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Heparin/Growth Factors‑Immobilized Aligned Electrospun Nanofibers Promote Nerve Regeneration in Polycaprolactone/Gelatin‑Based Nerve Guidance Conduits

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Advanced Fiber Materials 2023年第2期5卷 554-573页

作者： Yasuhiro Ikegami Muhammad Shafiq shinichi aishima Hiroyuki Ijima Department of Chemical Engineering Faculty of EngineeringGraduate SchoolKyushu University744 MotookaNishi‑KuFukuoka 819‑0395Japan Department of Biotechnology Faculty of Science and TechnologyUniversity of Central Punjab(UCP)Lahore 54000Pakistan Department of Pathology and Microbiology Faculty of MedicineSaga UniversityNabeshima 5‑1‑1Saga 849‑8501Japan

Injuries to the nervous system account for the widespread morbidity,mortality,and discomfort worldwide.Artificial nerve guidance conduits(NGCs)offer a promising platform for nerve reconstruction,however,they require extracellular matrix(ECM)-like features to better mimic the in vivo microenvironment.Consequently,this research was aimed to fabricate heparin/growth factors(GFs)-immobilized artificial NGCs.Heparin was covalently immobilized onto aligned electrospun polycapro-lactone/gelatin(PCL/Gel)nanofibers.Thereafter,basic fibroblast growth factor(bFGF)and nerve growth factor(NGF)were preferentially immobilized on heparinized nanofibers;the immobilization efficiency of GFs was found to be 50%with respect to(w.r.t.)their initial loaded amounts.The in vivo implantation of NGCs in a sciatic nerve defect model revealed the successful retention(~10%w.r.t the initial loaded amount)and bioactivity of NGF for up to 5 days.The permeability of bovine serum albumin(BSA)from nanofibrous membranes was further assessed and found to be comparable with the commercialized cel-lulose acetate membranes.The bioactivity of NGCs was assessed in a sciatic nerve defect model in rats for short-term(1 week)and long-term(1-month).The NGCs displayed good structural stability and biocompatibility in vivo.The in vivo evaluation revealed the accumulation of host cells into the transplanted NGCs.Taken together;these heparin/GFs-immobilized artificial NGCs may have broad implications for nerve regeneration and related tissue engineering disciplines.

关键词： Heparin Growth factor-immobilized scaffolds Aligned nanofibers Core/shell nanofibers Nerve tissue engineering Scaffolds Co-axial electrospinning

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Inverse correlation between CD8^+ inflammatory cells and E-cadherin expression in gallbladder cancer:Tissue microarray and imaging analysis

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World Journal of Clinical Cases 2017年第1期5卷 1-8页

作者： Keita Kai Masanori Masuda shinichi aishima Department of Pathology Saga University Hospital Department of Pathology and Microbiology Saga University Faculty of Medicine

AIM To investigated the association between the tumor cells' expression of E-cadherin and the numbers of several types of inflammatory cells infiltrating into the invasive portion of gallbladder cancer(GBC).METHODS We analyzed 50 GBC cases for which a sufficient amount of tumor tissues for tissue microarray(TMA) had been saved. Three tissue cores(3.0 mm) of invasive lesion from each case were used for the TMA. The 4-μm cut sections on slides were immunostained using primary antibodies including E-cadherin for cancer cells, leukocyte common antigen for leukocyte, myeloperoxidase for neutrophils, CD3 for T cells, CD4 for helper T cells, CD8 for killer T cells, CD20 for B cells and CD68 for macrophages. The immunostained slides were digitally analyzed by imaging analysis software.RESULTS A significant inverse correlation between the number of infiltrating CD8^+ cells at invasive areas and the expression of E-cadherin by cancer cells was observed(P = 0.0001), although the degree of this correlation was relatively weak(R = 0.32). The number of CD8^+ cells and the cancer cells' E-cadherin expression were also significantly correlated with tumor differentiation(welldifferentiated vs poorly differentiated)(P = 0.0467 and P = 0.0294, respectively). Inverse correlation of T-stageand the number of CD8^+ cell infiltration was observed with statistical significance in comparison of T2 and T3 cases(P = 0.0324).CONCLUSION Our findings indicate an inverse correlation of CD8^+ T cell infiltration and cancer cells' E-cadherin expression at invasive areas of GBC. Further analyses are essential to test these findings.

关键词： E-cadherin Inflammation CD8 Gallbladder cancer Tissue microarray

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Formalin fixation on HER-2 and PD-L1 expression in gastric cancer:A pilot analysis using the same surgical specimens with different fixation times

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World Journal of Clinical Cases 2019年第4期7卷 419-430页

作者： Keita Kai Yukie Yoda Atsushi Kawaguchi Akimichi Minesaki Hironori Iwasaki shinichi aishima Hirokazu Noshiro Department of Pathology Saga University Hospital Department of Surgery Saga University Faculty of Medicine Center for Comprehensive Community Medicine Saga University Faculty of Medicine Department of Pathology and Microbiology Saga University Faculty of Medicine Department of Otolaryngology - Head and Neck Surgery Saga University Faculty of Medicine

BACKGROUND The needs for human epidermal growth factor receptor 2(HER-2) and/or programmed death-ligand 1(PD-L1) evaluations in gastric cancer are dramatically increasing. Although the importance of standardization of sample fixation has been widely recognized, most of the evidence regarding the fixation duration or type of fixing solution are based on breast cancer.AIM To investigate the real effects of fixation conditions on HER-2 testing or PD-L1 testing for gastric cancer using gastrectomy specimens.METHODS Thirty-two patients who underwent gastrectomy for gastric cancer were enrolled.Their resected specimens were each divided into four pieces and fixed in four strictly controlled different durations(6 h, 24 h, and 48 h, and 1 wk) by 10%formalin(n = 22) or 10% neutral buffered formalin(NBF)(n = 10).Immunohistochemistry(IHC) of HER-2 and PD-1 was performed, and a pathology examination was conducted. In the HER-2-immunoreactive cases, all four specimens were subjected to dual-color in situ hybridization(DISH). Five cases were assessed as HER-2-positive by IHC and DISH. We used the cut-off values of 1%, 10%, and 50% to assess the IHC findings of PD-L1.RESULTS No significant difference was observed in comparisons between the shorter fixation period groups(6 h, 24 h, and 48 h) and the prolonged fixation period(1 wk) group in the HER-2 and PD-L1 analyses. Although no significant difference was observed between 10% formalin and 10% NBF within 1 wk of fixation, the superiority of 10% NBF was confirmed in a long-term(> 3 mo) fixation in both the HER-2 and PD-L1 analyses.CONCLUSION In this small-numbered pilot study, prolonged fixation within 1 wk showed no inferiority in HER-2 or PD-L1 testing. However, a large-numbered prospective study is needed to obtain conclusive results.

关键词： Gastric cancer Programmed death-ligand1 Human epidermal growth factor receptor2 Neutral buffered formalin Fixation time

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Impact of smoking habit on surgical outcomes in non-B non-C patients with curative resection for hepatocellular carcinoma

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World Journal of Gastroenterology 2017年第8期23卷 1397-1405页

作者： Keita Kai Hiroki Koga shinichi aishima Atsushi Kawaguchi Koutaro Yamaji Takao Ide Junji Ueda Hirokazu Noshiro Department of Pathology Saga University Hospital Departments of Surgery Saga University Hospital Pathology and Microbiology Saga University Hospital Center for Comprehensive Community Medicine Saga University Faculty of Medicine

AIM To analyzed the correlation between smoking status and surgical outcomes in patients with non-B non-C hepatocellular carcinoma(NBNC-HCC), and we investigated the patients' clinicopathological characteristics according to smoking status.METHODS We retrospectively analyzed the consecutive cases of 83 NBNC-HCC patients who underwent curative surgical treatment for the primary lesion at Saga University Hospital between 1984 and December 2012. We collected information about possibly carcinogenic factors such as alcohol abuse, diabetes mellitus, obesity and smoking habit from medical records. Smoking habits were subcategorized as never, ex- and current smoker at the time of surgery. The diagnosis of nonalcoholic steatohepatitis(NASH) was based on both clinical information and pathological confirmation.RESULTS Alcohol abuse, diabetes mellitus, obesity and NASH had no significant effect on the surgical outcomes. Current smoking status was strongly correlated with both overall survival(P = 0.0058) and disease-specific survival(P = 0.0105) by multivariate analyses. Subset analyses revealed that the current smokers were significantly younger at the time of surgery(P = 0.0002) and more likely to abuse alcohol(P = 0.0188) and to have multiple tumors(P = 0.023).CONCLUSION Current smoking habit at the time of surgical treatment is a risk factor for poor long-term survival in NBNC-HCC patients. Current smokers tend to have multiple HCCs at a younger age than other patients.

关键词： Hepatocellular 癌 Non-B Non-C 吸烟外科预后

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Correlation between smoking habit and surgical outcomes on viral-associated hepatocellular carcinomas

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World Journal of Gastroenterology 2018年第1期24卷 58-68页

作者： Keita Kai Sho Komukai Hiroki Koga Koutaro Yamaji Takao Ide Atsushi Kawaguchi shinichi aishima Hirokazu Noshiro Department of Pathology Saga University Hospital Clinical Research Center Saga University Hospital Department of Surgery Saga University Faculty of Medicine Department of Pathology and Microbiology Saga University Faculty of Medicine Center for Comprehensive Community Medicine Saga University Faculty of Medicine

AIM To investigate the association between smoking habits and surgical outcomes in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)(B-HCC) and hepatitis C virus(HCV)-related HCC(C-HCC) and clarify the clinicopathological features associated with smoking status in B-HCC and C-HCC patients.METHODS We retrospectively examined the cases of the 341 consecutive patients with viral-associated HCC(C-HCC,n = 273; B-HCC, n = 68) who underwent curative surgery for their primary lesion. We categorized smoking status at the time of surgery into never, exand current smoker. We analyzed the B-HCC and C-HCC groups' clinicopathological features and surgical outcomes, i.e., disease-free survival(DFS), overall survival(OS), and disease-specific survival(DSS).Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. We also performed subset analyses in both patient groups comparing the current smokers to the other patients.RESULTS The multivariate analysis in the C-HCC group revealed that current-smoker status was significantly correlated with both OS(P = 0.0039) and DSS(P = 0.0416).In the B-HCC patients, no significant correlation was observed between current-smoker status and DFS, OS,or DSS in the univariate or multivariate analyses. The subset analyses comparing the current smokers to the other patients in both the C-HCC and B-HCC groups revealed that the current smokers developed HCC at significantly younger ages than the other patients irrespective of viral infection status.CONCLUSION A smoking habit is significantly correlated with the overall and disease-specific survivals of patients with C-HCC. In contrast, the B-HCC patients showed a weak association between smoking status and surgical outcomes.

关键词： Hepatocellular carcinoma Hepatitis B virus Hepatitis C virus Smoking Surgery Prognosis

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Occult hepatitis B virus infection and surgical outcomes in non-B, non-C patients with curative resection for hepatocellular carcinoma

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World Journal of Hepatology 2017年第35期9卷 1286-1295页

作者： Hiroki Koga Keita Kai shinichi aishima Atsushi Kawaguchi Koutaro Yamaji Takao Ide Junji Ueda Hirokazu Noshiro Department of Surgery Saga University Faculty of Medicine Department of Pathology Saga University Hospital Department of Pathology and Microbiology Saga University Faculty of Medicine Center for Comprehensive Community Medicine Saga University Faculty of Medicine

AIM To investigate the prevalence, clinicopathological characteristics and surgical outcomes of occult hepatitis B virus(HBV) infection(OBI) in patients with non-B, non-C(NBNC) hepatocellular carcinoma(HCC).METHODS This study retrospectively examined the cases of 78 NBNC patients with curative resection for HCC for whom DNA could be extracted from formalin-fixed paraffin-embedded tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqM an realtime polymerase chain reaction. Possibly carcinogenetic factors such as alcohol abuse, diabetes mellitus, obesity and non-alcoholic steatohepatitis(NASH) were examined. Surgical outcomes were evaluated according to diseasefree survival(DFS), overall survival(OS) and diseasespecific survival(DSS).RESULTS OBI was found in 27/78 patients(34.6%) with NBNC HCC. The OBI patients were significantly younger than the non-OBI cases at the time of surgery(average age 63.0 vs 68.1, P = 0.0334) and the OBI cases overlapped with other etiologies significantly more frequently compared to the non-OBI cases(P = 0.0057). OBI had no impact on the DFS, OS or DSS. Only tumorrelated factors affected these surgical outcomes.CONCLUSION Our findings indicate that OBI had no impact on surgical outcomes. The surgical outcomes of NBNC HCC depend on early tumor detection; this reconfirms the importance of a periodic medical examination for individuals who have NBNC HCC risk factors.

关键词： Hepatocellular carcinoma Non-B non-C Occult hepatitis B virus infection Surgery Surgical outcome

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Gallbladder cancer: Clinical and pathological approach

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World Journal of Clinical Cases 2014年第10期2卷 515-521页

作者： Keita Kai shinichi aishima Kohji Miyazaki Department of Pathology and Microbiology Faculty of Medicine Saga University Department of Pathology Saga University Hospital Department of Surgery Faculty of Medicine Saga University

Gallbladder cancer(GBC) shows a marked geographical variation in its incidence. Middle-aged and elderly women are more commonly affected. Risk factors for its development include the presence of gallstones, chronic infection and pancreaticobiliary maljunction. Controversy remains in regard to the theory of carcinogenesis from adenomyomatosis, porcelain gallbladder and adenoma of the gallbladder. The surgical strategy and prognosis after surgery for GBC differ strikingly according to T-stage. Discrimination of favorable cases, particularly T2 or T3 lesions, is useful for the selection of surgical strategies for individual patients. Although many candidate factors predicting disease progression, such as depth of subserosal invasion, horizontal tumor spread, tumor budding, dedifferentiation, Ki-67 labeling index, p53 nuclear expression, CD8+ tumor-infiltrating lymphocytes, mitotic counts, Laminin-5-gamma-2 chain, hypoxia-inducible factor-1a, cyclooxygenase-2 and the Hedgehog signaling pathway have been investigated,useful prognostic makers or factors have not been established. As GBC is often discovered incidentally after routine cholecystectomy and accurate preoperative diagnosis is difficult, close mutual cooperation between surgeons and pathologists is essential for developing a rational surgical strategy for GBC.

关键词： Gallbladder cancer Surgical strategy Pathology Prognostic factors

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Occult HBV infection status and its impact on surgical outcomes in patients with curative resection for HCV-associated hepatocellular carcinoma

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Hepatobiliary Surgery and Nutrition 2018年第6期7卷 443-453页

作者： Koutaro Yamaji Keita Kai Sho Komukai Hiroki Koga Takao Ide Atsushi Kawaguchi Hirokazu Noshiro shinichi aishima Department of Surgery Saga University Faculty of MedicineSaga 849-8501Japan Department of Pathology&Microbiology Saga University Faculty of MedicineSaga 849-8501Japan Department of Pathology Saga University HospitalSaga 849-8501Japan Clinical Research Center Saga University HospitalSaga 849-8501Japan Center for Comprehensive Community Medicine Saga University Faculty of MedicineSaga 849-8501Japan

Background:We sought to clarify the prevalence of occult hepatitis B virus(HBV)infection(OBI)and to determine whether OBI affects the surgical outcomes in curatively resected Japanese patients with hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC).Methods:A total of 257 patients with HCV-related HCC who underwent curative surgical resection were enrolled.All enrolled patients were serologically negative for HBV surface antigen and positive for HCV antibody.DNA was extracted from formalin-fixed paraffin-embedded liver tissue.OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqMan real-time polymerase chain reaction.Surgical outcomes were evaluated according to overall survival(OS),disease-specific survival(DSS),and disease-free survival(DFS).Results:OBI was identified in 15 of the 257(5.8%)cases.In the multivariate analyses,the factors significantly correlated with OS were BMI>25(P=0.0416),portal vein invasion(P=0.0065),and multiple tumors(P=0.0064).The only factor significantly correlated with DSS was T-stage(P=0.0275).The factors significantly correlated with DFS were liver fibrosis(P=0.0017)and T-stage(P=0.0001).The status of OBI did not show any significant correlation with OS,DSS or DFS,but a weak association with DSS(P=0.0603)was observed.Conclusions:The prevalence of OBI was 5.8%in 257 cases of HCV-related HCC.Although a weak association between DSS and OBI was observed,and statistical analyses were limited by small number of OBI cases,no significant correlation between OBI and surgical outcomes was detected.

关键词： Occult hepatitis B virus infection(OBI) hepatocellular carcinoma(HCC) hepatitis C virus(HCV) surgery prognosis

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Granulomatous reaction in hepatic inflammatory angiomyolipoma after chemoembolization and spontaneous rupture

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World Journal of Gastroenterology 2015年第32期21卷 9675-9682页

作者： Keita Kai Atsushi Miyosh shinichi aishima Kota Wakiyama Shunya Nakashita Shinji Iwane Shinya Azama Hiroyuki Irie Hirokazu Noshiro Department of Pathology Saga University Hospital Department of Surgery Saga University Faculty of Medicine Department of Pathology and Microbiology Saga University Faculty of Medicine Department of Internal Medicine Saga University Faculty of Medicine Department of Radiology Saga University Faculty of Medicine

A 77-year-old Japanese woman was transported to a nearby hospital due to sudden abdominal pain and transient loss of consciousness. Abdominal computed tomography(CT) suggested hemoperitoneum and hepatic nodule. She was conservatively treated. Contrast-enhanced CT two months later revealed an increased mass size, and the enhancement pattern suggested the possibility of hepatocellular carcinoma(HCC). Under a clinical diagnosis of HCC, transcatheter arterial chemoembolization(TACE) was performed. A subsequent imaging study revealed that most of the lipiodol used for the embolization was washed out. Therefore, surgical resection was performed. Histologically, the nodule contained numerous inflammatory cells including small lymphocytes, plasma cells and macrophages. Notably, epithelioid granulomatous features with multinucleated giant cells were observed in both the nodule and background liver. Some of the multinucleated giant cells contained oil lipid. Among the infiltrating inflammatory cells,spindle-shaped, histiocytoid or myoid tumor cells with eosinophilic cytoplasm were found. The tumor cells were positive for Melan A and HMB45. The nodule contained many Ig G4-positive plasma cells; these were counted and found to number 72.6 cells/HPF(range: 61-80). The calculated Ig G4:Ig G ratio was 33.2%. The nodule was finally diagnosed as previously ruptured inflammatory angiomyolipoma modified by granulomatous reaction after TACE.

关键词： Angiomyolipoma Inflammatory Rupture Lipiodol Liver

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Correction to:Heparin/Growth Factors‑Immobilized Aligned Electrospun Nanofibers Promote Nerve Regeneration in Polycaprolactone/Gelatin‑Based Nerve Guidance Conduits

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Advanced Fiber Materials 2023年第2期5卷 696-696页

Correction to:Advanced Fiber Materials https://***/10.1007/s42765-022-00244-6 In this article the affiliation details for Author Muhammad Shafiq were incorrectly given.They should have been assigned as shown below.The... 详细信息

关键词： fibers details Regeneration

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