Postoperative radiation therapy for extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that is usually treated with surgery. Patients with positive surgical margins require adjuvant therapy, but there have been few reports on the use of radiation therapy. OBJECTIVES: To investigate the effectiveness of postoperative radiation therapy in EMPD. MATERIALS AND METHODS: Twenty-one patients with EMPD involving the genitalia underwent radiation therapy as adjuvant therapy after surgery. Ten patients had inguinal lymph node involvement before radiation therapy, but none had distant metastases. A median total dose of 59·4 Gy (range, 45-64·8 Gy) was delivered to the tumour bed in 30 fractions (range, 23-36 fractions). RESULTS: At a median follow-up period of 38 months, all patients had local control. However, six patients had developed distant metastases 6-43 months after radiation therapy. The distant metastasis-free rates were 66% at 3 years and 55% at 5 years. Inguinal lymph node involvement was a significant risk factor for distant metastases. Four patients died 33-58 months after irradiation; the causes of death were tumour progression in three patients and infectious pneumonia in one. The overall and cause-specific survival rates were both 92% at 3 years, and 62% and 71% at 5 years, respectively. No therapy-related toxicities of grade ≥ 3 were observed. CONCLUSIONS: Postoperative radiation therapy is safe and effective in maintaining local control in patients with EMPD.

Radiation therapy for extramammary Paget's disease: treatment outcomes and prognostic factors.

BACKGROUND: Extramammary Paget's disease (EMPD) is a relatively rare malignancy, and there are few reports related to radiation therapy. In the present study, we investigated the outcome of radiation therapy for EMPD. PATIENTS AND METHODS: Forty-one patients with EMPD in the genitalia underwent radiation therapy with curative intent. Fifteen patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 45-80.2 Gy (median, 60 Gy) were delivered to tumor sites in 23-43 fractions (median, 33 fractions). RESULTS: At a median follow-up period of 41 months, 16 patients had developed recurrences, including 5 with local progression within the radiation field and 12 with lymph node or/and distant metastases outside the radiation field. The local progression-free and disease-free rates were 88% and 55% at 3 years, and 82% and 46% at 5 years, respectively. Nine patients died at 6-73 months after irradiation; the causes of death were tumor progression in five patients, infectious pneumonia in two, renal failure in one and old age in one. The overall and cause-specific survival rates were 93% and 96% at 3 years, and 68% and 84% at 5 years, respectively. Tumor invasion into the dermis and regional lymph node metastasis were significant prognostic factors for both distant metastasis and survival. No therapy-related toxicities of grade ≥3 were observed. CONCLUSIONS: Radiation therapy is safe and effective for patients with EMPD. It appeared to contribute to prolonged survival owing to good tumor control, and to be a promising curative treatment option.

Radiation therapy for primary carcinoma of the eyelid: tumor control and visual function.

BACKGROUND AND PURPOSE: Surgical excision remains the standard and most reliable curative treatment for eyelid carcinoma, but frequently causes functional and cosmetic impairment of the eyelid. We therefore investigated the efficacy and safety of radiation therapy in eyelid carcinoma. PATIENTS AND METHODS: Twenty-three patients with primary carcinoma of the eyelid underwent radiation therapy. Sebaceous carcinoma was histologically confirmed in 16 patients, squamous cell carcinoma in 6, and basal cell carcinoma in 1. A total dose of 50-66.6 Gy (median, 60 Gy) was delivered to tumor sites in 18-37 fractions (median, 30 fractions). RESULTS: All but 3 of the 23 patients had survived at a median follow-up period of 49 months. The overall survival and local progression-free rates were 87% and 93% at 2 years, and 80% and 93% at 5 years, respectively. Although radiation-induced cataracts developed in 3 patients, visual acuity in the other patients was relatively well preserved. There were no other therapy-related toxicities of grade 3 or greater. CONCLUSION: Radiation therapy is safe and effective for patients with primary carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid.

Reduction cranioplasty for craniocerebral disproportion due to chronic subdural hematoma in infants. A technical report.

Advanced craniocerebral disproportion due to chronic subdural hematoma in infants which is resistant to conventional treatments requires reduction cranioplasty as the last resort. The present paper deals with our experience with two such cases originated from head injury. Since the volume of the hematoma cavity was calculated based on the pre-operative CT scans, we devised a mathematical formula to design how the cranial vault could be reconstructed for reduction. This enabled us to pre-determine the extent of cranial reduction which was tailored to each patient. Furthermore, the present methodology is characterized by the modification that the midline bone strip overlying the superior sagittal sinus was shortened at its anterior end and bent down using the posterior end as a hinge. Since the follow-up results were favorable, this technique of reduction cranioplasty is reported in detail.

Gamma-ray induced hepatocarcinogenesis in p53-deficient mice.

BACKGROUND: Mutations in the p53 gene are frequent genetic alterations in human hepatocellular carcinoma (HCC), but, little is known of the molecular genetic changes that occur during murine hepatocarcinogenesis. MATERIALS AND METHODS: To characterize the properties of constitutive p53 deficiency that contribute to liver tumor development, a total of 168 F1 mice of two different strains (C3H, which are susceptible to hepatocarcinogenesis and MSM [Mus. M. molossinus] with a single null p53 allele) were exposed to a single 3-Gy dose of whole-body gamma-irradiation at 4 weeks of age and observed for a period of 360 days. The genotype of the mice and the p53 spectrum of the tumors were investigated by polymerase chain reaction (PCR) analysis. RESULTS: Thirty-five gamma-ray-induced HCCs were obtained as a result of this experiment. 11 (40%) of the mice with liver tumor were wild-type for p53. All liver tumors examined retained the wild-type p53 allele, indicating that p53 itself may not be a target for radiation-induced alteration. Only two p53-deficient mice in the liver tumor group developed thymic lymphomas. The p53-deficient mice showed no significant differences in the number, size, or growth rate of HCC or in the apparent development of HCC. CONCLUSION: These results indicate that p53 deficiency does not enhance the rate of development or degree of malignancy of radiation-induced HCC in mice but may instead favor the development of multiple primary cancers.

Transcranial approach for transsphenoidal encephalocele: report of two cases.

BACKGROUND: Whereas the transcranial approach has been regarded as the therapy of choice for transethmoidal encephalocele, its feasibility for transsphenoidal encephalocele has remained controversial, particularly in neonates and infants. CASE REPORT: Two cases of transsphenoidal encephalocele operated transcranially are presented. In the first case, this 6-year-old boy underwent a transpalatal operation with repair of a cleft palate in another hospital before admission. Reoperation via the transcranial route was carried out because of postoperative recurrent meningitis. With partial resection of the anterior wall, the encephalocele could be separated from the underlying tissue, and the interspace was filled with the pericranial flap. He made an uneventful recovery and has been well for the past 3 years. The second was a 3-month-old baby with a large encephalocele filling the nasopharyngeal space. As the cleft palate was absent, the transcranial approach was employed. In this case, the herniated tissue was excised at the lowest level possible. Postoperatively, panhypopituitarism became manifest. Re-evaluation of the preoperative magnetic resonance imaging (MRI) disclosed a small mass far below the dorsum sellae, which turned out to be an anomalous pituitary gland on histologic examination. CONCLUSIONS: The transcranial approach is considered a valid alternative for the therapy of transsphenoidal encephalocele, particularly when the transpalatal approach is unfeasible. While the anterior wall of the herniated sac may be safely resected, the posterior wall should under no circumstances be sacrificed. The preoperative MRI is essential, as it may provide valuable information as to the location of vital structures within the herniated tissue.

Pairing of DNA fragments containing (GGA:TCC)n repeats and promotion by high mobility group protein 1 and histone H1.

Tandemly repeated DNA sequences of (GGA:TCC)n are found in tracts up to 50 base pairs long, dispersed at thousands of sites throughout the genomes of eukaryotes. Here we demonstrate the formation of complexes paired between two DNAs containing such repeats in vitro and show enhancement of the pairing by glutathione S-transferase fusion proteins of high mobility group protein 1 and histone H1. This assembly depends on incubation time at 37 degrees C and concentrations of the proteins and DNA, and the enhancement is inhibited by distamycin and actinomycin D interacting DNA through the minor groove. Structure of the DNA-DNA complex is deduced by comparison of its mobility in gel electrophoresis with those of synthetic markers of heterotetramers. Three synthetic and genomic DNA fragments containing repeats that have different arrangements exhibit different efficiencies of DNA pairing, implying that the pairing is affected by the number of repeat units and the arrangement of repeats in a sequence. Intriguingly, pairing occurs between homologous fragments but not between heterologous DNAs among the three. These results suggest that the repeat-mediated DNA pairing plays a role in organization of higher order architecture of chromatin and possibly chromosome segregation requiring sequence-specific association events of DNA molecules.

The role of active smooth-muscle contraction in the occurrence of chronic vasospasm in the canine two-hemorrhage model.

To evaluate the pathogenetic role of alterations in the physical properties of the arterial wall (the passive component) and of active smooth-muscle contraction (the active component) in the occurrence of chronic vasospasm, the temporal profiles of these events were examined using the canine "two-hemorrhage" model. In the in vivo study, the basilar artery was exposed via the transclival approach on Day 0, 2, 4, 7, or 14. Nicardipine, followed by the protein kinase C inhibitor H-7, then papaverine were administered in a cumulative fashion, and the change in the basilar artery diameter induced by the addition of each agent was recorded angiographically. Drug administration markedly reversed the arterial narrowing caused by chronic vasospasm. When the vasodilatory effect of each agent was compared, the dilation induced by nicardipine or papaverine progressively decreased from Day 2 to Day 7, whereas that induced by H-7 increased. The in vitro experiment using arterial segments excised from the basilar artery revealed a progressive increase in arterial stiffness from Day 2 to Day 7. Also, there was a significant decrease in the initial half-circumference of the arterial segment, which was at its maximum on Days 4 and 7. However, the alteration in the initial half-circumference was considerably less than that in the angiographic diameter following subarachnoid hemorrhage. These data indicate that the augmented spontaneous tonus of the smooth muscle plays the predominant role in the occurrence of chronic vasospasm. Thus, the involvement of the protein kinase C-mediated contractile system is strongly suggested.

Effect of antioxidative lactic acid bacteria on rats fed a diet deficient in vitamin E.

Lactic acid bacteria, including Bifidobacterium, with antioxidative activity were selected by in vitro screening. The effect of the antioxidative activity was investigated by in vivo experiments using rats that were deficient in vitamin E. In the first stage of screening, 570 strains were examined; intracellular cell-free extracts of 19 strains (16 lactobacilli, 2 streptococci, and 1 lactococci) had antioxidative activity as determined by an assay using rat liver microsomes and thiobarbituric acid. In the second stage of screening, 7 strains of lactobacilli showed over 70% inhibition of oxidation activity. The highest activity was obtained by heterofermentative Lactobacillus sp. SBT 2028. The effect of two strains, Lactobacillus sp. SBT 2028 and Lactobacillus casei ssp. rhamnosus SBT 2257, was evaluated for improvement of the condition of rats fed a diet deficient in vitamin E. Intracellular cell-free extracts of those two strains were also used for in vivo experiments. Hemolysis of red blood cells was inhibited in rats that were administered the extract of Lactobacillus sp. SBT 2028, which proved that the extract improved the vitamin E deficiency status. Antioxidative activity of an extract from L. casei ssp. rhamnosus SBT 2257 determined by hemolysis was relatively weak compared with the activity of Lactobacillus sp. SBT 2028 extract.

Possible involvement of C-kinase in occurrence of chronic cerebral vasospasm after subarachnoid hemorrhage.

The present study aimed to examine the turnover of phospholipids such as PI, PC and PE, the time course of PKC activity and the phosphorylation of 20 kDa MLC in the canine BA undergoing chronic VS. The phosphorylation of 20 kDa MLC was not augmented in the spastic BA. Turnover of PC and PE was detectably stimulated on day 7. The cytosolic PKC activity was down-regulated on days 4 and 7, while the membrane PKC activity remained unchanged during these periods. The present results indicate that a process which affected the membrane lipid metabolism, PKC metabolism and PKC activity occurred in spastic BA.

Primary empty sella syndrome caused by an abnormal dilatation of the optic recess.

A new variety of primary empty sella syndrome is reported. A partial herniation of the optic chiasm into an enlarged empty sella compressed by a dilated optic recess mimicking a cystic tumor was confirmed at operation. The pathogenesis and the treatment of this type of empty sella syndrome are discussed.

[The effectiveness of FID-CT (functional image of dynamic CT) for the evaluation of early cerebral ischemia].

A computer program was newly developed to display the ischemic area from the serial dynamic CT scan, namely the functional image of the dynamic CT (FID-CT). The principles of FID-CT are as follows; Seven rapid-sequence dynamic CT scans were taken following a peripheral bolus intravenous injection of 40 ml of iopamidol. As the data from each scan can be separated into three consecutive segments, we obtained 21 images during 44 seconds. Time density curves of each pixel were calculated employing Gamma variate fitting method. Eight functional parameters obtained from this curve were displayed with gray-scale pixel by pixel. These eight images were functional images obtained from dynamic CT. Only three or four minutes were required to complete all the calculations. Twenty-two patients were examined with both FID-CT and 123I-SPECT. In each case, the lesion detected by FID-CT was remarkably consistent with that shown by SPECT. Two representative cases were presented. The authors believe that FID-CT is a very useful diagnostic method in the acute stage of cerebral ischemia because the method can be quickly and easily performed and it discloses the ischemic area with fair certainty.

Iodine-123 IMP SPECT before and after bypass surgery in a patient with occlusion of left anterior and middle cerebral arteries with basal abnormal telangiectasis (unilateral Moyamoya disease).

A case of left anterior and middle cerebral arterial occlusion with angiographic features similar to Moyamoya disease was reported. IMP SPECT of the patient revealed the success of bypass surgery clearly. The patient complained of transient right hemiparesis with aphasia 4 times. The cerebral arteriography disclosed occlusions of left anterior and middle cerebral arteries at their proximal portions. Right internal carotid and its branches were normal. I-123 IMP SPECT study showed hypoperfusion in left temporal lobe, basal ganglia with incomplete reperfusion on the delayed (4 hours after injection) SPECT images. After the superficial temporal-middle cerebral artery anastomosis, I-123 IMP SPECT showed improvement of the brain blood flow. I-123 IMP SPECT was very useful in detecting the ischemic areas and evaluating the revascularizing surgery in this case.

Optimal preprocessing Butterworth-Wiener filter for Tl-201 myocardial SPECT.

The optimal frequency characteristic of Butterworth-Wiener filters (BWF) for improving the image quality of 201Tl myocardial SPECT was determined by a phantom experiment. Thirty two projection images of the phantom containing 11.1 MBq of 201Tl with 4 different cold lesions were collected during a 180 degree arc of a gamma camera. A set of the projection images were processed with each of 27 different BWFs, and SPECT images were reconstructed by Shepp-Logan filtered backprojection. The SPECT images were evaluated for their diagnostic ability to visibly detect the cold lesions by four nuclear medicine physicians. The lesion contrasts were used as an adjunctive tool to determine the optimum filter. The optimal combination of the parameters determining BWF characteristics (for the data of about 100 count/pixel at the myocardium) is: 1) cutoff of 0.25/pixel, 2) FWHM of 3 pixels, 3) noise/signal ratio of 0.02. FWHM and noise/signal ratio affected lesion contrast much less than cutoff frequency. Clinical myocardial SPECT images processed with the optimal BWF showed less noise and sharper delineation of the myocardium.

[The study of a two-dimensional polar representation of the cardiac SPECT image--a new method of displaying left ventricular wall motion].

A new method was developed to display left ventricular wall motion using two dimensional polar representation of cardiac SPECT image. After intravenous administration of 740 MBq (20 mCi) 99mTc (in vivo labeling of red blood cell), ECG-gated SPECT image of cardiac pool was recorded (32 directions, 180 degrees). The short axis images of left ventricle were constructed at end-diastole (ED) and end-systole (ES). Then the functional images of (ED-ES)/ED were calculated at each compatible slices and displayed in color according the degree of wall motion. In 8 cases with cardiac diseases this method was applied and clinically useful functional images could be obtained. The area of akinesia or hypokinesia are successfully demonstrated clearly separated from the area of normokinesia. We conclude that this method is useful to show left ventricular wall motion and to evaluate the segment and grade of abnormal wall motion of left ventricle.