Yoshihiro Toyama

Selective Eosinophil Adhesion to Fibroblast Via IFN-γ-Induced Galectin-9

Among galectin family members, galectin-9 was first described as a potent eosinophil chemoattractant derived from Ag-stimulated T cells. In the present study a role of galectin-9 in the interaction between eosinophils and fibroblasts was investigated using a human lung fibroblast cell line, HFL-1. RT-PCR, real-time PCR, and Western blot analyses revealed that both galectin-9 mRNA and protein in HFL-1 cells were up-regulated by IFN-γ stimulation. On the one hand, IL-4, known as a Th2 cytokine, did not affect the galectin-9 expression in HFL-1 cells. We further confirmed that IFN-γ up-regulated the expression of galectin-9 in primary human dermal fibroblasts. Flow cytometric analysis revealed that IFN-γ up-regulated surface galectin-9 expression on HFL-1 cells. Stimulation of HFL-1 cells with IFN-γ up-regulated adhesion of eosinophils, but not neutrophils, to HFL-1 cells. This adherence of eosinophils to HFL-1 cells was inhibited by both lactose and anti-galectin-9 Ab. These findings demonstrate that IFN-γ-induced galectin-9 expression in fibroblasts mediates eosinophil adhesion to the cells, suggesting a crucial role of galectin-9 in IFN-γ-stimulated fibroblasts as a physiological modulator at the inflammatory sites.

FDG PET as a procedure for detecting simultaneous tumours in head and neck cancer patients.

AimThe presence of simultaneous primary tumours in other regions affects the prognosis and management decisions of head and neck cancer patients. Therefore, early detection of these tumours is necessary. Recent improvements in positron emission tomography (PET) have made it possible to examine the patients whole body. The present study was undertaken to evaluate the clinical contribution of whole-body PET using fluorodeoxyglucose (FDG) for head and neck cancer patients. MethodsFifty-three consecutive patients with previously untreated head and neck cancer were examined. Whole-body FDG PET imaging was performed at 1 h after injection of 18F-FDG. A 3-D acquisition was undertaken and iterative reconstruction was performed. The final diagnosis of simultaneous primary tumour was established by histological findings or clinical follow-up. ResultsOf 53 patients, six (11%) had evidence of simultaneous primary tumour. In five of these six patients, simultaneous primary tumours (two gastric cancer; one colon cancer; one pancreatic cancer; one thyroid cancer) were found by FDG PET. One more patient was found to have prostate cancer on the basis of blood test but this was not detected by FDG PET. In none of the remaining 47 patients, were additional simultaneous primary tumours found by FDG PET or any of the other routine examinations or during follow-up. ConclusionsThe results of this study show a high rate of simultaneous primary tumour in patients with primary head and neck cancer. FDG PET appears to be a promising imaging modality for the detection of simultaneous tumours in head and neck cancer patients.

Usefulness of FDG-PET imaging for the radiotherapy treatment planning of pyothorax-associated lymphoma

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin’s lymphoma developing in the pleural cavity after a long-standing history of chronic pyothorax (CP). F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is a useful modality for determination of disease extent of various malignant tumors, including malignant lymphoma, but there have been no reports describing the usefulness of FDG-PET imaging in PAL. Here we report a case of PAL that relapsed after chemotherapy and was successfully treated by radiotherapy. FDG-PET imaging revealed that the tumor was localized to a soft-tissue attenuation mass behind the CP cavity in the right thorax, but did not infiltrate the CP cavity. A total dose of 40 Gy was administered to the area that included the PET-positive lesion, instead of including the entire CP cavity in the radiation field. Although computed tomography (CT) showed a residual mass, no FDG uptake was indicated by FDG-PET imaging performed just after the end of radiotherapy, and additional irradiation was not performed. No sign of relapse was found by FDG-PET imaging 3 months later. FDG-PET imaging was useful for both the planning of radiotherapy and assessing the treatment response of PAL.

Diagnostic value of TI-201 and three-phase bone scintigraphy for bone and soft-tissue tumors.

PURPOSE Although TI-201 is highly sensitive for detecting bone and soft-tissue tumors, its uptake is not specific for malignant lesions. This study assessed the differentiation of malignant and benign lesions and evaluated the sensitivity, specificity, and accuracy of TI-201 imaging and three-phase bone scans. MATERIALS AND METHODS Forty bone and soft-tissue tumors (16 malignant and 24 benign) were evaluated. TI-201 static images were acquired 10 minutes (early) and 2 hours (delayed) after injection of the radionuclide. Within 14 days, three-phase bone scintigraphy was performed using Tc-99m HMDP with the patient in the same position. The count ratio of the lesion compared with the normal contralateral or adjacent site (L:N ratio) was measured. RESULTS With TI-201 scintigraphy, mean (+/- SD) values of early and delayed L:N ratios were 3.36 +/- 1.25 and 2.88 +/- 1.20, respectively, in malignant lesions; and 1.88 +/- 1.14 and 1.48 +/- 0.76, respectively, in benign lesions. TI-201 accumulation in benign lesions was significantly less than that of malignancies on early and delayed images. However, an overlap of both ratios between malignant and benign lesions was seen. No such significance was detected on three-phase bone scintigraphy (L:N ratios of malignant and benign tumors were 2.57 +/- 1.22 and 2.24 +/- 2.11, respectively, for blood flow imaging; 2.41 +/- 0.78 and 2.26 +/- 1.54, respectively, for blood pool imaging; and 2.80 +/- 2.10 and 2.89 +/- 4.55, respectively, for bone imaging). When we assumed that the tumor was malignant when the delayed TI-201 L:N ratio exceeded the blood pool phase L:N ratio with bone scintigraphy, the sensitivity rate was 81%, specificity rate was 100%, and accuracy rate was 93%. CONCLUSIONS TI-201 imaging for bone and soft-tissue tumors was better than three-phase bone scintigraphy alone but was not good enough to clearly differentiate malignant lesions from benign ones. TI-201 scintigraphy, performed in combination with three-phase bone scintigraphy, may be superior to either one of the two imaging procedures alone for bone and soft-tissue tumor diagnosis.

A case of non-Hodgkin’s lymphoma of the ovary: Usefulness of18F-FDG PET for staging and assessment of the therapeutic response

Primary ovarian lymphoma as the initial manifestation is rare. A 27-year-old woman presented to our hospital with the symptoms of lower abdominal fullness and pollakisuria. CT scan and MRI revealed bilateral ovarian tumors, which showed heterogeneous masses.18F-FDG PET revealed strong uptake by the abdominal masses, and the maximum standardized uptake value (SUVmax) was 12.5. Abnormal uptake was not shown by other regions. An exploratory laparotomy was performed. Histological findings revealed diffuse large B-cell lymphoma. The clinical stage was IV according to the Ann Arbor system. International prognostic index (IPI) was 3 (high-intermediate risk). Chemotherapy was administered consisting of three courses of an R-CHOP regimen, and18F-FDG PET and CT scan revealed no signs of involvement 3 months after initiation of the chemotherapy.18F-FDG PET was a useful method for staging and assessment of the therapeutic response in primary ovarian lymphoma.

Usefulness of67Ga scintigraphy in extranodal malignant lymphoma patients

Objective:67Ga scintigraphy has a well-documented role in nodal lymphoma for both disease staging and assessment of treatment response. The objective of the present study was to examine the role of67Ga scintigraphy in diagnosis and assessment of treatment response, in patients with extranodal malignant lymphoma.Methods: Seventy-one patients with extranodal malignant lymphoma were studied. Whole body scans in all and SPECT scans in some selected patients were performed 72 hours after injection of67Ga-citrate. The influence of tumor site, histological classification and tumor size on67Ga scintigraphy sensitivity was analyzed. Twenty-one of the seventy-one patients also had a second67Ga scintigraphy to assess response to treatment.Results: The overall67Ga scintigraphy sensitivity was 83.1% (59/71). The sensitivity was low in patients whose extranodal lymphoma occurred in skin (0/3) and urinary bladder (0/1), as compared to other tumor sites. According to the histological classification of the lesion, the sensitivity was lower in low-grade than in intermediate and high-grade lymphoma. According to the tumor size, the sensitivity was low in lesions less than 2 cm in diameter than those more than 2 cm in diameter. The results changed from positive to negative accumulation in 20 (95.2%) of the 21 patients who had67Ga scintigraphy to assess the response to treatment. These 20 patients showed a good clinical course.Conclusions: Although67Ga scintigraphy did not show positive accumulation in patients with skin and urinary bladder lymphoma, it was helpful to confirm the diagnosis and to evaluate the therapeutic effect in most patients with extranodal malignant lymphoma.

Unknown primary carcinoma, diagnosed as inflammatory breast cancer,and successfully treated with trastuzumab and vinorelbine.

Occult breast cancer presenting with axillary lymph node metastases is uncommon, and inflammatory breast cancer (IBC), as a subtype, is quite rare. Here we describe a case of IBC, which arose as an unknown primary carcinoma; the patient presented with axillary lymph node metastasis, and was successfully treated with trastuzumab and vinorelbine. Specifically, a 55-year-old woman presented with right axillary lymphadenopathy. Although she underwent various examinations, the primary site of the disease was not revealed. Axillary lymph node dissection was performed, and the lesion was diagnosed as a poorly differentiated adenocarcinoma. The patient chose to be treated by alternative medicine. About 6 months later, she was referred to our hospital, due to marked bilateral neck and axillary lymph node swelling. She presented withdiffuse right breast enlargement, redness, and peau d’orange. Computed tomography (CT) of the breast showed skin thickening and swelling of the right breast.F-18 Fluorodeoxyglucose positron emission tomography (FDG-PET) showed FDG uptake in the right breast. The patient was clinically diagnosed with IBC. Because overexpression of the human epidermal growth factor receptor 2 (HER2) was found in the specimen from her right axillary lymph node, she was treated with trastuzumab and vinorelbine. Two months after the start of chemotherapy, CT revealed a complete response in the lymph nodes, and the skin thickening and parenchymal edema of the right breast had improved. FDG-PET was also performed at this time, and revealed no FDG uptake in either the right breast or the lymph nodes.

Superimposed dual-isotope SPECT using99mTc-hydroxymethylene diphosphonate and201Tl-chloride to assess cartilage invasion in laryngohypopharyngeal cancer

ObjectiveCartilage invasion in laryngohypopharyngeal cancer has a significant impact on the choice of treatment modality and outcome of the disease. We examined invasion of cartilage in laryngohypopharyngeal cancer by simultaneous bone and tumor dual-isotope SPECT using99mTc-hydroxymethylene diphosphonate and20lTl-chloride.MethodsEarly and delayed simultaneous bone and tumor dual-isotope SPECT were performed on 19 patients with laryngohypopharyngeal cancer. Dual-isotope SPECT images were superimposed to project tumor location from tumor SPECT onto the osseous structures shown by bone SPECT. The presence or absence of cartilage invasion was evaluated histopathologically or by radiological studies such as CT and/or MRI.ResultsHistopathological or radiological examination of the cartilage revealed invasion in 5 patients and no invasion in 14 patients. The results of both early and delayed dual-isotope SPECT were exactly the same. Using dual-isotope SPECT, the sensitivity, specificity, and accuracy in detecting cartilage invasion by laryngohypopharyngeal cancer were: 80% (4/5), 92.9% (13/14), and 89.5% (17/19), respectively.ConclusionsResults of the present study suggest that superimposed early bone and tumor dual-isotope SPECT images may be sufficient for the diagnostic evaluation of cartilage invasion by laryngohypopharyngeal cancer. Superimposed dual-isotope SPECT imaging is a useful technique in the evaluation of cartilage invasion in laryngohypopharyngeal cancer.

Detection of small fenestral otosclerotic lesions by high-resolution computed tomography using multiplanar reconstruction

OBJECTIVE The aim of this study was to assess the value of multislice computed tomography (MSCT) using multiplanar reconstruction (MPR) to detect the small fenestral lesions in patients with otosclerosis. METHODS MSCT with MPR imaging was used to evaluate 27 ears of 17 patients with otosclerosis (3 male and 14 females) ranging in age from 33 to 69 years with a mean of 49.8 year. MSCT imaging was performed using Aquilion®. Axial spiral scans with a 0.5-mm slice thickness were obtained. The acquired high-resolution data were transferred to a workstation (ALATO VIEW). MPR images were created in the planes parallel to the stapedial crus and then analyzed on the monitor screen by two radiologists (Y.T. and N.K.). RESULTS MPR images showed abnormal findings in 26 of 27 ears with otosclerosis (96%), whereas axial images showed abnormal findings in only 15 of 27 ears (56%). The similar classification between both images was shown only in 9 of 27 ears (33%). In 16 ears (67%) axial images under-evaluated the lesions compared with MPR images. MPR images detected smaller foci than axial images. Air-bone gap at 0.5-4kHz tended to increase dependently on the extension of fenestral lesions evaluated by MPR images. CONCLUSION MPR images detected fenestral lesions in otosclerosis more frequently and more precisely than axial images. The extent of fenestral lesions observed on MPR images tends to be related to the degree of conductive hearing loss.

A comparative study of2O1T1 scintigraphy and three-phase bone scintigraphy following therapy in patients with bone and soft-tissue tumors

Objective: The purpose of this study was to evaluate the usefulness of201T1 scintigraphy in comparison with three-phase bone scintigraphy in the differentiation of residual/recurrent tumors from post-therapeutic changes, in patients previously treated for bone and soft-tissue tumors.Methods: Thirty-five201T1 and three-phase bone scintigraphy scans were obtained for 30 patients with a history of bone or soft-tissue tumor who had undergone chemotherapy, radiation therapy, tumor resection, or a combination of these treatments. The planar201Tl images were acquired 10 mins (early) and 2 hrs (delayed) after the intravenous injection of 111 MBq201Tl-chloride. Three-phase bone scintigraphy was performed using 740 MBq99mTc-HMDP at the same lesion site as for201T1 imaging. The blood flow images were obtained every 10 sec for 2 mins and were immediately followed by the blood pool image after 5 mins. Three to 4 hrs later, bone images were obtained.201Tl and three-phase bone scintigraphies were correlated with the histopathologic findings and/or clinical follow-up of more than 3 months.Results: Of the 35 cases, 15 were free of disease and 20 had residual or recurrent tumors. Of the 20 residual or recurrent cases, all had true-positive201T1 early and delayed scans, while bone scintigraphy was true-positive on the blood flow, blood pool and bone images in 16, 18 and 12 cases, respectively.201T1 early and delayed images and99mTc-HMDP blood flow and blood pool images were false-positive in one patient. The histology of this false-positive case showed the presence of lymph proliferative tissue.Conclusions: Although201Tl uptake after treatment does not always indicate recurrence,201T1 scintigraphy may still be more useful than three-phase bone scintigraphy in the follow-up of patients with bone and soft-tissue tumors following therapy.