Hironori Nishibori

Impact of [11C]Methionine Positron Emission Tomography for Target Definition of Glioblastoma Multiforme in Radiation Therapy Planning

PURPOSE The purpose of this work was to define the optimal margins for gadolinium-enhanced T(1)-weighted magnetic resonance imaging (Gd-MRI) and T(2)-weighted MRI (T(2)-MRI) for delineating target volumes in planning radiation therapy for postoperative patients with newly diagnosed glioblastoma multiforme (GBM) by comparison to carbon-11-labeled methionine positron emission tomography ([(11)C]MET-PET) findings. METHODS AND MATERIALS Computed tomography (CT), MRI, and [(11)C]MET-PET were separately performed for radiation therapy planning for 32 patients newly diagnosed with GBM within 2 weeks after undergoing surgery. The extent of Gd-MRI (Gd-enhanced clinical target volume [CTV-Gd]) uptake and that of T(2)-MRI of the CTV (CTV-T(2)) were compared with the extent of [(11)C]MET-PET (CTV--[(11)C]MET-PET) uptake by using CT--MRI or CT--[(11)C]MET-PET fusion imaging. We defined CTV-Gd (x mm) and CTV-T(2) (x mm) as the x-mm margins (where x = 0, 2, 5, 10, and 20 mm) outside the CTV-Gd and the CTV-T(2), respectively. We evaluated the relationship between CTV-Gd (x mm) and CTV-- [(11)C]MET-PET and the relationship between CTV-T(2) (x mm) and CTV-- [(11)C]MET-PET. RESULTS The sensitivity of CTV-Gd (20 mm) (86.4%) was significantly higher than that of the other CTV-Gd. The sensitivity of CTV-T(2) (20 mm) (96.4%) was significantly higher than that of the other CTV-T(2) (x = 0, 2, 5, 10 mm). The highest sensitivity and lowest specificity was found with CTV-T(2) (x = 20 mm). CONCLUSIONS It is necessary to use a margin of at least 2 cm for CTV-T(2) for the initial target planning of radiation therapy. However, there is a limit to this setting in defining the optimal margin for Gd-MRI and T(2)-MRI for the precise delineation of target volumes in radiation therapy planning for postoperative patients with GBM.

Evaluation of organ involvement in intravascular large B-cell lymphoma by 18F-fluorodeoxyglucose positron emission tomography.

To evaluate the role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in intravascular large B-cell lymphoma (IVLBCL), we retrospectively analyzed four consecutive IVLBCL patients receiving FDG-PET before treatment between May 2006 and November 2007. Patients were two men and two women (median age 62 years, range 54–76 years). All patients received bone marrow biopsies and random skin biopsies and two of the four patients underwent renal biopsy for diagnosis. Accuracy of FDG-PET for the detection of organ involvements was analyzed by comparing results of pathological findings. Concordant results with respect to bone marrow involvement were accurately obtained for two patients. Skin and renal involvements were undetectable by FDG-PET regardless of positive pathological findings. One patient with a false-negative FDG-PET result showed fewer lymphoma cells in the bone marrow specimen than patients with concordant FDG-PET results. These results suggest false-negative results for some types of organ involvement. Careful interpretation of the results of FDG-PET in IVLBCL is thus required.

Molecular and clinical analysis of Japanese patients with persistent congenital hyperinsulinism: predominance of paternally inherited monoallelic mutations in the KATP channel genes.

BACKGROUND Preoperative identification of the focal form of congenital hyperinsulinism is important for avoiding unnecessary subtotal pancreatectomy. However, neither the incidence nor the histological spectrum of the disease is known for Japanese patients. AIMS The aim of the study was to elucidate the molecular and histological spectrum of congenital hyperinsulinism in Japan. SUBJECTS Thirty-six Japanese infants with persistent congenital hyperinsulinism were included in the study. METHODS All exons of the ATP-sensitive potassium channel (K(ATP) channel) genes (KCNJ11 and ABCC8), the GCK gene, and exons 6 and 7 and 10-12 of the GLUD1 gene were amplified from genomic DNA and directly sequenced. In patients with K(ATP) channel mutations, the parental origin of each mutation was determined, and the results were compared with the histological findings of surgically treated patients. In one of the patients with scattered lesions, islets were sampled by laser capture microdissection for mutational analysis. RESULTS Mutations were identified in 24 patients (66.7%): five in GLUD1 and 19 in the K(ATP) channel genes. Sixteen had a paternally derived, monoallelic K(ATP) channel mutation predictive of the focal form. In 10 patients who underwent pancreatectomy, the molecular diagnosis correctly predicted the histology, more accurately than [18F]-3,4-dihydroxyphenylalanine positron emission tomography scans. Three patients showed focal lesions that occupied larger areas of the pancreas. Preferential loss of the maternal allele was observed in these islets. CONCLUSION The majority of the Japanese patients with K(ATP) channel hyperinsulinism (84.2%) demonstrated paternally inherited monoallelic mutations that accurately predicted the presence of the focal form.

Target Definition by C11-Methionine-PET for the Radiotherapy of Brain Metastases

PURPOSE To evaluate the ability of 11C-methionine positron emission tomography (MET-PET) to delineate target volumes for brain metastases and to investigate to what extent tumor growth is presented by magnetic resonance imaging (MRI) and MET-PET. MATERIALS AND METHODS Three observers undertook target definition in 19 patients with 95 brain metastases by MRI and MET-PET images. MRI gross target volume (GTV) (GTV-MRI) was defined as the contrast-enhanced area on gadolinium-enhanced T1-weighted MRI. MET-PET GTV (GTV-PET) was defined as the area of an accumulation of MET-PET apparently higher than that of normal tissue on MET-PET images. The size of occupation ratio was determined using the following equation: SOR (%) of MET are within x mm margin outside GTV-MRI = the volume of the GTV-PET within x mm outside the GTV-MRI/the volume of the GTV-PET. RESULTS For GTV-MRI volumes of <or=0.5 mL, the sensitivity of tumor detection by MET-PET was 43%. For GTV-MRI volume of >0.5 mL, GTV-PET volumes were larger than GTV-MRI volumes and a significant correlation was found between these variables by linear regression. For all tumor sizes and tumor characteristics, a 2-mm margin outside the GTV-MRI significantly improved the coverage of the GTV-PET. CONCLUSIONS Although there were some limitations in our study associated with spatial resolution, blurring effect, and image registrations with PET images, MET-PET was supposed to have a potential as a promising tool for the precise delineation of target volumes in radiotherapy planning for brain metastases.

Efficacy and safety of long-term, continuous subcutaneous octreotide infusion for patients with different subtypes of KATP-channel hyperinsulinism.

To evaluate the efficacy of long‐term, continuous, subcutaneous octreotide infusion for congenital hyperinsulinism caused by mutations in the KATP‐channel genes, KCNJ11 and ABCC8.

Diagnostic accuracy of [18F]-fluoro-l-dihydroxyphenylalanine positron emission tomography scan for persistent congenital hyperinsulinism in Japan

Objective  We aimed to elucidate the accuracy and limitations of [18F]‐fluoro‐l‐dihydroxyphenylalanine ([18F]DOPA) positron emission tomography (PET) for Japanese patients with congenital hyperinsulinism. Although [18F]DOPA PET is reported to be useful for precisely localizing the focal form of congenital hyperinsulinism, previous reports are mostly from European and North American centres.

Lasting 18F-DOPA PET Uptake after Clinical Remission of the Focal Form of Congenital Hyperinsulinism

Background: Positron emission tomography (PET) using 18F-DOPA is a useful tool for detecting the focal forms of congenital hyperinsulinism. 18F-DOPA is taken up by aromatic L-amino acid decarboxylase in pancreatic β-cells. However, the role of this enzyme in insulin secretion is unknown. Subjects and Methods: A Japanese boy who presented with symptomatic hyperinsulinemic hypoglycemia at the age of 2 days and spontaneous resolution at 1 year and 10 months was subjected to mutational analysis and repeated 18F-DOPA PET scans. Results: Mutational analysis revealed a paternally inherited monoallelic mutation, c.4186G>T (p.D1396Y), in the ABCC8 gene, and an 18F-DOPA PET scan revealed focal uptake in the body of the pancreas. The patient was successfully treated with frequent feeding. A follow-up PET scan revealed virtually identical uptake to that observed previously. However, in the arterial stimulation-venous sampling procedure, no significant insulin release was observed. He was placed on a normal diet, and no hypoglycemia recurrence was observed. Conclusion: This case demonstrates two important findings. Firstly, the uptake of 18F-DOPA does not correlate with the insulin-secreting capacity of the lesion. Secondly, clinical remission could be a functional process not necessarily accompanied by the apoptotic death of abnormal β-cells.

Congenital hyperinsulinism: global and Japanese perspectives.

Over the past 20 years, there has been remarkable progress in the diagnosis and treatment of congenital hyperinsulinism (CHI). These advances have been supported by the understanding of the molecular mechanism and the development of diagnostic modalities to identify the focal form of ATP‐sensitive potassium channel CHI. Many patients with diazoxide‐unresponsive focal CHI have been cured by partial pancreatectomy without developing postsurgical diabetes mellitus. Important novel findings on the genetic basis of the other forms of CHI have also been obtained, and several novel medical treatments have been explored. However, the management of patients with CHI is still far from ideal. First, state‐of‐the‐art treatment is not widely available worldwide. Second, it appears that the management strategy needs to be adjusted according to the patients ethnic group. Third, optimal management of patients with the diazoxide‐unresponsive, diffuse form of CHI is still insufficient and requires further improvement. In this review, we describe the current landscape of this disorder, discuss the racial disparity of CHI using Japanese patients as an example, and briefly note unanswered questions and unmet needs that should be addressed in the near future.

Is “black geode” sign a characteristic MRI finding for extracranial schwannomas?

To evaluate whether the “black geode” sign is a characteristic magnetic resonance imaging (MRI) finding for extracranial schwannomas.

Intraosseous schwannoma of the ilium

We presented a 27-year-old male diagnosed with intraosseous schwannoma of the ilium. Computed tomographic images revealed a well-demarcated, lobulated, expansile, osteolytic lesion in the right supraacetabular region of the ilium. In addition, an intratumoral punctate calcification and a sclerotic rim were observed. T2-weighted magnetic resonance (MR) images demonstrated a heterogeneously hyperintense lesion with a hypointense rim. Major parts of the lesion, excluding some central areas, were enhanced on gadolinium-enhanced MR images. Pathological examination revealed an intraosseous schwannoma. Our findings indicate that intraosseous schwannoma should be considered when images demonstrate a well-demarcated, lobulated, expansile, osteolytic lesion with a sclerotic rim.