Publications by authors named "Kenji Sakai"

193 Publications

[Cerebral Amyloid Angiopathy-Related Inflammation/Vasculitis].

Brain Nerve 2021 May;73(5):489-495

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences.

Cerebral amyloid angiopathy (CAA) is a disorder characterized by the deposition of amyloid in the leptomeningeal and cortical blood vessels. Sporadic amyloid β (Aβ)-type CAA is the most common form of CAA. Although CAA is a well-known cause for recurrent cerebral lobar hemorrhage, inflammation, and vasculitis, CAA-related inflammation/vasculitis (CAA-ri/vasculitis) induced by Aβ deposition on vessel walls is emerging as a treatable condition. The estimated total number of cases of and prevalence of CAA-ri/vasculitis in Japan were 170 and 0.13 per 100 000 population, respectively. Patients with CAA-ri/vasculitis show acute or subacute-onset of cognitive impairment, behavioral changes, and headache. Brain magnetic resonance imaging, showing asymmetrical white matter abnormalities and occasional meningeal enhancement, is a useful tool for the diagnosis of CAA-ri/vasculitis. Moreover, elevation of anti-Aβ antibodies and inflammatory markers in the cerebrospinal fluid can help in clinical diagnosis. Although several clinical diagnostic criteria have been proposed, neuropathological examination of a brain biopsy remains the gold standard for detecting severe Aβ deposition and vasculopathic changes with lymphocytic infiltrations and/or granulomatous vasculitis. No validated treatment regimen has been established to date. Nearly 80% patients with CAA-ri/vasculitis improved after immunosuppressant therapy with corticosteroid and/or cyclophosphamide. Early treatment is essential to prevent irreversible sequelae in the brain.
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http://dx.doi.org/10.11477/mf.1416201790DOI Listing
May 2021

Hybrid approach with laparoscopic wall-inversion surgery and single-incision intragastric surgery for intraluminal gastrointestinal stromal tumor: A case report.

Asian J Endosc Surg 2021 Feb 16. Epub 2021 Feb 16.

Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan.

Laparoscopic wedge resection (LWR) for intraluminal gastrointestinal stromal tumor (GIST) leads to excessive resection of normal gastric wall. We report a case of GIST around the cardia successfully treated with full-thickness partial resection using a hybrid approach of laparoscopic surgery and single-incision intragastric surgery (SIIGS). A 69-year-old woman had a 5 cm intraluminal GIST at the posterior wall around the cardia. Submucosal injection of glycerin and indigo carmine was performed with transoral endoscopy. Circumferential seromuscular incision followed by placement of seromuscular sutures to invert the lesion into the stomach was performed under laparoscopy. By SIIGS, resection of the inverted mucosa and retrieval of the tumor were completed. A hybrid approach consisting of laparoscopic wall-inversion surgery and SIIGS was useful for intraluminal GIST and may expand the indications for laparoscopic wall-inversion surgery by removing size limitations.
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http://dx.doi.org/10.1111/ases.12927DOI Listing
February 2021

[Laparoscopic Surgery for Synchronous Retroperitoneal Tumor and Ovarian Mature Teratoma-A Case Report].

Gan To Kagaku Ryoho 2020 Dec;47(13):2329-2331

Dept. of Surgery, Japan Community Health care Organization(JCHO)Osaka Hospital.

A 72-year-old woman was transferred to our hospital after being diagnosed with retroperitoneal and ovarian tumors. Abdominal computed tomography revealed a well-defined mass lesion measuring 35 mm on the dorsal side of the descending part of the duodenum that was surrounded by the head of the pancreas and inferior vena cava. In addition, a cystic mass measuring 90 mm was found in the pelvis. Hence, the patient was diagnosed synchronous retroperitoneal tumor and teratoma. Laparoscopic retroperitoneal tumor resection and right adnexectomy were performed. The pathological findings indicated that the retroperitoneal tumor was a diffuse large B-cell lymphoma and the pelvic tumor was a mature cystic teratoma of the ovary. On the basis of the computed tomography findings, we judged that the tumor had a poor tendency to infiltrate and could be peeled off and resected using laparoscopic surgery. In this rare case, the retroperitoneal tumor and mature teratocarcinoma were simultaneously resected laparoscopically.
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December 2020

[A Case of Fibrolamellar Hepatocellular Carcinoma in a 25-Year-Old Vietnamese Male].

Gan To Kagaku Ryoho 2020 Dec;47(13):2326-2328

Dept. of Surgery, Japan Community Health care Organization(JCHO)Osaka Hospital.

We report a rare case of hepatic fibrolamellar hepatocellular carcinoma(FLC). A 25-year-old Vietnamese male experienced loss of appetite and abdominal pain. He was referred for further examination of a 20 cm tumor in the left lobe of the liver detected in mass screening ultrasonography. He tested negative for HBs-antigen and HCV-antibody. The serum PIVKA- Ⅱ level was elevated. Liver function test findings were normal. The arterial phase of contrast enhanced abdominal CT revealed a 20×30 cm tumor that was well-enhanced, except for a central scar in the left lobe of liver. Enhanced MRI showed a high intensity tumor. T2-weighted MRI showed an iso-intensity tumor with a low-intensity central fibrous scar. Upon diagnosing the patient with FLC, we performed left hepatic trisegmentectomy. Pathological findings of the surgical specimen showed eosinophilic large neoplastic cells surrounded by fibrous stroma arranged in a lamellar fashion. This confirmed the diagnosis. FLC, which occurs in noncirrhotic livers of young patients, is a distinct clinicopathological variant of hepatocellular carcinoma. Hepatectomy for FLC should be accompanied with regional lymphadenectomy because of its association with lymph node metastasis. We also reviewed cases reported in Japan.
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December 2020

[Pathological Complete Response in a Case of Advanced Gastric Cancer with Para-Aortic Lymph Nodes Metastasis Treated by Preoperative Chemotherapy with S-1 and Oxaliplatin(SOX Therapy)].

Gan To Kagaku Ryoho 2020 Dec;47(13):2278-2280

Dept. of Surgery, Japan Community Health care Organization(JCHO)Osaka Hospital.

The patient was a 73-year-old man, diagnosed as advanced gastric cancer with para-aortic lymph nodes(PAN)metastasis. He was treated by 3 courses of neoadjuvant chemotherapy(NAC)with S-1 and oxaliplatin(SOX therapy). CT showed significant reduction of both primary tumor and metastatic lymph nodes. We performed distal gastrectomy with D2 plus PAN dissection. The histopathological findings showed no residual viable tumor cell. The pathological effect of chemotherapy was judged Grade 3(pCR)in both primary tumor and dissected lymph nodes. He is alive without recurrence 21 months after surgery.
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December 2020

[A Long-Term Survival Case of Neuroendocrine Carcinoma of Gallbladder-Report of a Case].

Gan To Kagaku Ryoho 2020 Dec;47(13):2272-2274

Dept. of Surgery, Japan Community Health care Organization(JCHO)Osaka Hospital.

The patient is 77-year-old man. He received open cholecystectomy and choledocholithotomy when he was 74 years old. Because postoperative diagnosis was small cell neuroendocrine carcinoma(NEC), the resection of gallbladder bed and hilus lymph nodes were performed. During the follow up period, the liver metastases and portal vein tumor thrombosis appeared. Therefore, chemotherapy was performed according to small cell lung cancer. In addition to chemotherapy, radiation therapy was performed for the purpose of local control. He is still alive about 3 years after the first operation. This case suggested the efficacy of multidisciplinary treatment including operation, chemotherapy, and radiation therapy in NEC of gallbladder patient with liver metastasis.
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December 2020

Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy.

J Neuropathol Exp Neurol 2021 01;80(2):102-111

Institute of Neurology, Medical University of Vienna, Vienna, Austria.

Primary age-related tauopathy (PART) is a neurodegenerative entity defined as Alzheimer-type neurofibrillary degeneration primarily affecting the medial temporal lobe with minimal to absent amyloid-β (Aβ) plaque deposition. The extent to which PART can be differentiated pathoanatomically from Alzheimer disease (AD) is unclear. Here, we examined the regional distribution of tau pathology in a large cohort of postmortem brains (n = 914). We found an early vulnerability of the CA2 subregion of the hippocampus to neurofibrillary degeneration in PART, and semiquantitative assessment of neurofibrillary degeneration in CA2 was significantly greater than in CA1 in PART. In contrast, subjects harboring intermediate-to-high AD neuropathologic change (ADNC) displayed relative sparing of CA2 until later stages of their disease course. In addition, the CA2/CA1 ratio of neurofibrillary degeneration in PART was significantly higher than in subjects with intermediate-to-high ADNC burden. Furthermore, the distribution of tau pathology in PART diverges from the Braak NFT staging system and Braak stage does not correlate with cognitive function in PART as it does in individuals with intermediate-to-high ADNC. These findings highlight the need for a better understanding of the contribution of PART to cognitive impairment and how neurofibrillary degeneration interacts with Aβ pathology in AD and PART.
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http://dx.doi.org/10.1093/jnen/nlaa153DOI Listing
January 2021

Short-term and long-term outcomes of laparoscopic colectomy with multivisceral resection for surgical T4b colon cancer: Comparison with open colectomy.

Ann Gastroenterol Surg 2020 Nov 20;4(6):676-683. Epub 2020 Jul 20.

National Hospital Organization Osaka National Hospital Osaka Japan.

Aim: In response to the rising use of laparoscopic surgery, recent studies have shown that laparoscopic multivisceral resections for locally advanced colon cancer are safe, feasible, and provide acceptable oncological outcomes. However, the usefulness of laparoscopic multivisceral resection remains controversial. Here, we aimed to compare short-term and long-term outcomes between laparoscopic and open multivisceral resection approaches for treating locally advanced colon cancer.

Methods: We retrospectively collected data on 1315 consecutive patients admitted to the National Hospital Organization, Osaka National Hospital, for surgical treatment of colorectal cancer between 2010 and 2017. We assessed invasiveness in terms of operating times, blood loss, and complications. Oncological outcomes included 5-year survival rates and recurrences.

Results: We included 85 patients that underwent a colectomy with a multivisceral resection for locally advanced colon cancer; of these, 38 were treated with a laparoscopic approach and 47 were treated with an open approach. Compared to the open surgery group, the laparoscopic group had significantly less blood loss (median volume: 25 vs 140 mL,  <0.001), a lower complication rate (10.5% vs 29.8%,  = 0.036), and shorter hospital stays (12 vs 15 days,  = 0.028). After excluding patients with stage Ⅳ colon cancer, the groups showed similar pathologic outcomes and no significant differences in 5-year disease-free survival (73.9% vs 67.4%;  = 0.664) or 5-year overall survival (75.8% vs 67.7%;  = 0.695).

Conclusion: A laparoscopic approach for locally advanced colon cancer could be less invasive than an open approach without affecting oncological outcomes in selected patients.
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http://dx.doi.org/10.1002/ags3.12372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726680PMC
November 2020

A new computerized assessment battery for cognition (C-ABC) to detect mild cognitive impairment and dementia around 5 min.

PLoS One 2020 11;15(12):e0243469. Epub 2020 Dec 11.

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

This study aimed to develop a new computerized assessment battery for cognition (C-ABC) to detect mild cognitive impairment (MCI) and dementia. We performed C-ABC in subjects with dementia (n = 422), MCI (n = 145), and normal cognition (NC; n = 574), and analyzed by age stratum (50s, 60s, and 70-85 years). To distinguish MCI from NC, the C-ABC total combined score, which were calculated by dividing the C-ABC total score by the C-ABC required time, revealed the best area under the curves (AUC) at 0.838 and 0.735 in the 50s and 60s age groups, respectively; notably, this entire procedure took approximately 5 min. To distinguish dementia from NC and MCI, the partial items of C-ABC (items 3 + 6 combined score) revealed the best AUCs at 0.910, 0.874, and 0.882 in the 50s, 60s, and 70-85 age groups, respectively. Furthermore, the items 3 + 6 combined score established the best AUC at 0.794 in the 70-85 age group to distinguish MCI from NC; this entire procedure took around 2 min. Hence, this study suggests that C-ABC could be a useful tool for detecting dementia or MCI in a short time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243469PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732101PMC
January 2021

Cerebrospinal fluid cytokines and metalloproteinases in cerebral amyloid angiopathy-related inflammation.

Acta Neurol Scand 2021 Apr 11;143(4):450-457. Epub 2020 Dec 11.

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Objectives: To clarify pathomechanisms of cerebral amyloid angiopathy-related inflammation/vasculitis (CAA-ri).

Methods: We collected cerebrospinal fluid (CSF) samples of nine patients with CAA-ri of before (acute CAA-ri group) and after treatment (post-treatment CAA-ri group) and nine patients with CAA (CAA without inflammation group). We examined anti-amyloid β protein (Aβ) antibody titer by ELISA, and measured 27 Cytokines, nine matrix metalloproteinases (MMPs), and four tissue inhibitors of MMPs (TIMPs) by multiplexed fluorescent bead-based immunoassay.

Results: We demonstrated TIMP-2 (median) in CSF of the acute CAA-ri group (30,994.49 pg/ml, p = 0.007) and the post-treatment CAA-ri group (36,430.97 pg/ml, p = 0.001) was significantly elevated compared to that of the CAA without inflammation group (22,013.58 pg/ml). TIMP-1 was also higher in the post-treatment CAA-ri group than that in the CAA without inflammation group (58,167.75 pg/ml vs. 45,770.03 pg/ml, p = 0.005). There was a significant positive correlation between TIMP-1 and anti-Aβ antibodies in CAA-ri (r  = 0.900, p = 0.037). Median MMP-2 tended to be higher in the acute and post-treatment CAA-ri groups (10,619.82 pg/ml and 8396.98 pg/ml, respectively) than in the CAA without inflammation group (4436.34 pg/ml). Platelet-derived growth factor (PDGF)-BB levels before treatment were higher than those after treatment (median, 12.66 pg/ml vs. 6.39 pg/ml; p = 0.011) and correlated with the titer of anti-Aβ antibodies (r  =0.900, p = 0.037).

Conclusions: Elevated levels of MMP-2, TIMP-1, and TIMP-2 might be related to the development of CAA-ri. Elevation of PDGF-BB could be a useful marker for clinical diagnosis of CAA-ri.
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http://dx.doi.org/10.1111/ane.13382DOI Listing
April 2021

Relationship between the bacterial community structures on human hair and scalp.

Biosci Biotechnol Biochem 2020 Dec 29;84(12):2585-2596. Epub 2020 Sep 29.

Laboratory of Soil and Environmental Microbiology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University , Fukuoka, Japan.

In this study, we investigated and compared characteristics of the bacterial community structures on hair (scalp hair) and scalp in 18 individuals. Significant differences were found between the sites, in terms of cell density, alpha and beta diversity, and relative abundance of the phyla, Firmicutes and Proteobacteria, whereas no difference was found in relative abundance of the phylum Actinobacteria. Bacteria of the genus showed similar relative abundance at both sites, whereas those of genus were highly abundant on hair, and those of genus were significantly lesser in abundance on hair than on scalp. Statistical correlations between the sites were high for the individual relative abundance of five major operational taxonomic units (OTUs). This suggests that the bacterial community structure on hair is composed of hair-specific genus, , and skin-derived genera, and , and is distinguishable from other human skin microbiomes.
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http://dx.doi.org/10.1080/09168451.2020.1809989DOI Listing
December 2020

MM2-type sporadic Creutzfeldt-Jakob disease: new diagnostic criteria for MM2-cortical type.

J Neurol Neurosurg Psychiatry 2020 11 24;91(11):1158-1165. Epub 2020 Aug 24.

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

Objective: To clinically diagnose MM2-cortical (MM2C) and MM2-thalamic (MM2T)-type sporadic Creutzfeldt-Jakob disease (sCJD) at early stage with high sensitivity and specificity.

Methods: We reviewed the results of Creutzfeldt-Jakob disease Surveillance Study in Japan between April 1999 and September 2019, which included 254 patients with pathologically confirmed prion diseases, including 9 with MM2C-type sCJD (MM2C-sCJD) and 10 with MM2T-type sCJD (MM2T-sCJD), and 607 with non-prion diseases.

Results: According to the conventional criteria of sCJD, 4 of 9 patients with MM2C- and 7 of 10 patients with MM2T-sCJD could not be diagnosed with probable sCJD until their death. Compared with other types of sCJD, patients with MM2C-sCJD showed slower progression of the disease and cortical distribution of hyperintensity lesions on diffusion-weighted images of brain MRI. Patients with MM2T-sCJD also showed relatively slow progression and negative results for most of currently established investigations for diagnosis of sCJD. To clinically diagnose MM2C-sCJD, we propose the new criteria; diagnostic sensitivity and specificity to distinguish 'probable' MM2C-sCJD from other subtypes of sCJD, genetic or acquired prion diseases and non-prion disease controls were 77.8% and 98.5%, respectively. As for MM2T-sCJD, clinical and laboratory features are not characterised enough to develop its diagnostic criteria.

Conclusions: MM2C-sCJD can be diagnosed at earlier stage using the new criteria with high sensitivity and specificity, although it is still difficult to diagnose MM2T-sCJD clinically.
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http://dx.doi.org/10.1136/jnnp-2020-323231DOI Listing
November 2020

Diffusion-weighted magnetic resonance imaging in dura mater graft-associated Creutzfeldt-Jakob disease.

J Neurol Sci 2020 Nov 13;418:117094. Epub 2020 Aug 13.

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8604, Japan. Electronic address:

Purpose: To elucidate the extension patterns of the hyperintense areas on diffusion-weighted magnetic resonance imaging (DW-MRI) in patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD).

Methods: We collected the DW-MRI of dCJD cases identified by the CJD Surveillance Committee in Japan, between April 1999 and February 2018. The dCJD cases were classified into non-plaque and plaque-types. The relationship among the abnormal signals, the pathological classification, and the sites of grafting were analyzed.

Results: We collected DW-MRI of 11 patients with dCJD, all of whom were methionine homozygous at codon 129 of the prion protein gene. The age at onset was 41 (26-76) [median (range)] years, the age at dural grafting was 19 (10-53) years, and the incubation period was 22 (16-29) years. Eight dCJD cases were classified as non-plaque-type and three cases were plaque-type. Five of the non-plaque-type cases and all the plaque-type cases were pathologically confirmed. Brain DW-MRI was performed 3 (1-22) months after the onset. Most of the non-plaque-type cases showed brighter hyperintensity in the cerebral cortex and basal ganglia on the side of dural grafting. Subsequent DW-MRI showed widespread hyperintense lesions in the brain. Regarding the plaque-type cases, initial scans showed hyperintensity in the basal ganglia and the thalamus in one patient. Another patient's lesion was confined to the basal ganglia. The third patient showed no abnormalities seven months post-onset; however, serial images showed a hyperintensity confined to the thalamus.

Conclusions: Non-plaque and plaque-types demonstrated different patterns of propagation of distinct prion strains.
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http://dx.doi.org/10.1016/j.jns.2020.117094DOI Listing
November 2020

Accumulation of phosphorylated TDP-43 in the cytoplasm of Schwann cells in a case of sporadic amyotrophic lateral sclerosis.

Neuropathology 2020 Dec 9;40(6):606-610. Epub 2020 Aug 9.

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

We report for the first time the presence of phosphorylated transactivation response DNA-binding protein of 43 kDa (p-TDP-43)-immunoreactive cytoplasmic inclusions in Schwann cells in an autopsy case of sporadic amyotrophic lateral sclerosis (ALS). An 81-year-old woman with no family history of neuromuscular disorders noticed difficulty in handling chopsticks due to weakness of the hands. She then developed weakness of the lower and upper limbs and dyspnea. Neurological examination at the age of 83 years revealed disorientation, severe weakness of the facial muscles, tongue, neck and extremities, and fasciculations in the thighs. She exhibited hyperactive jaw jerk and lower limb deep tendon reflexes and normal upper limb deep tendon reflexes, and left extensor plantar response was observed. The patient was diagnosed as having sporadic ALS. An autopsy performed at the age of 84 years revealed widespread p-TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions in the cerebrum, brain stem, and spinal cord, in addition to some Bunina bodies. Moreover, a small number of p-TDP-43-immunoreactive inclusions were found in the facial or accoustic nerve (indistinguishable), spinal cord anterior roots, cauda equina, and peripheral nerves in the dorsal root ganglia. Immunohistochemical staining for p-TDP-43 revealed just a few p-TDP-43-immunoreactive inclusions surrounding axons in the cervical and lumbar anterior roots. Double immunofluorescence analysis revealed that these inclusions were co-localized with S-100 protein β, suggesting that these inclusions were localized in the cytoplasm of Schwann cells. The peripheral nervous system including Schwann cells may be involved in TDP-43 pathology in ALS.
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http://dx.doi.org/10.1111/neup.12673DOI Listing
December 2020

Sarcoid neuropathy with conduction block showing nerve fascicle compression by perineurial granuloma formation.

Clin Neurol Neurosurg 2020 09 28;196:105962. Epub 2020 May 28.

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

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http://dx.doi.org/10.1016/j.clineuro.2020.105962DOI Listing
September 2020

Optimal timing of laparoscopic cholecystectomy after gallbladder drainage for acute cholecystitis: A multi-institutional retrospective study.

J Hepatobiliary Pancreat Sci 2020 Aug 21;27(8):451-460. Epub 2020 Jun 21.

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.

Background: There is no consensus on the optimal timing of laparoscopic cholecystectomy (LC) after gallbladder drainage for acute cholecystitis (AC). To obtain evidence for a consensus, we investigated surgical outcomes of LC after gallbladder drainage with respect to the time elapsed from gallbladder drainage to surgery in a multi-institutional retrospective study.

Methods: This study enrolled 347 patients who underwent LC after gallbladder drainage for AC at 15 institutions. Surgical outcome of LC was investigated in the cases based on the interval from gallbladder drainage to surgery.

Results: The median interval from gallbladder drainage to surgery of the patients was 34 days, with a mean ± standard deviation of 58 ± 99 days. Patients were divided into four groups based on quartiles of the interval: Group A, cases with an interval of 1-12 days; Group B, cases with an interval of 13-34 days; Group C, cases with an interval of 35-73 days; and Group D, cases with an interval of ≥74 days. Surgical outcomes, which were evaluated with respect to intraoperative blood loss, operation time, postoperative hospital stay, rate of intraoperative accident, conversion from laparoscopic to open surgery, and postoperative complication, were worse in Group B than in the other groups. The finding was verified by propensity score-matched analysis.

Conclusions: Surgical outcome of LC after gallbladder drainage for AC was inferior in Group B compared with the other groups. This finding could be useful for determining the optimal timing of LC after gallbladder drainage for AC.
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http://dx.doi.org/10.1002/jhbp.768DOI Listing
August 2020

Characterization of Sporadic Creutzfeldt-Jakob Disease and History of Neurosurgery to Identify Potential Iatrogenic Cases.

Emerg Infect Dis 2020 06;26(6):1140-1146

We previously reported a phenotype of Creutzfeldt-Jakob disease (CJD), CJD-MMiK, that could help identify iatrogenic CJD. To find cases mimicking CJD-MMiK, we investigated clinical features and pathology of 1,155 patients with diagnosed sporadic CJD or unclassified CJD with and without history of neurosurgery. Patients with history of neurosurgery more frequently had an absence of periodic sharp-wave complexes on electroencephalogram than patients without a history of neurosurgery. Among 27 patients with history of neurosurgery, 5 had no periodic sharp-wave complexes on electroencephalogram. We confirmed 1 case of CJD-MMiK and suspected another. Both had methionine homozygosity at codon 129 of the prion protein gene and hyperintensity lesions in the thalamus on magnetic resonance images of the brain, which might be a clinical marker of CJD-MMiK. A subgroup with a history of neurosurgery and clinical features mimicking dura mater graft-associated CJD might have been infected during neurosurgery and had symptoms develop after many years.
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http://dx.doi.org/10.3201/eid2606.181969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258447PMC
June 2020

Protective Effects of Recombinant Human Soluble Thrombomodulin on Lipopolysaccharide-Induced Acute Kidney Injury.

Int J Mol Sci 2020 Apr 5;21(7). Epub 2020 Apr 5.

Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan.

Thrombomodulin (TM) is a single transmembrane, multidomain glycoprotein receptor for thrombin, and is best known for its role as a cofactor in a clinically important natural anticoagulant pathway. In addition to its anticoagulant function, TM has well-defined anti-inflammatory properties. Soluble TM levels increase significantly in the plasma of septic patients; however, the possible involvement of recombinant human soluble TM (rTM) transduction in the pathogenesis of lipopolysaccharide (LPS)-induced nephrotoxicity, including acute kidney injury (AKI), has remained unclear. Mice were injected intraperitoneally with 15 mg/kg LPS. rTM (3 mg/kg) or saline was administered to the animals before the 3 and 24 h LPS-injection. At 24 and 48 h, blood urea nitrogen, the inflammatory cytokines in sera and kidney, and histological findings were assessed. Cell activation and apoptosis signal was assessed by Western blot analysis. In this study using a mouse model of LPS-induced AKI, we found that rTM attenuated renal damage by reducing both cytokine and cell activation and apoptosis signals with the accumulation of CD4+ T-cells, CD11c+ cells, and F4/80+ cells via phospho c-Jun activations and Bax expression. These findings suggest that the mechanism underlying these effects of TM may be mediated by a reduction in inflammatory cytokine production in response to LPS. These molecules might thereby provide a new therapeutic strategy in the context of AKI with sepsis.
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http://dx.doi.org/10.3390/ijms21072519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177880PMC
April 2020

Biochar enhanced the nitrifying and denitrifying bacterial communities during the composting of poultry manure and rice straw.

Waste Manag 2020 Apr 30;106:240-249. Epub 2020 Mar 30.

Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.

Biochar has proven to be a feasible additive for mitigating nitrogen loss during the composting process. This study aims to evaluate the influence of biochar addition on bacterial community and physicochemical properties changes, including ammonium (NH), nitrite (NO) and nitrate (NO) contents during the composting of poultry manure. The composting was carried out by adding 20% (w/w) of biochar into the mixture of poultry manure and rice straw with a ratio of 2:1, and the same treatment without biochar was prepared as a control. The finished product of control compost recorded the high contents of NO and NO (366 mg/kg and 600 mg/kg) with reduced the total NH content to 10 mg/kg. Meanwhile, biochar compost recorded a higher amount of total NH content (110 mg/kg) with low NO and NO (161 mg/kg and 137 mg/kg) content in the final composting material. The principal component analysis showed that the dynamics of dominant genera related to Halomonas, Pusillimonas, and Pseudofulvimonas, all of which were known as nitrifying and denitrifying bacteria, was significantly correlated with the dynamic of NO and NO content throughout the composting process. The genera related to Pusillimonas, and Pseudofulvimonas appeared as the dominant communities as the NO and NO increased. In contrast, as the NO and NO concentration decreased, the Halomonas genus were notably enriched in biochar compost. This study revealed the bacterial community shifts corresponded with the change of physicochemical properties, which provides essential information for a better understanding of monitoring and improving the composting process.
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http://dx.doi.org/10.1016/j.wasman.2020.03.029DOI Listing
April 2020

Efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for treating patients with stage III colon cancer (KSCC1303): final analysis of 3-year disease-free survival.

Int J Clin Oncol 2020 Jun 18;25(6):1115-1122. Epub 2020 Mar 18.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Adjuvant chemotherapy is an accepted treatment to improve survival rates in patients with stage III colon cancer, and regimens including oxaliplatin have been shown to be superior to those containing 5-FU alone. The purpose of this study was to examine the efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) as adjuvant chemotherapy for patients with stage III colon cancer following curative resection.

Methods: Patients with colon cancer who underwent curative resection were enrolled and received oral S-1 40-60 mg twice daily on days 1-14 every 3 weeks plus intravenous oxaliplatin 130 mg/m on day 1 for eight courses. The primary endpoint was 3-year disease-free survival rate. Secondary endpoints were the rate of treatment completion, adverse events, relative dose intensity, and overall survival.

Results: Between February 2014 and December 2014, 89 patients were enrolled. One patient was excluded from the analysis because of ineligibility, and the remaining 88 patients were included. The rate of protocol treatment completion was 72.3%. The relative dose intensity of S-1 and oxaliplatin was 72% and 76.3%, respectively. Hematological severe adverse events (Grade 3/4) were neutropenia (21.3%) and thrombocytopenia (15.7%). The most frequent symptom was diarrhea (Grade 3/4: 5.6%). The incidence of grade 2 neuropathy has decreased from 8.1 to 2.7% after 3 years of the therapy. Three-year disease-free survival rate was 73.9% (95% CI 63.8-81.9), and 3-year overall survival rate was 94.3% (95% CI 86.8-97.6) CONCLUSIONS: C-SOX is a safe and feasible adjuvant chemotherapy regimen in patients with stage III colon cancer undergoing curative resection.
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http://dx.doi.org/10.1007/s10147-020-01646-5DOI Listing
June 2020

[Laparoscopic Surgery for a Case of Double Digestive Cancers with X-Linked Agammaglobulinemia].

Gan To Kagaku Ryoho 2019 Dec;46(13):2571-2573

Dept. of Surgery, Japan Community Health care Organization(JCHO)Osaka Hospital.

A 65-year-old man was diagnosed with agammaglobulinemia at the age of 53 years. To investigate the cause of the increased CRP value, CT was performed and revealed thickening of the walls of the ascending colon and rectum. Colonoscopy revealed tumors and stenoses in the ascending colon and rectum. Both tumors were found to be adenocarcinomas in histological examinations. The preoperative diagnosis of the ascending colon and rectal cancers was cT4aN0M0, cStageⅡb. Preoperatively, we administered 10.0 g of immunoglobulin intravenously. We performed laparoscopic right hemicolectomy and high anterior resection with D3 dissection of the lymph node. On postoperative day 1, we again administered 10.0 g of immunoglobulin intravenously. The patient recovered uneventfully and was discharged on postoperative day 13. Laparoscopic colectomy for patients with agammaglobulinemia can be performed safely by administering immunoglobulin during the perioperative period.
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December 2019

[A Case of Superior Mesenteric Vein Thrombosis during Administration of Bevacizumab for Rectal Cancer].

Gan To Kagaku Ryoho 2019 Dec;46(13):2491-2493

Dept. of Surgery, Japan Community Healthcare Organization(JCHO)Osaka Hospital.

A colonoscopy to investigate fecal incontinence revealed a type 3 tumor in the rectum of a 67-year-old man. Histological findings demonstrated rectal adenocarcinoma. CT revealed multiple metastases in the liver, and the patient was diagnosed as having rectal cancer(Rb, Ant, type 3, T3, N3, M1a[H2], cStage Ⅳa). No intestinal stenosis due to the tumor was found, and chemotherapy(FOLFIRI plus bevacizumab)was initiated. After 5 courses of the chemotherapy, a thrombus was found in the superior mesenteric vein on enhanced CT. The patient had no subjective symptoms, and anticoagulation therapy was started after admission. After confirming the shrinkage of the thrombus, laparoscopic abdominoperineal resection(prxD3)was performed to remove the primary tumor. The thrombus did not grow during the perioperative time and disappeared after 6 months. For the next 2 years, no new thrombus was detected. Mesenteric vein thrombosis is a notable complication of chemotherapy with bevacizumab.
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December 2019

[A Case of Cystic Biliary Hamartoma with a Difficult Preoperative Diagnosis].

Gan To Kagaku Ryoho 2019 Dec;46(13):2345-2347

Dept. of Surgery, Japan Community Healthcare Organization(JCHO) Osaka Hospital.

Intrahepatic bile duct dilatation was detected in a 63-year-old man based on abdominal ultrasonography. The computed tomography and magnetic resonance imaging scans showed an intrahepatic cystic lesion in the hilar bile duct that led to intrahepatic bile duct dilatation. As a result, intraductal papillary neoplasm of the bile duct(IPNB)was suspected. Moreover, the intrahepatic bile duct dilatation was confirmed by endoscopic retrograde cholangiopancreatography(ERCP). Biliary and brushing cytology indicated that the cystic lesion was class Ⅱ and class Ⅲ, respectively. Radiological imaging test did not rule out the possibility of a malignant lesion. Hence, a radical left hepatectomy was performed. Histopathological examination of the resected specimen indicated that it was a non-malignant cystic biliary hamartoma. Cystic biliary hamartoma or the von Meyenburg complex is a relatively rare disease. Although this disease is categorized as benign, differential diagnosis between benign and malignant forms is difficult, and this is an important clinical issue.
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December 2019

[A Case of Resected Metachronous Pancreatic Metastasis from Rectal Carcinoma].

Gan To Kagaku Ryoho 2019 Dec;46(13):2306-2308

Dept. of Surgery, Japan Community Health care Organization(JCHO)Osaka Hospital.

A 69-year-old man underwent a Miles operation with D3 lymph node dissection for rectal cancer. The pathological diagnosis was adenocarcinoma(Rb, A, ly2, v3, N2M0P0H0, Stage Ⅲb). Adjuvant chemotherapy was added for 6 months after the rectal resection. Metastasis in the left lung was detected 1 year and 10 months after rectal resection for which large segmental resection was performed. Without the onset of any new lesions, the patient underwent subsequent follow-up examinations. Abdominal CT performed for increased tumor marker levels observed at 6 years and 8 months after rectal resection revealed a mass suggestive of pancreatic ductal adenocarcinoma for which distal pancreatectomy was performed. The pathological diagnosis was metastasis to the pancreas from the rectal cancer as the tumor cells were immunohistochemically negative for cytokeratin 7 and positive for cytokeratin 20. There has been no indication of recurrence for 13 months after the pancreatic surgery. Resectable pancreatic metastasis from colorectal cancer is rarely reported. However, pancreatic resection may result in long-term survival in some cases. Patients that tolerate pancreatectomy and have no metastasis in the other organs should be considered good candidates for pancreatic resection. We present this case with a review of the literature.
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December 2019

Non-carbon loss long-term continuous lactic acid production from mixed sugars using thermophilic Enterococcus faecium QU 50.

Biotechnol Bioeng 2020 06 4;117(6):1673-1683. Epub 2020 Mar 4.

Laboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Motooka, Nishi-ku, Fukuoka, Japan.

In this study, a non-sterile (open) continuous fermentation (OCF) process with no-carbon loss was developed to improve lactic acid (LA) productivity and operational stability from the co-utilization of lignocellulose-derived sugars by thermophilic Enterococcus faecium QU 50. The effects of different sugar mixtures on LA production were firstly investigated in conventional OCF at 50°C, pH 6.5 and a dilution rate of 0.20 hr . The xylose consumption ratio was greatly lower than that of glucose in fermentations with glucose/xylose mixtures, indicating apparent carbon catabolite repression (CCR). However, CCR could be efficiently eliminated by feeding solutions containing the cellobiose/xylose mixture. In OCF at a dilution rate ca. 0.10 hr , strain QU 50 produced 42.6 g L of l-LA with a yield of 0.912 g g -consumed sugars, LA yield of 0.655 g g based on mixed sugar-loaded, and a productivity of 4.31 g L  hr from simulated energy cane hydrolyzate. In OCF with high cell density by cell recycling, simultaneous and complete co-utilization of sugars was achieved with stable LA production at 60.1 ± 3.25 g L with LA yield of 0.944 g g -consumed sugar and LA productivity of 6.49 ± 0.357 g L  hr . Besides this, a dramatic increase in LA yield of 0.927 g g based on mixed sugar-loaded with prolonged operational stability for at least 500 hr (>20 days) was established. This robust system demonstrates an initial green step with a no-carbon loss under energy-saving toward the feasibility of sustainable LA production from lignocellulosic sugars.
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http://dx.doi.org/10.1002/bit.27313DOI Listing
June 2020

Antegrade Balloon Aortic Valvuloplasty for the Highly Frail Patient of Severe Aortic Stenosis Complicated with Transthyretin-type Cardiac Amyloidosis.

Intern Med 2020 Apr 26;59(8):1053-1057. Epub 2019 Dec 26.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Science, Japan.

Transcatheter aortic valve implantation (TAVI) is widely accepted as the treatment for patient with severe aortic stenosis (AS) whose prognosis may be over one year; however, there is no consensus concerning extremely high-risk patients whose prognosis may not exceed one year. We herein report a highly frail patient with severe AS complicated with transthyretin-type cardiac amyloidosis who had a very poor prognosis. Given his condition, we treated him by percutaneous antegrade balloon aortic valvuloplasty (A-BAV) instead of TAVI. A-BAV may be a beneficial option for treating extremely high-risk severe AS patients, including those with cardiac amyloidosis.
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http://dx.doi.org/10.2169/internalmedicine.3870-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205528PMC
April 2020

Inhibition of the IL-18 Receptor Signaling Pathway Ameliorates Disease in a Murine Model of Rheumatoid Arthritis.

Cells 2019 Dec 18;9(1). Epub 2019 Dec 18.

Department of Hematology and Rheumatology, Kindai University Faculty of Medicine ; Osaka-sayama, Osaka 589-8511, Japan.

Interleukin (IL)-18 expression in synovial tissue correlates with the severity of joint inflammation and the levels of pro-inflammatory cytokines. However, the role of the IL-18/IL-18 receptor-alpha (Rα) signaling pathway in autoimmune arthritis is unknown. Wild-type (WT) and IL-18Rα knockout (KO) mice were immunized with bovine type II collagen before the onset of arthritis induced by lipopolysaccharide injection. Disease activity was evaluated by semiquantitative scoring and histologic assessment. Serum inflammatory cytokine and anticollagen antibody levels were quantified by an enzyme-linked immunosorbent assay. Joint cytokine and matrix metalloproteinases-3 levels were determined by a quantitative polymerase chain reaction. Splenic suppressors of cytokine signaling (SOCS) were determined by Western blot analysis as indices of systemic immunoresponse. IL-18Rα KO mice showed lower arthritis and histological scores in bone erosion and synovitis due to reductions in the infiltration of CD4+ T cells and F4/80+ cells and decreased serum IL-6, -18, TNF, and IFN-γ levels. The mRNA expression and protein levels of SOCS3 were significantly increased in the IL-18Rα KO mice. By an up-regulation of SOCS, pro-inflammatory cytokines were decreased through the IL-18/IL-18Rα signaling pathway. These results suggest that inhibitors of the IL-18/IL-18Rα signaling pathway could become new therapeutic agents for rheumatoid arthritis.
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http://dx.doi.org/10.3390/cells9010011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017073PMC
December 2019

Acquired cerebral amyloid angiopathy: An emerging concept.

Prog Mol Biol Transl Sci 2019 18;168:85-95. Epub 2019 Jun 18.

Department of Neurology & Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Cerebral amyloid angiopathy (CAA) is commonly found in older people and in patients with Alzheimer's disease (AD) accompanying cerebrovascular disorders and dementia. Early-onset CAA cases generally have been found only in rare genetic forms of CAA. Interestingly, however, CAA-related hemorrhages have been recently reported in younger people who had histories of neurosurgery with or without evidence of cadaveric dura mater grafts in childhood. It has been established in experimental settings that amyloid β-protein (Aβ) pathology can be transmitted inter-individually with Aβ seeds. Incidental Aβ pathology, predominantly Aβ-CAA, has been recognized in recipients of cadaveric dura mater grafts or cadaveric human growth hormone. These findings suggest that transmission of Aβ seeds through dura mater grafts and other contaminated materials could lead to development of CAA. In addition, neurosurgery or brain injury may contribute to cerebrovascular Aβ deposition through the disturbance of vascular Aβ drainage pathways. Thus, a novel concept, "acquired CAA," has emerged.
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http://dx.doi.org/10.1016/bs.pmbts.2019.05.012DOI Listing
July 2020

Diagnostic Criteria for Dementia with Lewy Bodies: Updates and Future Directions.

J Mov Disord 2020 Jan 8;13(1):1-10. Epub 2019 Nov 8.

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

The aim of this article is to describe the 2017 revised consensus criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) with future directions for the diagnostic criteria. The criteria for the clinical diagnosis of probable and possible DLB were first published as the first consensus report in 1996 and were revised in the third consensus report in 2005. After discussion at the International DLB Conference in Fort Lauderdale, Florida, USA, in 2015, the International DLB Consortium published the fourth consensus report including the revised consensus criteria in 2017. The 2017 revised criteria clearly distinguish between clinical features and diagnostic biomarkers. Significant new information about previously reported aspects of DLB has been incorporated, with increased diagnostic weighting given to rapid eye movement (REM) sleep behavior disorder (RBD) and iodine-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. Future directions include the development of the criteria for early diagnosis (prodromal DLB) and the establishment of new biomarkers that directly indicate Lewy-related pathology, including α-synuclein imaging, biopsies of peripheral tissues (skin, etc.) for the demonstration of α-synuclein deposition, and biochemical markers (cerebrospinal fluid/blood), as well as the pathological evaluation of the sensitivity and specificity of the 2017 revised diagnostic criteria. In conclusion, the revised consensus criteria for the clinical diagnosis of DLB were reported with the incorporation of new information about DLB in 2017. Future directions include the development of the criteria for early diagnosis and the establishment of biomarkers directly indicative of Lewy-related pathology.
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http://dx.doi.org/10.14802/jmd.19052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987529PMC
January 2020