Publications by authors named "Yukiko Sato"

71 Publications

In-beam Mössbauer spectra of Mn implanted into lithium aluminum hydride.

Appl Radiat Isot 2021 Apr 20;170:109582. Epub 2021 Jan 20.

National Institute of Radiological Sciences, Inage, Chiba, Japan.

In-beam Mössbauer spectra of Mn implanted into LiAlH were measured at different temperatures between 17 and 300 K. The Mössbauer spectrum measured at 17 K showed two sets of doublets, which were assigned to Fe atoms at substitutional sites at Al and Li sites. The Debye temperatures θ for the Fe atoms at Al-substituted and Li-substituted sites were estimated to be 194 K and 117 K, respectively. The assignments were confirmed by density functional theory calculations.
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http://dx.doi.org/10.1016/j.apradiso.2020.109582DOI Listing
April 2021

Isolation of Severe Fever with Thrombocytopenia Syndrome Virus from Various Tick Species in Area with Human Severe Fever with Thrombocytopenia Syndrome Cases.

Vector Borne Zoonotic Dis 2021 May 3;21(5):378-384. Epub 2021 Feb 3.

Department of Veterinary Sciences, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.

Severe fever with thrombocytopenia syndrome (SFTS), caused by , generally called SFTS virus (SFTSV), is an emerging zoonosis in East Asia. In Japan, 50-100 cases of SFTS have been reported each year since the first case was reported in 2013. SFTS is a tick-borne infectious disease, and SFTSV has been isolated from ticks in China and South Korea. and are considered the primary vectors in Japan. However, the other tick species seldom feeding on humans might also play an important role in maintaining the virus in nature. In this study, we collected ticks on vegetation around the location where two SFTS patients were estimated to have been infected in Miyazaki Prefecture, Japan, isolated live SFTSV, and performed a phylogenetic analysis. A total of 257 ticks were collected, and SFTSV RNA was detected in 19.5% (9/46) of tick pools. A total of 10 infectious SFTSVs were successfully isolated from , , , , and . Furthermore, the whole viral sequences isolated from ticks were highly homologous to sequences isolated from SFTS patients in the same sampling area in the past. These results suggest that SFTSVs are maintained in these tick species in the sampling area and sporadically transmitted to humans. Surveillance of SFTSV in ticks provides important information about the risk of incidental transmission to humans.
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http://dx.doi.org/10.1089/vbz.2020.2720DOI Listing
May 2021

Direct Transmission of Severe Fever with Thrombocytopenia Syndrome Virus from Domestic Cat to Veterinary Personnel.

Emerg Infect Dis 2020 12;26(12):2994-2998

Two veterinary personnel in Japan were infected with severe fever with thrombocytopenia syndrome virus (SFTSV) while handling a sick cat. Whole-genome sequences of SFTSV isolated from the personnel and the cat were 100% identical. These results identified a nosocomial outbreak of SFTSV infection in an animal hospital without a tick as a vector.
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http://dx.doi.org/10.3201/eid2612.191513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706950PMC
December 2020

Secretory carcinoma around Stensen's duct misdiagnosed as salivary duct cyst.

Int J Clin Exp Pathol 2020 1;13(8):2211-2217. Epub 2020 Aug 1.

Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University Tokyo, Japan.

Secretory carcinoma (SC) of the salivary gland was identified in 2010, and it is characterized by a specific gene arrangement. The most common primary site for SC is the parotid gland; however, SC around the Stensen's duct is rare. Here we describe a rare case of a SC around the Stensen's duct that was initially misdiagnosed as a salivary duct cyst. A 59-year-old woman presented with a mass in the region of the left parotid papilla. Magnetic resonance imaging (MRI) revealed a well-circumscribed lesion and enhancement with a rim and an inner wall-like part that appeared in the late phase. Based on the initial clinical and imaging findings, a salivary duct cyst of the parotid gland was diagnosed. However, the lesion was histopathologically diagnosed as a SC based on immunohistochemical findings. The tumor cells showed diffuse positive staining for AE1/AE3, vimentin, and mammaglobin and focal positive staining for S-100 protein, SOX-10, and DOG-1. Fluorescence hybridization revealed gene rearrangement in the tumor. In cases of cystic lesions around the Stensen's duct, clinicians should bear in mind that the possibility that they could be minor salivary gland cancers, such as SC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476943PMC
August 2020

Promoter Mutation and Extent of Thyroidectomy in Patients with 1-4 cm Intrathyroidal Papillary Carcinoma.

Cancers (Basel) 2020 Jul 30;12(8). Epub 2020 Jul 30.

Department of Endocrine Surgery, Nippon Medical School, Tokyo 113-8603, Japan.

There are concerns regarding overtreatment in papillary thyroid carcinoma (PTC). and promoter mutations play important roles in the development of PTC. However, initial surgical approaches for PTC based on genetic characteristics remain unclear. The present study aimed to identify genetic mutations as predictors of prognosis and to establish proper indications for lobectomy (LT) in patients with 1-4 cm intrathyroidal PTC. Prospectively accumulated data from 685 consecutive patients with PTC who underwent primary thyroid surgery at the Cancer Institute Hospital, Tokyo, Japan, between 2001 and 2012 were retrospectively reviewed. Of the 685 patients examined, 538 (78.5%) had mutation and 133 (19.4%) had promoter mutations. Patients with promoter mutations displayed significantly worse outcomes than those without mutations (10-year cause-specific survival (CSS): 73.7% vs. 98.1%, < 0.001; 10-year disease-free survival (DFS): 53.7% vs. 93.3%, < 0.001). As for extent of thyroidectomy among mutation-negative patients with 1-4 cm intrathyroidal PTC, patients who underwent LT showed no significant differences in 10-year CSS and 10-year DFS compared to patients who had total thyroidectomy (TT) under propensity score-matching. Avoiding TT for those patients indicates a possible pathway to prevent overtreatment and reduce postoperative complications.
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http://dx.doi.org/10.3390/cancers12082115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464551PMC
July 2020

Galectin-3 enhances neutrophil motility and extravasation into the airways during Aspergillus fumigatus infection.

PLoS Pathog 2020 08 4;16(8):e1008741. Epub 2020 Aug 4.

Department of Microbiology and Immunology, McGill University, Montréal, Canada.

Aspergillus fumigatus is an opportunistic mold that infects patients who are immunocompromised or have chronic lung disease, causing significant morbidity and mortality in these populations. While the factors governing the host response to A. fumigatus remain poorly defined, neutrophil recruitment to the site of infection is critical to clear the fungus. Galectin-3 is a mammalian β-galactose-binding lectin with both antimicrobial and immunomodulatory activities, however the role of galectin-3 in the defense against molds has not been studied. Here we show that galectin-3 expression is markedly up-regulated in mice and humans with pulmonary aspergillosis. Galectin-3 deficient mice displayed increased fungal burden and higher mortality during pulmonary infection. In contrast to previous reports with pathogenic yeast, galectin-3 exhibited no antifungal activity against A. fumigatus in vitro. Galectin-3 deficient mice exhibited fewer neutrophils in their airways during infection, despite normal numbers of total lung neutrophils. Intravital imaging studies confirmed that galectin-3 was required for normal neutrophil migration to the airspaces during fungal infection. Adoptive transfer experiments demonstrated that stromal rather than neutrophil-intrinsic galectin-3 was necessary for normal neutrophil entry into the airspaces. Live cell imaging studies revealed that extracellular galectin-3 directly increases neutrophil motility. Taken together, these data demonstrate that extracellular galectin-3 facilitates recruitment of neutrophils to the site of A. fumigatus infection, and reveals a novel role for galectin-3 in host defense against fungal infections.
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http://dx.doi.org/10.1371/journal.ppat.1008741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428289PMC
August 2020

Efficacy of Nivolumab for Head and Neck Cancer Patients with Primary Sites and Histological Subtypes Excluded from the CheckMate-141 Trial.

Cancer Manag Res 2020 3;12:4161-4168. Epub 2020 Jun 3.

Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.

Background: In the CheckMate-141 trial, nivolumab conferred a survival benefit in patients with recurrent or metastatic refractory squamous cell carcinoma (SCC) head and neck cancer (HNC). Here, we examined the efficacy of nivolumab in patients with histological subtypes or primary sites of HNC not included in the CheckMate-141 trial.

Methods: This was a retrospective analysis of data collected prospectively from 97 patients who were treated with nivolumab for recurrent or metastatic HNC at our institution. The patients were assigned to three groups based on HNC primary site: 1) oral cavity, pharynx, and larynx, which were included in CheckMate-141 (n = 68), 2) nasopharynx (excluded in CheckMate-141, n = 7) and 3) other primary sites excluded in CheckMate-141 (n = 22) and assigned to two groups according to histological subtype: 1) SCC (included in CheckMate-141, n = 83) and 2) non-SCC (all sites excluded in CheckMate-141, n = 14). Survival outcomes and nivolumab treatment response were compared between the primary site and histological subgroups.

Results: The median number of nivolumab treatments was 7 cycles (range, 1-53 cycles) and the median follow-up time was 9.1 months (range, 0.66-33.0 months). There were no significant differences in response rates between the three primary site subgroups (CheckMate-141 sites 22%, nasopharynx 43%, others 18%; p=0) or the two histological subtype subgroups (SCC 25%, non-SCC 7%, p=0). Similarly, overall survival and progression-free survival were comparable for patients stratified by primary site or histological subtype.

Conclusion: No significant difference in response rates or survival outcomes was detected between nivolumab-treated HNC patients with primary sites and histological subtypes that were included versus excluded in the CheckMate-141 trial. These data provide a potential rationale for nivolumab therapy for all HNC patients in clinical practice.
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http://dx.doi.org/10.2147/CMAR.S249393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280058PMC
June 2020

The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma.

Virchows Arch 2020 Aug 26;477(2):291-299. Epub 2020 Feb 26.

Department of Otorhinolaryngology/Head & Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.

Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)-positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism-related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADP-positive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.
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http://dx.doi.org/10.1007/s00428-020-02777-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371671PMC
August 2020

Prognostic Implication of Histopathologic Indicators in Salivary Duct Carcinoma: Proposal of a Novel Histologic Risk Stratification Model.

Am J Surg Pathol 2020 04;44(4):526-535

Departments of Anatomic Pathology.

Salivary duct carcinoma (SDC) is a rare, aggressive malignancy that histologically resembles high-grade mammary duct carcinoma. Because of the rarity of this entity, data verifying the association between histologic features and patient survival are limited. We conducted a comprehensive histologic review of 151 SDC cases and performed an analysis of the association between various histomorphologic parameters and the clinical outcome with the aim of developing a histologic risk stratification model that predicts the prognosis of SDC patients. A multivariate analysis revealed that prominent nuclear pleomorphism (overall survival [OS]: P=0.013; progression-free survival [PFS]: P=0.019), ≥30 mitoses/10 HPF (PFS: P=0.013), high tumor budding (OS: P=0.011; PFS: P<0.001), and high poorly differentiated clusters (OS: P<0.001; PFS: P<0.001) were independent prognostic factors. Patients with vascular invasion demonstrated a marginally significant association with shorter PFS (P=0.064) in a multivariate analysis. We proposed a 3-tier histologic risk stratification model based on the total number of positive factors among 4 prognostically relevant parameters (prominent nuclear pleomorphism, ≥30 mitoses/10 HPF, vascular invasion, and high poorly differentiated clusters). The OS and PFS of patients with low-risk (0 to 1 point) (23% of cases), intermediate-risk (2 to 3 points) (54% of cases), and high-risk (4 points) (23% of cases) tumors progressively deteriorated in this order (hazard ratio, 2.13 and 2.28, and 4.99 and 4.50, respectively; Ptrend<0.001). Our histologic risk stratification model could effectively predict patient survival and may be a useful aid to guide clinical decision-making in relation to the management of patients with SDC.
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http://dx.doi.org/10.1097/PAS.0000000000001413DOI Listing
April 2020

The anion transporter SLC26A9 localizes to tight junctions and is degraded by the proteasome when co-expressed with F508del-CFTR.

J Biol Chem 2019 11 23;294(48):18269-18284. Epub 2019 Oct 23.

Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; Cystic Fibrosis Translational Research Center, McGill University, Montréal, Québec H3G 1Y6, Canada. Electronic address:

Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) disrupt epithelial secretion and cause cystic fibrosis (CF). Available CFTR modulators provide only modest clinical benefits, so alternative therapeutic targets are being explored. The anion-conducting transporter solute carrier family 26 member 9 (SLC26A9) is a promising candidate, but its functional expression is drastically reduced in cells that express the most common CF-associated CFTR variant, F508del-CFTR, through mechanisms that remain incompletely understood. Here, we examined the metabolic stability and location of SLC26A9 and its relationship to CFTR. Compared with SLC26A9 levels in BHK cells expressing SLC26A9 alone or with WT-CFTR, co-expression of SLC26A9 with F508del-CFTR reduced total and plasma membrane levels of SLC26A9. Proteasome inhibitors increased SLC26A9 immunofluorescence in primary human bronchial epithelial cells (pHBEs) homozygous for F508del-CFTR but not in non-CF pHBEs, suggesting that F508del-CFTR enhances proteasomal SLC26A9 degradation. Apical SLC26A9 expression increased when F508del-CFTR trafficking was partially corrected by low temperature or with the CFTR modulator VX-809. The immature glycoforms of SLC26A9 and CFTR co-immunoprecipitated, consistent with their interaction in the endoplasmic reticulum (ER). Transfection with increasing amounts of WT-CFTR cDNA progressively increased SLC26A9 levels in F508del-CFTR-expressing cells, suggesting that WT-CFTR competes with F508del-CFTR for SLC26A9 binding. Immunofluorescence staining of endogenous SLC26A9 and transfection of a 3HA-tagged construct into well-differentiated cells revealed that SLC26A9 is mostly present at tight junctions. We conclude that SLC26A9 interacts with CFTR in both the ER and Golgi and that its interaction with F508del-CFTR increases proteasomal SLC26A9 degradation.
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http://dx.doi.org/10.1074/jbc.RA119.010192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885613PMC
November 2019

Cystic Fibrosis: Proteostatic correctors of CFTR trafficking and alternative therapeutic targets.

Expert Opin Ther Targets 2019 08 9;23(8):711-724. Epub 2019 Jun 9.

b Cystic Fibrosis Translational Research centre , McGill University , Montréal , QC , Canada.

: Cystic fibrosis (CF) is the most frequent lethal orphan disease and is caused by mutations in the CFTR gene. The most frequent mutation F508del-CFTR affects multiple organs; infections and subsequent infections and complications in the lung lead to death. : This review focuses on new targets and mechanisms that are attracting interest for the development of CF therapies. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER) but has some function if it can traffic to the plasma membrane. Cell-based assays have been used to screen chemical libraries for small molecule correctors that restore its trafficking. Pharmacological chaperones are correctors that bind directly to the F508del-CFTR mutant and promote its folding and trafficking. Other correctors fall into a heterogeneous class of proteostasis modulators that act indirectly by altering cellular homeostasis. : Pharmacological chaperones have so far been the most successful correctors of F508del-CFTR trafficking, but their level of correction means that more than one corrector is required. Proteostasis modulators have low levels of correction but hold promise because some can correct several different CFTR mutations. Identification of their cellular targets and the potential for development may lead to new therapies for CF.
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http://dx.doi.org/10.1080/14728222.2019.1628948DOI Listing
August 2019

The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas: a study of 142 cases.

Histopathology 2018 Dec 25;73(6):943-952. Epub 2018 Sep 25.

Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.

Aims: Salivary duct carcinoma (SDC) is an uncommon, aggressive tumour that, histologically, resembles high-grade mammary ductal carcinoma, and is characterised by the expression of androgen receptor (AR). The androgen signalling pathway, a potential therapeutic target, can be regulated by FOXA1. This study aimed to evaluate the clinicopathological implications of FOXA1 in SDC.

Methods And Results: We examined the relationship between the immunoexpression of FOXA1 and FOXA1 mutations and clinicopathological factors, including the biomarker status and clinical outcome, in 142 SDCs. FOXA1 was expressed in 128 SDCs (90.1%); the immunoexpression was heterogeneous. SDCs with a higher FOXA1 labelling index (LI) (≥20%) more frequently showed less advanced tumors on T classification (P = 0.002). FOXA1 LI was correlated positively with the AR expression value (r = 0.430, P < 0.001). PI3K and p-mTOR positivity, and intact-PTEN, were associated with a higher FOXA1 LI. Twenty-two of 121 SDCs (18.2%) harboured FOXA1 gene mutations at the flanking regions in and around the forkhead DNA binding domain; however, the given gene mutation and the expression of FOXA1 were not significantly correlated. A multivariate analysis revealed that SDCs with a higher FOXA1 LI were associated with longer overall survival and progression-free survival (P = 0.029 and 0.016, respectively).

Conclusions: In SDC, FOXA1, which may biologically interact with the AR and PI3K signalling pathways, is a putative biomarker that may be associated with a favourable prognosis. Further studies are needed to apply the findings to the development of targeted personalised therapy for patients with SDC.
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http://dx.doi.org/10.1111/his.13706DOI Listing
December 2018

Indocyanine green lymphography for diagnosis of lymphedema following thigh lift surgery.

Microsurgery 2018 09 19;38(6):718-719. Epub 2018 Jun 19.

Department of Plastic and Reconstructive Surgery, Center Hospital of National Center for Global Health and Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1002/micr.30337DOI Listing
September 2018

Metastasizing pleomorphic adenoma in the multiple organs: A case report on FDG-PET/CT imaging.

Medicine (Baltimore) 2018 Jun;97(23):e11077

Department of Nuclear Medicine Department of Diagnostic Imaging Department of Pathology, The Cancer Institute Hospital of JFCR, Tokyo, Japan.

Rationale: Pleomorphic adenoma, the most common tumor of the salivary glands, is usually benign. It is well known, however, that pleomorphic adenomas occasionally undergo malignant transformation to carcinoma ex pleomorphic adenoma and can metastasize. More rarely pleomorphic adenomas can metastasize without histological malignant transformation. We herein report an unusual case of pleomorphic adenoma with multiple metastases comprehensively demonstrated on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).

Patient Concerns: A 63-year-old woman was referred to our hospital because of urine occult blood and lung nodules detected on a health checkup. She had a history of resection of a pleomorphic adenoma in the parotid gland at the age of 40 years and tumor recurrence at the age of 53 years. CT scan and magnetic resonance imaging revealed bilateral renal tumors, multiple pulmonary nodules, and an osteolytic lesion in the first lumbar vertebra.

Diagnoses: Ultrasonography-guided percutaneous biopsy of the right renal tumor revealed a myxoid epithelial tumor that was consistent with metastasis of the pleomorphic adenoma from the parotid gland.

Interventions: The patient was carefully observed with regular imaging examinations.

Outcomes: The multiple lesions gradually progressed, and FDG-PET/CT subsequently revealed additional metastases in the liver and perineum.

Lessons: Metastases of pleomorphic adenomas may occur years after the initial disease in association with local recurrences. Careful observation with whole-body imaging such as FDG-PET/CT is necessary.
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http://dx.doi.org/10.1097/MD.0000000000011077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999481PMC
June 2018

Epigenetic inactivation of galanin receptors in salivary duct carcinoma of the parotid gland: Potential utility as biomarkers for prognosis.

Oncol Lett 2018 Jun 18;15(6):9043-9050. Epub 2018 Apr 18.

Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.

Salivary duct carcinoma (SDC) constitutes one of the most aggressive cancers in the salivary gland and is associated with a poor prognosis; however, no established systemic therapy options are available. SDC exhibits biological similarity to prostate and breast cancers, therefore anti-hormone therapy and molecular target therapies are available, however with limited beneficial effects. Galanin and galanin receptors (GALRs) are well established as molecular biomarkers to predict the survival rate and risk of recurrence of head and neck squamous cell carcinoma. The present study investigated the clinicopathological features of patients with SDC and the methylation status of their galanin and GALR genes to demonstrate the prognostic value for this disease. The median overall survival (OS) was 37.2 months. T-stage, N-stage, disease stage, tumor size, and preoperative facial paralysis were significantly associated with OS, whereas human epidermal growth factor receptor 2 (HER2) overexpression was not. and methylation rates in tumor tissues were significantly increased compared with normal tissues with 9.85- and 4.49-fold increase, respectively. p27 and p57 expression significantly inversely correlated with the methylation rate of and . In addition, the observed and/or methylation rates were significantly correlated with a decrease in OS. These results suggest that and may serve as potential prognostic factors and therapeutic targets in SDC.
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http://dx.doi.org/10.3892/ol.2018.8525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958682PMC
June 2018

Hyalinizing clear cell carcinoma of the bronchial glands: presentation of three cases and pathological comparisons with salivary gland counterparts and bronchial mucoepidermoid carcinomas.

Mod Pathol 2018 06 12;31(6):923-933. Epub 2018 Feb 12.

Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan.

Hyalinizing clear cell carcinoma of the bronchial glands is a very rare tumor. Since only five reports describing six tumors have been published to date, only a little is known about specific histologic findings and clinical features. Because of its rarity, hyalinizing clear cell carcinoma has not been described in the latest WHO classification of pulmonary tumors yet. Here we present three cases of bronchial hyalinizing clear cell carcinomas, confirmed by both fluorescence in situ hybridization (FISH) and RT-PCR, focusing on histologic and immunohistochemical characteristics in a comparison with three cases of salivary gland origin. In addition, we compared immunohistochemical features with bronchial mucoepidermoid carcinoma, a lesion that needs to be taken into account in differential diagnosis of hyalinizing clear cell carcinoma. All our bronchial hyalinizing clear cell carcinoma cases were surgically resected. Histologically, tumor cells showed clear to eosinophilic cytoplasm with hyalinizing stroma in various proportions, resembling those of salivary gland origin. Immunohistochemically, tumor cells were positive for CK7, CK5/6, p40, p63, and ATF1, while they were negative for TTF1, Napsin A, HMB45, and SOX10. The CK5/6 staining pattern varied in mucoepidermoid carcinomas, while that of hyalinizing clear cell carcinoma was uniformly positive. FISH revealed EWSR1-ATF1 fusion, and RT-PCR with sequencing confirmed specificity of the chimeric gene for hyalinizing clear cell carcinoma. Clinically, bronchial hyalinizing clear cell carcinoma was characterized by occurrence in the fourth to sixth decades, no link with smoking history, and a predilection for the right lung, in line with previous reports. In summary, our study confirmed that the bronchial hyalinizing clear cell carcinoma is a histologically and genetically identical tumor to that of salivary gland origin, and that gene rearrangement analysis can play a critical role in distinction from mucoepidermoid carcinoma.
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http://dx.doi.org/10.1038/s41379-018-0025-7DOI Listing
June 2018

Prognostic and histogenetic roles of gene alteration and the expression of key potentially actionable targets in salivary duct carcinomas.

Oncotarget 2018 Jan 4;9(2):1852-1867. Epub 2017 Dec 4.

Department of Otorhinolaryngology, Showa University School of Medicine, Tokyo, Japan.

The molecular characteristics of therapeutically-relevant targets and their clinicopathological implications in salivary duct carcinomas (SDCs) are poorly understood. We investigated the gene alterations and the immunoexpression of crucial oncogenic molecules in 151 SDCs. The mutation rates that were identified, in order of frequency, were as follows: , 68%; , 18%; , 16%; , 4%; and , 1.5%. mutations were more common in SDC than in SDC ex-pleomorphic adenoma. Furthermore, these mutations were mutually exclusive for HER2 overexpression/amplification. mutations were frequently detected in cases with the aberrant p53 expression, and missense and truncating mutations were associated with p53-extreme positivity and negativity, respectively. DISH analysis revealed no cases of amplification. The rates of PI3K, p-Akt, and p-mTOR positivity were 34%, 22%, and 66%, respectively; PTEN loss was observed in 47% of the cases. These expressions were correlated according to the signaling axis. Cases with PI3K negativity and PTEN loss appeared to show a lower expression of androgen receptor. In the multivariate analysis, patients with SDC harboring truncating mutations showed shorter progression-free survival. Conversely, p-Akt positivity was associated with a favorable outcome. This study might provide information that leads to advances in personized therapy for SDC.
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http://dx.doi.org/10.18632/oncotarget.22927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788604PMC
January 2018

MYB and MYBL1 in adenoid cystic carcinoma: diversity in the mode of genomic rearrangement and transcripts.

Mod Pathol 2018 06 6;31(6):934-946. Epub 2018 Feb 6.

Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.

MYB-NFIB and MYBL1-NFIB have been reported in ~60% of adenoid cystic carcinoma cases, but driver alterations in the remaining ~40% of adenoid cystic carcinoma remain unclear. We examined 100 adenoid cystic carcinoma cases for MYB and MYBL1 locus rearrangements by fluorescence in situ hybridization (FISH) with originally designed probe sets using formalin-fixed paraffin-embedded materials. Approximately one-third of samples were also analyzed by fusion transcript-specific RT-PCR and capture RNA sequencing. In the 27 cases with frozen materials, MYB-NFIB and MYBL1-NFIB fusion transcripts were detected in 9 (33%) and 6 cases (22%) by RT-PCR, respectively. Meanwhile, high expression of MYB (18 cases, 67%) or MYBL1 (9 cases, 33%) was detected in all 27 cases in a mutually exclusive manner, regardless of its form (full-length, truncation, or fusion transcript). Interestingly, genomic rearrangements around the corresponding highly-expressed gene were observed in all 27 cases by FISH, suggesting a causative relationship between genomic rearrangements and gene expression. Among the 100 cases, including additional 73 cases, 97 harbored genomic rearrangements in the MYB (73 cases) or MYBL1 locus (24 cases) including 10 cases with atypical FISH patterns undetectable through ordinary split FISH approaches: breakpoints far distant from MYB (5 cases) and a small NFIB locus insertion into the MYB (3 cases) or MYBL1 locus (2 cases). In clinicopathological analyses, histological grade, primary tumor size, and lymph node metastasis were identified as prognostic factors, whereas MYB/MYBL1 rearrangements were not, but were associated with histological grade. In the present study, MYB or MYBL1 locus rearrangement was detected in nearly all adenoid cystic carcinoma cases, and therefore it would be a good diagnostic marker for adenoid cystic carcinoma. However, fusion transcript-specific RT-PCR for MYB-NFIB and MYBL1-NFIB and ordinary split FISH assays for MYB and MYBL1 were less sensitive, and thus detection methods should be judiciously designed because of the diversity of rearrangement modes in adenoid cystic carcinoma.
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http://dx.doi.org/10.1038/s41379-018-0008-8DOI Listing
June 2018

Central mucoepidermoid carcinoma arising from glandular odontogenic cyst confirmed by analysis of MAML2 rearrangement: A case report.

Pathol Int 2018 Jan 13;68(1):31-35. Epub 2017 Nov 13.

Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Central mucoepidermoid carcinoma (MEC) poses a diagnostic challenge because of its rarity and histological overlap with glandular odontogenic cyst (GOC). In MEC of both salivary glands and jaws, MAML2 arrangement has been well known as the specific gene alteration. We report a case of central MEC arising from GOC diagnosed by MAML2 fusion gene. A 57-year-old male presented a multilocular cystic lesion in left molar region of the mandible. Histopathologically, multiple cysts lined by thin cuboidal or non-keratinized squamous epithelium with small duct-like structures, mucous cells and ciliated cells were present. It was diagnosed as GOC. The recurrent lesion after nine years showed the proliferation of many cystic and solid nests composed of epidermoid, mucous and intermediated cells. Nested PCR revealed CRTC3-MAML2 fusion gene in the recurrent lesion, but not in the primary one. Similarly, MAML-2 rearrangement by FISH analysis was positive in the recurrent lesion, while negative for the primary one, thus confirming the diagnosis of central MEC arising from GOC. Analysis of MAML2 rearrangement can be used as a supportive evidence to distinguish central MEC from GOC.
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http://dx.doi.org/10.1111/pin.12609DOI Listing
January 2018

A comparison of weekly paclitaxel and cetuximab with the EXTREME regimen in the treatment of recurrent/metastatic squamous cell head and neck carcinoma.

Oral Oncol 2017 10 5;73:21-26. Epub 2017 Aug 5.

Departments of Medical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address:

Background: The effectiveness of the combination chemotherapy of weekly paclitaxel and cetuximab has not yet been compared to that of the current standard regimen, EXTREME (combination of 5-fluorouracil, cisplatin and cetuximab).

Methods: We retrospectively reviewed the clinical records of R/M SCCHN patients who received cetuximab-containing chemotherapy as a first-line therapy; from these, patients receiving a weekly paclitaxel and cetuximab regimen (cohort A) and the EXTREME regimen (cohort B) were extracted. The responses, prognoses and adverse events of these two cohorts were evaluated.

Results: A total of 86 patients were included (cohort A, 49; cohort B, 36). Patients with histories of platinum-based chemotherapy were more frequently given the cohort A treatment. Though the response rates were similar in the two cohorts (45% in cohort A and 51% in cohort B; p=0.83), the progression-free survival (PFS) was significantly more favorable in cohort A by the log-rank test (6.0monthsvs 5.0months; p=0.027). In the Cox-regression hazard analyses, male gender (hazard ratio [HR]=2.1, p=0.010), older age (≥ 70 yo) (HR=5.0, p=0.018), PS 0 (HR=2.2, p=0.027), no history of platinum chemotherapy (HR=3.2, p=0.003) and the presence of a tracheostomy (HR=2.3, p=0.039) were favorable factors within cohort A.

Conclusion: In selected R/M SCCHN patients, the combination of weekly paclitaxel and cetuximab could be the better treatment option than the EXTREME regimen.
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http://dx.doi.org/10.1016/j.oraloncology.2017.07.022DOI Listing
October 2017

Biomarker immunoprofile in salivary duct carcinomas: clinicopathological and prognostic implications with evaluation of the revised classification.

Oncotarget 2017 Aug 2;8(35):59023-59035. Epub 2017 Aug 2.

Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.

Salivary duct carcinoma (SDC) is an uncommon, aggressive malignant neoplasm histologically resembling high-grade mammary ductal carcinoma. SDC can arise or ex pleomorphic adenoma. To clarify the correlation of biomarker immunoprofile with clinicopathological findings and clinical outcome of SDC, we conducted immunohistochemistry for EGFR, HER2, HER3, AR, CK5/6, p53, and Ki-67, along with HER2 fluorescence hybridization in 151 SDCs. SDCs ex pleomorphic adenoma more commonly overexpressed EGFR, HER2, HER3, and Ki-67 than SDCs ( = 0.015, < 0.001, 0.045, and 0.02, respectively). In multivariate analysis, AR- and CK5/6+ were associated with shorter progression-free survival ( = 0.027 and 0.004, respectively). Moreover, patients with p53-extreme negative/positive demonstrated poorer overall survival ( = 0.007). On assessing the revised classification by the combination of biomarker expression, the percentages of each subtype were as follows: 'apocrine A' (AR+/HER2-/Ki-67-low) (24%), 'apocrine B' (AR+/HER2-/Ki-67-high) (18%), 'apocrine HER2' (AR+/HER2+) (35%), 'HER2-enriched' (AR-/HER2+) (12%), and 'double negative' (AR-/HER2-) (11%). 'Double negative' was further subclassified into 'basal-like' (EGFR and/or CK5/6+) (7%) and 'unclassified' (3%). Consequently, patients with 'apocrine A' showed a better progression-free survival than those with any other subtypes. Our revised immunoprofiling classification was valuable for predicting the survival and might be useful in personalized therapy for patients with SDC.
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http://dx.doi.org/10.18632/oncotarget.19812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601711PMC
August 2017

Molecular alterations of coexisting thyroid papillary carcinoma and anaplastic carcinoma: identification of TERT mutation as an independent risk factor for transformation.

Mod Pathol 2017 11 21;30(11):1527-1537. Epub 2017 Jul 21.

Department of Pathology, University of Yamanashi, Chuo, Yamanashi, Japan.

Thyroid papillary carcinoma is the most common endocrine neoplasm and generally carries a favorable prognosis. However, a small subset of papillary carcinomas transforms into anaplastic carcinoma, an undifferentiated cancer with a dismal prognosis. Recent studies using next-generation sequencing revealed the genomic landscape of papillary carcinoma and anaplastic carcinoma. However, risk factors for anaplastic transformation in papillary carcinoma remain obscure. In the present study, we investigated molecular alterations of papillary carcinoma and anaplastic carcinoma components in 27 tumors in which anaplastic carcinoma coexisted with antecedent papillary carcinoma. We conducted direct sequencing for BRAF, TERT promoter and PIK3CA, and immunohistochemistry for p53, TTF-1 and subunits of the SWI/SNF complex (ARID1A, ARID1B, ATRX, SMARCA2, SMARCA4, SMARCB1, and PBRM1). BRAF and TERT promoter mutated at the rate of 90% and 95%, respectively, and these mutational statuses were almost identical between the papillary carcinoma and anaplastic carcinoma components. PIK3CA mutation was positive in 33% of our samples with a heterogeneous mutation pattern of the papillary carcinoma and anaplastic carcinoma components. Aberrant expression of p53 and loss of TTF-1 were present in 63 and 59%, respectively, and these two alterations were confined to the anaplastic carcinoma components. There was a loss of the SWI/SNF complex in a subset of the tumors with a heterogeneous pattern of the papillary carcinoma and anaplastic carcinoma components: SMARCA4 in 4% and PBRM1 in 4%. In a multivariate comparison between the antecedent papillary carcinoma components and control papillary carcinomas without anaplastic transformation, TERT promoter mutation was independently associated with anaplastic transformation. Collectively, papillary carcinoma-derived anaplastic carcinomas are characterized by BRAF and TERT promoter mutations, and these mutations occur prior to anaplastic transformation. Alterations of PIK3CA and the SWI/SNF complex are relatively rare and temporally heterogeneous. Of note, a papillary carcinoma harboring TERT promoter mutation is at higher risk for anaplastic transformation.
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http://dx.doi.org/10.1038/modpathol.2017.75DOI Listing
November 2017

Validation of rapid algal bioassay using delayed fluorescence in an interlaboratory ring study.

Sci Total Environ 2017 Dec 3;605-606:842-851. Epub 2017 Jul 3.

Central Research Laboratory, Hamamatsu Photonics K.K., Japan.

Algal growth inhibition tests are generally used to determine the toxic effects of chemical substances on algae growth. In this report, we describe a rapid and simple test procedure using delayed fluorescence (DF) to determine chemical toxicities more rapidly than the conventional 72h or 96h growth inhibition tests. We assess the suitability of DF to serve as an alternative endpoint for biomass production and determine the variability by an interlaboratory ring study using a typical reference toxicant 3,5-dichlorophenol (DCP). The results suggest that DF has the potential to be used as a surrogate measure of photosynthetically-active biomass in the algal growth inhibition tests. The half maximal effective concentration (EC) values of DCP determined from the DF inhibition test in 6h and 24h (1.2±0.3mg/L and 2.7±0.5mg/L respectively) are in reasonable agreement with the EC value of DCP determined by the 72h conventional method (1.8mg/L). In the interlaboratory ring study, the intralaboratory and interlaboratory variabilities of the EC of the DF inhibition test for a 24h exposure period are 12% and 28% respectively. DF intensity can be considered as a surrogate of living biomass with active photosynthesis, and we conclude that a 24h exposure duration better estimates the toxic effects measured using conventional surrogate measures for dry weight such as cell counts, volume, optical density or fluorescence.
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http://dx.doi.org/10.1016/j.scitotenv.2017.06.228DOI Listing
December 2017

Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity.

Proc Natl Acad Sci U S A 2017 07 20;114(27):7124-7129. Epub 2017 Jun 20.

Department of Microbiology and Immunology, McGill University, Montreal, QC, H3A 2B4, Canada;

Galactosaminogalactan and Pel are cationic heteropolysaccharides produced by the opportunistic pathogens and , respectively. These exopolysaccharides both contain 1,4-linked -acetyl-d-galactosamine and play an important role in biofilm formation by these organisms. Proteins containing glycoside hydrolase domains have recently been identified within the biosynthetic pathway of each exopolysaccharide. Recombinant hydrolase domains from these proteins (Sph3 from and PelA from ) were found to degrade their respective polysaccharides in vitro. We therefore hypothesized that these glycoside hydrolases could exhibit antibiofilm activity and, further, given the chemical similarity between galactosaminogalactan and Pel, that they might display cross-species activity. Treatment of with Sph3 disrupted biofilms with an EC of 0.4 nM. PelA treatment also disrupted preformed biofilms with EC values similar to those obtained for Sph3 In contrast, Sph3 was unable to disrupt Pel-based biofilms, despite being able to bind to the exopolysaccharide. Treatment of hyphae with either Sph3 or PelA significantly enhanced the activity of the antifungals posaconazole, amphotericin B, and caspofungin, likely through increasing antifungal penetration of hyphae. Both enzymes were noncytotoxic and protected A549 pulmonary epithelial cells from -induced cell damage for up to 24 h. Intratracheal administration of Sph3 was well tolerated and reduced pulmonary fungal burden in a neutropenic mouse model of invasive aspergillosis. These findings suggest that glycoside hydrolases can exhibit activity against diverse microorganisms and may be useful as therapeutic agents by degrading biofilms and attenuating virulence.
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http://dx.doi.org/10.1073/pnas.1702798114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502622PMC
July 2017

Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene.

Oral Oncol 2017 06 10;69:46-55. Epub 2017 Apr 10.

Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. Electronic address:

Objective: Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumor (MOT) characterized by sheets and lobules of vacuolated and clear cells. To understand the biology of CCOC, we established a new cell line, CCOC-T, with EWSR1-ATF1 fusion gene from a mandible tumor with distant metastasis and characterized this cell line.

Materials And Methods: To detect the EWSR1-ATF1 fusion gene, we used three CCOC cases, including the present case, by RT-PCR and FISH analysis. We characterized established CCOC-T cells by checking cell growth, invasion and the expression of odontogenic factors and bone-related factors. Moreover, the gene expression profile of CCOC-T cells was examined by microarray analysis.

Results: Histologically, the primary tumor was comprised of cords and nests containing clear and squamoid cells separated by fibrous septa. In addition, ameloblastomatous islands with palisaded peripheral cells were observed, indicating probable odontogenic origin. This tumor expressed the fusion gene EWSR1-ATF1, which underlies the etiology of hyalinizing clear cell carcinoma (HCCC) and potentially that of CCOC. We found a breakpoint in the EWSR1-ATF1 fusion to be the same as that reported in HCCC. Established CCOC-T cells grew extremely slowly, but the cells showed highly invasive activity. Moreover, CCOC-T cells expressed bone-related molecules, odontogenic factors, and epithelial mesenchymal transition (EMT)-related molecules.

Conclusion: To the best of our knowledge, this is the first report on the establishment of a CCOC cell line. CCOC-T cells serve as a useful in vitro model for understanding the pathogenesis and nature of MOT.
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http://dx.doi.org/10.1016/j.oraloncology.2017.04.003DOI Listing
June 2017

Thick tumor capsule is a valuable risk factor for distant metastasis in follicular thyroid carcinoma.

Auris Nasus Larynx 2018 Feb 12;45(1):147-155. Epub 2017 May 12.

Department of Pathology, Cancer Institute Hospital, Japan.

Objective: While the biological behavior of follicular thyroid carcinoma (FTC) has been studied in great detail using clinical experience, few studies have investigated pre- or intraoperative factors related to the risk of distant metastasis (DM) among patients with FTC. The aim of this study was to analyze the characteristics of FTC with DM.

Methods: This study retrospectively investigated 102 patients with FTC who underwent surgery between 1988 and 2013. We compared clinicopathological characteristics between FTC with and without DM.

Results: Univariate analysis revealed nodal metastasis (p=0.045), serum thyroglobulin (Tg) at initial operation (≥1000ng/ml; p<0.0001), widely invasive appearance according to macroscopic findings (p<0.0001), thick tumor capsule (≥1mm; p<0.0001), vascular invasion (p=0.0003), extrathyroidal invasion (p=0.047), and venous tumor embolism (p=0.045) as significant risk factors for DM. Multivariate analysis conducted using pre- and intraoperative factors identified thick tumor capsule (≥1mm), serum Tg at initial operation (≥1000ng/ml), and macroscopically widely invasive appearance as risk factors independently associated with development of DM.

Conclusion: Patients with these risk factors should undergo total thyroidectomy and radioactive iodine ablation.
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http://dx.doi.org/10.1016/j.anl.2017.05.002DOI Listing
February 2018

Two Cases of Ectopic Hamartomatous Thymoma Masquerading as Sarcoma.

Case Rep Otolaryngol 2017 10;2017:1672919. Epub 2017 Jan 10.

Department of Head and Neck Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koutou-ku, Tokyo 135-8550, Japan.

Ectopic hamartomatous thymoma (EHT) is an extremely rare benign tumor. EHTs are difficult to differentiate from sarcomas, especially synovial sarcomas. We encountered two cases of EHT that were referred from other hospitals because sarcoma was suspected. In these cases, fusion gene detection via polymerase chain reaction or fluorescence in situ hybridization was useful for differentiating EHT from synovial sarcoma. EHT requires accurate diagnosis before surgery to avoid excessive treatment. Both tumor location and the presence of fat inside the tumor are important imaging findings for EHT, and confirmation of spindle cells, epithelial cells, and mature adipose cells in the tumor is an important pathological finding. It is important to exclude synovial sarcoma from the differential diagnosis via fusion gene analysis.
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http://dx.doi.org/10.1155/2017/1672919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259666PMC
January 2017

Structural Dynamics of the Heterodimeric ABC Transporter TM287/288 Induced by ATP and Substrate Binding.

Biochemistry 2016 Dec 28;55(48):6730-6738. Epub 2016 Nov 28.

Center for Biological Resources and Informatics, Tokyo Institute of Technology , B-62 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.

TM287/288 is a heterodimeric ATP-binding cassette (ABC) transporter, which harnesses the energy of ATP binding and hydrolysis at the nucleotide-binding domains (NBDs) to transport a wide variety of molecules through the transmembrane domains (TMDs) by alternating inward- and outward-facing conformations. Here, we conducted multiple 100 ns molecular dynamics simulations of TM287/288 in different ATP- and substrate-bound states to elucidate the effects of ATP and substrate binding. As a result, the binding of two ATP molecules to the NBDs induced the formation of the consensus ATP-binding pocket (ABP2) or the NBD dimerization, whereas these processes did not occur in the presence of a single ATP molecule or when the protein was in its apo state. Moreover, binding of the substrate to the TMDs enhanced the formation of ABP2 through allosteric TMD-NBD communication. Furthermore, in the apo state, α-helical subdomains of the NBDs approached each other, acquiring a conformation with core half-pockets exposed to the solvent, appropriate for ATP binding. We propose a "core-exposed" model for this novel conformation found in the apo state of ABC transporters. These findings provide important insights into the structural dynamics of ABC transporters.
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http://dx.doi.org/10.1021/acs.biochem.6b00947DOI Listing
December 2016

Impact of hematological inflammatory markers on clinical outcome in patients with salivary duct carcinoma: a multi-institutional study in Japan.

Oncotarget 2017 Jan;8(1):1083-1091

Department of Anatomic Pathology, Tokyo Medical University School of Medicine, Tokyo, Japan.

The prognostic role of modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with salivary duct carcinoma (SDC) remains unclear. We conducted a multi-institutional retrospective cohort study of 140 SDC patients. The survival impact of these hematological markers was evaluated using multivariate proportional hazard models.High mGPS (≥1) was significantly associated with worse survival (3-year overall survival (OS): 16.7% vs 66.1%, p-value=0.003; 3-year progression-free survival (PFS): 0.0% vs 27.9%, p-value<0.001). Additionally, high C-reactive protein (CRP) (≥0.39 mg/dl) was significantly associated with worse survival (3-year OS: 32.1% vs 68.2%, p-value=0.001; 3-year PFS: 7.1% vs 31.1%, p-value<0.001). These associations were consistent with multivariate analysis adjusted for established prognostic factors. Although we also found significant association of high NLR (≥2.5) with OS (HR 1.80; 95% confidence interval, 1.05-3.08) in multivariate analysis, this association were inconsistent with the results of PFS. In addition, we found no significant associations of PLR with survival. In conclusion, we found that mGPS, CRP and NLR were identified as prognostic factors associated with survival in SDC patients.
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http://dx.doi.org/10.18632/oncotarget.13565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352036PMC
January 2017

Efficacy of double-scope endoscopic submucosal dissection and long-term outcomes of endoscopic resection for superficial pharyngeal cancer.

Dig Endosc 2017 Mar 13;29(2):152-159. Epub 2016 Sep 13.

Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Background And Aim: Owing to increased awareness and use of narrow-band imaging, there are more opportunities to treat superficial pharyngeal cancer (SPC). The present study aimed to describe the short- and long-term outcomes of endoscopic resection (ER) for SPC.

Methods: This study included 166 consecutive SPC in 113 patients treated during 2006 to 2013 at one referral cancer center. In the first period, we treated patients using endoscopic mucosal resection (EMR), in the second period using conventional ESD (cESD) and in the recent period using double-scope ESD (dsESD), which involves a second thin endoscope for assistance to produce traction. Median follow-up period was 30 months.

Results: All lesions were diagnosed as squamous cell carcinoma. Complete resection rate of cESD and dsESD procedures was 56.4% and 82.3% (P < 0.01), and local recurrence rate was 2.6% and 0.0%, respectively. Procedure duration was significantly shorter for dsESD than for cESD (P < 0.05). Four cases of recurrent lymph node (LN) metastasis were observed; however, all patients with LN metastases survived to a 48-month median interval after neck dissection. Risk factors for LN metastasis included subepithelium invasion, tumor thickness >1000 μm, droplet infiltration, and lymphovascular invasion. Overall survival rate after 5 years was 79.5%; no patients died of SPC. Cumulative rate of metachronous SPC after 5 years was 46.5%.

Conclusion: ER for SPC is a feasible and effective treatment, although metachronous SPC occurred frequently. For the technique of ER, dsESD was effective.
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http://dx.doi.org/10.1111/den.12712DOI Listing
March 2017