The Outcomes of Hypertransfusion in Major ABO Incompatible Allogeneic Stem Cell Transplantation

Major ABO incompatibility may be potentially associated with immediate or delayed hemolysis and delayed onset of erythropoiesis in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To determine if hemolysis can be prevented by the inhibition of graft erythropoiesis, we performed hypertransfusion and assessed red cell transfusion requirement and independence. Between October 1995 and December 2001, 28 consecutive patients receiving major ABO incompatible HSCT at Samsung Medical Center were hypertransfused to maintain their hemoglobin levels at 15 g/dL or more. We retrospectively compared the outcomes of these patients with those of 47 patients at Asan Medical Center whose target hemoglobin levels were 10 g/dL. Reticulocyte engraftment was significantly delayed in hypertransfused group (51 days vs. 23 days; p=.001). There was no significant difference in the total amount of red cells transfused within 90 days post-HSCT (25 units vs. 26 units; p=.631). No significant difference in the time to red cell transfusion independence was observed between the two groups (63 days vs. 56 days; p=.165). In conclusion, we failed to improve red cell transfusion requirement and independence in major ABO incompatible HSCT with hypertransfusion

Pulmonary Complications After Hematopoietic Stem Cell Transplantation

Despite advanced effective prophylaxes, pulmonary complications still occur in a high proportion of all hematopoietic stem cell recipients, accounting for considerable morbidity and mortality. The aim of our study was to describe the causes, incidences and mortality rates secondary to pulmonary complications and risk factors of such complications following hematopoietic stem cell transplantation (HSCT). We reviewed the medical records of 287 patients who underwent either autologous or allogeneic HSCT for hematologic disorders from February 1996 to October 2003 at Samsung Medical Center (134 autografts, 153 allografts). The timing of pulmonary complications was divided into pre-engraftment, early and late period. The spectrum of pulmonary complications included infectious and non-infectious conditions. 73 of the 287 patients (25.4%) developed pulmonary complications. Among these patients, 40 (54.8%) and 29 (39.7%) had infectious and non-infectious conditions, respectively. The overall mortality rate from pulmonary complications was 28.8%. Allogeneic transplant, grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were the risk factors with statistical significance for pulmonary complications after HSCT. The mortality rates from pulmonary complications following HSCT were high, especially those of viral and fungal pneumonia, diffuse alveolar hemorrhage and idiopathic pneumonia syndrome

Prevalence and detection of low-allele-fraction variants in clinical cancer samples

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay

The effect of ion beam bombardment on the properties of Ta(C)N films deposited from pentakis-diethylamido-tantalum

TaN or TaCN films were deposited using a single source, pentakis-diethylamido-tantalum as diffusion barrier for copper metallization. N- and Ar-ion beams with energy of 120 eV were used for bombarding the film during growth to improve the film quality. The films deposited using N-ion beam showed a resistivity of approximately 950 muOhm cm and a density of 7.65 g/cm(3). The use of the N-ion beam, however, drastically degraded the step coverage of the film (similar to5% at the 0.5 mum contact holes with aspect ratio of 3:1). On the other hand, the films deposited using an Ar-ion beam showed a resistivity of approximately 600 muOhm cm and a density of 8.26 g/cm(3). The step coverage measured at the same contact was approximately 40%. The resistivity and density of the thermally-decomposed film were also measured for comparison and were found to be approximately 10 000 muOhm cm and 5.85 g/cm(3), respectively. Finally, the diffusion barrier performance of 50 nm thick films against Cu was investigated by X-ray diffractometry. The Cu/N- or Ar-ion beam bombarded film/Si structures showed formation of eta"-Cu3Si after annealing at 650 degreesC for I h, while Cu/thermally-decomposed film/Si showed this only after annealing at 600 degreesC. (C) 2002 Elsevier Science B.V. All rights reserved

Human Epidermal Growth Factor Receptor 2 Expression in Unresectable Gastric Cancers: Relationship with CT Characteristics

Objective: To retrospectively analyze the qualitative CT features that correlate with human epidermal growth factor receptor 2 (HER2)-expression in pathologically-proven gastric cancers. Materials and Methods: A total of 181 patients with pathologically-proven unresectable gastric cancers with HER2-expression (HER2-positive [n = 32] and negative [n = 149]) were included. CT features of primary gastric and metastatic tumors were reviewed. The prevalence of each CT finding was compared in both groups. Thereafter, binary logistic regression determined the most significant differential CT features. Clinical outcomes were compared using Kaplan-Meier method. Results: HER2-postive cancers showed lower clinical T stage (21.9% vs. 8.1%; p = 0.015), hyperattenuation on portal phase (62.5% vs. 30.9%; p = 0.003), and was more frequently metastasized to the liver (62.5% vs. 32.2%; p = 0.001), than HER2-negative cancers. On binary regression analysis, hyperattenuation of the tumor (odds ratio [OR], 4.68; p < 0.001) and hepatic metastasis (OR, 4.43; p = 0.001) were significant independent factors that predict HER2-positive cancers. Median survival of HER2-positive cancers (13.7 months) was significantly longer than HER2-negative cancers (9.6 months) (p = 0.035). Conclusion: HER2-positive gastric cancers show less-advanced T stage, hyperattenuation on the portal phase, and frequently metastasize to the liver, as compared to HER2-negative cancers

Multiparametric fully-integrated 18-FDG PET/MRI of advanced gastric cancer for prediction of chemotherapy response: a preliminary study

To investigate usefulness of multiparametric fully integrated 18-FDG PET/MRI in predicting treatment response after chemotherapy for unresectable advanced gastric cancers (AGCs). Eleven patients with unresectable AGCs underwent multiparametric 18-FDG PET/MRI examinations prior to chemotherapy. Perfusion parameters obtained via dynamic contrast-enhanced MRI, apparent diffusion coefficient values from diffusion-weighted images, and maximum standardized uptake values (SUVmax) from 18-FDG PET were measured. For parameters obtained from 18-FDG PET/MRI data, interobserver agreement was obtained using intraclass correlation coefficients (ICC) and chemotherapy response relationship was evaluated using the Mann-Whitney test and receiver operating characteristic analysis. After chemotherapy, six patients were classified into the responder group and five patients into the non-responder group. For all parameters, moderate to nearly perfect agreement was achieved (ICC = 0.452-0.911). K (trans) values (P = 0.018) and initial area under the curves (iAUCs) (P = 0.045) of gastric cancers were significantly higher in responder group than in non-responder group. The area under the curve was 0.917 for K (trans) and 0.867 for iAUC. However, SUVmax values were not significantly different between the two groups. Multiparametric approach using fully integrated 18-FDG PET/MRI was shown to be feasible for patients with unresectable gastric cancers. In addition, K (trans) and iAUC values can be used as early predictive markers for chemotherapy response. Multiparametric 18-FDG PET/MRI is feasible for patients with unresectable advanced gastric cancer K (trans) and iAUC were significantly higher in the responder group of patients K (trans) , iAUC can be utilized as early predictive markers for chemotherapeutic response

Usefulness of CT volumetry for primary gastric lesions in predicting pathologic response to neoadjuvant chemotherapy in advanced gastric cancer

To investigate the utility of CT volumetry for primary gastric lesions in the prediction of pathologic response to neoadjuvant chemotherapy in patients with resectable advanced gastric cancer (AGC). Thirty-three consecutive patients with resectable AGC stage a parts per thousand yenT2 and N1), who had been treated with neoadjuvant chemotherapy and radical gastric resection, were prospectively enrolled in this study. There were 30 men and 3 women with a mean age of 53.8 years. Contrast-enhanced CT was obtained after gastric distention with air before and after chemotherapy using a MDCT scanner. Pre- and post-chemotherapy thickness or short diameter and volume of the primary gastric tumor and largest lymph node (LN), were measured using a dedicated 3D software by two radiologists in consensus. PET/CT was also performed and the peak standardized uptake value (SUV) of primary gastric tumor and largest LN before and after chemotherapy was measured. The percentage diameter, volume, and SUV reduction rates for both the primary gastric tumor and the LN, were calculated and correlated with the histopathologic grades of regression using the Spearman correlation test. Differentiation between pathologic responders and nonresponders was assessed using receiver operating characteristic (ROC) analysis. Among the three CT parameters which showed significant correlation with the histopathologic grades of regression, the correlation factor was highest in the percentage volume reduction rate of primary gastric tumor (rho = 0.484, P = 0.004) followed by percentage volume reduction of the index node (rho = 0.397, P = 0.022), and percentage diameter reduction of the index node (rho = 0.359, P = 0.04). However, the percentage thickness decrease rate (P = 0.208) and the percentage SUV reduction rate (P = 0.619) of primary gastric tumor were not significantly correlated with the histopathologic grades of regression. When the optimal cutoff value of the percentage volume reduction rate of primary gastric tumor was determined to be 35.6%, a sensitivity of 100% (16/16) and a specificity of 58.8% (10/17) were achieved. CT volumetry for primary gastric tumor may be the most accurate tool in the prediction of pathologic response following neoadjuvant chemotherapy in patients with resectable AGC.

Diagnostic accuracy of T and N stages with endoscopy, stomach protocol CT, and endoscopic ultrasonography in early gastric cancer

BACKGROUND: Preoperative accurate diagnosis of the T and N stages in early gastric cancer (EGC) is important in determining the application of various limited treatments. The aim of this study is to analyze the accuracy of T and N staging of EGC with esophagogastroduodenoscopy (EGD), Stomach protocol CT (S-CT), and endoscopic ultrasonography (EUS), and the factors influencing the accuracy. METHODS: Four hundred and thirty-four patients preoperatively diagnosed as EGC using EGD or S-CT and undergoing curative gastrectomy at Seoul National University Hospital in 2005 were included. The T and N stage reviewed by experienced personnel were compared with the surgical pathology. RESULTS: The predictive values for EGC of EGD, S-CT, and EUS were 87.4%, 92.2%, and 94.1%, respectively. The predictive values for node negativity of S-CT, and EUS were 90.1% and 92.6%, respectively. The factors leading to underestimation of T stage with EGD were the upper third location, the size greater than 2 cm, and diffuse type of tumor. Those with S-CT were female sex, the upper third location and lesion size greater than 2 cm. CONCLUSIONS: Before applying limited treatment for EGC, a surgeon should consider the risk factors of underestimation of T stage with EGD or S-CT