Publications by authors named "Hiroshi Yamaguchi"

390 Publications

[A case of mucinous cystadenoma of the pancreas changed from multilocular to unilocular with cyst in cyst structure with an 8-year follow-up].

Nihon Shokakibyo Gakkai Zasshi 2021 ;118(4):340-347

Department of Gastroenterology and Hepatology, Tokyo Medical University.

A 57-year-old woman presented with multilocular cysts like a bunch of grapes, 30mm in diameter, in the tail of the pancreas. The number of cysts has increased, and each one had grown. Eventually, they turned into a unilocular cyst with a cyst in the cyst structure of about 50mm in diameter. Laparoscopic distal pancreatectomy was performed, and the resected specimen was diagnosed with mucinous cystadenoma. We report the rare morphological change in this case and consider the mechanism of its occurrence based on pathological considerations.
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http://dx.doi.org/10.11405/nisshoshi.118.340DOI Listing
January 2021

Adequate tissue sampling for the assessment of pathological tumor regression in pancreatic cancer.

Sci Rep 2021 Mar 22;11(1):6586. Epub 2021 Mar 22.

Oncology Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.

Standardized pathological evaluation of the regression assessment of neoadjuvant pancreatic cancer is necessary to improve prognostication and compare treatment outcomes in clinical trials. However, appropriate tissue sampling from surgically resected pancreatic cancer after neoadjuvant therapy has not been elucidated. We compared the tumor regression scores in the largest cancer slide determined macroscopically or histologically. We reviewed all slides and macroscopic photos of cut surfaces from resected pancreas of patients treated with neoadjuvant chemotherapy (n = 137; chemoradiotherapy or chemotherapy). The tumor regression scores (the Evans, College of American Pathologists, Japanese Pancreas Society grading systems, and Area of Residual Tumor [ART] score) were evaluated for the largest tumor slide determined by macroscopy or histologically as well as all slides from the resected pancreas. The largest cancer slides determined macroscopically and histologically were discrepant in 26% of the cases. Cancer cells were not detected in the largest macroscopically defined cut slides in 3%. Only ART scores assessed in the largest histological slides displayed significant difference in overall survival. We recommend obtaining the largest histological slides to provide adequate assessment for regression of neoadjuvant-treated pancreatic cancer. Sufficient sampling to detect the largest histological slides would be mandatory.
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http://dx.doi.org/10.1038/s41598-021-86152-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985517PMC
March 2021

Use of gadoxetic acid-enhanced MRI to predict the development of postoperative pancreatic fistulas by estimating the degree of pancreatic fibrosis.

Curr Med Imaging 2021 Mar 10. Epub 2021 Mar 10.

Department of Anatomic Pathology, Tokyo Medical University. Japan.

Background: Postoperative pancreatic fistula (POPF) can be life-threatening, and gadoxetic acid-enhanced MRI is routinely performed in patients undergoing pancreatic surgery. However, previous reports have not investigated if gadoxetic acid-enhanced MRI can be used to predict POPF risk.

Objective: This study aims to explore if gadoxetic acid-enhanced MRI can predict pancreatic fibrosis and the need for POPF treatment before surgery.

Method: We retrospectively analyzed gadoxetic acid-enhanced MR images from 142 patients who underwent pancreatic surgery between January 1, 2011, and April 30, 2018. Pre-dynamic signal intensity (SI) and values for portal, transitional, and hepatobiliary phase standardized based on pre-dynamic study values were analyzed. The diameter of the main pancreatic duct (DMPD) was measured, and the degree of pancreatic fibrosis was classified as F0-F3. We defined POPF higher than grade B as significant.

Results: Odds ratios for combinations that led to any degree of fibrosis higher than grade B were defined as significant risk factors. The highest odds ratio was obtained for F0 vs. F1-F3 (p = 0.038). DMPD (p < 0.001), pre-SI (p = 0.008), portal-SI/pre-SI (p < 0.001), transitional-SI/pre-SI (p < 0.001), and hepatobiliary-SI/pre-SI (p = 0.012) were significantly correlated with the presence of fibrosis. The presence of fibrosis was best detected by DMPD (AUC = 0.777). Individual specificity values of transitional-SI/pre-SI and DMPD were 95.5% and 86.6%, respectively, and their combined specificity was 97.7%.

Conclusion: The absence of pancreatic fibrosis is a risk factor for developing POPF higher than grade B. DMPD was the most useful diagnostic indicator of the presence of fibrosis among our analysis, and its specificity increased when combined with transitional-SI/pre-SI.
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http://dx.doi.org/10.2174/1573405617666210311114017DOI Listing
March 2021

A case of hypervascular tumors in the liver and pancreas: synchronous hepatocellular carcinoma and pancreatic metastasis from renal cell carcinoma 36 years after nephrectomy.

Clin Case Rep 2021 Feb 25;9(2):932-937. Epub 2020 Dec 25.

Department of Medical Oncology Sapporo Medical University School of Medicine Sapporo Japan.

It is sometimes difficult to distinguish between multiple cancers and metastases using only diagnostic imaging, particularly when multiple hypervascular tumors are found in multiple organs. We present a case in which the preoperative histological evaluation was essential to determine the management of a hypervascular pancreatic tumor and liver tumor.
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http://dx.doi.org/10.1002/ccr3.3691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869309PMC
February 2021

Histopathological evaluation of needle tract seeding caused by EUS-fine-needle biopsy based on resected specimens from patients with solid pancreatic masses: An analysis of 73 consecutive cases.

Endosc Ultrasound 2021 Feb 9. Epub 2021 Feb 9.

Third Department of Surgery, Tokyo Medical University, Tokyo, Japan.

Background And Objectives: EUS-guided fine-needle biopsy (EUS-FNB) is considered a safe and useful method for preoperative diagnosis of resectable solid pancreatic masses. However, needle tract seeding (NTS) after EUS-FNB has recently been reported, which may affect long-term outcome. The aim of this study was to evaluate NTS after EUS-FNB.

Materials And Methods: We reviewed 73 resected cases that underwent preoperative EUS-FNB for a pancreatic tumor from April 2014 to March 2016 and evaluated the utility and adverse events of EUS-FNB based on consecutively resected pathological specimens.

Results: The final diagnoses were pancreatic ductal adenocarcinoma (n = 67), neuroendocrine neoplasm (n = 5), and acinar cell carcinoma (n = 1). The diagnostic accuracy of preoperative EUS-FNB was 98.6%. Clinical adverse events were observed in 4.1% of cases (bleeding, n = 2; acute pancreatitis, n = 1) and abnormal pathological findings in 4.1% (NTS, n = 2; acute focal pancreatitis, n = 1).

Conclusions: Although EUS-FNB is useful for preoperative diagnosis of pancreatic tumors, we may need to reconsider the risk of NTS and use of EUS-FNB in patients with a resectable solid pancreatic mass unless the tract itself is planned to be resected.
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http://dx.doi.org/10.4103/EUS-D-20-00174DOI Listing
February 2021

Rare-Earth-Mediated Optomechanical System in the Reversed Dissipation Regime.

Phys Rev Lett 2021 Jan;126(4):047404

NTT Basic Research Laboratories, NTT Corporation, 3-1 Morinosato Wakamiya, Atsugi-shi, Kanagawa 243-0198, Japan.

Strain-mediated interaction between phonons and telecom photons is demonstrated using excited states of erbium ions embedded in a mechanical resonator. Owing to the extremely long-lived nature of rare-earth ions, the dissipation rate of the optical resonance falls below that of the mechanical one. Thus, a "reversed dissipation regime" is achieved in the optical frequency region. We experimentally demonstrate an optomechanical coupling rate g_{0}=2π×21.7  Hz, and numerically reveal that the interaction causes stimulated excitation of erbium ions. Numerical analyses further indicate the possibility of g_{0} exceeding the dissipation rates of erbium and mechanical systems, thereby leading to single-photon strong coupling. This strain-mediated interaction, moreover, involves the spin degree of freedom, and has a potential to be extended to highly coherent opto-electro-mechanical hybrid systems in the reversed dissipation regime.
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http://dx.doi.org/10.1103/PhysRevLett.126.047404DOI Listing
January 2021

[A case of distal bile duct carcinoma converted to neuroendocrine cancer and proliferated into the pancreas].

Nihon Shokakibyo Gakkai Zasshi 2021 ;118(2):168-174

Department of Gastroenterology and Hepatology, Tokyo Medical University.

A woman in her 50s was referred due to a solid mass in the head of the pancreas. It was diagnosed as a neuroendocrine carcinoma (NEC) by endoscopic ultrasound-guided fine-needle aspiration. Consequently, pancreatoduodenectomy was performed. A well-differentiated adenocarcinoma component was revealed in the resected bile duct, suggesting a relationship with the NEC component in the pancreas. Genetic examination suggested that cholangiocarcinoma, but not coexisting carcinoma, was converted to NEC after the interstitial invasion. Finally, it was diagnosed as the NEC derived from the extrahepatic bile duct, which is rare at about 0.2-2% in gastrointestinal neuroendocrine neoplasms.
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http://dx.doi.org/10.11405/nisshoshi.118.168DOI Listing
February 2021

Prediction of AESD and neurological sequelae in febrile status epilepticus.

Brain Dev 2021 May 7;43(5):616-625. Epub 2021 Feb 7.

Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan.

Objective: The clinical prediction rule (CPR) for acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was developed with an area under the receiver operating characteristic curve (AUC) of 0.95 - 0.96. Our objective was to verify the AESD CPR in a new cohort and compare the utilities of three CPRs of acute encephalopathy: the Tada, Yokochi, and Nagase criteria.

Methods: We reviewed the clinical data and medical charts of 580 consecutive patients (aged < 18 years) with febrile convulsive status epilepticus lasting for ≥ 30 min in 2002 - 2017 and measured the performance of the CPRs in predicting AESD and sequelae.

Results: The CPRs predicted AESD with an AUC of 0.84 - 0.88. The Tada criteria predicted AESD with a positive predictive value (PPV) of 0.25 and a negative predictive value (NPV) of 0.99. The Yokochi criteria predicted AESD with a PPV and NPV of 0.20 and 0.95, respectively, after 12 h. The Nagase criteria predicted AESD with a PPV and NPV of 0.14 and 1.00, respectively, after 6 h. The PPVs of the Tada, Yokochi, and Nagase criteria for sequelae were 0.28, 0.28, and 0.17, respectively; the corresponding NPVs were 0.97, 0.95, and 0.98, respectively.

Conclusions: The effectiveness of the AESD CPR in a new cohort was lower than that in the derivation study. CPRs are not sufficient as diagnostic tests, but they are useful as screening tests. The Nagase criteria are the most effective for screening among the three CPRs due to their high NPV and swiftness.
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http://dx.doi.org/10.1016/j.braindev.2021.01.004DOI Listing
May 2021

Novel method for evaluating the indication for endoscopic papillectomy in patients with ampullary adenocarcinoma.

Sci Rep 2021 Jan 12;11(1):600. Epub 2021 Jan 12.

Third Department of Surgery, Tokyo Medical University, Tokyo, Japan.

This study aimed to determine the clinicopathological features of the subtypes of ampullary carcinoma (AC) to explore the indications for endoscopic papillectomy (EP) in early AC. Fifty-seven patients with AC who underwent curative resection were retrospectively reviewed. The 0/IA stages were significantly more common in the intestinal type (I-type) than in the mixed and pancreatobiliary type (M&PB-type) (90.7% vs 35.7%, P < 0.001). Tis/T1a tumors limited to the ampulla [Tis/T1a(ampulla)] were significantly more likely to be I-type than M&PB-type (74.4% vs 14.3%, P = 0.002). The tub1 rate was significantly higher in the I-type than in the M&PB-type (81.4% vs 35.7%, P = 0.001). In the I-type, the tub1 rate was significantly higher for Tis/T1a(ampulla) than for T1a tumors limited to the sphincter of Oddi (100% vs 42.9%, P = 0.004). These observations suggest that I-type AC with tub1 is an indication for EP. The concordance rate of pathological subtypes between endoscopic biopsy and resected specimens was high (κ = 0.8053, P < 0.001). Tis/T1a(ampulla) showed no lymphovascular or perineural invasion. An endoscopic imaging finding of early AC with I-type and tub1 on biopsy could be an indication for EP. Identifying the pathological subtype of AC by endoscopic biopsy could be a novel preoperative approach for evaluating the indications for EP.
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http://dx.doi.org/10.1038/s41598-020-79836-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804087PMC
January 2021

Early non-convulsive seizures are associated with the development of acute encephalopathy with biphasic seizures and late reduced diffusion.

Brain Dev 2021 Apr 17;43(4):548-555. Epub 2020 Dec 17.

Department of Pediatrics, Kobe University Graduate School of Medicine, Japan. Electronic address:

Introduction: Children with either febrile seizure or acute encephalopathy exhibit seizures and/or impaired consciousness accompanied by fever of unknown etiology (SICF). Among children with SICF, we previously reported those who have refractory status epilepticus or prolonged neurological abnormalities with normal AST levels are at a high risk for the development of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), considered to be caused by excitotoxicity. Non-convulsive seizures (NCS) are common in critically ill children and cause excitotoxic neuronal injury. The aim of this study was to elucidate the prevalence of NCS in the acute phase of children at a high risk for developing AESD and the relationship between NCS in the acute phase and neurological outcomes.

Methods: We studied 137 children with SICF at a high risk for developing AESD and who underwent continuous electroencephalogram monitoring (cEEG) upon admission to a tertiary pediatric care center at Hyogo Prefectural Kobe Children's Hospital between October 2007 and August 2018. Patient characteristics and outcomes were compared between patients with NCS and without NCS.

Results: Of the 137 children, NCS occurred in 30 children; the first NCS were detected in cEEG at the beginning in 63.3%, during the first hour in 90%, and within 12 h in 96.7%. Neurological sequelae were more common in NCS patients (20.0%) than in non-NCS patients (1.9%; p = 0.001). Five in 30 NCS patients (16.7%) and 3 in 107 non-NCS patients (2.8%) developed AESD (p = 0.013).

Conclusion: The occurrence of NCS is associated with subsequent neurological sequelae, especially the development of AESD.
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http://dx.doi.org/10.1016/j.braindev.2020.11.012DOI Listing
April 2021

Effect of Rikkunshito, a Traditional Japanese Herbal Medicine, on Delayed Gastric Emptying and Oral Dietary Intake After Pancreaticoduodenectomy: A Prospective, Randomized, Single-Center, Open-Labeled Study.

Clin Exp Gastroenterol 2020 9;13:577-587. Epub 2020 Dec 9.

Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, School of Medicine, Sapporo, Japan.

Introduction: Delayed gastric emptying (DGE) remains an important problem after pancreaticoduodenectomy (PD). There is a lack of effective treatments for early recovery of oral dietary intake. Rikkunshito (RKT), a Japanese herbal medicine, has been gaining attention as a facilitator of gastric emptying. We evaluated the effects of RKT on DGE after PD.

Methods: In this prospective, randomized, open-labeled study, patients were randomly allocated before PD in a 1:1 ratio to the RKT group or the control group that received no additional treatment. The RKT group received 2.5 g of RKT three times daily (7.5 g/day) from postoperative day (POD) 1 to POD 21. The primary endpoint was the incidence of DGE. Secondary endpoints were short-term postoperative outcomes including oral dietary intake volume and perioperative changes in levels of the hormones ghrelin and leptin. Patients were observed until hospital discharge.

Results: Twenty-six patients in each group (n = 52) completed the protocol treatment and were included in the analysis set. There were no statistically significant differences in basic characteristics and operative factors. The overall incidence of DGE was not statistically different between the RKT and control groups (30.8% vs 30.8%, >0.9999). There were no statistically significant differences in the amount of postoperative oral dietary intake represented by total dietary intake (TDI) up to POD 14 and POD 21, complications, and length of hospital stay. No adverse events related to this study were observed. In the RKT group, total ghrelin and acyl-ghrelin were significantly upregulated and leptin was significantly downregulated earlier than in the control group.

Conclusion: RKT treatment from POD 1 to 21 did not reduce the incidence of DGE and had no clinically beneficial effect on short-term postoperative outcomes irrespective of changes in hormone levels.
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http://dx.doi.org/10.2147/CEG.S252913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734068PMC
December 2020

Prevalence of Wilson Disease Based on Genome Databases in Japan.

Pediatr Int 2020 Dec 1. Epub 2020 Dec 1.

Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene. In 1984, Scheinberg and Sternlieb estimated the prevalence of WD to be 1:30,000. However, recent epidemiological studies have reported increasing prevalence rates in different populations. The carrier frequency of ATP7B variants and the prevalence of WD in the Japanese population have not been reported using multiple databases.

Methods: Multiple public databases were used. First, we included mutations in the ATP7B gene that were registered in the Human Gene Mutation Database (HGMD) Professional, where 885 ATP7B variants were identified as pathogenic. Next, we investigated the allele frequencies of these 885 variants in Japanese individuals using the Human Genetic Variation Database (HGVD) and the Japanese Multi Omics Reference Panel (jMorp).

Results: Of the 885 variants of ATP7B, 7 and 12 missense and nonsense variants, 0 and 3 splicing variants, and 0 and 2 small deletions were found in the HGVD and in jMorp, respectively. The total allele frequencies of the ATP7B mutations were 0.011 in the HGVD and 0.014 in the jMorp. According to these data, the carrier frequencies were 0.022 (2.2%) and 0.028 (2.8%), respectively, and patient frequencies were 0.000121 (1.21/10,000 individuals) and 0.000196 (1.96/10,000 individuals), respectively.

Conclusion: This is the first study to report the carrier frequency of ATP7B variants and the prevalence of WD in Japan using multiple databases. The calculated prevalence of WD was comparatively higher than that of previous reports, indicating previous underdiagnosis or the existence of less severe phenotypes.
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http://dx.doi.org/10.1111/ped.14565DOI Listing
December 2020

Arteriovenous malformation in the pancreatic head initially mimicking a hypervascular mass treated with duodenum-preserving pancreatic head resection: a case report.

Surg Case Rep 2020 Dec 1;6(1):301. Epub 2020 Dec 1.

Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, 291 Minami-1-jo Nishi 16-chome, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

Background: The mainstay treatment for arteriovenous malformation in the pancreatic head (Ph-AVM) is standard pancreatectomy, especially pancreaticoduodenectomy (PD), or interventional endovascular treatment. We report the first case of Ph-AVM treated with duodenum-preserving pancreatic head resection (DPPHR) performed to preserve the periampullary organs.

Case Presentation: A 59-year-old man presenting with back pain underwent contrast-enhanced computed tomography followed by angiography of the anterior superior pancreaticoduodenal artery. He was diagnosed with Ph-AVM and indicated for DPPHR with preservation of the periampullary organs; Ph-AVM's benign nature seldom requires lymph node dissection. During the operation, the right colon was mobilized and the omental bursa was released to expose the periampullary structures. The pancreas was transected just above the superior mesenteric vein. The inferior pancreaticoduodenal artery and papillary arteries branching from the posterior superior pancreaticoduodenal artery were carefully preserved to maintain the blood flow to the lower bile duct and papilla of Vater. The remnant pancreas was reconstructed with pancreaticogastrostomy using the modified Blumgart method. Pathological examination of the resected specimen revealed an irregular course of the arteries and veins concomitant with marked dilation throughout the pancreatic head. The patient was pathologically diagnosed with Ph-AVM. He developed hematemesis caused by a rupture of the pseudoaneurysm on postoperative day 20 and underwent coil embolization. A bilio-enteric fistula and stenosis of the common bile duct were found and treated by placement of an endoscopic biliary stent. At the 8-month follow-up, the Ph-AVM had not recurred.

Conclusions: Compared to PD, DPPHR confers the clinical benefit of preserving the periampullary organs, although further studies are needed to confirm this. Therefore, the choice of this procedure should be based on the surgical morbidities and long-term outcome of the patient.
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http://dx.doi.org/10.1186/s40792-020-01075-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708544PMC
December 2020

Generic Rotating-Frame-Based Approach to Chaos Generation in Nonlinear Micro- and Nanoelectromechanical System Resonators.

Phys Rev Lett 2020 Oct;125(17):174301

Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan.

This Letter provides a low-power method for chaos generation that is generally applicable to nonlinear micro- and nanoelectromechanical systems (MNEMS) resonators. The approach taken is independent of the material, scale, design, and actuation of the device in question; it simply assumes a good quality factor and a Duffing type nonlinearity, features that are commonplace to MNEMS resonators. The approach models the rotating-frame dynamics to analytically constrain the parameter space required for chaos generation. By leveraging these common properties of MNEMS devices, a period-doubling route to chaos is generated using smaller forcing than typically reported in the literature.
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http://dx.doi.org/10.1103/PhysRevLett.125.174301DOI Listing
October 2020

Investigation of Factors Influencing the Occurrence of 3C-Inclusions for the Thick Growth of on-Axis C-Face 4H-SiC Epitaxial Layers.

Materials (Basel) 2020 Oct 28;13(21). Epub 2020 Oct 28.

National Institute of Advanced Industrial Science and Technology, Central 2 1-1-1 Umezono, Tsukuba 305-8568, Japan.

In this study, we grew homoepitaxial layers on 3-inch on-axis carbon-face 4H-silicon carbide substrates and attempted to suppress the generation of 3C-inclusions. It was found that the 3C-inclusion density decreased with increasing time spent on reaching an objective flow rate for the precursors. It is suggested that 3C-SiC nucleation occurred on large terraces of the on-axis substrates, which existed before the substrates were covered with spiral hillocks. This nucleation was suppressed owing to the decrease in the degree of supersaturation at the initial growth stage. Moreover, we found that the 3C-inclusions were also generated owing to contamination in the form of graphite products. Furthermore, we succeeded in growing a thick on-axis 4H-SiC homoepitaxial layer on a 3-inch substrate and demonstrating its free-standing epitaxial layer with a thickness of 182 μm and a 3C-inclusion density of 2.0 cm.
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http://dx.doi.org/10.3390/ma13214818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663319PMC
October 2020

Objective assessment of tumor regression in post-neoadjuvant therapy resections for pancreatic ductal adenocarcinoma: comparison of multiple tumor regression grading systems.

Sci Rep 2020 10 26;10(1):18278. Epub 2020 Oct 26.

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Warren 122, Boston, MA, USA.

Neoadjuvant therapy is increasingly used to control local tumor spread and micrometastasis of pancreatic ductal adenocarcinoma (PDAC). Pathology assessments of treatment effects might predict patient outcomes after surgery. However, there are conflicting reports regarding the reproducibility and prognostic performance of commonly used tumor regression grading systems, namely College of American Pathologists (CAP) and Evans' grading system. Further, the M.D. Anderson Cancer Center group (MDA) and the Japan Pancreas Society (JPS) have introduced other grading systems, while we recently proposed a new, simple grading system based on the area of residual tumor (ART). Herein, we aimed to assess and compare the reproducibility and prognostic performance of the modified ART grading system with those of the four grading systems using a multicenter cohort. The study cohort consisted of 97 patients with PDAC who had undergone post-neoadjuvant pancreatectomy at four hospitals. All patients were treated with gemcitabine and S-1 (GS)-based chemotherapies with/without radiation. Two pathologists individually evaluated tumor regression in accordance with the CAP, Evans', JPS, MDA and ART grading systems, and interobserver concordance was compared between the five systems. The ART grading system was a 5-tiered system based on a number of 40× microscopic fields equivalent to the surface area of the largest ART. Furthermore, the final grades, which were either the concordant grades of the two observers or the majority grades, including those given by the third observer, were correlated with patient outcomes in each system. The interobserver concordance (kappa value) for Evans', CAP, MDA, JPS and ART grading systems were 0.34, 0.50, 0.65, 0.33, and 0.60, respectively. Univariate analysis showed that higher ART grades were significantly associated with shorter overall survival (p = 0.001) and recurrence-free survival (p = 0.005), while the other grading systems did not show significant association with patient outcomes. The present study revealed that the ART grading system that was designed to be simple and more objective has achieved high concordance and showed a prognostic value; thus it may be most practical for assessing tumor regression in post-neoadjuvant resections for PDAC.
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http://dx.doi.org/10.1038/s41598-020-74067-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588464PMC
October 2020

Elevated cytokine, chemokine, and growth and differentiation factor-15 levels in hemorrhagic shock and encephalopathy syndrome: A retrospective observational study.

Cytokine 2021 Jan 5;137:155324. Epub 2020 Oct 5.

Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan.

Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a 'cytokine storm'. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1β (IL-1β), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.
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http://dx.doi.org/10.1016/j.cyto.2020.155324DOI Listing
January 2021

Hypothalamic circuitry underlying stress-induced insomnia and peripheral immunosuppression.

Sci Adv 2020 Sep 9;6(37). Epub 2020 Sep 9.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.

The neural substrates of insomnia/hyperarousal induced by stress remain unknown. Here, we show that restraint stress leads to hyperarousal associated with strong activation of corticotropin-releasing hormone neurons in the paraventricular nucleus of hypothalamus (CRH) and hypocretin neurons in the lateral hypothalamus (Hcrt). CRH neurons directly innervate Hcrt neurons, and optogenetic stimulation of LH-projecting CRH neurons elicits hyperarousal. CRISPR-Cas9-mediated knockdown of the gene in CRH neurons abolishes hyperarousal induced by stimulating LH-projecting CRH neurons. Genetic ablation of Hcrt neurons or gene knockdown significantly counteracts restraint stress-induced hyperarousal. Single-cell mass cytometry by time of flight (CyTOF) revealed extensive changes to immune cell distribution and functional responses in peripheral blood during hyperarousal upon optogenetic stimulation of CRH neurons simulating stress-induced insomnia. Our findings suggest both central and peripheral systems are synergistically engaged in the response to stress via CRH circuitry.
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http://dx.doi.org/10.1126/sciadv.abc2590DOI Listing
September 2020

Seizure prevalence in children aged up to 3 years: a longitudinal population-based cohort study in Japan.

BMJ Open 2020 09 10;10(9):e035977. Epub 2020 Sep 10.

Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.

Objective: To investigate the prevalence of seizures/febrile seizures in children up to 3 years of age and examine the effects of gestational age at birth on the risk for febrile seizures.

Design: Retrospective longitudinal population-based cohort study.

Setting: Kobe City public health center, Kobe, Japan, from 2010 to 2018.

Participants: Children who underwent a medical check-up at 3 years of age.

Methods: Information regarding seizures was collected from the parents of 96 014 children. We identified the occurrence of seizure/febrile seizure in 74 017 children, whose gestational ages at birth were noted. We conducted a multivariate analysis with the parameter, gestational age at birth, to analyse the risk of seizure. We also stratified the samples by sex and birth weight (<2500 g or not) and compared the prevalence of seizure between those with the term and late preterm births.

Results: The prevalence of seizure was 12.1% (11.8%-12.3%), 13.2% (12.2%-14.4%), 14.6% (12.4%-17.7%) and 15.7% (10.5%-22.8%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. The prevalence of febrile seizures was 9.0% (8.8%-9.2%), 10.5% (9.5%-11.5%), 11.8% (9.7%-14.5%) and 11.2% (6.9%-17.7%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. Male was an independent risk factor for seizures (OR: 1.15, 95% CI 1.09 to 1.20; absolute risk increase 0.014, 95% CI 0.010 to 0.019) and febrile seizures (OR: 1.21, 95% CI 1.15 to 1.28; absolute risk increase 0.016, 95% CI 0.012 to 0.020), respectively. Late preterm birth was not associated with an increased risk of seizure/febrile seizure.

Conclusions: Although very preterm birth may increase the risk of seizure/febrile seizure, the risk associated with late preterm birth is considerably small and less than that associated with male.
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http://dx.doi.org/10.1136/bmjopen-2019-035977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485243PMC
September 2020

Glenoid bone resorption after Bankart repair: finite element analysis of postoperative stress distribution of the glenoid.

J Shoulder Elbow Surg 2021 Jan 9;30(1):188-193. Epub 2020 Jun 9.

Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan.

Background: There are various modifications of the Bankart repair, and postoperative changes to the glenoid morphology after the repair are reported. Among the various procedures performed, a decrease in the lateral glenoid diameter might be related to the surgery that involves removal of the articular cartilage and repair of the labrum-anterior inferior glenohumeral ligament complex on the glenoid surface. This is in contrast to cases without significant bony Bankart lesions that are not on the edge of the glenoid. Thus, this study aimed to compare glenoid rim stress after Bankart repair using 2 methods of finite element analysis: a method of removing the anteroinferior cartilage and repairing the glenohumeral ligament complex on the glenoid and a method of preserving the cartilage and repairing the glenohumeral ligament complex on the glenoid edge.

Methods: Five preoperative computed tomography scans of patients with traumatic anterior instability who underwent arthroscopic Bankart repair were used. Two models simulating different surgical procedures were created as follows: in model G, a 5-mm-thick cartilage on the glenoid rim was removed between 2 and 7 o'clock, and the glenohumeral ligament complex was repaired on the medial edge of the glenoid bone where the cartilage was removed. In model E, the cartilage on the glenoid rim was not removed, and the glenohumeral ligament complex was repaired on the glenoid edge. The load stresses on the anteroinferior area of the glenoid after Bankart repair with models G and E were measured using finite element analysis.

Results: The stress on the glenoid at 3-4 o'clock was 3.16 MPa in model G and 6.42 MPa in model E (P = .043). The stress at 4-5 o'clock was 1.68 MPa in model G and 4.53 MPa in model E (P = .043). The stress at 5-6 o'clock was 2.26 MPa in model G and 3.93 MPa in model E (P = .043).

Conclusion: Significantly lower load stresses were observed at the anteroinferior rim of the glenoid in model G than in model E.
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http://dx.doi.org/10.1016/j.jse.2020.04.023DOI Listing
January 2021

Guidance for diagnosing autoimmune pancreatitis with biopsy tissues.

Pathol Int 2020 Oct 6;70(10):699-711. Epub 2020 Aug 6.

Kansai Medical University Kouri Hospital, Osaka, Japan.

The biopsy-based diagnosis of autoimmune pancreatitis (AIP) is difficult but is becoming imperative for pathologists due to the increased amount of endoscopic ultrasound-guided biopsy tissue. To cope with this challenge, we propose guidance for the biopsy diagnosis of type 1 AIP. This guidance is for pathologists and comprises three main parts. The first part includes basic issues on tissue acquisition, staining, and final diagnosis, and is intended for gastroenterologists as well. The second part is a practical guide for diagnosing type 1 AIP based on the AIP clinical diagnostic criteria 2018. Inconsistent histological findings, tips for evaluating IgG4 immunostaining and key histological features including the ductal lesion and others are explained. Storiform fibrosis and obliterative phlebitis are diagnostic hallmarks but are sometimes equivocal. Storiform fibrosis is defined as spindle-shaped cells, inflammatory cells and fine collagen fibers forming a flowing arrangement. Obliterative phlebitis is defined as fibrous venous obliteration with inflammatory cells. Examples of each are provided. The third part describes the differentiation of AIP from pancreatic ductal adenocarcinoma (PDAC), focusing on histological features of acinar-ductal metaplasia in AIP, which is an important mimicker of PDAC. This guidance will help standardize pathology reports of pancreatic biopsies for diagnosing type 1 AIP.
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http://dx.doi.org/10.1111/pin.12994DOI Listing
October 2020

Clinical usefulness of saphenous vein graft in major arterial reconstruction during extended pancreatectomy.

Langenbecks Arch Surg 2020 Nov 31;405(7):1051-1059. Epub 2020 Jul 31.

Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, S1 W16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

Purpose: Extended pancreatectomy for locally advanced pancreatobiliary malignancy often involves combined major arterial resection (AR) and reconstruction (ARc). By limiting candidate inflow for ARc after combined resection of the celiac arterial system over a long distance, we evaluated whether great saphenous vein graft (GSVG) is an alternative conduit for obtaining non-anatomical arterial inflow.

Methods: ARc with GSVG conduit was undertaken prior to resection. GSVG was harvested and anastomosed end-to-side with the reconstructing artery and then mostly passed via the retroperitoneal para-inferior vena cava route. Side-to-end anastomosis of GSVG inflow was established with the right common iliac artery or abdominal aorta.

Results: Among 468 consecutive pancreatobiliary surgeries, ARc with GSVG was undertaken in seven cases. Primary cancers were in the pancreas in six patients and distal bile duct in one. Radical surgery was performed with pancreaticoduodenectomy in six patients and total pancreatectomy in one. Hepatic artery (HA) was concomitantly resected and reconstructed by GSVG in six patients or by the jejunal artery in one patient. Median operative time and intraoperative blood loss were 763 min and 350 ml, respectively. Serum level of AST, ALT, and LDH in patients with HA reconstruction by GSVG peaked by the second postoperative day and promptly normalized. Postoperative morbidity (CD ≥ III) was encountered in one patient. No surgical mortality was observed. Postoperative serum liver enzymes promptly decreased in ARc patients with GSVG to HA.

Conclusion: Arterial reconstruction with GSVG prior to resection was performed securely and might help to reduce postoperative liver dysfunction.
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http://dx.doi.org/10.1007/s00423-020-01947-3DOI Listing
November 2020

Three Cases of Ampullary Neuroendocrine Tumor Treated by Endoscopic Papillectomy: A Case Report and Literature Review.

Intern Med 2020 Oct 30;59(19):2369-2374. Epub 2020 Jun 30.

Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan.

We herein report three cases of patients with an ampullary neuroendocrine tumor (NET), who underwent endoscopic papillectomy (EP). No tumor recurrence or metastasis was detected in the patients for more than two years after EP. Generally, surgical resection is recommended for ampullary NETs by the European Neuroendocrine Tumor Society. However, as EP is less invasive than surgical resection, there are some reports of low-grade small ampullary NETs curatively treated by EP with long-term follow-up. We consider that EP may be a curative treatment for small and low-grade ampullary NETs without regional or distant metastasis.
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http://dx.doi.org/10.2169/internalmedicine.4568-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644498PMC
October 2020

Thiamylal anaesthetic therapy for febrile refractory status epilepticus in children.

Seizure 2020 Aug 14;80:12-17. Epub 2020 May 14.

Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address:

Purpose: To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children.

Methods: This was a review of a prospectively-collected database between April 2012-March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications.

Results: All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis.

Conclusion: We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration.
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http://dx.doi.org/10.1016/j.seizure.2020.03.012DOI Listing
August 2020

Humeral bone resorption after reverse shoulder arthroplasty using uncemented stem.

JSES Int 2020 Mar 14;4(1):138-143. Epub 2020 Jan 14.

Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Japan.

Background: Humeral stem loosening has gained attention as it has been identified as a cause of revision surgery in reverse shoulder arthroplasty (RSA). In RSA, humeral stem revision is very difficult if there is humeral bone loss because of stress shielding. Some studies of humeral bone resorption after anatomic shoulder arthroplasty have been published, but there are few detailed reports of humeral bone resorption after RSA. This study aimed to investigate the prevalence of humeral bone resorption after RSA procedures and to evaluate the risk factors for bone resorption.

Methods: This study included 48 shoulders that underwent RSA with an uncemented humeral stem from July 2014 to May 2017 and were followed up for more than 1 year. The prevalence of humeral bone resorption and risk factors were investigated. Logistic, multiple logistic, and multivariate logistic regression analyses were performed to evaluate the data.

Results: Grade 0 bone resorption, the most advanced grade, occurred in 8 shoulders (16.7%); grade 1, in 0 (0%); grade 2, in 17 (35.4%); grade 3, in 14 (29.2%); and grade 4, in 9 (18.8%). A high occurrence of bone absorption was observed in zones 1, 2, and 7. Grade 4 bone resorption did not occur in zones 3, 5, and 6. Female sex and an onlay-type stem were significant independent risk factors for grade 4 bone resorption.

Conclusions: Bone resorption was frequently observed in the greater tuberosity, lateral diaphysis, and calcar region. Significant risk factors included female sex and an onlay-type stem.
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http://dx.doi.org/10.1016/j.jses.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075776PMC
March 2020

Tau Accumulation and Network Breakdown in Alzheimer's Disease.

Adv Exp Med Biol 2019 ;1184:231-240

Brain and Mind Research Center, Nagoya University, Nagoya, Japan.

Misfolded and aggregated tau and amyloid β (Aβ) proteins are the pathological hallmarks of Alzheimer's disease (AD). These aberrant proteins lose their physiological roles, acquire neurotoxicity, and propagate across neural systems. Despite the growing understanding of the molecular pathophysiology, the relationship among molecular alterations, pathological changes, and dementia onset and progression remain to be elucidated. Connectivity is an exclusive characteristic of the brain, and the integrity and segregation of the functional and anatomical networks are crucial for normal functioning. Interestingly, a lot of magnetic resonance imaging (MRI) studies have demonstrated successive structural and functional disconnection among brain regions supporting the idea that AD is a disconnection syndrome. Recent several studies using the combination of cutting-edge Aβ and tau PET tracers integrated by data-driven statistical methods, resting-state functional MRI, and diffusion tensor imaging have shed light on the spatial distribution pattern of tau retention as well the relationship between tau retention and functional/structural network disruption in AD. Regional retention of tau PET traces is associated with gray matter changes, structural network disruption, and cognitive function tests. The tau retention will mainly spread along with cognition-related resting state networks and be more common in the network hubs which exhibit many strong interconnections with other regions within the network as well as without the networks. Mainly, precuneus and posterior cingulate gyrus are commonly involved and can be the critical nodes associated with clinically manifested dementia from the normal cognitive state.
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http://dx.doi.org/10.1007/978-981-32-9358-8_19DOI Listing
April 2020

Precise anatomical resection based on structures of nerve and fibrous tissue around the superior mesenteric artery for mesopancreas dissection in pancreaticoduodenectomy for pancreatic cancer.

J Hepatobiliary Pancreat Sci 2020 Jun 11;27(6):342-351. Epub 2020 Mar 11.

Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan.

Background: The aim of the present study was to investigate the feasibility of resection based on the nerve and fibrous tissue (NFT) structures around the superior mesenteric artery (SMA) for resectable pancreatic adenocarcinoma (R-PDAC) patients.

Methods: NFTs around the SMA were classified into four "intensive NTFs area" with spreading the NFTs around the SMA and three SMA nerve plexus regions without branching nerves according to autopsy findings. Complete dissection of four "intensive NTFs areas" was performed by pre-exposing three SMA nerve plexus regions without branching nerves as "dissection-guiding points" with SMA nerve plexus preservation (NFT-based resection). Among 157 R-PDAC patients undergoing pancreaticoduodenectomy, surgical outcomes of 78 patients with NFT-based resection were compared with 59 patients with half-SMA nerve plexus dissection and 20 patients without NFTs dissection.

Results: In the NFT-based resection group, 76.5% had tumor involvement and metastasis in each intensive NTFs area. Operative time, blood loss, and postoperative diarrhea rate were significantly lower in NFT-based resection than in half-SMA nerve plexus group (321 vs 390 min; P < .01, 228 vs 550 mL; P < .01, 5.1% vs 15.3%; P = .04, respectively). R0 rate and median overall survival significantly improved in NFT-based resection than in non-NFT dissection group (93.6% vs 65.0%; P < .01, 49.6 vs 23.6 months, P = .01).

Conclusion: NFT-based resection may become a novel method for R-PDAC patients.
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http://dx.doi.org/10.1002/jhbp.725DOI Listing
June 2020

Glucose-Dependent FOXM1 Promotes Epithelial-to-Mesenchymal Transition Via Cellular Metabolism and Targeting Snail in Human Pancreatic Cancer.

Pancreas 2020 02;49(2):273-280

From the Department of Surgery, Surgical Oncology and Science.

Objectives: Transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in the progression of cancer including epithelial-to-mesenchymal transition (EMT). The aim of this study is to characterize the regulatory mechanisms of FOXM1 in EMT via pancreatic cancer metabolism.

Methods: We investigated the regulation of EMT via mitochondrial respiration by FOXM1 using pancreatic cancer cell lines HPAC and PANC-1 and normal human pancreatic duct epithelial cells.

Results: Forkhead box protein M1 and Snail were strongly expressed in HPAC and PANC-1. Epithelial-to-mesenchymal transition-modulated claudin-1 level was lower in PANC-1 than in HPAC. In both cell lines in low-glucose medium, FOXM1 and Snail were decreased and claudin-1 was increased. Knockdown of FOXM1 increased claudin-1 and decreased Snail in both cell lines. Low-glucose medium and downregulation of FOXM1 inhibited the cell migration in both cell lines. In both cell lines, mitochondrial respiration was at higher levels in low-glucose medium than in high-glucose medium. Downregulation of FOXM1 induced mitochondrial respiration in high-glucose medium. In normal human pancreatic duct epithelial cells, FOXM1 and Snail were low and claudin-1 was highly expressed, whereas overexpression of FOXM1 decreased claudin-1.

Conclusions: Glucose-dependent FOXM1 promoted EMT via Snail and pancreatic cancer metabolism.
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http://dx.doi.org/10.1097/MPA.0000000000001485DOI Listing
February 2020

Prediction of the Probability of Malignancy in Mucinous Cystic Neoplasm of the Pancreas With Ovarian-Type Stroma: A Nationwide Multicenter Study in Japan.

Pancreas 2020 02;49(2):181-186

Department of Surgery, Kyorin University School of Medicine, Mitaka, Tokyo.

Objective: The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma.

Methods: A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed.

Results: A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22.

Conclusions: The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.
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http://dx.doi.org/10.1097/MPA.0000000000001475DOI Listing
February 2020

Detailed characteristics of acute encephalopathy with biphasic seizures and late reduced diffusion: 18-year data of a single-center consecutive cohort.

J Neurol Sci 2020 Apr 16;411:116684. Epub 2020 Jan 16.

Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan.

Objective: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a syndrome characterized by biphasic seizures with impaired consciousness. AESD is rare outside Asia, and consecutive cohort studies are therefore scarce. Herein, we aimed to describe the detailed characteristics of AESD, including clinical course, electroencephalogram data, laboratory data, imaging findings, treatment, and outcomes.

Methods: We reviewed the clinical database and medical charts of 43 consecutive pediatric patients (<18 years old) who developed AESD between October 1, 2002, and September 30, 2019.

Results: We found that AESD occurred even though patients did not develop prolonged seizures. A comparison between the two groups (first seizure duration <30 min and first seizure duration ≥30 min) revealed three main findings: first, patients with AESD who had shorter seizures had better prognosis than those with prolonged seizures; second, patients with AESD who had shorter seizures tended to have earlier occurrence of a second seizure; and third, high signal intensity on diffusion-weighted magnetic resonance imaging was observed mainly in frontal areas, not diffusely, in patients with shorter seizures, and in a broader area in patients with prolonged seizures.

Conclusions: Our description of the detailed clinical picture of AESD may add new insight into its pathophysiology.
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http://dx.doi.org/10.1016/j.jns.2020.116684DOI Listing
April 2020