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Study Design: Retrospective cohort study. Objective: To develop a grading method for cervical paraspinal soft tissue damage after cervical spinal cord injury (CSCI) without major fracture based on the short T1 inversion recovery (STIR) mid-sagittal magnetic resonance image (MRI) for prediction of neurological improvements. Methods: This study included 34 patients with CSCI without major fracture, treated conservatively for at least 1 year and graded using the STIR-MRI Grade. This system consists of anterior grades; A0: no high-intensity area (HIA), A1: linear HIA, and A2: fusiform HIA, and posterior grades; P0: no HIA, P1: HIA not exceeding the nuchal ligament, and P2: HIA exceeding the nuchal ligament, within 24 hours postinjury. The American Spinal Injury Association impairment scale (AIS) and the Japanese Orthopedic Association (JOA) scores were examined. Results: Anterior grades were not significantly correlated with the AIS and JOA score. At both injury and final follow-up, the AIS in P2 patients was significantly more severe ( P = 0.007, P = 0.015, respectively) than that in P0 patients. At the injury, the AIS in P2 patients was significantly more severe ( P = 0.008) than that in P1 patients. Among P2 patients only, the JOA score at the injury (1.4 points) did not improve by the final follow-up (3.9 points). The final follow-up JOA score (3.9 points) in P2 patients was significantly lower than that (13.6 points) in P0 patients ( P = 0.016). Conclusions: Grade P2 led to poor neurological outcomes. The STIR-MRI Grade is a prognostic indicator for neurological improvements past-CSCI.

Study design A retrospective comparison of the surgical outcome after cervical laminoplasty for cervical spondylotic myelopathy (CSM) using a modified K-line based on lordosis in neck extension as a predictor: in K-line Back CSM (KB group), the K-line crosses the ventral edge of any of the spinous processes, whereas in K-line Front CSM (KF group), the K-line does not. Objective To investigate the neurological and radiological outcomes 5 years after surgery and the contact between the spinal cord and posterior elements after laminoplasty for CSM using the modified K-line. Summary of background data No indicators on a lateral radiograph can predict the neurological outcome after laminoplasty for CSM. Methods Patients with CSM were divided into KB (n = 20) and KF groups (n = 13). We compared the postoperative Japanese Orthopedic Association (JOA) score, recovery rate, grip-and-release (GR) and foot-tapping (FT) test results, alignment, and contact between the spinal cord and posterior elements between the two groups. Results The postoperative JOA score and its recovery rate were significantly lower in the KB group (12.4 points and 34.1%, respectively) than in the KF group (14.1 points and 59.0%, respectively) at final follow-up (P = 0.0415 and 0.0458). The GR and FT test results improved significantly in the KF group but not in the KB group. In the KB group, a larger lordotic angle in extension at 1 year postoperatively continued until final follow-up. The rate of recovery of the JOA score in patients with contacts at both C4/5 and C5/6 and any contact in the KB group (-1.5% and 31.9%, respectively) were lower (P = 0.0013 and 0.0534, respectively) than those in the KF group (58.6% and 60.7%, respectively). Conclusions The K-line Back predicts a poor neurological outcome after laminoplasty for CSM. Decompression with fusion may be recommended for these patients. Level of evidence 4.

This study aims to clarify the association between cervical spondylotic myelopathy (CSM) and cervical arteriosclerosis using ultrasonography that comprehensively includes spinal cord stenosis. Eighty-two consecutive patients aged over 60 years who underwent spine surgery were divided into those with CSM (n = 31; CSM group) and those with lumbar spinal stenosis without cervical myelopathy (n = 51; LSS group). Maximum spinal cord compression (MSCC) was evaluated for cervical stenosis severity using magnetic resonance (MR) images. The intima–media thickness (IMT) of the common carotid artery (CCA) and pulsatility index (PI) of the bilateral internal carotid artery (ICA) and vertebral artery (VA) were evaluated for cervical arteriosclerosis using pulsed-wave Doppler ultrasonography. Symptom severity was evaluated using the Japanese Orthopaedic Association (JOA) score. Spearman’s correlation coefficient was used to determine the relationship between the JOA score and MSCC or IMT and PI in each group. Stepwise multiple linear regression analyses were conducted with the JOA score as a dependent variable and age, sex, body mass index, cervical arteriosclerosis assessment, and MSCC as independent variables. Bilateral IMT and left-side ICA-PI were significantly negatively correlated with JOA scores in the CSM group (Right-CCA-IMT: R = − 0.412, Left-IMT: R = − 0.549, Left-ICA -PI: R = − 0.205, P

The smaller cross-sectional areas of the dural sacs in patients without C5 palsy after posterior cervical spine surgery may lead to less neurological improvement. The aim of this retrospective study was to clarify the differences in the cross-sectional area of the dural sac in the cervical spine and neurological improvement in patients with and without C5 palsy after posterior cervical spinal surgery. We retrospectively evaluated the postoperative cross-sectional areas of the dural sacs and neurological outcomes in patients with and without C5 palsy after posterior cervical spine surgery. We compared the postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 on magnetic resonance images between the C5 palsy group (n = 19) and the no-C5 palsy group (n = 84) after posterior cervical spinal surgery 1 year postoperatively. Performance tests, namely, the 10-s grip-and-release test and the 10-s single-foot-tapping (FT) test, were compared between the two groups. Postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 (233.3 mm2 and 226.6 mm2, respectively) in the C5 palsy group were significantly larger (P = 0.0036 and P = 0.0039, respectively) than those (195.0 mm2 and 193.8 mm2, respectively) in the no-C5 palsy group. Postoperative gain in the grip-and-release test was similar between the two groups. Postoperative gain in the FT test (4.9 times) in the C5 palsy group was significantly larger (P = 0.0060) than that (1.8 times) in the no-C5 palsy group. In the C5 palsy group 1 year after posterior cervical spine surgery, the cross-sectional areas of the dural sac were larger, and the 10-s single FT test improved noticeably.

Lumbar degenerative disease and dementia are increasing in super-aging societies and are both related to physical dysfunction and pain. However, the relationship between these diseases remains unclear. This cross-sectional study aimed to investigate the comorbidity rates of lumbar spinal canal stenosis (LSS) and mild cognitive impairment (MCI) and clarify the association between LSS presence, lumbar symptoms, and quality of life (QOL) related to low back pain and cognitive impairment in the Japanese population. We enrolled 336 participants (men 124; women 212; mean age 72.2 years) from a medical checkup program. LSS was diagnosed using a self-administered questionnaire, and lumbar symptoms were evaluated using the visual analog scale (low back pain, and pain and numbness of the lower limb). QOL related to low back pain was evaluated using the Japanese Orthopedic Association Back-Pain Evaluation Questionnaire (JOABPEQ: pain, and lumbar, and gait function). Radiological lumbar degeneration was classified using Kellgren-Lawrence grading and lateral radiographs of the lumbar spine. Cognitive function was measured using the Mini Mental State Examination (MMSE), and MCI was defined by a summary score of MMSE ≤27. Logistic and multiple linear regression analyses were performed to analyze the association between MCI, summary score of MMSE, and lumbar degenerative disease. The comorbidity rate of MCI and LSS was 2.1%, and the rate of MCI was 41% in participants with LSS. Lumbar function in JOABPEQ was associated with MCI. The presence of LSS and lumbar function in JOABPEQ were associated with MMSE. Over one-third of the people with LSS had MCI. The presence of LSS and deterioration of QOL due to low back pain were related to cognitive impairment. We recommend evaluating cognitive function for patients with LSS because the rate of MCI was high in LSS participants.

Purpose Although the use of intraoperative computed tomography (CT)-based navigation systems is unlikely to cause intraoperative contamination more than the use of intraoperative fluoroscopy, the association between intraoperative CT/navigation and surgical site infections (SSIs) remains unclear. We investigated the incidence of SSIs and the association between intraoperative CT/navigation and SSIs for spinal surgeries. Methods Of the 512 patients who underwent spinal surgery between April 2016 and December 2020, 304 underwent C-arm intraoperative fluoroscopy and/or Medtronic O-arm intraoperative CT/navigation system. We investigated the incidence of SSIs in patients with four techniques; no intraoperative imaging C-arm only, O-arm only, and both O- and C-arm used. Multivariate logistic analyses were conducted using the prevalence of SSIs as the dependent variable. The independent variables were age, sex, and potential confounders including preoperative Japanese Orthopaedic Association (JOA) score, use of instrumentation, C-arm, and/or O-arm. Results The incidence of the SSIs in patients with no imaging, C-arm only, O-arm only, and both modalities used was 1.9%, 7.3%, 4.7%, and 8.3%, respectively. There was no significant difference in the incidence of SSIs between the four techniques. Multivariate logistic analyses showed a significant correlation between the prevalence of SSI and JOA scores (odds ratio, 0.878; 95% CI 0.759–0.990) and use of instrumentation (odds ratio, 6.241; 95% CI 1.113–34.985), but not use of O-arm. Conclusions The incidence of the SSIs in patients with only O-arm used was 4.7%. Preoperative clinical status and use of instrumentation, but not use of the O-arm, were associated with SSIs after spinal surgeries.

Study design A multicenter, retrospective study. Objective To clarify the clinical and radiological effects of removing interspinous contextures in lumbar decompression surgery for patients with lumbar spinal stenosis. Summary of background data There have seldom been reports that have compared both clinical results and radiological changes among minimally invasive decompression methods. Methods Consecutive 52 patients underwent lumbar spinous process-splitting laminectomy (LSPSL), following which 50 patients underwent trans-interspinous lumbar decompression (TISLD). All patients presented with cauda equina type of lumbar spinal stenosis and underwent a minimum 1-year follow-up. The Japanese Orthopaedic Association (JOA) score and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score were evaluated to determine the extent of daily living activities. Propensity score (PS)-matched analysis was used to match patients' age and preoperative JOA scores between the two groups. Lumbar lordosis (LL), disc height (DH), segmental range of motion (ROM), and vertebral anterior translation were measured by functional lumbar lateral X-ray, and changes between preoperative and 1-year postoperative values were evaluated. Results Twenty-nine pairs of patients were selected by PS-matching. Mean JOA scores increased from 14.4 to 23.5 (mean recovery rate was 62.3%) in the LSPSL group and from 14.0 to 23.2 (61.3%) in the TISLD group at preoperative and 1-year follow-up, respectively. There were no significant differences in clinical results and changes in LL, ROM, and vertebral anterior translation in each group. The DH at L4/5 level at 1-year after surgery revealed significant decrease in the TISLD group compared to the LSPSL group. There was a correlation between preoperative DH and DH decrease in the LSPSL group, but not in TISLD group. Conclusions Removal of interspinous contextures did not influence clinical outcomes at 1 year after surgery, but it may be likely to cause disc height loss when it applied at the L4/5 level.Level of Evidence: 3.

BackgroundThis cross-sectional study sought to determine the neck-shoulder stiffness/low back pain (NSS/LBP) comorbidity rate in a Japanese community population and to compare the quality of life (QOL) in individuals with comorbid NSS/LBP, asymptomatic individuals, and those with symptoms of NSS or LBP alone.MethodsThe sample included 1122 subjects (426 men; 696 women) with NSS and LBP symptoms in the previous 3 months, and were grouped according to NSS, LBP, comorbid NSS and LBP symptoms (Comorbid), or no symptoms (NP). They completed the MOS 36-Item Short-Form Health Survey (SF-36). Health QOL was evaluated by the eight domain scores and the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores after adjusting for age. The primary outcome was to examine the association between NSS/LBP, NSS, or LBP and bodily pain of the eight domains of SF-36. Secondary outcome was to compare health-related QOL among the four groups.ResultsMorbidity was 45.6% for NSS and 51.9% for LBP. Comorbidity affected 23% of men and 33% of women. Comorbid NSS/LBP, NSS, and LBP alone were independently associated with bodily pain after adjusting for potential confounders. Men who exhibited comorbidity had significantly lower MCS scores than asymptomatic men. Women who exhibited comorbidity and LBP had significantly lower MCS scores than those with no symptoms or NSS alone. Women who exhibited comorbidity had significantly lower MCS scores than those with no symptoms or LBP alone.ConclusionsComorbidity of the two diseases is prevalent in 23% of the men and 33% of women in the Japanese sample. Although NSS, LBP, and comorbidity were independently associated with QOL in terms of pain, QOL was worse in individuals who exhibited comorbidity than in those without symptoms or with NSS alone.

Background This study aimed to assess orthopedic surgeons’ attitudes and behaviors toward occupational radiation exposure and investigate the prevalence of occupational radiation-induced skin injury among orthopedic surgeons. Similarly, risk factors for the presence of radiation-induced skin injury were investigated. Methods Overall, 108 orthopedic surgeons were administered self-reported questionnaires about occupational radiation exposure, and their hands were then photographed. Their fields of expertise were classified into spine, arthroplasty, sports medicine, hand, oncology, rheumatoid arthritis, pediatric orthopedic, and resident. Dermatologists evaluated the surgeons’ skin conditions and classified into 3 grades of injury: grade 0, no clinical symptoms; grade 1, careful observation required; and grade 2, detailed examination required. Logistic regression analysis was performed to investigate the factors related to the presence of radiation-induced skin injury. Crude and adjusted logistic regression analysis using the backward stepwise selection method was similarly conducted. Receiver operating characteristic curve (ROC) analysis was performed to estimate the predictive power of exposure time, occupational period, and accumulated annual exposure time for radiation-induced skin injury. Results In total, 93.5% of the surgeons were careful about occupational radiation exposure, of which 76.8% used a dosimeter. Skin changes in the hands were self-reported by 42.5% of the surgeons, and radiation-induced skin injury was diagnosed in 31.4%. The accuracy of the self-reported skin changes was 100% for grade 2 and 61.5% for grade 1. Adjusted regression analysis showed that dermatologists’ diagnosis-related factors were self-reported skin changes (odds ratio [OR] 3.1) and spine surgeons (OR 3.2). ROC analysis demonstrated that an occupational period >21 years and an accumulated exposure time >6696 min were considered risk factors, with ORs of 4.07 and 5.99, respectively. Conclusions Orthopedic surgeons, particularly spine surgeons, should be regularly examined by dermatologists early in their careers for early detection of radiation-induced skin injury on the hands.

To prospectively examine whether laminoplasty with maximal expansion induces C5 palsy, even with prophylactic bilateral C4/5 foraminotomy. Thirty-five consecutive patients with cervical myelopathy underwent laminoplasty (n = 19: LP group) or posterior decompression and fusion (n = 16: PDF group) with maximal expansion. Prophylactic bilateral C4/5 foraminotomy was performed alternately in consecutive five patients undergoing each type of surgery. In each type of surgery, the first and third consecutive five patients did not undergo foraminotomy (NF subgroup: 20 patients), while the second and fourth consecutive five patients underwent foraminotomy (F subgroup: 15 patients). The widths between the gutters was equivalent to the diameter of the spinal canal, and an inclination angle of the lamina of approximately 90° was created during laminoplasty. The incidence and severity of postoperative C5 palsy were investigated. Patients with a manual muscle testing score for the deltoid muscle and/or biceps brachii muscle of ≤ 2 were diagnosed with severe palsy. The respective incidences of C5 palsy in the F and NF subgroups were 33% and 20% in the LP group and 50% and 20% in the PDF group. Severe palsy occurred in 67% and 0% of patients who had developed palsy in F and NF subgroups, respectively, in the LP group, and in 100% of patients in the PDF group. Furthermore, 40% of the patients with severe palsy took more than 6 months to recover. Laminoplasty with maximal expansion induced C5 palsy in both the LP and PDF groups, even with the addition of prophylactic bilateral C4/5 foraminotomy.

Background Associations between whiplash injuries and quality of life (QOL) have been previously published by conducting surveys among patients. This study aimed to investigate the prevalence of whiplash injuries in a Japanese community, and the association between whiplash injuries and QOL was also determined. Methods In all, 1140 volunteers participated in this study, filled out a questionnaire about whether they had experienced a whiplash injury, or had any neck pain or neck-shoulder stiffness in the previous 3 months, and completed the Medical Outcomes Study 36-Item Short-Form Health Survey. QOL was evaluated from the eight domain scores, and the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. We compared the characteristics, habits, history, medication, body mass index, and health-related QOL (eight domains, PCS and MCS scores) between the groups with whiplash injuries and no whiplash injuries for each sex. Multiple linear regressions with the forced-entry procedure were performed to evaluate the effects of a whiplash injury on the PCS and MCS. A p-value of Results The prevalence of whiplash injuries was 7.7% and 9.6% in men and women, respectively. The percentage of those who experienced whiplash injuries with symptoms persisting for more than 3 months was 34.3% and 24.2% in men and women, respectively. The prevalence of neck symptoms was significantly higher in the whiplash injury group than in the non-whiplash injury group. Multiple linear regression analysis showed that, although whiplash injuries were associated with poor health-related QOL in men, age was more associated with health-related QOL than whiplash injuries in both sexes. Conclusion The prevalence of whiplash injuries was 7.7% and 9.6% in men and women in local residents in Japan, respectively. Whiplash injuries were poorly associated with a poor health-related QOL in men (P = 0.015).

To compare surgical outcomes after tympanoplasty without ossiculoplasty for chronic otitis media between transcanal endoscopic ear surgery (TEES) and postauricular microscopic ear surgery (PAMES).Case-control study.Tertiary care university hospital.Consecutive patients (The surgical success rate for hearing (air-bone gap ≤20 dB) was 95.7% in the TEES group and 84.0% in the PAMES group. Lower middle ear risk resulted in similar mean (95% CI) closure of air-bone gaps (TEES: 9.6, 6.5-12.6; PAMES: 8.0, 6.4-9.7;Under favorable conditions of the middle ear, TEES and PAMES resulted in similar hearing improvement by tympanoplasty without ossiculoplasty. However, under adverse conditions of the middle ear, TEES was a more beneficial approach for hearing improvement than PAMES.

Neoadjuvant endocrine therapy has been reported to decrease tumor size, which leads to increased breast conservation rates. To improve the clinical response, metronomic chemotherapy with endocrine therapy is a promising strategy. A multicenter phase II single‐arm neoadjuvant trial with letrozole and cyclophosphamide was conducted. Eligibility criteria included postmenopausal status, T2–4 N0–1, and estrogen receptor‐positive breast carcinoma. Letrozole (2.5 mg) plus cyclophosphamide (50 mg) was given orally once a day for 24 weeks. The primary endpoint was the clinical response rate (CRR). To investigate anti‐angiogenic effects, circulating endothelial cells (CECs) were quantified using the CellSearch system. From October 2007 to March 2010, 41 patients were enrolled. The CRR was 67.5% (52.0–80.0%), which was above the prespecified threshold (65%). The conversion rate from total mastectomy to breast‐conserving surgery was 64% (18/28). Grade 3 or greater nonhematological toxicity was not reported. Clinical response was associated with improved disease‐free survival (DFS) (P = 0.020). The increase in CEC counts at 8 weeks was observed in nonresponders (P = 0.004) but not in responders. Patients with higher CEC counts at baseline or post‐treatment showed worse DFS than those with lower counts (P

S‐1 and irinotecan combination is attractive for breast cancer refractory to anthracyclines and taxanes. Patients with advanced human epidermal growth factor receptor 2 (HER2)‐negative breast cancer previously treated with anthracyclines and taxanes were eligible. Patients with brain metastases and homozygous for UGT1A1 *6 or *28 or compound heterozygous (*6/*28) were excluded. A dose‐escalation design was chosen for the phase I portion (level 1: irinotecan 80 mg/m2 days 1–8 and S‐1 80 mg/m2 days 1–14 every 3 weeks; level 2: irinotecan 100 mg/m2 and S‐1 80 mg/m2). Study objectives included determination of the recommended dose for phase II, response rate, progression‐free survival (PFS), and safety. Pharmacokinetics and CD34+ circulating endothelial cells (CECs) as pharmacodynamics were also analyzed. Thirty‐seven patients were included. One patient at each level developed dose‐limiting toxicities; therefore, level 2 was the recommended dose for phase II. Diarrhea was more common in patients possessing a *6 or *28 allele compared with wild‐type homozygous patients (46% and 25%). Among 29 patients treated at level 2, PFS was longer for UGT1A1 wt/*6 and wt/*28 patients than for wt/wt patients (12 vs. 8 months, P = 0.06). PFS was significantly longer in patients with a larger‐than‐median SN‐38 area under the curve (AUC) than in those with a smaller AUC (P = 0.039). There was an association between clinical benefit and reduction in baseline CD34+ CECs by S‐1 (P = 0.047). The combination of irinotecan and S‐1 is effective and warrants further investigation.

Introduction: Lumbar spinal canal stenosis (LSS) is a very common disease. When the responsible level is considered to be L4/5 despite the appearance of double-level (L3/4 and L4/5) stenosis on magnetic resonance imaging (MRI), it is difficult for spinal surgeons to decide whether prophylactic decompression should be performed at the L3/4 level. The purpose of this study was to investigate the relationship between the dural sac cross-sectional area (DCSA) at the L3/4 level and clinical symptoms in patients with double-level stenosis. Methods: Thirty-five patients with double-level stenosis were registered in this study. All patients underwent decompression surgery at the L4/5 responsible level. The severity of patients' symptoms was evaluated by the Japanese Orthopaedic Association (JOA) score and its rate of recovery. A measurement program on MRI was used to determine the DCSA. Results: The clinical course of LSS according to the JOA score recovery rate at the final follow-up revealed that the good group (50%) included 27 patients, and the poor group (

Study design A retrospective study. Objective To compare long-term clinical and radiologic outcomes between conventional double-door laminoplasty (LP) (group A) and cervical LP with C3 laminectomy (group B). Summary of background data Cervical LP with C3 laminectomy preserving the semispinalis cervicis inserted into the axis decreased the patients' postoperative axial pain and muscle atrophy, prevented interlaminar bony fusion, decreased limitations of daily living activity, including reduced postoperative neck mobility, and maintained the cervical range of motion (ROM) more effectively than conventional cervical LP reattaching the semispinalis cervicis in the short-term. Materials and methods Group A included 14 patients with an average age of 56.6 years at the time of surgery (follow-up rate 58.1%), and group B included 21 patients with an average age of 56.3 years at the time of surgery (follow-up rate 29.1%). We evaluated the clinical results, which included the Japanese Orthopaedic Association (JOA) score, JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and radiologic results, including C2-C7 ROM, number of interlaminar bony fusions and presence of new spondylolisthesis at C3. Results There were no significant differences in preoperative and postoperative JOA scores, recovery rate of JOA score, and JOACMEQ. Significantly fewer patients in group B experienced interlaminar bony fusion at C2-C3 compared with those in group A. There was no significant difference in the presence of new spondylolisthesis at C3. In patients with cervical spondylotic myelopathy, the rate of decrease of C2-C7 ROM was significantly less in group B than in group A. In patients with ossification of the posterior longitudinal ligament, there was no significant difference in the rate of decrease of C2-C7 ROM between the groups. Conclusions C3 laminectomy prevented interlaminar bony fusion at C2-C3. C3 laminectomy maintained cervical ROM in patients with cervical spondylotic myelopathy. There were no adverse events due to C3 laminectomy at 10 years postsurgery.

Background Osteoporotic fractures constitute a major health concern in both women and men, particularly with the aging population. Many potential risk factors of vertebral fractures (VFx) have been identified in women, but not in men. Several reports have focused on the quality of life (QOL) of clinically diagnosed VFx, but not much has been reported on quantified QOL scores of incidental radiographic VFx in men. This cross-sectional study aimed to investigate the associated factors and the influence of incident radiographic VFx on QOL of men. Methods A total of 401 volunteer men aged 40 years or older (40–92 years) participated in this study. The mean age was 60.5 ± 11.8 years. Prevalent VFx were identified on the lateral lumbar spinal radiographs using the semiquantitative method. Bone mineral density, body composition, smoking, alcohol intake, past medical history, Mini-Mental State Examination, grip strength, gait speed, and biochemical markers were examined. QOL was evaluated using the 36-Item Short-Form Health Survey and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. Results Of the 401 subjects, 35 men (8.7%) had the prevalence of VFx. After adjustment for age, the presence of VFx was significantly associated with IGF-1 (odds ratio 0.985; p = 0.02). QOL scores were not significantly associated with VFx after adjustment for age. Conclusions IGF-1 is the mediator of growth hormone, and IGF-1 stimulates the proliferation, differentiation, and mineralization of osteoblastic cells. The prevalence of VFx in men was 8.7%, and IGF-1 was significantly lower in the VFx group than in the non-VFx group.

Circulating endothelial progenitor cells are a potential surrogate marker for angiogenesis. Little is known about the alteration of circulating endothelial progenitor cell counts during neoadjuvant chemotherapy. Our goal was to reveal the alteration in CEP counts in association with response to neoadjuvant chemotherapy in patients with breast cancer. We measured the number of circulating endothelial progenitor cells (CD31+CD34+CD133+CD45dim) by four-color flow cytometry using blood samples from 57 patients with breast cancer who received neoadjuvant chemotherapy (5-fluorouracil + epirubicin + cyclophosphamide (FEC), docetaxel + cyclophosphamide (TC), cisplatin + docetaxel (TP)). There was no significant difference in the baseline circulating endothelial progenitor cell counts with respect to the clinical and pathological background factors. Circulating endothelial progenitor cell counts increased after the initiation of chemotherapy (pre-1st vs. pre-2nd cycle, p = 0.0035; pre-1st vs. pre-4th cycle, p = 0.047). An increase of circulating endothelial progenitor cell counts from pre-1st to pre-2nd cycle was associated with pCR (p = 0.013 for χ 2 test). A multivariate analysis, including subtype, and clinical response showed that the lack of circulating endothelial progenitor cell increases from pre-1st to pre-2nd cycle was an independent negative predictor of pCR (p = 0.002). Our data suggest that alterations in circulating endothelial progenitor cell counts are associated with treatment response. The circulating endothelial progenitor cell count could be a useful biomarker for monitoring chemotherapeutic response., Breast cancer: Circulating cell counts predict chemo response Breast cancer patients do better after preoperative chemotherapy if their numbers of circulating endothelial progenitor cells (CEPs) go up. A team from Japan led by Takayuki Ueno from the Kyorin University School of Medicine in Tokyo studied 57 women who underwent neoadjuvant chemotherapy to shrink the size of their tumors before surgery. The researchers measured the number of CEPs—cells that derive from the bone marrow and can help build new blood vessels around tumors—both before and during chemotherapy. They found no link between overall CEP counts and treatment response. However, patients whose CEP numbers went up between cycles of chemotherapy had better outcomes. The authors suggest that CEP counts could be used as a diagnostic tool for predicting responses to neoadjuvant chemotherapy, although larger studies are needed to confirm their initial findings

Background: We compared and evaluated three 6-cycle, docetaxel and cyclophosphamide (TC)-containing chemotherapy regimens in a multicenter randomized phase II study. The main aim was to investigate whether anthracyclines are needed or can be omitted, and whether the order of chemotherapy is important, for treating luminal-type breast cancer. Methods: We recruited patients (pts) with ER-positive, HER2-negative breast cancer aged 20–70 years, and histo-pathologically invasive breast cancer (T1c-3, N0-1, M0), T≤7cm. Pts were randomized to 3 groups for the following treatments: 6 cycles of TC; 3 cycles of 5-FU/epirubicin/cyclophosphamide (FEC) followed by 3 cycles of TC (FEC-TC); and 3 cycles of TC followed by 3 cycles of FEC (TC-FEC). TC treatment consisted of administration of docetaxel at 75 mg/m2 and cyclophosphamide at 600 mg/m2 once every 3 weeks. FEC treatment consisted of administration of 5-FU at 500 mg/m2, epirubicin at 100 mg/m2, and cyclophosphamide at 500 mg/m2 once every 3 weeks. We aimed to enroll 65 pts per group based on an expected pCR rate among regimens of adding 10% at a threshold of 9%. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints were overall response rate (ORR), breast conservation rate and safety. Results: A total of 195 pts (median age, 49.5 years (range, 26–69); median tumor size, 32.8 mm (range, 9–82); 91 pts with N(+) (51%)) were enrolled and randomized as follows: FEC-TC (n = 65), TC-FEC (n = 63), and TC group (n = 67). There were no differences in backgrounds among groups. Both the intention-to-treat population and the safety analysis set included 65, 63 and 65 pts in these groups, respectively. The 6-cycle treatment completion rates were 96.9%, 96.8% and 84.6%, respectively. pCR, defined as yT0/isyN0, was achieved by 9.2% of pts in the FEC-TC group, 8.1% in the TC-FEC group, and 15.9% in the TC group (p = 0.321). A quasi pCR in breast (yT0/is and near pCR) was achieved by 13.9%, 14.5%, and 17.5%, respectively. These responses did not differ among the 3 groups. ORRs, assessed by MRI or CT, were 75.8% (CR: 12.9%), 75% (CR: 5%), and 82.2% (CR: 17.9%) in the FEC-TC, TC-FEC and TC groups, respectively. Breast conservation rates were 50.8%, 45.2%, and 73.0%, respectively.Adverse events of Grade≥3 were observed in 20.0%, 27.0%, and 20.3% of pts in the FEC-TC, TC-FEC, and TC groups, respectively, with no significant differences. Febrile neutropenia was observed in 17.2%, 21.0%, and 11.3%, respectively, but in most cases it was managed sufficiently on an outpatient basis. Of 28, 27 and 23 pts in these groups in whom mastectomy was planned, 9 (32%), 5 (19%), and 10 (44%) were successfully converted to undergo breast-conserving surgery. Of 37, 35 and 40 pts in the FEC-TC, TC-FEC and TC groups in whom breast-conserving surgery was planned, 13 (35%), 12 (34%), and 4 (10%) underwent mastectomy. Conclusion: Six cycles of TC had therapeutic effects and safety equivalent to FEC-TC and TC-FEC. The 3 treatment groups showed similar pCR rates, although the breast conservation rate was significantly higher in the TC group than in the other 2 groups. It may be possible to conduct preoperative chemotherapy for pts with ER-positive breast cancer without using an anthracycline. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-05.

Background Circulating cell-free DNA (cfDNA) has recently been recognized as a resource for biomarkers of cancer progression, treatment response, and drug resistance. However, few have demonstrated the usefulness of cfDNA for early detection of cancer. Although aberrant DNA methylation in cfDNA has been reported for more than a decade, its diagnostic accuracy remains unsatisfactory for cancer screening. Thus, the aim of the present study was to develop a highly sensitive cfDNA-based system for detection of primary breast cancer (BC) using epigenetic biomarkers and digital PCR technology. Methods Array-based genome-wide DNA methylation analysis was performed using 56 microdissected breast tissue specimens, 34 cell lines, and 29 blood samples from healthy volunteers (HVs). Epigenetic markers for BC detection were selected, and a droplet digital methylation-specific PCR (ddMSP) panel with the selected markers was established. The detection model was constructed by support vector machine and evaluated using cfDNA samples. Results The methylation array analysis identified 12 novel epigenetic markers (JAK3, RASGRF1, CPXM1, SHF, DNM3, CAV2, HOXA10, B3GNT5, ST3GAL6, DACH1, P2RX3, and chr8:23572595) for detecting BC. We also selected four internal control markers (CREM, GLYATL3, ELMOD3, and KLF9) that were identified as infrequently altered genes using a public database. A ddMSP panel using these 16 markers was developed and detection models were constructed with a training dataset containing cfDNA samples from 80 HVs and 87 cancer patients. The best detection model adopted four methylation markers (RASGRF1, CPXM1, HOXA10, and DACH1) and two parameters (cfDNA concentration and the mean of 12 methylation markers), and, and was validated in an independent dataset of 53 HVs and 58 BC patients. The area under the receiver operating characteristic curve for cancer-normal discrimination was 0.916 and 0.876 in the training and validation dataset, respectively. The sensitivity and the specificity of the model was 0.862 (stages 0-I 0.846, IIA 0.862, IIB-III 0.818, metastatic BC 0.935) and 0.827, respectively. Conclusion Our epigenetic-marker-based system distinguished BC patients from HVs with high accuracy. As detection of early BC using this system was comparable with that of mammography screening, this system would be beneficial as an optional method of screening for BC. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0788-z) contains supplementary material, which is available to authorized users.

Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine has been classified into four types by lateral plain radiographs, but the reliability of the classification and of the diagnosis of either cervical OPLL or cervical spondylotic myelopathy (CSM) was unknown. We investigated the interobserver and intraobserver reliability of the classification and diagnosis for OPLL by radiographs and computed tomography (CT) images.A total of 16 observers classified each patient's images into five groups; OPLL continuous, segmental, mixed, circumscribed type, or CSM. To evaluate interobserver reliability, the observers first classified only radiograph images, and next both radiographs and CT images. On another day they followed the same procedure to evaluate intraobserver reliability. We also evaluated interobserver and intraobserver reliability of the diagnosis of either cervical OPLL or CSM.Interobserver reliability of the classification with radiographs only showed moderate agreement, but interobserver reliability with both radiographs and CT images showed substantial agreement. Intraobserver of reliability the classification was also improved by additional CT images. Interobserver reliability of the diagnosis with both radiographs and CT images was almost similar to with radiographs only. Intraobserver reliability of the diagnosis was improved by additional CT images.This study suggested that the reliability of the classification and diagnosis for cervical OPLL was improved by additional CT images. We propose that diagnostic criteria for OPLL include both radiographs and CT images.

Context:Circulating endothelial cells (CECs) and progenitor cells (CEPs) have been intensively studied as a promising tool for treating ischemic diseases and monitoring cancer treatments, but how the menstrual cycle affects the variation in their counts remains unclear. Objective:The aims of the study were to determine the influence of the menstrual cycle on the number of CECs and CEPs and to investigate the association of their counts with circulating hormones and angiogenesis-associated factors. Design:CEP and CEC counts by flow cytometry and the CellSearch system and circulating factor levels were measured eight times during the menstrual cycle in 18 volunteers. The menstrual cycle was divided into six phases based on hormone concentrations. Results:CEP counts peaked in the periovulatory and middle luteal phases with a drop in the early luteal phase. CEC counts showed no significant variation. There were significant correlations between the CEP counts and the serum concentrations of estradiol (E2), LH, and granulocyte colony-stimulating factor (G-CSF) (P < 0.0001, P < 0.0001, and P = 0.01, respectively). The difference in CEP counts between two adjacent phases was significantly correlated with that in E2, LH, G-CSF, and serum vascular endothelial growth factor (P < 0.0001, P < 0.0001, P = 0.02, and P = 0.006, respectively). Conclusion:CEP counts peaked in the periovulatory and middle luteal phases, with a drop in the early luteal phase, and were correlated with serum E2, LH, and G-CSF concentrations. Consideration of the variation in CEP counts would be important for the clinical application of CEPs.

Mesenchymal stem cells (MSCs) have a fibroblast-like morphology, multilineage potential, long-term viability and capacity for self-renewal. While several articles describe isolating MSCs from various human tissues, there are no reports of isolating MSCs from human spinal ligaments, and their localization in situ. If MSCs are found in human spinal ligaments, they could be used to investigate hypertrophy or ossification of spinal ligaments. To isolate and characterize MSCs from human spinal ligaments, spinal ligaments were harvested aseptically from eight patients during surgery for lumbar spinal canal stenosis and ossification of the posterior longitudinal ligament. After collagenase digestion, nucleated cells were seeded at an appropriate density to avoid colony-to-colony contact. Cells were cultured in osteogenic, adipogenic or chondrogenic media to evaluate their multilineage differentiation potential. Immunophenotypic analysis of cell surface markers was performed by flow cytometry. Spinal ligaments were processed for immunostaining using MSC-related antibodies. Cells from human spinal ligaments could be extensively expanded with limited senescence. They were able to differentiate into osteogenic, adipogenic or chondrogenic cells. Flow cytometry revealed that their phenotypic characteristics met the minimum criteria of MSCs. Immunohistochemistry revealed the localization of CD90-positive cells in the collagenous matrix of the ligament, and in adjacent small blood vessels. We isolated and expanded MSCs from human spinal ligaments and demonstrated localization of MSCs in spinal ligaments. These cells may play an indispensable role in elucidating the pathogenesis of numerous spinal diseases.

Study Design. We categorized the four types of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine into two groups. We biochemically investigated the genetic differences in the osteogenic differentiation potency between the two groups. Objective. To investigate the genetic differences in the osteogenic differentiation potency according to the OPLL classification. Summary of Background Data. Clinical studies on OPLL have revealed that the risk of progression of the ossification area is greatest for continuous and mixed type OPLL. However, until now, these four types of OPLL have been studied as a single condition. Methods. We categorized the four types of OPLL into the OPLL continuous (continuous or mixed type) and OPLL segmental groups (segmental or circumscribed type). Paraspinal ligaments were aseptically obtained from OPLL patients during surgery. The fibroblast-like cells that migrated from the explants were used for experiments. The cells were placed in a 60-mm culture dishes for total ribonucleic acid preparation and 12 well microplates for alkaline phosphatase (ALP) activity staining. After cultures reached confluence, the cells were cultured in osteogenic medium. The messenger ribonucleic acid expression of bone morphogenetic protein-2 (BMP-2), osterix, tumor necrosis factor-α-stimulated gene-6, and ALP was analyzed by quantitative real time-polymerase chain reaction. Osteogenic differentiation of fibroblast-like cells was determined by histochemically detecting ALP production. Results. After osteogenic induction, BMP-2 expression increased in the OPLL continuous and segmental groups. Osterix expression increased in the OPLL continuous group only. Tumor necrosis factor-α-stimulated gene-6 expression was suppressed in the OPLL continuous and segmental groups. ALP expression as well as ALP activity staining was higher in the OPLL continuous group than in the OPLL segmental group. Conclusion. The study revealed genetic differences in the osteogenic differentiation potency between the OPLL continuous and segmental groups. We propose to distinguish OPLL continuous group from segmental group in biochemical studies on OPLL.

Deep neck infection (DNI) is an emergent otolaryngologic disease. We examined 69 patients, 52 males and 17 females, with DNI, who were treated in our hospital between 1995 and 2004. The mean age of DNI patients is 50.0 years old and peak incidence is in the sixth decade. Twenty patients suffered from diabetes mellitus (DM). The primary lesion of DNI was found in the tonsils in 34 cases, the oral cavity in 16 cases, the pharynx in 12 cases, and other regions in 7 cases, respectively. Among 69 DNI patients, infection remained in the suprahyoid region in 31 cases, whereas it extended to the infrahyoid region in 33 cases and to the mediastinum in 5 cases. The titer of serum C-reactive protein (CRP) and the duration of admission were considered parameters of DNI severity. CRP was significantly higher and the duration of admission was significantly longer in elderly patients, in patients with DM, and in patients with infrahyoid and mediastinal DNI, whereas no significant difference was found between males and females, and among the primary lesions. Therefore, we consider that age, DM, and the extension of DNI are important factors determining the severity of DNI. We also refer to the etiology, diagnosis, treatment and complications of DNI.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic ossification in the spinal ligaments, which enlarges with time and compresses the spinal cord, resulting in serious neurological symptoms. We previously reported that Runx2 expression was enhanced in spinal ligament cells from OPLL patients (OPLL cells). To clarify genes regulated by Runx2, Runx2 expression was first enhanced by culturing primary OPLL cells in osteogenic medium (OS induction) and then inhibited by siRNAs targeted to Runx2. DNA microarray demonstrated that in addition to chondrogenic factors such as connective tissue growth factor and cartilage oligomeric matrix protein, angiopoietin-1 was also significantly increased by OS induction and decreased by siRNAs for Runx2 in OPLL cells, suggesting that these genes are regulated by Runx2. However, these changes were not observed in non-OPLL control cells (from cervical spondylotic myelopathy patients). Furthermore, Runx2 was not decreased by siRNAs for angiopoietin-1. OS induction and RNAi inhibition of angiopoietin-1 expression was also observed in osteoblasts. Both siRNAs for Runx2 and angiopoietin-1 completely inhibited aggrecan-1 expression. These results suggest that angiopoietin-1 is downstream of Runx2 in both OPLL primary cells and osteoblasts. Angiopoietin-1 may play an important role in ectopic ossification. Keywords:: Runx2/Cbfa1, angiopoietin-1, microarray, osteochondrogenesis, ossification of the posterior longitudinal ligament (OPLL)

馬尾腫瘍に特徴的な症状・所見およびその手術的治療による症状の改善効果について検討した．対象は，馬尾腫瘍18例(男性9例，女性9例)．組織型はneurinomaが最も多く，発生高位は，第4～第5腰椎レベルが最も多かった．初発症状の出現から診断までの期間は，平均25.2カ月であった．馬尾腫瘍に特徴的な症状は，根性疼痛が50%にみられたことと疼痛の出現に変動があることであった．67%で疼痛の出現に変動があり，そのうち75%で体動による増強がみられた．内訳は立位・歩行動作が67%，咳・くしゃみが33%であった．特徴的な神経学的所見はなかった．手術成績は良好で，術後に加療を要するほどではないが，しびれの訴えが多かった．馬尾腫瘍の治療においてはしびれの残存が課題である．馬尾腫瘍を早期に診断し，不可逆的な神経症状を残す前に治療することが重要である．

Adverse prognostic impact of KIT mutations in childhood CBF-AML: the results of the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 trial

OBJECTIVE To describe the clinical course and treatment of a patient presenting with thrombophlebitis of the head and the neck with eosinophilic otitis media (EOM). PATIENT The patient was a 32-year-old woman with bronchial asthma and chronic sinusitis. She was treated for EOM, which presented as intractable otitis media with viscous effusion. Subsequently, she experienced sudden onset of nausea and headache. No signs of improvement were observed after the intravenous administration of several antibiotics. Magnetic resonance imaging (MRI) revealed right thrombophlebitis extending from the sigmoid sinus to the jugular vein. INTERVENTIONS Systemic administration of adrenocortical steroid hormone after intravenous antibiotic therapy. MAIN OUTCOME MEASURES Radiologic features and patient symptoms. RESULTS Intravenous antibiotic therapy was ineffective, but the patient's symptoms were relieved less than 1 day after the initiation of prednisolone treatment (30 mg/d for 5 d). MRI performed 3 days after treatment revealed that thrombophlebitis of the head and neck had disappeared. CONCLUSION Adrenocortical steroid hormone therapy may be an effective treatment for thrombophlebitis with EOM. Chemoattractants activated by EOM might be associated with the pathogenesis of thrombophlebitis of the head and neck.

Background and objective: Bevacizumab suppressed tumor angiogenesis by blocking the VEGFA signal into endothelial cells. Although, bevacizumab, in combination with chemotherapy, has exhibited some therapeutic efficacy for metastatic breast cancer, its impact on overall survival has not been proved. According to recent studies, VEGF is a multi-function molecule targeting not only endothelial cells but also other cell members in tumor microenvironment, including cancer cells, fibroblasts, immune cells, and so on. In this study, we aimed to reveal VEGF-related molecular mechanisms on breast cancer cells itself. Methods and Results: A VEGF-expressing basal-like type breast cancer cell line, MDA-MB-231 cells (231 cells) were used. VEGFA of 231 cell was knocked out using Crisper-Cas9 system (VEGFA-KO). Compared to the wild type (WT) 231 cells, VEGFA-KO 231 cells showed rounded and weakened adhesive morphology. Scratch assay and motion picture assay demonstrated the VEGFA-KO 231 cells had impaired cell motility. Bevacizumab treatment to WT 231 cells did not induce this morphologic change. Next, we generated soluble neuropilin-1 (sNRP1) overexpressed 231 cells. sNRP1 consists of the NRP1 extracellular domain that includes a VEGFA-binding site, traps VEGFA to function as an antagonist. sNRP1-231 cells exhibited rounded and lower adhesive morphology similar to that of VEGFA-KO 231 cells. Bevacizumab and NRP1 bind VEGFA at amino acid motifs from exon 3-4 and exon 7 of VEGFA, respectively. Thus, our findings suggested that VEGFA could play a role in cell morphology and motility via NRP1 for 231 cells, and that bevacizumab could not block the VEGFA/NRP1 signal. Discussion NRP1 is a transmembrane protein that has been identified as a VEGF-A receptor. NRP1 is expressed by endothelial cells and functions as a co-receptor of VEGFRs, enhancing VEGF-A binding and promoting downstream signaling. NRP1 is also expressed in variety of cancer cells including breast cancer. Since NRP1 molecule lacks kinase activity, there have been efforts to find the mechanisms of NRP1 signaling. To date, NRP1 expression of tumor cells has been shown to contribute to proliferative signal transduction from VEGF-A. Previous study showed VEGF-A/NRP1 signals induced the phosphorylation of Akt leading to breast cancer cell survival (Bachelder et al., 2001). And another study showed that the NRP1 cytoplasmic region enhanced the interaction between NRP1 and GIPC1/Syx/RhoA, and promoted tumor cell proliferation. However, the precise mechanisms regarding NRP1 signaling remains unknown. In conclusion, knocking out of VEGFA and trapping of VEGFA by sNRP1 induced weakened adhesive morphology and impaired cell motility in 231 cells. Because cell adhesion and motility are important factors for tumor metastasis, VEGFA /NRP1 signaling in breast cancer might be related to breast cancer metastasis, and can be a useful therapeutic/preventive target for breast cancer. Citation Format: Marina Kiso, Fumiaki Sato, Sunao Tanaka, Masakazu Toi. VEGFA/NRP1 signal contributes to cell adhesion and motility in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 683.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments. We previously reported that P2 purinoceptor Y1 (P2Y1) expression is elevated in the spinal ligament cells of OPLL patients, but the role of P2Y1 in the spinal ligament calcification process is unknown. To verify the hypothesis that P2Y1 expression causes ossification of the spinal ligaments, we forced expression of P2Y1 in spinal ligament cells obtained from OPLL and non-OPLL patients using a cytomegaloviral vector. The expression of mRNA and protein was investigated by quantitative real-time polymerase chain reaction and immunofluorescence staining, respectively. After transfection, bone morphogenetic protein-2 (BMP-2) and Sox9 mRNA expression was significantly increased in spinal ligament cells derived from OPLL patients (4.36- and 6.44-fold, respectively) compared with cells from non-OPLL patients (0.57- and 3.64-fold, respectively) 2 days after P2Y1 transient transfection. Furthermore, a statistically significant correlation was observed between BMP-2 and P2Y1 mRNA expression levels in cells obtained from OPLL patients but not from non-OPLL patients. Immunofluorescence analysis showed that BMP-2 and P2Y1 expression was increased in OPLL patients only, while Sox9 expression was increased in OPLL and non-OPLL patients. MRS2279, a selective P2Y1 antagonist, blocked the upregulation of Sox9 and BMP-2 after forced expression of P2Y1. Furthermore, 4 days after transient transfection of P2Y1, mineralization was observed only in spinal ligament cells from OPLL patients. These results suggest that P2Y1 expression plays an important role in ectopic bone formation in the spinal ligaments of OPLL patients.

CCAAT/enhancer-binding protein alpha (CEBPA) mutations are a favorable prognostic factor in adult acute myeloid leukemia (AML) patients; however, few studies have examined their significance in pediatric AML patients. Here we examined the CEBPA mutation status and clinical outcomes of pediatric AML patients treated in the AML-05 study. We found that 47 (14.9%) of the 315 evaluable patients harbored mutations in CEBPA; 26 cases (8.3%) harbored a single mutation (CEBPA-single) and 21 (6.7%) harbored double or triple mutations (CEBPA-double). After excluding core-binding factor-AML cases, patients harboring CEBPA mutations showed better overall survival (OS; P=0.048), but not event-free survival (EFS; P=0.051), than wild-type patients. Multivariate analysis identified CEBPA-single and CEBPA-double as independent favorable prognostic factors for EFS in the total cohort (hazard ratio (HR): 0.47 and 0.33; P=0.02 and 0.01, respectively). CEBPA-double was also an independent favorable prognostic factor for OS (HR: 0.30; P=0.04). CEBPA-double remained an independent favorable factor for EFS (HR: 0.28; P=0.04) in the normal karyotype cohort. These results suggest that CEBPA mutations, particularly CEBPA-double, are an independent favorable prognostic factor in pediatric AML patients, which will have important implications for risk-stratified therapy.

A 66-year-old woman developed a malignant rhabdoid tumor of the breast, with a tumor doubling time of 10 days. One month after radical mastectomy, there was local recurrence, followed by multiple pulmonary metastases, and the patient died of respiratory failure 5 months after surgery. The gray-white-colored tumor measured 13 x 12 x 10 cm, and its border was well defined. The tumor was composed of diffusely growing round or polygonal cells with vesicular nuclei, prominent nucleoli, and ample cytoplasm containing eosinophilic inclusions. Lymph node involvement was widespread. Both vimentin and keratin were clearly demonstrated by immunohistochemical staining. Ultrastructural studies revealed that the MRT cells contained cytoplasmic whorls of intermediate filaments.