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 degrees 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 degrees 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 degrees 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.

Sclerosing stromal tumor of the ovary: US, MR, and dynamic MR findings.

The US, MR, and dynamic MR findings in four patients with sclerosing stromal tumor of the ovary are reported. US showed a tumor with multilocular cystic components and irregularly thickened septa and tumor walls or a solid tumor including several small cystic components. On T2-weighted MR images, signal intensities of the cystic components were high and those of the solid components were inhomogeneous, ranging from intermediate-high to high. Dynamic MRI demonstrated marked early enhancement of the solid components.

Negative MRI findings with invasive cervical biopsy may indicate stage IA cervical carcinoma.

OBJECTIVE: We attempted to prospectively determine the role of magnetic resonance imaging (MRI) in very early cervical cancer. STUDY DESIGN: T2-weighted and T1-dynamic enhanced images from patients with invasive or noninvasive lesions of the cervix were reviewed by two radiologists who had no clinical information on these patients. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. RESULTS: Seventy-nine cases were entered into the study and 75 were evaluable. Accuracy of T2 MR images for invasive and noninvasive disease by Radiologist 1 and Radiologist 2 was 0.8533 and 0.7733, respectively. Accuracy was greater (0.9867 and 0.9467, respectively) for the detection of noninvasive plus microinvasive lesions 5 mm. Dynamic technique provided only limited additional value in the detection of microinvasive cervical carcinoma. CONCLUSION: Simple T2 MRI is useful in differentiating noninvasive or microinvasive cervical lesions from invasive cervical carcinoma of the cervix >5 mm.

Role of magnetic resonance imaging (MRI) in early cervical cancer.

The aim of this study was to prospectively determine if invasive carcinoma of the cervix can be ruled out by negative magnetic resonance image (MRI) findings. Eligible patients were those who were scheduled to undergo either hysterectomy or conization because of invasive or non-invasive lesions of the cervix. T2-weighted and T1-dynamic enhancement images were reviewed by two radiologists who had no information on these patients except for the preoperative diagnosis. Clinical information regarding location of the disease was not given. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist who was not provided with MRI information. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. Seventy cases were entered and 66 were evaluable. Sensitivities of T2 and dynamic MRI for invasive and non-invasive disease by radiologist 1 were 0.8824 and 0.8235, respectively, and those by radiologist 2 were 0.6296 and 0.7647, respectively. Specificities were 0.8776 and 0.8571, respectively, for radiologist 1 and 0.8974 and 0.8367, respectively, for radiologist 2. When sensitivities and specificities were calculated for prediction of non-invasive plus microinvasive lesions < or = 5 mm vs. invasive lesions > 5 mm, specificities of T2 and dynamic MRI became 1.0000 for both radiologists. Negative findings on T2 and/or dynamic MRI indicated non-invasive or early invasive cervical diseases < or = 5 mm. The dynamic technique provided only limited additional value in the detection of early invasive cervical carcinoma.

Assessment of secondary necrosis of Jurkat cells using a new microscopic system and double staining method with annexin V and propidium iodide.

Using a new system developed by us for acquiring microscopic images automatically, we compared the morphological changes that apoptotic cells undergo with changes in the staining pattern of annexin V-enhanced green fluorescent protein (AV-EGFP) and propidium iodide (PI) in individual cells. Jurkat cells were treated with 5 mM CaCl2 alone, anti-Fas antibody and heating at 42 degrees C for 30 min or 46 degrees C for 60 min, and then were incubated in medium with 5 mM CaCl2. Time-lapse DNA fragmentation analysis and morphological observation revealed that the anti-Fas antibody and heating at 42 degrees C for 30 min induced typical apoptosis in the cells, and heating at 46 degrees C for 60 min induced typical necrosis. Time-lapse observation of individual cells stained with AV-EGFP and PI confirmed that apoptotic cells were stained at first with AV-EGFP alone, and thereafter also with PI when the cellular membrane ruptured and the cell underwent secondary necrosis. Most of the cells which underwent necrosis were stained simultaneously with AV-EGFP and PI. There was a significant time interval between the staining of individual cells with AV-EGFP, indicating apoptosis, and staining of these cells with PI, which indicated the occurrence of secondary necrosis. These results suggest that time-lapse examinations are necessary to distinguish apoptosis, secondary necrosis and necrosis in cells from one another. This study presents direct evidence that apoptotic cells undergo secondary necrosis, which could be recognized with PI.

Endometrial carcinoma: efficacy of thin-section oblique axial MR images for evaluating cervical invasion.

BACKGROUND: To investigate the efficacy of thin-section oblique axial magnetic resonance (MR) images in evaluating cervical invasion by endometrial carcinoma. METHODS: Sixty-seven patients with endometrial carcinoma were evaluated with pathologic correlation. We compared the accuracy in the assessment of cervical invasion by endometrial carcinoma between parasagittal MR images and thin-section oblique axial MR images by using T2-weighted and contrast-enhanced T1-weighted pulse sequences. RESULTS: Cervical invasion by endometrial carcinoma was confirmed by pathologic examination. Cervical invasion was seen in 16 patients. The accuracy rates of parasagittal T2-weighted images, thin-section oblique axial T2-weighted images, parasagittal contrast-enhanced T1-weighted images, and thin-section oblique axial contrast-enhanced T1-weighted images were 74.7%, 89.5%, 82.0%, and 95.5%, respectively. Statistically significant differences were seen between parasagittal T2-weighted images and thin-section oblique axial T2-weighted images (p = 0.002) and between parasagittal contrast-enhanced T1-weighted images and thin-section oblique axial contrast-enhanced T1-weighted images (p = 0.003). CONCLUSION: Thin-section oblique axial MR images are considered to be useful for the assessment of cervical invasion by endometrial carcinoma.

Cervical carcinoma: efficacy of thin-section oblique axial T2-weighted images for evaluating parametrial invasion.

BACKGROUND: To investigate the efficacy of thin-section oblique axial T2-weighted images in the assessment of parametrial invasion by cervical carcinoma. METHODS: One hundred parametria of 50 patients with cervical carcinoma were evaluated with pathologic correlation. We compared the sensitivity, specificity, and diagnostic accuracy in the assessment of parametrial invasion by cervical carcinoma between axial T2-weighted images and thin-section oblique axial T2-weighted images. RESULTS: Thin-section oblique axial T2-weighted images provided accurate cross sections of the cervix with excellent detail and detected parametrial invasion more accurately than did axial T2-weighted images showing cross sections of the trunk. Although the sensitivity, specificity, and accuracy for parametrial invasion were 46.4%, 91.7%, and 79.0%, respectively, on axial T2-weighted images, the corresponding values were 67.9%, 97. 2%, and 89.0%, respectively, on thin-section oblique axial T2-weighted images. There were statistically significant differences in the sensitivity (p = 0.014), specificity (p = 0.046), and accuracy (p = 0.002) in detecting parametrial invasion between these two types of images. CONCLUSIONS: Thin-section oblique axial T2-weighted images are useful for the assessment of parametrial invasion by cervical carcinoma.

Endometrial carcinoma: multisection dynamic MR imaging using a three-dimensional FLASH technique during breath holding.

PURPOSE: Our aim was to investigate the usefulness of multisection dynamic MR imaging using a 3D FLASH technique during breath holding in assessing myometrial invasion by endometrial carcinoma. MATERIALS AND METHODS: Twenty-eight endometrial carcinomas were evaluated with pathologic correlation. Dynamic MR imaging was performed using the 3D FLASH technique during breath holding. We compared accuracy in the assessment of myometrial invasion by endometrial carcinoma between T2-weighted images, contrast-enhanced T1-weighted images, and dynamic MR images. RESULTS: The accuracy rates in estimating myometrial invasion with T2-weighted images, contrast-enhanced T1-weighted images, and dynamic MR images were 64.3%, 67.8%, and 85.7%, respectively. Statistically significant differences were seen between dynamic MR images and both T2-weighted images and contrast-enhanced T1-weighted images. CONCLUSION: Multisection dynamic MR imaging using the 3D FLASH technique during breath holding is useful for the evaluation of myometrial invasion by endometrial carcinoma with polypoid growth or an unclear junctional zone on T2-weighted images.

Cepharanthin enhances thermosensitivity without a resultant reduction in the thermotolerance of a murine mammary carcinoma.

Cepharanthin (Ce) is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. The results of our previous in vitro study indicated that Ce reduces thermotolerance by enhancing thermosensitivity. In the present study, we investigated the in vitro and in vivo effects of Ce on thermosensitivity and thermotolerance using a murine mammary carcinoma, MCa, and C3H/HeN mice. Ce enhanced the thermosensitivity of MCa cells for heating at 44 degrees C not only in vitro but also in vivo. The in vivo enhancement ratio +/- SD of Ce at 100 mg/kg for heating at 44 degrees C was 1.3+/-0.3. The fractionated heat treatments at 44 degrees C for 30 and 60 min with an interval time of 0-6 days resulted in the development of remarkable thermotolerance and the expression of heat shock protein 70 in MCa tumors after the first heating. Ce at 100 mg/kg given immediately after the first heating increased the expression of heat shock protein 70 in MCa tumors, and did not reduce the development of thermotolerance. Ce given immediately before the first or second heating also did not inhibit the thermotolerance. The results of this study suggest that Ce enhances the thermosensitivity of MCa tumors as a thermosensitizer, but that this mild thermosensitizing property of Ce might be insufficient to conquer the remarkable thermotolerance in MCa tumors that develops after the first heating.

The results of radiotherapy for T1 glottic cancers; influence of radiation beam energy.

We analyzed the influence of various parameters on the results of radiotherapy for T1 glottic cancer by assessing the outcomes of 60 patients with this cancer who received definitive radiotherapy between 1985 and 1994. Seven patients were treated with a cobalt-60 unit, and the other 53 with a linear accelerator (26 patients at 3-MV, 10 at 6-MV, and 17 at 10-MV). Of the 17 patients treated at 10-MV, 4 also received part of their treatment with a cobalt-60 unit. The total radiation dose ranged from 56 Gy to 70 Gy (mean, 61 Gy). The total radiation dose of 51 patients (85%) was 60 Gy. The factors found to influence local control were the strength of the radiation beam energy and whether or not there was gross tumor invasion of the anterior commissure. The local control rate was 71% in the patients treated with a 10-MV linear accelerator, 56% in those treated with a 6-MV linear accelerator and, 97% in those treated with a cobalt-60 unit or a 3-MV linear accelerator (P = 0.0173). The local control rate was 43% in the patients with gross anterior commissure invasion and 88% in those without (P = 0.0075). We conclude that low energy photon beams are more suitable for the treatment of early glottic cancers, especially if the lesion grossly invades the anterior commissure.

Comparison of differential diagnostic capabilities of 201Tl scintigraphy and fine-needle aspiration of thyroid nodules.

UNLABELLED: We assessed the ability of 201TI planar scintigraphy and fine-needle aspiration (FNA) biopsy to differentiate malignant from benign lesions by comparing the findings of these techniques with those of surgical histopathology for 107 patients with 109 thyroid nodules. METHODS: 201TI (74 MBq) was injected intravenously, and an early image and a delayed image were acquired after 10 and 120 min, respectively, for 10 min each. For 201TI planar scintigraphy, accumulation of the tracer in the nodules was visually scored and the nodules were grouped. Group A showed high activity in both early and delayed images. Group B revealed high activity in only the early image. Group C showed activity in the early image equal to that in normal tissues. Quantitative calculation of the washout rate was less than 0 in group CI and 0 or higher in group CII. Group D revealed low activity in the early image and variable activity in the delayed image. Three differential diagnosis methods were used for 201TI planar scintigraphy: method 1, in which only group A was considered malignant; method 2, in which both group A and group B were considered malignant; and method 3, in which groups A, B and CI were considered malignant. FNA results were assessed and classified by experienced pathologists. Two differential diagnosis methods were used for FNA: method a, in which malignancy was assigned to class IV (probably malignant or higher), and method b, in which malignancy was assigned to class III (possibly malignant or higher). RESULTS: Concerning 201TI methods 1, 2 and 3, sensitivity was 74.0%, 84.0% and 92.0%, respectively; specificity was 83.1%, 64.4% and 54.2%, respectively; and accuracy was 78.9%, 73.4% and 71.6%, respectively. For FNA, method a and method b had a sensitivity of 36.0% and 50.0%, respectively, and a specificity of 96.6% and 84.7%, respectively. The accuracy of both methods was 68.8%. For follicular lesions, sensitivity ranged from 80.0% to 90.0% for 201TI scintigraphy and from 10.0% to 30.0% for FNA. CONCLUSION: 201TI planar scintigraphy was found to be easier to use and more accurate than FNA in the differentiation of diagnosis of benign and malignant thyroid nodules based on visual scoring combined with quantitative evaluation.

MR appearance of endometrial carcinoma and mucinous cystadenoma in a postmenopausal patient treated with tamoxifen for breast cancer.

We present a case of endometrial carcinoma accompanied with mucinous cystadenoma in a 70-year-old postmenopausal woman treated with tamoxifen for breast cancer demonstrated by MR imaging. Tamoxifen therapy (20 mg/day) had been carried out for more than 11 years since the surgical procedure for the primary tumor. MR images showed a markedly enlarged uterus containing endometrial carcinoma, cystic atrophy of the endometrium, and a right adnexal mass with multicystic components of various signal intensities.

Technetium-99m-DTPA-galactosyl human serum albumin liver scintigraphy evaluation of regional CT/MRI attenuation/signal intensity differences.

UNLABELLED: Regional attenuation/signal intensity differences seen on CT/magnetic resonance imaging can be a clue in detecting regional hepatic blood flow abnormality. Sometimes, however, they can be misinterpreted as a hepatic neoplasm or, in the case of a true neoplasm, they can lead to an overestimation of its size because these regions often have similar attenuation or signal intensity to hepatic neoplasms. We evaluated 99mTc-diethylenetriaminepentaacetic acid-galactosyl human serum albumin (99mTc-DTPA-GSA) liver scintigrams in patients manifesting regional attenuation/signal intensity differences to further analyze the findings. METHODS: Technetium-99m-DTPA-GSA scintigrams of 23 patients with regional attenuation/signal intensity differences in the liver at dynamic contrast-enhanced CT/magnetic resonance imaging were evaluated. The causes of the differences were arterioportal (AP) shunts in seven patients, decreases in the portal venous flow in seven patients, occlusion of right hepatic vein in one patient, confluent hepatic fibrosis in one patient and unknown in seven patients. The accumulation of 99mTc-DTPA-GSA was compared with each known cause of attenuation/signal intensity difference. Count ratios of the regions to normal hepatic parenchyma also were calculated in all cases. RESULTS: In AP shunts, none of seven patients showed any decreased accumulation in the region. Accumulation of 99mTc-DTPA-GSA decreased in six of seven patients who had decreases in portal venous flow; this incidence was significantly higher than that in patients who had AP shunts (p < 0.005). In cases of unknown cause, two of seven patients showed a decrease in accumulation, but the other five showed no such decrease. The one patient with occlusion of the right hepatic vein showed no decrease, but the confluent hepatic fibrosis showed a significant decrease. The count ratio in AP shunts was significantly larger than that of the decrease in the portal venous flow (p < 0.005). CONCLUSION: Technetium-99m-DTPA-GSA accumulation in AP shunts has a different pattern from that found in patients with a decrease in portal venous flow. Therefore, differentiation between AP shunts, which showed no decrease in 99mTc-DTPA-GSA accumulation, and hepatic neoplasms can be made more easily.

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.

Struma ovarii: appearance on MR images.

BACKGROUND: The purpose of this multi-institutional study was to examine the appearance of struma ovarii on magnetic resonance (MR) images. METHODS: MR images of 12 patients with histologically proven struma ovarii were retrospectively reviewed. All patients underwent T1-weighted and T2-weighted imaging. Contrast-enhanced T1-weighted images with Gd-DTPA were available in 10 patients. The following determinations were made: tumor morphology, signal intensities, contrast-enhancement effects of solid components with Gd-DTPA, and comparison of MR images with resected specimens. RESULTS: All 12 patients had both cystic and solid components, with a multilobulated surface and thickened septa. Signal intensities on T1-weighted images were mainly low, partly intermediate to high, or high, and those on T2-weighted images were mainly high, with different signal intensities. Contrast-enhancement effects were marked or moderate. The contents that showed low signal intensities on T1-weighted images and signal voids or low signal intensities on T2-weighted images were viscid gelatinous materials. CONCLUSIONS: A multicystic tumor with a solid component, a multilobulated surface, and signal intensities that indicate the presence of viscid gelatinous materials appear to be a characteristic MR finding of struma ovarii.

[Preoperative evaluation for volume reduction surgery of pulmonary emphysema using MRI: usefulness of HASTE (half-Fourier single-shot turbo SE) sequence during deep respiration].

Volume reduction surgery has recently been an important surgical procedure for patients with severe pulmonary emphysema. We compared the sagittal and coronal images taken by the HASTE sequence with those obtained by turbo FLASH during deep breathing and with CT images obtained under deep inspiration. Clear images were obtained from both sequences, without cardiac or respiratory motion artifacts. The emphysematous areas were demonstrated as low signal intensity areas, as in CT images. The ratio of signal intensity in the expiratory phase to that in the inspiratory phase was lower than that of volunteers in the HASTE sequence. The HASTE sequence provides useful information about respiratory movement as well as about changes in the pulmonary parenchyma when used for preoperative examination.

Preoperative multidisciplinary treatment with hyperthermia for soft tissue sarcoma.

We report the results of phase I/II studies of preoperative multidisciplinary treatment of 14 patients with soft tissue sarcoma using hyperthermia from November 1990 to April 1995. The preoperative treatment was conducted with thermo-radio-chemotherapy in 11 cases of stage III, and with thermo-radiotherapy as well as thermo-chemotherapy in three cases of stages I and II. Hyperthermia was carried out twice a week with totals ranging from 4 to 14 times (average: 8.4 times); each session lasted 60 min. Radiotherapy was administered four or five times per week, and the dose was 1.8 2Gy/fraction, with a total of 30-40 Gy in a four week period. Chemotherapy was mainly in the form of MAID regimen (2-mercaptoethanesulphonic acid (mesna), adriamycin, ifosfamide and dacarbazine). The tumors were surgically resected in all patients after completing the preoperative treatment. The efficacy rate, as expressed by the percentage of either tumors in which reduction rate was 50% or more, or tumors for which post-treatment contrast enhanced CT image revealed low density volumes occupying 50% or more of the total mass, was 71% (ten of the 14 tumors). The mean tumor necrosis rate in the resected specimens was 78%. The tumor necrosis rate was significantly high (P < 0.05) in patients whose Time > or = 42 degrees C was of long duration. Postoperative complications were observed in six patients; among these, two patients developed wound infection that required surgical treatment as a complication of surgery performed in the early stage following the preoperative treatment. After a mean postoperative follow-up of 27 months, distant metastasis occurred in four patients resulting in three fatalities. The three-year cumulative survival rate was 64.3%. No local recurrence was observed in any patient during the follow-up, thus confirming our hypothesis that preoperative multidisciplinary treatment has an excellent local efficacy. We think that it would be valuable to conduct, at many facilities, phase III studies on the treatment of soft tissue sarcoma by a combination of surgery and preoperative multidisciplinary treatment using hyperthermia, paying close attention to the interval between these two modalities.

Cervical carcinoma: dynamic MR imaging with a turbo-FLASH technique.

The purpose of this study was to evaluate the characteristic findings of cervical carcinoma in dynamic MR imaging with a turbo-FLASH technique and to investigate the cause of the hyperintense rim surrounding the tumor on dynamic MR images by comparing them with the pathological findings in the resected specimens. Sixty consecutive patients with cervical carcinoma were included in this study. Dynamic MR imaging was performed with the rapid administration of Gd-DTPA using the turbo-FLASH technique. After dynamic MR imaging, T1-weighted spin echo (SE) images were obtained. Dynamic patterns of the lesions were investigated from images acquired in the early and late phases of dynamic MR imaging. The causes of the hyperintense rim were investigated by comparing dynamic MR images with the pathological findings. Most of the cervical carcinomas showed higher signal intensity than normal cervical stroma in the early phase of dynamic MR imaging. The pathological findings of the hyperintense rim on dynamic MR images differed according to the time of appearance of the hyperintense rim. Dynamic MR imaging with the turbo-FLASH technique, which shows high contrast between the lesion and normal cervical stroma, should be performed before obtaining contrast-enhanced T1-weighted SE images in patients with cervical carcinoma.

Overexpression of manganese superoxide dismutase gene changes the metastasis associated-character of the mouse fibrosarcoma, FSa-II.

The tumor metastatic ability and tumorigenicity of the mouse fibrosarcoma cell line (FSa-II) were significantly reduced due to overexpression of manganese superoxide dismutase (MnSOD) as reported previously. We investigated changes in the in vitro basic character of FSa-II cells transfected with the human MnSOD cDNA which was employed in the previous studies. FSa-II and the control vector-transfected cell line NEO, had no detectable MnSOD activity. SOD-H, into which MnSOD cDNA was transfected, is the cell line with high MnSOD activity. The malignant phenotype, characterized by serum-independence, was suppressed with elevated MnSOD activity. A quantitative comparison of transferrin receptor (TfR) by flow cytometry showed the amount of TfR on the membrane of SOD-H cells to be significantly less than that on the membrane of NEO cells. The amount of CD44 expression on SOD-H cells was almost the same as that on NEO cells. The results of this study suggest that the overexpression of MnSOD is related to suppression of the malignant phenotype and that changes of iron metabolism may play an important role in this process.