Publications by authors named "Jun Miyauchi"

38 Publications

The in vitro effects of hepatoblastoma cells on the growth and differentiation of blasts in transient abnormal myelopoiesis associated with Down syndrome.

Leuk Res 2021 06 31;105:106570. Epub 2021 Mar 31.

Department of Pediatrics, National Defense Medical College, Tokorozawa, Saitama-ken, Japan.

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome, which spontaneously resolves within several weeks or months after birth, may represent a special form of leukemia developing in the fetal liver (FL). To explore the role of hepatoblasts, one of the major constituents of the FL hematopoietic microenvironment, in the pathogenesis of TAM, we investigated the influence of a human hepatoblastoma cell line, HUH-6, on the in vitro growth and differentiation of TAM blasts. In a coculture system with membrane filters, which hinders cell-to-cell contact between TAM blasts and HUH-6 cells, the growth and megakaryocytic differentiation of TAM blast progenitors were increased in the presence of HUH-6 cells. The culture supernatant of HUH-6 cells contained hematopoietic growth factors, including stem cell factor (SCF) and thrombopoietin (TPO). The neutralizing antibody against SCF abrogated the growth-stimulating activity of the culture supernatant of HUH-6 cells, demonstrating that, among the growth factors produced by HUH-6 cells, SCF may be the major growth stimulator and that TPO may be involved in megakaryocytic differentiation, rather than growth, of TAM blasts. This suggests that hepatoblasts function in the regulation of the growth and differentiation of TAM blasts in the FL through the production of hematopoietic growth factors, including SCF and TPO, and are involved in the leukemogenesis of TAM.
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http://dx.doi.org/10.1016/j.leukres.2021.106570DOI Listing
June 2021

Heterochronous Suture Line Recurrences in the Jejunal Pouch following Total Gastrectomy for Stage II Gastric Cancer: A Case Report and Literature Review.

Case Rep Oncol 2020 Jan-Apr;13(1):225-232. Epub 2020 Mar 19.

Department of Surgery, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan.

We report the case of a 65-year-old male who developed heterochronous local recurrences of gastric cancer in the jejunal pouch (J-pouch) four times after total gastrectomy. He underwent total gastrectomy, J-pouch, and Roux-en-Y reconstruction for stage II gastric cancer in 2005. Four local recurrences appeared on the esophago-jejunal anastomosis, the suture line within the pouch, the esophago-jejunal anastomosis, and the anastomosis between the jejunum and Y-loop, which were resected by partial excision or endoscopic submucosal dissection. Suture line recurrence of gastric cancer is rare. The common features for each recurrence included the surgically negative resection margins, observation of the same histopathological subtype, absence of remote metastasis or peritoneal seeding, and the recurrence on the anastomotic suture line, suggesting that the cause of recurrence was the implantation of exfoliated cancer cells probably in the suture line. However, there is no established procedure for preventing implantation recurrence currently, the effectiveness of lumen lavage is suggested.
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http://dx.doi.org/10.1159/000505392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154264PMC
March 2020

Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis.

Stem Cell Reports 2019 06 30;12(6):1366-1379. Epub 2019 May 30.

Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address:

Zygotic genome activation (ZGA) begins after fertilization and is essential for establishing pluripotency and genome stability. However, it is unclear how ZGA genes prevent mitotic errors. Here we show that knockout of the ZGA gene Zscan5b, which encodes a SCAN domain with C2H2 zinc fingers, causes a high incidence of chromosomal abnormalities in embryonic stem cells (ESCs), and leads to the development of early-stage cancers. After irradiation, Zscan5b-deficient ESCs displayed significantly increased levels of γ-H2AX despite increased expression of the DNA repair genes Rad51l3 and Bard. Re-expression of Zscan5b reduced γ-H2AX content, implying a role for Zscan5b in DNA damage repair processes. A co-immunoprecipitation analysis showed that Zscan5b bound to the linker histone H1, suggesting that Zscan5b may protect chromosomal architecture. Our report demonstrates that the ZGA gene Zscan5b is involved in genomic integrity and acts to promote DNA damage repair and regulate chromatin dynamics during mitosis.
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http://dx.doi.org/10.1016/j.stemcr.2019.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565874PMC
June 2019

A Well-Differentiated Liposarcoma in the Digit: A Case Report of the 5-Year Post-Surgical Follow-Up.

J Hand Surg Asian Pac Vol 2018 Sep;23(3):415-418

* Department of Orthopaedic Surgery, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Japan.

A liposarcoma is extremely rare in the digits. A 73-year-old woman was diagnosed with a lipoma in her middle finger 10 years ago. As this tumor increased in size and presented with imaging findings that were atypical of lipomas, careful marginal resection biopsy outside the pseudo-capsule was performed, and the tumor was diagnosed as a well-differentiated liposarcoma. At the 5-year follow-up, the patient showed no evidence of local recurrence or metastasis, with no loss of hand function. The findings from this case suggest that even for a lipomatous tumor in the digits, further imaging examination and resection biopsy should be considered if the tumor presents with features that are atypical of lipomas.
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http://dx.doi.org/10.1142/S242483551872027XDOI Listing
September 2018

Esophageal carcinosarcoma comprised of minimally invasive squamous cell carcinoma and undifferentiated pleomorphic sarcoma: A collision cancer?

Pathol Int 2018 Jun 22. Epub 2018 Jun 22.

Department of Surgery, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Chiba-ken, Japan.

Esophageal carcinosarcoma is a rare neoplasm with components of squamous cell carcinoma and sarcomatous spindle cell stroma. The latter may show overt mesenchymal differentiation but is thought to be derived from carcinoma cells in most cases. Here, we report a case of esophageal carcinosarcoma that appeared to be comprised of different origins of epithelial and mesenchymal tumor cells. The sarcomatous component formed an intralumial pedunculated large mass lesion that consisted of pleomorphic atypical histiocyte-like cells. The squamous epithelium exhibited features of mostly dysplasia with minor foci of microinvasive squamous cell carcinoma. The invasive carcinoma was apart from the sarcoma, and no transitions were observed between the epithelial and sarcomatous cells. Immunohistochemistry showed that the sarcoma cells did not express any lineage-specific markers, including those for epithelial cells and histiocytes, which lead to the diagnosis of undifferentiated pleomorphic sarcoma. Although cyclin D1 was overexpressed in the carcinoma cells, it was nearly negative in the sarcoma cells. These findings indicate that the tumor may be a collision carcinosarcoma. It is highly likely that the patient's history of heavy smoking and alcohol consumption were relevant to the pathogenesis, at least for the epithelial component, of the tumor.
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http://dx.doi.org/10.1111/pin.12689DOI Listing
June 2018

Role of monocyte chemoattractant protein-1 in liver fibrosis with transient myeloproliferative disorder in down syndrome.

Hepatol Commun 2018 03 1;2(3):230-236. Epub 2018 Feb 1.

Department of Pediatrics Hyogo Kenritsu Amagasaki Sogo Iryo Center Amagasaki Japan.

Liver fibrosis is a common complication associated with transient myeloproliferative disorder (TMD) in Down syndrome (DS). The exact molecular pathogenesis that regulates disease progression is largely unknown. We recently found serum and/or urinary monocyte chemoattractant protein-1 (MCP-1) as a novel biomarker of liver fibrosis. This study was an analysis to investigate the fibrogenic activity of MCP-1 using the collagen-producing LX-2 human hepatic stellate cell line. We also examined the fibrogenic activity of serum from a male neonate with DS in whom late-onset liver fibrosis developed even after the resolution of TMD. MCP-1 stimulated both cell growth and collagen synthesis of LX-2 in a dose-dependent manner. Patient serum obtained during the active disease phase significantly up-regulated fibrogenic activity, which was suppressed in the presence of MCP-1-blocking antibody. Transient transforming growth factor beta 1 stimulation primed LX-2 to induce prolonged hypersecretion of MCP-1 in the culture supernatant and in collagen synthesis, which was suppressed with MCP-1 blocking antibody as well. MCP-1 accounts for the prolonged activation of collagen-producing hepatic stellate cells in both a paracrine and autocrine manner, thereby promoting liver fibrosis. Anti-cytokine therapy targeting the fibrogenic cytokines of MCP-1, for example, herbal medicine, could provide a new therapeutic intervention for liver fibrosis associated with TMD in DS. ( 2018;2:230-236).
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http://dx.doi.org/10.1002/hep4.1150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831021PMC
March 2018

Lymph Node Collision Tumor Consisting of Metastatic Pulmonary Adenocarcinoma and Diffuse Large B-cell Lymphoma.

Intern Med 2018 Apr 21;57(8):1135-1139. Epub 2017 Dec 21.

Department of Respiratory Medicine, Tokyo Dental College Ichikawa General Hospital, Japan.

A 67-year-old man presented with a fever and general malaise. Computed tomography showed multiple nodules in the lungs and liver, associated with mediastinal and para-aortic lymphadenopathy. Bone marrow aspiration revealed diffuse large B-cell lymphoma (DLBCL). Renal and liver dysfunction and pancytopenia inhibited chemotherapy administration; the patient subsequently died of multiorgan failure. An autopsy revealed pulmonary adenocarcinoma with metastases to the lungs, liver, and adrenal glands; the DLBCL spread to the liver, spleen, and bone marrow. Adenocarcinoma and DLBCL collision was observed in the mediastinal and para-aortic lymph nodes. This was a rare case of collision metastasis occurring in the lymph node.
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http://dx.doi.org/10.2169/internalmedicine.9280-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938506PMC
April 2018

Cutoff Pepsinogen Level for Predicting Unintendedly Eradicated Cases of Helicobacter pylori Infection in Subjects with Seemingly Normal Pepsinogen Levels.

Digestion 2017 30;95(3):229-236. Epub 2017 Mar 30.

Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan.

Backgrounds/aims: In the ABC method, which is a method for risk stratification of gastric cancer using serum anti-Helicobacter pylori antibody and pepsinogen (PG) test, subjects with normal PG and seronegative for H. pylori are named as "Group A" and are regarded as having a low risk of gastric cancer. These "Group A" subjects include unintentionally eradicated cases at relatively high risk, and this study aimed to identify these subjects.

Methods: Of the 109 subjects, 76 were classified as uninfected Group A subjects with negative histologic H. pylori infection and no histologic and endoscopic atrophy, and 33 subjects were classified serologically as Group A after successful eradication, which are serologically equal to the unintendedly eradicated cases in Group A. The usefulness of measuring PG levels to detect post-eradication cases was validated by using a receiver operating characteristic (ROC) curve analysis.

Results: The area under the ROC curve for PGI level was 0.736 ± 0.06 (p < 0.01; cutoff value, 37.0 ng/mL; sensitivity, 77.6%; specificity, 72.7%), and that for the PGI/II ratio was 0.660 ± 0.06 (p < 0.01; cutoff value, 5.1; sensitivity, 84.2%; specificity, 43.4%).

Conclusion: PGI levels of ≤37 ng/mL and PGI/II ratios of ≤5.1 effectively identified unintendedly eradicated cases in Group A.
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http://dx.doi.org/10.1159/000469705DOI Listing
February 2018

Monocyte Chemoattractant Protein-1 (MCP-1) as a Potential Therapeutic Target and a Noninvasive Biomarker of Liver Fibrosis Associated With Transient Myeloproliferative Disorder in Down Syndrome.

J Pediatr Hematol Oncol 2017 07;39(5):e285-e289

Departments of *Pediatrics ¶Pediatric Surgery #Diagnostic Pathology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo Departments of †Pediatric Hematology and Oncology Research ‡Pathology, National Research Institute for Child Health and Development, Tokyo §Department of Pathology and Laboratory Medicine, Tokyo Dental College Ichikawa General Hospital, Chiba ∥Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.

Liver fibrosis is one of the common complications of transient myeloproliferative disorder (TMD) in Down syndrome (DS), but the exact molecular pathogenesis is largely unknown. We herein report a neonate of DS with liver fibrosis associated with TMD, in which we performed the serial profibrogenic cytokines analyses. We found the active monocyte chemoattractant protein-1 expression in the affected liver tissue and also found that both serum and urinary monocyte chemoattractant protein-1 concentrations are noninvasive biomarkers of liver fibrosis. We also showed a prospective of the future anticytokine therapy with herbal medicine for the liver fibrosis associated with TMD in DS.
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http://dx.doi.org/10.1097/MPH.0000000000000809DOI Listing
July 2017

Association of Epithelial Atypia With Recurrence After Surgical Excision in Conjunctival Papilloma.

Eye Contact Lens 2018 Sep;44 Suppl 1:S77-S81

Departments of Ophthalmology (H.Y., M.D., T.Y., S.D., Y.S., J.S.), and Pathology and Laboratory Medicine (J.M., Y.T.), Ichikawa General Hospital, Tokyo Dental College, Chiba, Japan; and Department of Ophthalmology (H.Y., M.D., K.T.), Keio University School of Medicine, Tokyo, Japan.

Purpose: To investigate the association between recurrence of conjunctival papillomas and presence of atypical epithelial changes in patients undergoing surgical excision for conjunctival papilloma.

Methods: We retrospectively reviewed 1,195 ophthalmic pathology specimens from 2004 to 2014 at Ichikawa General Hospital. Pathologic specimens of 5 patients with a final diagnosis of "conjunctival papilloma" were stained with hematoxylin-eosin, Ki 67, p53, human papillomavirus (HPV) 16 and 18 antibodies.

Results: Of 1,195 patients, 5 patients (4 men, 1 woman; age range: 27∼57 years, mean age: 38.4 years) had a diagnosis of conjunctival papilloma, which constituted to 0.42% of the pathologic diagnosis made for the ophthalmology specimens. All specimens displayed multiple fronds of thickened conjunctival epithelium that enclosed cores of vascularized connective tissues. Three patients with recurrence after surgical excision demonstrated moderate to severe epithelial atypia, who also showed higher staining with Ki67 and p53 compared with patients with no recurrence. HPV16 and 18 antibodies staining did not appear to relate to recurrences.

Conclusions: Conjunctival papillomas with higher positive staining for Ki67 and p53 seem to have a higher risk of recurrence even after complete surgical excision and necessitate careful follow-up.
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http://dx.doi.org/10.1097/ICL.0000000000000330DOI Listing
September 2018

Anaplastic carcinoma of the pancreas: Case report and literature review of reported cases in Japan.

World J Gastroenterol 2016 Oct;22(38):8631-8637

Sojun Hoshimoto, Junichi Matsui, Ryohei Miyata, Yutaka Takigawa, Department of Surgery, Tokyo Dental College Ichikawa General Hospital, Chiba 272-8513, Japan.

We report a case of a 64-year-old woman with anaplastic carcinoma of the pancreas (ACP) with cyst formation and review 60 ACP cases reported in Japan. In 20% of cases, laboratory tests revealed severe anemia (hemoglobin level < 10.0 g/dL) and elevated leucocyte counts (> 12000/mm), which were likely attributable to rapid tumor growth, intratumoral hemorrhage, and necrosis. Elevated serum CA19-9 levels were observed in 55% of cases. Cyst-like structures were observed on imaging in 47% of cases, and this finding appears to reflect subsequent cystic degeneration in the lesion. Macroscopically, hemorrhagic necrosis was observed in 77% of cases, and cyst formation was observed in 33% of cases. ACP should be considered when diagnosing pancreatic tumors with a cyst-like appearance, especially in the presence of severe anemia, elevated leucocyte counts, or elevated serum CA19-9 levels.
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http://dx.doi.org/10.3748/wjg.v22.i38.8631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064045PMC
October 2016

Caruncular and Pericaruncular Sebaceous Gland Hyperplasia: A Report of 2 Cases and Literature Review.

Eye Contact Lens 2018 Sep;44 Suppl 1:S316-S319

Department of Ophthalmology (M.O., M.S., M.D., J.S.), Tokyo Dental College Ichikawa General Hospital, Chiba, Japan; Department of Ophthalmology (M.O., M.D., K.T.), Keio University School of Medicine, Tokyo, Japan; Department of Ophthalmology (M.S.), Fukushima University School of Medicine, Fukushima, Japan; Department of Pathology and Laboratory Medicine (J.M., Y.T.), Tokyo Dental College Ichikawa General Hospital, Chiba, Japan; and Department of Ophthalmology (H.O.), Jichi Medical University, Saitama, Japan.

Purpose: To report the clinical and histopathological features of two patients with caruncular and pericaruncular sebaceous gland hyperplasia (SGH) with a literature review.

Methods: We performed a retrospective pathology database search of 1195 ophthalmic specimens receiving the clinical diagnosis of SGH for caruncular/pericaruncular lesions during 2004 to 2014 at Tokyo Dental College, Ichikawa General Hospital. Paraffin sections were stained with hematoxylin and eosin. A retrospective patient record and literature review was also performed.

Results: Database search disclosed 2 male patients with SGH of 1195 specimens (0.15%). Pathological specimens revealed neither any cellular/nuclear atypia nor any mitotic figures and invasive features. No recurrences were observed in these 2 cases 12 to 18 months after excision.

Conclusions: Caruncle and pericaruncular SGH is an uncommon lesion which needs careful histopathological evaluation for differentiation especially from caruncular neoplasias.
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http://dx.doi.org/10.1097/ICL.0000000000000278DOI Listing
September 2018

A Rare Case of an Osteoid Osteoma of the Rib Treated under Computed Tomography Guidance: A Case Report and Review of the Literature.

Case Rep Oncol 2015 Sep-Dec;8(3):509-14. Epub 2015 Nov 21.

Department of Orthopedic Surgery, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan.

Osteoid osteoma (OO) usually occurs in the extremities of young adults. The tumor can arise in any part of the skeletal tissue; however, it is rarely found in the rib, with limited reports to date. In this report, we present a rare case of OO arising in the rib, which was successfully treated under computed tomography guidance with minimal invasiveness. At the final follow-up after 4 years, no local recurrence was observed.
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http://dx.doi.org/10.1159/000441835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677704PMC
December 2015

Predictors of Gastric Neoplasia in Cases Negative for Helicobacter pylori Antibody and with Normal Pepsinogen.

Anticancer Res 2015 Dec;35(12):6765-71

Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan.

Background/aim: Individuals negative for Helicbacter pylori antibody and with a normal pepsinogen test (group A) are regarded as being at low risk in serum gastric cancer screening known as the ABC method, and endoscopy is not recommended; however, this group may include 2-10% of gastric cancer cases.

Patients And Methods: A total of 345 individuals who underwent upper gastrointestinal endoscopy and were classified by ABC as group A (H. pylori antibody titer <10 U/ml, and pepsinogen-I >70 ng/ml or I/II ratio >3) were enrolled, and predictors of gastric neoplasia were investigated.

Results: Ten gastric neoplasia cases (gastric cancer and adenoma) were found to be included. Multiple logistic regression analyses identified H. pylori antibody titer ≥3 U/ml (odds ratio=14.4, 95% confidence interval=2.7-76.9; p<0.01) and pepsinogen-I/II ratio ≤4.3 ng/ml (odds ratio=10.0, 95% confidence interval=2.1-47.9; p<0.01), but not age as independent predictive factors of neoplasia.

Conclusion: Endoscopy should be considered in individuals with H. pylori antibody titer of ≥3 U/ml and a pepsinogen-I/II ratio of ≤4.3 in those classed as group A by ABC method.
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December 2015

Clear cell adenocarcinoma arising from adenomyotic cyst: A case report and literature review.

J Obstet Gynaecol Res 2016 Feb 4;42(2):217-23. Epub 2015 Nov 4.

Pathology and Laboratory Medicine, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan.

Ovaries are the primary sites of cancerous disease that is derived from endometriosis. Uterine cancer originating from endometriosis is very rare. The most frequent histological subtype of cancer derived from endometriosis is endometrioid adenocarcinoma, a subtype of clear cell carcinoma which is exceedingly rare. We report a case of a 40-year-old Japanese woman with a six year history of uterine leiomyoma. The patient was clinically and radiologically suspected to have degenerative uterine myoma with a possible malignant association and underwent a transabdominal total hysterectomy. Histopathological examination of the specimens revealed clear cell adenocarcinoma arising from the adenomyotic cyst. A literature review of clear cell adenocarcinomas arising from uterine adenomyotic cysts (cystic adenomyosis), emphasizes the clinically and radiologically important features of this very rare entity. Clear cell carcinoma association should be suspected in patients who are under follow-up for uterine myomas and present with cystic uterine changes with solid component on magnetic resonance imaging or computed tomography scans.
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http://dx.doi.org/10.1111/jog.12866DOI Listing
February 2016

Mirror syndrome associated with fetal transient abnormal myelopoiesis in Down syndrome.

Pathol Int 2015 Aug 23;65(8):443-5. Epub 2015 Mar 23.

Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, Suita, Japan.

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http://dx.doi.org/10.1111/pin.12291DOI Listing
August 2015

[Staging and evaluation of bone marrow involvement in lymphoma].

Nihon Rinsho 2014 Mar;72(3):456-61

Staging of lymphoma is important for predicting the prognosis and deciding on the treatment strategy for each patient. The Ann Arbor classification and its Cotswolds revised version are widely used, and now comprise the standard staging system for lymphoma. Bone marrow involvement is one of the most important factors in the staging system. Pathological patterns of lymphoma cell infiltration in the marrow are categorized into the following types: 1) nodular/patchy, 2) paratrabecular, 3) interstitial, 4) diffuse, and 5) intrasinusoidal. The frequency and patterns of bone marrow involvement in association with the subtypes of lymphoma are reviewed. PET/CT analysis has become a powerful method for staging lymphoma, and may complement or substitute for bone marrow biopsy in some subtypes of lymphoma.
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March 2014

Fundic gland polyps accurately predict a low risk of future gastric carcinogenesis.

Clin Res Hepatol Gastroenterol 2014 Sep 14;38(4):505-12. Epub 2014 Mar 14.

Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, 272-8513 Chiba, Japan.

Objectives: Few reports have analyzed the clinical importance of sporadic fundic gland polyps (FGPs). The aim of this study was to investigate the relationship between sporadic FGPs and condition of the gastric mucosa stratified by serum pepsinogen levels and Helicobacter pylori antibody level.

Methods: Three hundred and seventy-five subjects undergoing gastrointestinal endoscopy were enrolled. Subjects on proton pump inhibitors were excluded. Pathologically proven FGPs, and other endoscopic findings (reflux esophagitis, gastric and duodenal ulcer) were examined and serum pepsinogen levels, H. pylori antibody concentration and gastric juice pH were measured simultaneously. Subjects with normal serum pepsinogen and negative H. pylori antibodies were defined as having "low risk" stomachs, suggesting low risk of gastric carcinogenesis.

Results: Of the 375 subjects, 44 showed FGPs. The prevalence of "low risk" stomach in subjects with and without FGPs was 98% and 48%, respectively. Multivariable logistic regression analysis indicated three variables as independent factors positively associated with "low risk" stomachs: FGPs (odds ratio [OR] 38.6), reflux esophagitis (OR 4.8), and age<60 years (OR 1.89). Gastric juice pH, which is associated with mucosal atrophy grade and low pH indicates less mucosal atrophy, was significantly lower in subjects with (1.64 ± 0.64) than without FGPs in "low risk" (1.94 ± 1.12) and "high risk" stomachs (3.99 ± 2.31).

Conclusions: Sporadic FGPs tend to be related to the least atrophic mucosa among non-gastric atrophy subjects without H. pylori infection, and can be used as predictors of a low risk of gastric carcinogenesis.
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http://dx.doi.org/10.1016/j.clinre.2014.01.008DOI Listing
September 2014

Fetal liver stromal cells support blast growth in transient abnormal myelopoiesis in Down syndrome through GM-CSF.

J Cell Biochem 2014 Jun;115(6):1176-86

Department of Pathology and Laboratory Medicine, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Chiba-ken, Japan.

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome, which spontaneously resolves within several weeks or months after birth, may represent a very special form of leukemia arising in the fetal liver (FL). To explore the role of the fetal hematopoietic microenvironment in the pathogenesis of TAM, we examined the in vitro influences of stromal cells of human FL and fetal bone marrow (FBM) on the growth of TAM blasts. Both FL and FBM stromal cells expressed mesenchymal cell antigens (vimentin, α-smooth muscle actin, CD146, and nestin), being consistent with perivascular cells/mesenchymal stem cells that support hematopoietic stem cells. In addition, a small fraction of the FL stromal cells expressed an epithelial marker, cytokeratin 8, indicating that they could be cells in epithelial-mesenchymal transition (EMT). In the coculture system, stromal cells of the FL, but not FBM, potently supported the growth of TAM blast progenitors, mainly through humoral factors. High concentrations of hematopoietic growth factors were detected in culture supernatants of the FL stromal cells and a neutralizing antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) almost completely inhibited the growth-supportive activity of the culture supernatants. These results indicate that FL stromal cells with unique characteristics of EMT cells provide a pivotal hematopoietic microenvironment for TAM blasts and that GM-CSF produced by FL stromal cells may play an important role in the pathogenesis of TAM.
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http://dx.doi.org/10.1002/jcb.24764DOI Listing
June 2014

Bilateral intralobar sequestration of the lung with a bridging isthmus: pathologic and radiologic findings.

Pediatr Dev Pathol 2014 Jan-Feb;17(1):55-8. Epub 2013 Oct 21.

1  Department of Pathology, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo 183-8561, Japan.

A 4-year-old boy presented with pneumonia. Computed tomography demonstrated a multicystic mass at the posteromedial bilateral lower lobe segments, which were connected by a bronchus behind the heart. Enhanced computed tomography revealed that an anomalous artery arose from the left gastric artery and inserted into the left sequestrated lung and branched to the right one. The diagnosis of bilateral intralobar sequestration (ILS) with a bridging isthmus was made. After removal of the bilateral ILS, radiologic and pathologic approaches were undertaken to reconstruct the vascular and bronchial architectures. The following observations were made: (1) histologically, the region near the anomalous artery insertion site contained bronchial structures, which looked like an ectopic pulmonary hilus. This bronchial structure was continuously observed in the isthmus and its opening of the right sequestrated lung; (2) radiologically, the shape and course of the bronchi within the ILS indicated a distinct bronchial origin that arose from the pulmonary hilus-like structure, and the anomalous artery that ran along with those bronchi, resembled a pulmonary artery. These features suggested that this bilateral ILS might have originated from an accessory lung tissue.
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http://dx.doi.org/10.2350/13-08-1371-CR.1DOI Listing
May 2014

[Epidural abscess in the spine extended from pulmonary zygomycosis during consolidation chemotherapy for acute lymphoblastic leukemia].

Rinsho Ketsueki 2011 Aug;52(8):718-21

Department of Internal Medicine, Tokyo Dental College Ichikawa General Hospital.

A 37-year-old woman with acute lymphoblastic leukemia developed fever and pneumonia during persistent neutropenia after consolidation chemotherapy. Pneumonia was rapidly followed by the formation of abscess in adjacent subcutaneous tissues, muscles and bones. She subsequently developed sudden onset of paraplegia and loss of all sensation below Th4. Epidural abscess was detected by MRI. Emergency drainage was performed, but the patient died 4 days after the operation. Rhizopus oryzae grew from culture of the epidural abscess. Since the incidence of zygomycosis appears to have increased over the recent years, clinicians should be aware of the possibility of zygomycosis in case of any infection that is resistant to antibiotics.
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August 2011

Clinico-pathologic conference: case 4. Langerhans cell histiocytosis (LCH).

Head Neck Pathol 2010 Dec 19;4(4):343-6. Epub 2010 Nov 19.

Department of Pathology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan.

A 13-month-old Japanese boy presented with painless swelling in a left mandible and cheek. Intraoral examination revealed swelling in the left mandible and hemorrhage of oral mucosa due to biting. CT images revealed a wide osteolytic lesion of the left mandible with floating teeth. Biopsy was carried out and histopathological diagnosis was discussed.
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http://dx.doi.org/10.1007/s12105-010-0224-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996504PMC
December 2010

Expression of megakaryocytic and myeloid markers in blasts of transient abnormal myelopoiesis in a stillbirth with Down syndrome: report of histopathological findings of an autopsy case.

Hum Pathol 2011 Jan 20;42(1):141-5. Epub 2010 Oct 20.

Department of Pathology, Shiga University of Medical Science, Otsu, Shiga-ken 520-2192, Japan.

Transient abnormal myelopoiesis in neonates with Down syndrome is an unusual leukemia that spontaneously regresses within several months of life and is thought to arise in the fetal liver. It is largely unknown how the leukemic blasts proliferate and differentiate in fetal tissues. We report the histopathological findings of an autopsy case of a stillbirth with transient abnormal myelopoiesis. Blood vessels in almost all organs were filled with immature leukemic cells, most of which expressed megakaryocyte antigen CD42b. In contrast, leukemic cells infiltrating the tissues, including the pericardium, expressed myeloperoxidase. These findings indicate that leukemic progenitors in transient abnormal myelopoiesis can differentiate along both megakaryocytic and myeloid lineages, which may be influenced by microenvironmental factors. Numerous dysplastic mature/immature megakaryocytes and blasts were present in the liver, whereas the bone marrow contained predominantly myeloid cells at various stages of differentiation, suggesting that the fetal liver is the major organ for proliferation of blasts in transient abnormal myelopoiesis.
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http://dx.doi.org/10.1016/j.humpath.2010.06.012DOI Listing
January 2011

[A case of advanced adenocarcinoma of the lung which maintained complete response for 5 years by treatment with gefitinib].

Nihon Kokyuki Gakkai Zasshi 2010 Aug;48(8):600-3

Department of Internal Medicine, Tokyo Dental College.

A 73-year-old woman smoker presented with dyspnea on exertion due to massive left pleural effusion. A CT scan after drainage of the pleural effusion demonstrated a nodule in the left lung, and cytology of the pleural effusion showed adenocarcinoma. We diagnosed advanced adenocarcinoma of the lung, and clinical stage IIIB. Chemotherapy with carboplatin and docetaxel was discontinued after the second course because of anorexia, and gefitinib was administered from October 2004. The lung nodule and pleural effusion had disappeared on CT by November 2004. A complete response continued for 5 years. We report a 5-year complete response in a case of advanced adenocarcinoma of the lung by treatment with gefitinib.
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August 2010

[A case of miliary tuberculosis showing acute respiratory distress syndrome in rheumatoid arthritis].

Nihon Kokyuki Gakkai Zasshi 2010 Mar;48(3):235-9

Department of Internal Medicine, Tokyo Dental College.

A 62-year-old man, treated with corticosteroids and immunosuppressants for rheumatoid arthritis, visited hospital with high fever and dyspnea on exertion. A CT scan of the chest demonstrated bilateral diffuse ground glass opacities. On the basis of the findings of the CT scan, he was initially given a diagnosis of interstitial pneumonia. He was then referred to our hospital and admitted to the intensive care unit (ICU), where because of progressive respiratory failure, he was put on mechanical ventilation. A bronchoscopy specimen after intubation turned out to be positive for acid-fast bacilli, which were confirmed to be mycobacterium tuberculosis by a polymerase chain reaction test. He was given a diagnosis of miliary tuberculosis complicated with acute respiratory distress syndrome (ARDS). He died of respiratory failure despite treatment with antituberculosis drugs. The autopsy revealed necrotizing epithelioid granulomas in both lungs, mediastinal lymph nodes, the liver, both kidneys, vertebrae and other organs. Diffuse alveolar damage was also found in both lungs. It is often difficult to detect disseminated nodules in the miliary tuberculosis with ARDS. Miliary tuberculosis should be suspected in patients in an immunosuppressant state with rheumatoid arthritis, and who have respiratory symptoms or fever of unknown origin.
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March 2010

Blasts in transient leukaemia in neonates with Down syndrome differentiate into basophil/mast-cell and megakaryocyte lineages in vitro in association with down-regulation of truncated form of GATA1.

Br J Haematol 2010 Mar 11;148(6):898-909. Epub 2010 Jan 11.

Department of Pathology and Laboratory Medicine, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba-ken, Japan.

Mutations of GATA1, leading to aberrant expression of a truncated form of GATA1 (called GATA1s), are present in transient leukaemia (TL) in neonates with Down syndrome. Using these molecular markers of TL, we investigated the growth and differentiation potential of TL blasts in the presence of hematopoietic growth factors (HGFs). Interleukin-3, stem cell factor and granulocyte-macrophage colony-stimulating factor potently stimulated the growth of TL blast progenitors and induced differentiation towards basophil/mast cell lineages, whereas thrombopoietin induced differentiation towards megakaryocytes. GATA1s was expressed in TL blasts in all five patients examined but was down-regulated during differentiation induced by these HGFs, while full-length GATA1 was not expressed throughout the culture. GATA1 mutations were detected in TL blasts in four patients, including one patient with two distinct mutations. The cells of this patient exhibited identical and only mutated sequences both before and after culture with HGFs, confirming the leukemic cell origin of these differentiated cells. Erythroid differentiation of TL blasts was not evident with any HGFs. These data indicate that TL blasts have the potential to grow and differentiate towards particular hematopoietic lineages in the presence of specific HGFs and that the down-regulation of GATA1s might be involved in blast cell differentiation.
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http://dx.doi.org/10.1111/j.1365-2141.2009.08038.xDOI Listing
March 2010

Histologic survey of neuroblastomas after intensive induction chemotherapy.

Pediatr Blood Cancer 2005 Oct;45(5):656-62

Department of Surgery, Gunma Children's Medical Center, Gunma, Japan.

Background: Histology after intensive induction chemotherapy is expected to become a beacon indicating when and how extensively radical surgery and lymph node dissection should be performed in advanced neuroblastoma. A thorough histologic review of surgical specimens was undertaken.

Procedure: All specimens from 34 patients who were pretreated intensively (> or =3 cycles) with recent chemotherapy were reviewed. Thirty patients were >12 months of age with stage 3/4 disease, and 4 were <12 months of age but with MYCN-amplified stage 4 diseases. After 3 to 7 cycles (mean, 4.3 cycles) of induction chemotherapy, patients underwent radical surgery of the primary tumor and lymph nodes in all retroperitoneal sections. A single pathologist reviewed all of the specimens, and histologic chemotherapeutic effects were graded as: (+++), <1% viable tumor; (++), 1%-10% viable tumor; (+), 11%-50% viable tumor; (+/-), 51%-90% viable tumor; and (-), >91% viable tumor.

Results: Grade (+++) effects were observed in 56% of patients treated with the new regimens, whereas grade (+++) was seen in only 20% treated with regimens before 1991. Operation time and blood loss were 7 hr and 6 min (P = 0.087) and 646 ml (P = 0.064), respectively, in patients with >5 cycles (mean, 5.3 cycles) of chemotherapy, while they were 7 hr and 50 min and 1,168 ml, respectively, in those with approximately 3 cycles (mean, 3.2 cycles). Histologically, metastases were found in the contralateral nodes beyond the aorta in 92% of those whose tumor originated on the left, and in 80% of those with tumors occurring on the right.

Conclusions: Five cycles of induction chemotherapy did not improve histologic chemotherapeutic effects, but helped to facilitate a shorter operation time and less blood loss than 3 cycles of chemotherapy. Surgery after 5 cycles of (98)A(3) also appears to be easier to perform than that after 3 cycles of A(1)/new A(1). Only 14% of the children treated before 1985 with the St. Jude protocols experienced grade (+++) chemotherapeutic effects, and 22% of the patients treated before 1991 with regimen A(1), or new A(1) of the Study Group of Japan showed grade (+++) effects, whereas 56% of the patients treated after 1991 with either regimen A(3) or (98)A(3) exhibited grade (+++) chemotherapeutic effects. Histologic chemotherapeutic effects were roughly parallel with a good prognosis.
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http://dx.doi.org/10.1002/pbc.20345DOI Listing
October 2005

Clonality analysis of childhood neuroblastoma by polymerase chain reaction for the human androgen receptor gene.

Int J Oncol 2005 May;26(5):1329-35

Department of Clinical Laboratory, National Children's Hospital, Setagaya-ku, Tokyo 154-8509, Japan.

Neuroblastoma is a unique tumor that occurs during childhood. Tumors in infants less than one year of age often regress spontaneously and usually have an excellent prognosis, whereas those in older patients are aggressive, leading to a fatal outcome. To shed light on these unique aspects of this tumor, we investigated the clonality of neuroblastomas by analyzing the inactivation patterns through methylation of the human androgen receptor gene on the X chromosomes in female patients. Neuroblastoma tissue samples were obtained from 12 patients, including 10 patients less than one year of age with tumors at stage 1, 2 or 4S and 2 older patients with stage 4 tumors. Except for 3 uninformative samples of infants, all the informative samples unexpectedly exhibited random methylation pattern, and tumor tissues purified with microdissection technique exhibited the same results. These data indicate that neuroblastomas examined are polyclonal in origin, an unusual finding for a neoplasm, which might be relevant to the unique aspects of neuroblastoma.
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May 2005

Life-threatening airway obstruction caused by mediastinal germinoma in a 9-year-old girl.

J Pediatr Surg 2005 Mar;40(3):588-90

Department of Surgery, National Center for Child Health and Development, Tokyo 157-8535, Japan.

The authors report a case of a 9-year-old girl with a mediastinal germinoma that required emergent surgical extirpation because of tracheal compression and asphyxia. The tumor was successfully debulked under general anesthesia with the capability of extracorporeal circulation immediately available. Postoperatively, the tumor responded to adjuvant chemotherapy and irradiation and the patient survived without evidence of recurrence.
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http://dx.doi.org/10.1016/j.jpedsurg.2004.11.021DOI Listing
March 2005
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