Publications by authors named "Hiroyuki Okada"

679 Publications

Efficacy of double-balloon enteroscopy-assisted endoscopic balloon dilatation combined with stent deployment for hepaticojejunostomy anastomotic stricture.

Dig Endosc 2021 Jul 29. Epub 2021 Jul 29.

Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan.

Background: Hepaticojejunostomy anastomotic stricture (HJAS) is a significant complication of biliary reconstruction surgery. Endoscopic management of HJAS using double-balloon enteroscopy has expanded; however, retrospective reports in this setting are limited. This study aimed to evaluate the efficacy of endoscopic balloon dilatation combined with stent deployment for HJAS.

Methods: This was a single-arm prospective clinical trial involving 40 patients with treatment-naïve HJAS enrolled between March 2016 and August 2019 at 4 endoscopy units in Japan. For HJAS, plastic stents combined with balloon dilatation were placed for 6 months after initial stenting. The primary outcome was HJ anastomosis patency 12 months after stent removal.

Results: The technical success rate was 97.5% (39/40). The failed case required percutaneous transhepatic biliary drainage using the rendezvous technique. All cases achieved successful endoscopic treatment. During the treatment period, 4 of 40 patients (10%) ended the study protocol due to unrelated causes and were excluded from the primary analysis. Among the 36 patients, clinical success was achieved in 34 (94.4%) patients. The remaining 2 patients achieved HJAS resolution after an additional 3 months. All 36 patients achieved HJAS resolution. AEs were observed in 2 patients (5.0%) who developed moderate cholangitis. During a median follow-up of 21.3 months, HJAS recurrence was observed in 8.3% (3/36) with a median time to recurrence of 4.3 months and HJ anastomosis patency at 12 months was 94.4%.

Conclusions: Endoscopic balloon dilatation combined with plastic stent deployment for six months was safe and effective strategy for HJAS. (Clinical Trial Registry no. UMIN000020613).
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http://dx.doi.org/10.1111/den.14097DOI Listing
July 2021

A prospective multicenter study of the magnifying endoscopic evaluation of the invasion depth of superficial esophageal cancers.

Surg Endosc 2021 Jul 28. Epub 2021 Jul 28.

Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata, Okayama, 700-8558, Japan.

Background: Treatment strategies for superficial esophageal squamous cell carcinoma (SESCC) are determined mainly on the basis of the invasion depth. The Japan Esophageal Society (JES) developed a simplified magnifying endoscopic classification for estimating the invasion depth of SESCC. We aimed to evaluate its accuracy.

Methods: We prospectively applied the JES classification for estimating the invasion depth of SESCC to 204 consecutive lesions from 6 hospitals in Japan between April 2016 and October 2018. We analyzed the accuracy of the endoscopic diagnosis by adding the following two categories to the JES classification: ≥ 7 mm lesion in B2 vessels (defined as B2 ≥ 7 mm) and B2 vessels with inflammation (defined as B2i).

Results: After applying the exclusion criteria, 201 lesions remained in the analysis. The diagnostic value of type B1, B2, B3 vessels were as follows: sensitivity, 93.9%, 68.0%, 25.0%; specificity, 81.1%, 89.2%, 99.4%; positive predictive value (PPV), 95.6%, 47.2%, 75.0%; negative predictive value (NPV), 75.0%, 95.1%, 95.4%; and accuracy, 91.5%, 86.5%, 95.0%, respectively. A retrospective analysis showed that the diagnostic accuracy was higher in type B2 vessels (86.5% to 92.0%). An avascular area (AVA) was found in 55 (27%) of the 201 lesions, which tended to be associated with a deeper pathological diagnosis of each Type B vessel. In an additional analysis, B2 ≥ 7 mm and B2i improved the diagnostic accuracy of type B2 vessels from 86.5% to 92.0%.

Conclusions: The JES classification is useful for estimating the invasion depth of SESCC. The diagnostic accuracy for type B2 vessels was low, which may be improved by using B2 ≥ 7 mm and B2i.
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http://dx.doi.org/10.1007/s00464-021-08666-wDOI Listing
July 2021

Isolation of lymphocytes from the human gastric mucosa.

World J Methodol 2021 Jul 20;11(4):199-207. Epub 2021 Jul 20.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Flow cytometry is widely used for lymphocyte immunophenotyping in clinical settings. However, few studies have applied it for analyzing lymphocytes of the gastric mucosa. This review offers an overview of methodologies for isolating lymphocytes from the human stomach. Previously reported articles were reviewed, focusing on procedures for isolating human gastric mucosal lymphocytes. -associated peptic diseases and gastric cancer are two major subjects of research in this field. Enzymatic dissociation, mechanical dissociation, or a combination of the two have been used to isolate lymphocytes from the stomach. Intra-epithelial and lamina propria lymphocytes were separately isolated in several studies. We also summarize the history and present trends in analyzing lymphocytes in patients with gastric disease.
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http://dx.doi.org/10.5662/wjm.v11.i4.199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299908PMC
July 2021

Dietary intake of vegetables, fruit, and antioxidants and risk of ulcerative colitis: A case-control study in Japan.

Nutrition 2021 Jun 2;91-92:111378. Epub 2021 Jun 2.

Department of Otolaryngology, Head and Neck Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.

Objectives: Oxidative stress is considered one of the etiologic factors involved in ulcerative colitis (UC), yet there is limited epidemiologic information regarding the relationship between antioxidant intake and the risk of UC. The aim of the present case-control study in Japan was to examine the association between intake of green and yellow vegetables, other vegetables, fruit, vitamin C, vitamin E, retinol, alpha-carotene, beta-carotene, and cryptoxanthin and UC risk.

Methods: A total of 384 cases within 4 y of diagnosis with UC and 665 controls were included in the study. Data on dietary intake and confounders were obtained using a self-reported questionnaire. Information on dietary factors was collected using a 169-item semiquantitative food-frequency questionnaire. Adjustment was made for sex, age, pack-y of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index.

Results: Higher intake levels of other vegetables, vitamin C, and retinol were independently associated with a reduced risk of UC. The adjusted odds ratio between extreme quartiles was 0.51 (95% confidence interval [CI], 0.34-0.76; P for trend ≤ 0.001) for other vegetables, 0.45 (95% CI, 0.30-0.69, P for trend ≤ 0.001) for vitamin C, and 0.64 (95% CI, 0.43-0.95, P for trend = 0.04) for retinol. There were no associations between intake of green and yellow vegetables, fruit, vitamin E, alpha-carotene, beta-carotene, or cryptoxanthin and UC risk (P for trend = 0.29, 0.56, 0.89, 0.20, 0.69, and 0.22, respectively).

Conclusions: Intake of other vegetables, vitamin C, and retinol was inversely associated with UC risk.
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http://dx.doi.org/10.1016/j.nut.2021.111378DOI Listing
June 2021

Study protocol for endoscopic ultrasonography-guided ethanol injection therapy for patients with pancreatic neuroendocrine neoplasm: a multicentre prospective study.

BMJ Open 2021 Jul 12;11(7):e046505. Epub 2021 Jul 12.

Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan.

Introduction: The management of small pancreatic neuroendocrine neoplasms (PNENs) remains controversial. The standard treatment for PNENs is surgical resection; however, invasiveness of surgical procedure remains higher and the incidence of postoperative adverse events is still high. Recently, the efficacy and safety of endoscopic ultrasonography (EUS)-guided ethanol injection for small PNENs has been preliminarily demonstrated. Thus, a multicentre prospective study is being conducted to evaluate the efficacy and safety of EUS-guided ethanol injection therapy for small PNENs.

Methods And Analysis: The major eligibility criteria are the presence of pathologically diagnosed grade (G) 1 tumour, a tumour size of ≤15 mm and non-functional PNEN or insulinoma. For treatment, we will use a 25-gauge needle and pure ethanol. Contrast-enhanced CT (CE-CT) will be performed on postoperative day 3-5, and if enhanced areas of the tumour are still apparent, an additional session is scheduled during the same hospitalisation period. We set the total amount of ethanol per session to 2 mL. To evaluate the efficacy and safety, CE-CT will be performed at 1 and 6 months after treatment. The primary endpoint is the percentage of subjects who achieved all of the following evaluated points. Efficacy will be evaluated based on the achievement of complete ablation (defined as no enhanced area within the tumour on CE-CT) at 1 and 6 months. Safety will be evaluated based on the avoidance of severe adverse events within 1 month after treatment, continuing severe pancreatic fistula at 1 month after treatment and the incidence and/or exacerbation of diabetes mellitus at 6 months after treatment.

Ethics And Dissemination: This protocol has been approved by Okayama University Certified Review Board (approval number. CRB19-007). The results will be submitted to peer-reviewed journals and will be presented at international conferences.

Trial Registration Number: jRCTs061200016.
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http://dx.doi.org/10.1136/bmjopen-2020-046505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276291PMC
July 2021

Randomized trial comparing the 25G and 22G Franseen needles in endoscopic ultrasound-guided tissue acquisition from solid pancreatic masses for adequate histological assessment.

Dig Endosc 2021 Jul 10. Epub 2021 Jul 10.

Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan.

Background: The effects of the Franseen needle size in endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) of solid pancreatic masses remain unclear. This study aimed to compare 25G and 22G Franseen needles in terms of adequate tissue acquisition from solid pancreatic masses.

Methods: In this single-center, crossover, randomized noninferiority trial, eligible patients underwent EUS-FNB with both 25G and 22G Franseen needles in a randomized order between November 2018 and August 2020. Tissue specimens from each pass were separately evaluated based on the cellularity scoring system. The primary outcome was the proportion of acquired specimens allowing adequate histological assessment (cellularity score ≥3). A -15% noninferiority margin was assumed.

Results: Data from 88 patients were analyzed, which showed malignant and benign lesions in 84 (95.5%) and four (4.5%) patients, respectively. Of the 88 specimens, 62 (70.5%) and 69 (78.4%) acquired using 25G and 22G needles, respectively, allowed adequate histological assessment. The adjusted proportion difference was -6.6% (95% confidence interval -8.8% to -4.5%), indicating noninferiority of the 25G Franseen needle (P < 0.001). The diagnostic accuracies of the 25G and 22G needles were 86.4% and 89.8%, respectively, with no significant difference (P = 0.180). Adverse events occurred in one patient.

Conclusions: The 25G Franseen needle showed a noninferior adequate tissue acquisition and similar diagnostic performance compared to that of the 22G Franseen needle. However, a 15% noninferiority margin was high for clinical use; thus, further consideration is needed (Clinical Trial Registry no. UMIN000034596).
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http://dx.doi.org/10.1111/den.14079DOI Listing
July 2021

Encouraging participation in colorectal cancer screening for people with schizophrenia: A randomized controlled trial.

Acta Psychiatr Scand 2021 Jul 9. Epub 2021 Jul 9.

Department of Psychiatry, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan.

Objective: We examined the efficacy of a case management approach to improve participation in colorectal cancer screening among people with schizophrenia.

Methods: This was a randomized, parallel group trial. We recruited outpatients with schizophrenia aged 40 years or over from two psychiatric hospitals in Japan. Participants were randomly assigned (1:1) to treatment as usual or case management intervention plus treatment as usual using a web-based system. Attending clinicians and participants were unmasked to the allocation. Case management included education and patient navigation for colorectal cancer screening using a fecal occult blood test. Treatment as usual included direct mail government recommendations. The primary endpoint was participation in colorectal cancer screening assessed using municipal records. We also assessed the secondary endpoint of participation in other cancer screenings (lung, gastric, breast, and cervical).

Results: Between June 3 and September 9, 2019, 172 eligible participants were randomly assigned to the case management plus treatment as usual group (n=86) or treatment as usual group (n=86). One participant was ineligible and another withdrew consent; both were excluded from analysis. A significantly higher proportion of participants received colorectal cancer screening in the case management plus treatment as usual group than in the treatment as usual group (40 [47.1%] of 85 participants vs. 10 [11.8%] of 85 participants, P<0.0001). The proportion of lung cancer screening also increased. No serious adverse events associated with the study intervention occurred.

Conclusion: The case management intervention to encourage participation in colorectal cancer screening was effective for patients with schizophrenia.
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http://dx.doi.org/10.1111/acps.13348DOI Listing
July 2021

Nonrecurrence Rate of Underwater EMR for ≤20-mm Nonampullary Duodenal Adenomas: A Multicenter Prospective Study (D-UEMR Study).

Clin Gastroenterol Hepatol 2021 Jul 2. Epub 2021 Jul 2.

Department of Gastroenterology, Okayama University Hospital, Okayama, Japan.

Background And Aims: Endoscopic resection of nonampullary duodenal adenoma is often challenging, and its technique has not yet been standardized. To overcome the practical difficulty of conventional endoscopic mucosal resection, underwater endoscopic mucosal resection (UEMR) was recently developed; therefore, we investigated the effectiveness and safety of UEMR for nonampullary duodenal adenoma.

Methods: A multicenter, prospective cohort study was conducted at 21 institutions in Japan. We enrolled patients with no more than 2 nonampullary duodenal adenomas ≤20 mm in size, who were scheduled to undergo UEMR. After UEMR, follow-up endoscopies were scheduled at 2 and 12 months after the procedure, and biopsy specimens were taken from the post-UEMR scars. The primary endpoint was the proportion of patients with histologically proven nonrecurrence at follow-up endoscopy and biopsy.

Results: A total of 155 patients with 166 lesions underwent UEMR. One patient with a non-neoplastic lesion in the resected specimen and 10 patients with 10 lesions who were lost to follow-up were excluded. Finally, 144 patients with 155 lesions who received all follow-up endoscopies were analyzed for the primary endpoint. The proportion of patients with proven nonrecurrence was 97.2% (n = 140 of 144; 95% confidence interval, 92.8%-99.1%) which exceeded the predefined threshold value (92%). Two cases of delayed bleeding (1.2%) occurred and they were successfully managed by clips. All recurrences were successfully treated by additional endoscopic treatment.

Conclusions: This multicenter, prospective cohort study demonstrated effectiveness and safety of UEMR for nonampullary duodenal adenomas ≤20 mm in size. (University Hospital Medical Network Clinical Trials Registry, Number: UMIN000030414).
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http://dx.doi.org/10.1016/j.cgh.2021.06.043DOI Listing
July 2021

Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients.

Sci Rep 2021 Jun 10;11(1):12298. Epub 2021 Jun 10.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.

Circulating microRNAs (miRNAs) in serum extracellular vesicles (EVs) are a promising biomarker in cancer. We aimed to elucidate the serum EVs miRNA biomarkers to identify patients with gallbladder cancer (GBC) and to clarify their potential roles. One hundred nineteen serum EVs from GBC and non-GBC individuals were isolated by pure-EVs-yieldable size-exclusion chromatography, and then were analyzed using a comprehensive miRNAs array and RT-qPCR-based validation. The functional roles of the identified miRNAs were also investigated using GBC cell lines. Serum EVs miR-1246 and miR-451a were significantly upregulated and downregulated, respectively in GBC patients (P = 0.005 and P = 0.001), in line with their expression levels in cancer tissue according to an in silico analysis. The combination of CEA and CA19-9 with miR-1246 showed the highest diagnostic power (AUC, 0.816; Sensitivity, 72.0%; Specificity, 90.8%), and miR-1246 was an independent prognostic marker of GBC (Hazard ratio, 3.05; P = 0.017) according to a Cox proportional hazards model. In vitro, miR-1246 promoted cell proliferation and invasion, while miR-451a inhibited cell proliferation and induced apoptosis with the targeting of MIF, PSMB8 and CDKN2D. Taken together, miR-1246 in serum EVs has potential application as a diagnostic and prognostic marker and miR-451a may be a novel therapeutic target in GBC.
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http://dx.doi.org/10.1038/s41598-021-91804-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192895PMC
June 2021

Management of Cirrhotic Ascites under the Add-on Administration of Tolvaptan.

Int J Mol Sci 2021 May 25;22(11). Epub 2021 May 25.

Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.

Tolvaptan is a recently available diuretic that blocks arginine vasopressin receptor 2 in the renal collecting duct. Its diuretic mechanism involves selective water reabsorption by affecting the water reabsorption receptor aquaporin 2. Given that liver cirrhosis patients exhibit hyponatremia due to their pseudo-aldosteronism and usage of natriuretic agents, a sodium maintaining agent, such as tolvaptan, is physiologically preferable. However, large scale studies indicating the patients for whom this would be effective and describing management under its use have been insufficient. The appropriate management of cirrhosis patients treated with tolvaptan should be investigated. In the present review, we collected articles investigating the effectiveness of tolvaptan and factors associated with survival and summarized their management reports. Earlier administration of tolvaptan before increasing the doses of natriuretic agents is recommended because this may preserve effective arterial blood volume.
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http://dx.doi.org/10.3390/ijms22115582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197450PMC
May 2021

Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease.

Sci Rep 2021 May 27;11(1):11086. Epub 2021 May 27.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.
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http://dx.doi.org/10.1038/s41598-021-90441-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160157PMC
May 2021

Antibacterial Effects of Disulfiram in .

Infect Drug Resist 2021 12;14:1757-1764. Epub 2021 May 12.

Graduate School of Health Science Okayama University, Okayama, 700-8558, Japan.

Background: infection poses a risk of the occurrence of gastrointestinal diseases, such as gastric cancer. Its incidence rate is significantly reduced by eradication, and thereby, eradication therapy is generally performed. Disulfiram is an oral prescription drug mainly used for the treatment of alcohol dependence. In recent years, reports have been made on its anticancer and antibacterial effects, and thus, it has recently become an interesting subject. This study aimed to examine the antibacterial activity of disulfiram, investigate the presence or absence of its antibacterial activity on , and determine whether it could be a new bactericidal drug against drug-resistant .

Materials And Methods: Drug-sensitive strains of and amoxicillin-resistant, clarithromycin-resistant, and metronidazole-resistant strains were used, and a growth inhibition test of using disulfiram was performed. Furthermore, the expression of urease, vacuolating cytotoxin A (VacA), and CagA, the virulence proteins of , was quantitatively analyzed using the Western blotting method. In addition, for used in this study, the 16SrDNA sequence, a ribosomal gene involved in protein production, was analyzed to examine the presence or absence of gene mutation.

Results: Disulfiram suppressed the growth of 7 out of 12 strains at 1 µg/mL, and no correlation was observed between their susceptibility/resistance to current eradication antimicrobial drugs and disulfiram resistance. Disulfiram reduced the expression levels of urease, VacA, and CagA proteins. , which showed resistance to disulfiram, tended to have fewer gene deletions/insertions in the 16S rDNA sequence; however, no specific mutation was detected.

Conclusion: Disulfiram has a bactericidal effect on at low concentrations, suggesting that it can be used as a supplement for current eradication drugs.
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http://dx.doi.org/10.2147/IDR.S299177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126873PMC
May 2021

Linked Color Imaging (LCI) Emphasizes the Color Changes in the Gastric Mucosa After Helicobacter pylori Eradication.

Dig Dis Sci 2021 May 12. Epub 2021 May 12.

Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-Ku, Okayama, 700-8558, Japan.

Background: Diffuse redness is a characteristic endoscopic finding that indicates current infection of Helicobacter pylori, which is reduced after successful eradication. Linked color imaging (LCI) has been reported to improve the visibility of diffuse redness compared to white light imaging (WLI); however, quantitative evaluation has not been reported.

Aims: This study aimed to objectively evaluate the color change of the gastric mucosa after H. pylori eradication.

Methods: Images of the greater curvature of the antrum and corpus were captured, and the sites were biopsied during esophagogastroduodenoscopy (EGD) before and 1 year after eradication. The region of interest (ROI) was set around the biopsied area on the images. The color difference (ΔE) before and after eradication was calculated using the CIE L*a*b* color space. The association between the histological evaluation and the color value of the corresponding ROI was determined.

Results: At the antrum, there was no significant color change with either mode. At the corpus, the a* value, which reflected redness, decreased significantly after eradication with both modes (WLI: 41.2 to 36.0, LCI: 37.5 to 25.5); the b* value, reflecting yellowish, decreased with WLI, but increased significantly with LCI (WLI: 44.6 to 41.6, LCI: 23.9 to 29.2). The ΔE was significantly larger with LCI than with WLI (16.5 vs. 8.6). The a* values at the corpus were generally associated with histological neutrophil infiltration.

Conclusions: Quantitative evaluation revealed that LCI emphasizes the change in color of the gastric mucosa due to the reduction in diffuse redness.
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http://dx.doi.org/10.1007/s10620-021-07030-1DOI Listing
May 2021

Risk Factors for the Development of High-risk Stigmata in Branch-duct Intraductal Papillary Mucinous Neoplasms.

Intern Med 2021 May 7. Epub 2021 May 7.

Department of Gastroenterology and Hepatology, Okayama University Hospital, Japan.

Objective Strict follow-up is recommended for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) to avoid missing the development of high-risk stigmata (HRS) at a premalignant stage. This study explored the risk factors associated with the development of HRS during follow-up. Methods We performed a retrospective analysis of 283 patients with BD-IPMN, treated at Okayama University Hospital in Japan between January 2009 and December 2016. Only patients with imaging studies indicative of classical features of BD-IPMN without HRS and followed for over one year were included in the study. We performed radiological follow-up every six months and collected patients' demographic data, cyst characteristics, and clinical outcomes and used univariate logistic regression models to determine the odds of developing HRS. Results Ten patients (3.5%) developed HRS after a median surveillance period of 55.8 months. The main pancreatic duct (MPD) size (5-9 mm) and cyst growth rate (>2.5 mm/year) were both suggested to be possible risk factors for the development of HRS (odds ratio, 14.2; 95% confidence interval [CI], 3.1-65.2, p=0.0006, and odds ratio, 6.1; 95% CI 1.5-25.5, p=0.014). Regarding the number of worrisome features (WFs), the rate of HRS development was 2.0% (4/199) in cases with no WF, 1.6% (1/62) in cases with single WF and 22.7% (5/22) in cases with multiple WFs, respectively. The rate of HRS development was significantly higher in cases with multiple WFs than in the other cases (p<0.0001). Conclusion MPD dilation, rapid cyst growth, and multiple WFs were significant risk factors for the development of HRS. In the presence of such features, it is necessary to closely follow the development of HRS and avoid missing the best opportunity to perform surgical intervention.
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http://dx.doi.org/10.2169/internalmedicine.7168-21DOI Listing
May 2021

The contingency symmetry bias (affirming the consequent fallacy) as a prerequisite for word learning: A comparative study of pre-linguistic human infants and chimpanzees.

Cognition 2021 Sep 3;214:104755. Epub 2021 May 3.

Language and Intelligence Section, Primate Research Institute, Kyoto University, 41-2, Kanrin, Inuyama, Aichi 484-8506, Japan.

Humans are known to possess an "affirming the consequent fallacy," which assumes that a learned contingency holds true even when the order is reversed. In contrast, non-human animals do not fall for this fallacy, as they do not have the contingency symmetry bias. Importantly, language is founded on the symmetrical relationship between symbols and referents, and the contingency symmetry bias plays a key role in word learning. A critical problem for the ontogenesis of language is whether the contingency symmetry bias has been acquired through the experience of word learning or if it is present before infants begin word learning. Using a habituation switch paradigm, 8-month-old human infants and adult chimpanzees were familiarized with two object-then-movement sequences, whereby Object A (or B) was always paired with Movement A (or B). At test, the order of the contingency was reversed. The infants showed surprise when observing the violation of the object-movement pairings in the reversed sequence (Experiment 1). In contrast, despite the chimpanzees being able to detect the violation of the pairings in the original direction (Experiment 2a), they did not discriminate the learned and novel pairings when the order of the contingency was reversed (Experiment 2b). The results suggest that the contingency symmetry bias is a uniquely human cognitive bias, one which plays a critical role for language acquisition ontogenetically. This contingency symmetry bias likely gives humans a great advantage, by enabling them to rapidly expand their knowledge without direct training and making them strikingly different from other animal species. (250 words).
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http://dx.doi.org/10.1016/j.cognition.2021.104755DOI Listing
September 2021

Propensity score-matched analysis of endoscopic resection for recurrent colorectal neoplasms: A pilot study.

J Gastroenterol Hepatol 2021 Apr 11. Epub 2021 Apr 11.

Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.

Background And Aim: Local residual/recurrent colorectal lesions after endoscopic resection (ER) are difficult to treat with conventional ER. Underwater endoscopic mucosal resection (UEMR) and endoscopic submucosal dissection (ESD) are reportedly effective. We investigated the appropriate indications of ESD and UEMR for recurrent colorectal lesions.

Methods: This single-center, retrospective, observational study was conducted at a tertiary cancer institute. Patients who underwent UEMR or ESD for residual/recurrent colorectal lesions after ER from October 2013 to February 2019 were enrolled. Propensity score matching was performed between the UEMR and ESD groups to compare the clinical characteristics, treatment, and outcomes.

Results: In total, 30 UEMRs and 21 ESDs were performed. Median (range) diameter of the lesions was 8 mm (2-22 mm) in UEMR and 15 mm (2-58 mm) in ESD. Median procedure time in UEMR was significantly shorter than that of ESD (4 min [2-15 min] vs 70 min [17-193 min], P < 0.001). En bloc and complete resection rates of ESD were significantly higher than that of UEMR (73% vs 100%, 41% vs 81%, respectively). No adverse events occurred with UEMR, but there were two cases (10%) of delayed perforation with ESD. Neither group reported recurrence after treatment. Propensity score-matched cases showed significantly shorter procedure time and hospitalization period in UEMR than in ESD.

Conclusions: The outcomes of UEMR and ESD were comparable. UEMR could be a useful salvage therapy for small local residual/recurrent colorectal lesions after ER with shorter procedure time and hospitalization period.
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http://dx.doi.org/10.1111/jgh.15519DOI Listing
April 2021

Gastric Adenoma: A High Incidence Rate of Developing Carcinoma and Risk of Metachronous Gastric Cancer according to Long-Term Follow-Up.

Digestion 2021 Apr 9:1-9. Epub 2021 Apr 9.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

Introduction: Gastric adenomas are histologically defined as benign epithelial tumors. While some of them remain adenomas for a long time, others progress to carcinomas. However, long-term outcomes of such cases are not entirely clear. Here, we explored the risk factors and incidence of developing carcinoma from gastric adenoma as well as metachronous gastric cancer.

Methods: This study was conducted at a facility that adopted a follow-up strategy for gastric adenoma. Lesions histologically diagnosed as gastric intestinal-type adenomas between January 2004 and December 2016 were analyzed. Clinicopathological data were collected from patients' medical records, and histological changes from adenoma to carcinoma during endoscopic follow-up and risk factors of cancer development were evaluated.

Results: This study involved 409 lesions from 376 patients. The analysis of the development of gastric cancer from adenoma and metachronous gastric cancer was ultimately performed for 282 lesions from 258 patients and 269 lesions from 246 patients, respectively, due to different follow-up periods. The 5-year rate of carcinoma development was 34.0%. Risk factors for carcinoma development upon multivariate analysis were lesion size ≥15 mm and morphological depression. All cases with both factors developed gastric carcinoma, and 50.5% of those with either factor developed carcinoma within 5 years. Gastric adenoma was accompanied by metachronous gastric cancer in 1.5% of the patients annually. The only risk factor for metachronous gastric carcinoma was primary adenoma progressing to carcinoma during the follow-up period.

Discussion/conclusion: Given the high rate of carcinoma development in patients with risk factors, resection of gastric adenoma should be considered during the initial examination. Careful observation and follow-up should also be conducted to detect not only changes in the primary adenoma but also the occurrence of metachronous carcinoma, especially in cases of adenoma progressing to carcinoma.
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http://dx.doi.org/10.1159/000515213DOI Listing
April 2021

Diffuse Esophageal Wall Thickening Due to Lymphoma.

Intern Med 2021 Apr 5. Epub 2021 Apr 5.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.

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http://dx.doi.org/10.2169/internalmedicine.7307-21DOI Listing
April 2021

Deep learning-based attenuation correction for brain PET with various radiotracers.

Ann Nucl Med 2021 Jun 3;35(6):691-701. Epub 2021 Apr 3.

Department of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.

Objectives: Attenuation correction (AC) is crucial for ensuring the quantitative accuracy of positron emission tomography (PET) imaging. However, obtaining accurate μ-maps from brain-dedicated PET scanners without AC acquisition mechanism is challenging. Therefore, to overcome these problems, we developed a deep learning-based PET AC (deep AC) framework to synthesize transmission computed tomography (TCT) images from non-AC (NAC) PET images using a convolutional neural network (CNN) with a huge dataset of various radiotracers for brain PET imaging.

Methods: The proposed framework is comprised of three steps: (1) NAC PET image generation, (2) synthetic TCT generation using CNN, and (3) PET image reconstruction. We trained the CNN by combining the mixed image dataset of six radiotracers to avoid overfitting, including [F]FDG, [F]BCPP-EF, [C]Racropride, [C]PIB, [C]DPA-713, and [C]PBB3. We used 1261 brain NAC PET and TCT images (1091 for training and 70 for testing). We did not include [C]Methionine subjects in the training dataset, but included them in the testing dataset.

Results: The image quality of the synthetic TCT images obtained using the CNN trained on the mixed dataset of six radiotracers was superior to those obtained using the CNN trained on the split dataset generated from each radiotracer. In the [F]FDG study, the mean relative PET biases of the emission-segmented AC (ESAC) and deep AC were 8.46 ± 5.24 and - 5.69 ± 4.97, respectively. The deep AC PET and TCT AC PET images exhibited excellent correlation for all seven radiotracers (R = 0.912-0.982).

Conclusion: These results indicate that our proposed deep AC framework can be leveraged to provide quantitatively superior PET images when using the CNN trained on the mixed dataset of PET tracers than when using the CNN trained on the split dataset which means specific for each tracer.
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http://dx.doi.org/10.1007/s12149-021-01611-wDOI Listing
June 2021

Endoscopic resection is a suitable initial treatment strategy for oxyntic gland adenoma or gastric adenocarcinoma of the fundic gland type.

Sci Rep 2021 Apr 1;11(1):7375. Epub 2021 Apr 1.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8558, Japan.

The aim of this study was to reveal the histological features of oxyntic gland adenomas and gastric adenocarcinoma of the fundic-gland type (GA-FG). We retrospectively examined the histological features of 126 lesions of oxyntic gland adenoma and/or GA-FG in 116 patients. The prevalence of oxyntic gland adenomas and GA-FG was approximately equal. The majority of the lesions were resected by endoscopic mucosal resection using a diathermic snare (EMR, n = 42) or endoscopic submucosal dissection (ESD, n = 72). Histologically, there were no lesions with invasion at the level of the muscularis propria or deeper, and lymphovascular invasion was present in 1.6%. Of the ESD and EMR specimens, there were no lesions that were positive for vertical margins. Among the eight GA-FG patients with deep (≥ 500 μm) submucosal invasion, six were treated with endoscopic resection alone, and no recurrence was documented. No patients died of the disease during the median follow-up period of 14.5 months. In conclusion, all lesions were confined to the mucosa or submucosa and were negative for vertical margins. Lymphovascular invasion was present in only 1.6% of the patients. Thus, we believe that endoscopic resection is a suitable initial treatment method for oxyntic gland adenoma and GA-FG.
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http://dx.doi.org/10.1038/s41598-021-86893-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016920PMC
April 2021

Efficacy and safety of endoscopic submucosal dissection for gastric tube cancer: A multicenter retrospective study.

World J Gastroenterol 2021 Mar;27(11):1043-1054

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Okayama, Japan.

Background: Recent improvements in the prognosis of patients with esophageal cancer have led to the increased occurrence of gastric tube cancer (GTC) in the reconstructed gastric tube. However, there are few reports on the treatment results of endoscopic submucosal dissection (ESD) for GTC.

Aim: To evaluate the efficacy and safety of ESD for GTC after esophagectomy in a multicenter trial.

Methods: We retrospectively investigated 48 GTC lesions in 38 consecutive patients with GTC in the reconstructed gastric tube after esophagectomy who had undergone ESD between January 2005 and December 2019 at 8 institutions participating in the Okayama Gut Study group. The clinical indications of ESD for early gastric cancer were similarly applied for GTC after esophagectomy. ESD specimens were evaluated in 2-mm slices according to the Japanese Classification of Gastric Carcinoma with curability assessments divided into curative and non-curative resection based on the Gastric Cancer Treatment Guidelines. Patient characteristics, treatment results, clinical course, and treatment outcomes were analyzed.

Results: The median age of patients was 71.5 years (range, 57-84years), and there were 34 men and 4 women. The median observation period after ESD was 884 d (range, 8-4040 d). The median procedure time was 81 min (range, 29-334 min), the resection rate was 91.7% (44/48), and the curative resection rate was 79% (38/48). Complications during ESD were seen in 4% (2/48) of case, and those after ESD were seen in 10% (5/48) of case. The survival rate at 5 years was 59.5%. During the observation period after ESD, 10 patients died of other diseases. Although there were differences in the procedure time between institutions, a multivariate analysis showed that tumor size was the only factor associated with prolonged procedure time.

Conclusion: ESD for GTC after esophagectomy was shown to be safe and effective.
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http://dx.doi.org/10.3748/wjg.v27.i11.1043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985736PMC
March 2021

Randomized controlled study to examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before radiofrequency ablation for hepatocellular carcinoma.

Hepatol Res 2021 Jun 29;51(6):694-701. Epub 2021 Mar 29.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Aim: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin is beneficial to patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. This study aimed to examine the effect of HAIC with cisplatin before radiofrequency ablation (RFA) in patients with HCC.

Methods: This was a multicenter, single-blinded, randomized controlled study (UMIN000007267). Early-stage HCC patients were randomly assigned (1:1) to receive HAIC with cisplatin before RFA therapy (HAIC group) or RFA monotherapy (non-HAIC group). The primary end-point was recurrence-free survival. Efficacy analysis and safety analysis followed the intention-to-treat principle.

Results: Between August 2012 and July 2016, 74 patients were recruited. A total of 70 eligible patients were randomly assigned to the HAIC group (n = 35) and non-HAIC group (n = 35). Recurrence-free survival rates at 1 (3) year in the HAIC group and non-HAIC group were 82.9% (54.3%) and 74.3% (34.3%), respectively (hazard ratio [HR], 0.597; 95% confidence interval [CI], 0.320-1.091; p = 0.094]. Subgroup analysis showed that the beneficial effect of HAIC was observed in patients with a single nodule and Child-Pugh score 5. Intrahepatic distant recurrence-free survival rate in the HAIC group was significantly better than that in the non-HAIC group (HR, 0.468; 95% CI, 0.235-0.896; p = 0.022). Adverse events were observed in just two patients in the HAIC group (6%) - grade 2 cholecystitis and grade 2 hyperkalemia.

Conclusions: HAIC with cisplatin before RFA did not significantly decrease recurrence in patients with early-stage HCC. However, it might be effective in preventing intrahepatic distant recurrence.
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http://dx.doi.org/10.1111/hepr.13633DOI Listing
June 2021

Plasma Arginase-1 Level Is Associated with the Mental Status of Outpatients with Chronic Liver Disease.

Diagnostics (Basel) 2021 Feb 16;11(2). Epub 2021 Feb 16.

Department of Environmental Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku City 783-8505, Japan.

While plasma arginase-1 has been suggested as a biomarker of mental status in healthy individuals, it has not been evaluated in patients with chronic liver disease. This cross-sectional study investigated the utility of plasma arginase-1 for screening mental status in patients with chronic liver disease. This study included outpatients with chronic liver disease who underwent regular check-ups at Okayama University Hospital between September 2018 and January 2019. In addition to the standard blood tests, the plasma arginase-1 level was analyzed. The patients' mental status was assessed using the Japanese version of the General Health Questionnaire-28 (GHQ-28). The associations between mental status and various parameters, including plasma arginase-1, were investigated using logistic regression analysis. Among 114 participating patients, 8 were excluded, comprising 6 with insufficient blood samples for plasma arginase-1 measurement and 2 with incomplete questionnaires. Multivariate binomial logistic regression analysis revealed that plasma arginase-1 was significantly and negatively associated with the GHQ-total score, especially somatic symptoms. Therefore, plasma arginase-1 may be a useful biomarker for assessing the mental status of outpatients with chronic liver disease.
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http://dx.doi.org/10.3390/diagnostics11020317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920070PMC
February 2021

Endoscopic ultrasonography findings of pancreatic parenchyma for predicting subtypes of intraductal papillary mucinous neoplasms.

Pancreatology 2021 Apr 17;21(3):622-629. Epub 2021 Feb 17.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.

Background And Aims: The subtypes of intraductal papillary mucinous neoplasms (IPMNs) are closely associated with the clinicopathological behavior and recurrence after surgical resection. However, there are no established non-invasive methods to confirm the subtypes of IPMNs without surgery. The aim of this study is to predict the subtypes of IPMNs using the findings of endoscopic ultrasonography (EUS).

Methods: Sixty-two consecutive patients with IPMNs who underwent EUS before surgery were retrospectively reviewed. The following EUS findings were analyzed and their relationship with the subtypes was evaluated: diameter of the main pancreatic duct, cyst size, number of cysts, height of mural nodule, early chronic pancreatitis (CP) finding, fatty parenchyma and atrophic parenchyma.

Results: The subtypes of IPMNs were as follows: gastric (G)-type 38 (61%), intestinal (I) -type 14 (23%) and pancreatobiliary (PB) -type 10 (16%). Fatty parenchyma was significantly associated with G-type (P < 0.0001). Early CP findings ≥2 and atrophic parenchyma were significantly correlated with I-type (P < 0.0001). PB-type was significantly associated with pancreatic parenchyma without early CP findings or fatty degeneration in comparison to the other subtypes (P < 0.0001). Using the above characteristic EUS findings, the sensitivity, specificity, and accuracy were as follows: 63%, 92% and 74%, respectively, in G-type, 57%, 96% and 87% in I-type, and 90%, 94% and 94% in PB-type.

Conclusions: The evaluation of EUS findings, especially focused on the pancreatic parenchyma, has the potential to predict the subtypes of IPMN.
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http://dx.doi.org/10.1016/j.pan.2021.01.026DOI Listing
April 2021

Laminin-411 and -511 Modulate the Proliferation, Adhesion, and Morphology of Gastric Cancer Cells.

Cell Biochem Biophys 2021 Jun 25;79(2):407-418. Epub 2021 Feb 25.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.

Laminins (Ln), a type of extracellular matrix glycoprotein, are key regulators of cellular behavior. Recent work revealed that in various tumor cell lines, laminin isoforms influence specific responses, such as cell anchorage, survival, proliferation, migration, organization, and specialization. The contribution of laminin isoforms to the function of gastric cancer cells, however, remain unclear. Here, we revealed that in gastric cancer, laminin isoforms Ln411, Ln421, Ln511, and Ln521 promote cellular proliferation; Ln511 and Ln521 increase cell cytoplasmic volume; Ln511 hampers invadopodia formation in some cells, Ln511 enables prompt adhesion of cells to plates, and Ln411 and Ln511 do not alter the gastric cancer stem cell markers CD44 and Lgr5. These results indicate that Ln411 and Ln511 dynamically modulate the proliferation, adhesion, and morphology of gastric cancer cells in different ways that are independent of stem cell properties. In particular, Ln511 showed a high affinity for gastric cancer cells. Our observations broaden the possible options for controlling cancer cell progression and metastasis by modulating laminin-integrin interactions.
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http://dx.doi.org/10.1007/s12013-021-00972-3DOI Listing
June 2021

Squamous Metaplasia of the Stomach Associated with Lymphoma Infiltration.

Intern Med 2021 Jul 22;60(14):2229-2234. Epub 2021 Feb 22.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.

We herein report a patient who presented with follicular lymphoma. Although the stomach was initially intact, mucosal redness and multiple erosions appeared in the gastric body owing to infiltration of the follicular lymphoma cells. Subsequently, a slightly depressed, white area lacking gastric mucosal structure was detected in the lesser curvature of the gastric cardia and body, where lymphoma cell infiltration was also pathologically observed beneath the stratified squamous epithelium. This case indicated that, although infrequent, prolonged mucosal injury owing to lymphoma infiltration can cause squamous metaplasia in the stomach.
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http://dx.doi.org/10.2169/internalmedicine.6271-20DOI Listing
July 2021

Abnormal fucosylation of alpha-fetoprotein in patients with nonalcoholic steatohepatitis.

Hepatol Res 2021 May 19;51(5):548-553. Epub 2021 Mar 19.

Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

Aim: Nonalcoholic steatohepatitis (NASH) is a risk factor for nonvirus-related hepatocellular carcinoma, which is increasing in prevalence. The aim of this study was to clarify the clinical application of fucosylated alpha-fetoprotein (AFP-L3) in the process of nonalcoholic fatty liver (NAFL) disease development.

Methods: Serum samples from 115 diabetes mellitus (DM), 36 NAFL, and 119 NASH patients were analyzed for AFP-L3 expression using raw data of a micro total analysis system. These data were then compared with the clinical characteristics of the patients. A validation study was also undertaken with 55 samples (17 NAFL and 38 NASH).

Results: Trace amounts of AFP-L3 were detected in 3.5%, 16.7%, and 58.0% of patients with DM, NAFL, and NASH, respectively. The odds ratio of AFP-L3 positivity for the diagnosis of NASH in multivariate analysis was 9.81 (95% confidence interval, 3.77-25.5). The rates in patients without fibrosis or with stage 1, stage 2, stage 3, and stage 4 fibrosis were 14.7%, 31.3%, 63.0%, 86.2%, and 100%, respectively. The rates were significantly increased according to the advancement of liver fibrosis (p < 0.001); however, no difference in the positive rate of AFP-L3 was observed between patients with and without fatty livers and between patients with normal and abnormal transaminase. The same relationship was also observed in the validation cohort.

Conclusion: Abnormal fucosylation of AFP occurred in patients with NASH, so it could be useful for the screening of NASH in patients with DM, as well as for the differential diagnosis of NASH and the evaluation of fibrosis.
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http://dx.doi.org/10.1111/hepr.13626DOI Listing
May 2021

Excessive risk of second-cancer incidence and cancer mortality in patients with esophageal cancer.

J Gastroenterol 2021 May 11;56(5):434-441. Epub 2021 Feb 11.

Cancer Control Center, Osaka International Cancer Institute, Osaka, Japan.

Background: Second primary cancers have impact on survival in patients who achieved cure for the first esophageal cancer. We, therefore, assessed the risk of incidence and mortality for second primary cancer by calculating standardized incidence ratio (SIR) and standardized mortality ratio (SMR) in patients with superficial or localized esophageal cancer without lymph node metastases as the first cancer (index cancer).

Methods: Data on cancer development and subsequent causes of deaths were collected from integrated database of the Osaka Cancer Registry and the Vital Statistics of Japan. Records with information on patients with index esophageal cancer diagnosed between 2004 and 2013 were extracted from the database. Then, SIR and SMR for second primary cancers that developed in other organ were calculated with the reference to the general population during the same period. All probability values are two-tailed.

Results: Of 473,784 case records, 3022 cases of patients with index esophageal cancer were identified. Significantly higher SMRs/SIRs for cancers in mouth/pharynx, larynx, pancreas, and leukemia were confirmed with the values of 10.78/16.16, 8.56/6.44, 2.33/2.31, and 3.96/4.42, respectively. Significantly, higher SIRs for stomach, lung, and skin cancers were confirmed with the values of 2.84, 2.36, and 3.38, respectively, while SMRs were not significantly higher in these cancers.

Conclusions: Significantly higher risks for mouth/pharynx, larynx, pancreas, and leukemia as second cancers were clarified. Careful surveillance for these cancers is required for esophageal cancer patients.
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http://dx.doi.org/10.1007/s00535-021-01767-2DOI Listing
May 2021

The Progress of Stem Cell Technology for Skeletal Regeneration.

Int J Mol Sci 2021 Jan 30;22(3). Epub 2021 Jan 30.

Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

Skeletal disorders, such as osteoarthritis and bone fractures, are among the major conditions that can compromise the quality of daily life of elderly individuals. To treat them, regenerative therapies using skeletal cells have been an attractive choice for patients with unmet clinical needs. Currently, there are two major strategies to prepare the cell sources. The first is to use induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs), which can recapitulate the skeletal developmental process and differentiate into various skeletal cells. Skeletal tissues are derived from three distinct origins: the neural crest, paraxial mesoderm, and lateral plate mesoderm. Thus, various protocols have been proposed to recapitulate the sequential process of skeletal development. The second strategy is to extract stem cells from skeletal tissues. In addition to mesenchymal stem/stromal cells (MSCs), multiple cell types have been identified as alternative cell sources. These cells have distinct multipotent properties allowing them to differentiate into skeletal cells and various potential applications for skeletal regeneration. In this review, we summarize state-of-the-art research in stem cell differentiation based on the understanding of embryogenic skeletal development and stem cells existing in skeletal tissues. We then discuss the potential applications of these cell types for regenerative medicine.
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http://dx.doi.org/10.3390/ijms22031404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866793PMC
January 2021

Hemosuccus Pancreaticus Due to the Rupture of a Pseudoaneurysm That Developed in an Intraductal Papillary Mucinous Neoplasm.

Intern Med 2021 Jul 8;60(13):2033-2038. Epub 2021 Feb 8.

Department of Gastroenterology, Okayama University Hospital, Japan.

A 76-year-old woman with branch duct intraductal papillary mucinous neoplasm (IPMN) was admitted with epigastric pain and vomiting. She had received warfarin due to a history of deep vein thrombosis. A blood test showed decreased serum hemoglobin and elevated serum amylase. Contrast-enhanced computed tomography revealed acute pancreatitis and formation of a pseudoaneurysm in the IPMN. We suspected rupture of a pseudoaneurysm and performed trans-catheter angiography. Angiography showed extravasation from the posterior superior pancreaticoduodenal artery, and coil embolization was performed. It is important to be alert for the formation of pseudoaneurysm in patients with cystic neoplasms.
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http://dx.doi.org/10.2169/internalmedicine.6445-20DOI Listing
July 2021
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