bluuebunny/crossref_metadata_2025 huggingface dataset:
RT-02 POTENTIAL OF PROTON BEAM THERAPY FOR THE TREATMENT OF GLIOBLASTOMA
Authors: Matsuda Masahide , Ishikawa Eiichi , Mizumoto Masashi , Kohzuki Hidehiro , Sugii Narushi , Matsumura Akira
Published: December 2019

INTRODUCTION

Recently, proton beam therapy has attracted increasing interest in the Japanese neuro-oncological field because of the insurance approval for pediatric brain tumor, chordoma, and chondrosarcoma. We have developed the high dose radiotherapeutic strategy using proton beam for malignant glioma in our institution since long before. Here we retrospectively analyzed the efficacy of this treatment strategy.

METHODS

Thirty-four patients with newly diagnosed GBM who underwent high dose proton beam therapy were investigated. All patients received hyperfractionated concomitant radiotherapy consisting of X-ray radiotherapy (50.4Gy in 28 fractions) and proton beam therapy (46.2Gy [RBE] in 28 fractions). Concurrent chemotherapy consisted of ACNU in the early 6 cases or TMZ in the late 28 cases. The survival outcome and adverse events were analyzed.

RESULTS

The median overall survival time and progression free survival time for all 34 patients were 35.7 months (95%CI, 28.1–43.4) and 11.2 months (95%CI, 6.8–15.7), respectively. No significant survival difference according to the chemotherapy regimen was shown. Failure patterns after proton beam therapy include 19 cases of local recurrence, 3 cases of distant recurrence, and 5 cases of dissemination. Although there was no significant difference in time to recurrence according to the failure pattern, there was a tendency of longer survival in the local recurrence group. As for adverse events, symptomatic radiation necrosis was observed in 9 cases. The median time to onset of necrosis after radiation was 18.2 months (95%CI, 10.2–26.2). There were 8 cases of long survivors over 5 years out of 34 cases (23.5%). Of these, 6 cases developed symptomatic radiation necrosis.

CONCLUSIONS

Our results indicate that high dose proton beam therapy of 96.6Gy (RBE) prolonged survival in selected GBM patients. With appropriate patient selection and potent treatment for radiation necrosis, high dose proton beam therapy has a great potential to improve survival in GBM patients.
RT-03 POSTOPERATIVE CYBERKNIFE HYPOFRACTIONATED RADIOTHERAPY FOR THE ELDERLY PATIENTS WITH GLIOBLASTOMA
Authors: Tabei Yusuke , Sato Kengo , Kimura Toshikazu , Irie Koreaki , Ichi Shunsuke
Published: December 2019

INTRODUCTION

In recent years, hypofractionated radiotherapy (HRT) 40Gy in 15 fractions with concomitant temozolomide(TMZ) has come to be used as standard treatment for elderly glioblastoma. However, the treatment duration of 3–4 weeks for radiation is not enough short, and there is also a problem of radiation sickness. We performed hypofractionated stereotactic radiotherapy with CyberKnife (CK) for less than 2weeks. We retrospectively analyzed eight newly diagnosed elderly patients with glioblastoma treated by CK.

METHODS

Surgical cavity, contrast enhanced lesion, FLAIR high signal intensity area were set as gross tumor volume (GTV). To planned target volume (PTV) as GTV + 2 mm, Marginal dose (D95) 35 Gy in 5 fractions (Fr) was prescribed. The dose prescription and number of fractions were adjusted taking into consideration dose distribution, dose-limiting for important organs such as optic chiasm and brainstem.

RESULTS

The eight patients consisted of 3 men and 5 women. The median age was 78 (range 68–84) years old. All patients were pathologically diagnosed as glioblastoma. Two of 8 cases had undergone gross total removal of contrast area. Median postoperative KPS was 70 (40–80). Thirty three (28–33.5) Gy was administered in 5 (3–10) Fr to PTV 117 (44–243) ml. TMZ was used in 7 patients. Bevacizumab (BEV) was used together from 4 weeks after surgery in 5 patients. Progression-free survival was 6.5 (2.9–10.6) months and overall survival was 17.5 (7.1–28.5) months. 7 patients had experienced controllable hypertension with antihypertensive agents, Two patients had suffered from deep vein thrombosis, and anticoagulation therapy was used. One patient had nausea and malaise due to TMZ and had continue BEV alone. Asymptomatic cerebral infarction in the radiation field was observed in a patient.

CONCLUSION

CK treated in less than half duration of conventional HRT is expected as less invasive treatment.
MPC-06 LRG1 HAS MULTIPLE POTENTIAL FOR CLINICOPATHOLOGICAL BIOMARKER OF GLIOBLASTOMA
Authors: Furuta Takuya , Sugita Yasuo , Komaki Satoru , Ohshima Kouichi , Morioka Motohiro , Uchida Yasuo , Tachikawa Masanori , Otsuki Sumio , Terasaki Tetsuya , Nakada Mitsutoshi
Published: December 2019

BACKGROUND AND AIM

Leucine-rich α-2 glycoprotein 1 (LRG1) is one of the candidate proteins as a diagnostic marker for glioblastoma. Although association with angiogenesis has been reported, it has been suggested that the role as a biomarker differs depending on the tumor types. The role of LRG1 as a biomarker in glioblastoma was examined clinicopathologically.

METHODS

Tumor tissues of 156 cases diagnosed as diffuse glioma (27 astrocytomas, 15 oligodendrogliomas, 114 glioblastomas) according to WHO 2016 classification at Kurume University from January 2001 to April 2019 were used. The immunohistochemical intensity of LRG1 was scoring as 4 stages and classified into 2 groups; score 0–1 was defined as low expression and score 2–3 was defined as high expression. Mutations of IDH1/2 and TERT promoter were analyzed by Sanger method. In glioblastoma, the relationship between LRG1 expression and clinical parameters such as age, preoperative Karnofsky Performance Scale, tumor location, extent of resection, MGMT promoter, and prognosis were examined.

RESULTS

LRG1 high expression rate was 41.2% (47/114) in glioblastoma, 3.7% (1/27) in astrocytoma, 20% (3/15) in oligodendroglioma, and glioblastoma showed significant higher expression level of LRG1 compared with lower-grade glioma (p = 0.0003). High expression of LRG1 was an independent favorable prognostic factor (HR 0.41, 95% CI 0.18–0.86, p=0.019) in IDH-wildtype glioblastoma, and correlated with gross total resection (p = 0.002) and the tumor location of the non-subventricular zone (SVZ) (p = 0.00007).

CONCLUSION

LRG1 demonstrated multiple potential as diagnostic, prognostic, and regional biomarker for glioblastoma.
MPC-16 RAPID PROGRESSIVE SPINAL DIFFUSE MIDLINE GLIOMA, A CASE REPORT
Authors: Takezaki Tatsuya , Shinojima Naoki , Kuroda Junichiro , Yamamoto Takahiro , Makino Keishi , Yokoo Hideaki , Mikami Yoshiki , Mukasa Akitake
Published: December 2019

A 17-year-old boy presented with a 2-week history of lower back pain, progressive gait difficulty and sensory deficit of bilateral lower limbs. Magnetic resonance imaging of neuroaxis showed intramedullary tumor with spinal cord expansion from Th12 to L2 and irregular areas of enhancement. Emergent laminoplasty and biopsy was performed. Histopathological examination showed small atypical cells, but most cells had too much degeneration and necrosis to confirm the diagnosis definitively. Leptomeningeal dissemination caused conscious disturbance, nuchal rigidity and epilepsy. 2 weeks after decompression, we performed cordotomy again for advanced diagnosis, to be found diffuse midline glioma, H3K27M mutant by immunohistopathological examination and DAN sequence. He was treated with combination of whole brain and spine radiation therapy and chemotherapy with temozolomide and bevacizumab. He is still alive over 6 months. The clinical significance of H3K27M mutant in spinal gliomas is unclear. Further examinations are needed.
MPC-17 USEFULNESS OF INTRAOPERATIVE MOLECULAR DIAGNOSIS OF GLIOMA USING REAL-TIME PCR
Authors: Koriyama Shunichi , Nitta Masayuki , Masui Kenta , Maruyama Takashi , Saito Taiichi , Komori Takashi , Muragaki Yoshihiro , Kawamata Takakazu
Published: December 2019

BACKGROUNDS

Based on the comprehensive gene association studies in recent years, the revision was issued in 2016 WHO classification, integrating genetic information in glioma diagnosis. Many studies have been reported the correlation between each molecular subtype and prognosis in the new classification. Gliomas surgery is required to maximum tumor resection with functional preservation. Currently, our institute decides a surgical strategy based on the morphological diagnosis and genetic information from the obtained tissue during the operation. We evaluated the IDH 1/2 gene mutations and 1p/19q codeletion by using real-time PCR intraoperatively. We report the usefulness of this method in this presentation.

OBJECTIVE

58 specimens obtained during surgery from March to November 2017, IDH 1/2 gene mutations and 1p/19q codeletion were evaluated intraoperatively by real-time PCR. IDH 1/2 gene mutations were detected using HRM, and SNP genotyping was used for TERT promoter mutations expected as a surrogate marker for 1p/19q codeletion.

RESULT

Each gene mutation was detected in approximately 90 minutes from DNA extraction of obtained surgical tissue to analysis. The accuracy of HRM of IDH 1/2 mutations was 97.3% (72/74 cases) evaluated by the result of IDH1-R132H IHC or Sanger sequencing, and SNP genotyping of TERT promoter mutations was 94.3% (50/53 cases). There was almost no difference from final genetic information.

CONCLUSION

Real-time PCR is feasible as an intraoperative molecular diagnosis. The accuracy of diagnosis is very high and it can be evaluated in a short time, so it’s useful for decision making during operation.
NI-08 TRIAL AND PROBLEM OF USING ASL IN INTRAOPERATIVE MRI
Authors: Nishiyama Jun , Yonemochi Takuya , Yokota Kazuma , Atsumi Hideki , Sorimachi Takatoshi , Chang Han Soo , Matsumae Mitsunori , Shibukawa Shuhei , Takano Susumu , Kajihara Nao
Published: December 2019

INTRODUCTION

Magnetic resonance perfusion imaging is considered to be available as grading of brain tumor and follow-up of brain treatment. One of the methods, arterial spin labeling (ASL), is a test that is useful for patients with renal impairment and contrast agent allergy and has low invasiveness because it does not use a contrast agent. However, there have been no reports of ASL in intraoperative MRI (iMRI).

PURPOSE

In this hospital iMRI (1.5T), it was examined whether ASL could be used to evaluate residual tumor in patients under general anesthesia.

CASE STUDY

A 75-year-old woman with right temporal lobe Glioblastoma. 43-year-old man, left temporal lobe Diffuse astrocytoma. All performed ASL at the time of MRI imaging for navigation before induction of anesthesia just before surgery and iMRI. In all cases, the blood pressure at iMRI was maintained, and Post Label Delay (PLD) calculated the optimal PLD from the carotid artery velocity measured by iMRI, and defined it as 1800–2200 ms, and performed ASL.

RESULTS

Actually, imaging by iMRI was almost difficult to visualize, and reflux was not recognized not only in the tumor but also in the gray matter.

DISCUSSION

The blood flow velocity measurement in the internal carotid artery is performed by the phase contrast method by intraoperative MRI, and the CBF decreases because propofol used during the operation decreases the CBF and also the brain metabolism. However, it has been suggested that it is one of the factors that make evaluation with ASL difficult. Although the iMRI of our hospital is 1.5 T, which is also a subject of investigation, it is thought that there is a limit to ASL imaging in the case of general anesthesia with propofol even from the calculated PLD.

CONCLUSION

ASL in iMRI at our hospital was not useful.
NI-10 AVAILABILITY OF AMIDE PROTON TRANSFER-WEIGHTED MRI METRICS IN GLIOMA
Authors: Yamashita Shinji , Azuma Minako , Saito Kiyotaka , Watanabe Takashi , Yokogami Kiyotaka , Takeshima Hideo
Published: December 2019

OBJECTIVE

Chemical exchange saturation transfer (CEST) is a novel MR imaging contrast technique that relies on the molecular characteristics of the sample. Amide proton transfer (APT) imaging is an emerging CEST-based MR imaging technique that is sensitive to mobile proteins and peptides in the tissue. APT imaging has become increasingly recognized as a promising imaging modality for glioma. Several reports suggest that APT signals are a promising imaging biomarker for glioma grading and prediction of molecular marker status. In this study, we assessed the utility of APT imaging in glioma by evaluating the relationship between APT signals and clinical parameters in glioma.

METHODS

We enrolled 23 glioma patients (25 lesions) who underwent preoperative MRI with APT imaging and surgery at our institution between May 2018 and July 2019. The median age of patients was 64 years old (range, 14–84). 2 patients had Grade 2, 1 patient had Grade 3, and 22 patients had Grade 4. APT signals were measured inside the ROI that was manually placed in the solid portion of tumor that best represented the entire tumor signal on raw APT images.

RESULTS

We could see that the high APT signals seemed to be related to IDH wild status and high glioma grading (IDH status; p=0.171, Grade; p=0.113). Moreover, the high APT signals were significantly strong related to high Mib-1 LI (p=0.0068, cutoff: 3.295%, sensitivity: 83%, specificity: 71%).

CONCLUSIONS

APT imaging might be associated with IDH mutation status and glioma grading. Especially, high APT signal was a great predictor of high MIB-1 LI in glioma.
NI-18 INVASIONS OF WHITE MATTER AS A PROGNOSTIC FACTOR IN LOW GRADE GLIOMAS
Authors: Nakahara Yukiko , Ito Hiroshi , Koguchi Motofumi , Wakamiya Tomihiro , Masuoka Jun , Abe Tatsuya
Published: December 2019

INTRODUCTION

Gliomatosis cerebri (GC), which was characterized by widespread infiltration of the brain involving three lobes, was deleted in the 2016 WHO classification. However, it is known that gliomas with GC growth pattern have a poor prognosis even in low histological grading. In this study, we focused on tumor invasion into white matter fibers. We analyzed the MRI findings focusing on white matter fibers and compared in patients with histologically proven low grade gliomas (LGGs) with GC pattern and localized LGGs.

METHOD

The patients can be classified into four groups according to the range of tumor invasion in T2-weighted image as follows: group 1, more than 3 lobes (n=6); group 2, 1 or 2 lobes infiltrate the basal ganglia (n=5); group 3, multicentric (n=2) and group 4 (n=12), localized. In reference to the human brain white matter atlas, the infiltration to the major white matter fibers (uncinate fasciculus, genu &splenium of corpus callosum, inferior fronto-occipital fasciculus, superior& inferior longitudinal fasciculus) was examined.

RESULTS

Twenty-five patients (median 39.5 years) were included in the study. Of these, 20 patients were histologically diagnosed with diffuse astrocytomas, and 5 patients with oligodendrogliomas. The infiltrations into ifo, slf, and ilf of white matter fibers were a poor prognostic factor. The number of infiltrating white matter fibers correlated significantly with the Kaplan-Meier survival curve.

CONCLUSIONS

The 2016 WHO classification defines diagnostic entities by combining molecular and histological information and remove GC as a distinct glioma entity. LGGs with GC pattern should be considered to be detected in different types of histologically and molecularly defined gliomas. As the patient numbers analyzed here were small, and larger series reproducing these results would be desirable. MRI findings particularly focusing on infiltration of LGGs into white matter fibers might be important to estimate the prognosis of patients.
NQPC-09 PROGNOSIS AND DELAYED COMPLICATIONS OF MEDULLOBLASTOMA IN KOBE CHILDREN’S HOSPITAL
Authors: Kawamura Atsufumi , Koyama Junji , Akutsu Nobuyuki , Yamanishi Shunsuke
Published: December 2019

Medulloblastoma is the most common pediatric malignant tumor and about 84.2% of cases are under 15 years old. With a current combined-modality approach that includes surgical approach, chemotherapy and radiation therapy, 5 year-survival rates have become 70–85% and also the so-called long-term survivors have increased in our country. This report reviews the prognosis and delayed complications of medulloblastoma in our institute. Cases were 14 boys and 11 girls from January,2010 to May 2019. Mean age was 6.1 years old (4 months to 14 years old). 18 cases receiver gross total removal and 12 cases were high risk group. Exclude recent 4 cases, 15 cases have indicated complete reaction though 6 cases had relapsed or new tumor. The results are that 5 year-survival rates in our institute is 86.7%, but 4 cases had neuro-psychological complications. 5 cases suffered from endocrinal disorders which were not confirmed after the end of all treatments. 2 secondary cancer had appeared 5 and 8 years after the first treatments. The more the survivor in medulloblastoma cases increase, neurosurgeons have to consider long term follow up more than 5 years and pay more attention to support activity of daily life of these patients.
ML-08 THE ROLE OF MAINTENANCE HIGH-DOSE METHOTREXATE CHEMOTHERAPY IN ELDERLY PRIMARY CNS LYMPHOMA PATIENTS
Authors: Mishima Kazuhiko , Shirahata Mitsuaki , Adachi Jun-Ichi , Suzuki Tomonari , Fujimaki Takamitsu , Nishikawa Ryo
Published: December 2019

BACKGROUND

The addition of high-dose methotrexate (HD-MTX)-based chemotherapy to whole brain irradiation (WBRT) has improved the prognosis of primary central nervous system lymphoma (PCNSL). However, the high neurotoxicity rates observed, especially in the elderly, raised interest in chemotherapy-only treatments. Withholding radiotherapy substantially decreases the risk of neurotoxicity, however, disease control may be compromised. In the elderly who cannot tolerate WBRT as a consolidation, maintenance treatment may serve as a feasible approach after an initial response. We treated ePCNSL with induction immunochemotherapy, maintenance chemotherapy with HD-MTX and deferred WBRT. Here, we retrospectively investigated the prognosis for ePCNSL that became CR after the induction chemotherapy.

MATERIAL AND METHODS

Newly diagnosed ePCNSL (median age: 74 years) received biweekly rituximab/HD-MTX for 6 cycles (induction) followed by monthly rituximab/HD-MTX for 2 cycles (consolidation) and then were treated differently according to the radiological response. With CR patients, HD-MTX was continued with every 3 months (maintenance) for 2 years. Patients who did not obtain consent for maintenance therapy were followed up. For PD patients, immunochemotherapy was interrupted and WBRT initiated immediately. Patients with PR and SD were treated with alternative chemotherapy with temozolomide and/or stereotactic radiotherapy or WBRT.

RESULTS

The median PFS was 24.6 months and median OS was 27 months for the entire cohort. Of the 42 ePCNSL, 26 had CR after induction and consolidation, of which 18 cases were carried out maintenance (M+) and 8 cases were followed up (M-). Median PFS was 73 months in the M+ group and 24.5 months in the M- group. Median OS is 102.2months versus 27.6 months, respectively. Both mPFS (P= 0.0125) and mOS (P =0.0015) were significantly prolonged by maintenance therapy.

CONCLUSION

It was suggested that maintenance treatment with HD-MTX may improve the prognosis for ePCNSL that reached complete response after induction therapy.
ML-10 PRIMARY DIFFUSE LARGE B-CELL LYMPHOMA OF THE CRANIAL VAULT: A CASE REPORT
Authors: Nitta Naoki , Fukami Tadateru , Sasao Akifumi , Nozaki Kazuhiko
Published: December 2019

BACKGROUND

Tumors other than meningiomas, cavernous malformations and metastatic tumors rarely originate in the cranial vault. We report a case of primary diffuse large B-cell lymphoma of the cranial vault.

CASE DESCRIPTION

A 58-year-old woman was referred to our hospital because of a right frontal subcutaneous mass that had rapidly increased in size. The patient had been well until approximately 2 months before this referral, when she had slight difficulty in opening the right eye. Thereafter she had headaches and a swelling of the forehead. She was seen in a neurosurgery clinic and referred to our hospital. She had no past history of serious illnesses, operations or hospitalizations. On examination, there was a fixed firm mass, 13 cm in size, in the right side of the forehead. The skin on the center of the mass was stretched and took on a reddish hue. Neurological examination was negative. Blood chemistry tests showed lactate dehydrogenase four times above normal and a slight increase in alkaline phosphatase, amylase and lipase. Beta-2-microglobulin was normal. Bone windows of computed tomography (CT) of the head showed hyperostosis and permeative lytic changes of the frontal bone. Postcontrast MRI showed a large enhanced subgaleal lesion extending through the bony calvarium with a large subdural component. Histological examination after a biopsy was characteristic for a diffuse large B-cell lymphoma. Postcontrast CT of the abdomen and FDG-PET showed metastatic lesions in the pancreas, kidneys and cervical lymph nodes. The patient has been treated by CHOP chemotherapy and has been well.

CONCLUSIONS

We present a case of primary diffuse large B-cell lymphoma of the cranial vault. We recommend including this tumor variant in the differential diagnosis of rapid growing cranial vault tumors.
ML-13 AN ATTEMPT OF RECHALLENGE OF HD-MTX AND MAINTENANCE THERAPY OF MTX FOR PATIENTS WITH PCNSL
Authors: Yamaguchi Takashi , Nagayama Rie , Gomi Akira , Kawai Kensuke
Published: December 2019

PURPOSE

High dose methotrexate (HD-MTX) followed by radiotherapy (RT) is a standard therapy for primary CNS malignant lymphoma. However, the delayed neuronal toxicity due to RT is a serious problem especially for elderly patients. To avoid RT toxicity, we performed re-challenge of HD-MTX until complete remission (CR). Furthermore, we started maintenance therapy (MT) with MTX for elderly and poor Karnofsky Performance Scale (KPS) patients and reported the interim results.

METHODS

We performed HD-MTX (3.5g/m2) therapy until achieving CR for patients whose ages were older than 70 years old and KPS were less than or equal to 60%. After having CR, 3 courses of MT of MTX (3g/patient) for 3 weeks were introduced every 3–4 months for 2 years. In cases of recurrence, HD-MTX was repeated. But when CR was not achieved by HD-MTX, RT was introduced.

RESULTS

Number of patients was 8. Median age, median KPS, and median follow up periods were 73.5y.o. (71–78), 40% (30–60), and 4.5mo. (1–42), respectively. CR rate was 75% but two patients did not achieve CR. One patient had a complication of acute tubular necrosis just after first use of HD-MTX and another died due to pneumocystis pneumonia after 4th HD-MTX. Two patients without RT maintained CR and good KPS over 2 years. Four patients with RT maintained CR but their KPS gradually deteriorated.

DISCUSSION

Rechallenge of HD-MTX exhibits better results and comparable safety with standard treatment, but RT was unavoidable. In order to avoid RT, we started MTX maintenance therapy for elderly and poor KPS patients before recurrence. Our maintenance therapy is easy and good disease control for patients who had not received RT, however there were two serious adverse events.

CONCLUSION

Rechallenge of HD-MTX and maintenance therapy of MTX might be promising but dangerous for elderly patients. Further careful assessment is needed.
MNG-03 PD-L1 EXPRESSION, PATIENT PROGNOSIS AND INITIAL WHO GRADE IN GRADE II/III MENINGIOMA
Authors: Kamamoto Dai , Sasaki Hikaru , Sasao Ryota , Fujiyama Takumi , Yoshida Kazunari
Published: December 2019

The optimal treatment for grade II/III meningioma is operation with or without radiation therapy. However, their natural course is sometimes aggressive with high recurrent rate. There is no effective treatment other than operation and radiation therapy, therefore, a new therapeutic strategy for grade II/III meningioma is urgently required.PD-1 and PD-L1 play important roles as immune-checkpoint mediators within tumor microenvironment and the antibodies to these molecules are now approved for the treatment of various kinds of cancers. In Japan, anti-PD-1 antibody and anti-CTLA-4 antibody are approved for unresectable melanoma or advanced / recurrent non-small cell lung cancer and their high effectiveness has been reported. We investigated the expression of PD-L1 (clone:28-8) in 51 cases of grade II/III meningioma by immunohistochemistry and analyzed the relationship between the expression with overall survival, progression free survival and initial WHO grade. For now, we have evaluated 25 cases of PD-L1 immunohistochemistry and PD-L1 showed positivity in 15 cases. There is no correlation observed between PD-L1 expression and patients’ prognosis. Although it does not reach a significant difference, the WHO grade at the time of initial operation tends to be high in those with high PD-L1 staining rate.Similar studies that were previously reported did not use antibodies targeting clone 28-8, which was used as a companion diagnosis for nivolumab administration, but “Correlation between PD-L1 expression and WHO grade”, or “PD-L1 expression is an independent prognostic factor” have been reported. In our investigation, which was using antibodies for companion diagnosis, PD-L1 was positive in more than half of Grade II / III meningiomas and it also related to WHO grade. These results suggest the possibility that tumor immune evasion mechanisms are also working in meningiomas. At the conference, we will report it with the specific data from all cases with a literature review.
CS-05 EXTRA-PARENCHYMAL (PERIPHERAL) ATYPICAL TERATOID / RHABDOID TUMORS
Authors: Oka Hidehiro , Kusumi Mari , Kondo Koji , Koremura Masafumi
Published: December 2019

AT/RT is a malignant embryonal tumor reported by Rorke in 1996. Authors reported first AT/RT in Japan in 1998. This tumor entity was included as new malignant embryonal tumor in WHO 2000, and tumors of Japanese patients has been reported more than 60 cases in the past. This AT/RT is a tumor in the brain parenchyma that a medulloblastoma and PNET and the possibility that it has been misdiagnosed have had pointed out. On the other hand, it is reported that there is the type that we should call peripheral AT/RT which rarely occurs in extra-parenchyma. We want to propose that there is such special tumor group. In the results, age: 6 infants were main (2nd - 14 years old after birth). tumor location: 6 sellar region, 3 civuses, 2 petrous bone or cerebellum and 2 conexities. treatment: duration of survival significantly improved all macroscopic tumor resection by the operation, but, in small pontine part AT/RT, an outcome tended to be poor. On the other hand, in AT/RT which occurred in the sellar region, all cases adult woman tended to have good prognosis. It is necessary for AT/RT (central AT/RT) in the brain to recognize that there is extra-parenchymal AT/RT (peripheral AT/RT) tumor which we reported this time which came to be recognized widely.
COT-01 SYMPTOMATIC EPILEPSY INDUCED BY MALIGNANT BRAIN TUMOR
Authors: Oyama Hirofumi
Published: December 2019

CASES

We report about 41 cases of malignant brain tumor which were treated with operation, irradiation, chemotherapy during past 62 months. 34 cases of glioblastoma, 2 cases of malignant glioma(WHO grade III), 2 cases of medulloblastoma, 1 case of germ cell tumor, 1 case of malignant neurocytoma, and 1 case of malignant ependymoma were included in 41 cases. Two cases of glioblastoma survived over than 25 years, but the median survival of dead 11 glioblastoma cases was 22 months. 4 cases were expired among another 7 cases.

RESULTS

6 cases showed mutation in ATRX and one case had mutation of IDH-1 among 34 cases of glioblastoma. One case showed mutation in ATRX and IDH-1 among 2 cases of malignant glioma. But the mutation in ATRX and IDH-1 had no correlation with convulsion. The initial symptom was epilepsy in 3 cases of glioblastoma and another 3 cases of glioblastoma showed convulsive seizure thereafter. One case of glioblastoma showed rapid aggravation of symptom after convulsion. The initial symptom was epilepsy in 1 case of malignant glioma. One case of malignant ependymoma and one case of medulloblastoma showed rapid aggravation of symptom after convulsion.

DISCUSSION

Nine cases showed convulsion among our 41 cases. Convulsion happened as initial symptom in 4 cases but it happened during treatment in 5 cases. Three cases among these 5 cases showed rapid aggravation of symptom after convulsion. So pre- and post-operative anti-epileptic treatment seems to be necessary.
COT-03 EVALUATING FUNCTIONING AND DISABILITY OF A PATIENT WITH BRAIN TUMOR BY WHODAS
Authors: Ishita Kohei , Ikeda Mitsuyo , Yamada Shin , Okajima Yasutomo , Saito Kuniaki , Kobayashi Keiichi , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

BACKGROUND

The WHO Disability Assessment Schedule (WHODAS) is a practical assessment instrument which measures level of functioning in the following six domains of life. Here we report a case of brain tumor who was evaluated with the 36-item full version of WHODAS 2.0 (self-administered mode), and discuss usefulness of the WHODAS.

CASE PRESENTATION

A 69-year-old man was referred to our hospital with cognitive problems because of which he needed assistance for his ADLs at home. He was diagnosed as having primary central nervous system lymphoma (PCNSL) following open brain biopsy, and was transferred to our hospital for chemotherapy at 23 days after the biopsy. He showed no sign of motor or sensory impairments, but initial evaluation revealed that he had troubles in judgment in his ADLs mainly because of marked memory deficits. Motor, cognitive and total FIM score was 65/91, 22/35, and 87/126, respectively and MMSE score was 24/30. After 48 days of chemotherapy (3 courses of initial DeVIC and following R-MPV regimens), he was temporally discharged home before readmission for another chemotherapy. According to him and his family, he was then basically independent in ADLs at home. We implemented WHODAS 2.0 to demonstrate minute ADL problems of this patient at home so that we might focus on rehabilitation for specific problems at home. Sub-scores of the WHODAS were 15/30 for Cognition, 10/25 for Mobility, 4/20 for Self-care, 14/25 for Getting along, 12/20 for Life activities, and 27/40 for participation. In fact, he felt difficulty in the areas of “activity and participation”.

DISCUSSION

The WHODAS is useful to identify various problems in their daily livings even though patients were independent in ADLs. Patients with brain tumors often repeat hospitalization for medical treatment. We have to be alert to not only objective but subjective changes in ADLs at home.
Quantification of rhBMP2 in bioactive bone materials
Authors: Lian Huan , Wang Han , Han Qianqian , Wang Chunren
Published: December 2019

Bone morphogenetic protein (BMP), belongs to transforming growth factor-β (TGF-β) superfamily except BMP-1. Implanting BMP into muscular tissues induces ectopic bone formation at the site of implantation, which provides opportunity for the treatment of bone defects. Recombinant human BMP-2 (rhBMP-2) has been used clinically, but the lack of standard methods for quantifying rhBMP-2 biological activity greatly hindered the progress of commercialization. In this article, we describe an in vitro rhBMP-2 quantification method, as well as the data analyzation pipeline through logistic regression in RStudio. Previous studies indicated that alkaline phosphatase (ALP) activity of C2C12 cells was significantly increased when exposed to rhBMP-2, and showed dose-dependent effects in a certain concentration range of rhBMP-2. Thus, we chose to quantify ALP activity as an indicator of rhBMP-2 bioactivity in vitro. A sigmoid relationship between the ALP activity and concentration of rhBMP-2 was discovered. However, there are tons of regression models for such a non-linear relationship. It has always been a major concern for researchers to choose a proper model that not only fit data accurately, but also have parameters representing practical meanings. Therefore, to fit our rhBMP-2 quantification data, we applied two logistic regression models, three-parameter log-logistic model and four-parameter log-logistic model. The four-parameter log-logistic model (adj-R2 > 0.98) fits better than three-parameter log-logistic model (adj-R2 > 0.75) for the sigmoid curves. Overall, our results indicate rhBMP-2 quantification in vitro can be accomplished by detecting ALP activity and fitting four-parameter log-logistic model. Furthermore, we also provide a highly adaptable R script for any additional logistic models.
Actavis Group PTC EHF v ICOS Corporation
Authors:   Supreme Court
Published: December 2019

H1 Patents – European Patents – Pharmaceuticals – Tadalafil – Dosing regimens – Revocation – Obviousness – Obvious to try – Fair expectation of success – Relevant factors – Dose ranging studies – Routine tests – Whether permissible to take into account information not available at priority date – The “patent bargain” – The “problem-and-solution” approach – Role of the appellate court – Appeal to Supreme Court
The development of a noninvasive behavioral test for assessment of goat–human interactions
Authors: Markland M L , Goering M J , Mumm J M , Jones C K , Crane A R , Hulbert L E
Published: December 2019

The objective was to develop a protocol for a noninvasive behavioral test to assess goat–human interactions. Boer goats (n = 45) were housed in groups of 3 at the K-State Sheep and Meat Goat Unit. A 3-min human approach test (HAT) was conducted after their first- and seventh-handling experience (i.e., moved by group through the chute and scale). Video footage was analyzed using specialized software (Observer 11.5 XT, Leesburg, VA, USA). The ethogram included three main categories (mutually exclusive within category): 1) spatial (close, middle, far); 2) orientation (facing vs. turned-away); and 3) structural (lie, stand, and nutritive and nonnutritive oral behaviors). The durations of these behavior outcomes were converted to percent, and then applied to a weighted formula to create an approach index (AI). This index placed behaviors on a 0 to 100% scale (0 = lying in back of the pen; 100 = closest to the human, performing oral behaviors). The Proc Univariate (SAS v.9.3, SAS Inst. Inc., Cary, NC, USA) was used to evaluate descriptive statistics and calculate sample size for future projects from all behavior outcomes. In addition, each goat AI categorized as great approach (GA; ≥75% quartile), moderate approach (MA; 25% to 75% quartiles), or least approach (LA; ≤ 25%) and the 1st vs. 7th handling experience was evaluated using Chi-square (χ 2) analysis. The CV% was low for the AI outcome; therefore, less animals are needed if the AI is used rather than other behavior outcomes used. After the first-handling experience, there were less GA-goats than what was expected from the χ 2 analysis (χ 2 = 17.6; P ≤ 0.01; residual = 0.26; expected = 24.5). After the seventh-handling experience, there were more MA-goats than expected (χ 2 = 17.6; P ≤ 0.01; residual = 1.92; expected = 52.0). Repeated handling appeared to moderately improve goat approach to humans, which indicates that this protocol is a promising behavioral test to assess welfare of goats.
Rice Stripe Mosaic Virus–Encoded P4 Is a Weak Suppressor of Viral RNA Silencing and Is Required for Disease Symptom Development
Authors: Zhang Chao , Chen Dong , Yang Guoyi , Yu Xiyuan , Wu Jianguo
Published: December 2019

Viral suppressors of RNA silencing (VSRs) are a cluster of viral proteins that have evolved to counteract eukaryotic antiviral RNA silencing pathways, thereby contributing to viral pathogenicity. In this study, we revealed that the matrix protein P4 encoded by rice stripe mosaic virus (RSMV), which is an emerging cytoplasmic rhabdovirus, is a weak RNA silencing suppressor. By conducting yeast two-hybrid, bimolecular fluorescence complementation, and subcellular colocalization assays, we proved that P4 interacts with the rice endogenous suppressor of gene silencing 3 (OsSGS3). We also determined that P4 overexpression has no effect on OsSGS3 transcription. However, P4 can promote the degradation of OsSGS3 via ubiquitination and autophagy. Additionally, a potato virus X–based expression system was used to confirm that P4 enhances the development of mosaic symptoms on Nicotiana benthamiana leaves by promoting hydrogen peroxide accumulation but not cell death. To verify whether P4 is a pathogenicity factor in host plants, we generated transgenic P4-overexpressing rice plants that exhibited disease-related developmental defects including decreased plant height and excessive tillering. Our data suggest that RSMV-encoded P4 serves as a weak VSR that inhibits antiviral RNA silencing by targeting OsSGS3.
Pathotype Grouping of Cercospora sojina Isolates on Soybean and Sensitivity to QoI Fungicides
Authors: Mengistu Alemu , Ray Jeffery D. , Kelly Heather M. , Lin Binbin , Yu Hao , Smith James R. , Arelli Prakash R. , Bellaloui Nacer
Published: December 2019

Frogeye leaf spot (FLS), caused by Cercospora sojina, is a common disease of soybean in the southern and northern United States and causes significant yield loss. The use of the current race scheme for classification for C. sojina does not take into account the range of disease severity reactions within each differential. The objective of this research was to better understand the diversity among C. sojina isolates through the development and use of pathogenicity groups. In this study, 83 isolates acquired from 2006 to 2009 were screened using 12 soybean (Glycine max) differentials. Disease severity on the 12 differentials ranged from 0 to 9, where 0 is immune and 9 is very susceptible. The average severity for each isolate across differentials ranged from 1 to 7. The 83 isolates were grouped into five pathogenicity groups (PG): PG1, PG2, PG3, PG4, and PG5, reflecting the severity grouping. Using the 12 differentials, PG1 isolates were differentiated by the lack of infection on Davis, Peking, Kent, Palmetto, Hood, CNS, Tracy, and Richland. PG2 had a range of infections on a scale of 1 to 2 on all differentials except on Davis; PG3 isolates had severity ranging from 3 to 4 except on Davis. PG4 isolates caused no infection on Davis, a maximum disease severity of 5 on Peking, while the rest of differentials had severities from 5 to 6. PG5 isolates caused no infection on Davis, severity of 7 on CNS, and severity of 8 on Kent, Hood, and Palmetto. The remaining seven differentials had severities of 9. Across the geographical locations, the predominant pathotypes were PG3 and PG4 and represented 84% of the tested isolates. Azoxystrobin fungicide sensitivity tests showed that 88% of the isolates were sensitive and dominated the population, while only 6% had a high level of fungicide resistance, suggesting that FLS resistance to the QoI fungicide group was not yet completely developed and had not spread to other areas at the time when these isolates were acquired. The overall virulence profile of the isolates indicated that there was variation in disease severity, suggesting that selection of resistance for each PG may produce lines with more precisely defined interactions to specific pathotypes of C. sojina. This may improve the screening and selection of useful resistance genes that could be pyramided for resistance to each pathogenicity group.
Prevalence and Epidemics of Neoscytalidium Stem and Fruit Canker on Pitahaya (Hylocereus spp.) in South Florida
Authors: Hong Cheng-Fang , Gazis Romina , Crane Jonathan H. , Zhang Shouan
Published: December 2019

Since the 2000s, production of pitahaya (Hylocereus spp.) has increased significantly in South Florida. However, very limited information is available on the main diseases affecting this crop, particularly in regard to disease epidemiology and economic impact on the commodity. In this study, we surveyed five local pitahaya orchards and documented the most prevalent diseases and their causal agents. Three genera of fungal pathogens (Neoscytalidium, Alternaria, and Colletotrichum) were the major groups associated with symptoms on pitahaya cladodes (stems) during the early growing season. Among these, N. dimidiatum was identified as the most prevalent pathogen, with an overall isolation frequency of 29.8% (range, 13.9 to 47.2%). Hence, the temporal progress of N. dimidiatum stem canker infection was monitored and the relationship between stem canker intensity (incidence and severity) and fruit canker incidence was investigated. A significant positive correlation was found between fruit canker incidence and the standardized area under the disease incidence or severity curve on cladodes, suggesting that high stem canker intensity in the early season may contribute to high fruit canker incidence and thereby impact the aesthetic and market value of fruits. In vitro assays showed that both conidial germination and mycelial growth of N. dimidiatum are positively correlated with increasing temperature, with a maximum growth area at 32°C. This finding suggests a higher risk of infection, under an environment with high temperatures, which is common in South Florida. Data obtained in this study represent baseline knowledge for the future development of integrative management programs for controlling major diseases of pitahaya in South Florida.
Assessing Swallowing of the Breastfeeding NICU Infant Using Fiberoptic Endoscopic Evaluation of Swallowing
Authors: Armstrong Erika S. , Reynolds Jenny , Sturdivant Chrysty , Carroll Sandra , Suterwala Mustafa S.
Published: December 2019

Background:

Premature infants may demonstrate feeding difficulties requiring an instrumental swallowing assessment. Fiberoptic endoscopic evaluation of swallowing (FEES) is one assessment that can evaluate bottle feeding and breastfeeding.

Purpose:

This pilot study investigated the safety and feasibility of FEES for neonatal intensive care unit (NICU) infants during breastfeeding.

Methods:

The setting for this prospective, descriptive study was an urban level III NICU that provided care for premature and critically ill infants. Participants were 5 infants recruited from a convenience sample who were at least 37 weeks postmenstrual age, demonstrated feeding difficulties during a bedside feeding and swallowing examination, and were breastfeeding. Each participant received a FEES assessment while breastfeeding (FEES-B). Adverse events and vital signs including prefeeding and postfeeding respiratory rate, heart rate, and oxygen saturation level were recorded to assess safety. Visualization of milk, laryngeal penetration, and tracheal aspiration assessed feasibility.

Results:

Participants had a mean postmenstrual age of 39.8 weeks. No adverse events, including epistaxis or laryngospasm, were reported; there were no instances of autonomic instability; and there were no statistically significant differences between prefeeding and postfeeding respiratory rate, heart rate, or oxygen saturation level. Two infants successfully breastfed during FEES-B. Human milk was observable, and laryngeal penetration was noted with 1 infant.

Implication for Practice:

FEES-B was found to be safe, with limited data supporting feasibility. Infants demonstrated no physiologic instability during FEES-B, and milk was visualized in the pharynx during breastfeeding with 2 infants.

Implication for Research:

Further studies are warranted to assess effectiveness of FEES-B in infants.
Safe Zone for Anterior Retractor Placement in Total Hip Arthroplasty: A Cadaveric Study
Authors: Mathew John K. , Nithyananth Manasseh , Kumar Govindaraju Santhosh
Published: December 2019

Aim:

Femoral nerve entrapment during placement of anterior retractors for total hip replacement results in considerable morbidity, although it is uncommon. The aim of this study is to describe a safe zone for placement of anterior retractors during total hip arthroplasty by studying anatomy in cadavers.

Materials and Methods:

Ten hips from 6 cadavers were dissected and studied. The clock face anatomy of the acetabulum was used as pins were placed at various clock positions before proceeding with the sectioning of the surrounding muscles. For the left hip 6, 5, 3, 1, and 12’o clock positions and for the right hip 6, 7, 9, 11, and 12’o clock positions were pinned along the anterior acetabular wall. The limbs were dissected axially, beginning from the inferior aspect of the acetabulum and proceeding in a proximal sequence with an interval of 1 cm. The plane of the first section passed through the distal end of the acetabulum and was named plane A. The subsequent proximal planes were named planes B, C, and D, respectively. The distance between the femoral nerve and the anterior acetabular wall was measured.

Results:

The distance from the anterior acetabular rim to the femoral nerve was closest at plane C, measuring 10.76±2.58 mm (which coincides with the 3’o clock position in the left hip and the 9’o clock position in the right hip). The anteroposterior diameter of Iliacus muscle was maximum at plane A, measuring 17.56±3.90 mm (which coincides with the 6’o clock position in both the right and left hips), and mediolateral diameter of iliopsoas was maximum at plane D, measuring 28.50±3.74 mm (which coincides with the 11’o clock position in the right hip and the 1’o clock position in the left hip).

Conclusions:

The femoral nerve is closest to the anterior acetabular rim at plane C (9’o clock position of the right hip/3’o clock position of the left hip). Hence, the Hohmann retractor should not be placed on this plane. Anterior retractors can be safely placed adjacent the acetabular rim at planes A, B, and D.
Effectiveness of a Faculty Mentor Development Program for Scholarship at an Academic Health Center
Authors: Sood Akshay , Qualls Clifford , Tigges Beth , Wilson Bronwyn , Helitzer Deborah
Published: December 2019

Introduction:

Mentors are in short supply at academic health centers (AHCs). The effectiveness of training mentors (without preselection for their research skills) to support faculty mentees in scholarly activities at AHCs is not well known.

Methods:

The University of New Mexico Health Sciences Center has a two-component program to develop effective mentors for scholarship for faculty mentees. It has an online component supplemented by an optional face-to-face (F2F) component. Study outcomes included changes in self-reported knowledge scores for online users and Mentoring Competency Assessment scores for F2F users.

Results:

One hundred five mentors, mostly women associate professors, used the online program. Online users demonstrated improvement in self-reported knowledge scores. Thirty-eight users additionally completed the F2F program—63% on a clinician–educator track and none with a National Institutes of Health–funded K-award mentee. The self-reported Mentoring Competency Assessment composite score rose from 4.3 ± 1.0 to 5.5 ± 0.8 (pairedt= 7.37, df = 37,P< .001) for the F2F participants, with similar improvement noted in the clinician–educator subgroup.

Discussion:

Users of the online and F2F components of the program improved their self-assessed knowledge and mentoring skill, respectively, demonstrating the effectiveness of the program. Such programs may help AHCs enhance the scholarship and the diversity of their scientific and clinician–educator workforce.