Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Clinical Trial.

PURPOSE: External-beam radiation therapy (RT) is standard of care (SOC) for pain relief of symptomatic bone metastases. We aimed to evaluate the efficacy of radiation to asymptomatic bone metastases in preventing skeletal-related events (SRE). METHODS: In a multicenter randomized controlled trial, adult patients with widely metastatic solid tumor malignancies were stratified by histology and planned SOC (systemic therapy or observation) and randomly assigned in a 1:1 ratio to receive RT to asymptomatic high-risk bone metastases or SOC alone. The primary outcome of the trial was SRE. Secondary outcomes included hospitalizations for SRE and overall survival (OS). RESULTS: A total of 78 patients with 122 high-risk bone metastases were enrolled between May 8, 2018, and August 9, 2021, at three institutions across an affiliated cancer network in the United States. Seventy-three patients were evaluable for the primary end point. The most common primary cancer types were lung (27%), breast (24%), and prostate (22%). At 1 year, SRE occurred in one of 62 bone metastases (1.6%) in the RT arm and 14 of 49 bone metastases (29%) in the SOC arm (P < .001). There were significantly fewer patients hospitalized for SRE in the RT arm compared with the SOC arm (0 v 4, P = .045). At a median follow-up of 2.5 years, OS was significantly longer in the RT arm (hazard ratio [HR], 0.49; 95% CI, 0.27 to 0.89; P = .018), which persisted on multivariable Cox regression analysis (HR, 0.46; 95% CI, 0.23 to 0.85; P = .01). CONCLUSION: Radiation delivered prophylactically to asymptomatic, high-risk bone metastases reduced SRE and hospitalizations. We also observed an improvement in OS with prophylactic radiation, although a confirmatory phase III trial is warranted.

A robust control system for targeting melanoma by a supermolecular DDMC/paclitaxel complex.

A DEAE-dextran-MMA copolymer (DDMC)-paclitaxel (PTX) conjugate was prepared using PTX as the guest and DDMC as the host. The resistance of B16F10 melanoma cells to PTX was confirmed, while the DDMC-PTX conjugate showed excellent anticancer activity that followed the Hill equation. The robustness in the tumor microenvironment of the allosteric system was confirmed via BIBO stability. This feedback control system, explained via a transfer function, was very stable and showed the sustainability of the system via a loop, and it showed superior anti-cancer activity without drug resistance from cancer cells. The block diagram of this signal system in the tumor microenvironment used its loop transfer function G(s) and the dN(s) of the external force. This indicial response is an ideal one without a time lag for the outlet response. The cell death rate of DDMC-PTX is more dependent on the Hill coefficient n than on the Michaelis constant Km. This means that this supermolecular reaction with tubulin follows an "induced fit model".

Impact of NADiA ProsVue PSA slope on secondary treatment decisions after radical prostatectomy.

BACKGROUND: Selecting appropriate candidates for postprostatectomy radiotherapy is challenging, because adverse pathological features cannot accurately predict clinical recurrence. Biomarkers that identify residual disease activity may assist clinicians when counseling patients on the risks, benefits and costs of secondary treatment. NADiA ProsVue PSA slope results ≤2.0 pg ml(-1) month(-1) are predictive of a reduced risk of clinical recurrence; however, its clinical utility has not yet been studied. METHODS: We prospectively enrolled men treated by radical prostatectomy in a multicenter, institutional review board-approved clinical trial. At postsurgical follow-up, investigators (N=17) stratified men into low-, intermediate- or high-risk groups for prostate cancer recurrence based on clinicopathological findings and other factors. Investigators documented their initial treatment plan for each subject and serially collected three serum samples for ProsVue testing. After the ProsVue result was reported, investigators recorded whether or not the initial treatment plan was changed. The proportion of cases referred for secondary treatment before and after ProsVue was reported, and the significance of the difference determined. RESULTS: Complete assessments were reported for 225 men, 128 (56.9%) of whom were stratified into intermediate- and high-risk groups. Investigators reported that they would have referred 41/128 (32.0%) at-risk men for secondary treatment. However, after results were known, they referred only 15/128 (11.7%) men. The difference in proportions (-20.3%, 95% confidence interval (CI) -29.9 to -10.3%) is significant (P<0.0001). Odds of a referral was significantly reduced after results were reported (odds ratio 0.28, 95% CI 0.15-0.54, P<0.0001). CONCLUSIONS: Knowledge of a ProsVue result had significant impact on the final treatment plan. A ProsVue result ⩽2.0 pg ml(-1) month(-1) significantly reduced the proportion of men at risk of recurrence who otherwise would have been referred for secondary treatment.

Safety of snake antivenom immunoglobulins: efficacy of viral inactivation in a complete downstream process.

Viral safety remains a challenge when processing a plasma-derived product. A variety of pathogens might be present in the starting material, which requires a downstream process capable of broad viral reduction. In this article, we used a wide panel of viruses to assess viral removal/inactivation of our downstream process for Snake Antivenom Immunoglobulin (SAI). First, we screened and excluded equine plasma that cross-reacted with any model virus, a procedure not published before for antivenoms. In addition, we evaluated for the first time the virucidal capacity of phenol applied to SAI products. Among the steps analyzed in the process, phenol addition was the most effective one, followed by heat, caprylic acid, and pepsin. All viruses were fully inactivated only by phenol treatment; heat, the second most effective step, did not inactivate the rotavirus and the adenovirus used. We therefore present a SAI downstream method that is cost-effective and eliminates viruses to the extent required by WHO for a safe product.

Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations.

Despite initial dramatic response, epidermal growth factor receptor (EGFR) mutant lung cancer patients always acquire resistance to EGFR-tyrosine kinase inhibitors (TKIs). Gatekeeper T790M mutation in EGFR is the most prevalent genetic alteration underlying acquired resistance to EGFR-TKI, and EGFR mutant lung cancer cells are reported to be addictive to EGFR/Akt signaling even after acquired T790M mutation. Here, we focused on Akt kinase-interacting protein1 (Aki1), a scaffold protein of PI3K (phosphoinositide 3-kinase)/PDK1 (3-phosphoinositide-dependent protein kinase)/Akt that determines receptor signal selectivity for non-mutated EGFR, and assessed its role in EGFR mutant lung cancer with or without gatekeeper T790M mutation. Cell line-based assays showed that Aki1 constitutively associates with mutant EGFR in lung cancer cells with (H1975) or without (PC-9 and HCC827) T790M gatekeeper mutation. Silencing of Aki1 induced apoptosis of EGFR mutant lung cancer cells. Treatment with Aki1 siRNA dramatically inhibited growth of H1975 cells in a xenograft model. Moreover, silencing of Aki1 further potentiated growth inhibitory effect of new generation EGFR-TKIs against H1975 cells in vitro. Aki1 was frequently expressed in tumor cells of EGFR mutant lung cancer patients (53/56 cases), including those with acquired resistance to EGFR-TKI treatment (7/7 cases). Our data suggest that Aki1 may be a critical mediator of survival signaling from mutant EGFR to Akt, and may therefore be an ideal target for EGFR mutant lung cancer patients, especially those with acquired EGFR-TKI resistance due to EGFR T790M gatekeeper mutation.

Treprostinil, a prostacyclin analog, ameliorates ischemia-reperfusion injury in rat orthotopic liver transplantation.

Prostaglandins have been evaluated for their ability to reduce IRI after liver transplantation; however, poor stability, side effects and the inability to show a significant difference in primary endpoint have limited their clinical application. Treprostinil, a prostacyclin (PGI(2) ) analog, has a higher potency and longer elimination half-life than other commercially available PGI(2) analogs. We examined the efficacy of treprostinil to prevent IRI during OLT. OLT was performed in syngeneic Lewis rats after 18 h of cold preservation (4°C) in the UW solution. IRI significantly increased serum ALT and AST levels, neutrophil infiltration, hepatic necrosis and mRNA levels of proinflammatory cytokines post-OLT, while treatment with treprostinil decreased all the parameters. Cold storage of liver grafts significantly reduced ATP levels and treprostinil restored energy levels in liver grafts early postreperfusion. In addition, treprostinil preserved the sinusoidal endothelial cell lining and reduced platelet deposition early post-transplantation compared to placebo. Hepatic tissue blood flow was significantly compromised in the placebo group, whereas treprostinil maintained blood-flow similar to normal levels. Treprostinil protected the liver graft against IRI during OLT. Treprostinil has the potential to serve as a therapeutic option to protect the liver graft against I/R injury in patients undergoing OLT.

Effect of sonoporation on cationic liposome-mediated IFNbeta gene therapy for metastatic hepatic tumors of murine colon cancer.

To examine the efficacy of ultrasound-mediated gene therapy in the treatment of hepatic cancer, we performed cationic liposome-mediated interferon-beta (IFNbeta) gene therapy combined with sonoporation, using metastatic hepatic tumors of murine colon cancer. The combination of liposome/DNA treatment and ultrasound gave higher transgene IFNbeta expression in Colon26 colon adenocarcinoma cells than that with microbubble/DNA in combination with ultrasound and that with liposome/DNA alone. Cationic liposome-mediated IFNbeta gene therapy combined with ultrasound showed an antitumor effect in vitro and combination use of the anticancer drug cis-diamminedichloroplatinum (CDDP) showed a synergistic effect with the IFNbeta gene therapy. The survival of mice with metastatic hepatic tumor of Colon26 cells was significantly prolonged by cationic liposome-mediated IFNbeta gene therapy alone, and sonoporation had a synergistic effect on prolongation of survival and inhibition of tumor growth rate in these mice. Combination use of CDDP with IFNbeta gene therapy also showed a synergistic effect on prolongation of survival and inhibition of tumor growth rate. In conclusion, ultrasound-mediated gene therapy for the treatment of hepatic cancers may be effective in a clinical setting.

Spinal cord hemangioblastomas in von Hippel-Lindau disease.

STUDY DESIGN: Retrospective data analysis. OBJECTIVE: To clarify the clinical features and surgical management of spinal cord hemangioblastomas in patients with von Hippel-Lindau disease (VHL). SETTING: Clinical VHL Research Group in Japan, Japan. METHODS: Forty-eight out of 66 patients with associated spinal cord hemangioblastoma among 142 VHL patients were retrospectively examined with respect to clinical features, accompanying lesions and outcome of surgical treatment. RESULTS: Among these 48 patients, 46 of them (95.8%) also had a central nervous system (CNS) hemangioblastoma at another site: 42 (87.5%) with cerebellar hemangioblastoma and 11 (22.9%) with brain stem hemangioblastoma. Twenty-three patients (47.9%) had more than one spinal cord hemangioblastoma. The 48 patients with spinal cord hemangioblastomas collectively had a total of 74 tumors. The tumor was accompanied with a syrinx in 64 and without it in 10 patients. Forty of the 48 patients underwent surgical treatment for their spinal cord hemangioblastomas, and 7 of these 40 underwent surgical treatment twice. When functional changes in the patients after these 47 operations were examined by postoperative evaluation by McCormick's classification, 39 of these operations (83.0%) resulted in improvement/no change and 8 (17.0%) in aggravation of symptoms. CONCLUSION: Von Hippel-Lindau disease patients bearing spinal cord hemangioblastomas mostly had a CNS hemangioblastoma at another site. These tumors can be removed in the majority of VHL patients without aggravation. In these patients, when the timing of treatment for spinal cord hemangioblastoma is determined, the probability of occurrence and treatment of other lesions should be considered.

Problems in the current diagnostic standards of clinical N1 non-small cell lung cancer.

BACKGROUND: Although clinical N1 (cN1) non-small cell lung cancer (NSCLC) is considered to be locoregional, the postoperative outcome is disappointing, with a 5 year survival of less than 50%. One possible reason may be that cN1disease diagnosed by current standard imaging modalities often contains unexpected N2 disease. This study was conducted to evaluate the surgical and pathological results of patients with cN1 NSCLC. METHODS: Among 1782 patients with NSCLC who underwent intended curative resection from 1993 to 2003, 143 patients were identified as having cN1 disease and were enrolled in this study. The clinicopathological records and CT films of each patient were retrospectively reviewed to identify predictors for pN2-3 disease. RESULTS: The pathological nodal status was pN0 in 23% (n = 33), pN1 in 47% (n = 67) and pN2-3 in 30% (n = 43) of patients. Patients with pN2-3 showed a significantly worse 5 year survival rate of 38% compared with patients with pN0 (68%) and pN1 (60%) (p = 0.017 and 0.007, respectively). Multivariate analysis showed that adenocarcinoma histology was a significant predictor for pN2-3 disease (OR 3.312, 95% CI 1.439 to 7.784; p = 0.005). The presence of N1 node separate from the main tumour on CT scans tended to predict pN2-3 disease although this did not reach statistical significance (OR 2.103, 95% CI 0.955 to 4.693; p = 0.066). Pathological N2-3 disease was found in 53% of patients with adenocarcinoma with a separate N1 pattern and in only 12% of patients with non-adenocarcinoma with a continuous N1 pattern. CONCLUSIONS: The diagnosis of N1 status by contrast enhanced CT scans is unsatisfactory with a high rate of unexpected pN2 disease. To avoid infertile lung resection, patients with CT diagnosed N1 adenocarcinoma, especially with a separate N1 pattern on CT, should be considered for additional invasive node biopsy modalities, including mediastinoscopy.

Human neural stem cells target and deliver therapeutic gene to experimental leptomeningeal medulloblastoma.

Medulloblastomas are highly malignant neuroectodermal cerebellar tumors of children. One of the reasons for the difficulty for the treatment of medulloblastomas is their inherent tendency to metastasize through the cerebrospinal fluid (CSF) pathway leading to leptomeningeal dissemination. Recently, genetically modified neural stem cells (NSCs) were shown to have the capability of selectively migrating into glioma mass and delivering therapeutic agents with significant therapeutic benefits. In the present study, we applied the NSC strategy to target medulloblastomas, particularly their leptomeningeal dissemination. We used NSCs that were retrovirally transduced with the cytosine deaminase gene (CD-NSCs). In vitro studies demonstrated that CD-NSCs had sufficient migratory activity toward medulloblastoma cells and exerted a remarkable bystander effect on these cells following the application of 5-fluorocytosine (5-FC). It is noteworthy that neutralization of the hepatocyte growth factor blocked their migration In animal studies using our leptomeningeal dissemination model, CD-NSCs implanted directly into CSF space were shown to distribute diffusely within the disseminated tumor cells and could provide remarkable antitumor effect after intraperitoneal administration of 5-FC. Furthermore, CD-NSC treatment followed by 5-FC administration prolonged survival periods significantly in experimental animals. Our data suggest that the CD-NSC strategy can also be applied to target leptomeningeal dissemination of medulloblastomas.

Structure-based design of an agonistic peptide targeting Fas.

A small agonistic peptide FRAP-4 (WEWT, Fas reactive peptide-4) that binds to the human Fas molecule was discovered using our computer screening strategy named the Amino acid Complement Wave (ACW) method, which is based on the complementarities of interacting amino acids between comprehensive testing peptides and a target protein surface pocket. In silico docking studies demonstrated the specific interaction of FRAP-4 with the main Fas ligand (FasL) binding domain in the Fas molecule. An octamer of this peptide produced by carboxyl terminal linkages of polylysine branches (MAP), (FRAP-4)8-MAP, effectively induced apoptosis in human ovarian cancer cell line NOS4 cells that was associated with the activation of caspases-8, -9 and -3, and the cleavage of PARP. Alanine substitution of the N-terminal W in FRAP-4 resulted in complete loss of FasL-mimetic action of (FRAP-4)8-MAP, suggesting that the aromatic functionality at the N-terminal position W appears to play an essentially important role in Fas binding ability. These observations indicate that the FasL-mimetic peptide should serve as an excellent starting point for the design of effective compounds with FasL-mimetic activity. Furthermore, the ACW method for the structure-based design of optimized small peptides against receptor molecules such as Fas could open new avenues for the development of peptide mimetic and nonpeptidic organic forms to generate novel effective pharmaceuticals.

Vascular supply of the subcutaneous pedicle of Nagata's method in microtia reconstruction.

Nagata's method is a two-stage method for total ear reconstruction in patients with microtia. In the first stage of this procedure, mastoid flap and posterior lobule flap are elevated with a subcutaneous pedicle. However, contribution to the vascular supply by this pedicle has been controversial. We investigated the presence or absence of apparent vessels in the subcutaneous pedicle in 14 primary cases of microtia in the first stage operation. In all cases some vessels were included in the pedicle. In lobular and small concha type microtia, the vessels originated from the parotid fascia or aponeurotic tissue behind the remnant cartilage. In concha type microtia, apparent vessels could be preserved by including the perichondrium of the conchal cartilage. These findings suggest that the mastoid and posterior lobule flaps or W-shaped flap in Nagata's first stage operation are actually the perforator-based flaps. The source vessel of the perforators seemed to be the posterior auricular artery because of its location although further dissection was not performed in order not to damage the vascular supply. The presence of the vessels can augment the blood supply of not only W-shaped flaps but also the skin flap cephalad to them. By confirming the preservation of the perforators in the subcutaneous pedicle the surgeon may be able to trim the covering skin more safely.

Sequential delivery of interferon-alpha gene and DCs to intracranial gliomas promotes an effective antitumor response.

Effective presentation of tumor antigens by dendritic cells (DCs) is considered to be essential for the induction of antitumor T-cell responses. Apoptotic and necrotic tumors have been noted to be a robust antigen source for DCs. Because glioma cells undergo apoptosis after transfection with the type I interferon (IFN) gene and type I IFNs promote the stimulatory activity of DCs, we hypothesized that transfection of glioma cells with type I IFN genes and provision of DCs would promote particularly effective antitumor activity by both facilitating apoptosis of glioma cells and the presentation of the glioma antigens, thereby inducing specific immune responses against glioma cells. We have previously reported the proof of this hypothesis in vitro and in a subcutaneous tumor model. Here we report an extension of this approach in intracranial (i.c.) gliomas using adenoviral IFN-alpha (Ad-IFN-alpha) vector. Mice bearing day-5 i.c. GL261 glioma received sequential intratumoral (i.t.) delivery of Ad-IFN-alpha and bone marrow-derived syngeneic DCs. This treatment prolonged survival in that nine of 17 animals survived long term (> 60 days versus 0 of 10 control animals). Specific CTL activity was demonstrated following this regimen in the cervical lymph nodes, and the therapeutic efficacy was dependent upon CD8+ cells. Furthermore, these animals were protected against subsequent re-challenge with GL261 gliomas. DCs injected i.t. survived in the tumor and migrated into cervical lymph node. In vitro migration assays revealed the ability of DCs to migrate toward the tumor, suggesting that i.t. injected DCs migrate through the glioma. Taken together, this combination of gene therapy and cellular immunotherapy may be an effective future strategy for treating human gliomas.

Expression of Ki-67 antigen and vascular endothelial growth factor in sporadic and neurofibromatosis type 2-associated schwannomas.

Neurofibromatosis type 2 (NF2) is a formidable disease with considerable morbidity. Among tumors associated with NF2, schwannomas are the most difficult to treat because they are multiple and tend to recur. Vascular endothelial growth factor (VEGF) has been reported to act as a survival factor for Schwann cells. We, therefore, investigated VEGF expression in NF2-associated and sporadic schwannomas. We also evaluated the proliferative potential of these tumors by Ki-67 staining (MIB-1 labeling index) and microvascular density by CD34 staining. Immunohistochemistry was performed in 8 schwannomas from 6 NF2 patients, 2 schwannomas from 2 probable NF2 patients and 10 sporadic schwannomas. VEGF immunostaining was present in most schwannomas: all sporadic schwannomas and 8 of 10 schwannomas from NF2 or probable NF2 patients (NF2 group). No difference was evident in VEGF staining between the 2 groups. MIB-1 labeling index was significantly higher in the NF2 group (3.8 +/- 1.7) than the sporadic group (2.0 +/- 1.0, p < 0.01). Microvascular density was higher in the NF2 group (12.9 +/- 6.0) than the sporadic group (9.4 +/- 3.5), but not significantly (p = 0.06). Although VEGF alone cannot explain the higher proliferative potential in NF2-associated schwannomas, VEGF could be a factor influencing the proliferative potential of schwannomas.

[Salvage operation for esophageal cancer after radical chemoradiotherapy].

We reviewed salvage surgery cases for esophageal cancer following radical chemoradiotherapy. From January 1998 through January 2001, 6 patients (4 men, 2 women) underwent salvage operation at our department. Mean age was 56 years (range: 46-66). According to the Japanese Society for Esophageal Diseases localization schema, there was one case in the upper third of the thoracic esophagus, 3 cases in the middle third and 2 cases in the lower third. The histology was squamous cell carcinoma in all cases. Our radical chemoradiotherapy regimen for esophageal cancer was fluorouracil (5-FU) 400 mg/m2/24 hours i.v. on days 1 to 5 and 8 to 12, cisplatin (CDDP) 40 mg/m2/2 hours i.v. on days 1 and 8, and concurrent radiation therapy (2 Gy/day on days 1 to 5, 8 to 12 and 15 to 19). This regimen was repeated in 5 weeks, followed by 5-FU 800 mg/m2/24 hours i.v. on days 1 to 5 and CDDP 80 mg/m2/2 hours i.v. on day 1, which was repeated in 4 weeks. After these chemoradiotherapy, patients who were confirmed to have local recurrence or esophagobronchial fistula underwent salvage operation. Postoperative complications were anastomosis leakage in 1 patient, and anastomosis stenosis in 2 and esophagobronchial fistula in 1. Although no postoperative hospitalized death occurred, 1 patient died because of empyema 3 months after salvage operation. Another patient died due to respiratory failure 15 months later. The salvage operation outcomes are not acceptable. Salvage procedure and indication for salvage intervention need to be changed.

Process of apoptosis induced by TNF-alpha in murine fibroblast Ltk-cells: continuous observation with video enhanced contrast microscopy.

Apoptosis is originally defined by unique morphological changes of dying cells, and the biochemical hallmark associated with apoptosis is internucleosomal DNA fragmentation. However, few report has shown the precise time course of the apoptotic events. The present study was designed to try to clarify apoptotic processes using a video-enhanced contrast-differential interference contrast (VEC-DIC) microscopy. The morphological changes of murine fibroblast Ltk-cells treated with TNF-alpha were divided into four stages: (i) pre-apoptotic, (ii) cytoplasmic shrinkage, (iii) membrane blebbing, and (iv) ballooning. Almost of the cells underwent cytoplasmic shrinkage and membrane blebbing within 6 hours after TNF-alpha exposure, and at about 9 hours, they were in the ballooning stage. Based on these data, we investigated the relationship between morphological changes and other biochemical features. The earliest event was exposure of phosphatidyl-serine at the cytoplasmic membrane, which was already observed in the pre-apoptotic stage. Loss of mitochondrial membrane potential was observed in the cytoplasmic shrinkage stage. Caspase-8/-3 activities already started increasing in the pre-apoptotic stage, and reached their peak at 6 hours after TNF-alpha exposure. DNA fragmentation occurred in the late phase of the membrane blebbing.

[Adjuvant GM-CSF cytokine gene therapy for breast cancer].

UNLABELLED: The aim of this study was to examine the enhancement of antitumor immunity of irradiated granulocyte macrophage-colony-stimulating factor (GM-CSF) gene-transduced mouse breast cancer cells. METHODS: BALBMC mouse were vaccinated subcutaneously with saline or irradiated mouse breast cancer cells, BALBMC (1 x 10(6)/mouse), infected or not infected with recombinant adenovirus harboring GM-CSF gene on day-7. Mice were injected with parental cells (1 x 10(5)/mouse) on day 0. RESULTS: No mice vaccinated with irradiated GM-CSF producing BALBMC cells developed a tumor during the observation period of up to 16 weeks, whereas 100% of mice injected with saline developed a tumor. CONCLUSION: Our study demonstrates the feasibility of this immunotherapeutic approach as a novel adjuvant cancer therapy after surgery for breast cancer.

[Docetaxel was effective as neoadjuvant chemotherapy for patients after failure of trans-arterial neoadjuvant chemotherapy with CEF in 2 cases of advanced breast cancer].

Docetaxel was effective as a second line neoadjuvant chemotherapy after failure of cyclophosphamide, epirubicin and 5-FU (CEF) in 2 cases of breast cancer. In Case 1, 4 cycles of trans-arterial neoadjuvant chemotherapy of docetaxel showed a PR effect after failure of 2 cycles of trans-arterial neoadjuvant chemotherapy with CEF. This patient died of pleuritis carcinomatosa 18 months after surgery for breast cancer (latissimus dorsi muscle myocutaneous flap after radical mastectomy). In Case 2, 6 cycles of neoadjuvant venous drip infusion of docetaxel resulted in a CR effect after failure of 2 cycles of transarterial neoadjuvant chemotherapy with CEF. This patient is alive and disease-free 27 months after the operation for breast cancer (same operation as for Case 1). Docetaxel was effective as neoadjuvant chemotherapy for patients after failure of trans-arterial neoadjuvant chemotherapy with CEF.

MRI of cortical dysplasia--correlation with pathological findings.

Cortical dysplasia (CD) is the most epileptogenic structural lesion associated with epilepsy and patients with intractable seizures caused by this condition are good surgical candidates. MRI plays an important role in detecting the abnormalities of CD. We clarified the MRI characteristics of CD by comparing imaging and histological findings in 20 patients with intractable seizures who underwent surgical resection. There were 12 males and eight females, mean age at operation was 15 years. MRI was performed at 1.5 tesla; T1-weighted, T2- and proton density-weighted spin-echo and fluid-attenuated inversion-recovery (FLAIR) images were obtained. The lesions were in the frontal lobe in nine cases, temporal in two, occipital in another two, insular in one and multilobar in six. Blurring of the grey/white matter junction was seen in all patients, and T2 prolongation in white matter and/or at the grey/white matter junction in 19. Abnormal signal intensity was more frequent in the white matter or at the grey/white matter junction than in the grey matter. FLAIR images made this abnormal high signal easier to appreciate, and we thought them very useful in this context. In areas of T2 prolongation, we saw dysplastic neurones and/or balloon cells, dysmyelination, and ectopic neuronal clustering histologically; glial proliferation played an important role in prolonging T2.

Thymoma with osseous metaplasia.

A 69-year-old woman with a 15-year history of abnormal chest shadow was referred to our hospital. An enhanced chest CT scan of the anterior mediastinum revealed a mass containing a high-density area. The preoperative radiologic diagnosis was thymoma. Operation was performed in October 2000. Histologically, multiple ossified areas were observed within the tumor. Intratumoral ossification has never been reported in thymoma. Therefore, we report the first case of thymoma associated with multiple foci of osseous metaplasia.