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1.
Int J Oral Maxillofac Surg ; 52(6): 621-629, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36470693

ABSTRACT

The aim of this study was to assess changes in the quality of life and psychological distress of patients with tongue cancer undergoing total/subtotal glossectomy (TG) or extended hemiglossectomy (HG) and free flap transfer. Differences between the two groups were compared using the Short Form 8-Item Health Survey (SF-8) and Hospital Anxiety and Depression Scale (HADS). Of the 43 patients with tongue cancer, 24 (56%) underwent TG and 19 (44%) underwent HG. The general health and social functioning scores in the SF-8 and depression in the HADS were significantly worse in the TG group than in the HG group at 12 months after surgery, indicating that patients in the TG group may experience social isolation and psychological distress, and have difficulty in employability even 12 months after surgery. In contrast, all items of the SF-8 in the HG group were nearly equal to those in the general population. Due to the extensive psychological impact on patients with tongue cancer who are planned for an extended resection, curative surgery with free flap transfer and multidisciplinary psychiatric support are essential to improve quality of life and manage psychological distress.


Subject(s)
Free Tissue Flaps , Plastic Surgery Procedures , Psychological Distress , Tongue Neoplasms , Humans , Glossectomy , Tongue Neoplasms/surgery , Quality of Life , Forearm , Tongue/surgery
2.
J Dairy Sci ; 106(1): 576-588, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36424322

ABSTRACT

Bovine leukemia virus (BLV), which causes enzootic bovine leukosis and immunosuppression, is widely prevalent on Japanese dairy farms. However, in the absence of a national eradication scheme with compensation programs, it is important to estimate BLV-associated economic losses to raise farmers' awareness. Mastitis (includes both clinical and subclinical) is a common disease in the dairy industry and the most common reason for culling. We hypothesized that immunosuppression due to BLV predisposes subclinical mastitis. A retrospective cohort study was conducted to trace Holstein cows at 9 commercial dairy farms in the Nemuro and Kushiro regions of Hokkaido Prefecture, Japan, where monitoring of BLV proviral load is routine. Information regarding Dairy Herd Improvement data, parity number, and delivery day was collected at each farm. Cows with no confirmed infection with BLV during lactation were defined as non-infected. Low-proviral-load and high-proviral-load (H-PVL) cows were defined as those in which proviral load was below and over 2,465 copies/50 ng of DNA, respectively, or 56,765 copies/105 cells, respectively, throughout the lactation period. Survival analysis was performed using the frailty model to estimate the hazard ratio of subclinical mastitis for BLV infection status using data from 1,034 dairy cows after adjusting for parity number and delivery season as confounding factors. Kaplan-Meier survivor curves demonstrated that half of the H-PVL cows developed subclinical mastitis within 52 d after calving. The hazard ratio of subclinical mastitis for H-PVL cows was 2.61 times higher than that of non-infected cows. In 2017, there were 264,443 clinical mastitis cases in Hokkaido. Using field and published data, annual economic losses were estimated using Monte Carlo simulation. The economic loss due to mastitis associated with BLV infection per H-PVL cow was $418.59 (¥43,952), with the annual economic loss in Hokkaido Prefecture due to mastitis caused by BLV infection estimated at $6,097,225 (¥640,208,633). In summary, H-PVL cows were more susceptible to subclinical mastitis than non-infected and low-proviral-load cows, and mastitis due to BLV infection was projected to cause significant economic losses.


Subject(s)
Cattle Diseases , Enzootic Bovine Leukosis , Leukemia Virus, Bovine , Mastitis, Bovine , Pregnancy , Animals , Cattle , Female , Retrospective Studies , Proviruses
3.
Front Aging ; 3: 817371, 2022.
Article in English | MEDLINE | ID: mdl-35821858

ABSTRACT

Context: Good health and longevity depend on dynamic interactions between biological, social, psychological, and environmental factors. Aging is globally a big challenge, particularly with the demographic transition, including population growth, and an emerging burden to society. Knowledge, behavior, diet, and consumption of animal source food were related to aging and emerged as the key factors modulating healthy aging. Objective: The study was designed to understand the main healthy aging factors, such as knowledge, social network, and diet of elders, and to derive mutual learning from it for healthy aging. Methods: A qualitative approach has been applied to explore health-related knowledge, attitude, and diet of elders from Ebetsu (Japan) and Tiassalé (Côte d'Ivoire) health districts, using focus group discussions and comparative context analysis between high- and low-income countries. Results: The study shows that living longer is a common feature of people in Japan compared to Côte d'Ivoire, where the life expectancy is still low. Both groups of elders have social networks that support them, and both offer their gained experience to society. While Japanese elders depend on pension and insurance for income and medical treatments, Ivorians depend mostly on their children and social network in old age. The worries of elders differ between the two regions. In Ebetsu, elder members of the community are concerned about the future burden they pose for the younger generation if they develop ill-health, making them more resilient to aging. In Taabo, elders are considered to be culturally and socially useful to the society. Elders in Ebetsu pointed out that for healthy aging, education on diet at a younger age, physical activities, and access to basic social services are the key aspects. This was not observed in Taabo's context. Being inactive and dependent on others were described as the most worrying situations for elders in Ebetsu, as it is perceived to increase the risk of non-communicable diseases and anxiety. Elders in Ebetsu have good knowledge on what constitutes a healthy diet, and they believe that diversifying their diet, reducing portions, and substituting red meat with good animal and vegetable proteins are best eating practices to maintain good health. In Côte d'Ivoire, the diet is imbalanced and the whole family consumes the same meal made mainly with high-energy staples and little protein. However, it is observed in both societies that adopting a good diet is very expensive. Conclusion: The consciousness of aging is universal, but healthy aging varies according to the social systems, education, and knowledge on diet transition. Physical activities, protein-energy balance in diet, and social networks are the key for healthy aging in both contexts. The challenge is to find ways to increase knowledge regarding healthy aging and to strengthen the support system so that healthy aging becomes affordable.

4.
Int J Oral Maxillofac Surg ; 50(3): 316-322, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32826125

ABSTRACT

In the head and neck region, preoperative evaluation of the free flap volume is challenging. The current study validated preoperative three-dimensional (3D) virtual surgical simulation for soft tissue reconstruction by assessing flap volume and evaluated fat and muscle volume changes at follow-up in 13 head and neck cancer patients undergoing anterolateral craniofacial resection. Patients received 3D virtual surgical simulation, and the volume of the planned defects was estimated by surgical simulation. Following en bloc resection of the tumor, the defect in the skull base was covered using a rectus abdominis myocutaneous flap. Following surgery, computed tomography scans were acquired at day 1 and at 6 and 12 months. Virtual planned defect was on average 227 ml (range, 154-315) and was 10% smaller than the actual flap volume in patients without skin involvement of the tumor. Between day 1 and 12 months post-surgery, the volume of fat and muscle tissue in the free flap dropped by 9% and 58%, respectively. Our results indicate that 3D virtual surgical simulation provides essential information in determining the accurate volume of the required free flap for surgical defect repair and may thus help improve surgical planning and functional and esthetic outcome.


Subject(s)
Free Tissue Flaps , Head and Neck Neoplasms , Myocutaneous Flap , Plastic Surgery Procedures , Esthetics, Dental , Feasibility Studies , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/surgery , Humans
5.
Biotech Histochem ; 95(1): 1-7, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31423857

ABSTRACT

Fluorescence-activated cell sorting (FACS) is a powerful tool for analyzing stem cells. When using fixed cells, however, it is sometimes difficult to analyze RNA extracted from sorted cells due to RNA degradation. We established a protocol for immunocytochemistry before FACS to prevent RNA degradation. Cells were fixed with a methanol-based fixative (UM-Fix), then subjected to immunocytochemistry. The addition of RNase inhibitor and dithiothreitol (DTT) to some buffers used for immunocytochemistry increased RNA integrity after cell recovery. We found increased copy numbers of mRNA in recovered cells using quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. When RNase inhibitor and DTT were added, amplification of mRNA using T7 promoter was possible with RNA extracted from recovered cells after FACS. Our protocol ensures high quality RNA in cells recovered by FACS; therefore, gene expression analysis with a smaller number of cells is possible using pre-amplification of mRNAs. Our protocol for immunocytochemistry also might be applicable to RNA recovery after immunostaining.


Subject(s)
Cadherins/metabolism , Flow Cytometry/methods , Immunohistochemistry/methods , RNA/chemistry , Thyroid Nuclear Factor 1/metabolism , Animals , Cell Line , Dithiothreitol/metabolism , Fixatives , Humans , RNA Stability , Rats , Thyroglobulin/metabolism
6.
Sci Rep ; 9(1): 10155, 2019 Jul 12.
Article in English | MEDLINE | ID: mdl-31300690

ABSTRACT

Water, methane, and ammonia are commonly considered to be the key components of the interiors of Uranus and Neptune. Modelling the planets' internal structure, evolution, and dynamo heavily relies on the properties of the complex mixtures with uncertain exact composition in their deep interiors. Therefore, characterising icy mixtures with varying composition at planetary conditions of several hundred gigapascal and a few thousand Kelvin is crucial to improve our understanding of the ice giants. In this work, pure water, a water-ethanol mixture, and a water-ethanol-ammonia "synthetic planetary mixture" (SPM) have been compressed through laser-driven decaying shocks along their principal Hugoniot curves up to 270, 280, and 260 GPa, respectively. Measured temperatures spanned from 4000 to 25000 K, just above the coldest predicted adiabatic Uranus and Neptune profiles (3000-4000 K) but more similar to those predicted by more recent models including a thermal boundary layer (7000-14000 K). The experiments were performed at the GEKKO XII and LULI2000 laser facilities using standard optical diagnostics (Doppler velocimetry and optical pyrometry) to measure the thermodynamic state and the shock-front reflectivity at two different wavelengths. The results show that water and the mixtures undergo a similar compression path under single shock loading in agreement with Density Functional Theory Molecular Dynamics (DFT-MD) calculations using the Linear Mixing Approximation (LMA). On the contrary, their shock-front reflectivities behave differently by what concerns both the onset pressures and the saturation values, with possible impact on planetary dynamos.

7.
Osteoarthritis Cartilage ; 26(10): 1263-1273, 2018 10.
Article in English | MEDLINE | ID: mdl-29890262

ABSTRACT

Osteoarthritis (OA) is a potentially disabling disease whose progression is dependent on several risk factors. OA management usually involves the use of non-steroidal anti-inflammatory drugs (NSAIDs) that are the primary pharmacological treatments of choice. However, NSAIDs have often been associated with unwanted side effects. Cyclooxygenase (COX)-2 specific inhibitors, such as celecoxib, have been successfully used as an alternative in the past for OA treatment and have demonstrated fewer side effects. While abundant data are available for the clinical efficacy of drugs used for OA treatment, little is known about the disease-modifying effects of these agents. A previous review published by Zweers et al. (2010) assessed the available literature between 1990 and 2010 on the disease-modifying effects of celecoxib. In the present review, we aimed to update the existing evidence and identify evolving concepts relating to the disease-modifying effects of not just celecoxib, but also other NSAIDs. We conducted a review of the literature published from 2010 to 2016 dealing with the effects, especially disease-modifying effects, of NSAIDs on cartilage, synovium, and bone in OA patients. Our results show that celecoxib was the most commonly used drug in papers that presented data on disease-modifying effects of NSAIDs. Further, these effects appeared to be mediated through the regulation of prostaglandins, cytokines, and direct changes to tissues. Additional studies should be carried out to assess the disease-modifying properties of NSAIDs in greater detail.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase 2 Inhibitors/therapeutic use , Osteoarthritis/drug therapy , Humans , Treatment Outcome
8.
BMC Cancer ; 17(1): 314, 2017 05 05.
Article in English | MEDLINE | ID: mdl-28476132

ABSTRACT

BACKGROUND: Recent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC). METHODS: Patients aged 20-75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee. RESULTS: From April 2014 to August 2015, 97 patients with HNC were enrolled, of whom 94 received treatment. The incidence of grade ≥ 3 oral mucositis was 29% and 25% in the rebamipide 2% and 4% groups, respectively, compared with 39% in the placebo group. The proportion of patients who did not develop grade ≥ 3 oral mucositis by day 50 of treatment was 57.9% in the placebo group, whereas the proportion was 68.0% in the rebamipide 2% group and 71.3% in the rebamipide 4% group. The incidences of adverse events potentially related to the study drug were 16%, 26%, and 13% in the placebo, rebamipide 2%, and rebamipide 4% groups, respectively. There was no significant difference in treatment compliance among the groups. CONCLUSIONS: The present phase II study suggests that mouth washing with rebamipide may be effective and safe for patients with HNC receiving chemoradiotherapy, and 4% liquid is the optimal dose of rebamipide. TRIAL REGISTRATION: ClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March 11, 2014).


Subject(s)
Alanine/analogs & derivatives , Chemoradiotherapy/adverse effects , Head and Neck Neoplasms/drug therapy , Quinolones/administration & dosage , Stomatitis/drug therapy , Adult , Aged , Alanine/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Female , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Stomatitis/chemically induced , Stomatitis/pathology
9.
Insect Mol Biol ; 26(3): 286-297, 2017 06.
Article in English | MEDLINE | ID: mdl-28121379

ABSTRACT

In this study, we identified ecdysteroidogenic enzymes in the cabbage armyworm, Mamestra brassicae, and demonstrated reduced expression of these genes during diapause. Some insects employ a temporary developmental arrest, diapause, to survive in severe environments. The titres of the moulting hormone ecdysteroid were reduced in diapause pupae of M. brassicae; therefore, ecdysteroidogenesis might be suppressed by a diapause-specific mechanism. To clarify expression changes of ecdysteroidogenic enzyme genes during diapause in M. brassicae, we first identified the genes for seven ecdysteroidogenic enzymes: Neverland, Non-molting glossy (Nm-g), CYP307A1 (Spook), CYP306A1 (Phantom), CYP302A1 (Disembodied), CYP315A1 (Shadow) and CYP314A1 (Shade). Enzymatic assays using heterologous expression in Drosophila Schneider 2 (S2) cells and analysis of mRNA distribution indicated that the identified genes were ecdysteroidogenic enzymes of M. brassicae. Expression levels of these ecdysteroidogenic enzyme genes were compared between prothoracic glands in different pupal stages throughout diapause. Immediately after pupation, diapause-destined pupae showed similar expression levels of ecdysteroidogenic enzyme genes to those of nondiapause pupae. All of these genes showed reduced gene expression after diapause initiation. Expression was immediately increased in diapause-destined pupae at the postdiapause quiescence phase. These results indicate that reduced expression of ecdysteroidogenic enzyme genes suppresses ecdysteroidogenesis and maintains developmental arrest during diapause.


Subject(s)
Diapause, Insect , Ecdysteroids/biosynthesis , Moths/enzymology , Animals , Cell Line , Female , Gene Expression , Male , Moths/genetics , Pupa/enzymology
10.
J Laryngol Otol ; 130(10): 914-922, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27604559

ABSTRACT

OBJECTIVES: To verify the effectiveness and safety of the addition of adipose-derived regenerative cells to autologous fat injection therapy. METHODS: Unilateral vocal fold paralysis models were made by cutting the right recurrent laryngeal nerve in two pigs. At day 30, 0.5 ml adipose-derived regenerative cells mixed with 1 ml autologous fat was injected into the right vocal fold of one pig, with the other receiving 0.5 ml Ringer's solution mixed with 1 ml autologous fat. At day 120, fibrescopy, laser Doppler flowmeter, computed tomography, vocal function evaluation and histological assessment were conducted. RESULTS: Although histological assessment revealed atrophy of the thyroarytenoid muscle fibre in both pigs, there was remarkable hypertrophy of the thyroarytenoid muscle fibre in the area surrounding the adipose-derived regenerative cells injection site. CONCLUSION: The addition of a high concentration of adipose-derived regenerative cells to autologous fat injection therapy has the potential to improve the treatment outcome for unilateral vocal fold paralysis.


Subject(s)
Adipocytes/transplantation , Adipose Tissue/transplantation , Stem Cell Transplantation/methods , Vocal Cord Paralysis/therapy , Adipocytes/cytology , Adipose Tissue/cytology , Animals , Disease Models, Animal , Hypertrophy/etiology , Laryngeal Muscles/pathology , Larynx/pathology , Muscular Atrophy/etiology , Pilot Projects , Swine , Transplantation, Autologous , Treatment Outcome , Vocal Cords/pathology
11.
Br J Surg ; 103(12): 1608-1615, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27550722

ABSTRACT

BACKGROUND: The use of oral prophylactic antibiotics for the prevention of surgical-site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer is controversial. The aim of this RCT was to evaluate whether intravenous perioperative antibiotics are inferior to combined preoperative oral and perioperative intravenous antibiotics in this setting. METHODS: Patients undergoing elective laparoscopic colorectal resection in a single cancer centre were assigned randomly to combined preoperative oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group) or to perioperative intravenous antibiotics (cefmetazole) alone (IV-only group). Patients were stratified for the analyses based on type of operation (colonic surgery, anterior resection or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy and the presence of diabetes mellitus. The primary endpoint was the overall rate of SSI. Secondary endpoints were the rates of incisional site infection, organ/space infection, anastomotic leakage, intra-abdominal abscess, adverse events and postoperative complications. RESULTS: Of 540 patients offered participation in the trial in 2013-2014, 515 agreed to take part and were randomized. Some 256 patients in the IV-only group and 255 in the oral/IV group completed the treatment per protocol. The overall rate of SSI was 7·8 per cent (20 of 256) in the IV-only group and 7·8 per cent (20 of 255) in the oral/IV group, confirming that perioperative administration of intravenous antibiotics alone was not inferior to the combined regimen (P = 0·017). There were no differences in rates of incisional site infection (5·5 versus 5·9 per cent respectively), organ/space infection (2·3 versus 2·0 per cent) or other secondary endpoints between the two groups. CONCLUSION: Intravenous perioperative antimicrobial prophylaxis alone is not inferior to combined preoperative oral and intravenous perioperative prophylaxis with regard to SSI in patients with colorectal cancer undergoing elective laparoscopic resection. Registration number: UMIN000019339 ( http://www.umin.ac.jp/ctr/).


Subject(s)
Anti-Bacterial Agents/administration & dosage , Antibiotic Prophylaxis/methods , Colorectal Neoplasms/surgery , Laparoscopy/methods , Surgical Wound Infection/prevention & control , Administration, Oral , Adult , Aged , Aged, 80 and over , Anastomotic Leak/etiology , Cefmetazole/administration & dosage , Colectomy/methods , Drug Therapy, Combination , Female , Humans , Infusions, Intravenous , Intraoperative Care/methods , Kanamycin/administration & dosage , Laparoscopy/adverse effects , Male , Metronidazole/administration & dosage , Middle Aged , Postoperative Complications/etiology , Preoperative Care/methods
12.
Acta Virol ; 60(1): 41-8, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26982466

ABSTRACT

Cell entry of herpes simplex virus type 2 (HSV-2) requires the interaction of viral glycoprotein D (gD) with the receptor nectin-1 and herpesvirus entry mediator (HVEM). In addition, it is known that nectin-2 is also functional as a receptor for HSV-2, although the binding to the gD is weak. To examine an antiviral potential of a soluble form of human nectin-2 (hNectin-2Ig), transfected Vero cells expressing the entire ectodomain of nectin-2 fused to the Fc portion of human IgG were established. Specific binding of hNectin-2Ig to HSV-2 gD was confirmed by ELISA. Competitive ELISA demonstrated that accumulation of hNectin-2Ig in transfected cells increased significantly in a cell culture time dependent manner. Viral growth of several HSV-2 strains was significantly inhibited in the transfected cells that were cultured for 72 hr compared with control Vero cells, but not in cells that were cultured for 24 hr. These results indicate that accumulation of a soluble form of nectin-2 is required for exerting the resistance against HSV-2 infection.


Subject(s)
Cell Adhesion Molecules/immunology , Herpes Simplex/immunology , Herpesvirus 2, Human/physiology , Animals , Cell Adhesion Molecules/genetics , Chlorocebus aethiops , Herpes Simplex/genetics , Herpes Simplex/virology , Herpesvirus 2, Human/genetics , Herpesvirus 2, Human/growth & development , Humans , Nectins , Transfection , Vero Cells , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism
13.
AJNR Am J Neuroradiol ; 37(1): 44-50, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26381556

ABSTRACT

BACKGROUND AND PURPOSE: Noninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas. MATERIALS AND METHODS: Thirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival. RESULTS: Grade III gliomas showed significantly higher average tumor-to-normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C-methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor-to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 ± 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 ± 6.9 months in patients with maximum tumor-to-normal tissue ratio of >2.0 (P = .0044). CONCLUSIONS: (11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas.


Subject(s)
Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Neoplasm Grading/methods , Positron-Emission Tomography/methods , Aged , Brain Neoplasms/mortality , Carbon Radioisotopes , Disease-Free Survival , Female , Glioma/mortality , Humans , Male , Methionine , Middle Aged , Prognosis , Radiopharmaceuticals , Retrospective Studies , Young Adult
14.
Pharmacogenomics J ; 16(4): 312-9, 2016 08.
Article in English | MEDLINE | ID: mdl-26370619

ABSTRACT

The Hippo pathway regulates tissue growth and cell fate. In colon cancer, Hippo pathway deregulation promotes cellular quiescence and resistance to 5-Fluorouracil (5-Fu). In this study, 14 polymorphisms in 8 genes involved in the Hippo pathway (MST1, MST2, LATS1, LATS2, YAP, TAZ, FAT4 and RASSF1A) were evaluated as recurrence predictors in 194 patients with stages II/III colon cancer treated with 5-Fu-based adjuvant chemotherapy. Patients with a RASSF1A rs2236947 AA genotype had higher 3-year recurrence rate than patients with CA/CC genotypes (56 vs 33%, hazard ratio (HR): 1.87; P=0.017). Patients with TAZ rs3811715 CT or TT genotypes had lower 3-year recurrence rate than patients with a CC genotype (28 vs 40%; HR: 0.66; P=0.07). In left-sided tumors, this association was stronger (HR: 0.29; P=0.011) and a similar trend was found in an independent Japanese cohort. These promising results reveal polymorphisms in the Hippo pathway as biomarkers for stages II and III colon cancer.The Pharmacogenomics Journal advance online publication, 15 September 2015; doi:10.1038/tpj.2015.64.


Subject(s)
Biomarkers, Tumor/genetics , Colonic Neoplasms/genetics , Neoplasm Recurrence, Local , Polymorphism, Single Nucleotide , Signal Transduction/genetics , Transcription Factors/genetics , Tumor Suppressor Proteins/genetics , Acyltransferases , Aged , Antimetabolites, Antineoplastic/therapeutic use , California , Chemotherapy, Adjuvant , Colectomy , Colonic Neoplasms/pathology , Colonic Neoplasms/therapy , Female , Fluorouracil/therapeutic use , Genetic Association Studies , Genetic Predisposition to Disease , Heterozygote , Homozygote , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Phenotype , Proportional Hazards Models , Risk Factors , Time Factors , Tokyo , Treatment Outcome
15.
Dis Esophagus ; 29(6): 598-602, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26338205

ABSTRACT

Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.


Subject(s)
Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/therapy , Esophagectomy , Head and Neck Neoplasms/therapy , Laryngeal Neoplasms/therapy , Laryngectomy , Neoplasms, Multiple Primary/therapy , Pharyngeal Neoplasms/therapy , Pharyngectomy , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Cisplatin/administration & dosage , Esophageal Squamous Cell Carcinoma , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoadjuvant Therapy , Retrospective Studies , Salvage Therapy , Squamous Cell Carcinoma of Head and Neck , Treatment Outcome
16.
Clin Exp Immunol ; 184(1): 126-36, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26560892

ABSTRACT

Our previous work revealed that the recipients with the highest pre-existing numbers of CD8(+) effector T cells (TE ) [hyperparathyroidism (HPT)E recipients] occupied approximately 30% of adult transplant recipients performed in our hospital. HPTE recipients demonstrated very poor clinical outcome compared with the remaining 70% of recipients with the lowest pre-existing TE (LPTE recipient). This study aimed to clarify the best combined immunosuppressive regimen related to function of cytotoxic T lymphocytes (CTLs) for HPTE recipients. Eighty-one HPTE recipients were classified into three types, according to the immunosuppressive regimens: type 1, tacrolimus (Tac)/glucocorticoid (GC); type 2, Tac/mycophenolate mofetil (MMF)/GC; and type 3, Tac/MMF. Frequencies of severe infection, rejection and hospital death were the highest in types 1 and 2, whereas the lowest occurred in type 3. The survival rate in type 3 was the highest (100%) during follow-up until post-operative day 2000. Regarding the immunological mechanism, in type 1 TE perforin and interferon (IFN)-γ were generated through the self-renewal of CD8(+) central memory T cells (TCM ), but decreased in the early post-transplant period due to marked down-regulation of interleukin (IL)-12 receptor beta-1 of TCM. In type 2, the self-renewal TCM did not develop, and the effector function could not be increased. In type 3, in contrast, the effectors and cytotoxicity were correlated inversely with IL-12Rß1(+) TCM levels, and increased at the highest level around the pre-transplant levels of IL-12Rß1(+) TCM . However, the immunological advantage of Tac/MMF therapy was inhibited strongly by additive steroid administration.


Subject(s)
Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Liver Transplantation , Methylprednisolone/adverse effects , Mycophenolic Acid/analogs & derivatives , T-Lymphocytes, Cytotoxic/drug effects , Tacrolimus/therapeutic use , Aged , Female , Gene Expression , Graft Rejection/immunology , Graft Rejection/mortality , Graft Rejection/pathology , Graft Survival , Humans , Hyperparathyroidism/immunology , Hyperparathyroidism/mortality , Hyperparathyroidism/pathology , Hyperparathyroidism/surgery , Immunologic Memory , Interferon-gamma/genetics , Interferon-gamma/immunology , Living Donors , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Perforin/genetics , Perforin/immunology , Receptors, Interleukin-12/genetics , Receptors, Interleukin-12/immunology , Retrospective Studies , Survival Analysis , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/pathology , Unrelated Donors
17.
Colorectal Dis ; 17(10): O213-6, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26277783

ABSTRACT

AIM: The lateral pelvic lymph nodes are one of the major sites and sources of local recurrence (LR) after surgery for rectal cancer. Salvage lateral pelvic lymph node dissection (LPLD) is potentially curative, but the value of laparoscopic surgery in such cases is unknown. Our aim was to report the technical details of laparoscopic salvage LPLD for LR at these nodes after rectal cancer surgery. METHOD: The study was based on nine patients who underwent laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes after surgery for rectal cancer. The safety and feasibility of this procedure were determined. RESULTS: The median operation time was 381 min and the median estimated blood loss was 130 ml. There were no conversions. Adjacent structures removed en bloc were the pelvic plexus in four patients, the internal iliac artery in seven patients and the seminal vesicle in one patient. The median number of metastatic lymph nodes was 1 (range 1-11). CONCLUSION: Our novel technique of laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes is safe and feasible.


Subject(s)
Laparoscopy/methods , Lymph Node Excision/methods , Lymph Nodes/surgery , Neoplasm Recurrence, Local/surgery , Rectal Neoplasms/surgery , Salvage Therapy , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Lymph Nodes/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Pelvis , Rectal Neoplasms/pathology , Retrospective Studies , Risk Assessment , Survival Rate , Treatment Outcome
18.
Transpl Infect Dis ; 17(5): 671-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26201686

ABSTRACT

BACKGROUND: Herpes zoster (HZ) is the most common manifestation of latent varicella zoster virus reactivation, which occurs naturally as a result of aging or in immunocompromised patients. Solid organ transplant recipients are at increased risk for HZ owing to their chronic immunosuppression. Although several reports investigated risk factors for the development of HZ in heart or renal transplantation, data in liver transplantation (LT) are limited. METHODS: We evaluated clinical data retrospectively in 377 adult patients undergoing LT between January 2005 and December 2012 in our institution. We analyzed the incidence rate of HZ and the standardized incidence ratio (SIR) by comparing with the general Japanese population. We additionally investigated risk factors for HZ after LT. RESULTS: HZ developed in 27 (7.16%) of the 377 patients after LT. The incidence rate of HZ after LT was 17.83 per 1000 person-years, which was significantly higher than in the general Japanese population (SIR = 4.61; 95% confidence interval [CI], 4.13-5.14). Multivariate analysis showed that older age (hazard ratio [HR] = 3.95; P < 0.001) and exposure to mycophenolate mofetil (HR = 3.03; P = 0.007) were independent risk factors for HZ after LT. CONCLUSIONS: This is the first and largest study, to our knowledge, to investigate the incidence rate of HZ and risk factors for development of HZ after LT in the Japanese population. Further investigations to focus on immunosuppressive regimens to reduce the risk for HZ incidence in this high-risk population could establish a new protocol of immunosuppression after LT.


Subject(s)
Herpes Zoster/etiology , Immunocompromised Host , Liver Transplantation , Opportunistic Infections/etiology , Postoperative Complications/etiology , Adolescent , Adult , Aged , Female , Follow-Up Studies , Herpes Zoster/epidemiology , Herpes Zoster/immunology , Humans , Immunosuppression Therapy/adverse effects , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Opportunistic Infections/epidemiology , Opportunistic Infections/immunology , Postoperative Care/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/immunology , Proportional Hazards Models , Retrospective Studies , Risk Factors , Young Adult
19.
Transplant Proc ; 47(3): 804-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25891735

ABSTRACT

A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases.


Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Liver Failure/surgery , Liver Neoplasms/radiotherapy , Liver Transplantation , Living Donors , Neoplasm Recurrence, Local/radiotherapy , Salvage Therapy , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/surgery , Combined Modality Therapy , Humans , Liver Failure/etiology , Liver Neoplasms/complications , Liver Neoplasms/surgery , Liver Transplantation/methods , Male , Middle Aged , Neoplasm Recurrence, Local/complications , Neoplasm Recurrence, Local/surgery
20.
Clin Exp Immunol ; 181(2): 373-84, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25603847

ABSTRACT

This study aimed to investigate the role of initial priming of interleukin (IL)-12 receptor beta-1 in CD8(+) central memory T cells (initial IL-12RTCM priming) and CCR7-negative subsets (CNS) in effector cell expansion and clinical outcome after living donor liver transplantation (LDLT). One hundred and six patients who underwent LDLT were classified into the following three groups according to hierarchical clustering of CD8(+) CD45 isoforms before LDLT: I, naive-dominant; II, effector memory-dominant; and III, effector-dominant. The pre-existing CD8(+) effector cells (TE ) and activated immune status increased progressively from group I to group II to group III. Groups I, II and III received tacrolimus (Tac)/glucocorticoid (GC) regimens. Eighteen group III recipients received Tac/mycophenolate mofetil (MMF) and were defined as group IV. Initial IL-12RTCM priming was slightly, moderately and markedly decreased in droups I, II, and III, respectively. Initial priming of IL-12Rß1 in CNS was decreased markedly in the three groups with marked decreases of TE , perforin and interferon (IFN)-γ; all parameters were restored by up-regulation of IL-12Rß1(+) TCM through the self-renewal of TCM . The lag time required until coupled up-regulation of IL-12Rß1 of TCM and CNS to above baseline was 12, 20 and 32 days in groups I, II and III, respectively. Inferior clinical outcomes were associated with increasing lag time. In contrast, the initial priming of IL-12Rß1 in TCM and CNS remained above baseline in group IV due to MMF-mediated increase of IL-12Rß1. Early coupled up-regulation of TCM and CNS leads to efficient TE differentiation and optimal clinical outcomes.


Subject(s)
CD8 Antigens/immunology , Immunosuppressive Agents/therapeutic use , Liver Transplantation , Receptors, Interleukin-12/immunology , T-Lymphocytes, Cytotoxic/immunology , Tacrolimus/therapeutic use , Adult , CD8 Antigens/genetics , Cell Differentiation/drug effects , Female , Gene Expression , Glucocorticoids/therapeutic use , Humans , Immunologic Memory/drug effects , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Leukocyte Common Antigens/genetics , Leukocyte Common Antigens/immunology , Liver/immunology , Liver/pathology , Liver/surgery , Living Donors , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Perforin/genetics , Perforin/immunology , Receptors, CCR7/deficiency , Receptors, CCR7/genetics , Receptors, CCR7/immunology , Receptors, Interleukin-12/agonists , Receptors, Interleukin-12/genetics , T-Lymphocytes, Cytotoxic/drug effects , Time Factors , Transplant Recipients , Treatment Outcome , Up-Regulation
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