Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Bone marrow lesions, subchondral bone cysts and subchondral bone attrition are associated with histological synovitis in patients with end-stage knee osteoarthritis: a cross-sectional study.

OBJECTIVE: The aim of this study was to examine the osteoarthritis (OA)-related structural changes associated with histological synovitis in end-stage knee OA patients. METHODS: Forty end-stage knee OA patients (female: 88%, mean age: 71.8 y) were enrolled. All participants underwent 3.0-T MRI. The structural changes, such as cartilage morphology, subchondral bone marrow lesion (BML), subchondral bone cyst (SBC), subchondral bone attrition (SBA), osteophytes, meniscal lesion and synovitis, were scored using the whole-organ MRI scoring (WORMS) method. Synovial samples were obtained from five regions of interest (ROIs) of the knee joint during total joint replacement surgery. The associations between the histological synovitis score (HSS) and WORMS or the synovial expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1ß, IL-6 and transforming growth factor (TGF)-ß were examined using Spearman's correlation coefficient. RESULTS: Among the seven OA-related structural changes, the BML, SBC, SBA and synovitis were significantly associated with the HSS (r = 0.33, 0.35, 0.48 and 0.36, respectively), while other morphological changes were not. Although synovial COX-2, IL-1ß or IL-6 expression levels were not associated with the HSS, the synovial TGF-ß expression levels were associated with the HSS. CONCLUSION: The presence of BML, SBC and SBA was associated with histological synovitis in end-stage knee OA patients.

The degeneration and destruction of femoral articular cartilage shows a greater degree of deterioration than that of the tibial and patellar articular cartilage in early stage knee osteoarthritis: a cross-sectional study.

OBJECTIVE: The aim of the present study was to examine whether the degenerative and morphological changes of articular cartilage in early stage knee osteoarthritis (OA) occurred equally for both femoral- and tibial- or patellar- articular cartilage using magnetic resonance imaging (MRI)-based analyses. DESIGN: This cross-sectional study was approved by the ethics committee of our university. Fifty patients with early stage painful knee OA were enrolled. The patients underwent 3.0 T MRI on the affected knee joint. Healthy volunteers who did not show MRI-based OA changes were also recruited as controls (n = 19). The degenerative changes of the articular cartilage were quantified by a T2 mapping analysis, and any structural changes were conducted using Whole Organ Magnetic Resonance Imaging Score (WORMS) technique. RESULTS: All patients showed MRI-detected OA morphological changes. The T2 values of femoral condyle (FC) (P < 0.0001) and groove (P = 0.0001) in patients with early stage knee OA were significantly increased in comparison to those in the control, while no significant differences in the T2 values of patellar and tibial plateau (TP) were observed between the patients and the control. The WORMS cartilage and osteophyte scores of the femoral articular cartilage were significantly higher than those in the patellar- (P = 0.001 and P = 0.007, respectively) and tibial- (P = 0.0001 and P < 0.0001, respectively) articular cartilage in the patients with early stage knee OA. CONCLUSIONS: The degradation and destruction of the femoral articular cartilage demonstrated a greater degree of deterioration than those of the tibial- and patellar- articular cartilage in patients with early stage knee OA.

An autopsy report on multiple system atrophy diagnosed immunohistochemically despite severe ischaemic damage: a new approach for investigation of medical practice associated deaths in Japan.

A 60-year old man with a 10-year history of multiple system atrophy (MSA) was found in respiratory arrest. After 4 months of respiratory support with two episodes of septic shock, he died. Autopsy disclosed severe atrophy of the mesencephalon, brainstem, medulla oblongata and cerebellum. Gallyas-Braak, alpha-synuclein and ubiquitin-positive inclusions in the cytoplasm of glial cells were evident, despite the severe ischaemic damage due to respiratory arrest and subsequent respiratory support for 4 months. The cause of respiratory arrest was not identified, but could be explained by the natural history of MSA. The bereaved family, who had suspected malpractice, was satisfied with the explanation based on the investigation performed by eight expert doctors, one expert nurse, two coordinator nurses and two lawyers in the model project promoted by the Japanese government.

[Thymic carcinoma involving aortic arch; report of a case].

Adenocarcinoma of the thymus is a very rare malignant tumor. The standard treatment for advanced thymic carcinoma has not yet been established, and the prognosis is poor. We report a case of thymic carcinoma that involving the aortic arch and the innominate vein. A 78-year-old woman was admitted to our hospital complaining of hoarseness in April 2007. The computed tomography (CT) scan showed an anterior mediastinal tumor contiguous to the aortic arch and the innominate vein with swelling lymphnodes. Microspcopic examinations of specimens obtained by CT-guided needle biopsy revealed poorly differenciated adenocarcinoma. The carcinoembryonic antigen (CEA) level of serum elevated at 54.9 ng/ml. Thymic carcinoma was diagnosed. The chemoradiotherapy [concurrent, carboplatin (CBDCA) + paclitaxel(TXL)-->vinorelbine (NVB), 60 Gy] was performed, but the effect of the therapy was limited. The resection of the tumor with a part of aortic arch and other peripheral tissues was performed in Augast 2007. The postoperative course was uneventful and the CEA level of serum lowered to the normal. She was discharged 30 days after surgery.

Immunohistochemical localisation of D-beta-aspartic acid-containing proteins in climatic droplet keratopathy.

AIM: Biologically uncommon D-beta-aspartic acid (D-beta-Asp) accumulates in the body with age and is involved in the ageing process. In the present study, the localisation of D-beta-Asp-containing proteins was investigated in surgical specimens with climatic droplet keratopathy (CDK), one of the ocular changes related to the ageing process. METHODS: Immunohistochemical localisation of D-beta-Asp-containing proteins using polyclonal antibodies raised against D-beta-Asp-containing peptides was examined in three corneas with CDK, three corneas with interstitial keratitis, six corneas with bullous keratopathy, and three corneas without any corneal diseases. RESULTS: Strong immunoreactivity to D-beta-Asp-containing peptide was detected in all the surgical specimens with CDK. In contrast, no immunoreactivities to D-beta-Asp-containing peptides were detected in the surgical specimens with bullous keratopathy, interstitial keratitis, or no corneal diseases. CONCLUSIONS: CDK was regarded as aggregations of D-beta-Asp-containing proteins. The formation of D-amino acids in protein causes the different side chain orientations and beta-linkage of Asp residues elongates the main chain of proteins. Therefore, D-beta-Asp formation will result in a partial unfolding of proteins leading to the aggregation of proteins seen in CDK.

ST/G ACL reconstruction: double strand plus extra-articular sling vs double bundle, randomized study at 3-year follow-up.

Several investigators have reported the presence of biomechanical, kinematic, anatomic, fiber orientation patterns and biological differences between the anteromedial bundle and the posterolateral bundle of ACL. The purpose of this prospective randomized study was to compare the clinical, instrumental and X-ray outcome of two ACL reconstruction techniques with hamstring tendons: one with a single intra-articular bundle associated to an extra-articular sling, the second with a more anatomic double-bundle technique that reproduces better the native ACL function. From an initial group of 100 patients who underwent ACL reconstruction, 72 patients (35 single bundle plus lateral plasty and 37 double bundle) were evaluated with IKDC, Tegner score, KT2000 arthrometer, Activity Rating Scale, Psychovitality Questionnaire and Ahlback radiographic score at a mean 3 years follow-up. Double-bundle group showed significantly better results regarding IKDC, ROM, Activity Rating Scale and time to return to sport. Also KT 2000 showed significant differences in objective stability. The double-bundle technique for ACL reconstruction described in this paper has demonstrated significantly better subjective, objective and functional results compared with a double-stranded hamstrings plus extra-articular sling at a minimum 3-year follow-up.

Advanced glycation end product deposits in climatic droplet keratopathy.

BACKGROUND: Climatic droplet keratopathy (CDK), known as spheroid degeneration of the cornea, is one of the most frequent degenerative corneal disorders affecting visual function. However, the histochemical nature of the deposits seen in CDK is still unclear. AIM: To investigate the pathogenesis of CDK, we investigated the immunohistochemical localisation of advanced glycation end products (AGEs) in surgical specimens of CDK. METHODS: Immunohistochemical localisation of N(epsilon)-(carboxymethyl)-l-lysine (CML), N(epsilon)-(carboxyethyl)-l-lysine (CEL), pyrraline, pentosidine and imidazolone was examined in three corneas with CDK, six corneas with bullous keratopathy and three corneas without any corneal diseases. RESULTS: In all the specimens with CDK, immunoreactivity was strong in CML, moderate in pyrraline and pentosidine, and weak in imidazolone. Immunoreactivity was absent in CEL. In contrast, no immunoreactivity to CML, pyrraline, pentosidine, imidazolone or CEL was detected in corneas with bullous keratopathy, or in corneas without any corneal diseases. CONCLUSIONS: CDK is caused by an aggregation of AGE-modified proteins. The result is consistent with etiological findings that ultraviolet irradiation and ageing, both of which are accelerators of AGE formation, are closely related to the development of CDK.

Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model.

Peritoneal sclerosis is a major and serious complication in patients on long-term continuous ambulatory peritoneal dialysis (PD). The involvement of angiogenesis and proangiogenic factors such as vascular endothelial growth factor (VEGF)-A in progressing peritoneal sclerosis has been reported. We previously reported the therapeutic efficacy of endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen, in a mouse diabetic nephropathy model. Here, we examined the therapeutic effect of endostatin peptide in preventing progression in a mouse peritoneal sclerosis model. Male ICR mice received intraperitoneal injections of chlorhexidine gluconate (CG) every other day to induce peritoneal sclerosis. Endostatin peptide (1 or 4 mg/kg/day) was administered via subcutaneously implanted osmotic minipumps. Peritoneal sclerosis (day 24) was significantly suppressed by endostatin peptide in a dose-dependent manner. Peritoneal accumulation of type III collagen was significantly suppressed by endostatin peptide. Increase in the number of CD31(+) blood vessels, F4/80(+) monocyte/macrophage accumulation, and 5-bromodeoxyuridine(+) proliferating cells was significantly inhibited by endostatin peptide. Increase in peritoneal expression of VEGF-A, profibrotic transforming growth factor-beta1, and alpha-smooth muscle actin was suppressed by endostatin peptide. Immunoreactivity for endogenous endostatin (whole molecule) and endostatin receptor alpha5beta1-integrin was increased and colocalized to CD31(+) blood vessels in the thickened peritonea of CG-injected mice. These results demonstrate the potential use of antiangiogenic endostatin peptide as a novel therapeutic agent in preventing peritoneal sclerosis, a severe complication in patients undergoing long-term PD.

Acquired type 3-like von Willebrand syndrome preceded full-blown systemic lupus erythematosus.

We report a quite rare case of acquired type 3-like von Willebrand syndrome (vWS) that preceded full-blown systemic lupus erythematosus (SLE). A 16-year-old woman with no previous disease history and no family history of hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis and gingival bleeding. She was diagnosed as having atypical type 3 von Willebrand disease because of prolonged bleeding time with normal platelet count and prolonged activated partial thromboplastin time (aPTT), and an almost complete absence of von Willebrand factor (vWF) antigen, ristocetin cofactor activity (vWF:RCo) and ristocetin-induced platelet agglutination (RIPA). Furthermore, electrophoretic analysis of plasma vWF revealed a trace amount of vWF and an absence of the multimeric form of vWF. Infusions of either vasopressin or factor VIII/vWF concentrates improved bleeding symptoms and corrected the aPTT and RIPA. However, she complained of low-grade fever, general fatigue and polyarthralgia 5 months later, and leukocytepenia and hypo-complementemia developed. Anti-double-stranded DNA antibodies and lupus erythematosus cells became positive. These findings were compatible with SLE. Mixing the patient's platelet-poor plasma (PPP) with normal platelet-rich plasma (PRP) (PPP/PRP = 2/1) resulted in a complete inhibition of RIPA, suggesting the presence of vWF inhibitor in her plasma. Treatment with prednisolone (40 mg/day) started and the bleeding tendency gradually improved. One month later, all of the laboratory data including aPTT, bleeding time, RIPA and vWF:RCo became normal. These findings indicate that she has an acquired type 3-like vWS associated with SLE.

Gastrointestinal stromal tumors and KIT-positive mesenchymal cells in the omentum.

Gastrointestinal stromal tumor (GIST) is currently considered to be derived from the interstitial cells of Cajal (ICC). To test the hypothesis that omental mesenchymal tumor is also a type of GIST, we evaluated the expression of specific molecules in GIST, and c-kit gene mutation in omental mesenchymal tumors, and we identified a possible counterpart of ICC in the omentum. Immunohistochemically, all of the omental mesenchymal tumors (n = 5) were positive for both KIT and CD34, and three of the five tumors were also positive for an embryonic form of smooth-muscle myosin heavy chain (SMemb). Polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing revealed mutations in c-kit gene exon 11 in all five tumors. As for the ICC counterparts in the omentum, there were some KIT-positive mesenchymal cells resembling ICC at the surface of the omentum. Double fluorescence immunostaining, using anti-KIT polyclonal antibodies and monoclonal antibodies against other molecules, demonstrated that KIT-, CD34- and SMemb-positive cells were present just beneath the mesothelial cells of the omentum. These results show that omental mesenchymal tumor corresponds to GIST of the omentum, and that KIT-positive bipolar mesenchymal cells may be a counterpart of ICC in the gastrointestinal tract. Identification of a new type of KIT-positive mesenchymal cell in the omentum may lead to the discovery of a new physiological role for this organ.