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1.
J Surg Res ; 200(1): 73-81, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26233688

ABSTRACT

BACKGROUND: The objectives were to investigate the accuracy of sentinel lymph node (SLN) biopsy, detect the predictors for undetected or false-negative cases, evaluate the indications for SLN-navigated gastrectomy, and characterize the problems of SLN mapping in gastric cancer. The SLN concept may be applicable to early gastric cancer, particularly clinical T1N0M0 or T2N0M0 with tumor diameter ≤4Ā cm. METHODS: A total of 385 consecutive patients diagnosed with cT1N0M0 or cT2aN0M0 operable gastric cancer from April 1999 to December 2007 underwent radical gastrectomy with SLN mapping. SLNs were identified using radio-guided and dye-guided methods. Predictors for undetected or false-negative cases on SLN mapping were examined by multivariate regression analysis. RESULTS: The detection rate of hot and/or blue nodes was 96.6% (372 of 385). The accuracy of metastatic status based on SLNs was 98.9% (368 of 372) for all cases in whom SLNs could be detected. Furthermore, the accuracy of metastatic status based on SLNs was 99.1% (344 of 347) in cT1 gastric cancer and 96.0% (24 of 25) in cT2 gastric cancer. Pathologically, the tumors invaded to the muscularis propria or deeper in three of four false-negative cases. All but one case had metastatic lymph nodes within the sentinel basins. In terms of 5-y recurrence free survival, positive SLN cases (SLN(+)) had a worse prognosis than negative SLN cases (SLN(-); PĀ =Ā 0.008). Moreover, SLN(+) and non-SLN(-) cases (SLN(+)/non-SLN(-)) had a similar prognosis as SLN(+) and non-SLN(+) cases (SLN(+)/non-SLN(+)) (PĀ =Ā 0.511). On multivariate regression analysis, undetected or false-negative cases were significantly associated with the time period. CONCLUSIONS: The present results appeared to validate the SLN concept for untreated cT1 gastric cancer with tumor diameter ≤4Ā cm. SLN mapping may provide an effective method of staging the lymph node status of patients undergoing minimized gastrectomy. Sentinel basin dissection guards against the possibility of leaving positive lymph nodes. Stabilization of the procedure and experience with SLN mapping in gastric cancer might decrease undetected or false-negative cases.


Subject(s)
Gastrectomy , Sentinel Lymph Node Biopsy/methods , Stomach Neoplasms/surgery , Adult , Aged , Aged, 80 and over , False Negative Reactions , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Analysis
2.
Ann Surg Oncol ; 21(9): 2987-93, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24682720

ABSTRACT

BACKGROUND: When pathological diagnosis following endoscopic resection (ER) for early gastric cancer (EGC) suggests probable lymph node metastasis, additional surgery with lymphadenectomy should be performed. The sentinel node (SN) concept has yet to be applied to tumors following ER. The aim of this study was to evaluate the feasibility of SN navigation surgery for such tumors. METHODS: Forty patients diagnosed with EGC lesions <4 cm in diameter underwent gastrectomy with SN mapping following ER. A technetium-99 m tin colloid solution and a dye were injected into the submucosal layer around the post-ER scar in all four abdominal quadrants. We then compared the SN distribution and metastases among the patients who underwent ER and controls (n = 192). RESULTS: SNs were identifiable in all patients, and the mean number of SNs per case was 4.9. The location of the SN basin was similar in the patients who underwent ER and the controls. One patient (3 %) whose primary tumor had invaded the submucosal layer had a metastatic SN. The median time from ER to surgery was 73 days. No postoperative recurrence was observed in any patient over a median follow-up of 1,023 days. CONCLUSIONS: Our findings suggest that the SN basin is not greatly affected by ER. The SN concept could be suitable for tumors following ER, but conventional gastrectomy with lymphadenectomy involving the SN basin should be used at present.


Subject(s)
Gastrectomy , Gastroscopy , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy/statistics & numerical data , Stomach Neoplasms/pathology , Aged , Case-Control Studies , Female , Follow-Up Studies , Humans , Laparoscopy , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Risk Assessment , Stomach Neoplasms/surgery
3.
Gastric Cancer ; 17(2): 273-80, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23743877

ABSTRACT

BACKGROUND: The accurate diagnosis of lymph node (LN) metastasis is important for making treatment decisions for gastric cancer patients. This multicenter study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay (Sysmex Corp.), an automated system that detects cytokeratin 19 (CK19) mRNA, in detecting LN metastases in gastric cancer patients. METHODS: LNs retrieved from patients who had undergone gastric cancer surgery at one of the four Japanese hospitals involved in this study were divided into blocks at 2-mm intervals. Alternate blocks were examined with the OSNA assay and the remaining blocks were assessed histologically. RESULTS: A total of 394 LNs from 61 patients were examined. The concordance rate between the OSNA assay and the histological examination was 0.942 (95Ā % CI, 0.914-0.963). Sensitivity and specificity of the OSNA assay compared to the histological examination were 0.833 (95Ā % CI, 0.707-0.921) and 0.959 (95Ā % CI, 0.932-0.977), respectively. Discordant results were observed in 23 LNs (5.8Ā %), and these were mainly the result of tissue allocation bias and/or low CK19 protein expression. CONCLUSION: The OSNA assay can detect lymph node metastases in gastric cancer patients as accurately as the histological examination of blocks sectioned at 2-mm intervals. The OSNA assay is a useful tool for the intraoperative diagnosis of LN metastasis in gastric cancer patients.


Subject(s)
Adenocarcinoma, Mucinous/secondary , Adenocarcinoma/secondary , Biomarkers, Tumor/analysis , Carcinoma, Papillary/secondary , Carcinoma, Signet Ring Cell/secondary , Nucleic Acid Amplification Techniques/methods , Stomach Neoplasms/pathology , Adenocarcinoma/genetics , Adenocarcinoma/surgery , Adenocarcinoma, Mucinous/genetics , Adenocarcinoma, Mucinous/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Papillary/genetics , Carcinoma, Papillary/surgery , Carcinoma, Signet Ring Cell/genetics , Carcinoma, Signet Ring Cell/surgery , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Sentinel Lymph Node Biopsy , Stomach Neoplasms/genetics , Stomach Neoplasms/surgery
4.
World J Surg ; 38(9): 2337-44, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24752362

ABSTRACT

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing, but the surgical strategy for AEG remains controversial. We hypothesized that sentinel node (SN) mapping for AEG could be validated to avoid unnecessary lymphadenectomy and permit minimally invasive surgery. We examined the feasibility of SN mapping for AEG. METHODS: We enrolled 15 patients with preoperatively diagnosed cT1 N0 M0 primary AEG (Siewert type I, N = 3; Siewert type II, N = 12) lesions measuring <4 cm in diameter. The dual tracer method employing radioactive colloid and blue dye was used to detect SNs. The distribution of SNs was compared with that of metastatic lymph nodes in 52 patients who were surgically treated without SN mapping. RESULTS: SNs were successfully identified in all the patients. Two patients with lymph node metastasis had positive SNs identified via an intraoperative pathological examination, and the diagnostic sensitivity and accuracy based on the SN status were both 100 %. For Siewert type II AEG, the SNs were not detected in the lower mediastinum by intraoperative gamma probing. Thus, all surgical procedures were performed via a transhiatal approach. No patient without SN metastasis experienced cancer recurrence during a 38-month median follow-up. The distribution of SNs was similar to that of lymph node metastasis in the patients who were surgically treated without SN mapping. CONCLUSIONS: We achieved 100 % SN detection. Our results suggested that SN mapping is feasible for AEG and highly sensitive and accurate in diagnosing lymph node metastasis. SN mapping may clarify the necessity of mediastinal lymph node dissection and individualize minimally invasive surgery.


Subject(s)
Adenocarcinoma/secondary , Esophageal Neoplasms/pathology , Esophagogastric Junction , Lymph Node Excision/methods , Lymph Nodes/pathology , Neoplasm Recurrence, Local/pathology , Sentinel Lymph Node Biopsy/methods , Adenocarcinoma/surgery , Aged , Coloring Agents , Esophageal Neoplasms/surgery , Esophagectomy , Feasibility Studies , Female , Humans , Indocyanine Green , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Radiopharmaceuticals , Rosaniline Dyes , Sensitivity and Specificity , Technetium Compounds , Tin Compounds
5.
J Foot Ankle Surg ; 53(1): 71-4, 2014.
Article in English | MEDLINE | ID: mdl-24238967

ABSTRACT

Desmoplastic fibroma (DF) of the bone is a rare locally aggressive tumor usually occurring in adolescents and young adults. These tumors most commonly occur in the mandibles and metaphyses of long bones but are extremely rare in small bones, often resulting in diagnostic problems. The occurrence of these tumors in the foot is especially limited. We report the clinical, radiographic, and histologic features of DF arising in the distal phalanx of the great toe and a review of the published data.


Subject(s)
Bone Neoplasms/diagnostic imaging , Fibroma, Desmoplastic/diagnostic imaging , Hallux/diagnostic imaging , Adolescent , Bone Neoplasms/surgery , Bone Transplantation , Fibroma, Desmoplastic/surgery , Hallux/surgery , Humans , Male , Radiography , Transplantation, Homologous
6.
Nat Med ; 12(10): 1151-9, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16980969

ABSTRACT

The avascularity of cardiac valves is abrogated in several valvular heart diseases (VHDs). This study investigated the molecular mechanisms underlying valvular avascularity and its correlation with VHD. Chondromodulin-I, an antiangiogenic factor isolated from cartilage, is abundantly expressed in cardiac valves. Gene targeting of chondromodulin-I resulted in enhanced Vegf-A expression, angiogenesis, lipid deposition and calcification in the cardiac valves of aged mice. Echocardiography showed aortic valve thickening, calcification and turbulent flow, indicative of early changes in aortic stenosis. Conditioned medium obtained from cultured valvular interstitial cells strongly inhibited tube formation and mobilization of endothelial cells and induced their apoptosis; these effects were partially inhibited by chondromodulin-I small interfering RNA. In human VHD, including cases associated with infective endocarditis, rheumatic heart disease and atherosclerosis, VEGF-A expression, neovascularization and calcification were observed in areas of chondromodulin-I downregulation. These findings provide evidence that chondromodulin-I has a pivotal role in maintaining valvular normal function by preventing angiogenesis that may lead to VHD.


Subject(s)
Aorta/pathology , Heart Valve Diseases/pathology , Intercellular Signaling Peptides and Proteins/physiology , Membrane Proteins/physiology , Mitral Valve/pathology , Neovascularization, Pathologic , Aged , Angiogenesis Inhibitors/pharmacology , Animals , Aorta/metabolism , Culture Media, Conditioned/metabolism , Echocardiography , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Male , Membrane Proteins/metabolism , Mice , Mice, Inbred ICR , Mice, Transgenic , Middle Aged , Mitral Valve/metabolism , Rats , Rats, Wistar
7.
Ann Surg Oncol ; 19(2): 469-77, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22065193

ABSTRACT

PURPOSE: Described is a novel real-time multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay suitable for intraoperative detection of micrometastasis (MM) in sentinel nodes (SNs) dissected from patients with clinical N0 (cN0) gastric carcinoma. METHODS: One hundred three patients with gastric cancer, who were preoperatively diagnosed with cN0 and clinical T1 or T2, were enrolled. The patients underwent SN mapping followed by standard radical gastrectomy with lymph node dissection. In addition to all SNs, non-SNs (NSNs) within the SN lymphatic basin and NSN from a different lymphatic basin were randomly sampled. All SNs and NSNs were examined by routine histologic diagnosis and RT-PCR for the expression of cytokeratin (CK) 19, CK20, and carcinoembryonic antigen (CEA). RESULTS: The RT-PCR assay and histologic examination were performed in 512 SNs and 299 NSNs from 103 patients. Pathologic l lymph node metastasis was revealed in 13 (12.6%) of 103 patients. All metastatic lymph nodes were identified within SNs. SNs of these 13 patients had positive findings on RT-PCR. Twenty-eight (27.2%) of 103 patients had negative histopathology but positive findings on RT-PCR. In 7 patients (6.8%), SNs were negative but NSNs were positive on RT-PCR. RT-PCR-positive NSNs were present in the same station as corresponding SNs in 3 of these 7 patients and in the same basin as SNs in 4 patients. CONCLUSIONS: The real-time multiplex RT-PCR assay is a useful tool for the detection of MM in SNs and NSNs in patients with gastric cancer.


Subject(s)
Biomarkers, Tumor/genetics , Lymph Nodes/pathology , Neoplasm Micrometastasis/diagnosis , Sentinel Lymph Node Biopsy , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Carcinoembryonic Antigen/genetics , Carcinoembryonic Antigen/metabolism , Female , Follow-Up Studies , Humans , Keratins/genetics , Keratins/metabolism , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Micrometastasis/genetics , Neoplasm Staging , Prognosis , RNA, Neoplasm/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate
8.
Ann Surg Oncol ; 19(6): 1831-40, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22396001

ABSTRACT

BACKGROUND: Studies have suggested that HOXB9 expression in breast cancer cells promotes cellular invasiveness, metastatic ability, and tumor neovascularization in the surrounding tissue in in vitro and in vivo assays. These findings imply that HOXB9 overexpression may alter tumor-specific cell fates and the tumor stromal microenvironment, contributing to breast cancer progression. The objective of this study was to analyze whether these results could be applied to clinical practice. METHODS: A total of 141 consecutive, invasive ductal carcinoma patients who underwent surgical treatment were examined. Immunohistochemical staining was performed to evaluate the expression of HOXB9, Ki-67, CD31, and CD34, and the association of tumor proliferation and angiogenesis with HOXB9 expression was analyzed. RESULTS: Of the 141 tumor specimens immunostained for HOXB9, 69 (48.9%) stained positive. Larger primary tumor size, hormone receptor negativity, HER2 positivity, higher nuclear grade, and number of pathologic nodal metastases were significant variables associated with HOXB9 expression. Notably, 12 (92.3%) of 13 triple-negative breast cancer cases showed HOXB9 expression. Disease-free survival and overall survival were significantly different between the HOXB9-positive and HOXB9-negative groups (hazard ratio 20.714, P = 0.001; and hazard ratio 9.206, P = 0.003, respectively). Multivariate analysis indicated that HOXB9 expression was the only independent prognostic factor for disease-free survival (hazard ratio 15.532, P = 0.009). HOXB9-positive tumors showed a significant increase in the number of vasculature and the Ki-67 ratio compared with HOXB9-negative tumors. CONCLUSIONS: HOXB9 expression, which promotes tumor proliferation and angiogenesis, is a significant prognostic factor in breast cancer.


Subject(s)
Breast Neoplasms/blood supply , Breast Neoplasms/pathology , Cell Proliferation , Homeodomain Proteins/metabolism , Neovascularization, Pathologic , Adenocarcinoma/blood supply , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/blood supply , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/pathology , Female , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Survival Rate
9.
BMC Cancer ; 12: 444, 2012 Oct 02.
Article in English | MEDLINE | ID: mdl-23031740

ABSTRACT

BACKGROUND: Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy. CASE PRESENTATION: The patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10. CONCLUSION: This case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo.


Subject(s)
Li-Fraumeni Syndrome/complications , Liver Neoplasms/complications , Osteosarcoma/complications , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers/blood , Child , Female , Genes, p53 , Germ-Line Mutation , Humans , Hyaluronan Receptors/genetics , Li-Fraumeni Syndrome/genetics , Liver/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Osteosarcoma/diagnosis , Osteosarcoma/drug therapy , Osteosarcoma/genetics , Protein Isoforms/genetics , Treatment Outcome
10.
World J Surg ; 36(2): 424-30, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22187130

ABSTRACT

BACKGROUND: The evolution of diagnostic procedures has resulted in an increase in early detection of pathologically T1 (pT1) colorectal cancer (CRC). However, the risk factors affecting long-term outcomes of patients with pT1 CRCs have been unclear. The aim of the present study was to identify risk factors for postoperative recurrence and overall survival in patients with pT1 CRC. METHODS: Between January 1990 and January 2003, a total of 284 patients with pT1 CRC underwent radical surgery in the authors' institution. The impact of clinicopathological factors on postoperative recurrence and overall survival was estimated by univariate and multivariate analysis. RESULTS: The median follow-up period was 55 months (interquartile range: 47.1 months). Postoperative recurrence occurred in 8 (2.8%) patients. The overall 5-year and 10-year disease-free survival rates were 98.4 and 92.7%. Multivariate analysis showed the presence of lymphatic invasion only was an independent risk factor for postoperative recurrence in pT1 CRC patients (hazard ratio: 11.622; P = 0.003). The 5-year and 10-year disease-free survival rates of the patients in N-ly- group, the N-ly + group, and the N+ group were 99.5%/98.2% and 96.3%/75.2%, and 93.3%/93.3%, respectively. Additionally, 4 of the 8 recurrences were found more than 5 years after the operation. CONCLUSIONS: Lymphatic invasion was an independent risk factor for recurrence in pT1 CRC patients.


Subject(s)
Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Neoplasm Recurrence, Local/etiology , Aged , Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Female , Follow-Up Studies , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/etiology , Liver Neoplasms/mortality , Lung Neoplasms/diagnosis , Lung Neoplasms/etiology , Lung Neoplasms/mortality , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Population Surveillance , Risk Factors , Survival Analysis , Survival Rate
11.
Pathol Int ; 62(12): 823-6, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23252872

ABSTRACT

Mesenchymal chondrosarcoma (MC) is an extremely rare subtype of chondrosarcoma. A tumor specific fusion gene, HEY1-NCOA2 fusion, was recently identified in this tumor. The finding raises the possibility that the diagnosis of MC can be improved by examining the fusion gene. In the present study, we aimed to evaluate the efficacy of fluorescence in situ hybridization (FISH) in detecting HEY1-NCOA2 fusion for the diagnosis of MC. Specimens from 10 patients diagnosed with MC were used for the study. Dual-color FISH was performed using two different probes that specifically hybridize to HEY1 and NCOA2, respectively. Fusion signals were identified in all but two specimens, in which no signal was detected, presumably because of inadequate sample preparation. In accordance with results of a previous study, FISH analysis was highly sensitive in detecting HEY1-NCOA2 fusion in adequately prepared MC samples. The current study adds further support for the use of HEY1-NCOA2 fusion as a valid diagnostic marker for MC.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/analysis , Bone Neoplasms/diagnosis , Cell Cycle Proteins/analysis , Chondrosarcoma, Mesenchymal/diagnosis , In Situ Hybridization, Fluorescence/methods , Nuclear Receptor Coactivator 2/genetics , Oncogene Proteins, Fusion/analysis , Adolescent , Adult , Basic Helix-Loop-Helix Transcription Factors/genetics , Bone Neoplasms/genetics , Cell Cycle Proteins/genetics , Chondrosarcoma, Mesenchymal/genetics , Formaldehyde , Humans , Nuclear Receptor Coactivator 2/analysis , Oncogene Proteins, Fusion/genetics , Paraffin Embedding , Tissue Fixation , Young Adult
12.
Int J Clin Oncol ; 17(4): 412-6, 2012 Aug.
Article in English | MEDLINE | ID: mdl-21927829

ABSTRACT

Sunitinib, a multitargeted tyrosine kinase inhibitor, is widely used in the treatment of carcinoma. Adverse events associated with this treatment, including fatigue, diarrhea, and hematotoxicity, have been reported in clinical trials. Bowel perforation is a surgical emergency that requires immediate treatment depending on the location and progression of the tumor. We report 2 cases of bowel perforation during sunitinib treatment. The patients presented with diffuse peritonitis, and emergency exploratory laparotomy was performed. We speculate that the underlying mechanisms were decrease in capillary density of the normal mucosa in case 1 and tumor shrinkage because of sunitinib treatment in case 2. To the best of our knowledge, this is the first study to report the pathological findings implicating bowel perforation due to sunitinib treatment. Further investigations are needed to clarify the risk factors for intestinal perforations associated with sunitinib treatment.


Subject(s)
Carcinoma, Renal Cell/drug therapy , Indoles/adverse effects , Kidney Neoplasms/drug therapy , Peritonitis , Pyrroles/adverse effects , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/pathology , Female , Humans , Indoles/administration & dosage , Intestinal Perforation/complications , Intestinal Perforation/pathology , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Middle Aged , Peritonitis/chemically induced , Peritonitis/complications , Peritonitis/surgery , Pyrroles/administration & dosage , Sunitinib
13.
Sarcoma ; 2012: 345161, 2012.
Article in English | MEDLINE | ID: mdl-22550416

ABSTRACT

Myxoid/round cell liposarcoma (MRCL), unlike other soft tissue sarcomas, has been associated with unusual pattern of metastasis to extrapulmonary sites. In an attempt to elucidate the clinical features of MRCL with metastatic lesions, 58 cases, from the medical database of Keio University Hospital were used for the evaluation. 47 patients (81%) had no metastases, whereas 11 patients (11%) had metastases during their clinical course. Among the 11 patients with metastatic lesions, 8 patients (73%) had extrapulmonary metastases and 3 patients (27%) had pulmonary metastases. Patients were further divided into three groups; without metastasis, with extrapulmonary metastasis, and with pulmonary metastasis. When the metastatic patterns were stratified according to tumor size, there was statistical significance between the three groups (P = 0.028). The 8 cases with extrapulmonary metastases were all larger than 10 cm. Similarly, histological grading had a significant impact on metastatic patterns (P = 0.027). 3 cases with pulmonary metastatic lesions were all diagnosed as high grade. In conclusion, large size and low histological grade were significantly associated with extrapulmonary metastasis.

14.
Lab Invest ; 91(10): 1443-58, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21808237

ABSTRACT

The Snail family transcription factors have been proposed as important mediators of epithelial-mesenchymal transition because of their role in down-regulation of E-cadherin and up-regulation of matrix metalloproteinases (MMPs). The present study was undertaken to investigate the expression of Snail, Slug and their associations with cancer invasion and prognosis in renal cell carcinomas (RCCs). Ninety-seven primary RCCs were analyzed for the protein expression of Snail, Slug, MMP2 and MMP9 by immunohistochemistry. Snail protein expression level was positively correlated with pathological tumor stage, histological grade and the presence of sarcomatoid carcinoma. On the contrary, Slug protein expression level was negatively correlated with pathological tumor stage, suggesting that Slug was down-regulated in advanced RCCs. Because Snail was positively associated with malignant potential of RCCs, involvement of Snail in the invasiveness of an RCC cell line 786-O was examined in the Matrigel invasion assay by down-regulating the gene expression with small interfering RNA (siRNA). Targeting the Snail, not Slug, expression in 786-O cells with siRNA caused down-regulation of the gene expression of Snail, vimentin, MMP2 and MMP9, but up-regulated the E-cadherin. Invasion of the cells through Matrigel in vitro was inhibited under this condition. Furthermore, expression levels of MMP2 and MMP9 were positively correlated with pathological tumor stage and the presence of sarcomatoid carcinoma. Statistical analysis indicated that elevated Snail, MMP2 and MMP9 protein expression are significantly worse predictors of disease-free and disease-specific survival of the patients with RCC. In conclusion, these data suggest that Snail has an important role in invasion and metastasis, and that silencing the gene may be a potential therapeutic target in RCCs.


Subject(s)
Cadherins/antagonists & inhibitors , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Transcription Factors/metabolism , Cadherins/metabolism , Carcinoma/metabolism , Carcinoma/pathology , Cell Line, Tumor , Down-Regulation , Female , Gene Targeting , Humans , Immunohistochemistry , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Snail Family Transcription Factors , Transcription Factors/genetics , Up-Regulation
15.
Nat Med ; 8(9): 1011-7, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12195435

ABSTRACT

Studies have shown that bone marrow cells have the potential to differentiate into a variety of cell types. Here we show that bone marrow cells can repopulate the epithelia of the human gastrointestinal tract. Epithelial cells of male donor origin were distributed in every part of the gastrointestinal tract of female bone marrow transplant recipients. Donor-derived epithelial cells substantially repopulated the gastrointestinal tract during epithelial regeneration after graft-versus-host disease or ulcer formation. Regeneration of gastrointestinal epithelia with donor-derived cells in humans shows a potential clinical application of bone marrow-derived cells for repairing severely damaged epithelia, not only in the gastrointestinal tract but also in other tissues.


Subject(s)
Bone Marrow Transplantation , Digestive System Physiological Phenomena , Digestive System/cytology , Adult , Biopsy , Cell Differentiation , Digestive System/pathology , Epithelium/pathology , Epithelium/physiology , Female , Humans , In Situ Hybridization, Fluorescence , Male , Regeneration , Tissue Donors , Y Chromosome
16.
Pathol Int ; 61(7): 430-4, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21707847

ABSTRACT

Duplications of the digestive organs, especially in the retroperitoneum, are rare malformations. We present the case of a 20-year-old man who had recurrent abdominal pain because of a solid and cystic mass located in the retroperitoneum, posterior to the pancreatic body. Preoperative diagnosis was difficult and a resection was performed. Histopathologically, intestinal mucosa, respiratory mucosa, aberrant pancreatic tissue, smooth muscle coat, and an external fibrous capsule were found. The mass was diagnosed as a duplication of the digestive organs. Findings in the pancreatic tissue indicated chronic pancreatitis and mild atypia in the pancreatic duct epithelium. Currently, many terms are used to describe these series of malformations, including duplication, foregut cyst, gastrointestinal duplication cyst, and enteric duplication cyst. Consequently, diagnosis and investigation can be difficult. In the atlas produced by the Armed Forces Institute of Pathology, duplication is used as a standardized diagnostic nomenclature with subclassification according to the site, but this has not been uniformly accepted. In addition, there are cases whose origins are unclear, especially in the retroperitoneum. In this report, we propose that the term duplication should be uniformly used for all cases in the digestive organs, and that they may then be distinguished according to their mechanisms.


Subject(s)
Digestive System Abnormalities/pathology , Peritoneal Cavity/pathology , Terminology as Topic , Abdominal Pain/etiology , Abdominal Pain/pathology , Biomarkers/metabolism , Choristoma/pathology , Chronic Disease , Cysts/pathology , Digestive System Abnormalities/metabolism , Digestive System Abnormalities/surgery , Humans , Immunohistochemistry , Male , Pancreas , Pancreatitis/etiology , Pancreatitis/pathology , Peritoneal Diseases , Treatment Outcome , Young Adult
17.
Article in English | MEDLINE | ID: mdl-21832864

ABSTRACT

Non-Hodgkin diffuse large B-cell lymphomas of the mastoid that extend from the nasopharynx are extremely rare in children. Moreover, in lymphoproliferative diseases, the presence of otoneurological signs prior to systemic disease involvement is rare. Here, we present a rare case of non-Hodgkin B-cell lymphoma invading the middle ear and mastoid in a 1-year-old boy that mimicked acute mastoiditis with complete facial nerve palsy. As this case illustrates, physicians should consider a diagnosis of malignant lymphoma if a patient presents with otitis media and mastoiditis accompanied by facial palsy.


Subject(s)
Lymphoma, B-Cell/diagnosis , Mastoiditis/diagnosis , Otitis Media/diagnosis , Antineoplastic Agents/therapeutic use , Diagnosis, Differential , Fatal Outcome , Follow-Up Studies , Humans , Infant , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/surgery , Magnetic Resonance Imaging , Male , Salvage Therapy , Tomography, X-Ray Computed
18.
Carcinogenesis ; 31(2): 287-95, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19755661

ABSTRACT

Aryl hydrocarbon receptor (AhR) and the activation of the AhR pathway are involved in xenobiotic-induced toxicity and carcinogenesis. Although xenobiotics, such as cigarette smoke, contribute to the development of urothelial carcinoma (UC), the relationship between AhR and UC is unclear. In the present study, we investigated AhR expression in 209 patients with upper urinary tract UC. The nuclear expression of AhR was significantly associated with histological grade, pathological T stage, lymphovascular invasion and lymph node involvement. A multivariate Cox analysis revealed that nuclear AhR expression was a significant and independent predictor for disease-specific survival (hazard ratio = 2.469, P = 0.013). To determine whether the AhR pathway can be activated in the T24 UC cell line, we examined the expression of cytochrome P450 (CYP) 1A1 and CYP1B1, which are target genes of the AhR pathway, following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a ligand of AhR. TCDD treatment upregulated the expression levels of AhR, CYP1A1 and CYP1B1. TCDD enhanced T24 cell invasion associated with the upregulation of matrix metalloproteinase (MMP)-1 and MMP-9. Furthermore, targeting AhR messenger RNA (mRNA) expression in T24 cells with small interfering RNA (siRNA) downregulated the mRNA expression of AhR, CYP1A1, CYP1B1, MMP-1, MMP-2 and MMP-9; furthermore, the cells transfected with siRNA for AhR showed decreased invasion activity in comparison with the cells transfected with a non-targeting siRNA. Our results therefore suggest that AhR plays a role in the invasiveness of UC cells and can serve as a marker for the prognosis of upper urinary tract UC.


Subject(s)
Carcinoma, Transitional Cell/metabolism , Kidney Neoplasms/metabolism , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 9/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Ureteral Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Apoptosis , Aryl Hydrocarbon Hydroxylases , Blotting, Western , Carcinoma, Transitional Cell/pathology , Cell Adhesion , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1B1 , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Female , Humans , Immunoenzyme Techniques , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness , Polychlorinated Dibenzodioxins/pharmacology , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/pharmacology , Receptors, Aryl Hydrocarbon/antagonists & inhibitors , Receptors, Aryl Hydrocarbon/genetics , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate , Ureteral Neoplasms/pathology , Urothelium/metabolism
19.
Gastrointest Endosc ; 72(3): 643-6, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20579647

ABSTRACT

BACKGROUND: The endocytoscopy system (ECS) is a new method to provide real-time super-magnifying microscopic imaging in vivo. Routine diagnosis of amebic colitis requires multiple tests that are both time consuming and costly. OBJECTIVE: To determine the feasibility of ECS to directly detect the amebic parasites in vivo. DESIGN: Prospective, single-center, pilot study. SETTING: Tertiary-care university hospital. PATIENTS: This study involved 5 patients who were suspected to have amebic colitis by conventional colonoscopy in our institute. INTERVENTIONS: A super-magnifying ECS with 450 x magnification. MAIN OUTCOME MEASUREMENTS: We compared ECS findings with those of conventional methods-serum antibody tests and histology of colon biopsy specimens. RESULTS: We successfully visualized the amebic trophozoites in all 5 cases. In contrast, 3 specimens had positive results on serology, and 3 had positive histology results on hematoxylin and eosin staining. LIMITATIONS: Pilot study with a limited number of patients. Findings were compared only with serology and histology findings. CONCLUSIONS: ECS would be a useful tool for the prompt diagnosis of amebic colitis via the real-time in vivo visualization of amebic trophozoites.


Subject(s)
Colonoscopes , Dysentery, Amebic/diagnosis , Image Enhancement/instrumentation , Image Processing, Computer-Assisted/instrumentation , Trophozoites , Adult , Biopsy , Diagnosis, Differential , Dysentery, Amebic/pathology , Entamoeba histolytica , Feasibility Studies , Female , Humans , Intestinal Mucosa/pathology , Male , Middle Aged , Pilot Projects
20.
J Pathol ; 218(4): 530-9, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19455604

ABSTRACT

Receptor activator of NF-kappaB ligand (RANKL) and its receptor, receptor activator of NF-kappaB (RANK), play a key role in osteoclastogenesis, and osteoprotegerin (OPG) acts as a decoy receptor for RANKL. We investigated the role of the RANKL-RANK-OPG system in renal cell carcinomas (RCCs), which frequently metastasize to bones. Real-time quantitative PCR revealed that RANKL mRNA expression was higher in clear cell RCCs than in papillary and chromophobe RCCs. Similarly, RANKL protein expression level in clear cell RCCs was higher than that in papillary and chromophobe RCCs, showing positive correlations with the primary tumour stage and distant metastasis. There was no significant association between the expression level of RANK, OPG and histological subtypes of RCC. RANKL and RANK expression was observed in metastatic RCCs in the bone and other organs, suggesting that they play a role in metastasis to the bone and other organs. Recombinant RANKL protein stimulated migration of a clear cell RCC cell line, Caki-1, in vitro, and this enhanced migration was inhibited by the administration of recombinant OPG protein. Furthermore, multivariate Cox analysis revealed that elevated RANKL and RANK expression with low-OPG expression was a significant and independent predictor of recurrence, bone metastasis and a poor prognosis. These data suggest that the RANKL-RANK-OPG system is involved not only in the bone metastasis of RCCs but also in metastasis to other organs through the stimulation of cancer cell migration.


Subject(s)
Carcinoma, Renal Cell/metabolism , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/metabolism , RANK Ligand/metabolism , Up-Regulation , Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Movement , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Osteoprotegerin/analysis , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , Prognosis , RANK Ligand/analysis , RANK Ligand/genetics , RNA, Messenger/analysis , Receptor Activator of Nuclear Factor-kappa B/analysis , Receptor Activator of Nuclear Factor-kappa B/genetics , Receptor Activator of Nuclear Factor-kappa B/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Statistics, Nonparametric , Survival Analysis
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