Evaluation of the radiosensitizing effects of RK28 intravenous, intraarterial, and intratumoral injections on the rabbit VX2 tumor system.

PURPOSE: To evaluate the differences in the radiosensitizing effects of intravenous (i.v.) injection, intraarterial (i.a.) injection, and intratumoral (i.t.) injections of the hypoxic cell radiosensitizer RK28 ([1-(4'-hydroxy-2'-butenoxy)methyl-2-nitroimidazole], a 2-nitroimidazole with an acyclic sugar analogue substituted at the N-1 position of the imidazole ring) using an animal experimental system. METHODS AND MATERIALS: Rabbit VX2 tumors, which were implanted in the muscle of left hind legs and grown to 3 cm in diameter, were treated with RK28 (80 mg/kg x b.wt.) before 15 Gy of local x-ray irradiation. The auricular vein and the left saphenous artery were used for systemic injection and regional injection, respectively. For i.t. injection, a 21-gauge needle with three lateral holes was positioned in the central area of the tumor. Tumor regression was precisely evaluated by computed tomograpy (CT), and survival time was also studied. Using high-performance liquid chromatography (HPLC), pharmacokinetic studies for RK28 and its seven major metabolites were performed in tumor and serum at 0, 10, 20, 30, and 60 min after drug injection was completed. RESULTS: Radiosensitizing effects of RK28 were considered present after i.a. injection (p < 0.05) and i.t. injection (p < 0.05) after analyzing tumor volumes on day 21 after treatment. Increased survival was not observed in any group with RK28 injection compared with survival in the group treated by x-ray irradiation alone. Pharmacokinetic studies showed the average concentration of RK28 in the tumor during x-ray irradiation was 1.3 times higher after i.a. injection and 3.5 times higher after i.t. injection than that after i.v. injection. The time modifying factor50 (TMF50: ratio of time for tumor to decrease by 50%, radiation alone vs. radiation plus drug) was calculated to be 1.5 after i.v. injection, 1.7 after i.a. injection, and 2.3 after i.t. injection. The values of TMF50 correlated to the average concentrations of RK28 in the tumor. As to metabolites of RK28, beta-glucuronated compound and cysteine conjugate were highly detected. The concentrations of cysteine conjugate were higher in the tumor than in serum via i.v. injection. CONCLUSIONS: Radiosensitizing effects of RK28 were observed on the rabbit VX-2 tumor system after i.a. or i.t. injection. Pharmacokinetic studies proved that radiosensitizing effects depended on the concentration in the tumor, though the administration routes were different. Combined forms with nonprotein thiols were detected. However, survival benefits were not obtained by RK28. For clinical applications of RK28, i.a. or i.t. injection could facilitate better local control of cancer.

Is it possible to differentiate malignant mediastinal nodes from benign nodes by size? Reevaluation by CT, transesophageal echocardiography, and nodal specimen.

STUDY OBJECTIVE: To reevaluate whether it is possible to reliably differentiate malignant mediastinal lymph nodes from benign nodes by size, and to determine the frequency of metastases to normal-sized mediastinal lymph nodes that directly affects the sensitivity for detecting malignant mediastinal lymph nodes (N2 nodes) on CT. DESIGN: Prospective study of patients with non-small cell lung cancer. SETTING: Department of Radiology and First Department of Surgery, Yamaguchi University School of Medicine. PATIENTS: We examined 40 patients with non-small cell lung cancer, who underwent thoracotomy because of operable stage (stage I, II, IIIA) in preoperative staging, using CT and transesophageal echocardiography (TEE). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Lymph nodes 10 mm or greater in short-axis diameter on CT and TEE were considered abnormal. Furthermore, lymph node size was measured by TEE and nodal specimens in long- and short-axis diameter in each patient. Two hundred eight mediastinal lymph nodes were dissected and N2 nodes were present in 28% of patients (11/40); in 7 of these 11 patients (64%), mediastinal lymph node metastases were misdiagnosed on CT because of normal-sized N2 nodes. Furthermore, in 73% of N2 nodes, nodal size was normal on TEE. There were no significant difference in both diameters between malignant mediastinal lymph nodes and benign nodes on TEE and nodal specimens. CONCLUSIONS: It is not possible to reliably differentiate malignant mediastinal nodes from benign nodes by size alone, and we should be aware of high frequency of normal-sized N2 nodes in patients with operable stage of lung cancer.

Fulminant hepatitis caused by hepatitis C virus during treatment for multiple sclerosis.

A 55-year-old woman was treated at our hospital for multiple sclerosis. Therapy consisted of glucocorticosteroids and cyclosporin. In the 7th week after these drugs were discontinued the patient developed acute liver failure due to fulminant hepatitis (FH) and died. Post-mortem examination showed massive liver necrosis. Serologic examination was negative for hepatitis B virus-related markers. Antihepatitis C virus (anti-HCV) antibody and serum HCV RNA were negative on admission, but HCV RNA appeared concurrently with the onset of FH. Although HCV infection rarely causes FH, it was considered to be the cause of FH in this patient, since there were no other causes of acute liver injury. We suspect that underlying immunologic abnormalities in conjunction with HCV infection may have precipitated the FH.

Pilot study of ofloxacin and interferon-alpha combination therapy for chronic hepatitis C without sustained response to initial interferon administration.

A controlled trial comparing combination therapy with ofloxacin (OFLX) and interferon (IFN) versus IFN monotherapy was conducted in patients with chronic hepatitis C who failed IFN therapy. Twenty patients were assigned randomly to two groups. Equal doses of recombinant IFN alpha-2b were administered to each group for 24 weeks. For the IFN plus OFLX group, OFLX was administered for 12 weeks at a daily dose of 600 mg. Levels of hepatitis C virus RNA declined significantly from the first month after the start of IFN treatment compared with those before administration in both groups. Serum alanine aminotransferase levels were significantly lower in the IFN plus OFLX group at two and six months after the start of treatment than levels in the IFN group. The fraction of subjects whose levels of serum ALT normalized was also higher in the IFN plus OFLX group. Larger clinical trials should be undertaken.

GB virus C infection: clinical significance.

GB virus C (GBV-C) RNA positivity rates were examined in serum specimens from 231 patients with liver disease (23 patients with hepatitis B, 175 patients with hepatitis C, five patients with hepatitis B virus plus hepatitis C virus coinfection, and 28 patients with non-A, non-B, non-C hepatitis) to clarify the clinical significance of this virus. GBV-C RNA was detected in none of 12 patients with fulminant hepatitis, one of two patients with acute hepatitis positive for hepatitis B surface antigen and one of four patients with acute non-A, non-B, non-C hepatitis. Pathogenetic involvement of GBV-C was suspected in some patients in the latter group. Among patients with the non-B, non-C type of chronic disease, one of seven with cirrhosis (14%) and none with chronic hepatitis or hepatocellular carcinoma were GBV-C-positive. In chronic hepatitis C patients who had received interferon treatment, no difference was found in clinical findings, alanine aminotransferase (ALT) concentrations, histology or response to interferon between 11 patients who were GBV-C RNA-positive and 101 patients who were GBV-C RNA-negative. Moreover, changes in ALT after interferon therapy showed no relation to positivity for GBV-C RNA. On the basis of these findings, GBV-C appears to be an unlikely cause of initiation or progression of chronic hepatic diseases.

Assessment of 99Tcm-HMPAO tumour scintigraphy using VX-2 tumours implanted in a lower limb muscle of rabbits.

Tumour scintigraphy using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was investigated in VX-2 tumours implanted in the muscles of the lower legs of rabbits to assess the feasibility of using this agent clinically for this procedure. On the time-activity curves for 99Tcm-HMPAO in the tumour, an initial peak and a subsequent decrease of radioactivity immediately after the initial peak were observed, while there was a slow, gradual decrease of activity over the next hour. The tumour/normal muscle ratio of HMPAO activity during this period was high and constant, and was independent of time. Comparison of the static images of 99Tcm-HMPAO with angiography and histological findings suggests that the tumour image of 99Tcm-HMPAO reflects tumour blood perfusion. These findings indicate that the distribution of 99Tcm-HMPAO on static images can provide a qualitative assessment of the perfusion of the tumour, despite the limitations of this tracer for quantifying tumour blood flow due to its early efflux from the tumour.

Ruptured subcapsular giant hematoma of the spleen as a complication of chronic pancreatitis.

We present a 63-year-old man with chronic pancreatitis and the rare complication of giant subcapsular splenic hematoma. The hematoma showed no size reduction for 6 weeks. Then, the hematoma was infected with pseudomonas aeruginosa after the recurrence of the pancreatitis, and it finally ruptured. This case suggested that in cases of giant subcapsular splenic hematoma with chronic pancreatitis reductive pressure treatment should be administered as early as possible.

Poorly vascularized malignant insulinoma displaced the pancreatic ducts around the mass on endoscopic retrograde cholangiopancreatography.

A 66-year-old woman with an altered mental status caused by hypoglycemia was referred to Akita City Hospital. Abdominal ultrasonography (US) and endoscopic US revealed an isoechoic mass measuring 25 mm in the head of the pancreas. Endoscopic retrograde cholangiopancreatography (ERCP) revealed that the main pancreatic duct and its branches were displaced around the mass in the head of the pancreas. On arteriography, a poorly vascularized tumor was observed. Dynamic contrast-enhanced computed tomography (CT) showed a low-attenuation mass in the head of the pancreas. A pylorus-preserving pancreaticoduodenectomy was performed. Microscopically, the diagnosis was malignant insulinoma.

The role of gallium-67 imaging in the detection of foci in recent cases of fever of unknown origin.

We have assembled data from patients with fever of unknown origin who underwent gallium scintigraphy during the past 5 years in order to obtain a more current sampling of patients, and evaluated the role of gallium scintigraphy retrospectively. Of the 36 patients studied, gallium scintigraphy was positive and contributed to the detection of the foci or fever origins in 17 (47.2%). The ratio of neoplastic diseases with myeloproliferative and with lymphoproliferative disorders was relatively high compared with previous reports. However, gallium scintigraphy did not contribute to the diagnosis of collagen disease. With the ability to detect both inflammatory and neoplastic lesions, gallium scintigraphy was useful in detecting the foci of fevers of unknown origin.

Scintigraphic analysis of hemodynamics in a patient with a single large pulmonary arteriovenous fistula.

A pulmonary perfusion study was performed on a 54-year-old man with a single large pulmonary arteriovenous fistula (aneurysmal type) using Tc-99m MAA. On the static imaging, a defect corresponding to the location of the mass and right-to-left shunt was clearly documented. Decreased uptake of Tc-99m MAA in the lung field surrounding the lesion was observed and was thought to reflect a "steal" of blood flow by the fistula. One advantage of using radionuclide angiography with Tc-99m MAA rather than with Tc-99m pertechnetate was that it more easily provided a time-activity curve that added useful quantitative information about the altered pulmonary hemodynamics.

Uterine leiomyosarcoma metastasis to the skull--case report.

A 54-year-old female presented with a rare uterine leiomyosarcoma metastasis to the skull appearing as a gross mass beneath her scalp. She had no neurological or other physical symptoms on admission. Computed tomography and magnetic resonance imaging demonstrated an enhanced dumbbell-shaped mass at the mid-frontal region beneath the scalp. The tumor was totally removed with normal surrounding bone and dura. The histological diagnosis was leiomyosarcoma. Her postoperative course was uneventful, and she received adjuvant chemotherapy. However, multiple distant bone metastases developed 1 year later. Immediate and radical resection of such tumors is recommended.

[A case of intracranial hypoglossal neurinoma].

A case of intracranial hypoglossal neurinoma is reported. A 32-year-old man with a history of unsteady gait and headache for one and a half years was admitted to our hospital on September 23, 1983. Neurological findings on admission were nystagmus toward the left, left IXth and Xth cranial nerve paresis, left cerebellar signs, paresthesia of the left upper and lower extremities on neck flexion, and left pyramidal signs. Atrophy or fasciculation of the tongue was not noted. Computed tomography demonstrated a large isodensity and partially low density mass in the posterior fossa which was markedly enhanced and sharply margined with contrast medium. The tumor extended 45 mm over the edge of the foramen magnum. The maximum size was 45 mm X 40 mm. The coronal and sagittal reconstruction CT scan clearly demonstrated the attachment and extension of the tumor. Enlargement of the hypoglossal canal was clarified by changing the window level, window width and using 2 mm slice CT scan. Anterior-posterior x-ray view of the skull tomography showed enlargement of the hypoglossal canal, as indicated by the CT scan. The left hypoglossal canal was 7 mm and right was 3 mm in diameter. Vertebral angiography demonstrated that the tumor was located in the left posterior fossa, but no tumor stain appeared. This patient did not have XIIth cranial nerve palsy, but the neuroradiological findings strongly suggested a hypoglossal neurinoma, especially the findings of the CT scan and the anterior-posterior x-ray view of the skull tomography. On October 5, suboccipital craniotomy with Cl laminectomy was performed in prone position.(ABSTRACT TRUNCATED AT 250 WORDS)

[Unilateral visual field defect due to optic nerve compression by sclerotic internal carotid artery: a case report].

A case of unilateral visual field defect due to optic nerve compression by a sclerotic internal carotid artery was reported. A 71-year-old woman was admitted to our department because of constricted visual field of the right eye. MRI showed elevation of the right optic nerve compressed by an internal carotid artery. The right carotid angiography revealed elevation and distortion of the C1-2 portion. Frontal craniotomy was carried out and the optic nerve was visualized on this side. The right optic nerve was found to have been compressed by the sclerotic internal carotid artery. The optic canal was then unroofed. The post-operative course was uneventful. The visual field was improved. When last seen 6 months after surgery, her visual field remained in the improved condition. Nasal field abnormalities are most frequently encountered in retinal and anterior optic nerve pathology. Our success in improving the visual field disturbance may be accounted for by the fact that the preoperative period was short and the operation was performed before atrophy of ocular fundi occurred. Nasal field loss caused by intracranial lesions of the optic pathway is rare. It is probably impossible to determine degree of the symptomatology caused by direct-pressure compression as opposed to that caused by ischemia secondary to occlusion of small arterial supply branches. Vascular compressive neuropathy of optic nerve should not be diagnosed simply by the radiological finding of the optic nerve dislocation. However, optic nerve compression by surrounding arteries should be remembered as one of the possible causes of visual field defect which needs to be treated surgically.

[Experimental study on the mechanism of the intrapulmonary kinetics of 123I-IMP in a balloon occluded bronchus in rabbits].

To investigate the mechanism of intrapulmonary kinetics of N-isopropyl-p-123I-iodoamphetamine (123I-IMP), we performed lung scanning with 123I-IMP in 13 rabbits in which a unilateral bronchus was occluded by a balloon catheter. In 9 rabbits, on the delayed distribution images, an abnormal accumulation of 123I-IMP was detected in the hypoperfusion area of the peripheral lung field of the occluded bronchus, which was detected on lung perfusion images with 99mTc-MAA. Comparison of early (a summation image during 20 seconds immediately after injection) and delayed (a summation image from 70 to 90 minutes after injection) distribution images confirmed that during this period, 123I-IMP accumulated in the area of reduced distribution of 123I-IMP. Moreover, at the site of abnormal accumulation, washout of 123I-IMP from the lung was delayed compared with that in the normal lung field. We find this experimental study is similar to the results in 63 clinical cases, which we have reported previously, and confirm that pulmonary arterial perfusion, especially hypoperfusion, influences the intrapulmonary kinetics of 123I-IMP.

[The assessment of 99mTc-HMPAO tumor scintigraphy using VX-2 tumors in rabbits].

Tumor scintigraphy using 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) was performed in VX-2 tumors implanted in the muscles of the lower limbs of rabbits to evaluate the possibility that this agent could be used to estimate the blood perfusion of the tumor. The distribution of 99mTc-HMPAO in the tumor immediately after the intravenous injection of this radiopharmaceutical exhibited almost the same distribution on the static image 1 hour after administration. Tumor time-activity curve for 99mTc-HMPAO revealed initial peak after the injection followed by fading of 99mTc-HMPAO activity and subsequent gradual decrease in activity over the next 1 hour. The ratio of 99mTc-HMPAO activity in the tumor to that in normal muscle tissue during this next 1 hour was high and independent of time. These findings indicate that static 99mTc-HMPAO scintigraphy can provide qualitative but not quantitative data useful in the estimation of tumor blood perfusion. Moreover, comparison of distribution of 99mTc-HMPAO on the static images and angiographic, histological findings also suggest that static 99mTc-HMPAO images accurately reflect tumor blood perfusion.

[Clinical evaluation of bronchial artery infusion (BAI) in lung cancer].

Clinical evaluation of 32 cases of primary lung cancer treated with Bronchial Artery Infusion (BAI) were reported. As to the relationship between Bronchial Arteriogram (BAG) and therapeutic effect of BAI, the therapeutic effect of BAI was closely correlated with the degree of neovascularity. And as no correlation was shown between therapeutic effect and histology of lung cancer, the degree of neovascularity on BAG seemed to be more important factor. From the aspect of survival, neovascularity and B-P shunt on BAG showed no correlation with the survival time. On the relationship between survival and histology of lung cancer, squamous cell carcinoma and adenocarcinoma showed almost an equivalent survival. According to the stage of our cases, 25 out of 32 cases were stage III and IV, and they showed relatively better survival, especially stage III, of which MST was 16.6 months, and of which a two year survival rate was 33.5% considering MST and a two year survival rate of stage III A (N2) of non-resected non-small cell lung cancer in other reports are about 12 months and 20%, respectively. BAI is considered to be an effective method among several treatments against lung cancer.

Fusiform aneurysm of the vertebral artery presenting with hemifacial spasm treated by microvascular decompression.

We report a rare case of symptomatic hemifacial spasm caused by a fusiform vertebral artery aneurysm. A 59-year-old woman presented with left hemifacial spasm of 18 months duration. Magnetic resonance imaging showed an enlarged a fusiform aneurysm of the left vertebral artery which compressed the seventh cranial nerve at its exit from the caudal pons. Microvascular decompression of the facial nerve with moving of the aneurysm resulted in complete relief of the hemifacial spasm. No enlargement of the aneurysm was shown on follow-up for a period of 6 years.