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1.
Auris Nasus Larynx ; 51(6): 911-916, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39265196

ABSTRACT

OBJECTIVE: Airway stenosis impairs the quality of life of patients. However, the epidemiology and pathophysiology of airway stenosis remain underexplored owing to its rarity. Airway stenosis may go undetected for a long period without accurate diagnosis or treatment owing to the lack of established treatment guidelines. Thus, clinical information must be accumulated and analyzed to generate evidence-based treatment strategies for this rare entity. METHODS: A retrospective nationwide epidemiological survey was conducted targeting patients with pharyngeal, laryngeal, or tracheal stenosis in Japan. The initial survey was conducted across 1393 facilities between 2013 and 2017 to evaluate the treatment of airway stenosis. The clinical information of the patients was collected via a secondary survey. RESULTS: The primary survey revealed that airway stenosis was treated at only 43 % of the facilities over the 5-year period. The secondary survey revealed that 284 cases were registered across 57 facilities. The number of patients with acquired stenosis exceeded that of those with congenital stenosis. The larynx or cervical trachea was the most common site of stenosis, and intubation or tracheostomy was the most common cause of stenosis. Approximately 76 % of patients underwent surgical treatment, and tracheostomy was the most common procedure. Stenosis persisted in > 70 % of patients at the last visit. CONCLUSIONS: This study clarified the clinical background of patients with pharyngeal, laryngeal, and tracheal stenosis in Japan and the surgical treatment received. The findings of this study confirmed the rarity of airway stenosis and the difficulty in treating this entity.

2.
Tissue Eng Part A ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-38970444

ABSTRACT

Tracheal cartilage provides structural support to the airways to enable breathing. However, it can become damaged or impaired, sometimes requiring surgical resection and reconstruction. Previously, we clinically applied an artificial trachea composed of a polypropylene mesh and collagen sponge, with a favorable postoperative course. However, the artificial trachea presents a limitation, as the mesh is not biodegradable and cannot be used in pediatric patients. Compared to a polypropylene mesh, regenerated cartilage represents an ideal material for reconstruction of the damaged trachea. The use of mesenchymal stem cells (MSCs) as a source for cartilage regeneration has gained widespread acceptance, but challenges such as the invasiveness of harvesting and limited cell supply persist. Therefore, we focused on the potential of human-induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) for tracheal cartilage regeneration. In this study, we aimed to regenerate tracheal cartilage on an artificial trachea as a preliminary step to replace the polypropylene mesh. iMSCs were induced from hiPSCs through neural crest cells and transplanted with a polypropylene mesh covered with a collagen sponge into the damaged tracheal cartilage in immunodeficient rats. Human nuclear antigen (HNA)-positive cells were observed in all six rats at 4 weeks and in six out of seven rats at 12 weeks after transplantation, indicating that transplanted iMSCs survived within the tracheal cartilage defects of rats. The HNA-positive cells coexpressed SOX9, and type II collagen was detected around HNA-positive cells in four of six rats at 4 weeks and in three of seven rats at 12 weeks after transplantation, reflecting cartilage-like tissue regeneration. These results indicate that the transplanted iMSCs could differentiate into chondrogenic cells and promote tracheal cartilage regeneration. iMSC transplantation thus represents a promising approach for human tracheal reconstruction.

3.
Tissue Eng Part A ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38832872

ABSTRACT

Investigating the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the airway epithelium and developing effective defense strategies against infection are important. To achieve this, establishing appropriate infection models is crucial. Therefore, various in vitro models, such as cell lines and primary cultures, and in vivo models involving animals that exhibit SARS-CoV-2 infection and genetically humanized animals have been used as animal models. However, no animal model has been established that allows infection experiments with human cells under the physiological environment of airway epithelia. Therefore, we aimed to establish a novel animal model that enables infection experiments using human cells. Human induced pluripotent stem cell-derived airway epithelial cell-transplanted nude rats (hiPSC-AEC rats) were used, and infection studies were performed by spraying lentiviral pseudoviruses containing SARS-CoV-2 spike protein and the GFP gene on the tracheae. After infection, immunohistochemical analyses revealed the existence of GFP-positive-infected transplanted cells in the epithelial and submucosal layers. In this study, a SARS-CoV-2 infection animal model including human cells was established mimicking infection through respiration, and we demonstrated that the hiPSC-AEC rat could be used as an animal model for basic research and the development of therapeutic methods for human-specific respiratory infectious diseases.

4.
Cell Transplant ; 33: 9636897241228026, 2024.
Article in English | MEDLINE | ID: mdl-38372247

ABSTRACT

No radical treatment is available for the regeneration of dysfunction and defects in airway epithelia. Artificial tracheae made of polypropylene and collagen sponge were used in clinical studies to reconstitute tracheae after resection. For early epithelialization of the luminal surface of the artificial trachea, a model was established, that is, an artificial trachea covered with human-induced pluripotent stem cell-derived airway epithelial cells (hiPSC-AECs) was transplanted into a tracheal defect in an immunodeficient rat. Unlike the cell types of hiPSC-derived cells that are currently used in clinical studies, AECs maintain tissues by proliferation and differentiation of basal cells into various cell types that constitute AECs constantly. Therefore, post-transplantation, the proportion of each cell type, such as ciliated and goblet cells, may change; however, no studies have examined this possibility. In this study, using our hiPSC-AEC-transplanted rat model, we investigated changes in the proportion of each cell type in hiPSC-AECs pre-transplantation and post-transplantation. As a result, the proportion of each cell type changed post-transplantation. The proportion of ciliated, basal, and club cells increased, and the proportion of goblet cells decreased post-transplantation. In addition, the proportion of each cell type in engrafted hiPSC-AECs is more similar to the proportion of each cell type in normal proximal airway tissue than the proportion of each cell type pre-transplantation. The results of this study are useful for the development of therapeutic techniques using hiPSC-AEC transplantation.


Subject(s)
Induced Pluripotent Stem Cells , Rats , Humans , Animals , Epithelial Cells , Epithelium , Trachea/transplantation , Collagen/metabolism
5.
Tissue Eng Part A ; 30(3-4): 144-153, 2024 02.
Article in English | MEDLINE | ID: mdl-37950719

ABSTRACT

The airway epithelia (AE) play a role in the clearance of foreign substances through ciliary motility and mucus secreted. We developed an artificial trachea that is made of collagen sponges and polypropylene mesh for the regeneration of the tracheal defect, and it was used for a clinical study. Then, a model in which the luminal surface of an artificial trachea was covered with a human-induced pluripotent stem cell-derived AE (hiPSC-AE) was transplanted into the tracheal defect of nude rats to promote epithelialization. In the future, this model was expected to be applied to research on infectious diseases and drug discovery as a trachea-humanized rat model. However, at present, sufficient engraftment has not been achieved to evaluate functional recovery in transplanted cells. Therefore, this study focused on immunosuppression in recipient rats. Nude rats lack T cell function and are widely used for transplantation experiments; however, more severe immunosuppressed recipients are preferred for xenotransplantation. Several strains of immunodeficient rats were created as rats that exhibit more severe immunodeficiency until now. In this study, to establish a trachea-humanized rat model in which human AE function can be analyzed to improve engraftment efficiency, engraftment efficiency in nude rats and X-linked severe combined immunodeficiency (X-SCID) rats following hiPSC-AE transplantation was compared. In the analysis of the proportion of engrafted cells in total cells at the graft site, the engraftment efficiency of epithelial cells tended to be high in X-SCID rats, although no statistical difference was found between the two groups, whereas the engraftment efficiency of mesenchymal cells was higher in X-SCID rats. Furthermore, the number of immune cells that accumulated in the grafts showed that a pan T cell marker, that is, CD3-positive cells, did not differ between the two strains; however, CD45-positive cells and major histocompatibility complex (MHC) class II-positive cells significantly decreased in X-SCID rats. These results indicate that X-SCID rats are more useful for the transplantation of hiPSC-AE into the tracheae to generate trachea-humanized rat models.


Subject(s)
Induced Pluripotent Stem Cells , X-Linked Combined Immunodeficiency Diseases , Humans , Rats , Animals , Mice , Rats, Nude , T-Lymphocytes , Trachea , Mice, SCID
6.
Tissue Eng Part C Methods ; 29(11): 526-534, 2023 11.
Article in English | MEDLINE | ID: mdl-37756360

ABSTRACT

The nasal cavity is covered with respiratory epithelia, including ciliated cells that eliminate foreign substances trapped in the mucus. In hereditary diseases such as primary ciliary dyskinesia and cystic fibrosis, respiratory epithelial functions are irreversibly impaired; however, no radical treatment has been established yet. Thus, we considered that the transplantation of normal airway epithelia (AE) into the nasal epithelia is one of the strategies that could lead to radical treatment in the future. In our previous study, human induced pluripotent stem cell-derived AE (hiPSC-AE) on the vitrigel membrane were transplanted into the scraped area of the nasal septal mucosa of nude rats. Although human-derived ciliated cells, club cells, and basal cells were observed, they were located in the cysts within the submucosal granulation tissue but not in the nasal mucosal epithelia and the transplanted cells may not contribute to the function of the nasal mucosa with this condition. Therefore, to achieve more functional transplantation, we prepared the graft differently in this study by wrapping the collagen sponge in hiPSC-AE on the vitrigel membrane. As a result, we found the transplanted cells surviving in the nasal mucosal epithelia. These results suggest that hiPSC-AE transplanted into the nasal cavity could be viable in the nasal mucosa. In addition, our method leads to the establishment of nasal mucosa-humanized rats that are used for the development of the drugs and therapeutic methods for hereditary diseases of nasal respiratory epithelia.


Subject(s)
Induced Pluripotent Stem Cells , Humans , Rats , Animals , Nasal Cavity , Epithelium , Epithelial Cells , Collagen
7.
Cell Transplant ; 32: 9636897231178460, 2023.
Article in English | MEDLINE | ID: mdl-37278405

ABSTRACT

Previous studies transplanted human-induced pluripotent stem cells (hiPSCs)-derived mesenchymal stem cells (iMSCs) into thyroid cartilage defect of X-liked severe combined immunodeficiency (X-SCID) rats and confirmed transplanted cell survival and cartilage regeneration. Thus, this study aimed to investigate the contribution of iMSC transplantation to thyroid cartilage regeneration of nude rats. iMSCs were induced from hiPSCs via a neural crest cell lineage. Then, clumps formed from an iMSC/extracellular matrix complex were transplanted into thyroid cartilage defects in nude rats. The larynx was removed and histological and immunohistochemical analyses were performed 4 or 8 weeks after the transplantation. Human nuclear antigen (HNA)-positive cells were observed in 11 of 12 (91.7%) rats, which indicated that transplanted iMSCs survived in thyroid cartilage defects in nude rats. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells in 8 of 12 rats (66.7%), which indicated cartilage-like regeneration. Cartilage-like regeneration in nude rats in this study was comparable to the previous report on X-SCID rats (HNA-positive cells were observed in all 14 rats and cartilage-like regeneration was observed in 10 of 14 rats). This result suggests that nude rats could be an alternative to X-SCID rats in thyroid cartilage regeneration experiments using iMSCs, and this nude rat cartilage transplantation model may develop cartilage regeneration research concerning fewer problems such as infection due to immunosuppression.


Subject(s)
Induced Pluripotent Stem Cells , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , X-Linked Combined Immunodeficiency Diseases , Humans , Rats , Animals , Induced Pluripotent Stem Cells/metabolism , Rats, Nude , X-Linked Combined Immunodeficiency Diseases/metabolism , Cell Differentiation , Laryngeal Cartilages , Mesenchymal Stem Cells/metabolism
8.
Int J Clin Oncol ; 28(4): 521-530, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36780098

ABSTRACT

BACKGROUND: Endoscopic laryngopharyngeal surgery (ELPS) is a minimally invasive transoral surgery for superficial pharyngeal and laryngeal cancer, but dysphagia occasionally occurs post-treatment. We investigated dysphagia following ELPS and its risk factors. METHODS: Of the 145 patients who underwent ELPS, 92 were evaluated in this study using the Hyodo score, Functional Outcome Swallowing Scale, Eating Assessment Tool-10 along with the total scores for the three items of the method of intake, time, and food preoperatively and on postoperative 1, 3, and 6 months. We examined the 6-month trends of these values. Furthermore, the fasting period post-surgery, the need for swallowing rehabilitation by a speech therapist, and postoperative pneumonia episodes were set as outcomes reflecting the short-term swallowing function. We determined the associations between these outcomes and patient background factors. RESULTS: Postoperatively, the Hyodo score worsened at 1 month but recovered at 3 months. The Hyodo scores of all patients who underwent postcricoid ELPS did not worsen. The diameter of the resected specimen (DRS) was significantly associated with the need for swallowing rehabilitation and postoperative fasting time. A DRS ≥ 35 mm was considered the threshold for the need of swallowing rehabilitation, postoperative pneumonia, and prolonged postoperative fasting time. CONCLUSION: ELPS exerts a temporal and limited impact on the swallowing function, which recovers within 3 months in every swallowing evaluation. This necessitates additional care during the treatment of patients with mucosal defects ≥ 35 mm, owing to the significant association between the DRS and short-term swallowing function.


Subject(s)
Deglutition Disorders , Laryngeal Neoplasms , Humans , Deglutition , Deglutition Disorders/etiology , Endoscopy/adverse effects , Endoscopy/methods , Laryngeal Neoplasms/surgery , Minimally Invasive Surgical Procedures/methods
9.
PLoS One ; 17(10): e0275488, 2022.
Article in English | MEDLINE | ID: mdl-36191019

ABSTRACT

Glutaraldehyde, a germicide for reprocessing endoscopes that is important for hygiene in the clinic, might be hazardous to humans. Electrolyzed acid water (EAW) has a broad anti-microbial spectrum and safety profile and might be a glutaraldehyde alternative. We sought to assess EAW disinfection of flexible endoscopes in clinical otorhinolaryngological settings and its in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bacteria commonly isolated in otorhinolaryngology. Ninety endoscopes were tested for bacterial contamination before and after endoscope disinfection with EAW. The species and strains of bacteria were studied. The in vitro inactivation of bacteria and SARS-CoV-2 by EAW was investigated to determine the efficacy of endoscope disinfection. More than 20 colony-forming units of bacteria at one or more sampling sites were detected in 75/90 microbiological cultures of samples from clinically used endoscopes (83.3%). The most common genus detected was Staphylococcus followed by Cutibacterium and Corynebacterium at all sites including the ears, noses, and throats. In the in vitro study, more than 107 CFU/mL of all bacterial species examined were reduced to below the detection limit (<10 CFU/mL) within 30 s after contact with EAW. When SARS-CoV-2 was treated with a 99-fold volume of EAW, the initial viral titer (> 105 PFU) was decreased to less than 5 PFU. Effective inactivation of SARS-CoV-2 was also observed with a 19:1 ratio of EAW to the virus. EAW effectively reprocessed flexible endoscopes contributing to infection control in medical institutions in the era of the coronavirus disease 2019 pandemic.


Subject(s)
COVID-19 , Disinfection , Bacteria , COVID-19/prevention & control , Cross-Sectional Studies , Endoscopes/microbiology , Endoscopes, Gastrointestinal/microbiology , Equipment Contamination/prevention & control , Glutaral , Humans , SARS-CoV-2 , Water
10.
Cureus ; 13(4): e14423, 2021 Apr 11.
Article in English | MEDLINE | ID: mdl-33996291

ABSTRACT

Programmed cell death ligand 1 (PD-L1) expression and tumor-associated immune cell (TAIC) density can be the biomarkers of survival outcome and for predicting the efficacy of immune checkpoint inhibitors in oral squamous cell carcinoma (OSCC), but whether single biopsy accurately reflects the values of these parameters in resected specimens is unclear. To clarify this, we evaluated the concordance of immune marker expression (PD-L1, PD-1, CD3, CD4, CD8, and CD68) between 39 paired biopsied and surgically resected specimens obtained from patients with OSCC at Kobe City Medical Center General Hospital between July 2011 and January 2016. Immune marker expression was assessed using immunohistochemistry. PD-L1 expression was consistent between the biopsied and surgically resected specimens in only 76.9% of cases. TAIC density was significantly lower in biopsied than in surgically resected specimens. There was considerable discordance in immune marker expression between biopsied and surgically resected specimens. We should take into consideration that PD-L1 positivity and TAIC density would be underestimated by single small biopsies compared to the estimations by surgically resected specimens.

11.
Head Neck ; 43(2): 534-543, 2021 02.
Article in English | MEDLINE | ID: mdl-33029887

ABSTRACT

BACKGROUND: The expression of PD-L1 in tumor cells and infiltration of tumor-associated immune cells (TAICs) might reflect the tumor biology of head and neck cancer. We aimed to characterize their prognostic roles in oral squamous cell carcinomas (OSCCs). METHODS: We enrolled 103 OSCC patients who underwent definitive surgery. Immune expression levels of PD-L1, PD-1, CD3, CD4, CD8, and CD68 were assessed in surgically resected specimens. We evaluated the effects of immune marker expression and localization on survival outcomes. RESULTS: Multivariate analysis results adjusted by the pathological stage, resection margin, and extracapsular extension showed that a high number of PD-1+ TAICs and intratumoral CD68+ TAICs were independent positive and negative prognostic markers (hazard ratio: 0.20 and 4.15, respectively; P = .02 and .01, respectively). CONCLUSION: PD-1+ TAICs in the tumor microenvironment and CD68+ TAICs in the intratumoral area could act as novel biomarkers for predicting overall survival outcomes in OSCC patients.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , B7-H1 Antigen , Biomarkers, Tumor , Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/surgery , Humans , Mouth Neoplasms/surgery , Prognosis , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment
12.
Ann Vasc Dis ; 14(4): 388-392, 2021 Dec 25.
Article in English | MEDLINE | ID: mdl-35082947

ABSTRACT

A 63-year-old man with a confirmed case of coronavirus disease 2019 and having complaints of severe pain and paralysis in his right lower limb was transported to our hospital in an ambulance. Because of thrombosis, a computed tomography angiogram revealed the occlusion of right common iliac artery and stenosis of abdominal aorta. Emergency angiography and thrombectomy were performed; after surgery, the patient was managed in the intensive care unit with mechanical ventilation and hemodialysis for renal failure. However, on postoperative day 7, thrombosis recurred, and he died because of multiple organ failure.

13.
Jpn J Clin Oncol ; 48(6): 529-534, 2018 Jun 01.
Article in English | MEDLINE | ID: mdl-29688530

ABSTRACT

OBJECTIVES: In performing an open biopsy of a neck mass, an incisional biopsy may increase the risk of cancer cell seeding and dissemination that, ultimately, worsens a patient's survival. The aim of this study was to compare the impact of incisional and excisional biopsies of cervical lymph node metastases of solid tumors on patients' survival. METHODS: A retrospective review was made of patients with cervical metastases of solid tumors who underwent an open biopsy for a diagnosis between 2005 and 2015. Sixty-four patients met the criteria out of 524 open biopsy cases undertaken during the period. Survival analyses were estimated from 33 cases whose initial symptoms were the presence of a neck mass, using two modes of biopsy: excisional and incisional. RESULTS: The 2-year overall survival rates in incisional and excisional biopsy groups were 65% and 43%, respectively, and 2-year disease-specific survival rates were 74% and 43%, respectively. The differences were not significant. For lung cancer or head and neck cancer subgroups, survival differences between incisional and excisional biopsy groups were also not significant. CONCLUSIONS: A carefully targeted physical examination and performing a fine needle aspiration are essential to establish a diagnosis for the etiology of an unknown neck mass. In performing an open biopsy, the effect of an incisional biopsy on patients' survival was no worse than that of an excisional biopsy, despite the latter being theoretically preferable.


Subject(s)
Cervical Vertebrae/pathology , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Animals , Biopsy , Chick Embryo , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
14.
Gan To Kagaku Ryoho ; 44(5): 413-415, 2017 May.
Article in Japanese | MEDLINE | ID: mdl-28536338

ABSTRACT

A 69-year-old woman underwent total gastrectomy for advanced gastric cancer with pyloric stenosis. She had a good postoperative course and was discharged 2 weeks after surgery. She received adjuvant chemotherapy with S-1 after discharge. One month after the initiation of the adjuvant chemotherapy, she complained of wobbling and weakness of her limbs. She stopped intake of S-1, but the symptoms did not improve. She was admitted to the hospital, but she became unconscious and had headache and blurred vision. We conducted a cerebrospinal fluid examination and made a diagnosis of meningeal carcinomatosis. After we started intrathecal infusion of methotrexate and Ara-C, referring to case reports clinical symptoms, including unconsciousness, headache, and left upper limb paralysis, improved and the CEA level in cerebrospinal fluid decreased.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Meningitis/etiology , Stomach Neoplasms/drug therapy , Aged , Arabinofuranosylcytosine Triphosphate/administration & dosage , Biopsy , Chemotherapy, Adjuvant , Female , Gastrectomy , Humans , Meningitis/pathology , Methotrexate/administration & dosage , Recurrence , Stomach Neoplasms/complications , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
15.
Gan To Kagaku Ryoho ; 44(5): 417-420, 2017 May.
Article in Japanese | MEDLINE | ID: mdl-28536339

ABSTRACT

The patient was a 66-year-old woman with a history of right breast cancer 20 years prior. Her chief complaint was hematochezia, and she was diagnosed as having rectal cancer. She underwent laparoscopic high anterior resection. We made a diagnosis of moderately differentiated adenocarcinoma, type 2, 25×20 mm, pMP, pN0, Stage I, KRAS being wild-type. Multiple liver metastases were detected 6 months after the surgery. Tumor contacted with grison. The tumor was not completely resected as evidenced by the small liver remnant volume. Conversion therapy was administered, and the patient received 6 courses of FOLFIRI plus cetuximab therapy. Alopecia and grade 1 eruption were observed as adverse effects of the chemotherapy. The tumor size was reduced, and we resected the tumor by performing right lobectomy and partial hepatectomy. At 1 year 3 months after surgery, no recurrence was observed.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Liver Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Cetuximab/administration & dosage , Colectomy , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Hepatectomy , Humans , Leucovorin/administration & dosage , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Treatment Outcome
16.
Article in English | MEDLINE | ID: mdl-26349944

ABSTRACT

A simple and sensitive method for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage in human urine, was developed using automated on-line in-tube solid-phase microextraction (SPME) coupled with stable isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Creatinine was also analyzed simultaneously to normalize urine volume by the in-tube SPME LC-MS/MS method, and 8-OHdG and creatinine were separated within 3 min using a Zorbax Eclipse XDB-C8 column. Electrospray MS/MS for these compounds was performed on an API 4000 triple quadruple mass spectrometer in the positive ion mode by multiple reaction monitoring. The optimum in-tube SPME conditions were 20 draw/eject cycles of 40 µL of sample at a flow rate of 200 µL/min using a Carboxen 1006 PLOT capillary column as an extraction device. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. The calibration curve for 8-OHdG using its stable isotope-labeled internal standard was linear in the range of 0.05-10 ng/mL, and the detection limit was 8.3 pg/mL. The intra-day and inter-day precision (relative standard deviations) were below 3.1% and 9.6% (n=5), respectively. This method was applied successfully to the analysis of urine samples without any other pretreatment and interference peaks, with good recovery rates above 91% in spiked urine samples. The limits of quantification of 8-OHdG and creatinine in 0.1 mL urine samples were about 0.32 and 0.69 ng/mL (S/N=10), respectively. This method was utilized to assess the effects of smoking, green tea drinking and alcohol drinking on the urinary excretion of 8-OHdG.


Subject(s)
Chromatography, Liquid/methods , Deoxyguanosine/analogs & derivatives , Oxidative Stress , Solid Phase Microextraction/methods , Tandem Mass Spectrometry/methods , 8-Hydroxy-2'-Deoxyguanosine , Adult , Automation , Biomarkers , Deoxyguanosine/urine , Humans , Limit of Detection , Male , Young Adult
17.
J Pharm Biomed Anal ; 112: 36-42, 2015 Aug 10.
Article in English | MEDLINE | ID: mdl-25956225

ABSTRACT

We have developed a simple and sensitive method for the determination of the oxidative stress biomarker 8-isoprostane (8-IP) in human urine by automated online in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a Zorbax Eclipse XDB-8 column and 0.1% formic acid/methanol (25/75, v/v) as a mobile phase. Electrospray MS/MS for 8-IP was performed on an API 4000 triple quadruple mass spectrometer in negative ion mode. The optimum in-tube SPME conditions were 20 draw/eject cycles with a sample size of 40 µL using a Carboxen 1006 PLOT capillary column for the extraction. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Total analysis time of this method including online extraction and analysis was about 30 min for each sample. The in-tube SPME LC-MS/MS method showed good linearity in the concentration range of 20-1000 pg/mL with a correlation coefficient r = 0.9999 for 8-IP using a stable isotope-labeled internal standard, 8-IP-d4. The detection limit of 8-IP was 3.3 pg/mL and the proposed method showed 42-fold higher sensitivity than the direct injection method. The intra-day and inter-day precisions (relative standard deviations) were below 5.0% and 8.5% (n = 5), respectively. This method was applied successfully to the analysis of urine samples without pretreatment or interference peaks. The recovery rates of 8-IP spiked into urine samples were above 92%. This method is useful for assessing the effects of oxidative stress and antioxidant intake.


Subject(s)
Biomarkers/chemistry , Biomarkers/urine , Dinoprost/analogs & derivatives , Oxidative Stress/physiology , Antioxidants/chemistry , Chromatography, Liquid/methods , Dinoprost/chemistry , Dinoprost/urine , Humans , Male , Online Systems , Solid Phase Microextraction/methods , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods
19.
Updates Surg ; 66(4): 265-8, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25266894

ABSTRACT

Cholecystectomy is the standard treatment for symptomatic gallstone or acute cholecystitis, and a growing number of elderly patients are undergoing resection. The aim of this study is to evaluate the clinical outcome of cholecystectomy in elderly patients. We retrospectively reviewed the medical records of 337 patients with symptomatic gallstone or acute cholecystitis who underwent cholecystectomies between January 2011 and June 2013. Perioperative data were compared between octogenarians and younger patients. A subgroup undergoing cholecystectomy for acute cholecystitis (n = 146, 43.3 %) was further analyzed. The octogenarian group included 34 patients (10.1 %), while the younger patient group included 303 patients (89.9 %). The octogenarian group was associated with higher rates of comorbidities and acute cholecystitis. The octogenarian group had significantly low laparoscopic completed rates, high postoperative complication rates, and longer postoperative hospital stays. Among the acute cholecystitis group, 24 patients (16.4 %) were octogenarians and 122 patients (83.6 %) were younger patients. No significant difference was found in the morbidity and postoperative hospital stay between the two groups. Only one patient (0.3 %), an octogenarian, died of pneumonia. Cholecystectomy for symptomatic gallstone or acute cholecystitis can be safely performed even in octogenarians. However, care should be taken because they have comorbidities and limited functional reserves.


Subject(s)
Cholecystectomy , Cholecystitis/surgery , Gallstones/surgery , Acute Disease , Age Factors , Aged, 80 and over , Cholecystectomy/adverse effects , Cholecystectomy, Laparoscopic/adverse effects , Female , Humans , Length of Stay , Male , Retrospective Studies , Risk Factors
20.
Jpn J Clin Oncol ; 43(1): 74-7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23136240

ABSTRACT

Carcinoid tumors located in the minor duodenal papilla are extremely rare, with only a few cases reported in the literature. Herein, we report the case of a 71-year-old man with a 12-mm carcinoid tumor at the minor duodenal papilla with lymph node metastases. Multidetector-row computed tomography with contrast enhancement revealed a 12-mm well-enhanced tumor in the duodenum. Upper gastrointestinal endoscopy showed a 12-mm submucosal tumor at the minor papilla of the duodenum. Biopsy specimens revealed a carcinoid tumor, and a subtotal stomach-preserving pancreatoduodenectomy was performed. Carcinoid tumors at the minor duodenal papilla have a high prevalence of nodal disease, even for tumors <2 cm in diameter. Therefore, we believe that radical resection with tumor-free margins (i.e. pancreatoduodenectomy) is the treatment of choice.


Subject(s)
Carcinoid Tumor/pathology , Duodenal Neoplasms/pathology , Pancreatic Ducts/pathology , Aged , Carcinoid Tumor/surgery , Duodenal Neoplasms/surgery , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Multidetector Computed Tomography , Pancreatic Ducts/surgery , Pancreaticoduodenectomy , Prognosis
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