Shiro Akaki

The effect of various chemotherapeutic agents given with mild hyperthermia on different types of tumours

It has been shown that hyperthermia can enhance the cytotoxicity of some chemotherapeutics. However, the most effective agent(s) at elevated temperatures have yet to be determined. A previous study suggests that the drug of choice at elevated temperatures may be different from that at the physiological temperature, and that the alkylating agents may be most effective at elevated temperatures. To further investigate these possibilities, the effect of chemotherapeutic agents were compared. These agents were cyclophosphamide, ifosfamide, melphalan, cis-diamminedichloroplatinum (II), 5-fluorouracil, mitomycin C and bleomycin. Three tumours (mammary carcinoma, osteosarcoma and squamous cell carcinoma) were used. They were transplanted into the feet of C3H/He mice. When tumours reached 65 mm 3 , a test agent was injected intraperitoneally. Tumours were immediately heated at 41.5°C for 30 min, and the tumour growth (TG) time was studied for each tumour. Using the TG times, the TG-50 (the time required for one-half of the total number of the treated tumours to reach the volume of 800 mm 3 from 65 mm 3 ) was calculated. Subsequently, the tumour growth delay time (GDT) and the thermal enhancement ratio (TER) were obtained. The GDT was the difference between the TG-50 of treated tumours and that of non-treated control tumours. The TER was the ratio of the GDT of a group treated with an agent at 41.5°C to that of a group treated with the agent at room temperature. Results showed that the top three effective agents tested at 41.5°C were solely alkylating agents--CY, IFO and L-PAM--for each kind of tumour. A GDT of cisplatin was smaller than those of the alkylating agents. The smallest TER, 1.1, was observed for 5-fluorouracil, which was given for mammary carcinoma, and for mitomycin C, which was given for squamous cell carcinoma. It could be concluded that the alkylating agents at elevated temperatures might be the drugs of choice for many types of tumours. The possible mechanisms of thermal enhancement associated with these agents are discussed.

Preliminary retrospective investigation of FDG-PET/CT timing in follow-up of ablated lung tumor

ObjectiveThe aim of this study was to clarify the most appropriate follow-up initiation time point for positron emission tomography (PET)/computed tomography (CT) following radio frequency ablation (RFA) of lung tumors, and the cutoff values of maximum standard uptake value (SUVmax) to evaluate local tumor progression.MethodsWe enrolled 15 patients (8 men, median age 62 years) with 60 tumors, who were treated with RFA of lung tumors and underwent fluorodeoxyglucose (FDG)-PET/CT following RFA. Local tumor progression was assessed by periodic chest CT images prior to and following intravenous administration of a contrast medium. The SUVmax of three periods, namely, 0–3 months, 3–6 months, and 6–9 months after RFA, was evaluated. The appropriate time point for follow-up initiation and the cutoff value of SUVmax were determined using receiver-operating characteristic (ROC) analysis.ResultsThe median follow-up period was 357 days. Of 60 tumors, 10 showed local progression. The area under the ROC curve (Az) for the 6–9 months (P = 0.044) was the largest and almost equal to that of the 3–6 months (P = 0.024). Az for the 0–3 months was the smallest and statistically insignificant (P = 0.705). The cutoff value of 1.5 of SUVmax at 3–9 months after RFA showed 77.8% sensitivity and 85.7–90.5% specificity.ConclusionsThe appropriate follow-up initiation time point is at least 3 months following RFA. Thus, SUVmax is a useful and reliable predictive indicator.

I-123 uptake in nonfunctional struma ovarii

A case of nonfunctional struma ovarii preoperatively diagnosed by scintigraphy of the pelvis using I-123 NaI is reported. US, CT, and MRI revealed a multilobulated mass composed of cystic and solid components. CT showed cystic components with slightly high density and MRI showed various signal intensities on T1- and T2-weighted images. I-123-scintigraphy of the pelvis showed uptake in the pelvic mass. Microscopic examination revealed the histologic appearance of thyroid tissue accompanied by follicular adenoma. I-123 scintigraphy of the pelvis was useful for reaching the correct preoperative diagnosis in this patient with nonfunctional struma ovarii.

Hepatectomy simulation discrepancy between radionuclide receptor imaging and CT volumetry: influence of decreased unilateral portal venous flow.

Background: Regional dysfunction demonstrated by Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (GSA) scintigraphy due to regional decrease in the portal venous flow has previously been reported. In this study, we call attention to the significance of unilateral portal venous flow decrease for preoperative hepatectomy simulation, and evaluate the hepatectomy simulation discrepancy between Tc-99m-GSA single-photon emission computed tomography (SPECT) and CT volumetry.Methods: Twenty-four hepatectomy candidates underwent preoperative hepatectomy simulation by both Tc-99m-GSA SPECT and CT volumetry. Both anatomical and functional resection ratios were calculated by means of CT volumetry and Tc-99m-GSA SPECT, respectively. The differences and ratios between anatomical and functional resection ratios were calculated in all patients, and compared in patients with and without unilateral portal venous flow decrease.Results: Anatomical resection ratios were 28.0±11.7 (mean±standard deviation) in patients with unilateral portal venous flow decrease, and 42.1±15.7 in patients without unilateral portal venous flow decrease (p=0.0127). Functional resection ratios were 14.7±12.8 in patients with unilateral portal venous flow decrease and 40.5±14.6 in patients without (p=0.0004). The differences between anatomical and functional resection ratios were 13.0±7.9 in patients with unilateral portal venous flow decrease and 5.6±3.1 in patients without (p=0.0009). The ratios between anatomical and functional resection ratios were 0.48±0.29 in patients with unilateral portal venous flow decrease and 0.86±0.10 in patients without (p=0.0018). In 12 of the 13 patients with unilateral portal venous flow decrease, anatomical resection ratios were found to be larger than functional resection ratios, whereas this happened in only 6 of 11 patients without unilateral portal venous flow decrease (p=0.0063).Conclusion: Unilateral portal venous flow decrease is suspected to be a major factor in the discreapancy between hepatectomy simulations with radionuclide receptor imaging and CT volumetry.

Bile duct stenosis due to portal cavernomas: MR portography and MR cholangiopancreatography demonstration.

We report two cases of bile duct stenosis due to portal cavernomas. Smooth stenoses were seen arising from both walls of the common bile duct on magnetic resonance (MR) cholangiopancreatography. On contrast-enhanced MR portography, peribiliary tortuous vessels were evident, indicating portal cavernomas. MR imaging can evaluate the biliary tree and portal systems noninvasively and was useful for evaluating this condition.

Comparison of Tc-99m-GSA scintigraphy with hepatic fibrosis and regeneration in patients with hepatectomy

Objective: Liver regeneration after hepatectomy is correlated with liver fibrosis. Retrospectively, we compared three quantitative indices (HH15, LHL15 and LU15) of Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99m-GSA) liver scintigraphy with liver fibrosis; in particular, we compared the HH15 index and the rate of remnant liver regeneration.Methods: Fifty-three patients who had undergone hepatectomy were enrolled in this study. The non-neoplastic parts of their resected specimens were divided into 5 groups (F0-F4) according to the degree of liver fibrosis, as determined using the New Inuyama classification system: F0, no fibrosis (n=12); F1, portal fibrosis widening (n=12); F2, portal fibrosis widening with bridging fibrosis (n=14); F3, bridging fibrosis plus lobular distortion (n=7); F4, liver cirrhosis (n=8).Results: When the cases were divided into a no or mild fibrosis group (F0 and F1) and a moderate or severe fibrosis or cirrhosis group (F2, F3 and F4), all of the indices were significantly different between the two groups. In this analysis, the areas (Az) under the receiver operating characteristic (ROC) curves for the HH15 and LHL15 indices were very similar, while the Az for the LU15 index was smaller. An HH15 index equal to 0.52 was the most accurate, producing a 79.3% sensitivity and a 75.0% specificity rating. When 18 patients that had received a CT scan one month after hepatectomy were divided into 2 groups according to their HH15 value (group A, HH15 ≤0.52; group B, HH15>0.52), group A exhibited a better regeneration rate.Conclusion: Tc-99m-GSA scintigraphy is well correlated with liver fibrosis and may be useful for non-invasive, preoperative evaluations of liver fibrosis. The HH15 index, in particular, may be useful for predicting the rate of liver regeneration after hepatectomy.

F-18 FDG PET demonstration of a thyroid metastasis in a patient with colon cancer.

A 51-year-old man with a history of surgical removal of sigmoid colon cancer underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to search for distant metastases and/or local recurrence because the carcinoembryonic antigen level was elevated. F-18 FDG PET images showed increased focal FDG uptake in the left lobe of the thyroid. Computed tomography images showed thyroid tumor in the left lobe as well as F-18 FDG PET images. Thereafter he underwent thyroidectomy and the resected specimen was histopathlogically shown to have thyroid metastasis from colon cancer. F-18 FDG PET was useful to detect thyroid metastasis from colon cancer as well as the most frequently seen metastatic sites such as liver, lungs, and lymph nodes.

Reduced radioactivity in the periphery of the liver in a patient with idiopathic portal hypertension.

The authors report a case of idiopathic portal hypertension in which radioaccumulation in the peripheral region of the liver decreased markedly. On dynamic CT, peripheral regional enhancement of the liver was seen in the arterial phase. The region was hypointense on T1-weighted MR images and hyperintense on T2-weighted images. On portograms via the superior mesenteric artery, markedly decreased portal venous perfusion was seen in the peripheral region of the liver. Tc-99m galactosyl human serum albumin (GSA) liver scintigrams showed decreased accumulation in the peripheral region and unchanged accumulation in the central region of the liver. Tc-99m GSA liver scintigraphy clearly showed localized liver dysfunction in the peripheral region.

Assessment of mean transit time in the engrafted lung with 133Xe lung ventilation scintigraphy improves diagnosis of bronchiolitis obliterans syndrome in living-donor lobar lung transplant recipients

ObjectiveStaging of bronchiolitis obliterans syndrome (BOS) following lung transplantation is based on declines in forced expiratory volume in 1 s (FEV1). The aim of this study was to evaluate the usefulness of 133Xe ventilation scintigraphy in the early detection of BOS following living-donor lobar lung transplantation (LDLLT), to compare 133Xe washout imaging with computed tomography (CT) findings for early detection of BOS following LDLLT, and to evaluate 133Xe washout imaging by quantitative analyses.MethodsSubjects comprised 30 double-lung recipients and 1 single-lung recipient, who had undergone LDLLT at our institution and survived more than 1 year. Clinically diagnosed BOS developed in six recipients. Declines in graft function were evaluated using a combination of three methods, namely, dynamic spirometry, high-resolution CT (HRCT), and 133Xe ventilation scintigraphy. Findings for all transplanted lungs were compared between CT and 133Xe washout imaging. 133Xe washout imaging was assessed using mean transit time (MTT) of bi-and unilateral lungs. Correlations between MTT of bilateral lungs and FEV1% were evaluated. Differences in MTT between BOS and non-BOS lungs, and between non-BOS and donor lungs were also evaluated on unilateral lungs. Appropriate cut-off values of MTT of unilateral lungs were set for the diagnosis of BOS.ResultsIn all six BOS cases, prolonged-washout images of engrafted lungs revealed early-phase BOS with declines from baseline FEV1, whereas only one BOS case could be detected using early CT findings of BO (bronchodilatation, decrease in number and size of pulmonary vessels, thickening of septal lines, and volume reduction). A significant correlation was identified between MTT and FEV1% (r = −0.346, P < 0.0001). MTT of unilateral lungs was significantly longer in BOS lungs than in non-BOS lungs (P < 0.0001). The cut-off MTT of unilateral lungs for the diagnosis of BOS was set at 64.77 s.ConclusionsOur data show that 133Xe washout imaging offers excellent potential for early detection of BOS compared with early CT findings. Using 133Xe washout imaging and MTT with radioactive tracer offers a noninvasive indication of selective ventilatory function in engrafted lungs following LDLLT. MTT appears useful for identifying BOS following LDLLT and allows quantitative evaluation of graft function in unilateral lungs.

The usefulness of serum thyroglobulin levels and Tl-201 scintigraphy in differentiating between benign and malignant thyroid follicular lesions

Objective: To compare the diagnostic capabilities of various serum thyroglobulin levels (Tg) and Tl-201 scintigraphy with regard to thyroid follicular lesions.Methods: We examined 80 thyroid follicular lesions (benign: 55, malignant: 25) in patients with nodular goiter for whom a pathological diagnosis was made based on surgical findings. Tg was measured by an I-125 (radioimmunoassay) method. In Tl-201 scintigraphy, 74 MBq of Tl-201 chloride was intravenously injected and imaged after 10 minutes (early image) and after 120 minutes (delayed image), and the scintigrams were evaluated both visually and quantitatively, with special attention paid to the part of the nodule with the highest accumulation of Tl-201 chloride. The cutoff levels of Tg for categorizing the lesions as malignant were set at 40, 100, 300, 500, 1,000 and 2,500 μg/l. In Tl-201 scintigraphy, method 1 involved high uptake on both early and delayed images, method 2 involved high uptake on only the early image, and method 3 involved high uptake on only the early image or the same accumulation in comparison with the normal region on the early image, with no washout being quantitatively judged as indicative of malignancy. A summary index of overall test performance can be calculated as the area under the receiver operating characteristic (ROC) curve (Area (Az)). Likelihood ratios for several cutoff levels were also calculated.Results: In the diagnosis, Az of Tl-201 (0.95) was larger than that of Tg (0.65). The sensitivity and accuracy of Tg at each cutoff level (sensitivity: 4.0% to 76.0%, accuracy: 50.0% to 72.5%) were lower than with Tl-201 scintigraphy (methods 1–3, sensitivity: 76.0–100%, accuracy: 77.5–88.8%). The likelihood ratio for the positive results of method 1 for Tl-201 scintigraphy, were greatest in the present study (13.9), and the likelihood ratio for the negative results of method 3 for Tl-201 scintigraphy, (0) was smallest in the present study.Conclusion: Diagnosis based on Tl-201 washout patterns in which quantitative evaluation is combined with visual evaluation appears to be more useful for the differentiation of malignant thyroid follicular lesions than diagnosis by Tg.