Publications by authors named "Yasuhiro Mitsui"

69 Publications

A rare combination of holocrine poroma with follicular germinative differentiation.

J Dermatol 2021 Apr 9;48(4):e192-e193. Epub 2021 Feb 9.

Department of Dermatology, Nara Medical University School of Medicine, Kashihara, Nara, Japan.

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http://dx.doi.org/10.1111/1346-8138.15791DOI Listing
April 2021

High Expression of Lactate Dehydrogenase A is a Potential Promoter of Malignant Behaviour in Extramammary Paget's Disease.

Acta Derm Venereol 2021 Jan 25;101(1):adv00379. Epub 2021 Jan 25.

Department of Dermatology, Nara Medical University, 840 Shijo, Kashihara, Nara 634-8522, Japan. E-mail:

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http://dx.doi.org/10.2340/00015555-3744DOI Listing
January 2021

S100P Expression via DNA Hypomethylation Promotes Cell Growth in the Sessile Serrated Adenoma/Polyp-Cancer Sequence.

Digestion 2021 Jan 4:1-14. Epub 2021 Jan 4.

Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan,

Background/aims: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor lesion of colon cancer. Although the relevance of DNA hypermethylation in the SSA/P-cancer sequence is well documented, the role of DNA hypomethylation is unknown. We investigated the biological relevance of DNA hypomethylation in the SSA/P-cancer sequence by using 3-dimensional organoids of SSA/P.

Methods: We first analyzed hypomethylated genes using datasets from our previous DNA methylation array analysis on 7 SSA/P and 2 cancer in SSA/P specimens. Expression levels of hypomethylated genes in SSA/P specimens were determined by RT-PCR and immunohistochemistry. We established 3-dimensional SSA/P organoids and performed knockdown experiments using a lentiviral shRNA vector. DNA hypomethylation at CpG sites of the gene was quantitated by MassARRAY analysis.

Results: The mean number of hypomethylated genes in SSA/P and cancer in SSA/P was 41.6 ± 27.5 and 214 ± 19.8, respectively, showing a stepwise increment in hypomethylation during the SSA/P-cancer sequence. S100P, S100α2, PKP3, and MUC2 were most commonly hypomethylated in SSA/P specimens. The mRNA and protein expression levels of S100P, S100α2, and MUC2 were significantly elevated in SSA/P compared with normal colon tissues, as revealed by RT-PCR and immunohistochemistry, respectively. Among these, mRNA and protein levels were highest for S100P. Knockdown of the S100P gene using a lentiviral shRNA vector in 3-dimensional SSA/P organoids inhibited cell growth by >50% (p < 0.01). The mean diameter of SSA/P organoids with S100P gene knockdown was significantly smaller compared with control organoids. MassARRAY analysis of DNA hypomethylation in the S100P gene revealed significant hypomethylation at specific CpG sites in intron 1, exon 1, and the 5'-flanking promoter region.

Conclusion: These results suggest that DNA hypomethylation, including S100P hypomethylation, is supposedly associated with the SSA/P-cancer sequence. S100P overexpression via DNA hypomethylation plays an important role in promoting cell growth in the SSA/P-cancer sequence.
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http://dx.doi.org/10.1159/000512575DOI Listing
January 2021

Apocrine mixed tumor of the skin with panfollicular differentiation: A rare case report with immunohistochemical evaluation.

J Dermatol 2020 Nov 4;47(11):e408-e410. Epub 2020 Aug 4.

Department of Dermatology, Nara Medical University School of Medicine, Kashihara, Japan.

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http://dx.doi.org/10.1111/1346-8138.15539DOI Listing
November 2020

Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma.

J Gastroenterol 2020 Nov 14;55(11):1072-1086. Epub 2020 Jul 14.

Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.

Background: The prognosis for patients with unresectable advanced hepatocellular carcinoma (HCC) is poor. Miriplatin is a hydrophobic platinum compound that has a long retention time in lesions after transarterial chemoembolization (TACE). We investigated anti-tumor activity of miriplatin combined with irradiation on HCC cells, and its underlying mechanism of apoptosis. We also analyzed the effectiveness of miriplatin-TACE and radiotherapy for locally advanced HCC.

Methods: Human HCC cell lines HepG2 and HuH-7 were treated with DPC (active form of miriplatin) and radiation, and synergy was evaluated using a combination index (CI). Apoptosis-related proteins and cell cycles were analyzed by western blotting and flowcytometry. We retrospectively analyzed treatment outcomes in 10 unresectable HCC patients with vascular/bile duct invasion treated with miriplatin-TACE and radiotherapy.

Results: DPC or X-ray irradiation decreased cell viability dose-dependently. DPC plus irradiation decreased cell viability synergistically in both cell lines (CI < 1, respectively). Cleaved PARP expression was induced much more strongly by DPC plus irradiation than by each treatment alone. Expression of p53 up-regulated modulator of apoptosis (PUMA) was significantly induced by the combination, and knockdown of PUMA with siRNA significantly decreased apoptosis in both cell lines. DPC plus irradiation caused sub-G1, G2/M, and S phase cell arrest in those cells. The combination of miriplatin-TACE and radiotherapy showed a high response rate for patients with locally advanced HCC despite small number of patients.

Conclusions: Miriplatin plus irradiation had synergistic anti-tumor activity on HCC cells through PUMA-mediated apoptosis and cell cycle arrest. This combination may possibly be effective in treating locally advanced HCC.
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http://dx.doi.org/10.1007/s00535-020-01705-8DOI Listing
November 2020

Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma including after treatment with sorafenib: Real-world evidence and assessment via protein phosphorylation array.

Oncotarget 2020 Jun 30;11(26):2531-2542. Epub 2020 Jun 30.

Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

The efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line LEN treatment, investigated the sensitivity of a SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and assessed their signal transduction pathways by protein array analysis. We retrospectively enrolled 57 patients with unresectable HCC. Fifty-three radiologically evaluated patients comprised 34 molecular-targeted agent (MTA)-naive (first-line), nine intolerant to SOR (second-line), and 10 resistant to regorafenib (third-line). The objective response rates (ORRs) were 61.8% in first-line, 33.3% in second-line, and 20.0% in third-line groups. The overall survival (OS) in the first-line was significantly longer than that in the third-line group ( < 0.05). Patients with better liver functional reserves (child score, ALBI grade) exhibited higher ORR and longer OS. The IC of LEN against PLC/PRF5-R2 was significantly higher than that against PLC/PRF5. LEN significantly inhibited more LEN-related signal transduction pathways in PLC/PRF5 than in PLC/PRF5-R2 cells. This suggests that LEN is active and safe as a second/third-line treatment for unresectable HCC. LEN seems more effective for patients with HCC with better hepatic reserve functions or before MTA-resistance is acquired because of the partial cross-resistance to SOR.
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http://dx.doi.org/10.18632/oncotarget.27640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335665PMC
June 2020

Preoperative hyaluronic acid injection modulates postoperative functional outcome in patients undergoing arthroscopic rotator cuff repair.

J Orthop Surg Res 2020 Jun 3;15(1):204. Epub 2020 Jun 3.

Department of Orthopedic Surgery, Kurume University Hospital, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.

Background: Arthroscopic rotator cuff repair (ARCR) generally yields acceptable clinical results. Hyaluronic acid (HA), a high-molecular-weight polysaccharide, is present in the extracellular matrix of soft connective tissue and synovial fluid, and its injection is known to significantly improve pain and clinical outcomes after rotator cuff injury. Some studies have described the role of HA injections as conservative therapy for rotator cuff tears. Since the subacromial bursa is believed to be the main source of shoulder pain in rotator cuff tears, subacromial injection is frequently used before surgery; however, its relationship with the clinical outcome after surgery remains unclarified. Therefore, we aimed to examine effects of preoperative subacromial HA injection on postoperative clinical outcome in patients with ARCR.

Methods: Ninety-eight patients were divided into a HA injection group and a non-injection group. The functional outcome measured was the University of California, Los Angeles (UCLA) score. Univariate analysis was performed to obtain variables with p values less than 0.1; we then used propensity score analysis, adjusting for pre- and post-operative confounding factors.

Results: The UCLA scores of all patients significantly improved 1 year postoperatively (PO) (p < 0.05). Subacromial HA injections were performed in patients with worse preoperative function. Univariate analysis showed significantly greater improvements in the injection group than in the non-injection group in terms of preoperative UCLA score, trauma, diabetes mellitus, UCLA score 3 months PO, abduction strength 4 months PO, and internal rotation (IR) strength 6 and 12 months PO. Propensity score analysis demonstrated that UCLA scores 3 months PO and IR strength 12 months PO in the injection group were significantly greater than those in the non-injection group. There were no significant differences in postoperative re-tear rates between the groups. In sub-analysis of the injection group, propensity scores showed that concurrent use of local anesthetics did not affect the data, suggesting that HA was effective.

Conclusion: Subacromial injection was administered to patients with worse function before ARCR. Propensity score analysis successfully demonstrated that functional outcome after surgery was improved in patients who were administered this injection compared with patients who were not administered this injection before surgery.
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http://dx.doi.org/10.1186/s13018-020-01715-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268750PMC
June 2020

Acquired agminated melanocytic nevus in the acral area is a potential mimicker of acral lentiginous melanoma: A three-case series report and published work review.

J Dermatol 2020 Jul 4;47(7):770-773. Epub 2020 May 4.

Department of Dermatology, Nara Medical University School of Medicine, Kashihara, Japan.

Agminated nevus refers to a clustered group of melanocytic nevi confined to a localized area of the body. It rarely involves acral skin, but recognition of acquired agminated nevus (AAN) in the acral area is clinically important because it may mimic acral lentiginous melanoma (ALM). However, acral AAN has only been described in a few case reports and its clinical characteristics remain unclear. We report three additional cases of acral AAN to further analyze the differential points between ALM. Clinical images, including those of dermoscopy, of three cases of acral AAN were reviewed. The lesions were located on the sole or lateral border of the foot. All acral AAN were flat and large in size (>20 mm in greatest dimension), and associated with asymmetry and irregular border. However, no parallel ridge pattern suggesting ALM was observed on dermoscopy. In two patients, the lesions on the sole were totally resected; microscopic evaluation of these two lesions confirmed junctional nests of banal melanocytes. AAN lesions on the sole with chronic mechanical pressure are slightly larger and more diffuse; thus, they may be more likely to be overdiagnosed as malignancy upon inspection than those in the non-acral area. Understanding the concept of the disease and careful dermoscopic evaluation leads to an accurate diagnosis.
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http://dx.doi.org/10.1111/1346-8138.15353DOI Listing
July 2020

First case report of the coexistence of hydrophilic polymer embolism and cholesterol crystal embolism associated with an endovascular procedure.

J Dermatol 2020 Mar 7;47(3):e93-e95. Epub 2020 Jan 7.

Department of Dermatology, Nara Medical University School of Medicine, Nara, Japan.

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http://dx.doi.org/10.1111/1346-8138.15223DOI Listing
March 2020

JMJD2A sensitizes gastric cancer to chemotherapy by cooperating with CCDC8.

Gastric Cancer 2020 05 1;23(3):426-436. Epub 2019 Nov 1.

Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan.

Background: Jumonji domain-containing protein 2A (JMJD2A) of the JMJD2 family of histone lysine demethylases has been implicated in tumorigenesis. However, its expression and role in gastric cancer (GC) drug resistance remain unknown. Here, we investigated the role of JMJD2A in GC chemotherapeutic susceptibility and its clinical relevance in GC.

Methods: We selected 12 relevant genes from previously identified gene signatures that can predict GC susceptibility to docetaxel, cisplatin, and S-1 (DCS) therapy. Each gene was knocked down using siRNA in GC cell lines, and cell viability assays were performed. JMJD2A expression in GC cell lines and tissues was assessed using qRT-PCR and immunohistochemistry, respectively. A JMJD2A downstream target related to drug susceptibility was examined using whole-gene expression array and immunoprecipitation.

Results: Among the 12 candidate genes, down-regulation of JMJD2A showed the maximum effect on GC susceptibility to anti-cancer drugs and increased the IC values for 5-FU, cisplatin, and docetaxel 15.3-, 2.7-, and 4.0-fold, respectively. JMJD2A was universally expressed in 12 GC cell lines, and its overexpression in GC tissue was positively correlated with tumor regression in 34 DCS-treated patients. A whole-gene expression array of JMJD2A-knockdown GC cells demonstrated a significant decrease in the expression of pro-apoptotic coiled-coil domain containing 8 (CCDC8), a downstream target of JMJD2A. Direct interaction between CCDC8 and JMJD2A was verified using immunoprecipitation. CCDC8 inhibition restored drug resistance to docetaxel, cisplatin, and S-1.

Conclusions: Our results indicate that JMJD2A is a novel epigenetic factor affecting GC chemotherapeutic susceptibility, and JMJD2A/CCDC8 is a potential GC therapeutic target.
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http://dx.doi.org/10.1007/s10120-019-01024-9DOI Listing
May 2020

Different phenotypes of gastric fundic gland polyposis and cancer in patients with familial adenomatous polyposis depending on Helicobacter pylori infection.

Gastric Cancer 2019 11 16;22(6):1294-1300. Epub 2019 Sep 16.

Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima city, Tokushima, 770-8503, Japan.

A 37-year-old male with tarry stool presented to our hospital. Esophagogastroduodenoscopy revealed advanced gastric cancer, fundic gland polyposis (FGPsis), and negativity for Helicobacter pylori (HP) infection. Computed tomography exhibited multiple liver tumors. Total colonoscopy (TCS) demonstrated 139 tubular adenomas. He was diagnosed as having unresectable gastric cancer and received systemic chemotherapy. His sister and mother had colorectal adenomatous polyposis as revealed by TCS. His sister had FGPsis and was negative for HP infection, whereas his mother had early gastric cancer with HP infection but not FGPsis. Genetic analysis revealed a novel mutation in exon 15 of the APC gene (NM_000038.5: c.7647_7648_delTG) for the patient, his mother, and his sister, whereas no mutation was found for his father who had no gastrointestinal polyps. Therefore, the pedigree was diagnosed as an FAP family with a novel APC germline mutation which had different gastric phenotypes depending on the status of HP infection.
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http://dx.doi.org/10.1007/s10120-019-01005-yDOI Listing
November 2019

Grouped apocrine gland component associated with sporadic syringocystadenoma papilliferum: A case report and BRAFV600E mutation analysis of the two components.

J Dermatol 2019 Nov 11;46(11):e395-e398. Epub 2019 Jul 11.

Department of Dermatology, Nara Medical University School of Medicine, Kashihara, Japan.

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http://dx.doi.org/10.1111/1346-8138.15020DOI Listing
November 2019

Facial pustules due to drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms may histopathologically mimic eosinophilic pustular folliculitis: A case report.

J Cutan Pathol 2019 May 18;46(5):363-367. Epub 2019 Feb 18.

Department of Dermatology, Nara Medical University School of Medicine, Nara, Japan.

Pustules with facial and/or neck edema is one characteristic feature of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) at the early stage. Although several retrospective histopathologic studies on DIHS/DRESS have been reported, the detailed histopathologic findings of facial pustules for DIHS/DRESS are unavailable. We herein report a case of DIHS/DRESS with facial pustules that was histopathologically similar to eosinophilic pustular folliculitis (EPF). Eosinophilic infiltration into expanded follicles and sebaceous glands, which is highly characteristic of EPF, was detected in pustules due to DIHS/DRESS in this case. There are numerous pathophysiological similarities between DIHS/DRESS and EPF, which may cause their histopathologic similarity. Our findings suggest that facial pustules of DIHS/DRESS may histopathologically mimic EPF.
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http://dx.doi.org/10.1111/cup.13428DOI Listing
May 2019

Prognostic factors affecting clinical outcomes after arthroscopic rotator cuff repair: importance of functional recovery by 3 months after surgery.

J Orthop Surg Res 2018 Dec 5;13(1):310. Epub 2018 Dec 5.

Department of Orthopedic Surgery, Kurume University Medical Center, 155-1 Kokubu-machi, Kurume, Fukuoka, 839-0863, Japan.

Background: To examine important factors that affect clinical outcomes following arthroscopic rotator cuff repair (ARCR).

Methods: Among 163 patients who underwent ARCR, we included 71 shoulders in 71 patients whose progress was monitored for > 2 years, postoperatively. We divided the patients into groups A (scores ≥ 83 points, 59 patients) and B (scores < 83 points, 12 patients) using the Japanese Orthopedic Association (JOA) score at 24 months. We then conducted univariate and multivariate analyses of pre- and postoperative (2 and 3 months, respectively) factors.

Results: The mean JOA score for all patients significantly improved from 63.7 ± 11.5 points preoperatively to 90.3 ± 9.6 points at 24 months postoperatively (P < 0.05). However, there were no significant between-group differences in the preoperative scores. In addition, there were no significant differences in the postoperative re-tear rate. Univariate analysis revealed that the range of motion (preoperative abduction and postoperative elevation, abduction, internal rotation, and external rotation), muscle strength (external rotation 3 months postoperatively), postoperative pain level [visual analog scale (VAS) maximum score, 10 points], partial repair, Cofield classification, and preoperative width were significant factors (P < 0.05 for all factors). Multivariate and receiver operating characteristic curve analyses showed that VAS at 2 months postoperatively and elevation at 3 months postoperatively were significant factors.

Conclusions: To obtain a JOA score of ≥ 83 points at 24 months postoperatively, following ARCR, a postoperative VAS of < 5 points at 2 months and postoperative elevation of ≥ 110° at 3 months should be achieved.
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http://dx.doi.org/10.1186/s13018-018-1014-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282280PMC
December 2018

Clinical and structural outcomes after arthroscopic rotator cuff repair: a comparison between suture bridge techniques with or without medial knot tying.

J Orthop Surg Res 2018 Nov 22;13(1):297. Epub 2018 Nov 22.

Department of Orthopaedic Surgery, Kurume University Hospital, 67 Asahi-machi, Kurume, Japan.

Purpose: To compare arthroscopic suture bridge (SB) techniques with medial tying to those without tying, considering clinical and structural outcomes.

Methods: We included 124 patients with rotator cuff tears after arthroscopic rotator cuff repair (ARCR). Fifty-three patients with clinical and structural evaluations 3, 12, and 24 months postoperatively were included and divided into 29 patients with medial tying (WMT group) and 24 without tying (WOMT group). Clinical outcomes comprised the University of California Los Angeles (UCLA) and Japanese Orthopaedic Association (JOA) scores. Structural outcomes were evaluated with magnetic resonance images (MRI) using Sugaya classifications.

Results: JOA and UCLA scores in the WMT and WOMT groups improved significantly from before surgery to 24 months after surgery (P < 0.01, respectively). No significant difference was noted between groups. No significant postoperative retears (Sugaya types 4 and 5) between WMT and WOMT groups were noted at 3 months (5 vs 3 cases), 12 months (6 vs 5 cases), and 24 months (7 vs 6 cases) postoperatively. Complete healing (Sugaya type 1) was noted at 3 months (8 vs 11 cases), 12 months (10 vs 10 cases), and 24 months (8 vs 13 cases, P = 0.024) postoperatively. Incomplete healing (Sugaya types 2 and 3) were noted at 3 months (16 vs 10 cases), 12 months (13 vs 9 cases), and 24 months (14 vs 5 cases, P = 0.024) postoperatively.

Conclusion: Clinical outcomes for both techniques were comparable, but the number of incompletely healed tendons in SB with medial tying was significantly larger at 24 months after surgery.

Level Of Evidence: This study is a level III, case-control study.

Clinical Relevance: This study revealed the influence of medial tying in rotator cuff repair.
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http://dx.doi.org/10.1186/s13018-018-0990-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251225PMC
November 2018

First report of an Asian family with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) revealed with the germline mutation of the APC exon 1B promoter region.

Gastric Cancer 2018 11 2;21(6):1058-1063. Epub 2018 Jul 2.

Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima city, Tokushima, 770-8503, Japan.

A 48-year-old Japanese female with left hypochondralgia presented at our hospital. Esophagogastroduodenoscopy (EGD) revealed gastric cancers and carpeting fundic gland polyposis (FGPs) without Helicobacter pylori infection. Computed tomography showed multiple liver metastases. Total colonoscopy revealed a colonic tubular adenoma but not polyposis. She was diagnosed as having advanced gastric cancer with liver metastasis and received chemotherapy. Her mother had died from gastric cancer, and her elderly brother and niece had FGPs as revealed by EGD. Thus, the pedigree was diagnosed as gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). Germline mutation analysis exhibited a point mutation in exon1B of the APC gene (c.-191T > C). Adenocarcinoma showed a gastric mucinous phenotype and was positive for a somatic mutation of p53, suggesting that p53 mutation may play a role in FGPs carcinogenesis. This is the first family with GAPPS in Asia in whom germline mutation of APC exon 1B has been detected.
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http://dx.doi.org/10.1007/s10120-018-0855-5DOI Listing
November 2018

Case of S100-positive benign cephalic histiocytosis involving monocyte/macrophage lineage marker expression.

J Dermatol 2018 Dec 15;45(12):e344-e345. Epub 2018 May 15.

Department of Dermatology, Nara Medical University School of Medicine, Kashihara, Japan.

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http://dx.doi.org/10.1111/1346-8138.14475DOI Listing
December 2018

First Japanese case of atypical Spitz tumor exhibiting ROS1 rearrangement.

J Dermatol 2018 Sep 25;45(9):e248-e249. Epub 2018 Mar 25.

Department of Dermatology, Nara Medical University School of Medicine, Kashihara, Japan.

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http://dx.doi.org/10.1111/1346-8138.14293DOI Listing
September 2018

Linked color imaging enhances endoscopic detection of sessile serrated adenoma/polyps.

Endosc Int Open 2018 Mar 7;6(3):E322-E334. Epub 2018 Mar 7.

Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Background And Study Aims:  Although new image-enhanced endoscopy (IEE) technologies such as blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) have been developed, their utility for the detection of sessile serrated adenoma/polyps (SSA/Ps) is still unclear. This study aimed to evaluate the utility of BLI, BLI-bright, and LCI for SSA/P detection in still image examinations and in a prospective randomized controlled trial (RCT).

Patients And Methods:  A group of 6 expert and non-expert endoscopists read 200 endoscopic still images containing SSA/P lesions using white light image (WLI), BLI, BLI-bright, and LCI. Color differences were calculated using the color space method. A prospective RCT of tandem colonoscopy with WLI and LCI was performed. Patients with SSA/P and those with a history of SSA/P that had been endoscopically removed were enrolled and randomly allocated to WLI-LCI or LCI-WLI groups. Additional endoscopic detection rates for SSA/P were compared between the 2 groups.

Results:  LCI showed the highest SSA/P detection rate among the 4 modes for both expert and non-expert endoscopists. The detection rate with LCI for the 6 expert endoscopists (mean 98.3 ± standard deviation 2.0 %) was significantly higher than that with WLI (86.7 ± 6.0 %,  < 0.01). Likewise, the detection rate with LCI for the 6 non-expert endoscopists (92.3 ± 2.9 %) was significantly higher than that with WLI (72.7 ± 11.5 %,  < 0.01). The color difference of SSA/P with LCI was the highest among the 4 modes, and was significantly higher than with WLI (median 15.9, (interquartile range 13.7 - 20.6) vs. 10.2, (7.6 - 14.2);  < 0.0001). In the RCT, a total of 44 patients (WLI-LCI 22 vs. LCI-WLI 22) underwent colonoscopy. The additional detection rate for SSA/P in the second inspection in the WLI-LCI group (21.6 %, 8/37) was significantly higher than in the LCI-WLI group (3.2 %, 1/31;  = 0.02). The small, flat, non-mucus and isochromatic SSA/Ps in the transverse colon were detected more frequently in the second inspection with LCI.

Conclusions:  LCI was the most sensitive mode for SSA/P detection among WLI, BLI, BLI-bright, and LCI in the still image examinations. Our RCT strongly suggests that LCI is superior to conventional WLI for SSA/P detection during colonoscopy. UMIN000017599.
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http://dx.doi.org/10.1055/s-0043-124469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842067PMC
March 2018

Hand lesion after arthroscopic rotator cuff repair: Association with complex regional pain syndrome.

J Orthop Sci 2018 Jan 23;23(1):70-74. Epub 2017 Sep 23.

Department of Orthopedic Surgery, Kurume University, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.

Background: It is known that complex regional pain syndrome (CRPS) occurs after arthroscopic rotator cuff repair (ARCR); however, few studies have investigated this complication. Therefore, the purpose of the present study was to evaluate CRPS after ARCR.

Methods: A total of 182 patients who underwent ARCR were enrolled in this study. The average age of patients was 62.8 ± 10.0 years, with an average follow-up period of 21.5 ± 38.1 months. CRPS criteria outlined by the Ministry of Health, Labor, and Welfare study team for CRPS in Japan (MHLWJ) and International Association for the Study of Pain (IASP 2005) were utilized for diagnosis. There are two rating systems for the "clinical purpose" and "research purpose" in both criteria, respectively. Clinical outcomes, including Japanese Orthopedic Association (JOA) and University of California, Los Angeles scores, were evaluated using univariate and multivariate analysis.

Results: CRPS exclusively occurred in the hand of the operated limb, developing within 3 months of surgery. Two or more of the following symptoms were noted in patients with the hand lesion associated with CRPS: edema (93.4%), restricted range of motion (83.4%), hyperalgesia (30.1%), paridrosis (20.4%), and atrophic change (12.2%). Under these conditions, the incidences of CRPS were 24.2% (44/182) when evaluated by the MHLWJ rating system for the "clinical purpose;" 11% (22/182) by the MHLWJ rating system for the "research purpose;" 6% (11/182) by the IASP 2005 for the "clinical purpose;" and 0.5% (1/182) by the IASP 2005 for the "research purpose." Results of multivariate analysis demonstrated that "Function" in the JOA score was a risk factor for the development of CRPS after ARCR, when evaluated by a system for the "clinical purpose" of the MHLWJ.

Conclusion: Following ARCR, CRPS-induced hand lesions occur more frequently than is generally believed, thereby suggesting that its impact on surgical outcomes should be clarified in the future.
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http://dx.doi.org/10.1016/j.jos.2017.09.007DOI Listing
January 2018

Risk factors for retear of large/massive rotator cuff tears after arthroscopic surgery: an analysis of tearing patterns.

J Orthop Surg Res 2017 Sep 25;12(1):140. Epub 2017 Sep 25.

Department of Orthopaedic Surgery, Kurume University School of Medicine, 67 Asahi-machi, kurume, Fukuoka, 830-0011, Japan.

Background: Previous studies have evaluated the risk factors for retear of large/massive rotator cuff tears (RCTs) that were treated arthroscopically; however, most studies did not evaluate tear patterns. The present study hypothesized that postoperative risk factors are affected by the tearing patterns in large/massive cuff tears in patients undergoing arthroscopic rotator cuff repair (ARCR).

Methods: One hundred fifty patients with large/massive cuff tears underwent ARCR at our institution. Of these, 102 patients were enrolled in this study, with an average symptom duration of 36.3 ± 43.9 months and average age of 63.9 ± 9.4 years. According to the arthroscopic findings and magnetic resonance imaging (MRI), the 102 patients were divided into three groups based on the tendon location: anterosuperior tears (N = 59, group AS), posteosuperior tears (N = 21, group PS), and anteroposterior-extending tears (N = 22, group APE). Functional outcome was evaluated preoperatively and postoperatively using the Japanese Orthopedic Association (JOA) score and the University of California, Los Angeles (UCLA) score. Retear was evaluated with MRI at a minimum of 1 year after surgery, using Sugaya's classification; Types IV and V were considered postoperative retears. Factors affecting postoperative retear were examined with univariate and multivariate analyses.

Results: JOA/UCLA scores significantly improved postoperatively in the three groups (P < 0.01 for all). Postoperative retear was noted in 26 of 102 patients (25.5%) in this series: 10 patients in group AS (16.9%), 9 in group PS (42.9%), and 7 in group APE (31.8%). The retear rate was significantly higher in group PS than in the other two groups (P = 0.02). Multivariate analysis showed that decreased preoperative active external rotation range was a unique risk factor for postoperative retear in the PS and APE groups (95% confidence interval: 0.02-0.18, cut-off value: 25°, with an area under the curve of 0.90, P = 0.0025).

Conclusions: Although multivariate analysis failed to detect significant risk factor for retear in patients with anterosuperior large/massive cuff tears who undergo ARCR, it demonstrated that active external rotation less than 25° before surgery is a significant risk factor in those with posterosuperior large/massive tears. This study may help surgeons understand the results of arthroscopic surgery in patients with large/massive tears.
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http://dx.doi.org/10.1186/s13018-017-0643-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613358PMC
September 2017

Effect of Preoperative Fatty Degeneration of the Rotator Cuff Muscles on the Clinical Outcome of Patients With Intact Tendons After Arthroscopic Rotator Cuff Repair of Large/Massive Cuff Tears.

Am J Sports Med 2017 Nov 14;45(13):2975-2981. Epub 2017 Sep 14.

Department of Orthopaedic Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Background: Fatty degeneration of the rotator cuff muscles is associated not only with postoperative retear but also with postoperative muscle weakness; therefore, fatty changes in the muscles may affect the clinical outcome even in patients with these tears who have intact tendons after arthroscopic rotator cuff repair (ARCR).

Purpose: To evaluate the effect of fatty infiltration on the clinical outcome in patients with intact tendons after arthroscopic repair of large/massive cuff tears.

Study Design: Case-control study; Level of evidence, 3.

Methods: One hundred fifty-five consecutive patients with large/massive rotator cuff tears underwent ARCR. Of these, 55 patients (mean ± SD age, 64.4 ± 9.1 years) in whom intact tendons after surgery were confirmed with magnetic resonance imaging at final follow-up (mean ± SD, 2.5 ± 1.4 years) were included in this study. Depending on their University of California Los Angeles (UCLA) score at the final follow-up, they were assigned to either the unsatisfactory group (score ≤27; n = 12) or the satisfactory group (score >27; n = 43). Various clinical parameters affecting the clinical outcome were examined through univariate and multivariate analyses.

Results: The UCLA score of all patients significantly improved from 18.1 ± 4.4 points preoperatively to 29.8 ± 4.5 points postoperatively ( P < .0001). The mean preoperative UCLA scores were not significantly different between the satisfactory and unsatisfactory groups ( P = .39). Multivariate analysis showed that the preoperative Goutallier stages of the infraspinatus (odds ratio [OR], 8.87; 95% confidence interval [CI], 1.51-52.0; P = .016) and/or subscapularis (OR, 7.53; 95% CI, 1.58-35.9; P = .011) were significantly associated with outcome. Receiver operating characteristic curve analysis revealed a cutoff value of Goutallier stage 1 in both muscles, with area under the curve values of 0.79 (sensitivity 91% and specificity 51%) and 0.84 (sensitivity 100% and specificity 54%) in the infraspinatus and subscapularis, respectively.

Conclusion: Preoperative fatty degeneration of the infraspinatus and/or subscapularis with Goutallier stage 2 or higher was significantly associated with worse outcome in patients with large/massive tears who had intact tendons after ARCR.
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http://dx.doi.org/10.1177/0363546517724432DOI Listing
November 2017

Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1.

Sci Rep 2017 07 26;7(1):6536. Epub 2017 Jul 26.

Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, 770-8503, Japan.

Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers (CRCs), are a good surrogate marker for CRC risk stratification and chemoprevention. However, the conventional ACF detection method with dye-spraying by magnifying colonoscopy is labor- and skill-intensive. We sought to identify rat and human ACF using a fluorescent imaging technique that targets a molecule specific for ACF. We found that glutathione S-transferase (GST) P1-1 was overexpressed in ACF tissues in a screening experiment. We then synthesized the fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the cytosol. Fluorescence intensities correlated significantly with GST activities in cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from azoxymethane-treated rats and surgically resected from CRC patients, ACF with strong fluorescent signals were clearly observed. The ACF number determined by postoperative DNAT-Me imaging was almost identical to that determined by preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT-Me images was significantly higher than that in methylene blue staining. Thus, we sensitively visualized ACF on rat and human colorectal mucosa by using a GST-activated fluorogenic probe without dye-spraying and magnifying colonoscopy.
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http://dx.doi.org/10.1038/s41598-017-06857-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529364PMC
July 2017

Response Predictors of S-1, Cisplatin, and Docetaxel Combination Chemotherapy for Metastatic Gastric Cancer: Microarray Analysis of Whole Human Genes.

Oncology 2017 17;93(2):127-135. Epub 2017 May 17.

Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

Objectives: The aim of this study was to identify biomarkers for predicting the efficacy of docetaxel, cisplatin, and S-1 (DCS) therapy for advanced gastric cancer using microarrays of biopsy specimens before chemotherapy.

Methods: Nineteen samples were taken from 19 patients with unresectable metastatic gastric cancer who received DCS as a first-line therapy. Laser capture microdissection was performed, and total cellular RNA was extracted from each microdissected sample. Whole-gene expression was analyzed by microarray, and the difference in mRNA expression observed with the microarrays was confirmed by quantitative real-time PCR. Immunohistochemical staining was performed using clinical tissue sections obtained by endoscopic biopsy.

Results: Eleven patients were identified as early responders and 8 patients as nonresponders to DCS therapy. Twenty-nine genes showed significant differences in relative expression ratios between tumor and normal tissues. A classifier set of 29 genes had high accuracy (94.7%) for distinguishing gene expression between 11 early responders and 8 nonresponders. Decreasing the size of the classifier set to 4 genes (PDGFB, PCGF3, CISH, and ANXA5) increased the accuracy to 100%. Expression levels by real-time PCR for validation were well correlated with those 4 genes in microarrays.

Conclusion: The genes identified may serve as efficient biomarkers for personalized cancer-targeted therapy.
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http://dx.doi.org/10.1159/000464329DOI Listing
October 2017

Efficacy of hybrid endoscopic submucosal dissection (ESD) as a rescue treatment in difficult colorectal ESD cases.

Dig Endosc 2017 Apr;29 Suppl 2:45-52

Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Background And Aim: Endoscopic submucosal dissection (ESD), which provides a higher en bloc resection rate than conventional endoscopic mucosal resection (EMR), is considered to be a useful treatment option for large colorectal tumors. However, colorectal ESD is not widely used because of its technical difficulty, risk of complications and time required. To overcome these drawbacks, a simpler modified technique, ESD with snaring (hybrid ESD), has been developed. The aim of the present study was to retrospectively compare the safety and efficacy of hybrid ESD and conventional ESD for colorectal tumors.

Methods: Between September 2008 and June 2016, ESD was carried out on 137 lesions and hybrid ESD on 27 lesions. All hybrid ESD cases were carried out as a rescue treatment in difficult ESD cases. We retrospectively investigated procedure time, and the rates of en bloc resection, perforation, bleeding, and local recurrence.

Results: In the hybrid ESD group, procedure time was shorter compared with the ESD group (108 ± 59.5 min vs 122 ± 72.2 min), but the en bloc resection rate was lower (66.7% vs 94.2%). However, there were no significant differences in procedure time, or in rates of en bloc resection, perforation and bleeding between the two groups. Local recurrence did not develop in any of our cases.

Conclusions: Hybrid ESD as a rescue treatment in difficult ESD cases may be less effective for en bloc resection of large colorectal tumors. Indication for hybrid ESD may be limited to scheduled treatment from the outset and emergency cases with patients who present unstable vital signs during ESD.
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http://dx.doi.org/10.1111/den.12863DOI Listing
April 2017

A Case Report of an Acromioclavicular Joint Ganglion Associated with a Rotator Cuff Tear.

Kurume Med J 2017 Apr 6;63(1.2):29-32. Epub 2017 Feb 6.

Department of Orthopedic Surgery, Kurume University School of Medicine.

We report a case of subcutaneous ganglion adjacent to the acromioclavicular joint with massive rotator cuff tear [1-7]. An 81-year-old woman presented with a ganglion adjacent to the acromioclavicular joint that had first been identified 9 months earlier. The ganglion had recurred after having been aspirated by her local physician, so she was referred to our hospital. The puncture fluid was yellowish, clear and viscous. Magnetic resonance imaging identified a massive rotator cuff tear with multi- lobular cystic lesions continuous to the acromioclavicular joint, presenting the "geyser sign". During arthroscopy, distal clavicular resection and excision of the ganglion were performed together with joint debridement. At present, the ganglion has not recurred and the patient has returned to normal daily activity. In this case, the ganglion may have developed subsequent to the concomitant massive cuff tear, due to subcutaneous fluid flow through the damaged acromioclavicular joint.
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http://dx.doi.org/10.2739/kurumemedj.MS6300002DOI Listing
April 2017

Cutoff value of Japanese Orthopaedic Association shoulder score in patients with rotator cuff repair: Based on the University of California at Los Angeles shoulder score.

J Orthop Sci 2017 May 21;22(3):438-441. Epub 2017 Jan 21.

Department of Orthopedic Surgery, Kurume University, Asahi-machi, Kurume, Fukuoka, Japan.

Background: The Japanese Orthopaedic Association shoulder score cutoff values were calculated in patients with rotator cuff repair using the University of California at Los Angeles shoulder score.

Methods: Overall, 175 patients with rotator cuff repair were subjects in this study. The University of California at Los Angeles and Japanese Orthopaedic Association shoulder scores were evaluated before surgery and at 3, 6, 9, and 12 months after surgery. The cutoff value of the Japanese Orthopaedic Association shoulder score was determined using the 4-stage criteria of the University of California at Los Angeles shoulder score and a University of California at Los Angeles shoulder score of 28 points, which is the boundary between an excellent/good group and a fair/poor group.

Results: Both the JOA shoulder and UCLA shoulder scores showed significant improvement at 6, 9, and 12 months from the preoperative scores (p < 0.0001). There was a strong correlation between the total values of the two scores (r = 0.85, p < 0.0001). The cutoff value of the Japanese Orthopaedic Association shoulder score based on the highest accuracy from receiver operating characteristic curve analysis was 83 points.

Conclusion: A Japanese Orthopaedic Association shoulder score cutoff value of 83 was equivalent to a University of California at Los Angeles shoulder score cutoff value of 28 for distinguishing between excellent/good and fair/poor outcomes after rotator cuff repair.
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http://dx.doi.org/10.1016/j.jos.2016.12.016DOI Listing
May 2017