A case of large-cell lung cancer with liver metastasis successfully treated using combination chemotherapy with CDDP and vinorelbine

A 38-year-old woman presented to our hospital with the chief complaint of dyspnea. A chest radiograph showed pleural effusion of the right lung and a CT scan revealed liver metastasis. A tumor biopsy done under bronchoscopy revealed large-cell carcinoma of the lungs. She was given 4 courses of a combination therapy consisting of CDDP (80 mg/m2) and vinorelbine (25 mg/m2). The primary tumor in the right lung and liver metastasis were markedly reduced in size and a partial response was obtained. The combination therapy of CDDP and vinorelbine may become a standard chemotherapy for advanced non-small cell lung cancer.     

The usefulness of 18F-FDG PET images obtained 2 hours after intravenous injection in liver tumor

Liver tumors, especially hepatocellular carcinomas (HCCs), often exhibit no contrast with surrounding non-tumorous liver tissue in F-18-fluoro-2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) images obtained at the usual interval of one hour after intravenous FDG injection. We evaluated the usefulness of FDG PET studies of liver tumors performed 2 hours after intravenous injection. METHODS AND MATERIALS: Fifteen pretherapeutic patients with 33 liver tumors were studied, including 11 patients with 18 HCCs, and 4 patients with 15 metastatic liver tumors (METAs) from 3 colorectal carcinomas and 1 esophageal carcinoma. After transmission scans, emission scans were obtained 45-55 minutes and 115-125 minutes after intravenous injection of 185-370 MBq FDG as early images and delayed FDG PET images, respectively. Visual analysis of early and delayed images was performed, and the FDG uptake in the tumor to that in nontumorous liver ratio (T/N ratio), the FDG uptake in tumor to that in soft-tissue ratio (T/S ratio) and the FDG uptake in non-tumorous liver to that in soft-tissue ratio (N/S ratio) were calculated for each image. RESULTS: In visual analysis, visual improvement seen in images was observed in 6 of 18 HCC lesions and all 15 META lesions. In quantitative analysis, the mean T/S ratio and T/N ratio of HCCs in early images were 4.97 and 1.90, respectively, and those in delayed images were 6.24 and 2.20, respectively. The mean T/S ratio and T/N ratio of METAs in early images were 5.97 and 2.21, respectively, and those in delayed images were 6.99 and 3.80, respectively. The T/S ratio of HCCs and T/S ratio and T/N ratio of METAs were significantly higher in delayed images than in early images. The mean N/S ratios of HCC cases were 2.58 in the early images and 2.57 in the delayed images, but the ratio showed no constant tendency in the images. All N/S ratios of META cases were decreased in delayed images, although the significance of the difference between early and delayed images in N/S ratios was not analyzed because of the small number of cases. CONCLUSION: FDG PET studies performed 2 hours after intravenous injection were useful for clear visualization of liver tumors, especially metastatic liver tumors.     

Physicochemical quality evaluation of natural compounds isolated from crude drugs

Aconite root has high toxicity caused by diester alkaloids, thus it was necessary to define the limiting value of diester alkaloids used in medicine formulation. To give the quality of “Processed Aconite Root” and “Powdered Processed Aconite Root” in the Japanese Pharmacopoeia (14th edn, supplement II), we established the official specification and evaluation methods of standard substances. High qualitative grade diester alkaloids, aconitine, hypaconitine, jesaconitine and mesaconitine, which were useful to evaluate the purity of processed aconite root and powdered processed aconite root, were prepared and evaluated for their stability. We studied the physicochemical specification and evaluation methods of these alkaloids. In addition, an “Aconitum diester alkaloids standard solution for purity”, which was used for the purity test, was prepared, and we also studied its physicochemical specification and evaluation methods. In addition, to evaluate the quality of processed aconite root and powdered processed aconite root, a TLC identification test was established. A monoester alkaloid of benzoylmesaconine hydrochloride was used as the reference standard in the latter test, and we also investigated its physicochemical specification and evaluation methods.     

New dammarane-type saponin from roots of Panax notoginseng

A new ginsenoside and 22 known compounds were isolated from the roots of Panax notoginseng (Araliaceae). The structure of the new compound was elucidated from 2D-NMR and other spectral evidence.     

Paclitaxel and carboplatin combination chemotherapy in a hemodialysis patient with advanced ovarian cancer.

BACKGROUND: There are few reports on the pharmacokinetics of paclitaxel combined with carboplatin or on the dose schedule of carboplatin in combination use during hemodialysis in patients with ovarian cancer. CASE: A 40-year-old woman with chronic renal failure on hemodialysis who had FIGO stage III ovarian cancer was treated with debulking surgery and carboplatin/paclitaxel combination chemotherapy. Paclitaxal was administered at 150 mg/m(2) as a 3-h intravenous infusion followed by a 30-min infusion of carboplatin on a nondialysis day. The carboplatin dose was chosen to produce a target area under the concentration/time curve (AUC) of 5.0 microg-min/ml according to the Calvert formula. The pharmacokinetic study showed that the AUCs of free platinum and paclitaxel were 4.43 microg-min/ml and 15.9 microg-h/ml, respectively. Dosing of carboplatin based on the AUC produced an acceptable degree of thrombocytopenia and neutropenia. After the completion of five cycles of the combination chemotherapy, the tumor showed complete response, and the patient remained disease free for 8 months. CONCLUSION: Paclitaxel and carboplatin combination chemotherapy can be given to patients undergoing hemodialysis, with dialysis performed 16 h after the administration and with a dose adjustment of carboplatin to reach a target AUC. In these conditions, tumor response can be obtained.     

Enhanced Tumor Localization of Radiolabeled Fab Fragments of Monoclonal Antibody A7 in Nude Mice Bearing Human Pancreatic Carcinoma Xenografts

Much recent research has been directed toward the use of monoclonal antibodies (MAb) for the inimunodetection of solid tumors. In pancreatic cancer, the results of conventional immunoscintigraphy using intact MAb remain disappointing. Clear immunoseintigrapliy with radiolabeled MAb requires a high tumor tissue/blood ratio of radioactivity and a low normal tissue/blood ratio of radioactivity. In this study, ¹²⁵I-labeled Fab fragments produced by papain digestion of MAb A7 were injected intravenously into nude mice bearing a human pancreatic cancer (HPC-YS) xenograft previously shown to react specifically with MAb A7. The radioactivity of tumors and normal organs was subsequently measured. The tumor tissue/blood ratio of ¹²⁵I-labeled Fab fragments of MAb A7 was 1.00±0.24 and 9.68±2.54 at 2 and 24 h after injection, respectively. The tumor tissue/blood ratio of radioactivity was significantly higher than those of normal organs at 24 h after injection. Moreover, the tumor tissue/blood ratio of ¹²⁵I-labeled Fab fragments of MAb A7 was greater than that of intact MAb A7, although the ¹²⁵I-labeled Fab accumulation level was much less than that of ¹²⁵I-labeled intact MAb A7 in the tumor. When mice bearing tumors which did not react with MAb A7 were studied, ¹²⁵I-labeled Fab fragments did not specifically localize to the tumors. These results suggest that Fab fragments of MAb A7 may be suitable carriers of radionuclides for the immunodetection of human pancreatic cancer.     

A role for the fyn oncogene in metastasis of methylcholanthrene-induced fibrosarcoma a cells

Expression of various oncogenes (ras, myc, erbB2, src, fyn, yes and sis) in a high-metastatic clone (MH-02) derived from a murine methylcholanthrene-induced fibrosarcoma A (Meth A) was compared with those of its parent clone (ML-01) by Northern blot analysis. Two oncogenes, fyn, belonging to the tyrosine-kinase family, and sis, belonging to the cellular-growth-factor family, were found to have higher signals (3.6-fold and 1.8-fold respectively) in MH-02 than in ML-01 cells. To explore the possibility that higher expression of these oncogenes is involved in enhanced metastasis of the MH-02 clone, ML-01 was transfected by a fyn vector and the metastatic potential of the transfectant was examined. Mice administered fyn-transfected ML-01 cells had significantly increased metastatic nodules in the lung, as compared with those whose ML-01 cells were transfected with control vector without the fyn gene. The result indicates that the fyn gene is one of the factors governing the metastatic potential of Meth A cells.     

A novel arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma after vascular supply distribution via superselective embolization

BACKGROUND: Patients with American Joint Committee on Cancer Stage IV advanced pancreatic carcinoma have been treated by systemic chemotherapy, intraarterial chemotherapy, radiation therapy, and multidisciplinary treatment using a combination of these. However, the outcome has not always been satisfactory. In the current study the authors describe the method and results of a new chemotherapy for advanced pancreatic carcinoma. METHODS: To restrict the blood flow into the pancreas (mainly to the great pancreatic artery and the caudal pancreatic artery), the peripancreatic blood vessels were embolized superselectively with microcoils. In 31 patients with advanced pancreatic carcinoma, the catheter tip for the arterial infusion chemotherapy was placed in the splenic artery just proximal to the branching of the great pancreatic artery when the treatment was given for primary tumors, and in the common hepatic artery when the treatment was given for a metastatic liver lesion. The other end of the catheter was connected to an implanted injection port embedded in the femoral region, and 5-fluorouracil and cisplatin were administered by continuous arterial infusion. RESULTS: Of the 31 patients with advanced pancreatic carcinoma, 23 (74%) underwent hemodynamic change and arterial infusion chemotherapy, with a response rate of 73.9% (complete response rate of 8.7% and a partial response rate of 65.2%) and a mean survival period of 18.26 +/- 10.06 months. The 1-year, 2-year, and 3-year survival rates were 90.9%, 42. 8%, and 18.3%, respectively, with a mean survival period of 19.0 months. Of these 23 patients, the 16 patients with liver metastases had a response rate of 68.8% and a mean survival period of 16.25 +/- 8.35 months, whereas the 7 patients without liver metastases had a response rate of 87.5% and a mean survival period of 22.86 +/- 12.69 months. CONCLUSIONS: In patients with Stage IV advanced pancreatic carcinoma, arterial infusion chemotherapy after hemodynamic change was found to be effective against both primary tumors and metastatic liver lesions. The authors believe that the treatment presented in the current study should be attempted, even in patients with advanced pancreatic carcinoma, as long as the blood vessels for vascular supply distribution exist.     

High resolution MR imaging of the bilateral hips with dual phased-array coil

We applied dual-flex coils in a phased-array configuration to obtain high resolution MR images of the bilateral hips and compared the image quality with non-phased-array imaging. Multiple fast spin-echo images of both hips were obtained in a single acquisition. Two consecutive acquisitions with and without phased-array capability were performed in 22 hips and a fluid-filled phantom. The signal-to-noise ratio (S/N) enhancement values were calculated. Subjective image analysis was also obtained from three independent reviewers. High quality MR images were obtained using dual-array coils with a S/N enhancement value of 1.40 for a phantom and 1.83 to 2.22 for subject hips. On subjective analysis, the dual array enhanced delineation of the acetabular labrum, articular cartilage, and retained fluid. The dual array may be of diagnostic value with a higher S/N enhancement and subjective superiority of the images obtained.     

Slightly flexed knee position within a standard knee coil: MR delineation of the anterior cruciate ligament

The purpose of this study was to assess the value of positioning the knee slightly flexed within a standard MR knee coil in delineation of the anterior cruciate ligament (ACL). Within the confined space of a commercially available knee coil, knee could bend as much as 30 °, average 17 °of flexion. Sets of oblique sagittal MR images were obtained at both fully extended and slightly flexed positions. Twenty-two normal knees and 18 knees with ACL tears were examined and paired MR images were evaluated by two observers. Compared with knee extension, the MR images for knee flexion provided better clarity in 57 % of reviews of full length of the ACL and 53 % of the femoral attachment. In the extended position the anterior margin of the ligament was obscured due to partial averaging with the intercondylar roof. We recommend examining the knee in an achievable flexed position within the standard knee coil. Received 3 December 1996; Revision received 24 February 1997; Accepted 9 April 1997