Univariate analyses using Cox-Hazard model for predicting recurrence were performed with clinical characteristics. Survival analysis was performed using Kaplan-Meier method and log-rank test. RESULTS: Thirty patients (66.7%) completed AC using UFT/LV. Fifteen patients (33.3%) did not complete AC because of adverse events, tumor recurrence and others. Sixteen patients (35.6%) had recurrence. Univariate analyses revealed that lymph node metastasis (N2/N1) (p=0.002) was associated with tumor recurrence. Survival analysis showed that lymph node metastasis (N2/N1) could stratify recurrence-free survival (p<0.001). CONCLUSION: N2 lymph node metastasis can predict tumor recurrence in patients with stage III RC undergoing AC using UFT/LV.

[Systemic varicella-zoster infection during ixazomib-containing multiagent chemotherapy for multiple myeloma].

A 58-year-old man received high-dose melphalan with autologous peripheral blood stem cell transplantation for multiple myeloma in stringent complete response (sCR). Relapse occurred 4 years after the transplantation, and he was placed on ixazomib, lenalidomide, and dexamethasone (IRd) and achieved sCR. On the 10th day of the 10th course of IRd, he developed fever followed by generalized skin eruption with vesicles, headache, and dizziness. Varicella-zoster virus (VZV) antigen from the vesicle and VZV-DNA from the cerebrospinal fluid were detected, and he was diagnosed with systemic VZV infection. He was placed on intravenous acyclovir (ACV), and the infection resolved completely. VZV infection has been recognized as an important complication associated with the use of proteasome inhibitors; however, to our knowledge, there have been no reported cases of serious systemic VZV infection associated with ixazomib. The clinical course of this case strongly suggests the importance of prophylaxis for VZV infection during treatment with ixazomib.

Effects of branched-chain amino acids on postoperative tumor recurrence in patients undergoing curative resection for hepatocellular carcinoma: A randomized clinical trial.

BACKGROUND/PURPOSE: No effective postoperative adjuvant therapies have been established for patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the effect of oral administration of branched-chain amino acids (BCAA) on the recurrence-free survival (RFS) after hepatic resection in HCC patients. METHODS: In this randomized clinical trial, HCC patients undergoing curative resections were randomly assigned in a 1:1 ratio to the BCAA group or surgery-alone group. The BCAA group received BCAA (Livact® ) for up to 4 years. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Multivariate analysis was performed to detect the clinical characteristics significantly associated with RFS. RESULTS: Between January 2010 and October 2014, 156 patients (75 in BCAA group and 81 in surgery-alone group) were enrolled in the study. Of these, two patients were excluded from the efficacy analysis. Comparison of the survival curves by the log rank test demonstrated no significant difference in the RFS (P = .579) or OS (P = .268) between the BCAA and the control group. Multivariate analysis revealed that the RFS was significantly associated with age and number of tumors. A beneficial effect of BCAA on the RFS was found in patients younger than 72 years old with a HbA1c level of < 6.4%. CONCLUSIONS: Oral BCAA supplementation could not reduce the risk of recurrence after hepatic resection in HCC patients; however, the results suggested that BCAA supplementation may be beneficial for selected patients who were younger and had mildly impaired glucose tolerance.

[Copper deficiency anemia morphologically mimicking myelodysplastic syndrome].

A 64-year-old man underwent kidney transplantation for progressive chronic renal failure which had developed 8 years after allogeneic bone marrow transplantation for acute myeloid leukemia. Because of post-operative complications, he had been placed on intravenous hyperalimentation. Three months after the transplantation, anemia rapidly progressed (hemoglobin, 7.9 g/dl). The proportion of reticulocytes was 0.2%, but white blood cell and platelet counts remained within normal ranges. Serum iron, vitamin B12, and folate levels were normal. Bone marrow examination showed the presence of ringed sideroblasts and cytoplasmic vacuoles in a fraction of erythroid cells. Megakaryocytes were adequate in number with normal morphology. Although the findings were consistent with refractory anemia with ringed sideroblasts according to the WHO classification, cytoplasmic vacuolations were also observed in myeloid cells, suggesting copper deficiency. Indeed, serum copper and ceruloplasmin levels were found to be low (33 µg/dl and 11 mg/dl, respectively), and oral copper supplementation at a daily dose of 1 mg was initiated. There was a prompt increase in reticulocytes, and the hemoglobin level was normalized within one month, in response to this regimen. In progressive anemia cases with ringed sideroblasts in the bone marrow, copper deficiency should be considered in the differential diagnosis.

Effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury.

OBJECTIVES: The usefulness of omega-3 lipid emulsions has been extensively studied. The objectives of the present study were to examine the effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury and the underlying mechanism. METHODS: A total of 66 rats were divided into three dietary groups (lipid-free, soybean oil, and fish oil groups). Each animal was administered total parenteral nutrition for 3 days, followed by induction of intestinal ischemia for 100 min. Animals subjected to sham surgery served as the controls. Intestinal tissue and blood were harvested 6 and 12 h after the surgery, then, assessment of the histological damage score, plasma-related parameters, and statistical evaluation were performed. RESULTS: The histological damage score in the intestinal tissues was significantly lower in the fish oil group than in the soybean oil group (P = 0.0121). The late-phase urinary level of 8-hydroxy-2-deoxyguanosine was also significantly lower in the fish oil group as compared with that in the other groups (P = 0.0267). Furthermore, the plasma level of high-mobility group box 1 protein was also significantly lower in the fish oil group as compared with that in the lipid-free group (P = 0.0398). CONCLUSION: It appeared that intravenous administration of an omega-3 lipid emulsion prior to ischemia-reperfusion injury reduced the oxidative stress and severity of tissue damage. Modification of membrane fatty acids may serve as the mechanism underlying this reduction of tissue damage.

Effects of immunosuppressive agents on magnesium metabolism early after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The calcineurin inhibitors, cyclosporine A (CSA) and tacrolimus, cause hypomagnesemia by suppressing reabsorption of magnesium (Mg) from renal tubules. To assess whether the effect on Mg metabolism after allogeneic hematopoietic stem cell transplantation (HSCT) differs among calcineurin inhibitors, we prospectively evaluated the Mg metabolism in recipients of allogeneic HSCT who received CSA or tacrolimus METHODS: Patients who underwent allogeneic HSCT were enrolled. CSA and tacrolimus were given by continuous infusion starting from day -1. Serum Mg and the total amount of urinary Mg excretion were measured once before starting of CSA or tacrolimus, and once weekly after HSCT for 4 weeks. Mg was supplemented with magnesium l-aspartate by continuous infusion to maintain the serum Mg level >1.4 mEq/L. RESULTS: Thirty-six patients were evaluated (12 in the CSA group, 24 in the tacrolimus group). The serum Mg level began to decrease in both groups at the first week after HSCT, and the mean serum Mg levels were significantly lower in the tacrolimus group than in the CSA group from the first to the third week. The total amount of urinary Mg excretion and Mg supplementation began to increase in both groups at the second week after HSCT, and the amounts in the tacrolimus group were significantly higher than those in the CSA group. CONCLUSIONS: Although both calcineurin inhibitors increased urinary Mg excretion and caused hypomagnesemia shortly after HSCT, the effect was more significant with tacrolimus than with CSA. This observation may explain the higher incidence of renal impairment and encephalopathy in patients receiving tacrolimus.