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  • Author or Editor: Akira Matsumura x
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Eiichi Ishikawa, Akira Matsumura, Takashi Enomoto, Takao Tsurubuchi and Tadao Nose

✓ The authors present a case of a rare cutaneous lesion resembling a human finger that protruded from the posterior thoracic region of a 7-month-old girl who was examined after the fingerlike protrusion was noted at birth. The protrusion measured 3 cm in length and 1 cm in diameter. It was located at the level of T-12 and was surrounded by angiomatous and lipomatous tissue. A computerized tomography scan demonstrated three bones in the protrusion, including deformities of the T-9 and T-10 and T-11 dysraphism. Magnetic resonance imaging revealed a hyperintense signal on the T1-weighted sequence and a hypointense signal on the T2-weighted sequence, which was visualized at the attachment to the spinal cord from T9–11. After removal of the fingerlike structure and subcutaneous mass, a T10–11 laminectomy and removal of the intradural mass were performed. Histological examination showed that the appendage was composed of nail, three bones, cartilage, and normal skin. This appendage can be recognized not only as a variant type of caudal appendage but as an ectopic finger and fingernail. The authors discuss the developmental differences among the protrusion in the present case and ordinary caudal appendages.

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Akira Matsumura, Izumi Anno, Hiroshi Kimura, Eiichi Ishikawa and Tadao Nose

✓ The authors describe a case of spontaneous intracranial hypotension in which the leakage site was determined by using magnetic resonance (MR) myelography. This technique demonstrated the route of cerebrospinal fluid (CSF) leakage, whereas other methods failed to show direct evidence of leakage. Magnetic resonance myelography is a noninvasive method that is highly sensitive in detecting CSF leakage. This is the first report in which a site of CSF leakage was detected using MR myelography.

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Satoru Osuka, Akira Matsushita, Eiichi Ishikawa, Kousaku Saotome, Tetsuya Yamamoto, Aiki Marushima, Naoaki Satou, Alexander Zaboronok, Tomohiko Masumoto and Akira Matsumura

Object

For several decades, clinicians have predicted intraparenchymal brain pressure or brain tissue compression indirectly based on the degree of distortion of the midline structures (midline shift) and ventricle wall (ventriculomegaly) observed on conventional MRI. However, this method has several limitations. Diffusion tensor imaging (DTI) is a novel MRI technique that can provide information about the microstructural properties of compressed tissue. In this study, the authors evaluated whether DTI can precisely define the degree of tissue compression in patients with chronic subdural hematoma (CSDH).

Methods

The study sample consisted of 18 patients (mean age 71 years, 10 men and 8 women) with unilateral CSDH and 12 age-matched volunteers. Diffusion tensor imaging results were acquired before and after the surgical irrigation in the CSDH group. Subdural pressure during the operation was also measured. Fractional anisotropy (FA) values were evaluated at several locations, including the gray matter.

Results

The FA values of the gray matter, especially in the caudate nucleus and putamen, were increased in the patients with CSDH compared with the control group. The change in FA data before and after surgery (ΔFA) correlated with the degree of tissue compression evaluated by measurement of the subdural pressure. Furthermore, the increased FA values in patients with CSDH decreased after surgery.

Conclusions

These findings indicate that FA values of the gray matter, especially in the caudate nucleus and putamen, may be important markers of tissue compression. The assessment of FA values of the gray matter will result in a new, less-invasive diagnostic technique to evaluate the degree of brain compression.

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Satoru Osuka, Akira Matsushita, Tetsuya Yamamoto, Kousaku Saotome, Tomonori Isobe, Yasushi Nagatomo, Tomohiko Masumoto, Yoji Komatsu, Eiichi Ishikawa and Akira Matsumura

Object

Ventriculomegaly is a common imaging finding in many types of conditions. It is difficult to determine whether it is related to true hydrocephalus or to an atrophic process by using only imaging procedures such as MR imaging after traumatic injury, stroke, or infectious disease. Diffusion tensor (DT) imaging can distinguish the compression characteristics of white matter, indicating that increased diffusion anisotropy may be related to white matter compression. In this preliminary study, the authors compared the DT imaging findings of ventriculomegaly with those of chronic hydrocephalus or atrophy to clarify the potential of diffusion anisotropy in the identification of hydrocephalus.

Methods

Ten patients with chronic hydrocephalus, 8 patients with atrophy (defined by conventional devices and surgical outcome), and 14 healthy volunteers underwent DT imaging. Images were acquired before and after shunting or once in cases without shunting. The fractional anisotropy (FA) values at many points around the lateral ventricle were evaluated.

Results

The FA patterns around the lateral ventricle in the chronic hydrocephalus and atrophy groups were different. Especially in the caudate nucleus, FA was increased in the chronic hydrocephalus group compared with the atrophy group. Furthermore, the FA values returned to normal levels after shunt placement.

Conclusions

Assessment of the FA value of the caudate nucleus may be an important, less invasive method for distinguishing true hydrocephalus from ventriculomegaly. Further research in a large number of patients is needed to verify the diagnostic ability of this method.

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Yosuke Masuda, Hiroyoshi Akutsu, Eiichi Ishikawa, Masahide Matsuda, Tomohiko Masumoto, Takashi Hiyama, Tetsuya Yamamoto, Hidehiro Kohzuki, Shingo Takano and Akira Matsumura

OBJECTIVE

MRI scans obtained within 48–72 hours (early postoperative MRI [epMRI]), prior to any postoperative reactive changes, are recommended for the accurate assessment of the extent of resection (EOR) after glioma surgery. Diffusion-weighted imaging (DWI) enables ischemic lesions to be detected and distinguished from the residual tumor. Prior studies, however, revealed that postoperative reactive changes were often present, even in epMRI. Although intraoperative MRI (iMRI) is widely used to maximize safe resection during glioma surgery, it is unclear whether iMRI is superior to epMRI when evaluating the EOR, because it theoretically shows fewer postoperative reactive changes. In addition, the ability to detect ischemic lesions using iMRI has not been investigated.

METHODS

The authors retrospectively analyzed prospectively collected data in 30 patients with glioma (22 and 8 patients with enhancing and nonenhancing lesions, respectively) who underwent tumor resection. These patients had received preoperative MRI within 24 hours prior to surgery, postresection radiological evaluation with iMRI during surgery, and epMRI within 24 hours after surgery, with all neuroimaging performed using identical 1.5T MRI scanners. The authors compared iMRI or epMRI with preoperative MRI, and defined a postoperative reactive change as a new postoperative enhancement or T2 high-intensity area (HIA), if this lesion was outside of the preoperative original tumor location. In addition, postoperative ischemia was evaluated on DWI. The iMRI and epMRI findings were compared in terms of 1) postoperative reactive changes, 2) evaluation of the EOR, and 3) presence of ischemic lesion on DWI.

RESULTS

In patients with enhancing lesions, a new enhancement was seen in 8 of 22 patients (36.4%) on iMRI and in 12 of 22 patients (54.5%) on epMRI. In patients with nonenhancing lesions, a new T2 HIA was seen in 4 of 8 patients (50.0%) on iMRI and in 7 of 8 patients (87.5%) on epMRI. A discrepancy between the EOR measured on iMRI and epMRI was noted in 5 of the 22 patients (22.7%) with enhancing lesions, and in 3 of the 8 patients (37.5%) with nonenhancing lesions. The occurrence of ischemic lesions on DWI was found in 5 of 30 patients (16.7%) on iMRI, whereas it was found in 16 of 30 patients (53.3%) on epMRI (p = 0.003); ischemic lesions were underestimated on iMRI in 11 patients.

CONCLUSIONS

Overall, given the lower incidence of postoperative reactive changes on iMRI, it was superior to epMRI in evaluating the EOR in patients with glioma, both with enhancing and nonenhancing lesions. However, because ischemic lesions can be overlooked on iMRI, the authors recommend only the additional DWI scan during the early postoperative period. Clinicians need to be mindful about not overestimating the presence of residual tumor on epMRI due to the high incidence of postoperative reactive changes.

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Hitoshi Aiyama, Masaaki Yamamoto, Takuya Kawabe, Shinya Watanabe, Takao Koiso, Yasunori Sato, Yoshinori Higuchi, Eiichi Ishikawa, Tetsuya Yamamoto, Akira Matsumura and Hidetoshi Kasuya

OBJECTIVE

Although the conformity index (CI) and the gradient index (GI), which were proposed by Paddick and colleagues, are both logically considered to correlate with good posttreatment results after stereotactic radiosurgery (SRS), this hypothesis has not been confirmed clinically. The authors’ aim was to reappraise whether high CI values correlate with reduced tumor progression rates, and whether low GI values correlate with reduced complication incidences.

METHODS

This was an institutional review board–approved, retrospective cohort study conducted using a prospectively accumulated database including 3271 patients who underwent Gamma Knife SRS for brain metastases (BMs) during the 1998–2016 period. Among the 3271 patients, 925 with a single BM at the time of SRS (335 women and 590 men, mean age 66 [range 24–93] years) were studied. The mean/median CIs were 0.62/0.66 (interquartile range [IQR] 0.53–0.74, range 0.08–0.88) and the mean/median GIs were 3.20/3.09 (IQR 2.83–3.39, range 2.27–11.4).

RESULTS

SRS-related complications occurred in 38 patients (4.1%), with a median post-SRS interval of 11.5 (IQR 6.0–25.8, maximum 118.0) months. Cumulative incidences of post-SRS complications determined by a competing risk analysis were 2.2%, 3.2%, 3.6%, 3.8%, and 3.9% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed that only two clinical factors (i.e., peripheral doses and brain volume receiving ≥ 12 Gy) correlated with complication rates. However, neither CIs nor GIs impacted the incidences of complications. Among the 925 patients, post-SRS MRI was performed at least once in 716 of them, who were thus eligible for local progression evaluation. Among these 716 patients, local progression was confirmed in 96 (13.4%), with a median post-SRS interval of 10.8 (IQR 6.7–19.5, maximum 59.8) months. Cumulative incidences of local progression determined by a competing risk analysis were 7.7%, 12.6%, 14.2%, 14.8%, and 15.3% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed neurological symptoms, extracerebral metastases, repeat SRS, and CIs to correlate with incidences of local progression, whereas GIs had no impact on local tumor progression. Particularly, cumulative incidences of local progression were significantly lower in patients with CIs < 0.65 than in those with CIs ≥ 0.65 (adjusted hazard ratio 1.870, 95% confidence interval 1.299–2.843; p = 0.0034).

CONCLUSIONS

To the authors’ knowledge, this is the first analysis to focus on the clinical significance of CI and GI based on a large series of patients with BM. Contrary to the majority opinion that dose planning with higher CI and lower GI results in good post-SRS outcomes (i.e., low local progression rates and minimal complications), this study clearly showed that the lower the CIs were, the lower the local progression rates were, and that the GI did not impact complication rates.

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Takuma Hara, Hiroyoshi Akutsu, Shingo Takano, Hiroyoshi Kino, Eiichi Ishikawa, Shuho Tanaka, Hidetaka Miyamoto, Noriaki Sakamoto, Keiichiro Hattori, Mamiko Sakata-Yanagimoto, Shigeru Chiba, Takashi Hiyama, Tomohiko Masumoto and Akira Matsumura

OBJECTIVE

The Wnt/β-catenin signaling pathway is strongly implicated in the pathogenesis of adamantinomatous craniopharyngioma (adaCP). However, there is no evidence that the CTNNB1 mutation activates the target gene of Wnt/β-catenin signaling, and it is unknown whether it affects the tumorigenesis of adaCP. To assess the effect of the CTNNB1 mutation of adaCP, the authors analyzed the correlation between the mutation and clinical, radiological, pathological, and biological findings.

METHODS

Between 2003 and 2015, 42 patients (24 male and 18 female, median age 42 years) with either papillary craniopharyngioma (papCP) or adaCP underwent tumor resection at the authors’ institution. BRAF V600E and CTNNB1 in papCP and adaCP samples were sequenced by next-generation sequencing and the Sanger method, and mRNA expression levels of Axin2 and BMP4 were evaluated by RT-PCR. Axin2, BMP4, β-catenin, and BRAF expression were evaluated by immunohistochemistry. Other data were collected from clinical reports.

RESULTS

The BRAF V600E mutation was detected in all 10 cases of papCP (100%). CTNNB1 exon 3 mutations were detected in 21 of 31 (68%) cases of adaCP, excluding 1 case for which there were no available sequence data. The mRNA expression level of Axin2 was significantly higher in adaCPs with a CTNNB1 mutation than in those without (p < 0.05). The immunohistochemical findings of Axin2 and BMP4 did not correlate with CTNNB1 mutation positivity. When patients who received adjuvant radiation therapy were excluded, progression-free survival was shorter in the mutation-positive group than in the mutation-negative group (log-rank test, p = 0.031). Examination of clinical characteristics and immunohistochemical findings of adaCPs showed that there was no significant correlation between CTNNB1 mutation positivity and age, sex, tumor volume, gross-total resection, optic tract edema, calcification, or T1 signal intensity of cyst fluid on MRI, β-catenin, and MIB-1 index.

CONCLUSIONS

These results raise the possibility that the CTNNB1 mutation in adaCP may be associated with disease recurrence, and genes related to the Wnt/β-catenin signaling pathway might represent a therapeutic target.

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Eiichi Ishikawa, Yoshihiro Muragaki, Tetsuya Yamamoto, Takashi Maruyama, Koji Tsuboi, Soko Ikuta, Koichi Hashimoto, Youji Uemae, Takeshi Ishihara, Masahide Matsuda, Masao Matsutani, Katsuyuki Karasawa, Yoichi Nakazato, Tatsuya Abe, Tadao Ohno and Akira Matsumura

Object

Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM.

Methods

Twenty-four patients (age 16–75 years, Karnofsky Performance Scale score ≥ 60% before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ. After a 4-week interval, the patients received 3 AFTV injections and the first course of TMZ maintenance chemotherapy for 5 days, followed by multiple courses of TMZ for 5 days in each 28-day cycle.

Results

This treatment regimen was well tolerated by all patients. The percentage of patients with progression-free survival (PFS) ≥ 24 months was 33%. The median PFS, median overall survival (OS), and the actuarial 2- and 3-year survival rates of the 24 patients were 8.2 months, 22.2 months, 47%, and 38%, respectively. The median PFS in patients with a delayed-type hypersensitivity (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger surpassed the median length of follow-up for progression-free patients (29.5 months), which was significantly greater than the median PFS in patients with a smaller DTH-2 response.

Conclusions

The treatment regimen was well tolerated and resulted in favorable PFS and OS for newly diagnosed GBM patients. Clinical trial registration no.: UMIN000001426 (UMIN clinical trials registry, Japan).