Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA‐identical related donors

Watanabe N, Takahashi Y, Matsumoto K, Horikoshi Y, Hama A, Muramatsu H, Yoshida N, Yagasaki H, Kudo K, Horibe K, Kato K, Kojima S. Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA‐identical related donors.
Pediatr Transplantation 2011: 15: 642–649. © 2011 John Wiley & Sons A/S. Abstract: Although some studies have reported that TBI and MEL offer an effective conditioning regimen for autologous SCT in acute leukemia, little has been reported regarding outcomes of allogeneic SCT. We retrospectively evaluated outcomes for 50 pediatric patients who underwent allo‐SCT conditioned with intravenous MEL (180–210 mg/m²) and fractionated TBI (12–13.2 Gy) from HLA‐identical related donors. Nineteen patients were in CR1, 18 were in CR2, and 13 showed advanced‐stage disease (≥CR3). Patients had received allo‐SCT from HLA‐identical siblings (n = 45) or phenotypically HLA‐identical family donors (n = 5). Median duration of follow‐up for all disease‐free patients was 61 months (range, 8.8–177 months). At the time of analysis, 12 patients had died. Eleven of those died of relapse, and one died of TRM. DFS rates for all patients, patients with AML (n = 12), and patients with lymphoid malignancy (n = 38) were 61.4% and 82.1%, respectively. DFS rates for CR1, CR2, and ≥CR3 cases were 89.2%, 88.1%, and 23.1%, respectively (p < 0.05). MEL/TBI for pediatric patients with hematological malignancies was associated with lower relapse rates and no increase in toxicity, resulting in better survival.     

Induction of Apoptosis after Stent Implantation in Canine Portal Vein

The purpose of this study was to analyze apoptosis in the vessel wall after stent implantation in the canine portal vein and also to investigate the expression of the p21 cyclin-dependent kinase inhibitor, which may regulate cellular proliferation after vascular injury. Uninjured, control veins had few detectable TUNEL-positive cells in the intima and media (0.829 ± 0.413%). At 4 weeks after stent implantation, TUNEL-positive cells significantly increased to 50.5 ± 4.639%. These cells were predominantly located around the stent struts, and appeared to be smooth muscle cells morphologically. At 12 weeks, 44.7 ± 6.178% of the intimal and medial cells were still TUNEL positive, and there was no significant difference between 4 and 12 weeks. P21 was not detected in uninjured, normal veins. At 4 and 12 weeks after stent implantation, positive p21 immunostaining was sparsely expressed in the intima and media adjacent to the stent struts. Thus, stent implantation induced a prolonged apoptotic response and increased expression of p21 in the portal venous system. This prolonged apoptotic response, possibly regulated by p21, may have a significant role in modulating the cellularity of intimal formation.     

Safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with chronic myeloid leukemia treated with dasatinib: a case report

Purpose

The safety of S-1 in recurrent colorectal cancer patients with chronic myeloid leukemia (CML) treated with dasatinib has not been established. We evaluated the safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with CML treated with dasatinib.

Patient

A 70-year-old man had undergone surgery three times for sigmoid colon cancer and recurrence. Systemic chemotherapy with S-1 plus oxaliplatin plus bevacizumab as a clinical trial had already been administered because of metastatic colon cancer. The patient’s medical history was CML, and he had been receiving dasatinib treatment (100 mg once daily). Based on the diagnosis of unresectable and multiple metastases, S-1 monotherapy was started. S-1 (120 mg/day) was taken for 28 consecutive days, followed by a 14-day rest. Blood samples were obtained before and after the first administration of S-1. The plasma pharmacokinetics of S-1 were comparable to a pharmacokinetics study of S-1.

Results

The area under the plasma concentration–time curve (AUC_0–8) of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), oxonate (Oxo), and 5-fluorouracil (5-FU) was 4,309.2, 716.3, 86.8, and 492.75 ng h/mL, respectively, after S-1 administration. The pharmacokinetics of FT, CDHP, Oxo, and 5-FU after treatment with S-1 were not significantly different from a phase I pharmacokinetics study of S-1. During treatment with S-1 and dasatinib, CML relapse and serious myelosuppression were not observed.

Conclusions

Our report suggests that S-1 is an important treatment option for recurrent colorectal cancer in patients with CML treated with dasatinib.     

Quantification of tumor vascularity with contrast-enhanced ultrasound for early response of transcatheter arterial chemoembolization for hepatocellular carcinoma: a report of three cases

Many contrast-enhanced ultrasound (CE-US) studies have been conducted by qualitative analysis of blood flow, such as classification of enhancement pattern. We evaluated early response of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) by quantitative analysis of intratumoral vascularity with CE-US in three patients. Three patients (one man, two women) with HCCs were treated in July 2009. CE-US with perfluorocarbon microbubbles (Sonazoid) and CT were performed serially before and 5 days after TACE. Post-processing enhancement intensity on US was analyzed to determine mean transit time (s), time to peak (s), enhancement peak intensity (dB), and “A” (scaling factor) by ultrasound quantification software after the data were fitted to a gamma variate curve. Mean transit time was prolonged by TACE in all three patients. Mean transit time rates on CE-US were 64.3, 33.8, and 65.6%, respectively, whereas the avascular rates on CT were 59.07, 31.71, and 62.25%, respectively. Mean transit time rates on CE-US approximated avascular rates on CT. Mean transit time rate may quantitatively indicate the early response of HCC to TACE.     

Validation of completion lobectomy after wedge resection for ≤20 mm non-small cell lung cancer

BackgroundCompletion lobectomy after wedge resection is occasionally performed when final histopathology shows an unexpected primary lung cancer even though the primary lesion has already been resected. The objective of this study was to assess the necessity of completion lobectomy after wedge resection for ≤20 mm non-small cell lung cancer (NSCLC).MethodsBetween 2006 and 2016, a total of 112 patients with NSCLC underwent wedge resection in our department. After exclusions, 40 patients were analyzed. Of these, 17 patients underwent completion lobectomy and 23 patients underwent wedge resection alone. Age, sex, tumor size, histology, other malignant diseases and final surgical procedure were used as prognostic variables. Survival analyses were confirmed using the Kaplan-Meier method and log-rank test.ResultsMedian follow-up was 70.4 months. No significant difference in 5-year overall survival (OS) and relapse-free survival (RFS) were seen in patients who underwent wedge resection alone compared to the completion lobectomy group (OS: 72.6% vs. 62.5%, P=0.34; RFS: 64.2% vs. 50.0%, P=0.35). Multivariate analysis identified age (>65 years old) and male sex as independent prognostic factors for OS and RFS.ConclusionsCompletion lobectomy after wedge resection did not impact OS or RFS compared with wedge resection alone in patients with ≤20 mm NSCLC. These findings suggested that selected patients may not require resection of the remaining lobe or lymph node dissection after initial wedge resection.     

Neuroimaging using ultrahigh-field magnetic resonance imaging at 7 tesla: current concepts

The introduction of ultrahigh-field MRI at 7 tesla (7T) has increased the interest in the use of neuroimaging techniques in clinical research. The high signal-to-noise ratio and profound susceptibility effect at 7T can remarkably improve the spatial resolution and image contrast of structural imaging, susceptibility imaging, and functional imaging techniques, whereas the heating effects of the radio frequency and the inhomogeneities of the local magnetic field can have substantial negative effects on parameter setting, acquisition time, and image quality. T1 prolongation at 7T can improve the enhancement effects of gadolinium agents and the inflow effects on MR angiography and arterial spin labeling. Ultrahigh-field MRI is expected to have a high clinical impact in the near future; however, further technological advances tailored to ultrahigh-field systems as well as the accumulation of scientific evidence will be needed to establish its clinical significance.