Study Protocol: Prospective Study of Concurrent Chemoradiotherapy with S-1 and Hypofractionated Radiotherapy for Outpatients with Early Glottic Squamous Cell Carcinomas

Background: The recommended treatment strategies for early glottic carcinoma with intent of larynx preservation are primarily radiotherapy. However, the outcomes of radiotherapy for bulky T1 or T2 glottic carcinoma are unsatisfactory. We designed a protocol consisting of concurrent chemoradiotherapy using S-1 as the radiosensitizer. We have performed this protocol in patients with favorable T2 lesions and demonstrated its efficacy and safety. In contrast, we have treated non-bulky T1 glottic carcinomas with 2.25 Gy per fraction, for a total of 25-28 fractions, starting in 2011 to improve efficacy and shorten the treatment period. Since this treatment strategy was implemented for T1 disease, no local failure has occurred to date, and it appears to be almost as safe as radiotherapy using 2.0 Gy per fraction. With the aim of improving the local control rate and shortening the treatment period primarily for favorable T2 disease, we changed the dose of radiation in our protocol from 2.0 Gy to 2.25 Gy per fraction, for a total of 25 fractions (from 30 fractions). The present study aims to evaluate the efficacy and safety of this new protocol. Methods: This study will be conducted as a clinical, prospective, single-armed, non-randomized trial. Patients are to receive S-1 (55.3 mg /m2 /day, once daily) and radiotherapy (2.25 Gy per fraction, for a total of 25 fractions). S-1 and radiotherapy are started on the same day that radiotherapy is performed, 3-6 hours after oral administration of S-1. The primary study aim is the 3-year local control rate. The secondary study aims are overall survival, voice-preservation survival, disease-free survival, complete response rate, completion rate, and toxicity. Result and conclusion: This is the first single-center, non-randomized, prospective study of concurrent chemoradiotherapy with S-1 and hypofractionated radiotherapy to be conducted. The trial will evaluate the efficacy and safety of our protocol.

A new buckwheat dihydroflavonol 4-reductase (DFR), with a unique substrate binding structure, has altered substrate specificity.

BACKGROUND: Dihydroflavonol 4-reductase (DFR) is the key enzyme committed to anthocyanin and proanthocyanidin biosynthesis in the flavonoid biosynthetic pathway. DFR proteins can catalyse mainly the three substrates (dihydrokaempferol, dihydroquercetin, and dihydromyricetin), and show different substrate preferences. Although relationships between the substrate preference and amino acids in the region responsible for substrate specificity have been investigated in several plant species, the molecular basis of the substrate preference of DFR is not yet fully understood. RESULTS: By using degenerate primers in a PCR, we isolated two cDNA clones that encoded DFR in buckwheat (Fagopyrum esculentum). Based on sequence similarity, one cDNA clone (FeDFR1a) was identical to the FeDFR in DNA databases (DDBJ/Gen Bank/EMBL). The other cDNA clone, FeDFR2, had a similar sequence to FeDFR1a, but a different exon-intron structure. Linkage analysis in an F2 segregating population showed that the two loci were linked. Unlike common DFR proteins in other plant species, FeDFR2 contained a valine instead of the typical asparagine at the third position and an extra glycine between sites 6 and 7 in the region that determines substrate specificity, and showed less activity against dihydrokaempferol than did FeDFR1a with an asparagine at the third position. Our 3D model suggested that the third residue and its neighbouring residues contribute to substrate specificity. FeDFR1a was expressed in all organs that we investigated, whereas FeDFR2 was preferentially expressed in roots and seeds. CONCLUSIONS: We isolated two buckwheat cDNA clones of DFR genes. FeDFR2 has unique structural and functional features that differ from those of previously reported DFRs in other plants. The 3D model suggested that not only the amino acid at the third position but also its neighbouring residues that are involved in the formation of the substrate-binding pocket play important roles in determining substrate preferences. The unique characteristics of FeDFR2 would provide a useful tool for future studies on the substrate specificity and organ-specific expression of DFRs.

Clinical outcomes of 125I brachytherapy with and without external-beam radiation therapy for localized prostate cancer: results from 300 patients at a single institution in Japan.

The aim of this study was to determine the outcomes and adverse events for 300 men with prostate cancer treated with 125iodine (125I) brachytherapy with and without external-beam radiation therapy (EBRT) at a single institution in Japan. Between February 2005 and November 2011, 300 consecutive patients with clinically localized prostate cancer were treated with 125I brachytherapy at the Nagoya University Hospital. A total of 271 men were treated with implants with doses of 145 Gy, and 29 men were treated with implants with doses of 110 Gy combined with EBRT (40-50 Gy/20-25 fractions). The median patient age was 69 years (range, 53-83 years). The median follow-up period was 53 months (range, 5-99 months). According to the National Comprehensive Cancer Network risk classification, 132 men (44%) had low-risk, 147 men (29%) had intermediate-risk and 21 men (7%) had high-risk disease. The 5-year overall survival rate, biochemical relapse-free survival rate, and disease-specific survival rates were 93.5%, 97.3% and 98.5%, respectively. Two men (0.6%) died of prostate cancer and 10 men (3.3%) died of other causes. Seventeen men (5.6%) experienced Grade 2 rectal bleeding in all: 12 (41.4%) of 29 in brachytherapy with EBRT, and 5 (1.8%) of 271 in brachytherapy alone. The rates of Grade 2 and 3 genitourinary toxicity were 1.0% and 1.7%, respectively. Excellent local control was achieved at our hospital for localized prostate cancer with 125I brachytherapy with and without EBRT. Gastrointestinal and genitourinary toxicities were acceptable.

Optimized treatment strategy of radiotherapy for early glottic squamous cell carcinomas: An initial analysis.

The purpose of this study was to evaluate the clinical outcomes of radiotherapy for patients with T1/T2 glottic carcinoma. Patients with T1/T2 glottic carcinoma histopathologically diagnosed with squamous cell carcinoma and treated at our hospital between 2007 and 2015 were analyzed retrospectively. Our strategy for T1/T2 glottic carcinoma was as follows: radiotherapy alone with 2.25 Gy per fraction to a total of 25-28 fractions for patients with non-bulky T1 glottic carcinoma; concurrent chemoradiotherapy with oral S-1 and radiotherapy with 2 Gy per fraction to a total of 30 fractions for patients with T1 bulky/T2 favorable glottic carcinoma; or chemoradiotherapy with high-dose cisplatin and radiotherapy with 2 Gy per fraction to a total of 35 fractions for T2 unfavorable glottic carcinoma. Forty-eight patients were eligible. The median follow-up period among surviving patients was 38 months (range, 11-107). The disease was T1a in 23%, T1b in 13%, and T2 in 65% of patients. The 3-year local control rate in all patients, T1a, T1b, and T2 was 96.7%, 100%, 100%, and 96.0%, respectively. Of the 46 patients, one with T2 glottic carcinoma developed recurrent disease at the primary site, and one with T2 glottic carcinoma had lymph node recurrences in the neck. Acute Grade 3 dermatitis occurred in 8 (17%) patients and late Grade 2 hypothyroidism occurred in 2 (4%) patients. This retrospective study shows that our optimized treatment strategy of radiotherapy depending on the stage of early glottic carcinoma is not only effective but also well-tolerated.

Postoperative chemoradiation therapy using high dose cisplatin and fluorouracil for high- and intermediate-risk uterine cervical cancer.

The purpose of this retrospective study was to analyze data in patients with stage IB-IIB uterine cervical cancer who were treated with concurrent chemoradiotherapy (CCRT) with high dose cisplatin and fluorouracil as postoperative adjuvant therapy. Between February 2003 and November 2011, 76 patients with FIGO stage IB-IIB cervical cancer were analyzed. Seventy patients were treated with postoperative CCRT and 6 patients were treated with radiation therapy alone. Data related to overall survival (OS), disease-free survival (DFS), toxicity, and failure pattern were analyzed. The median patient age was 45 years (range, 20-80 years). The median follow-up duration was 63 months (range, 10-125 months). Fifty-eight patients (76.3%) had a squamous cell histologic type, 55 patients (72.4%) had lymphovascular invasion, 31 patients (40.8%) had parametrial invasion, and 28 patients (36.8%) had lymph node metastases. Five-year OS and DFS were 96% and 92%, respectively. Five-year DFS in stage IB1 patients was significantly higher than in stage IB2-IIB patients (p = 0.022). Nineteen patients (25%) had grade 3 or 4 neutropenia, 13 patients (17.1%) had grade 3 anemia, and 2 patients (2.6%) had grade 3 thrombocytopenia, but none of these patients died from the disease. Three patients experienced chronic toxicity: one had bladder perforation, one had hydronephrosis, and one experienced ileus. CCRT as postoperative adjuvant therapy resulted in good survival and outcome without severe toxicity.

A multicenter survey of stage T1 glottic cancer treated with radiotherapy delivered in 2.25-Gy fractions in clinical practice: An initial 5-year analysis.

The purpose of this study was to evaluate the acute and late toxicity as well as local control (LC) in T1 glottic cancer (GC) patients treated with hypofractionated radiotherapy (RT) in clinical practice. The Tokai Study Group for Therapeutic Radiology and Oncology started RT treatment with a dose of 2.25 Gy for T1 GC in 2011. Ten institutions combined data from 104 patients with T1 squamous cell carcinoma between 2011 and 2015. In total, 104 patients with T1 GC were irradiated with a standard radiation dose of 63 Gy in 28 fractions.The median follow-up duration was 18 (3.7-49.5) months. Acute grade 3 adverse events were observed in 7 patients, with 4 patients (5%) having dermatitis and 3 patients (4%) having mucositis. Late adverse events above grade 3 were not observed. Two patients developed local recurrence. The rates of acute adverse events in the present study were comparable to those in previous studies that have used 2 Gy fractions of RT.

Late Rectal Toxicity from Image-guided Intensity Modulated Radiotherapy for Prostate Cancer.

AIM: Late rectal toxicity (LRT) was retrospectively evaluated in men with prostate cancer treated with image-guided intensity modulated radiotherapy (IG-IMRT). PATIENTS AND METHODS: Between May 2008 and December 2009, 47 men with prostate adenocarcinoma were treated with IG-IMRT using in-room computed tomography (CT). RESULTS: The median time to grade 2 LRT was 12 months (range=1-24 months). Two of 3 men who developed grade 2 LRT had received treatment for diabetes, and the other was receiving anticoagulant/antiplatelet therapy (AC therapy). Their rectal wall V70 (the volume of rectal wall receiving 70 Gy) values were 12.6%, 13.0%, and 13.3%. Univariate analysis revealed that V70 of the rectal wall was the only significant risk factor for LRT (p=0.0073). CONCLUSION: No man with V70 ≤12.0% experienced grade 2 LRT. Strict rectal wall V70 ≤12% dose constraints should be considered when treating prostate cancer patients who are also receiving diabetic or AC therapy.

A Randomized, Double-Blind Pilot Trial of Hydrolyzed Rice Bran versus Placebo for Radioprotective Effect on Acute Gastroenteritis Secondary to Chemoradiotherapy in Patients with Cervical Cancer.

We aimed to evaluate the radioprotective effect of hydrolyzed rice bran (HRB) on acute gastroenteritis due to chemoradiotherapy for treatment of cervical cancer. This placebo-controlled, double-blind study was conducted as an exploratory investigation of the colitis-inhibiting effects of HRB in alleviating acute-phase gastrointestinal side effects of chemoradiotherapy. The study involved 20 patients (10 in the HRB group, 10 in the control group). The patients in the control group underwent the same chemoradiotherapy regimen as those in the HRB group, but they received a placebo instead of HRB. The diarrheal side effect assessment score was lower in the HRB than control group, and a trend toward a reduction in diarrhea symptoms was observed with the oral intake of HRB. Additionally, no significant difference was observed in the administration of intestinal regulators and antidiarrheal agents, but again the assessment score was lower in the HRB than control group, and diarrhea symptoms were alleviated with the oral intake of HRB. A trend toward no need for strong antidiarrheal agents was seen. Although this study was an exploratory clinical trial, the results suggest that HRB may relieve diarrhea, an acute-phase gastrointestinal side effect of chemoradiotherapy.

A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 5-year results of local control and cosmetic outcome.

BACKGROUND: To date, there are no reports of intraoperative radiotherapy (IORT) use with long-term follow up as a method of accelerated partial breast irradiation (APBI) in Asian countries. We initiated a prospective phase I/II clinical trial of IORT in Japan in 2007, and herein, we report the 5-year follow-up results. MATERIALS AND METHODS: The following inclusion criteria were used for enrollment in the trial: (1) tumor size < 2.5 cm, (2) desire for breast-conserving surgery, (3) age >50 years, and (4) negative margins after resection. In February 2009, the eligibility criteria were changed to include only patients with sentinel lymph node-negative disease. In phase I, the radiotherapy dose was escalated from 19 Gy/fr to 21 Gy/fr, incremented by 1 Gy per step, with 3 patients in each step. Doses were escalated after all patients in the preceding cohort had completed treatment and exhibited only grade 1 or 2 toxicities at a given dose level. The recommended phase II dose was set at 21 Gy at 90 % isodose. The primary endpoint was early toxicity. Secondary endpoints were long-term efficacy and late toxicity. In addition, Hypertrophic scarring was evaluated retrospectively as a cosmetic outcome by a radiation oncologist. RESULTS: Between December 2007 and March 2010, 32 women with breast cancer were enrolled in the trial. The median age was 65 years (51-80 years), and the median follow-up time was 6 years. No recurrence or metastasis was observed in any patient. Grade 2 fibrosis was detected in 3 patients as an acute adverse event and in 2 patients as a late adverse event. Ten patients developed a hypertrophic scar 1 year after the IORT; the number of patients decreased to 7 in the 3 years of follow-up. CONCLUSION: The first group of female Asian patients tolerated the treatment with IORT in this Phase I/II study and remained recurrence-free for more than 5 years after treatment. However, 24 % of the patients developed hypertrophic scarring, an event that is being further examined in our ongoing multi-center Phase II trial of IORT for early breast cancer.

Intraoperative spinal cord monitoring using combined motor and sensory evoked potentials recorded from the spinal cord during surgery for intramedullary spinal cord tumor.

OBJECTIVES: The risk of postoperative neurological impairment mandates the use of intraoperative spinal cord monitoring (IOM) during intramedullary spinal cord tumor (IMSCT) surgery. We have used spinal cord evoked potential after electrical stimulation of the cord(Sp-SCEP) to monitor the sensory tract, and SCEP after electrical stimulation to the brain (Br-SCEP) to monitor the motor tract. Both Sp-SCEP and Br-SCEP are stable under general anesthesia. We assessed the clinical utility of these multimodal spinal cord monitoring methods in a retrospective study of a cohort of patients undergoing IMSCT surgery. METHODS: Thirteen patients with IMSCTs underwent tumor resection using Sp-SCEP and/or Br-SCEP. RESULTS: Four patients underwent surgery using only Sp-SCEP monitoring, resulting in two false negatives. Nine patients underwent surgery monitored by Br-SCEP and Sp-SCEP. In three of the nine cases, Br-SCEP amplitude fell by 50% from control levels, despite there being no change in Sp-SCEP. In one of the nine cases, Sp-SCEP amplitude fell to 50% of control levels, but Br-SCEP amplitude was stable. CONCLUSIONS: During IMSCT surgery, localized regions of the cord may be damaged. Multimodal monitoring should be used to monitor.Combining Sp-SCEP and Br-SCEP is a useful means of monitoring the sensory and motor tracts.

Critical evaluation of a prospective study of concurrent chemoradiotherapy with S-1 for early glottic carcinoma.

AIM: To improve the outcomes of radiotherapy alone for T2 glottic carcinoma (GC), we initiated a prospective study of concurrent chemoradiotherapy with S-1 for patients with early GC, primarily T2 cases. We report the efficacy and safety of this protocol. PATIENTS AND METHODS: Eligible patients had T1b or T2 glottic squamous cell carcinomas. Patients received S-1 (55.3 mg/m(2)/day, once daily) and radiotherapy (2 Gy/day, five days/week, to a total of 30 fractions). RESULTS: Thirteen patients were eligible. Complete responses were observed in all 13 patients (100%). At a median follow-up duration of 53 months (range=23-68 months), the 3-year local control and overall survival rates were both 100%. Grade 3 dermatitis occurred in only one patient. CONCLUSION: This chemoradiotherapy protocol is well -tolerated and effective in patients with early glottic carcinoma. Furthermore, due to its once-daily administration, this protocol is considered to be easier than usual chemoradiotherapy, and makes outpatient-treatment possible.

Retrospective case series of 15 patients treated with chemoradiation using 5-FU and nedaplatin for gynecological malignancy: with regard to hemotoxicity.

We conducted a retrospective comparison of the hemotoxicity of the sequential administration of 5-Fluorouracil (5-FU) prior to Nedaplatin (NDP) (FN therapy) and that of its reverse sequence (NF therapy) for gynecological malignancy. From February 2002 to November 2004, a total of 15 gynecological malignancy patients were treated with radiation therapy combined with NDP and 5-FU. Of these 15 patients, 5 were treated with NF therapy, and 10 were treated with FN therapy. No significant differences were detected between the FN and NF groups with regard to white blood cell count (WBC), hemoglobin level (Hb), and platelet count. The results of this study do not show that the FN group has a lesser degree of hemotoxicity than the NF group.

Gene expression levels of ß4-galactosyltransferase 5 correlate with the tumorigenic potentials of B16-F10 mouse melanoma cells.

Our previous studies showed that mouse ß4-galactosyltransferase 5 (ß4GalT5) is a lactosylceramide (Lac-Cer) synthase, and that its gene expression increases by 2- to 3-fold upon malignant transformation of cells. In the present study, we examined whether or not the tumorigenic and metastatic potentials of B16-F10 mouse melanoma cells can be suppressed by reducing the expression of the ß4GalT5 gene. We isolated a stable clone named E5 whose ß4GalT5 gene expression level was reduced to 35% that of a control clone C1 by transfection of its antisense cDNA. Thin-layer chromatography analysis of glycosphingolipids showed that the amounts of Lac-Cer and ganglioside GM3 are significantly less in clone E5 than in clone C1. Clone C1 and E5 cells were each transplanted subcutaneously or injected intravenously into C57BL/6 mice, and the sizes of tumors and numbers of colonies formed in the lungs were determined. The average tumor size and average number of colonies formed with clone E5 were decreased to 44 and 49%, respectively, of those formed with clone C1. Furthermore, the numbers and sizes of colonies formed in the soft agarose gels, and the volumes of tumors formed in athymic mice with fibroblasts from wild type, heterozygous and homozygous ß4GalT5-knockout mouse embryos upon transformation with the polyoma virus oncogene correlated with the ß4GalT5 gene dosage. These results strongly indicate that the amounts of Lac-Cer synthesized by ß4GalT5 correlate with the tumorigenic potentials of malignantly transformed cells.

Primary CNS lymphoma treated with radiotherapy in Japan: a survey of patients treated in 2005-2009 and a comparison with those treated in 1985-2004.

BACKGROUND: The aim of our study was to analyze changes over time in the characteristics, treatment, and outcome of patients with primary central nervous system lymphoma (PCNSL). METHODS: Data on 315 patients with histologically proven PCNSL undergoing radiotherapy between 2005 and 2009 were collected from 20 Japanese institutions using a questionnaire. These data were then compared with data on 273 patients treated during the period 1995-2004 and those on 466 patients treated during the period 1985-1994. RESULTS: In terms of patient and tumor characteristics, we found a significant increase in mean patient age in the 2005-2009 period compared to the 1985-2004 period (63 vs. 58-59 years, respectively) and in the percentage of patients with better performance status (PS) during the 2005-2009 period compared with the 1995-2004 period (World Health Organization PS 0-2: 73 vs. 65 %, respectively). Regarding treatment, relative to the 1995-2004 period, significant changes in the 2005-2009 period were (1) decreased rate of attempting tumor resection (23 vs. 44 %); (2) increased use of chemotherapy (78 vs. 68 %), and (3) increased use of methotrexate (MTX)-containing regimens (84 vs. 53 %). The 5-year overall survival rates were 15.3, 30.1, and 36.5 % for patients seen during the 1985-1994, 1995-2004, and 2005-2009 periods, respectively, but relapse-free survival did not improve between the 1995-2004 and 2005-2009 periods (26.7 vs. 25.7 % at 5 years, respectively). Patients receiving MTX-containing chemotherapy had 5-year survival rates of 19, 50, and 44 % during these three periods, respectively. CONCLUSIONS: Although patient backgrounds differed among the study periods, recent trends were a high patient age, better PS, avoidance of extensive tumor resection, more frequent use of chemotherapy, and improved survival. The recent improvement in survival may be due to improvements in second-line treatment and supportive care.

Radiotherapy with or without chemotherapy for patients with T1-T2 glottic carcinoma: retrospective analysis.

BACKGROUND: To assess the results for local control (LC) and survival in patients with early-stage glottic cancer (GC) who were treated by radiotherapy (RT) with or without chemotherapy. METHODS: Fifty-eight patients with T1-T2 squamous cell carcinoma of the glottis who were treated between 2001 and 2006 were analyzed retrospectively. Potential prognostic factors for LC were evaluated by univariate analysis. RESULTS: The 5-year LC rate in all patients was 84.3%. The overall 5-year LC rates for patients with T1a, Tb, and T2 GC were 85.9%, 83%, and 85%, respectively. Of the 58 patients, eight developed recurrent disease at the primary site, and one had lymph node recurrences on the neck. In the final analysis, the total laryngectomy-free survival rate was 93% at five years, and the ultimate LC rates for T1a, Tb, and T2 were 100%, 90.9%, and 95.2%, respectively. In a univariate analysis of 55 patients, there was no statistical significance between the LC rate for RT alone and that for chemoradiation. Only two patients died of laryngeal carcinoma, and one died of intercurrent disease. Fifty-five patients were living disease-free at the end of the study period. The 5-year overall survival (OS) rate for all patients was 88.1%, and the 5-year OS rates for T1a, Tb, and T2 were 91.6%, 77.8%, and 89.9%, respectively. CONCLUSIONS: The retrospective analysis showed a high rate of LC and larynx preservation in patients with T1-T2 GC by means of RT with or without chemotherapy. There was, however, no statistical difference in LC rates for the two types of therapy.

Contrast-enhanced MR imaging of metastatic brain tumor at 3 tesla: utility of T(1)-weighted SPACE compared with 2D spin echo and 3D gradient echo sequence.

We evaluated the newly developed whole-brain, isotropic, 3-dimensional turbo spin-echo imaging with variable flip angle echo train (SPACE) for contrast-enhanced T(1)-weighted imaging in detecting brain metastases at 3 tesla (T). Twenty-two patients with suspected brain metastases underwent postcontrast study with SPACE, magnetization-prepared rapid gradient-echo (MP-RAGE), and 2-dimensional T(1)-weighted spin echo (2D-SE) imaging at 3T. We quantitatively compared SPACE, MP-RAGE, and 2D-SE images by using signal-to-noise ratios (SNRs) for gray matter (GM) and white matter (WM) and contrast-to-noise ratios (CNRs) for GM-to-WM, lesion-to-GM, and lesion-to-WM. Two blinded radiologists evaluated the detection of brain metastases by segment-by-segment analysis and continuously-distributed test. The CNR between GM and WM was significantly higher on MP-RAGE images than on SPACE images (P<0.01). The CNRs for lesion-to-GM and lesion-to-WM were significantly higher on SPACE images than on MP-RAGE images (P<0.01). There was no significant difference in each sequence in detection of brain metastases by segment-by-segment analysis and the continuously-distributed test. However, in some cases, the lesions were easier to detect in SPACE images than in other sequences, and also the vascular signals, which sometimes mimic lesions in MP-RAGE and 2D-SE images, were suppressed in SPACE images. In detection of brain metastases at 3T magnetic resonance (MR) imaging, SPACE imaging may provide an effective, alternative approach to MP-RAGE imaging for 3D T(1)-weighted imaging.

Contrast-enhanced MR imaging of the brain using T1-weighted FLAIR with BLADE compared with a conventional spin-echo sequence.

The BLADE and PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) techniques have been proposed to reduce the effect of head motion. Preliminary results have shown that BLADE also reduces pulsation artifacts from venous sinuses. The purpose of this study was to compare T1-weighted FLAIR acquired with BLADE (T1W-FLAIR BLADE) and T1-weighted spin-echo (T1W-SE) for the detection of contrast enhancement in a phantom and in patients with suspected brain lesions and to compare the degree of flow-related artifacts in the patients. A phantom filled with diluted Gd-DTPA was scanned in addition to 27 patients. In the phantom study, the peak contrast-to-noise ratio of T1W-FLAIR BLADE was larger than that of T1W-SE, and the position of the peak was shifted to a lower concentration. In patients, the degree of flow-related artifacts was significantly higher in T1W-SE. Among the 27 patients, 9 had metastatic tumor, and 18 did not. On a patient-by-patient basis, the sensitivity and specificity for the detection of metastatic lesions on axial T1W-SE were 100% and 55.6% respectively, while on axial T1W-FLAIR BLADE they were 100% and 100%. T1W-FLAIR BLADE seems to be capable of replacing T1W-SE, at least for axial post-contrast imaging to detect brain metastases.

History of the development of intraoperative spinal cord monitoring.

In the early 1970s, spinal instrumentation and aggressive surgical technology came into wide use for the treatment of severe spinal deformities. This background led to the development of intraoperative spinal cord monitoring by orthopaedic spine surgeons themselves. The author's group (T.T.) and Kurokawa's group invented a technology in 1972 to utilize the spinal cord evoked potential (SCEP) after direct stimulation of the spinal cord. In the United States, Nash and his group started to use SEPs. Following these developments, the Royal National Orthopaedic Hospital group of Stanmore, UK employed spinal somatosensory evoked potential in 1983. However, all of these methods were used to monitor sensory mediated tracts in the spinal cord. The only way to monitor motor function was the Wake up test developed by Vauzelle and Stagnara. In 1980, Merton and Morton reported a technology to stimulate the brain transcranially and opened the doors for motor tract monitoring. Presently, in the operating theatre, monitoring of motor-related functions is routinely performed. We have to remember that multidisciplinary support owing to the development of hardware and, software and the evolution of anesthesiology has made this possible. Furthermore, no single method can sufficiently cover the complex functions of the spinal cord. Multimodality combinations of the available technologies are considered necessary for practical and effective intra-operative monitoring (IOM). In this article, the most notable historic events and articles that are regarded as milestones in the development of IOM are reviewed.