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  • 1
    ISSN: 1442-2042
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The purpose of this study was to investigate the potential of combining cytosine deaminase/5-fluorocytosine (CD/5-FC) gene therapy and radiation therapy (either external beam radiation or radioimmunotherapy [RIT]), for the treatment of prostate cancer.Methods: Tumor xenografts of CD-transduced LNCaP cells grown in the testes of severe combined immunodeficiency (SCID) mice were used to evaluate antitumor effect. The mice were injected intraperitoneally with 500 mg/kg of 5-FC, or with 5, 15 or 30 mg/kg of 5-fluorouracil (5-FU), for 9 days. The tumors were treated with fractionated radiation at a dose of 1 or 3 Gy/day for 3 days, or I-131 labelled anti-prostate specific antigen (anti-PSA) monoclonal antibody (mAb) administration at a subtherapeutic dose of 20 or 80 µCi. Intratumoral and serum concentrations of 5-FU were measured using high performance liquid chromatography.Results: Mice treated with CD/5-FC gene therapy presented a significant tumor growth inhibition comparable to that obtained with 15 mg/kg, 5-FU systemic administration without marked weight loss. Treatment with CD/5-FC gene therapy resulted in higher tumor but lower serum concentrations of 5-FU than treatment with systemic 5-FU chemotherapy. An additive antitumor effect was obtained when CD/5-FC therapy was combined with 1 Gy irradiation, which by itself did not produce a significant antitumor effect. However, the efficacy of CD/5-FC therapy was not enhanced when combined with RIT, probably due to poor accumulation of the mAb as the tumor/blood ratio never exceeded 1.Conclusion: These findings indicate that CD/5-FC gene therapy for prostate cancer may function with enhanced antitumor effect when combined with external beam radiation. However, combining CD/5-FC gene therapy and RIT using an anti-PSA mAb may not be effective because of insufficient accumulation of the mAb at the target tumors.
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  • 2
    ISSN: 1432-1335
    Keywords: Key words Radioimmunotherapy ; 5-Fluorouracil ; Additive effect ; Colon cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:The feasibility of radioimmunotherapy (RAIT) combined with 5-fluorouracil (5-FU) was examined in colon cancer xenografts. The mode of interaction of the two treatments was also investigated. Methods : Mice bearing human colon cancer were treated with a combination of 4.63 MBq (L-RAIT) or 9.25 MBq (H-RAIT) 131I-A7, an IgG1 against 45-kDa glycoprotein, and 5-FU at a dose of 30 mg kg−1 day−1 for 5 days. Myelotoxicity was monitored by blood cell counts and intestinal toxicity was assessed by the dosimetry. The results were compared with those of a single-modality therapy. Results : The combination of 5-FU with H-RAIT enhanced the antitumor effect, improving the tumor quadrupling time from 25.3 ± 9.59 days to 31.3 ± 8.32 days (P 〈 0.05) and inducing tumor regression in 7 out of 10 mice, compared to 3 out of 9 mice treated with H-RAIT alone. The efficacy of L-RAIT was also improved by the combination. Analysis of the dose/response relationship showed an additive interaction of the two modalities. The combination of 5-FU with RAIT induced slightly more severe myelotoxicity than a single-modality treatment, but blood cell counts recovered similarly. Dose estimation suggested that RAIT does not increase the intestinal toxicity of 5-FU. Conclusion : The combination of two modalities would be feasible for the treatment of colon cancer, increasing antitumor effect with minor effect on toxicity.
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  • 3
    ISSN: 1434-0879
    Keywords: Key words Immunolocalization ; Placental alkaline phosphatase ; Testicular tumor ; Lymph node metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the ability of an anti-placental alkaline phosphatase (PLAP) monoclonal antibody (MAb) to localize to PLAP-expressing tumors, we established a model of testicular tumor with metastasis to lymph nodes and liver in severe combined immunodeficient (SCID) mice. 131I-labeled or 125I-labeled MAb was simultaneously administered via the intravenous or lymphatic route, respectively. Preferential accumulation of MAb in PLAP-expressing tumors at primary as well as metastatic sites was demonstrated. The percentage of the injected dose of MAb found in the tumor was generally higher when MAb was administered intravenously. Identical tumor/blood ratios were found with the two routes of administration. These data suggest that intravenous administration of a radiolabeled MAb is superior to lymphatic administration for tumor imaging and radioimmunotherapy.
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  • 4
    ISSN: 1432-0509
    Keywords: Acute cholecystitis, diagnosis ; Hepatobiliary imaging, technique ; Radionuclide angiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The diagnostic values of hyperperfusion to the gallbladder fossa and the rim sign were retrospectively evaluated in 24 histopathologically proven cases of gallbladder disease. Although 12 of 13 patients (92%) with acute cholecystitis had nonvisualization of the gallbladder, the positive predictive value with this finding was 71%. However, when the finding was associated with hyperperfusion to the gallbladder fossa or the rim sign, the positive predictive value with both (90%) was markedly increased compared to the prevalence ratio of 54%. Such a combination could be useful for preserving a high positive predictive value in the diagnosis of acute cholecystitis.
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  • 5
    ISSN: 1619-7089
    Keywords: Portal circulation ; Enteric coated capsule of thallium-201 ; Portal systemic shunting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new method of oral administration of an enteric coated capsule of 201Tl (201Tl-capsule) was developed to evaluate the portal circulation through the superior mesenteric vein (SMV). The 201Tl-capsule was not collapsed in the artificial gastric juice, whereas it melted soon after soaking in the artificial intestinal juice. In a clinical trial of 42 cases, 201Tl was satisfactory released in the duodenum in 36 cases where clear liver images were observed except in 1 patient. Heart to liver ratio (H/L) at 60 or 90 min after duodenal release of 201Tl was 0.32±0.07 (mean±1 s.d.) in normal controls, 0.34±0.12 in chronic hepatitis, 0.31±0.12 in acute hepatitis, 0.45±0.13 in liver cirrhosis and 0.48±0.32 in cirrhosis with hepatocellular carcinoma. In 11 patients who had both oral and rectal studies with 201Tl, 7 showed a high H/L ratio of more than 0.8 in the rectal study but only 1 showed a similarly high ratio of 1.07 in the oral study. In the group of varied liver disorders we have studied so far, it was found that most of the SMV blood flowed into the liver and the degree of portal systemic shunting (PSS) from the SMV was much smaller compared to that from the inferior mesenteric vein. The present study with oral administration of the 201Tl-capsule was of value in understanding portal circulation through the SMV, however, this technique seemed of limited usefulness for evaluating overall pathologic PSS.
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  • 6
    ISSN: 1619-7089
    Keywords: Thymus ; Thyroid carcinoma ; Iodine-131 treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two cases of papillary carcinoma of the thyroid are presented in which whole-body scans following therapeutic doses of iodine-131 revealed intense anterior mediastinal uptake. In both cases, the mediastinal uptake was absent from scans obtained after removal of the entire thymus. Histologically, the resected thymus glands showed hyperplasia and contained neither thyroid tissue nor metastatic foci of thyroid carcinoma. We therefore concluded that anterior mediastinal uptake of radioiodine may be caused by hyperplasia of the thymus.
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  • 7
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three cases of CSF leaks that did not communicate with the body surface were diagnosed and followed using radionuclide myelography or cisternography. The utility and advantages of this definitive diagnostic method are discussed.
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  • 8
    ISSN: 1573-7217
    Keywords: breast cancer ; BCT ; cosmesis ; local control ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the oncologic and cosmetic outcome in patients with breast cancer treated with wide excision, transposition of adipose tissue with latissimus dorsi muscle (LDM), and axillary dissection followed by radiotherapy. In this study, a wide excision of breast tissue was performed to obtain tumor-free margins. The subsequent breast deformity was not corrected in six patients in the early phase of the study (Group 1), and in 16 patients in the late phase (Group 2) in which the breast deformity was not remarkable at the time of operation. Breast deformity was corrected by transposing adipose tissue with LDM on a vascular pedicle in the remaining 51 patients (Group 3). Five year survival was 100%. Two patients developed distant metastases. None were found to have local recurrence. Fifty percent of the Group 1 patients, 69% of the Group 2 patients, and 67% of the Group 3 patients had an excellent or good cosmetic result. However, when the cosmetic results were evaluated in patients who underwent transposition and had small breasts, the results were excellent or good in 76%, compared to 38% in the patients who had reconstructions who had large breasts. The difference was statistically significant (p = 0.0309). Therefore, it was confirmed that wide excision and axillary dissection followed by breast radiation could provide adequate local control, but frequently resulted in breast deformity. However, transposition of adipose tissue may be useful to correct the breast deformity, especially in women with small breasts.
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  • 9
    ISSN: 1573-7217
    Keywords: axillary dissection ; breast cancer ; prognosis ; sentinel node dissection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seventy‐two patients underwent dye‐guided or dye‐ and gamma probe‐guided sentinel lymphadenectomy (SLND) followed by complete axillary lymph node dissection (ALND). The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) were compared to each other and to the histologic findings in the nonsentinel nodes. The SLN was identified in 62 (88%) of 72 patients. Evaluation of the SLN on the permanent sections yielded a diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100, although the reliability of SLN diagnosis using frozen sections or imprint cytology is limited. Therefore, it may be concluded that SLND with multiple sectioning and histopathologic examination of the SLNs can predict the presence or absence of axillary‐node metastases in patients with breast cancer. However, further studies will be needed to investigate the value of SLND in respect to the long‐term regional control and any possible detriment or benefit to survival, before it can replace routine ALND as the preferred staging operation for operable breast cancer.
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  • 10
    ISSN: 1573-7217
    Keywords: axillary dissection ; breast cancer ; sentinel lymphadenectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sentinel lymphadenectomy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. However, controversies remain concerning the optimal method to identify the sentinel lymph node (SLN) and detect micrometastases in this lymph node. We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of preoperative lymphoscintigraphy with intraoperative dye-guided and gamma probe-guided methods achieves a higher rate of identification of SLN than any of these techniques alone. (b) Immediate and reliable intraoperative assessment of sentinel node status is vital to the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot always be identified. (c) Hematoxylin and eosin (H&E) staining and/or immunohistochemistry on permanent sections are useful for the detection of micrometastases in the sentinel node. Although a reverse transcriptase–polymerase chain reaction (RT–PCR) method is more sensitive than H&E staining and immunohistochemistry, it would not distinguish benign from malignant epithelial cells in the SLN. Therefore, further study is required before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer.
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