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1.
Urol J ; 21(2): 133-139, 2024 Mar 24.
Article in English | MEDLINE | ID: mdl-37990797

ABSTRACT

PURPOSE: Few studies have evaluated the usefulness of anteroposterior dissection holmium laser enucleation of the prostate (HoLEP). Thus, this study investigated the incidence of stress urinary incontinence (SUI) after HoLEP and usefulness of anteroposterior dissection HoLEP in preventing postoperative SUI. MATERIALS AND METHODS: In total, 288 patients who underwent HoLEP performed by a single experienced surgeon between May 2014 and September 2021 were enrolled. Furthermore, 134 patients underwent retrograde dissection using the modified Gilling method (surgery 1) and 154 patients underwent anteroposterior dissection HoLEP (surgery 2). The risk factors for SUI, as well as the rates of SUI improvement for the two surgical procedures, were evaluated. RESULTS: Postoperative SUI was observed in 58 (20.1%) of 288 patients, of whom, 48 (82.8%) recovered continence within 6 months. Ten patients (17.2%) required more than 6 months to recover continence. SUI incidence 1 month after HoLEP was 29.9% (40/134 patients) for surgery 1 and 11.7% (18/154 patients) for surgery 2; a statistically significant difference was observed between the two groups (odds ratio [OR], 0.311; 95% confidence interval [CI], 0.168-0.575; p < 0.001). In addition, surgery 2 was significantly associated with early recovery from SUI compared with surgery 1 (stratified hazard ratio, 0.782; 95% CI, 0.615------0.995; p < 0.001). The multivariable analysis demonstrated that only surgical procedure (OR, 0.350; 95%CI, 0.168-0.732; p=0.005) was an independent predictor of SUI.- Conclusion: We reaffirmed that anteroposterior dissection HoLEP is a useful procedure for reducing the risk of postoperative SUI and early recovery of urinary continence.


Subject(s)
Laser Therapy , Lasers, Solid-State , Prostatic Hyperplasia , Transurethral Resection of Prostate , Urinary Incontinence, Stress , Male , Humans , Prostate , Urinary Incontinence, Stress/etiology , Urinary Incontinence, Stress/surgery , Lasers, Solid-State/therapeutic use , Prostatic Hyperplasia/surgery , Prostatic Hyperplasia/complications , Transurethral Resection of Prostate/adverse effects , Laser Therapy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Treatment Outcome , Retrospective Studies
2.
Urol Oncol ; 40(4): 162.e9-162.e16, 2022 04.
Article in English | MEDLINE | ID: mdl-35065881

ABSTRACT

BACKGROUND: For prostate cancer, accurate prediction of the pathological stage before surgery is very important. Therefore, the aim of the present study was establishing the prostate-specific antigen (PSA) threshold nomogram to predict pathologically advanced prostate cancer using the novel method of area under the receiver operating characteristic curve boosting (AUCBoost). METHODS: The medical records of patients with clinically localized prostate cancer who underwent robot-assisted radical prostatectomy were retrospectively reviewed. Multivariate logistic regression analysis was performed to identify clinical covariates significantly associated with pathological tumor stage ≥3a. The best combination of the variables was determined by validated values of the area under the curve (AUC). The optimal individualized PSA threshold values were developed using AUCBoost. RESULTS: In the multivariate logistic regression analysis, PSA, prostate volume, clinical tumor stage, Gleason Grade Group, the number of positive cores, and the percentage of positive cores were independent predictive factors for pathological tumor stage ≥3a. A combination model comprising PSA, prostate volume, clinical tumor stage, percent positive core, and Gleason Grade Group produced the highest AUC for predicting pathological tumor stage ≥3a (AUC = 0.777). The PSA threshold values for detecting pathological tumor stage ≥3a were calculated and a table of individualized PSA threshold nomogram was developed using AUCBoost. CONCLUSIONS: We developed a nomogram of the PSA threshold values for predicting adverse pathological tumor stages of prostate cancer using a novel statistical method. Further validation is necessary; however, the individualized PSA threshold nomogram may be useful in determining treatment strategies before surgery.


Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Area Under Curve , Humans , Male , Neoplasm Staging , Nomograms , Predictive Value of Tests , Prostatectomy , Prostatic Neoplasms/pathology , ROC Curve , Retrospective Studies
3.
Int J Clin Oncol ; 25(9): 1704-1710, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32500468

ABSTRACT

BACKGROUND: To determine prognostic factors associated with progression to castration-resistant prostate cancer following biochemical recurrence which is lethal prostate cancer and establish a risk stratification model of progression to castration-resistant prostate cancer. METHODS: We retrospectively reviewed the data of 550 patients who experienced biochemical recurrence after radical prostatectomy. The endpoint of the present study was progression to castration-resistant prostate cancer. The actuarial probabilities of progression to castration-resistant prostate cancer-free survival were determined using Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors of biochemical recurrence. RESULTS: Fifty-two patients experienced progression to castration-resistant prostate cancer during the follow-up period. The progression to castration-resistant prostate cancer-free survival rate after biochemical recurrence at 10 years was 76.8%. In multivariate analysis, pathological Gleason score ≥ 9, lymphovascular invasion, and prostate-specific antigen velocity ≥ 0.4 ng/mL/year were independent predictive factors for progression to castration-resistant prostate cancer. The patients were stratified into three groups using a risk stratification model incorporating these variables. The 10-year progression to castration-resistant prostate cancer-free survival rates were 96.7% in the low-risk group, 84.7% in the intermediate-risk group, and 24.5% in the high-risk group. CONCLUSIONS: The present results suggest that the pathological Gleason score, lymphovascular invasion, and prostate-specific antigen velocity were independent predictive factors for progression to castration-resistant prostate cancer. The risk stratification model established in the present study could be useful for patient counseling and in identifying patients with a poor prognosis.


Subject(s)
Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Aged , Disease-Free Survival , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Prostatectomy/methods , Prostatic Neoplasms/mortality , Prostatic Neoplasms, Castration-Resistant/mortality , Retrospective Studies , Risk Factors , Survival Rate
4.
Int J Clin Oncol ; 25(2): 377-383, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31673831

ABSTRACT

BACKGROUND: The development process of recurrence in prostate cancer patients with pathologically organ-confined (pT2) disease and negative surgical margins is unclear. The aim of the present study was to determine factors associated with the development of biochemical recurrence following robot-assisted radical prostatectomy among those prostate cancer patients. METHODS: We retrospectively reviewed the data of patients who underwent robot-assisted radical prostatectomy without neoadjuvant endocrine therapy. We evaluated prognostic factors in 1096 prostate cancer patients with pT2 disease and negative surgical margins. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors for biochemical recurrence. RESULTS: Of the 1096 patients, 55 experienced biochemical recurrence during the follow-up period. The 5-year biochemical recurrence-free survival rate for patients with pT2 and negative surgical margins was 91.8%. On univariate analysis, clinical stage, biopsy Gleason score, percent of positive core, pathological Gleason score, and the presence of micro-lymphatic invasion were significantly associated with biochemical recurrence. On a multivariate analysis, the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 were significant prognostic factors for biochemical recurrence. Based on these factors, we developed a risk stratification model. The biochemical recurrence-free survival rate differed significantly among the risk groups. CONCLUSIONS: The prognosis of prostate cancer patients with pT2 disease and negative surgical margins is favorable. However, patients with the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 tend to experience biochemical recurrence more often after surgery. Therefore, careful follow-up might be necessary for those patients.


Subject(s)
Prostatectomy/methods , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Robotic Surgical Procedures/methods , Aged , Biopsy , Humans , Lymphatic Metastasis/pathology , Male , Margins of Excision , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Prognosis , Prostatic Neoplasms/mortality , Retrospective Studies , Risk Factors
5.
Acute Med Surg ; 4(3): 262-270, 2017 07.
Article in English | MEDLINE | ID: mdl-29123873

ABSTRACT

Aim: The purpose of this study was to better understand the effects of introducing the Japan Triage and Acuity Scale (JTAS) in the emergency room for walk-in patients. Methods: A simple triage was used in Term A (from April 2006 to December 2010, 4 years and 9 months) and the JTAS was introduced in Term B (from January 2011 to September 2015, 4 years and 9 months). The number of patients who had a sudden turn for the worse after arrival in the emergency room and the time between attendance and emergency catheterization (TBAEC) due to acute coronary syndrome were reviewed. Results: There were 653 patients in Term A and 626 patients in Term B who were finally diagnosed as having serious causes. There was no significant difference in the frequency of a sudden turn for the worse between the two terms. There were 182 patients in Term A and 167 patients in Term B who underwent emergency catheterization due to acute coronary syndrome. When ST elevation was recognized in the first electrocardiogram, the median time between attendance and medical attention during Term B improved significantly, by 4.5 min. However, there was no significant difference in medians for TBAEC. When ST elevation was not recognized, there was no significant difference between the two terms, neither in terms of median time between attendance and medical attention, nor TBAEC. Conclusion: The data suggests that the effects of introducing the JTAS in the emergency room were restrictive in these two aspects.

6.
Int J Urol ; 24(2): 111-116, 2017 02.
Article in English | MEDLINE | ID: mdl-27875859

ABSTRACT

OBJECTIVES: To investigate the predictive values of perioperative factors and to develop a nomogram for intravesical recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. METHODS: A retrospective analysis of 144 patients who underwent radical nephroureterectomy from 1996 to 2014 was carried out. The actuarial probabilities of the intravesical recurrence-free survival rate were calculated using the Kaplan-Meier method. Prognostic indicators for intravesical recurrence were identified using competing-risks regression analyses. RESULTS: Intravesical recurrence occurred in 63 patients during the follow-up period. The intravesical recurrence-free survival rates at 1, 3, and 5 years were 65.7%, 50.6% and 47.1%, respectively. In univariate analysis, the presence of gross hematuria (P = 0.028) and the preoperative serum creatinine level (P = 0.033) were significantly associated with intravesical recurrence. In multivariate analysis, the presence of gross hematuria (subdistribution hazard ratio 2.03, 95% CI 1.145-3.496; P = 0.013) and the preoperative serum creatinine level (subdistribution hazard ratio 3.15, 95% CI 1.161-3.534; P = 0.021) were independent predictors for intravesical recurrence after radical nephroureterectomy. Accordingly, a nomogram based on the model was developed. The concordance index of this model was 0.632. CONCLUSION: The presence of gross hematuria and preoperative serum creatinine levels seem to be independent predictors for intravesical recurrence after radical nephroureterectomy. Our nomogram developed based on these factors might aid in appropriate patient selection for clinical trials of novel therapeutic interventions, including administration of intravesical chemotherapy.


Subject(s)
Carcinoma, Transitional Cell/pathology , Creatinine/blood , Hematuria/epidemiology , Neoplasm Recurrence, Local/diagnosis , Urinary Bladder/pathology , Urologic Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/surgery , Carcinoma, Transitional Cell/urine , Cystoscopy , Disease-Free Survival , Female , Hematuria/diagnosis , Hematuria/urine , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/prevention & control , Nephroureterectomy , Nomograms , Predictive Value of Tests , Preoperative Period , Retrospective Studies , Survival Rate , Urinary Bladder/diagnostic imaging , Urologic Neoplasms/blood , Urologic Neoplasms/surgery , Urologic Neoplasms/urine
7.
BMC Cancer ; 16: 629, 2016 08 12.
Article in English | MEDLINE | ID: mdl-27519597

ABSTRACT

BACKGROUND: Melanotic neuroectodermal tumor of infancy (MNTI) is exceptionally rare and occurs predominantly in the head and neck (92.8 % cases). The patient reported here is only the eighth case of MNTI presenting in an extremity, and the first reported in the fibula. CASE PRESENTATION: A 2-month-old female presented with a mass arising in the fibula. Exhaustive genomic, transcriptomic, epigenetic and pathological characterization was performed on the excised primary tumor and a derived cell line. Whole-exome analysis of genomic DNA from both the tumor and blood indicated no somatic, non-synonymous coding mutations within the tumor, but a heterozygous, unique germline, loss of function mutation in CDKN2A (p16(INK4A), D74A). SNP-array CGH on DNA samples revealed the tumor to be euploid, with no detectable gene copy number variants. Multiple chromosomal translocations were identified by RNA-Seq, and fusion genes included RPLP1-C19MC, potentially deregulating the C19MC cluster, an imprinted locus containing microRNA genes reactivated by gene fusion in embryonal tumors with multilayered rosettes. Since the presumed cell of origin of MNTI is from the neural crest, we also compared gene expression with a dataset from human neural crest cells and identified 185 genes with significantly different expression. Consistent with the melanotic phenotype of the tumor, elevated expression of tyrosinase was observed. Other highly expressed genes encoded muscle proteins and modulators of the extracellular matrix. A derived MNTI cell line was sensitive to inhibitors of lysine demethylase, but not to compounds targeting other epigenetic regulators. CONCLUSIONS: In the absence of somatic copy number variations or mutations, the fully transformed phenotype of the MNTI may have arisen in infancy because of the combined effects of a germline CDKN2A mutation, tumor promoting somatic fusion genes and epigenetic deregulation. Very little is known about the etiology of MNTI and this report advances knowledge of these rare tumors by providing the first comprehensive genomic, transcriptomic and epigenetic characterization of a case.


Subject(s)
Bone Neoplasms/genetics , Cyclin-Dependent Kinase Inhibitor p18/genetics , Fibula/pathology , Germ-Line Mutation , Neuroectodermal Tumor, Melanotic/genetics , Oncogene Proteins, Fusion/genetics , Cyclin-Dependent Kinase Inhibitor p16 , Female , Gene Expression Regulation, Neoplastic , Humans , Infant , Phosphoproteins/genetics , Ribosomal Proteins/genetics , Sequence Analysis, DNA , Sequence Analysis, RNA
9.
Histopathology ; 69(3): 470-8, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26896083

ABSTRACT

AIMS: To assess the immunophenotypic and mRNA expression of sclerostin in human skeletal tissues and in a wide range of benign and malignant bone tumours and tumour-like lesions. METHODS AND RESULTS: Sclerostin expression was evaluated by immunohistochemistry and quantitative polymerase chain reaction (PCR). In lamellar and woven bone, there was strong sclerostin expression by osteocytes. Osteoblasts and other cell types in bone were negative. Hypertrophic chondrocytes in the growth plate and mineralized cartilage cells in zone 4 of hyaline articular cartilage strongly expressed sclerostin, but most chondrocytes in hyaline cartilage were negative. In primary bone-forming tumours, including osteosarcomas, there was patchy expression of sclerostin in mineralized osteoid and bone. Sclerostin staining was seen in woven bone in fibrous dysplasia, in osteofibrous dysplasia, and in reactive bone formed in fracture callus, in myositis ossificans, and in the wall of solitary bone cysts and aneurysmal bone cysts. Sclerostin was expressed by hypertrophic chondrocytes in osteochondroma and chondroblasts in chondroblastoma, but not by tumour cells in other bone tumours, including myeloma and metastatic carcinoma. mRNA expression of sclerostin was identified by quantitative PCR in osteosarcoma specimens and cell lines. CONCLUSIONS: Sclerostin is an osteocyte marker that is strongly expressed in human woven and lamellar bone and mineralizing chondrocytes. This makes it a useful marker with which to identify benign and malignant osteogenic tumours and mineralizing cartilage tumours, such as chondroblastomas and other lesions in which there is bone formation.


Subject(s)
Biomarkers, Tumor/analysis , Bone Morphogenetic Proteins/biosynthesis , Bone Neoplasms/pathology , Adaptor Proteins, Signal Transducing , Bone Morphogenetic Proteins/analysis , Bone and Bones/pathology , Genetic Markers , Humans , Immunohistochemistry , Osteocytes/metabolism , Osteogenesis/physiology , Real-Time Polymerase Chain Reaction
10.
Cancer Res ; 74(20): 5866-77, 2014 Oct 15.
Article in English | MEDLINE | ID: mdl-25168481

ABSTRACT

Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor-bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc-Grb2-SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition.


Subject(s)
Adaptor Proteins, Signal Transducing/physiology , Drug Resistance, Neoplasm , Insulin-Like Growth Factor I/physiology , Phosphoproteins/physiology , Receptor, IGF Type 1/antagonists & inhibitors , ras Proteins/metabolism , Animals , Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Dishevelled Proteins , Gene Expression , Head and Neck Neoplasms/metabolism , Humans , Inhibitory Concentration 50 , Isoxazoles/pharmacology , MAP Kinase Signaling System , Male , Mice , Pyrimidines/pharmacology , Receptor, IGF Type 1/metabolism , Wnt Proteins/metabolism , Xenograft Model Antitumor Assays
11.
Am J Pathol ; 184(3): 859-70, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24418260

ABSTRACT

Overexpression of periostin (POSTN), an extracellular matrix protein, has been observed in several cancers. We investigated the importance of POSTN in gastric cancer. Genome-wide gene expression analysis using publicly available microarray data sets revealed significantly high POSTN expression in cancer tissues from stage II-IV gastric cancer, compared with background normal tissues. The POSTN/vimentin mRNA expression ratio was highly associated with gene groups that regulate the cell cycle and cell proliferation. IHC showed that periglandular POSTN deposition, comprising linear deposition abutting the glandular epithelial cells in normal mucosa, disappeared during intestinal gastric cancer progression. Stromal POSTN deposition was also detected at the invasive front of intestinal-type and diffuse-type cancers. In situ hybridization confirmed POSTN mRNA in cancer-associated fibroblasts, but not in tumor cells themselves. POSTN enhanced the in vitro growth of OCUM-2MLN and OCUM-12 diffuse-type gastric cancer cell lines, accompanied by the activation of ERK. Furthermore, coinoculation of gastric cancer cells with POSTN-expressing NIH3T3 mouse fibroblast cells facilitated tumor formation. The OCUM-2MLN orthotopic inoculation model demonstrated that tumors of the gastric wall in Postn(-/-) mice were significantly smaller than those in wild-type mice. Ki-67 and p-ERK positive rates were both lower in Postn(-/-) mice. These findings suggest that POSTN produced by cancer-associated fibroblasts constitutes a growth-supportive microenvironment for gastric cancer.


Subject(s)
Cell Adhesion Molecules/metabolism , Extracellular Matrix Proteins/metabolism , Fibroblasts/metabolism , MAP Kinase Signaling System/physiology , Stomach Neoplasms/pathology , Animals , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Cell Proliferation , Female , Fibroblasts/pathology , Gene Expression Profiling , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , NIH 3T3 Cells , Oligonucleotide Array Sequence Analysis , Transforming Growth Factor beta/metabolism , Vimentin/metabolism
12.
J Med Case Rep ; 7: 145, 2013 May 31.
Article in English | MEDLINE | ID: mdl-23724934

ABSTRACT

INTRODUCTION: Crystal violet was commonly used for the treatment of oral and vaginal candidiasis or for sterilization during operations up to the 1960s. Because crystal violet is potentially toxic to mucosal membranes, it has been replaced with other disinfectants, and crystal violet is rarely used. We report a case of chemical cystitis due to intravesical instillation of crystal violet dye. CASE PRESENTATION: Crystal violet dye was instilled into the bladder of a 47-year-old Japanese woman to confirm the presence of a vesicovaginal fistula. Our patient developed symptoms of gross hematuria, frequent urination and lower abdominal pain. Computed tomography showed thickening of her whole bladder wall with spotted high-density lesions. Cystoscopy demonstrated desquamated epithelial cells and a hemorrhagic bladder wall. We treated our patient conservatively with nonsteroidal anti-inflammatory drugs and glucocorticoids. During follow-up, magnetic resonance images showed that the detrusor muscle of her bladder was normal. Our patient's symptoms gradually improved and she completely recovered within six months. CONCLUSION: Considering the severe side effect of crystal violet, it would be better not to use this dye to examine conditions such as a vesicovaginal fistula. Magnetic resonance imaging may help to evaluate the level of damage in the bladder wall of patients with chemical cystitis.

13.
Hinyokika Kiyo ; 59(2): 133-5, 2013 Feb.
Article in Japanese | MEDLINE | ID: mdl-23552759

ABSTRACT

A 76-year-old man presented to our hospital with asymptomatic bleeding of the urethra. Endoscopic examination showed multiple urethral papillary tumors in the pendulous urethra, and the tumors were surgically resected. Histopathological examination indicated urethral condyloma acuminata, and the results of a polymerase chain reaction-based invader assay using urethral swabs taken after surgery suggested low risk human papilloma virus infection. This is a relatively rare case because urethral condyloma acuminata has been reported in only a few elderly patients so far. No obvious recurrence of condyloma acuminata has been observed for 18 months after surgery.


Subject(s)
Condylomata Acuminata/diagnosis , Urethral Diseases/diagnosis , Aged , Humans , Male
14.
Clin Sarcoma Res ; 3(1): 2, 2013 Feb 04.
Article in English | MEDLINE | ID: mdl-23379545

ABSTRACT

Ewing sarcoma (ES) is a high-grade malignant primary round cell tumour of bone in which there is commonly extension into extraosseous soft tissues at the time of diagnosis. This report details the clinical, radiological and pathological features of a case of ES of the tibia in which there was extensive osseous involvement but no infiltration beyond the periosteum into surrounding soft tissue. We also record the findings of one other ES case that exhibited similar behaviour. Both cases were male, involved the tibia and had the characteristic t (11;22) (q24;q12) translocation. No recurrence of tumour or metastasis has been seen in these two cases, both of which have had 6 years follow-up. Our findings indicate that there is heterogeneity in the behaviour of ES and show that localized ES is associated with a good prognosis.

15.
Skeletal Radiol ; 42(5): 635-47, 2013 May.
Article in English | MEDLINE | ID: mdl-22987247

ABSTRACT

PURPOSE: To review the reliability of MR imaging features for the purpose of distinguishing lipoma and atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL). MATERIALS AND METHODS: A retrospective review of 87 patients with histologically proven lipomatous tumors was performed. All underwent MR imaging, assessing lipomatous content, septation, and nodules. The associations between these features and tumor diagnosis based on morphology and the presence or absence of MDM2 amplification were explored. The age of the patient and the size and location of the lesion were also recorded for statistical analysis. RESULTS: Of the 87 patients, 54 were classified as lipomas and 33 as ALT/WDL. MR identified ALT/WDL with a sensitivity of 90.9 % (CI 74.5-97.6) and a specificity of 37.0 % (CI 24.6-51.3). The positive and negative predictive values were 46.9 % (CI 34.5-59.7) and 86.9 % (CI 65.3-96.6), respectively. The mean age of patients with ALT/WDL was greater (60 years [range 40-83 years]) than those with lipoma (52 years [range 10-79 years]) (p = 0.025). The mean size of ALT/WDL (18.7 cm [range 5-36 cm]) was significantly greater than lipoma (13.9 cm [range 3-32 cm]) (p = 0.003). Features that increased the likelihood of ALT/WDL included: patient age over 60 years, maximal lesion dimension over 10 cm, location in lower limb, and presence of non-fatty areas, by a factor of 2.61-6.25 times. CONCLUSIONS: ALT/WDL and lipoma have overlapping MR imaging characteristics. The most reliable imaging discriminators of ALT/WDL were size of lesion and lipomatous content, but due to the overlap in the MRI appearances of lipoma and ALT/WDL, discrimination should be based on molecular pathology rather than imaging.


Subject(s)
Lipoma/diagnosis , Lipoma/genetics , Liposarcoma/diagnosis , Liposarcoma/genetics , Proto-Oncogene Proteins c-mdm2/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Gene Amplification , Humans , In Situ Hybridization, Fluorescence , Lipoma/pathology , Liposarcoma/pathology , Male , Middle Aged , Retrospective Studies , Young Adult
16.
Lab Invest ; 92(10): 1398-406, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22906984

ABSTRACT

Giant cell tumour of bone (GCTB) is a primary bone tumour that contains numerous very large, hyper-nucleated osteoclastic giant cells. Osteoclasts form from CD14+ monocytes and macrophages in the presence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). GCTB contains numerous growth factors, some of which have been reported to influence osteoclastogenesis and resorption. We investigated whether these growth factors are capable of substituting for M-CSF to support osteoclast formation from cultured human monocytes and whether they influence osteoclast cytomorphology and resorption. Vascular endothelial growth factor-A (VEGF-A), VEGF-D, FLT3 ligand (FL), placental growth factor (PlGF) and hepatocyte growth factor (HGF) supported RANKL-induced osteoclastogenesis in the absence of M-CSF, resulting in the formation of numerous TRAP+ multinucleated cells capable of lacunar resorption. Monocytes cultured in the presence of M-CSF, HGF, VEGF-A and RANKL together resulted in the formation of very large, hyper-nucleated (GCTB-like) osteoclasts that were hyper-resorptive. M-CSF and M-CSF substitute growth factors were identified immunohistochemically in GCTB tissue sections and these factors stimulated the resorption of osteoclasts derived from a subset of GCTBs. Our findings indicate that there are growth factors that are capable of substituting for M-CSF to induce human osteoclast formation and that these factors are present in GCTB where they influence osteoclast cytomorphology and have a role in osteoclast formation and resorption activity.


Subject(s)
Bone Neoplasms/metabolism , Giant Cell Tumor of Bone/metabolism , Growth Substances/metabolism , Macrophage Colony-Stimulating Factor/metabolism , Osteoclasts/metabolism , Acid Phosphatase/analysis , Biomarkers, Tumor/analysis , Bone Neoplasms/pathology , Bone Resorption/metabolism , Bone Resorption/pathology , Giant Cell Tumor of Bone/pathology , Giant Cells/metabolism , Giant Cells/pathology , Growth Substances/pharmacology , Hepatocyte Growth Factor/metabolism , Hepatocyte Growth Factor/pharmacology , Humans , Isoenzymes/analysis , Macrophage Colony-Stimulating Factor/pharmacology , Membrane Proteins/metabolism , Membrane Proteins/pharmacology , Monocytes/metabolism , Monocytes/pathology , Osteoclasts/cytology , Placenta Growth Factor , Pregnancy Proteins/metabolism , Pregnancy Proteins/pharmacology , RANK Ligand/metabolism , RANK Ligand/pharmacology , Tartrate-Resistant Acid Phosphatase , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor D/metabolism , Vascular Endothelial Growth Factor D/pharmacology
18.
Mod Pathol ; 25(10): 1384-96, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22699518

ABSTRACT

This study assessed whether analysis of MDM2 copy number by fluorescence in situ hybridization (FISH) would help distinguish lipomas from atypical lipomatous tumors, otherwise referred to as well-differentiated liposarcomas, using a commercially available MDM2 FISH kit. 227 lipomatous and 201 non-lipomatous tumors were analyzed to assess its sensitivity and specificity. Of 178 mature lipomatous tumors, 86 were classified histologically as lipoma and 92 as atypical lipomatous tumor. Two of the lipomas harboring MDM2 amplification were reclassified as atypical lipomatous tumors. Overall, 13 atypical lipomatous tumors did not reveal MDM2 or CDK4 amplification, although this was reduced to 12 following analysis of multiple slides. Three of these cases revealed very occasional tumor cells harboring high-level MDM2 amplification, two had a dedifferentiated component, and MDM2 amplification was detected when one tumor recurred. The remaining six cases exhibited reactive/inflammatory features and were reclassified as lipomas. The findings indicate that MDM2 amplification is 93.5% sensitive for diagnosing atypical lipomatous tumor. A total of 2 of the 20 dedifferentiated liposarcomas failed to reveal MDM2 amplification. All atypical lipomatous tumors measured >10 cm, two dedifferentiated liposarcoma presented de novo at <10 cm, and ~50% of lipomas measured >10 cm. Spindle cell lipomas, lipoblastomas, hibernomas and pleomorphic liposarcomas did not reveal MDM2 amplification. Of 201 non-lipomatous tumors, eight revealed MDM2 amplification or multiple faint alphoid 12 signals and were reclassified as dedifferentiated liposarcoma. Multiple faint alphoid 12 signals were observed in nine tumors from seven patients, an observation not previously reported on paraffin sections: these included four atypical lipomatous tumors, and three dedifferentiated liposarcomas, one previously diagnosed as a myxofibrosarcoma, all of which also revealed amplification of CDK4, although two lacked MDM2 amplification. MDM2 FISH test is a useful adjunct to histology for distinguishing lipoma from atypical lipomatous tumor. The limitations of molecular genetic tests must be known before introducing them into a clinical service.


Subject(s)
DNA, Satellite/genetics , Gene Amplification , Gene Dosage , Lipoma/genetics , Liposarcoma/genetics , Proto-Oncogene Proteins c-mdm2/genetics , Soft Tissue Neoplasms/genetics , Adult , Aged , Centromere/genetics , Female , Genetic Markers/genetics , Humans , In Situ Hybridization, Fluorescence/methods , Lipoma/diagnosis , Lipoma/metabolism , Liposarcoma/diagnosis , Liposarcoma/metabolism , Male , Middle Aged , Proto-Oncogene Proteins c-mdm2/metabolism , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/metabolism
19.
J Endourol ; 26(9): 1159-64, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22471623

ABSTRACT

BACKGROUND AND PURPOSE: The usefulness of posterior rhabdosphincter reconstruction (PR) during robot-assisted radical prostatectomy (RARP) has still been controversial. We investigated the association of several factors, including the Rocco original double-layered PR, with early recovery of urinary continence after RARP. PATIENTS AND METHODS: Between August 2006 and April 2011, a single surgeon at Tokyo Medical University Hospital performed 206 RARPs. Of these 206 patients, 199 eligible patients were enrolled in this study. We retrospectively analyzed the correlation of several perioperative factors, including surgical techniques, with early recovery of urinary continence 1 month after catheter removal. Continence was defined as no use or the use of only one safety pad. RESULTS: Univariate analysis showed that surgeon experience, lateral approach of bladder neck preservation, bladder neck reconstruction, anterior reconstruction, and the Rocco double-layered PR were significantly associated with early recovery of urinary continence 1 month after catheter removal. Preoperative prostate-specific antigen level, body mass index, and attempted nerve-sparing (NS) procedures, however, were not significantly associated with early recovery of urinary continence. Multivariate logistic regression analysis showed that the Rocco PR and attempted NS were the only independent predictive factors of urinary continence recovery 1 month after catheter removal (odds ratio [OR], 15.01; 95% confidence interval [CI], 3.413-66.67; P=0.0003 and OR, 2.248; 95% CI, 1.048-4.975; P=0.0402, respectively). When we applied NS as well as the Rocco PR, the recovery rates of continence at 1 month after catheter removal was 85.3%. CONCLUSIONS: The Rocco double-layered PR and attempted NS and not surgeon experience were the significant independent predictive factors of early recovery of urinary continence after RARP. NS procedures positively influenced early recovery of urinary continence only when they were applied with the PR technique.


Subject(s)
Anal Canal/surgery , Plastic Surgery Procedures/methods , Prostatectomy/adverse effects , Recovery of Function , Robotics , Urinary Incontinence/etiology , Urinary Incontinence/physiopathology , Adult , Aged , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Urologic Surgical Procedures
20.
Lab Invest ; 92(4): 600-5, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22330339

ABSTRACT

Aneurysmal bone cyst (ABC) is a benign osteolytic bone lesion in which there are blood-filled spaces separated by fibrous septa containing giant cells. The nature of the giant cells in this lesion and the mechanism of bone destruction in ABC is not certain. In this study, we have analysed several characteristics of mononuclear and multinucleated cells in the ABC and examined the cellular and molecular mechanisms of ABC osteolysis. The antigenic and functional phenotype of giant cells in ABC was determined by histochemistry/immunohistochemistry using antibodies to macrophage and osteoclast markers. Giant cells and CD14+ and CD14- mononuclear cells were isolated from ABC specimens and cultured on dentine slices and coverslips with receptor activator of nuclear factor κB ligand (RANKL)+/- macrophage-colony stimulating factor (M-CSF) and functional and cytochemical evidence of osteoclast differentiation sought. Giant cells in ABC expressed an osteoclast-like phenotype (CD51+, CD14-, cathepsin K+, TRAP+) and were capable of lacunar resorption, which was inhibited by zoledronate, calcitonin and osteoprotegerin (OPG). When cultured with RANKL±M-CSF, CD14+, but not CD14-, mononuclear cells differentiated into TRAP+ multinucleated cells that were capable of lacunar resorption. M-CSF was not necessary for osteoclast formation from CD14+ cell cultures. CD14- cells variably expressed RANKL, OPG and M-CSF but supported osteoclast differentiation. Our findings show that the giant cells in ABC express an osteoclast-like phenotype and are formed from CD14+ macrophage precursors. CD14- mononuclear stromal cells express osteoclastogenic factors and most likely interact with CD14+ cells to form osteoclast-like giant cells by a RANKL-dependent mechanism.


Subject(s)
Bone Cysts, Aneurysmal/pathology , Cell Differentiation , Giant Cells/pathology , Monocytes/physiology , Osteoclasts/pathology , Adolescent , Adult , Cell Culture Techniques , Child , Child, Preschool , Female , Giant Cells/metabolism , Humans , Lipopolysaccharide Receptors/metabolism , Macrophage Colony-Stimulating Factor/metabolism , Male , Middle Aged , Osteoprotegerin/metabolism , Phenotype , RANK Ligand/metabolism , Young Adult
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