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2.
Sci Rep ; 10(1): 20157, 2020 Nov 19.
Article in English | MEDLINE | ID: mdl-33214592

ABSTRACT

The scientific and technical advances continue to support novel discoveries by allowing scientists to acquire new insights into the structure and properties of matter using new tools and sources. Notably, neutrons are among the most valuable sources in providing such a capability. At the Institute of Laser Engineering, Osaka, the first steps are taken towards the development of a table-top laser-driven neutron source, capable of producing a wide range of energies with high brightness and temporal resolution. By employing a pure hydrogen moderator, maintained at cryogenic temperature, a cold neutron ([Formula: see text]) flux of [Formula: see text]/pulse was measured at the proximity of the moderator exit surface. The beam duration of hundreds of ns to tens of [Formula: see text] is evaluated for neutron energies ranging from 100s keV down to meV via Monte-Carlo techniques. Presently, with the upcoming J-EPoCH high repetition rate laser at Osaka University, a cold neutron flux in orders of [Formula: see text] is expected to be delivered at the moderator in a compact beamline.

3.
Br J Surg ; 106(10): 1352-1361, 2019 09.
Article in English | MEDLINE | ID: mdl-31414718

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors, such as antibody against programmed cell death protein (PD-1), have demonstrated antitumour effects in patients with malignancies, including oesophageal cancer. A lymphocytic reaction observed by pathological examination is a manifestation of the host immune response to tumour cells. It was hypothesized that a stronger lymphocytic reaction to tumours might be associated with favourable prognosis in oesophageal cancer. METHODS: Using a database of resected oesophageal cancers, four morphological components of lymphocytic reactions (peritumoral, intranest, lymphoid and stromal) to tumours were evaluated in relation to clinical outcome, PD-1 expression by immunohistochemistry and total lymphocyte count in blood. RESULTS: Resected oesophageal cancer specimens from 436 patients were included in the study. Among the four morphological components, only peritumoral reaction was associated with patient prognosis (multivariable P for trend <0·001); patients with a higher peritumoral reaction had significantly longer overall survival than those with a lower reaction (multivariable hazard ratio 0·48, 95 per cent c.i. 0·34 to 0·67). The prognostic effect of peritumoral reaction was not significantly modified by other clinical variables (all P for interaction >0·050). Peritumoral reaction was associated with total lymphocyte count in the blood (P < 0·001), supporting the relationship between local immune response and systemic immune competence. In addition, higher morphological peritumoral reaction was associated with high PD-1 expression on lymphocytes in tumours (P = 0·034). CONCLUSION: These findings should help to improve risk-adapted therapeutic strategies and help stratify patients in the future clinical setting of immunotherapy for oesophageal cancer.


ANTECEDENTES: Los inhibidores de los puntos de control inmunitario (checkpoints) (p.ej. los anticuerpos anti-PD-1) han demostrado efectos antitumorales en pacientes con tumores malignos, incluido el cáncer de esófago. La reacción linfocítica detectada en estudios anatomopatológicos es una manifestación de la respuesta inmune del huésped a las células tumorales. Se estableció la hipótesis de que una mayor reacción linfocítica a los tumores podría asociarse con un mejor pronóstico en el cáncer de esófago. MÉTODOS: Usando una base de datos de 436 cánceres de esófago resecados, se evaluaron cuatro componentes morfológicos (peritumoral, intra-epitelial, linfoide y estromal) de las reacciones linfocíticas a tumores en relación con los resultados clínicos, la expresión inmunohistoquímica de PD-1 y el recuento total de linfocitos en sangre. RESULTADOS: De los cuatro componentes, solamente la reacción peritumoral se asoció con el pronóstico del paciente (P multivariable para tendencia < 0,001): los pacientes con mayor reacción peritumoral presentaron una supervivencia global significativamente más prolongada que aquellos pacientes con menor reacción peritumoral (cociente de riesgos instantáneos multivariable, hazard ratio, HR: 0,48; i.c. del 95%: 0,34 -0,67; P <0,001). El efecto pronóstico de la reacción peritumoral no se modificó significativamente por otras variables clínicas (todas las P para la interacción > 0,05). La reacción peritumoral se asoció con el recuento total de linfocitos en la sangre (P < 0,001), lo que respalda la relación entre la respuesta inmune local y la competencia inmune sistémica. Además, una elevada reacción morfológica peritumoral se asoció con una alta expresión de PD-1 en linfocitos tumorales (P = 0,034). CONCLUSIÓN: Estos hallazgos deberían ayudar a mejorar las estrategias terapéuticas adaptadas al riesgo y contribuir a estratificar a los pacientes en el entorno clínico futuro de la inmunoterapia para los pacientes con cáncer de esófago.


Subject(s)
Esophageal Neoplasms/surgery , Lymphocytes/immunology , Programmed Cell Death 1 Receptor/metabolism , Aged , Esophageal Neoplasms/immunology , Esophageal Neoplasms/mortality , Female , Humans , Lymphocyte Count , Lymphocytes/metabolism , Male , Prognosis , Retrospective Studies , Survival Analysis
4.
Sci Rep ; 9(1): 1252, 2019 02 04.
Article in English | MEDLINE | ID: mdl-30718745

ABSTRACT

Root caries is an increasingly problem in aging societies with severe implications for the general health and wellbeing of large numbers of people. Strengthening type-I collagen, a major organic component of human dentin, has proved effective in preventing root caries. This study sought to determine whether exposure to riboflavin followed by UVA irradiation (RF/UVA) could promote additional collagen crosslinking, and thus improve the acid and enzymatic resistance of human dentin under simulated oral environments. If so, it could offer potential for treatment of the intractable problem of root caries. The greatest flexural strengths were found in dentin exposed to a 0.1% riboflavin solution for 1 minute followed by 1,600 mW/cm2 UVA irradiation for 10 minutes. Mineral loss and lesion depth were significantly lower in the RF/UVA group than in the control group. The microstructures of dentinal tubules and collagen networks after RF/UVA treatment retained their original forms after acidic and enzymatic degradation. In conclusion, RF/UVA treatment may be a new method for preventing root caries with promising prospects for clinical application.


Subject(s)
Collagen/metabolism , Riboflavin/pharmacology , Root Caries/prevention & control , Vitamin B Complex/pharmacology , Dentin/metabolism , Humans , Root Caries/metabolism , Ultraviolet Rays , Ultraviolet Therapy
5.
Dis Esophagus ; 31(9)2018 Sep 01.
Article in English | MEDLINE | ID: mdl-29893796

ABSTRACT

Whereas smoking constitutes a significant risk factor for postesophagectomy morbidity, there is no reliable method to assess the smoking status of patients prior to the procedure. Since exhaled carbon monoxide (CO) is an indicator of recent smoking, this paper hypothesizes that this is a useful parameter in assessing current smoking status and may help predict morbidity following esophagectomy. Sixty-nine patients, who had undergone elective three-incision esophagectomy with two- or three-field lymphadenectomy for esophageal cancer, were prospectively studied between February 2015 and September 2017. At surgical admission, they were asked about their smoking history, their exhaled CO levels were evaluated, and they were grouped into three based on their CO levels. These were 0 parts per million (ppm), >0 and <7 ppm, and ≥7 ppm. Their postoperative morbidity was also assessed. Approximately 13.5% of the patients showed high levels of exhaled CO ≥ 7 ppm, despite preoperatively reporting smoking cessation for over a month. Morbidities of the Clavien-Dindo classification (CDc) ≥ II increased as exhaled CO levels increased and severe morbidity of CDc ≥ IIIb frequently was observed in patients with exhaled CO levels ≥7 ppm. The logistic regression analysis showed that exhaled CO level ≥7 ppm was an independent risk factor for severe postesophagectomy morbidity. Overall, the results of this study suggest that exhaled CO levels may be useful in estimating current smoking status and that it may also help give an estimation of the risk of postesophagectomy morbidity.


Subject(s)
Breath Tests/methods , Carbon Monoxide/analysis , Esophagectomy/adverse effects , Postoperative Complications/etiology , Preoperative Care/methods , Aged , Aged, 80 and over , Esophageal Neoplasms/surgery , Exhalation , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Risk Factors , Smoking/adverse effects
6.
Dis Esophagus ; 31(3)2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29579257

ABSTRACT

Weight loss after esophagectomy is common and is associated with unfavorable prognosis. However, the clinical features and surgical methods that influence postesophagectomy weight loss are not well characterized. This study aims to determine those features (especially the surgical methods) that may affect postoperative weight loss. We reviewed 221 esophageal cancer patients who had undergone esophagectomy at Kumamoto University Hospital (Kumamoto, Japan) between November 2012 and June 2015. Among these, we recruited 106 patients who had undergone transthoracic esophagectomy with gastric conduit reconstruction, had no cancer recurrence within 1 year, and no missing follow-up data. We tabulated the body weight changes and risk factors associated with weight loss exceeding 10% at 1-year postesophagectomy. The mean body weights at baseline and 1-year postsurgery were 60.3 kg (standard error (SE): 0.91) and 52.6 (SE: 0.91), respectively. One year postsurgery, the body weights had changed as follows: mean: -12.2%; median: -12.9%; standard deviation: 9.06; range: -36.1-18.56%; interquartile range: -10.5 to -14.0%. In the multivariate logistic regression analysis, the absence of pyloroplasty was the sole risk factor for more than 10% weight loss (OR: 3.22; 95% CI: 1.08-11.9; P = 0.036). Our data suggest that pyloroplasty with esophagectomy can overcome the post-surgical weight loss.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Gastroplasty/adverse effects , Postoperative Complications/etiology , Pylorus/surgery , Weight Loss , Aged , Body Weight , Esophageal Neoplasms/physiopathology , Esophagectomy/methods , Female , Gastroplasty/methods , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Retrospective Studies
7.
Dis Esophagus ; 31(6)2018 Jun 01.
Article in English | MEDLINE | ID: mdl-29444214

ABSTRACT

Evidence suggests that minimally invasive esophagectomy has several advantages with regard to short-term outcomes, compared to open esophagectomy in esophageal cancer patients. However, the impact of minimally invasive esophagectomy on long-term respiratory function remains unknown. The objective of this study is to assess the association between use of the minimally invasive esophagectomy and long-term respiratory dysfunction in esophageal cancer patients after esophagectomy. This retrospective single institution study using prospectively collected data included 87 consecutive esophageal cancer patients who had undergone esophagectomy. All patients underwent a respiratory function test before, and one year after esophagectomy. Logistic regression analysis was used to compute the hazard ratio for long-term respiratory dysfunction. Minimally invasive esophagectomies were performed in 53 patients, and open esophagectomies in 34 patients. The two groups showed no significant differences in terms of postoperative complications and postoperative course. Nor were any differences observed between the two groups in terms of volume capacity (L) and forced expiratory volume 1.0 (L) before esophagectomy (P > 0.34). However, one year after esophagectomy, the decreases in volume capacity and forced expiratory volume 1.0 were significantly less in the minimally invasive esophagectomy group than in the open esophagectomy group (P = 0.04 and P = 0.007, respectively). Multivariate analyses revealed that minimally invasive esophagectomy was an independent favorable factor for maintenance of forced expiratory volume 1.0 (hazard ratio = 0.17, 95% confidence interval 0.04-0.71; P = 0.01). Minimally invasive esophagectomy may be an independent favorable factor for maintenance of long-term respiratory function in esophageal cancer patients after esophagectomy.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Postoperative Complications/etiology , Respiration Disorders/etiology , Aged , Esophageal Neoplasms/physiopathology , Esophagectomy/methods , Female , Humans , Lung/physiopathology , Male , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Minimally Invasive Surgical Procedures/methods , Multivariate Analysis , Postoperative Period , Proportional Hazards Models , Prospective Studies , Retrospective Studies , Time , Treatment Outcome
8.
Sci Rep ; 7(1): 13450, 2017 10 18.
Article in English | MEDLINE | ID: mdl-29044178

ABSTRACT

The progress of caries has conventionally been evaluated by checking changes in mineral density using transverse microradiography (TMR). Recent advances have seen development of a new measurement system, using in-air micro proton induced X-ray/gamma-ray emission (PIXE/PIGE). PIXE/PIGE enables analysis of distributions and concentrations of multiple mineral elements in a carious lesion. The aim of this study was to evaluate the effectiveness of PIXE/PIGE for investigating the development of root caries. In summary, we successfully established a multi-elemental sequential measuring method using in-air micro-PIXE/PIGE to identify the dynamic distributions and concentrations of Ca and F in human root dentin. The PIXE/PIGE potentially offers a useful advantageous technique for studying carious development by using as a combination with conventional techniques such as TMR and Micro-computed tomography (µCT).


Subject(s)
Calcium/analysis , Gamma Rays , Radiography, Dental , Root Caries/diagnostic imaging , X-Rays , Humans , Minerals , Radiography, Dental/methods , Root Caries/metabolism , Root Caries/pathology , Tooth Demineralization/diagnostic imaging , Tooth Demineralization/metabolism , Tooth Demineralization/pathology
9.
Dis Esophagus ; 30(12): 1-9, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-28881886

ABSTRACT

Pneumonia is a major cause of postesophagectomy mortality and worsens the long-term survival in resected esophageal cancer patients. Moreover, preoperative treatments such as chemotherapy or chemoradiotherapy (which have recently been applied worldwide) might affect the bacterial flora of the sputum. To investigate the association among preoperative treatments, the bacterial flora of sputum, and the clinical and pathological features in resected esophageal cancer patients, this study newly investigates the effect of preoperative treatments on the bacterial flora of sputum. We investigated the association among preoperative treatments, the bacterial flora of sputum, and clinical and pathological features in 163 resected esophageal cancer patients within a single institution. Pathogenic bacteria such as Candida (14.1%), Staphylococcus aureus (6.7%), Enterobacter cloacae (6.1%), Haemophilus parainfluenzae (4.9%), Klebisiella pneumoniae (3.7%), Methicillin-resistant Staphylococcus aureus (MRSA) (3.7%), Pseudomonas aeruginosa (2.5%), Escherichia coli (1.8%), Streptococcus pneumoniae (1.8%), and Haemophilus influenzae (1.2%) were found in the sputum. The pathogen detection rate in the present study was 34.3% (56/163). In patients with preoperative chemotherapy and chemoradiotherapy, the indigenous Neisseria and Streptococcus species were significantly decreased (P= 0.04 and P= 0.04). However, the detection rates of pathogenic bacteria were not associated with preoperative treatments (all P> 0.07). There was not a significant difference of hospital stay between the sputum-monitored patients and unmonitored patients (35.5 vs. 49.9 days; P= 0.08). Patients undergoing preoperative treatments exhibited a significant decrease of indigenous bacteria, indicating that the treatment altered the bacterial flora of their sputum. This finding needs to be confirmed in large-scale independent studies or well-designed multicenter studies.


Subject(s)
Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Microbiota/drug effects , Microbiota/radiation effects , Sputum/microbiology , Aged , Candida/isolation & purification , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Enterobacter cloacae/isolation & purification , Escherichia coli/isolation & purification , Esophagectomy , Female , Haemophilus influenzae/isolation & purification , Haemophilus parainfluenzae/isolation & purification , Humans , Klebsiella pneumoniae/isolation & purification , Length of Stay , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Neisseria/isolation & purification , Neoadjuvant Therapy , Preoperative Period , Pseudomonas aeruginosa/isolation & purification , Retrospective Studies , Streptococcus pneumoniae/isolation & purification
10.
Dis Esophagus ; 29(6): 627-33, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26123787

ABSTRACT

Recently, depletion of skeletal muscle mass (sarcopenia) has been linked to poor prognosis in several types of cancers, but has not been investigated in esophageal squamous cell carcinoma (ESCC). This retrospective study investigates the relationship between sarcopenia and clinical outcome in ESCC patients treated by surgical resection or definitive chemoradiation therapy (dCRT). The study was retrospectively conducted in a single academic hospital in Kumamoto, Japan, and involved 325 ESCC patients (256 surgical cases and 69 dCRT cases) treated between April 2005 and April 2011. Skeletal muscle mass was quantified by radiologic measures using standard computed tomography scans. The skeletal muscle tissue in the 325 ESCC patients was distributed as follows: mean: 47.10; median: 46.88; standard deviation (SD): 7.39; range: 31.48-71.11; interquartile range, 46.29-47.90. Skeletal muscle tissue was greater in male patients than in female patients (P < 0.0001), but was independent of other clinical and tumor features. Sarcopenia was not significantly associated with overall survival (log rank P = 0.54). Lymph node involvement significantly altered the relationship between sarcopenia and survival rate (P for interaction = 0.026). Sarcopenia significantly reduced the overall survival of patients without lymph node involvement (log rank P = 0.035), but was uncorrelated with overall survival in patients with lymph involvement (log rank, P = 0.31). The anastomosis leakage rate was significantly higher in the sarcopenia group than in the non-sarcopenia group (P = 0.032), but other surgical complications did not significantly differ between the two groups. Sarcopenia in ESCC patients without lymph node involvement is associated with poor prognosis, indicating sarcopenia as a potential biomarker for identifying patients likely to experience an inferior outcome. Moreover, sarcopenia was associated with anastomosis leakage but no other short-term surgical outcome.


Subject(s)
Anastomotic Leak/epidemiology , Carcinoma, Squamous Cell/mortality , Chemoradiotherapy , Esophageal Neoplasms/mortality , Esophagectomy , Sarcopenia/epidemiology , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma , Female , Humans , Japan/epidemiology , Lymph Nodes/pathology , Male , Middle Aged , Muscle, Skeletal/diagnostic imaging , Neoplasm Staging , Postoperative Complications/epidemiology , Prognosis , Retrospective Studies , Survival Rate , Tomography, X-Ray Computed
11.
Br J Cancer ; 113(2): 252-8, 2015 Jul 14.
Article in English | MEDLINE | ID: mdl-26125451

ABSTRACT

BACKGROUND: The inactivation of the Hippo pathway lead to TAZ (PDZ-binding motif)/YAP (yes-associated protein) overexpression, and is associated with worse prognostic outcomes in various cancers including hepatocellular carcinoma (HCC). Although there are several reports of microRNA (miR) targeting for YAP, miR targeting for TAZ remains unclear. The aim of this study is to identify the miR targeting TAZ expression in HCC. METHODS: MicroRNA expression was analysed using the Human miFinder 384HC miScript miR PCR array, and was compared between low and high TAZ expression cell lines. Then, we extracted miR-9-3p as a tumour-suppressor miR targeting TAZ. We examined the functional role of miR-9-3p using miR-9-3p mimic and inhibitor in HCC cell lines). RESULTS: In HCC cell lines and HCC clinical samples, there was the inverse correlation between miR-9-3p and TAZ expressions. TAZ expression was induced by treatment of miR-9-3p inhibitor and was downregulated by treatment of miR-9-3p mimic. Treatment of miR-9-3p mimic inhibited cell proliferative ability with downregulated phosphorylations of Erk1/2, AKT, and ß-catenin in HLF. Inversely, treatment of miR-9-3p inhibitor accelerated cell growth compared with control in HuH1. CONCLUSIONS: MicroRNA-9-3p was identified as the tumour-suppressor miR targetting TAZ expression in HCC cells.


Subject(s)
Carcinoma, Hepatocellular/pathology , Genes, Tumor Suppressor/physiology , Intracellular Signaling Peptides and Proteins/genetics , Liver Neoplasms/pathology , MicroRNAs/physiology , Cell Line, Tumor , Cell Proliferation , Humans , MAP Kinase Signaling System , MicroRNAs/antagonists & inhibitors , Neoplasm Invasiveness , Proto-Oncogene Proteins c-akt/physiology , Trans-Activators , Transcription Factors , Transcriptional Coactivator with PDZ-Binding Motif Proteins , beta Catenin/physiology
12.
Lupus ; 23(4): 342-52, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24474704

ABSTRACT

OBJECTIVE: A glycosylated transmembrane protein, CD147, has been implicated in regulating lymphocyte responsiveness and leukocyte recruitment. As lupus nephritis (LN) often follows a relapsing-remitting disease course, accurate understanding of the disease activity would be extremely helpful in improving prognosis. Unfortunately, neither clinical nor serological data can accurately reflect the histological features of LN. The present study investigated whether CD147 can accurately predict pathological features of LN. METHODS: Plasma and spot urine samples were collected from 64 patients who underwent renal biopsy between 2008 and 2011. Disease activity for LN tissues was evaluated using the biopsy activity index, and compared to levels of biomarkers including CD147. RESULTS: In LN tissues, CD147 induction was striking in injured glomeruli and infiltrating inflammatory cells, but not in damaged tubules representing atrophy. Plasma CD147 levels accurately reflected the histological disease activity. However, prediction using a single molecule would be quite difficult because of the complex pathogenesis of LN. The diagnostic accuracy of multiplex parameters indicated that the combination including plasma CD147 might yield excellent diagnostic abilities for guiding ideal LN therapy. CONCLUSION: Plasma CD147 levels might offer useful insights into disease activity as a crucial biomarker in patients with LN.


Subject(s)
Basigin/blood , Lupus Nephritis/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Case-Control Studies , Female , Humans , Lupus Nephritis/blood , Lupus Nephritis/diagnosis , Male , Middle Aged , Prognosis , Young Adult
13.
Dis Esophagus ; 27(1): 36-41, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23384275

ABSTRACT

Radiofrequency ablation (RFA) is increasingly being used for the treatment of intrathoracic malignancies. Although RFA has been found to be promising in the treatment of lung metastases from some types of neoplasms, little is known concerning its clinical significance in the treatment of pulmonary metastasis from esophageal squamous cell carcinoma (ESCC). This retrospective study evaluated the feasibility, safety, and effectiveness of computed tomography-guided RFA for pulmonary metastasis from ESCC. A series of 10 ESCC patients with 17 pulmonary tumors were included. Correct placement of the ablation device into the target tumor proved to be feasible in all tumors (100%). The mean visual analog scale score, with values that ranged from 0 (no pain) to 10 (worst pain possible), was 1. This suggested that this procedure was well tolerated. No procedure-related deaths occurred. A pneumothorax needing drainage was a major complication in two patients. Local control of ablated tumor lasting for at least 1 year was achieved in 10 (83%) of 12 assessable tumors. Although locoregional recurrences developed in two tumors, these lesions could be recontrolled by repeat treatment with RFA. Three patients died of recurrent disease. The predicted 1- and 2-year overall survival rates after lung RFA were 77.8% and 62.2%, respectively. Percutaneous computed tomography-guided RFA yielded relatively high levels of local control in patients with pulmonary metastases from ESCC and was associated with an acceptable level of complications. It was concluded that a prospective study will be necessary to evaluate the effectiveness of a combination of systemic therapy and RFA for ESCC lung metastases.


Subject(s)
Carcinoma, Squamous Cell/surgery , Catheter Ablation/methods , Esophageal Neoplasms/pathology , Lung Neoplasms/surgery , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/secondary , Cohort Studies , Esophageal Neoplasms/surgery , Esophagectomy , Feasibility Studies , Humans , Lung Neoplasms/secondary , Male , Middle Aged , Retrospective Studies , Surgery, Computer-Assisted , Tomography, X-Ray Computed , Treatment Outcome
14.
Dis Esophagus ; 27(3): 255-61, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23672461

ABSTRACT

Reconstruction following pharyngolaryngectomy with total esophagectomy is a challenging surgery to perform. Between April 2008 and August 2012, three types of modified gastric pull-up reconstruction procedures, including a gastric tube creation combined with a free jejunal transfer (n = 7), elongated gastric tube creation with vascular anastomoses (n = 2) and pedunculated gastric tube creation with Roux-en-Y anastomosis (n = 5), were performed after pharyngolaryngectomy with total esophagectomy. To clarify feasibility of these reconstructive methods, we retrospectively analyzed the short-term outcomes. There were no graft failures. Salivary fistulae were observed in two cases after high pharyngoenteral anastomoses due to oropharyngeal extension of hypopharyngeal cancers. Overall morbidity rate was 21.4%, and no deaths occurred. Although the operation time was shortest for pedunculated gastric tube reconstructions, morbidity rates were similar among all methods. All three types of modified gastric pull-up reconstruction procedures can be performed safely. We can choose one of these methods according to the tumor status and the patient condition, understanding advantages and disadvantages of each procedure.


Subject(s)
Carcinoma/surgery , Esophageal Neoplasms/surgery , Esophagoplasty/methods , Hypopharyngeal Neoplasms/surgery , Jejunum/transplantation , Laryngoplasty/methods , Neoplasms, Multiple Primary/surgery , Pharynx/surgery , Salivary Gland Fistula/etiology , Stomach/surgery , Aged , Anastomosis, Roux-en-Y/adverse effects , Esophagectomy/adverse effects , Esophagoplasty/adverse effects , Graft Survival , Humans , Hypopharyngeal Neoplasms/complications , Laryngectomy/adverse effects , Laryngoplasty/adverse effects , Male , Middle Aged , Operative Time , Pharyngectomy/adverse effects , Retrospective Studies , Time Factors
15.
Dis Esophagus ; 27(4): 374-9, 2014.
Article in English | MEDLINE | ID: mdl-23927456

ABSTRACT

A limited number of patients with resectable advanced esophageal cancer can be cured by surgery alone. Although a regimen that consists of docetaxel, cisplatin, and 5-fluorouracil (DCF) is a potential preoperative chemotherapy (PCT) option for squamous cell carcinoma of the esophagus, the influence of DCF on subsequent esophagectomies remains unclear. A total of 80 patients who received preoperative DCF chemotherapy, and 174 patients who did not receive any preoperative treatment were retrospectively analyzed. There were no treatment-related deaths. No delays in surgery due to adverse events related to DCF were reported. Although patients who received PCT had significantly more advanced cancers and worse preoperative conditions, the incidence rates of complications did not increase. Although the frequency of severe complications was significantly higher in patients who received PCT, this treatment was not an independent factor for the occurrence of severe complications. PCT with DCF did not negatively affect subsequent esophagectomies with regard to the frequency of complications.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Esophageal Neoplasms/therapy , Esophagectomy , Postoperative Complications/epidemiology , Aged , Cisplatin/administration & dosage , Docetaxel , Esophageal Squamous Cell Carcinoma , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Taxoids/administration & dosage , Treatment Outcome
16.
Br J Cancer ; 110(4): 958-66, 2014 Feb 18.
Article in English | MEDLINE | ID: mdl-24300972

ABSTRACT

BACKGROUND: Circulating tumour cells (CTCs) have an important role in metastatic processes, but details of their basic characteristics remain elusive. We hypothesised that CD44-expressing CTCs show a mesenchymal phenotype and high potential for survival in hepatocellular carcinoma (HCC). METHODS: Circulating CD44(+)CD90(+) cells, previously shown to be tumour-initiating cells, were sorted from human blood and their genetic characteristics were compared with those of tumour cells from primary tissues. The mechanism underlying the high survival potential of CD44-expressing cells in the circulatory system was investigated in vitro. RESULTS: CD44(+)CD90(+) cells in the blood acquired epithelial-mesenchymal transition, and CD44 expression remarkably increased from the tissue to the blood. In Li7 and HLE cells, the CD44(high) population showed higher anoikis resistance and sphere-forming ability than did the CD44(low) population. This difference was found to be attributed to the upregulation of Twist1 and Akt signal in the CD44(high) population. Twist1 knockdown showed remarkable reduction in anoikis resistance, sphere formation, and Akt signal in HLE cells. In addition, mesenchymal markers and CD44s expression were downregulated in the Twist1 knockdown. CONCLUSIONS: CD44s symbolises the acquisition of a mesenchymal phenotype regulating anchorage-independent capacity. CD44s-expressing tumour cells in peripheral blood are clinically important therapeutic targets in HCC.


Subject(s)
Carcinoma, Hepatocellular/pathology , Hyaluronan Receptors/metabolism , Liver Neoplasms/pathology , Neoplastic Cells, Circulating/pathology , Nuclear Proteins/genetics , Twist-Related Protein 1/genetics , Anoikis/genetics , Apoptosis , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Movement , Cell Survival , Down-Regulation , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Humans , Hyaluronan Receptors/genetics , Liver Neoplasms/metabolism , Mesoderm/cytology , Nuclear Proteins/biosynthesis , Proto-Oncogene Proteins c-akt/biosynthesis , RNA Interference , RNA, Small Interfering , Thy-1 Antigens/metabolism , Twist-Related Protein 1/biosynthesis
17.
Br J Cancer ; 109(11): 2829-32, 2013 Nov 26.
Article in English | MEDLINE | ID: mdl-24201755

ABSTRACT

BACKGROUND: The clinical significance of circulating tumour cell (CTC) detection in gastrointestinal (GI) cancer remains controversial and the molecular biological characteristics of CTCs are poorly understood. METHODS: A total of 87 patients with metastatic or recurrent GI cancer were prospectively enrolled. Circulating tumour cells and their HER2 status were assessed using the CellSearch System. RESULTS: Among the 62 CTC-positive cases, we found 22 discordant cases (35.5%). Among the HER2-negative primary tumours, 17 of 54 developed HER2-positive CTCs. Five of eight had HER2-negative CTCs among the HER2-positive primary tumours. CONCLUSION: The findings in the current study suggest that it is critical to evaluate the HER2 status of not only the primary tumour but also the CTCs because the metastasising tumour cells are the primary target of systemic therapy.


Subject(s)
Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Neoplastic Cells, Circulating/metabolism , Receptor, ErbB-2/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Female , Gastrointestinal Neoplasms/epidemiology , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplastic Cells, Circulating/pathology , Recurrence
18.
Br J Cancer ; 109(2): 408-15, 2013 Jul 23.
Article in English | MEDLINE | ID: mdl-23764749

ABSTRACT

BACKGROUND: LINE-1 methylation level is a surrogate marker of global DNA methylation. LINE-1 methylation in primary colorectal cancers (CRCs) is highly variable and strongly associated with a poor prognosis. However, no study has examined LINE-1 methylation levels of metastatic CRCs in relation to prognosis or assessed the heterogeneity of LINE-1 methylation level within the primary CRCs. METHODS: Pyrosequencing was used to quantify LINE-1 methylation level in 42 liver metastases, 26 matched primary tumours, and 6 matched lymph node (LN) metastases. KRAS, BRAF, and PIK3CA mutation status and microsatellite instability (MSI) status were also examined. RESULTS: The distribution of LINE-1 methylation level in liver metastases was as follows: mean, 67.3; range, 37.1-90.1. Primary tumours showed LINE-1 methylation levels similar to those of matched liver and LN metastases. The difference in LINE-1 methylation level between superficial areas and invasive front areas was within 7.0 in all six cases evaluated. Prognostic impact of LINE-1 hypomethylation in liver metastases on overall survival was not observed. The concordance rate was 94% for KRAS, 100% for BRAF, 88% for PIK3CA, and 97% for MSI. CONCLUSION: Alteration of LINE-1 methylation level may occur in early CRC tumorigenesis, and the LINE-1 methylation level is relatively stable during CRC progression.


Subject(s)
Colorectal Neoplasms/pathology , DNA Methylation , Liver Neoplasms/secondary , Long Interspersed Nucleotide Elements/genetics , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Lymphatic Metastasis , Male , Matched-Pair Analysis , Middle Aged , Models, Biological
19.
Br J Cancer ; 107(8): 1233-8, 2012 Oct 09.
Article in English | MEDLINE | ID: mdl-22955852

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy - often using docetaxel in various combinatorial regimens - is a standard treatment choice for advanced oesophageal squamous cell carcinoma (ESCC) in Japan. However, no useful markers exist that predict docetaxel's effects on ESCC. Ribophorin II (RPN2) silencing, which reduces glycosylation of P-glycoproteins and decreases membrane localisation, promotes docetaxel-dependent apoptosis. We investigated whether RPN2 expression in ESCC biopsy specimens could be a predictive biomarker in docetaxel-based neoadjuvant chemotherapy. METHODS: We evaluated RPN2 expression immunohistochemically in biopsy specimens from 79 patients with node-positive ESCC, who received docetaxel-based adjuvant chemotherapy, and compared clinical and pathological responses between the RPN2-positive and RPN2-negative groups. We also studied susceptibility of RPN2-suppressed ESCC cells to docetaxel. RESULTS: The RPN2-negative group had better clinical and pathological responses to docetaxel than the RPN2-positive group. We also found RPN2 suppression to alter docetaxel susceptibility in vitro. CONCLUSION: Expression of RPN2 in biopsy specimens could be a useful predictive marker for response to docetaxel-based neoadjuvant chemotherapy in ESCC.


Subject(s)
Antineoplastic Agents/administration & dosage , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Esophageal Neoplasms/genetics , Proteasome Endopeptidase Complex/genetics , Taxoids/administration & dosage , Aged , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/surgery , Docetaxel , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Female , Hexosyltransferases , Humans , Male , Neoadjuvant Therapy
20.
Int Angiol ; 21(3): 228-32, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12384642

ABSTRACT

BACKGROUND: Arterial reconstructions for ischemia in patients with Buerger's disease are technically challenging. This retrospective review was conducted to identify the critical factor for a successful outcome in bypass surgery for Buerger's disease. DESIGN OF STUDY: retrospective review. SETTING: University hospital, hospitalized patients. PATIENTS: since 1993, we performed 10 arterial reconstructions in 8 patients with Buerger's disease. There were 8 tibial artery bypasses and 2 collateral artery bypasses. One bypass was performed in the upper extremity. INTERVENTIONS: bypass surgery with autogenous vein graft. MAIN OUTCOMES MEASUREMENTS: graft patency. RESULTS: Over a mean follow-up period of 41.8 months, there were 3 graft occlusions. Of these, 2 were of bypasses to a patent but diseased tibial artery. One graft was occluded due to a toe stenosis which had been previously detected. The 2 collateral artery bypasses were patent at the last follow-up. CONCLUSIONS: In Buerger's disease, distal arterial reconstruction is frequently necessary to prevent ischemic limb loss. Collateral artery bypass is an option when the main arteries are affected by the disease. A patent but diseased artery should be avoided as a target for reconstruction.


Subject(s)
Arm/blood supply , Arm/surgery , Collateral Circulation/physiology , Ischemia/etiology , Ischemia/surgery , Leg/blood supply , Leg/surgery , Plastic Surgery Procedures , Thromboangiitis Obliterans/complications , Thromboangiitis Obliterans/surgery , Vascular Surgical Procedures , Adult , Arm/physiopathology , Female , Humans , Ischemia/physiopathology , Leg/physiopathology , Male , Middle Aged , Outcome Assessment, Health Care , Retrospective Studies , Thromboangiitis Obliterans/physiopathology , Tibial Arteries/physiopathology , Tibial Arteries/surgery
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