Fukuoka University Repository / 福岡大学機関リポジトリ

application/pdfdepartmental bulletin pape

Oue, Asami

大上, 麻海

Japanese

テクノロジーが介護職従事者の職務成果に与える影響に関する探索的研究

福岡大学博士（医学）2024doctoral thesi

真田, 京一

サナダ, キョウイチ

博士論文要約 
 
Outcomes of Balloon Kyphoplasty for Vertebral Compression Fractures in Patients with 
Diffuse Idiopathic Skeletal Hyperostosis at the Distal End or Adjacent Vertebra of the 
Fused Segments  
(びまん性特発性骨増殖症の患者における癒合椎遠位端もしくは癒合椎隣接椎体の圧迫
骨折に対する balloon kyphoplasty の治療成績) 
掲載雑誌(巻、頁、発行年) 
Asian Spine Journal 2024 Apr;18(2):244-250. 
 
Introduction 
びまん性特発性骨増殖症（diffuse idiopathic skeletal hyperostosis : DISH）は、脊椎
の前縦靱帯の骨化によって可動性が低下し、脊椎が長管骨のように機能するため、外
力に弱くなり、骨折が生じやすいという特徴を持つ疾患である。特に高齢者に多く見
られるこの疾患では、骨折のリスクが著しく増大する。癒合部の中間部で発生する骨
折は不安定であるため固定術が一般的に推奨されるが、癒合部の遠位端や隣接椎体で
の骨折に対する治療戦略は未だ明確でなく、治療方針は議論の対象となっている。本
研究の目的は、DISH 患者において、骨折が癒合部の遠位端または隣接する椎体に発
生した場合の balloon kyphoplasty（BKP）の治療効果を評価することである。 
 
Patients and methods 
本研究は、2015 年から 2021 年にかけて実施された後ろ向きコホート研究であり、
福岡大学病院の倫理委員会の承認を得た上で行われた。研究対象は、BKP を受けた 72
名の患者で、全員が少なくとも 12 ヶ月以上のフォローアップを受けている。対象者
は、DISH を有する D 群（21 名）と、DISH を有さない ND 群（51 名）に分類され
た。BKP は、十分な保存療法を行った後も疼痛が改善しない AO 分類 A 型の椎体圧迫
骨折に対して施行された。 
DISH の診断基準は、Resnick らによる定義に基づき、X 線や CT で 3 つ以上の椎体
が連続して骨化している場合とされた。術前および術後の評価には、X 線撮影、
MRI、CT による画像診断が行われ、骨折の部位、骨密度、術前・術後の腰背部痛の
程度などが評価された。また、術後の疼痛の評価に Numeric Rating Scale（NRS）が
使用され、手術前、術後 3 ヶ月、および最終フォローアップ時に記録された。 
さらに、術後続発性隣接椎体骨折の発生率、再手術率、局所後弯の進行状況も調査し
た。術後続発性隣接椎体骨折は、X 線で椎体の高さが 15％以上減少し、MRI で骨髄信
号の変化が確認された場合に診断した。局所後弯の進行は、骨折した椎体の上位と下位
の椎体終板間の角度として計測し、術前、術後直後、最終フォローアップ時において比
較した。 
統計解析には、連続変数に Mann-Whitney U 検定、カテゴリー変数に Fisher の確率
検定を使用し、p<0.05 を統計学的に有意と判断した。 
 
Result 
本研究の対象となった 72 名の患者のうち、D 群の患者は全員、圧迫骨折が遠位端
または隣接椎体に発生しており、癒合の中間部分での骨折は見られなかった。両群の
患者背景に統計的には有意差は認められなかった。術前の NRS スコアは、D 群が 7.0
±1.5、ND 群が 6.9±1.4 であり、術後 3 ヶ月の NRS スコアは、D 群が 2.1±1.4、
ND 群が 2.3±1.6 であった。最終フォローアップ時の NRS スコアは、D 群で 2.0±
1.2、ND 群で 1.9±1.6 と、両群において術後の腰背部痛は有意に改善され、両群間で
有意な差はなかった。 
術後続発性隣接椎体骨折の発生率は、D 群で 3 例（14.3％）、ND 群で 11 例
（21.6％）であったが、これにも統計的に有意差は認められなかった。再手術は、D
群で 1 例（4.8％）、ND 群で 1 例（2.0％）が行われた。D 群における再手術は、骨セ
メントの前方逸脱によるものであり、ND 群では後弯の進行に伴う背部痛のために再
手術が行われた。 
局所後弯の進行に関しては、D 群では術前 19.0°±16.3°から術後直後 12.1°±
14.8°に改善したが、最終フォローアップ時には 23.5°±16.4°に進行していた。ND
群では、術前 21.9°±11.7°から術後直後 18.2°±13.2°に改善したものの、最終フ
ォローアップ時には 24.5°±12.9°まで進行した。局所後弯の進行に関して、D 群で
は 11.5°±5.9°、ND 群では 6.3°±6.7°の進行が確認され、D 群の進行が統計的に
有意に大きかった（p<0.01）。 
 
Discussion 
本研究の結果、BKP は DISH 患者における癒合部の遠位端または隣接椎体で発生し
た椎体骨折に対して有効であり、術後の腰背部痛が有意に改善されることが確認され
た。また、D 群では ND 群にくらべ局所後弯が有意に進行していたが、術後続発性隣
接椎体骨折の発生率や再手術率に関しては、DISH の有無による統計的な有意差は確
認されなかった。これらの結果から、BKP は特に高齢の DISH 患者に対して安全かつ
有効な治療法であると考えられるが、術後の局所後弯の進行リスクに対する長期的な
管理が重要である。また、今後さらに前向き研究を通じて、DISH 患者における最適
な治療戦略を確立することが期待される。 
 
Limitation 
1. 症例数が少なく、後ろ向き研究である点。 
2. 調査期間が短い点。 
3. 全脊椎レントゲンが取れていない。 
 
Conclusion 
DISH 患者において、癒合部位の遠位端または隣接椎体の VCF に対する BKP の転帰を
検討した。 局所的な後弯の進行は D 群で ND 群より有意に大きかったが、腰背部痛、
術後続発性隣接骨折の発生率、再手術率には群間で有意差はなかった。 DISH 患者の
癒合部遠位端、隣接椎体の骨折に対する BKP は、特に合併症率の高い高齢患者におい
て有効である。 


English

Outcomes of Balloon Kyphoplasty for Vertebral Compression Fractures in Patients with Diffuse Idiopathic Skeletal Hyperostosis at the Distal End or Adjacent Vertebra of the Fused Segments

廣田, 高志

ヒロタ, タカシ

1 
 
Title: 
Amyloid Detection Rate in Endoscopic Carpal Tunnel Release 
 
 
Authors: 
Takashi HIROTA1), Akira MAEYAMA1), Yuya HASHINO1), Yutaro YAMASAKI1), 
Mikiko AOKI2), Takuaki YAMAMOTO1) 
 
Affiliations: 
1) Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, 
Fukuoka, Japan 
2) Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan 
 
 
 
 
 
 
2 
 
Abstract 
Introduction: In recent years, obtaining pathology samples during carpal tunnel release 
(CTR) surgery has been proposed to confirm amyloid deposition and detect systemic 
amyloidosis at an early stage. However, most reports have been based on open CTR 
surgery, with few focused on endoscopic CTR (ECTR). This study was performed to 
examine the detection rate of amyloid in tissues obtained during ECTR. 
Methods: A total of 127 patients underwent ECTR for the diagnosis of carpal tunnel 
syndrome between January 2020 and September 2023. Pathology samples were collected 
intraoperatively from 79 patients who met the inclusion criteria. The cohort comprised 42 
men and 37 women with a mean age of 68.8 years (range, 32–88 years). Congo Red 
staining was performed on the extracted pathological tissues to investigate the amyloid 
positivity rate. 
Results: Of the 79 patients, 21 (26.6%) tested positive for amyloid. One patient was 
definitively diagnosed with transthyretin cardiac amyloidosis, and another was diagnosed 
with multiple myeloma associated with amyloid light chain amyloidosis. 
Conclusion: The detection rate of amyloid during ECTR was comparable to that reported 
in other studies, suggesting that screening for amyloidosis is feasible during this 
procedure. 
3 
 
 
Key words 
Carpal tunnel syndrome, Endoscopic carpal tunnel release, Amyloid, Biopsy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 
 
Correspondence to: Akira MAEYAMA, Department of Orthopaedic Surgery, Faculty of 
Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 810-0180, Japan 
Tel: +(81)-92-801-1011 
Fax: +(81)-92-864-9055 
E-mail: akira.maeyama0713@joy.ocn.ne.jp 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 
 
Introduction 
Carpal tunnel syndrome (CTS) is the most common compressive neuropathy of the upper 
extremity, with a prevalence of approximately 5%. It presents with pain and paresthesia 
in the median nerve region of the hand, atrophy of the thenar eminence, and decreased 
abductor pollicis muscle strength1). Its pathogenesis includes conditions such as 
pregnancy, obesity, diabetes, rheumatoid arthritis, sarcoidosis, purulent tenosynovitis, 
tuberculosis, systemic lupus erythematosus, hypothyroidism or hyperthyroidism, gout, 
and amyloidosis2). 
Amyloidosis is a systemic disease caused by extracellular aggregation of insoluble 
amyloid fibers in soft tissues and organs, such as the transverse carpal ligament, flexor 
tendons, biceps tendons, spinal ligaments, and myocardium. This can result in conditions 
such as CTS, spinal stenosis, bicipital tendon rupture, spinal canal stenosis, and 
symptomatic heart failure3)4). Typical systemic amyloidosis pathologies include those 
caused by amyloid transthyretin (ATTR), consisting of transthyretin (TTR), and amyloid 
light chain (AL), consisting of immunoglobulin light chain. In ATTR amyloidosis, TTR, 
a protein derived from the liver, misfolds to form amyloid fibers that are deposited 
extracellularly. In AL amyloidosis, bone marrow plasma cells produce immunoglobulin 
light chain protein, which misfolds to form amyloid fibers that are deposited 
6 
 
extracellularly3)4). Both AL and ATTR amyloidosis affect the heart. Patients with cardiac 
involvement have a particularly poor prognosis: the median survival time is 4 years for 
ATTR and 6 months for AL3)4)5). Current treatments for amyloidosis aim to slow 
progression by preventing further amyloid deposition rather than promoting the 
degradation of existing amyloid fibers, making early diagnosis and therapeutic 
intervention critical3). CTS may precede the onset of cardiomyopathy due to amyloidosis 
by 5 to 10 years4). 
Biopsying tendon synovial tissue during carpal tunnel release (CTR) (a treatment for 
CTS) to confirm amyloid deposition and screening for systemic amyloidosis may provide 
opportunities for early diagnosis and therapeutic intervention3)4)6). Prior studies have 
revealed amyloid deposition rates of 10.2% to 29.1% at the time of CTS surgery2)4)7)8)9). 
There are two methods of CTR: open CTR (OCTR) and endoscopic CTR (ECTR). 
Although ECTR is associated with concerns regarding higher complication and 
recurrence rates than OCTR, it is a less invasive procedure and is associated with an 
earlier return to work. Recent reports have indicated that 36% of members of the 
American Society of Hand Surgeons perform surgery using ECTR10)11)12)13). However, 
prior studies evaluating the amyloid-positive rate from tissue pathology collection during 
CTR have largely been based on OCTR. The detection rate of amyloid might be lower in 
7 
 
ECTR than in OCTR because less tissue can be collected during ECTR than during OCTR. 
The purpose of this study was to investigate the amyloid positivity rate during ECTR. 
 
Materials and Methods 
This study was approved by our institutional review board (approval number: 
H24−01−005). 
We retrospectively analyzed 127 patients who underwent ECTR for treatment of CTS at 
our hospital from January 2020 to September 2023. Patients with a history of trauma 
around the wrist, rheumatoid arthritis, a history of dialysis, or a preoperative diagnosis of 
cardiac amyloidosis were excluded. 
The primary endpoint was the rate of amyloid positivity. The secondary endpoints were 
age, sex, bilateral or unilateral cases, and the presence of hypertension, diabetes, and 
cardiac disease. We compared these variables between the amyloid-positive and amyloid-
negative groups to identify patient background factors associated with amyloid deposition. 
 
Surgical Method 
For ECTR, a CTS relief kit (Zimmer Biomet, Warsaw, IN, USA) was inserted into the 
carpal tunnel through an approximately 1-cm incision on the palmar side of the wrist joint. 
8 
 
The transverse carpal ligament was then released under direct visualization. For biopsy 
tissue collection, a portion of the proximal side of the transverse carpal ligament was 
removed through the incision (Fig. 1). 
The specimens were preserved in formalin and submitted for pathological examination. 
A pathologist microscopically examined the excised transverse carpal ligament, which 
was stained with Congo Red and further examined for amyloid deposition using polarized 
light microscopy (Fig. 2). Patients who tested positive for amyloid were referred to the 
Department of Cardiology. 
Patient background information, including age, sex, and biopsy results, was collected 
from the medical records. 
 
Statistical Analysis 
Statistical analysis was performed using IBM SPSS Statistics Version 29.0 (IBM Corp., 
Armonk, NY, USA). Two groups were created based on the biopsy results: amyloid-
positive and amyloid-negative cases. The chi-square test and Mann–Whitney U test were 
used for intergroup comparisons. Logistic regression models were employed to analyze 
predictors of amyloid-positive cases. 
The dependent variable was the presence or absence of amyloid, and the explanatory 
9 
 
variables were age, sex, bilateral cases, hypertension, diabetes, and heart disease. 
Univariate analysis was conducted for each explanatory variable, followed by 
multivariate analysis based on the univariate results. P-values of <0.05 were considered 
statistically significant. 
 
Results 
During the study period, 97 of the 127 patients underwent ECTR and intraoperative 
biopsy. Of these patients, 5 with a history of trauma, 5 with rheumatoid arthritis, 6 with a 
history of dialysis, and 2 with a preoperative diagnosis of cardiac amyloidosis were 
excluded, leaving 79 patients for analysis. The patients’ mean age was 68.8 ± 12.0 years, 
and they comprised 42 men and 37 women. A total of 31 underwent surgery on the right 
hand only, 23 on the left hand only, and 25 bilaterally. Additionally, 42 had pre-existing 
hypertension, 16 had diabetes, and 7 had cardiac disease. 
Of the 79 patients, 21 (26.6%) tested positive for amyloid. Among the 25 bilateral cases, 
4 were bilaterally positive for amyloid, 8 were positive on only one side, and 13 were 
bilaterally negative. 
In the comparison of the positive and negative amyloid deposition groups, the patients in 
the positive group were significantly older than those in the negative group (mean age, 
10 
 
73.8 ± 7.6 vs. 67.1 ± 12.8 years, respectively; p = 0.037). In the positive group, 90.5% 
(19 of 21) patients were male, whereas in the negative group, only 39.7% (23 of 58) 
patients were male (p < 0.001). The percentage of bilateral cases was 57.1% (12 of 21 
patients) in the positive group and 22.4% (13 of 58 patients) in the negative group (p = 
0.003). Regarding pre-existing medical conditions, hypertension was present in 81.0% 
(17 of 21 patients) in the positive group and 43.1% (25 of 58 patients) in the negative 
group (p = 0.003). There were no significant differences in diabetes or heart disease 
between the positive and negative groups (p = 0.212 and p = 0.271, respectively) (Table 
1). 
The results of the logistic regression analysis of predictors related to amyloid positivity 
are shown in Table 2. Univariate analysis showed that female sex (odds ratio [OR] = 0.086, 
95% confidence interval [CI] = 0.015–0.489, p = 0.006) and bilateral cases (OR = 4.394, 
95% CI = 1.148–16.822, p = 0.031) were significantly associated with amyloid positivity. 
Subsequent multivariate analysis using the variables that were significant in the univariate 
analysis showed that female sex was the only predictor significantly associated with 
amyloid positivity (OR = 0.088, 95% CI = 0.018–0.426, p = 0.003). 
During the postoperative course, systemic amyloidosis was diagnosed in one patient with 
a definitive diagnosis of ATTR cardiac amyloidosis, and treatment was initiated. Another 
11 
 
patient was diagnosed with AL amyloidosis. 
 
Discussion 
Amyloidosis is a disease caused by the deposition of misfolded proteins called amyloids, 
and CTS often precedes the onset of systemic amyloidosis3)14). Typical amyloidoses 
affecting the heart are AL and ATTR. AL is derived from bone marrow plasma cells, with 
approximately 20% of multiple myeloma cases overlapping with amyloidosis3). By 
contrast, TTR-type amyloidosis is of hepatic origin. Both types are deposited in the heart, 
peripheral nerves, autonomic nerves, gastrointestinal tract, and soft tissues3)14). In recent 
years, performing a biopsy during CTR to detect amyloid deposition and screen for early 
amyloidosis has been suggested3)4). When amyloid deposition is observed, referral to a 
cardiologist or neurologist is recommended for further diagnostic evaluation, including 
electrocardiography, echocardiography, and pyrophosphate scintigraphy, leading to 
therapeutic intervention3). 
In the present study, amyloid deposition was observed in 26.6% of the patients who 
underwent biopsy during ECTR. Although several reports have documented amyloid 
biopsy results during CTR, most have focused on OCTR2)4)7)8)9), with only a few 
evaluating ECTR alone (Table 2). Ozdag et al.15) compared the positive rate of amyloid 
12 
 
deposition in ECTR and OCTR, reporting rates of 3.5% (5 of 143) for ECTR and 23% 
(32 of 139) for OCTR, with a significantly higher rate in OCTR. Technical issues with 
biopsies during ECTR include the smaller amount of tendinous membrane available at 
the wrist incision than the carpal tunnel and the greater difficulty of obtaining large 
specimens of both the transverse carpal ligament and tendon sheath than in OCTR15). In 
our study, 21 of 79 cases (26.6%) were positive for amyloid deposition, a higher rate than 
that reported by Ozdag et al.15) Because the biopsy method was identical, the discrepancy 
between our results and those of Ozdag et al.15) may be attributed to differences in race, 
patient age, and test accuracy. 
Regarding risk factors for amyloid positivity, Sperry et al.4) reported that all amyloid-
positive cases were bilateral, and Gannon and Ward9) found that men over 50 years of 
age and bilateral cases were risk factors. DiBenedetto et al.8) found that the patients in the 
amyloid-positive group were significantly older, were more likely to be male, and had a 
higher prevalence of atrial fibrillation and spinal canal stenosis. Gray et al.16) reported 
amyloid deposition in 24% of patients with multiple trigger digits, indicating that similar 
patterns may apply to other diseases. In our study, the patients in the positive group were 
significantly older, were more likely to be male, and had a higher prevalence of bilateral 
cases and hypertension, consistent with previous studies. Among the 25 bilateral cases, 4 
13 
 
were positive on both sides and 8 were positive on only one side, indicating that amyloid 
detection may occur unilaterally in bilateral cases. This finding underscores the need for 
bilateral biopsies, especially in ECTR, in which the sample collection volume is small. 
In terms of the intervention rate for systemic amyloidosis, one case of cardiac amyloidosis 
in the present study was diagnosed and treated, and another case of multiple myeloma 
was diagnosed and followed up. Sperry et al.4) reported that 3% (3 of 98) of patients were 
treated for systemic amyloidosis, and Gannon and Ward9) reported a 1.3% (1 of 75) 
treatment rate, similar to our findings. Recently developed treatments for amyloidosis aim 
to slow or halt disease progression by preventing further amyloid deposition rather than 
promoting the breakdown of existing fibers. Early recognition, diagnosis, and 
management are therefore crucial. Orthopedic surgeons treating CTS may diagnose 
systemic amyloidosis earlier by performing biopsies during CTR, which is applicable to 
both OCTR and ECTR. 
Our study had three main limitations. First, it was a single-center study involving 
primarily Japanese subjects. Sood et al.17) reported that being Black/African American is 
a risk factor for amyloidosis, suggesting that racial differences may influence results. 
Second, biopsies were not initially performed in all cases. Although the biopsy rates 
improved over time, there was potential selection bias by surgeons. Third, ECTR requires 
14 
 
a smaller sample collection volume, which may result in more false-negative result than 
with OCTR. This point should be kept in mind. 
 
Conclusion 
The rate of amyloid deposition on biopsy during ECTR was comparable to that reported 
in previous studies, suggesting that screening for systemic amyloidosis is feasible during 
ECTR. Notably, however, the volume of specimens collected may be more limited in 
ECTR than in OCTR. 
 
Conflict of interest 
The authors declare that they have no conflict of interest. 
 
Acknowledgment  
We thank Angela Morben, DVM, ELS, from Edanz (https://jp.edanz.com/ac) for editing 
a draft of this manuscript. 
 
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18 
 
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Legends for Figures 
Fig. 1. (A) Specularly opened carpal tunnel using the one-portal technique. An 
arthroscope is inserted through a small skin incision on the palmar side of the wrist joint. 
(B) The transverse carpal ligament is incised under the arthroscope, and a portion of the 
transverse carpal ligament is removed through the small incision. 
19 
 
 
Fig. 2. Histopathology of the excised transverse carpal ligament. (A) Hematoxylin–eosin 
staining. (B) Congo Red staining showing salmon pink coloration. (C) Polarized light 
microscopy showing apple green birefringence, indicative of amyloid positivity. 
 
 
 
20 
 
 
 
21 
 
 


Amyloid Detection Rate in Endoscopic Carpal Tunnel Release

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Fukunaga, Fumio

福永, 文美夫

ディシプリンとしての経営学 : 批判的実在論の可能性

Takizawa, Rin

滝沢, 凜

公益法人会計基準と公益認定制度の関係に係る一考察 : 純資産の拘束性区分に焦点を当てて

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テクノロジーが介護職従事者の職務成果に与える影響に関する探索的研究

Outcomes of Balloon Kyphoplasty for Vertebral Compression Fractures in Patients with Diffuse Idiopathic Skeletal Hyperostosis at the Distal End or Adjacent Vertebra of the Fused Segments

Amyloid Detection Rate in Endoscopic Carpal Tunnel Release

Long-term observation of prognostic factors and clinical outcome of vernal keratoconjunctivitis in childhood

A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via depletion of NK cells in an experimental lung metastasis mouse model of colon cancer

海外レポート

ディシプリンとしての経営学 : 批判的実在論の可能性

公益法人会計基準と公益認定制度の関係に係る一考察 : 純資産の拘束性区分に焦点を当てて

中国の共同富裕政策と社会的共通資本

D&O保険の倒産免責条項の効力 : ドイツ法の検討

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