Comparisons of direct costs,outcomes, and cost-utility of decompression surgery with fusion versus decompression alone for degenerative lumbar spondylolisthesis

Background

Cost-utility analysis of surgery for degenerative lumber spondylolisthesis (DS) is essential for healthcare providers and patients to select appropriate treatment. The purpose of this study was to review the cost-utility of decompression alone versus decompression with fusion for DS.

Phase II study of KRN8602, 3′-deamino-3′-morpholino- 13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 · HCl in patients with metastatic breast cancer

Purpose: KRN8602 (3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 · HCl) is a newly developed anthracycline that has been found to be effective against multidrug-resistant tumor cells in vitro and in vivo. In order to clinically confirm these promising preclinical observations, we performed a phase II trial of KRN8602 in patients with anthracycline-resistant metastatic breast cancer. Methods: Of 41 patients registered with metastatic breast cancer, 37 were eligible and were given at least two cycles of KRN8602 15 mg/m² per day at 3–4 week intervals by intravenous bolus injection on days 1, 2, and 3. Results: Of the 37 patients, 6 (16.2%, with a 95% confidence interval of 4.3–28.1%) had a partial response (PR). No complete responses (CRs) were observed. The difference between response rates according to prior history of anthracycline administration was not significant. Myelosuppression was moderately severe, with grade 3 or 4 leukopenia occurring in 65%. Severe nausea/vomiting was observed in 44% of the patients. Conclusions: The results indicate that KRN8602 has modest activity in refractory metastatic breast cancer and is associated with relatively severe toxicity. Furthermore, the preclinical finding that KRN8602 overcomes anthracycline resistance was not reliably reproduced in this clinical phase II trial. Received: 20 May 1998 / Accepted: 15 October 1998     

Demonstration of enhanced iodine K-edge imaging using an energy-dispersive X-ray computed tomography system with a 25 mm/s-scan linear cadmium telluride detector and a single comparator

An energy-dispersive (ED) X-ray computed tomography (CT) system is useful for carrying out monochromatic imaging. To perform enhanced iodine K-edge CT, we developed an oscillation linear cadmium telluride (CdTe) detector with a scan velocity of 25 mm/s and an energy resolution of 1.2 keV. CT is performed by repeated linear scans and rotations of an object. Penetrating X-ray photons from the object are detected by the CdTe detector, and event signals of X-ray photons are produced using charge-sensitive and shaping amplifiers. The lower photon energy is determined by a comparator device, and the maximum photon energy of 60 keV corresponds to the tube voltage. Rectangular-shaped comparator outputs are counted by a counter card. In the ED-CT, tube voltage and current were 60 kV and 0.30 mA, respectively, and X-ray intensity was 14.8 μGy/s at 1.0m from the source at a tube voltage of 60 kV. Demonstration of enhanced iodine K-edge X-ray CT for cancer diagnosis was carried out by selecting photons with energies ranging from 34 to 60 keV.     

Significance of remyelination by neural stem/progenitor cells transplanted into the injured spinal cord

Previous reports of functional recovery from spinal cord injury (SCI) in rodents and monkeys after the delayed transplantation of neural stem/progenitor cells (NS/PCs) have raised hopes that stem cell therapy could be used to treat SCI in humans. More research is needed, however, to understand the mechanism of functional recovery. Oligodendrocytes derived from grafted NS/PCs remyelinate spared axons in the injured spinal cord. Here, we studied the extent of this remyelination's contribution to functional recovery following contusive SCI in mice. To isolate the effect of remyelination from other possible regenerative benefits of the grafted cells, NS/PCs obtained from myelin-deficient shiverer mutant mice (shi-NS/PCs) were used in this work alongside wild-type NS/PCs (wt-NS/PCs). shi-NS/PCs behaved like wt-NS/PCs in vitro and in vivo, with the exception of their myelinating potential. shi-NS/PC-derived oligodendrocytes did not express myelin basic protein in vitro and formed much thinner myelin sheaths in vivo compared with wt-NS/PC-derived oligodendrocytes. The transplantation of shi-NS/PCs promoted some locomotor and electrophysiological functional recovery but significantly less than that afforded by wt-NS/PCs. These findings establish the biological importance of remyelination by graft-derived cells for functional recovery after the transplantation of NS/PCs into the injured spinal cord.     

Central neuropathic pain after surgical resection in patients with spinal intramedullary tumor

Study designRetrospective case series.ObjectiveTo examine central neuropathic pain after surgical resection of intramedullary spinal cord tumor (IMSCT).Summary of background dataBecause of the rarity of IMSCT, there is little information about postoperative neuropathic pain after surgical resection.MethodsEighty-five of 105 patients treated surgically for IMSCT at our hospital between 2000 and 2008 completed the Neuropathic Pain Symptom Inventory (NPSI) and the short form (SF)-36 health inventory. The NPSI score was analyzed against the tumor type and the postoperative Japanese Orthopaedic Association (JOA) score for neurological symptoms.ResultsThe mean NPSI score of the patients was 13.5. The subscore for paresthesia/dysesthesia was significantly higher than the other subscores. Analysis of the NPSI scores by tumor type revealed no significant differences among patients with ependymoma, astrocytoma, and vascular tumors. The postoperative JOA score showed a weak negative correlation with the NPSI score in patients with thoracic spinal cord tumor, and no correlation in those with cervical tumor. In the 11 patients with hemangioblastoma, intense pain was reported at the level of the tumor, although postoperative paralysis was mild. All the postoperative SF-36 subscores of our study patients were significantly lower than the national average, and a significant negative correlation was observed between the SF-36 and the NPSI subscores.ConclusionNeuropathic pain after surgical resection reduces the QOL of patients with IMSCTs, and pain severity varies with the tumor's location and histological features, the severity of paralysis, and the location of pain relative to the tumor.     

Postoperative adjuvant therapy with tamoxifen, tegafur plus uracil, or both in women with node-negative breast cancer: a pooled analysis of six randomized controlled trials.

PURPOSE: This article reports the results of a pooled analysis of six randomized trials conducted to study the efficacy of uracil and tegafur (UFT) in the adjuvant treatment of node-negative breast cancer patients. PATIENTS AND METHODS: Six randomized controlled trials on node-negative breast cancer patients were conducted from 1992 through 1995 in Japan that included the three, three-arm trials (control [no adjuvant], UFT, and tamoxifen [TAM] groups) and the three, four-arm trials (control, UFT, TAM, and UFT plus TAM groups). Pooled analysis was performed on the data obtained from these six trials (involving 2,934 patients). RESULTS: Overall survival was compared between the UFT group (including both the UFT group and the TAM plus UFT group) and the non-UFT group (control group and TAM group). A significant difference (P = .04) was observed in 5-year survival rates between the UFT (95.9%) and the non-UFT (94.0%) groups. Overall survival was also compared between the TAM group (TAM group and TAM plus UFT group) and the non-TAM group (control group plus UFT group). The 5-year survival rate (95.2%) in the TAM group was not significantly different from that (93.9%) in the non-TAM group, but the subset analysis showed a significant (P = .01) improvement in the estrogen receptor-positive subset. CONCLUSION: Adjuvant UFT improves the overall survival of node-negative breast cancer patients. Given that UFT has milder adverse effects, it is suggested that UFT can be a useful alternative to doxorubicin and cyclophosphamide, or cyclophosphamide, methotrexate, and fluorouracil in the adjuvant treatment for node-negative breast cancer.     

Detection of Increased Fecal Carcinoembryonic Antigen and Its Characterization as a Membrane-bound Form in Colorectal Carcinoma and Other Gastrointestinal Disorders

The levels and character of carcinoembryonic antigen (CEA) in feces were investigated by sandwich radioimmunometric assay using anti-CEA monoclonal antibodies NCC-CO-411 and NCC-CO-432. Mean CEA concentration was significantly higher ( P < 0.001) in the feces from patients with colorectal carcinoma and other gastrointestinal disorders as compared to normal adults. More than 90% of the fecal CEA was trapped by a 0.22 μ m membrane filter and solubilized by treatment with 1% Triton X-100 or phosphatidyl-inositol specific phospholipase C. In hydrophobic chromatography, most of the fecal CEA was eluted at the lowest (NH₄)₂SO₄ concentration while serum CEA appeared in the more hydrophilic fractions. These results suggest that the majority of CEA exists in feces as an amphiphilic molecule or a membrane-bound form. The increase of fecal CEA may reflect the destruction and abrasion of epithelial cells in various gastrointestinal disorders.     

Immunohistochemical study of medullary thyroid carcinoma: Relationship of clinical features to prognostic factors in 36 patients

This study was designed to identify 11 different antigens including calcitonin (CT), calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), and carcinoembryonic antigen (CEA), in the tumors of 36 patients with medullary thyroid carcinoma (MTC) using immunoperoxidase staining techniques. In addition, clinical features of MTC patients were compared with the immunohistochemical findings to establish factors influencing prognosis. MTC was found to contain various products in many patients and CT and CEA were positive in all patients. CGRP and GRP showed positive staining in 96.6% and 82.9% of MTC patients, respectively, suggesting that CGRP and GRP are novel tumor markers for MTC. In tumor cells, CT, CGRP, and GRP were often revealed in identical cells. Familial patients showed more multiple substances than sporadic patients. In the 2 inoperable patients with extremely aggressive progression, tumors showed undifferentiated histology and poor staining for peptide hormones, suggesting that specific qualities such as neuroendocrine tumor had been lost. These 2 patients particularly revealed an inverse relationship between CT and CEA distribution such that small amounts of CT were present in cells which have homogenous staining for CEA. This study suggests that CGRP and GRP, in addition to CT and CEA, may be a histologically potential tumor marker for MTC. CT and CEA may be possible markers for differentiating patients with high malignancy from those with ordinary malignancy.

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Resumen Este estudio fue diseñado con el fín de identificar 11 antígenos diferentes, incluyendo calcitonina (CT), péptido calcitonina gen-relacionada (PCGR), péptido liberador de gastrina (PLG), y antígeno carcinoembriónico (ACE), en los tumores de 36 pacientes con carcinoma medular de tiroides (CMT) utilizando técnicas de coloración con inmunoperoxidasa. Además, se compararon las características clínicas del CMT con los hallazgos inmunohistoqufmicos para definir factores que tengan influencia sobre el pronóstico. Se encontró que el CMT contiene una variedad de productos en muchos de los pacientes y que la CT y el ACE fueron positivos en la totalidad de los pacientes. El PCGR y PLG mostraron coloración positiva en 96.6% y 82.9% de los pacientes, respectivamente, lo cual sugiere que el PCGR y el PLG son noveles marcadores tumorales del CMT. En las células tumorales comparadas en secciones adyacentes apareadas, las 3 hormonas, CT, PCGR, y PLG fueron frecuentemente demostrados en células idénticas. Los pacientes con enfermedad de tipo familiar exhibieron mayor número de sustancias múltiples que los pacientes con enfermedad esporádica. En los 2 pacientes inoperables con progresión tumoral de extrema agresividad, los tumores mostraron indiferenciación en la histología y pobre coloración para las hormonas péptidos, lo cual sugiere que se habían perdido sus cualidades específicas como tumores neuroendocrinos. Estos 2 pacientes, en particular, revelaron una relación inversa entre la distribución de CT y de ACE, tal que pequeñas cantidades de CT estaban presentes en células que exhibían coloración homogénica para ACE. Este estudio sugiere que el PCGR y el PLG, además de la CT y el ACE, pueden ser potenciales marcadores tumorales para CMT. La CT y el ACE pueden ser posibles marcadores para diferenciar los pacientes con severo grado de malignidad de aquellos con malignidad ordinaria.

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Résumé Cette étude a été élaborée pour identifier 11 antigènes différents, y compris la calcitonine (CT), la peptide codée par le gène calcitonine (PCGC), la peptide de stimulation de la gastrine (PSG), et ACE dans les tumeurs de 36 patients ayant un cancer médullaire de la thyroïde (CMT) avec la technique de coloration immunopéroxidase. La clinique des patients ayant un CMT a été comparée aux données immunohistochimiques pour établir des facteurs influençant le pronostic. Les CMT contenaient de nombreuse substances chimiques chez la plupart des patients. La CT et ACE étaient positifs chez tous les patients. La PCGC et la PSG se coloraient positivement chez 96.6 et 82.9% des patients à CMT, respectivement, suggérant que la PCGC et la PSG sont des marqueurs tumoraux potentiels pour le CMT. Dans les cellules tumorales, CT, PSGC., et PSG ont été souvent identifiées dans les mêmes cellules. En général on a trouvé plus d'antigènes chez les patients à CMT familiaux que chez les patients à CMT sporadiques. Chez les 2 patients inopérables chez qui l'évolution était extrêmement agressive, ces tumeurs étaient histologiquement indifférenciéés et la coloration pour ces hormones, pauvres, suggèrant une perte des caractères spécifiques neurendocrines de la tumeur. Chez ces 2 patients, la distribution de CT et d'ACE était inversement proportionnelle l'une par rapport à l'autre: la quantité de CT était réduite dans les cellules alors que la coloration pour l'ACE était homogène. Les résultats de cette étude suggèrent que la PCGC et la PSG, comme le sont déjà la CT et l'ACE, sont peut-être des marqueurs tumoraux pour le CMT. Il est possible que la CT et l'ACE puissent être utilisés pour différencier les patients à haut degré de malignité.

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Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.     

Two cases of rectal carcinoma associating aorto-iliac occlusive disease

Two cases of rectal carcinoma associating aorto-iliac occlusive disease are presented. These two cases had complete obstruction of the affected vessels, but many collateral pathways from the aorta to the legs had developed, mainly through the superior rectal artery or parietal vessels. Changes in blood flow to the legs, following the radical operation for rectal carcinoma, were examined by both preoperative angiography and perioperative Doppler flow meter. Vascular reconstruction was carried out in one case prior to resection of the rectum, in order to prevent the ischemic legs from becoming worse, or necrotic. The indications for supportive vascular surgery in the case of rectal carcinoma with aorto-iliac occlusive disease are discussed herein.     

A standardized method of using nude mice for the in vivo screening of antitumor drugs for human tumors

Human tumors transplanted into nude mice have long been used to assess the effectiveness of antitumor drugs and yet there is still no established standard method in preclinical practice for screening new antitumor drugs in vivo using nude mice. Thus, a cooperative study on the feasibility of a human tumor / nude mouse system for the in vivo screening of drugs was conducted by the Japanese Research Society for Chemosensitivity of Cancer. Two human stomach cancers, H-111 and SC-6-JCK, and one human colon cancer, Co-4, were transplanted serially into nude mice and used as gastrointestinal tract tumors with stable tumor growth. The appropriate dosage of six well-known antitumor drugs [mitomycin C (MMC), cyclophosphamide (CPA), nimustine hydrochloride 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), cis-platinum (II) diaminodichloride (CDDP), adriamycin (ADM) and 5-fluorouracil (5-FU)] in human tumor-bearing nude mice was determined based on the maximum tolerance dose of the drug. The respective dosages were 6 mg/kg of MMC×1 (i.p.), 120 mg/kg of CPA×1 (i.p.), 30 mg/kg of ACNU×1 (i.p.), 8 mg/kg of CDDP×1 (i.p.), 8 mg/kg of ADM×1 (i.v.), and 50 mg/kg of 5-FU q4d×3 (i.p.). Three weeks after treatment, drug effectiveness was judged by the tumor growth inhibition rate. Treatment with these appropriate doses appeared to show the maximum effect of the respective drugs on the tumor-bearing nude mice. This standardized method using nude mice should contribute to the screening of new antitumor drugs against human tumors, especially those of the gastrointestinal tract. The antitumor activity of new drugs on human tumors in vivo may now be determined by comparison with that of well-known antitumor drugs on human tumor-bearing nude mice.Constituting The Japanese Research Society for Chemosensitivity of Cancer (JRSCC)Affiliated members of JRSCC (Chairman: Tatsuhei Kondo) are: NU; Nagoya University (Second department of Surgery) RIMDOU; Research Institute for Microbial Disease, Osaka University (Department of Surgery) KU; Keio University (Department of Surgery) RINMBHU; Research Institute for Nuclear Medicine and Biology, Hiroshima University (Department of Surgery) TH; Tenri Hospital (Thoracic Surgery) RITCTU; Research Institute for Tuberculosis and Cancer, Tohoku University (Department of Clinical Chemotherapy in Medicine)