Ga-67 scintigraphy in patients with breast lymphoma.

PURPOSE: The authors studied the utility of Ga-67 citrate scintigraphy in patients with breast lymphoma. METHODS: Seven patients with histologically proved breast lymphoma were examined. In three patients, both breasts were involved, and all patients had rapidly growing breast masses. Planar and SPECT images were obtained 72 hours after injection of Ga-67. RESULTS: Ga-67 scintigraphy showed intense accumulation in all lymphomas. SPECT images provided better contrast than did planar images. In one of the seven patients, the axilla and mediastinum were also involved. In six of the seven patients, Ga-67 scintigraphy was also performed after treatment and showed the disappearance of Ga-67 accumulation. In one patient with local recurrence and lung involvement, abnormal accumulation was depicted on follow-up Ga-67 scintigraphy. CONCLUSIONS: Ga-67 scintigraphy was helpful to confirm the diagnosis and the systemic extent of lymphoma and to evaluate the therapeutic effect during follow-up in patients with breast lymphoma.     

Influence of a Rotational Speed Modulation System Used With an Implantable Continuous‐Flow Left Ventricular Assist Device on von Willebrand Factor Dynamics

We have developed a rotational speed (RS) modulation system for a continuous‐flow left ventricular assist device (EVAHEART) that can change RS in synchronization with a patient's electrocardiogram. Although EVAHEART is considered not to cause significant acquired von Willebrand syndrome, there remains a concern that the repeated acceleration and deceleration of the impeller may degrade von Willebrand factor (vWF) multimers. Accordingly, we evaluated the influence of our RS modulation system on vWF dynamics. A simple mock circulation was used. The circulation was filled with whole bovine blood (650 mL), and the temperature was maintained at 37 ± 1°C. EVAHEART was operated using the electrocardiogram‐synchronized RS modulation system with an RS variance of 500 rpm and a pulse frequency of 60 bpm (EVA‐RSM; n = 4). The pumps were operated at a mean flow rate of 5.0 ± 0.2 L/min against a mean pressure head of 100 ± 3 mm Hg. The continuous‐flow mode of EVAHEART (EVA‐C; n = 4) and ROTAFLOW (ROTA; n = 4) was used as controls. Whole blood samples were collected at baseline and every 60 min for 6 h. Complete blood counts (CBCs), normalized indexes of hemolysis (NIH), vWF antigen (vWF:Ag), vWF ristocetin cofactor (vWF:Rco), the ratio of vWF:Rco to vWF:Ag (Rco/Ag), and high molecular weight multimers (HMWM) of vWF were evaluated. There were no significant changes in CBCs throughout the 6‐h test period in any group. NIH levels of EVA‐RSM, EVA‐C, and ROTA were 0.0035 ± 0.0018, 0.0031 ± 0.0007, and 0.0022 ± 0.0011 g/100 L, respectively. Levels of vWF:Ag, vWF:Rco, and Rco/Ag did not change significantly during the test. Immunoblotting analysis of vWF multimers showed slight degradation of HMWM in all groups, but there were no significant differences between groups in the ratios of HMWM to low molecular weight multimers, calculated by densitometry. This study suggests that our RS modulation system used with EVAHEART does not have marked adverse influences on vWF dynamics. The low NIH and the absence of significant decreases in CBCs indicate that EVAHEART is hemocompatible, regardless of whether it is operated with the RS modulation system.     

Congenital nephrotic syndrome with a novel NPHS1 mutation

Congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal recessive disorder. The incidence of CNF is relatively high in Finland but considerably lower in other countries. We encountered a male newborn with CNF, associated with compound heterozygous mutations in nephrosis 1, congenital, Finnish type (NPHS1). The patient was admitted to hospital as a preterm infant. Physical and laboratory findings fulfilled the diagnostic criteria of nephrotic syndrome, and were compatible with a diagnosis of CNF, but there was no family history of the disease. On genetic analysis of NPHS1 a paternally derived heterozygous frame‐shift mutation caused by an 8 bp deletion, resulting in a stop codon in exon 16 (c.2156‐2163 delTGCACTGC causing p.L719DfsX4), and a novel, maternally derived nonsense mutation in exon 15 (c.1978G>T causing p.E660X) were identified. Early genetic diagnosis of CNF is important for proper clinical management and appropriate genetic counseling.     

Analytical and Clinical Evaluation of the Epistem Genedrive Assay for Detection of Mycobacterium tuberculosis

The Epistem Genedrive assay rapidly detects the Mycobacterium tuberculosis complex from sputum and is currently available for clinical use. However, the analytical and clinical performance of this test has not been fully evaluated. The analytical limit of detection (LOD) of the Genedrive PCR amplification was tested with genomic DNA; the performance of the complete (sample processing plus amplification) system was tested by spiking M. tuberculosis mc²6030 cells into distilled water and M. tuberculosis-negative sputum. Specificity was tested using common respiratory pathogens and nontuberculosis mycobacteria. A clinical evaluation enrolled adults with suspected pulmonary tuberculosis, obtained three sputum samples from each participant, and compared the accuracy of the Genedrive to that of the Xpert MTB/RIF assay using M. tuberculosis cultures as the reference standard. The Genedrive assay had an LOD of 1 pg/μl (100 genomic DNA copies/reaction). The LODs of the system were 2.5 × 10⁴ CFU/ml and 2.5 × 10⁵ CFU/ml for cells spiked into water and sputum, respectively. False-positive rpoB probe signals were observed in 3/32 (9.4%) of the negative controls and also in few samples containing Mycobacterium abscessus, Mycobacterium gordonae, or Mycobacterium thermoresistibile. In the clinical study, among 336 analyzed participants, the overall sensitivities for the tuberculosis case detection of Genedrive, Xpert, and smear microscopy were 45.4% (95% confidence interval [CI], 35.2% to 55.8%), 91.8% (95% CI, 84.4% to 96.4%), and 77.3% (95% CI, 67.7% to 85.2%), respectively. The sensitivities of Genedrive and Xpert for the detection of smear-microscopy-negative tuberculosis were 0% (95% CI, 0% to 15.4%) and 68.2% (95% CI, 45.1% to 86.1%), respectively. The Genedrive assay did not meet performance standards recommended by the World Health Organization for a smear microscopy replacement tuberculosis test. Epistem is working on modifications to improve the assay.     

Relapsed childhood acute myeloid leukemia patient with inversion of chromosome 16 harboring a low FLT3 internal tandem duplication allelic burden and KIT mutations

Inversion of chromosome 16 [inv(16)] has a good prognosis in acute myeloid leukemia (AML), but additional genetic aberrations influence the outcome. We herein describe the case of a 15‐year‐old Japanese boy with inv(16) harboring a low‐allelic burden internal tandem duplication of FLT3 (FLT3‐ITD) and KIT mutations. Conventional chemotherapy eradicated a clone with a low‐allelic burden FLT3‐ITD mutation, although another clone with a KIT mutation occurred 17 months later. Further investigation is necessary to identify AML with inv(16) conferring poor prognosis, to facilitate appropriate treatment with additional drugs, such as dasatinib or gemtuzumab ozogamicin.     

Prediction of the efficacy of immunotherapy by measuring the integrity of cell‐free DNA in plasma in colorectal cancer

We previously reported a phase II study of a cancer vaccine using five novel peptides recognized by HLA‐A*2402‐restricted CTL in combination with oxaliplatin‐containing chemotherapy (FXV study) as first‐line therapy for patients with metastatic colorectal cancer and demonstrated the safety and promising potential of our five‐peptide cocktail. The objective of this analysis was to identify predictive biomarkers for identifying patients who are likely to receive a clinical benefit from immunochemotherapy. Circulating cell‐free DNA (cfDNA) in plasma has been reported to be a candidate molecular biomarker for the efficacy of anticancer therapy. Unlike uniformly truncated small‐sized DNA released from apoptotic normal cells, DNA released from necrotic cancer cells varies in size. The integrity of plasma cfDNA (i.e. the ratio of longer fragments [400 bp] to shorter fragments [100 bp] of cfDNA), may be clinically useful for detecting colorectal cancer progression. We assessed plasma samples collected from 93 patients prior to receiving immunochemotherapy. The cfDNA levels and integrity were analyzed by semi‐quantitative real‐time PCR. Progression‐free survival was significantly better in patients with a low plasma cfDNA integrity value than in those with a high value (P = 0.0027). Surprisingly, in the HLA‐A*2402‐matched group, patients with a low plasma cfDNA integrity value had significantly better progression‐free survival than those with a high value (P = 0.0015). This difference was not observed in the HLA‐A*2402‐unmatched group. In conclusion, the integrity of plasma cfDNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in metastatic colorectal cancer.