Assessment of regional lung functional impairment with co-registered respiratory-gated ventilation/perfusion SPET-CT images: initial experiences

In this study, respiratory-gated ventilation and perfusion single-photon emission tomography (SPET) were used to define regional functional impairment and to obtain reliable co-registration with computed tomography (CT) images in various lung diseases. Using a triple-headed SPET unit and a physiological synchroniser, gated perfusion SPET was performed in a total of 78 patients with different pulmonary diseases, including metastatic nodules (n=15); in 34 of these patients, it was performed in combination with gated technetium-99m Technegas SPET. Projection data were acquired using 60 stops over 120° for each detector. Gated end-inspiration and ungated images were reconstructed from 1/8 data centered at peak inspiration for each regular respiratory cycle and full respiratory cycle data, respectively. Gated images were registered with tidal inspiration CT images using automated three-dimensional (3D) registration software. Registration mismatch was assessed by measuring 3D distance of the centroid of the nine selected round perfusion-defective nodules. Gated SPET images were completed within 29 min, and increased the number of visible ventilation and perfusion defects by 9.7% and 17.2%, respectively, as compared with ungated images; furthermore, lesion-to-normal lung contrast was significantly higher on gated SPET images. In the nine round perfusion-defective nodules, gated images yielded a significantly better SPET-CT match compared with ungated images (4.9±3.1 mm vs 19.0±9.1 mm, P<0.001). The co-registered SPET-CT images allowed accurate perception of the location and extent of each ventilation/perfusion defect on the underlying CT anatomy, and characterised the pathophysiology of the various diseases. By reducing respiratory motion effects and enhancing perfusion/ventilation defect clarity, gated SPET can provide reliable co-registered images with CT images to accurately characterise regional functional impairment in various lung diseases.     

Pleomorphic carcinoma of the lung rapidly developed multiple metastases after surgery

Pleomorphic carcinoma of the lung is a type of carcinoma with spindle and/or giant cells with a poor diagnosis. A 73-year-old male was referred to our hospital because of the pulmonary tumor. Lung biopsy revealed that the tumor was poorly differentiated adenocarcinoma. No distant metastasis were observed by systemic examination. A right middle lobectomy with partial resection of the right upper lobe and lymph node dissection were performed, because the tumor (5.3 x 4.0 x 4.0 cm) was located in peripheral S' and invaded S3 via the interlobular space. Histological findings showed adenocarcinoma comprised of spindle cell components that reacted positively to epithelial membrane antigen (EMA) and no lymph node metastasis. Therefore, he was diagnosed with pleomorphic carcinoma of the lung, pT2N0M0, stage IB. But metastatic lesions newly appeared in the thoracic skin, the liver, the diaphragm, the bilateral adrenal glands, and the retroperitoneal space on the 30th postoperative day. He died of peritonitis and pleuritis on only 60 days after the operation.     

Intraoperative lavage cytologic analysis of surgical margins in patients undergoing limited surgery for lung cancer

BACKGROUND: One of the unfavorable recurrent patterns after limited surgery for lung cancer is local failure, especially at the surgical margin in the pulmonary parenchyma. To prevent this failure, we preliminarily introduced a novel intraoperative lavage cytologic technique to check surgical margin status for limited surgery. In this study we analyzed the clinical utility of this technique with a larger number of patients under long-term follow-up. METHODS: A total 112 consecutive lung cancer lesions prospectively treated by limited surgery with the intraoperative lavage cytologic technique between October 1997 and August 2000 were reviewed through a median follow-up period of 27 months. RESULTS: Eleven lesions (10%) showed cytologically positive results in the attempted surgery on the surgical margin. The positive result rate was significantly higher for lesions with more advanced stage, compromised indication, incurability, and larger size. Surgical modes were converted intraoperatively for 4 lesions; in the other 7 lesions no conversion was performed because of certain disadvantages. Local recurrence in the surgical margin occurred in a total of 4 lesions, including 3 for which the operative mode was unconverted and 1 lesion with cytologically unknown status of the surgical margin that had the mode converted, whereas there were no local recurrences in the surgical margins among the lesions with final cytologically negative results. CONCLUSION: Cytologically negative results of examination of the surgical margin by the technique of intraoperative lavage cytologic in limited surgery for lung cancer may be predict lack of local recurrence in the surgical margin. This intraoperative cytologic technique is clinically useful in checking for complete resection of this primary disease.     

Characterization of the chimeric SV40 large T antigen which has a membrane attachment sequence of polyoma virus middle T antigen

A chimeric SV40 mutant, pMTPY, was constructed which codes for a large T antigen having the putative membrane attachment sites of polyoma virus middle T antigen at the carboxy-terminal portion. The mutant T antigen was detected exclusively in the cytoplasm of CV-1 cells transfected with pMTPY by a fluorescent antibody test. This mutant could not support viral DNA replication, but could immortalize secondary cultured rat brain (RB) cells. Immortalized RB cells produced nonkaryophilic large T antigen and also small T antigen. The amount of p53 expressed in those cells was larger than that in control RB cells. In addition, this mutant had the ability to transform NIH3T3 cells. The mutant nonkaryophilic large T antigen in NIH3T3 transformant was localized in cytoplasmic membrane fractions.     

Toll‐like receptor 2‐mediated modulation of growth and functions of regulatory T cells by oral streptococci

This study was designed to determine whether oral streptococci modulate the growth and functions of regulatory T cells. Heat‐killed cells of wild‐type strains of Streptococcus gordonii and Streptococcus mutans induced the Toll‐like receptor 2 (TLR2) ‐mediated nuclear factor‐κB (NF‐κB) activation, but their lipoprotein‐deficient strains did not. Stimulation with these streptococci resulted in a significant increase in the frequency of CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells in splenocytes derived from both TLR2^+/+ and TLR2^?/? mice, but the level of increase in TLR2^+/+ splenocytes was stronger than that in TLR2^?/? splenocytes. Both strains of S. gordonii enhanced the proliferation of CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells isolated from TLR2^+/+ mice at the same level as those from TLR2^?/? mice in an interleukin‐2‐independent manner. However, wild‐type and lipoprotein‐deficient strains of both streptococci did not enhance the suppressive activity of the isolated regulatory T cells in vitro, but rather inhibited it. TLR ligands also inhibited the suppressive activity of the regulatory T cells. Inhibition of the suppressive activity was recovered by the addition of anti‐IL‐6 antibody. Pretreatment of antigen‐presenting cells with the NF‐κB inhibitor BAY11‐7082 enhanced the suppressive activity of the regulatory T cells. These results suggested that interleukin‐6 produced by antigen‐presenting cells inhibits the suppressive activity of the regulatory T cells. Wild‐type strain, but not lipoprotein‐deficient strain, of S. gordonii reduced the frequency of CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells in the acute infection model, whereas both strains of S. gordonii increased it in the chronic infection model mice. Hence, this study suggests that oral streptococci are capable of modulating the growth and functions of regulatory T cells in vitro and in vivo.     

Radiation therapy for pelvic lymph node metastasis from uterine cervical cancer

Objectives

This study aimed to evaluate the efficacy of radiation therapy for pelvic lymph node metastasis from uterine cervical cancer and identify an optimal radiation regimen.

Methods

A total of 111 metastatic pelvic lymph nodes, ranging from 11 to 56 mm (median, 25 mm) on CT/MRI, in 62 patients with uterine cervical cancer were treated initially with curative radiation therapy, with 46 patients receiving concurrent chemotherapy. Total radiation doses ranged from 45 to 61.2 Gy (median, 50.4 Gy) in 1.8–2 Gy (median, 1.8 Gy) fractions.

Results

At a median follow-up of 33 months, 46 of the 62 patients survived. Only 2 irradiated lymph nodes, 24 and 28 mm in diameter, in 1 patient progressed after irradiation alone with 50.4 Gy in 1.8 Gy fractions. All 33 metastatic lymph nodes ≥ 30 mm in diameter were controlled by irradiation at a median dose of 55.8 Gy. The 3-year lymph node-progression free rates were 98.2% in all 62 patients and 98.0% in all 111 metastatic lymph nodes. Except for transient hematologic reactions, 2 patients developed grade ≥ 3 therapy-related toxicities, 1 with an ulcer and the other with perforation of the sigmoid colon. In addition, 2 patients experienced ileus after irradiation.

Conclusions

Radiation therapy effectively controlled pelvic lymph node metastases in patients with uterine cervical cancer, with most nodes < 24 mm in diameter controlled by total doses of 50.4 Gy in 1.8 Gy fractions and larger nodes controlled by 55.8 Gy, particularly with concurrent chemotherapy. Higher doses to metastatic lymph nodes may increase intestinal toxicities.     

<Superscript>18</Superscript>F-fluoride uptake in bone metastasis: morphologic and metabolic analysis on integrated PET/CT

Objective  

The aim of our study was to evaluate detectability of bone metastatic lesions and evaluate the correlation between ¹⁸F-fluoride uptake patterns on positron emission tomography (PET) and morphologic changes on CT using integrated PET/CT.     

Bone tunnel enlargement after anterior cruciate ligament reconstruction using hamstring tendons

We retrospectively reviewed 87 anterior cruciate ligament reconstructions using autogenous hamstring tendons with the Endobutton technique to investigate the relationship between bone tunnel enlargement and clinical outcome and to identify factors that contribute to the enlargement. The clinical outcome was evaluated using the Lysholm score and KT-1000 arthrometer. The location of the femoral tunnel with respect to Blumensaat's line, the tibial tunnel with respect to the tibial plateau, and the angle between the femoral tunnel and Blumensaat's line (femoral tunnel angle) were measured. Bone tunnel enlargement was observed in 32 patients (37%). Enlargement occurred in 22 of the femoral tunnels and 26 of the tibial tunnels. Enlargement of both tunnels occurred in 16 knees. There was no statistical difference in Lysholm scores or KT-1000 arthrometer measurements between the enlarged group and the unenlarged group. The femoral tunnel was placed more anteriorly in the enlarged femoral tunnel group than in the unenlarged femoral tunnel group. The tibial tunnel was placed more anteriorly in the enlarged tibial tunnel group than in the unenlarged tibial tunnel group. The femoral tunnel angle was significantly smaller in the enlarged femoral tunnel group than in the femoral unenlarged group. Gender, patient age, intraoperative isometricity, and graft size were not significant factors. Bone tunnel enlargement was not correlated with the clinical outcome measures. We conclude that the main factor associated with tunnel enlargement are the locations and angles of the tunnels. The windshield-wiper motion of the graft may be enhanced by changing tension in the graft due to tunnel malposition. An acute femoral tunnel angle may increase the mechanical stress on the anterior margin of the femoral tunnel.     

Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging

The purpose of this study was to assess the clinical potential of methyl-¹¹C-choline (¹¹C-choline) in the diagnosis of brain tumours. To this end, the results of ¹¹C-choline positron emission tomography (PET) in 22 patients suspected of having brain tumours were compared with the findings of contrast-enhanced magnetic resonance (MR) imaging and fluorine-18 fluorodeoxyglucose PET. A histopathological diagnosis was made for each patient during open surgery. The standardised uptake values of brain tumours and the tumour-to-white matter count (T/W) ratios were determined. The degree of ¹¹C-choline accumulation noted in PET images was compared with the gadolinium-enhanced areas of MR images. The mean T/W ratio of ¹¹C-choline in high-grade gliomas was found to be higher than that in low-grade gliomas. This difference was statistically significant (mean-SD: 8.7Lj.2, n=9 versus 1.5ǂ.7, n=5, P<0.03) when data pertaining to the prominent uptake of ¹¹C-choline in a patient with a pilocytic astrocytoma were excluded. ¹¹C-choline PET failed to detect non-neoplastic lesions in two patients. Areas of ¹¹C-choline accumulation in PET scans were larger than areas enhanced on MR images in five cases involving high-grade gliomas. ¹¹C-choline PET differentiated between low-grade gliomas and high-grade gliomas, but did not differentiate between low-grade gliomas and non-neoplastic lesions. The combination of ¹¹C-choline PET and MR imaging may provide investigators with an accurate means by which to identify high-grade gliomas.