Prognostic factors in metaplastic carcinoma of the breast: a multi-institutional study.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare type of breast cancer that has basal-like characteristics and is perceived to have poorer prognosis when compared with conventional no specific type/ductal carcinomas (ductal/NST). However, current data on MBC are largely derived from small case series or population-based reports. This study aimed to assess the clinicopathological features and outcome of MBC identified through an international multicentre collaboration. METHODS: A large international multicentre series of MBC (no=405) with histological confirmation and follow-up information has been included in this study. The prognostic value of different variables and outcome has been assessed and compared with grade, nodal status and ER/HER2 receptor-matched ductal/NST breast carcinoma. RESULTS: The outcome of MBC diagnosed in Asian countries was more favourable than those in Western countries. The outcome of MBC is not different from matched ductal/NST carcinoma but the performance of the established prognostic variables in MBC is different. Lymph node stage, lymphovascular invasion and histologic subtype are associated with outcome but tumour size and grade are not. Chemotherapy was associated with longer survival, although this effect was limited to early-stage disease. In this study no association between radiotherapy and outcome was identified. Multivariate analysis of MBC shows that histologic subtype is an independent prognostic feature. CONCLUSIONS: This study suggests that MBC is a heterogeneous disease. Although the outcome of MBC is not different to matched conventional ductal/NST breast carcinoma, its behaviour is dependent on the particular subtype with spindle cell carcinoma in particular has an aggressive biological behaviour. Management of patients with MBC should be based on validated prognostic variables.

Metaplastic carcinoma of the breast with chondroid differentiation (matrix-producing carcinoma): study of the diagnostic cost-effectiveness of fine-needle aspiration biopsy and needle core biopsy.

UNLABELLED: Metaplastic carcinoma with chondroid differentiation (MMPC) is a subtype of breast metaplastic carcinoma with mesenchymal differentiation. Although fine-needle aspiration (FNAB) and core-needle biopsy (CNB) are commonly used for the diagnosis of breast cancer, not enough studies proving the diagnostic cost-effectiveness of these techniques for the identification of MMPC have been published so far. The aim of this study was to investigate the concordance between the presurgical diagnosis using FNAB/CNB and the definitive diagnosis in the surgical specimen in pure MMPC. A case of MMPC is also reported. STUDY DESIGN: All cases of MMPC diagnosed in our institution from 1995 to 2011 were reviewed. The presence of chondroid differentiation in cytological studies or biopsies and the proportion of chondroid matrix in the surgical specimen were evaluated. RESULTS: A total of 13 cases of pure MMPC were collected. The diagnosis was suspected in 25% of FNABs and was rendered in 40% of CNBs. CONCLUSIONS: The chondroid component in MMPC is hard to identify by FNAB and CNB. The random distribution and proportion of the chondroid differentiation in the tumour and the expertise in performing the technique and in identifying the chondroid component may play an important role in the diagnosis of MMPC using these techniques.

Peritoneal concentrations of transforming growth factor beta in horses with colic.

REASONS FOR PERFORMING THE STUDY: In man, peritoneal transforming growth factor beta (TGF-beta) is associated with peritoneal diseases and subsequent adhesion formation. No studies on plasma and peritoneal TGF-beta concentrations in horses with colic are available. OBJECTIVES: 1) To determine both plasma and peritoneal TGF-beta(1) and TGF-beta(3) concentrations in horses with different types of colic (not previously subjected to abdominal surgery); 2) to compare these concentrations according to the type of peritoneal fluid (transudate, modified transudate and exudate); and 3) to compare and correlate plasma and peritoneal concentrations of TGF-beta(1) and TGF-beta(3) and the types of peritoneal fluid according to the colic group and outcome. METHODS: Peritoneal fluid and plasma samples from 78 horses with colic and 8 healthy horses were obtained. Patients were classified according to diagnosis (obstructions, enteritis, ischaemic disorders and peritonitis), peritoneal fluid analysis (transudate, modified transudate and exudate), and outcome (survivors and nonsurvivors). Plasma and peritoneal TGF-beta(1) and TGF-beta(3) concentrations were determined by ELISA. Data were analysed by parametric and nonparametric tests. P< or =0.05 was considered as statistically significant. RESULTS: Concentrations of peritoneal fluid TGF-beta(1) were significantly (P = 0.01) higher in horses with peritonitis in comparison with all other colic groups and controls. Horses with ischaemic lesions had significantly (P = 0.01) higher concentrations of peritoneal TGF-beta(1) in comparison with controls and the group of horses with obstructions. Peritoneal TGF-beta(1) concentration also was significantly (P = 0.01) higher in exudates in comparison with transudates. Peritoneal TGF-beta(1) and TGF-beta(3) concentrations and plasma TGF-beta(1) concentration were significantly increased in nonsurvivors compared to survivors (P = 0.001, P = 0.004 and P = 0.05, respectively). CONCLUSIONS: Peritoneal TGF-beta(1) concentration was higher in horses with severe gastrointestinal diseases (ischaemic intestinal lesions and peritonitis), in horses with an altered peritoneal fluid (exudate), and in nonsurvivors. POTENTIAL RELEVANCE: Peritoneal TGF-beta concentration increases in horses with severe gastrointestinal disease as an anti-inflammatory response.

Allogeneic hematopoietic stem cell transplantation for patients with relapsed/refractory systemic anaplastic large cell lymphoma. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

Information regarding the curative role of allogeneic stem cell transplantation (allo-HCT) in systemic anaplastic large cell lymphoma (sALCL) is scarce. We analyzed the results of allo-HCT in patients with relapsed/refractory sALCL with special emphasis on the role of brentuximab vedotin (BV) as a bridge to allo-HCT. Forty-four patients (24 females, median age 38 years) with sALCL were included. Twenty-three patients (52%) received BV before allo-HCT; BV-treated patients were more heavily pretreated (≥3 lines of therapy in 74% vs. 38%, p = 0.04). Twenty-three patients (52%) were in complete remission (CR) at allo-HCT. Three-year nonrelapse mortality and incidence of relapse (IR) after allo-HCT were 7% and 40%, respectively. With a median follow-up of 39 (12-69) months for survivors, 3-year progression-free survival (PFS) and overall survival were 53% and 74%, respectively. Univariate analysis showed that heavily pretreated patients and those not in CR had a higher IR and a lower PFS. The use of BV before transplant did not impact on any of the outcomes. Allo-HCT is a curative therapeutic strategy in a significant proportion of patients with relapsed/refractory sALCL; BV does not seem to modify transplant-related outcomes but might be able to render more patients candidates for this curative treatment.

Autologous hematopoietic stem cell transplantation for relapsed/refractory systemic anaplastic large cell lymphoma. A retrospective analysis of the lymphoma working party (LWP) of the EBMT.

Systemic anaplastic large cell lymphoma (sALCL) is a rare histological entity expressing the CD30 antigen that comprises around 11% of peripheral T-cell lymphoma. We analysed the outcome of patients with relapsed/refractory sALCL treated with autologous stem cell transplantation (auto-HCT). We included 65 adult patients (42 males; median age, 44 years); 24 patients had an ALK-ve sALCL. Fifty-one patients had chemosensitive disease at the time of transplant. Ten patients (15%) were treated with brentuximab vedotin (BV) before auto-HCT (median number of doses: 5). The median follow-up for surviving patients was 35 months (3-71). Three-year cumulative incidence of nonrelapse mortality and of relapse were 1.7% and 34%, respectively. Three-year progression-free survival and overall survival were 64% and 73%, respectively. No prognostic factors for any of the outcomes analysed were found in univariate analysis. There were no significant differences in any of the outcomes between patients who had received BV and the remainder. This is the largest analysis presented so far analysing the role of auto-HCT in patients with relapsed/refractory sALCL, showing a promising PFS and OS in this high-risk population. The potential impact of the administration of BV as salvage strategy before the procedure needs to be further elucidated.

Modified technique for the repair of third-degree rectovaginal lacerations in mares.

Eight mares with third-degree rectovestibular lacerations were treated by a two-stage surgical technique. The rectovestibular shelf was corrected with three parallel 'circular' continuous suture rows distributed along the longitudinal axis of the vagina, and the perineal body was reconstructed with three divergent simple continuous rows. Primary healing of the first-stage surgery occurred in all the mares. Seven of the mares completed the two-stage surgery and primary healing occurred in all of them. One of them returned to endurance racing competition and one was lost to follow-up. The other five were bred and became pregnant; one foaled four times, two foaled three times, one foaled once and the other was pregnant at the time of writing. The condition did not recur in any of the mares after foaling.

Autologous platelet concentrates as a treatment for musculoskeletal lesions in five horses.

Two horses with acute tendinopathy of a superficial digital flexor tendon (SDFT) and three horses with chronic proximal desmitis of the suspensory ligament (PDSL) were treated by injecting autologous concentrates of their platelets into the lesions. The lesions were monitored ultrasonographically and clinically. There were significant ultrasonographic and clinical improvements in the two horses with SDFT, but no ultrasonographic improvements in the horses with PDSL; however, they improved clinically and became less lame. All the horses had returned to their pre-injury level of performance by six months after the completion of the treatment, and none of them had suffered a recurrence after 20 months.

Eosinophilic synovitis of the tarsocrural joint in a horse.

Eosinophilic synovitis (ES) is a rare disease described in human and veterinary medicine. Only three cases have been reported in the horse. A case of tarsocrural synovitis in an Hispano-Arabian gelding is presented in this report. The patient presented with severe joint effusion and lameness of the right tarsocrural joint on admission. Synovial fluid analysis revealed an increased WBC of 12800 leukocytes/microliter with 76% of eosinophils. Lavage of the diseased joint and medical treatment with antibiotics and non-steroidal anti-inflammatory drugs produced remission of the clinical problem.

[Amyotrophic lateral sclerosis that begins with voice and deglution alterations]. / Ela que debuta con alteraciones en la voz y en la deglución.

Amyotrophic lateral sclerosis is a progressive degenerative neuromuscular disease of insidious onset. It involves upper and lower motor neurons and causes both spastic and atrophic muscular symptoms. More than one fourth of patients have complaints relating to the head and neck (bulbar palsy); thus, the otolaryngologist may be the first physician to see them. In bulbar forms of Amyotrophic Lateral Sclerosis, voice and/or swallowing difficulties are often the initial signs of disturbance. Predominant symptoms are slurred speech, hoarseness, dysphagia, and dyspnea. Muscular weakness, atrophy, and fasciculation are noted on examination. We show a case and revise bibliography.

Inhibition of phosphoglucomutase by fructose 2,6-bisphosphate.

Fructose 2,6-bisphosphate inhibits phosphoglucomutase. The inhibition is mixed with respect to glucose 1,6-bisphosphate and non-competitive with respect to glucose 1-phosphate. In contrast with fructose 1,6-bisphosphate and glycerate 1,3-bisphosphate, which also possess inhibitory effect, fructose 2,6-bisphosphate does not phosphorylate phosphoglucomutase. Fructose 2,6-bisphosphate preparations contain contaminants which can explain artefactual results previously reported.

Effect of vanadate on the formation and stability of the phosphoenzyme forms of 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase and of phosphoglucomutase.

2,3-Bisphosphoglycerate-dependent phosphoglycerate mutase (2,3-bisphospho-D-glycerate:2-phospho-D-glycerate phosphotransferase, EC 2.7.5.3) and phosphoglucomutase (alpha-D-glucose-1,6-bisphosphate:alpha -D-glucose-1-phosphate phosphotransferase, EC 2.7.5.1), which are markedly inhibited by vanadate, possess a ping-pong mechanism involving an intermediate phosphoenzyme. The formation and the stability of these phosphoenzymes have been examined spectrophotometrically in the absence of vanadate. Vanadate does not inhibit the phosphorylation of either mutase by its cofactor. The instability of the phosphoenzyme form of phosphoglycerate mutase increases in the presence of vanadate, but the stability of the phosphorylated phosphoglucomutase is not affected.

Interactions of histones and histone peptides with DNA Thermal denaturation and solubility studies.

The interactions of DNA with the five histone components (H1, H2B, H2A, H3 and H4) and with a number of histone fragments (N-H1 (1--72), C-H1 (73--216), N-H2B (l--59), C-H2B, (63--125), N-H2A (1-39), C-H2A (58--129), N-H4 (1--84) and C-H4 (85--102) have been studied by using the techniques of thermal denaturation and solubility behaviour. Complexes in 10(-3) M phosphate buffer, 2 - 10(-5) M Na(2)-EDTA, pH 7.0 were prepared by the direct mixing method. For lysine-rich histones (H1 and H2B) it has been found that the main characteristics which governs the interaction with DNA are located in the very lysine-rich part of the molecules, i.e. in the C-H1 and N-H2B segments. These regions are also responsible for a cooperative distribution of the histone along the DNA molecules in the artificial complexes. It appears from our studies that the tertiary structure of the moderately, arginine-rich histone (H2A) is an essential feature for its interaction with DNA. The two arginine-rich histones (H3 and H4) complexed with DNA behave in a similar way, both in thermal denaturation and in DNA precipitation. In the case of C-H4, a marked shift of the melting profile has been observed which is correlated with the presence in the peptide of the hydrophilic cluster Lys-Arg-Gln-Gly-Arg-Thr. Our results suggest that large segments rich in lysine and basic clustering within histones give rise to different modes of electrostatic interaction with DNA.

Immunological properties of rat phosphoglycerate mutase isozymes.

In mammalian tissues three phosphoglycerate mutase (D-phosphoglycerate 2,3-phosphomutase, EC 5.4.2.1) isozymes result from the homo-dimeric and hetero-dimeric combinations of two subunits (types M and B). Whereas rabbit antisera against type M subunit (purified from rat muscle) and against type BB isozyme (purified from rat brain) possessed a high degree of specificity, both antisera reacted with type BB and MM isozymes, as demonstrated by immunoneutralization and ELISA. Both the M subunit and B subunit were more immunoreactive than their respective dimeric isozymes. Subunits type M and B may possess common antigenic determinants, and some of these determinants may be sterically hindered in their dimeric structures.

Glycolytic enzyme activities are decreased during acute rejection in transplanted rat hearts.

Metabolic alterations have been characterized in various heart diseases. However, no data are available concerning metabolic changes during acute rejection episodes. Heterotopic heart transplantations in rats were done using Lewis rats as donors and recipients as a control group. The rejection group included Brown-Norway rat donors to Lewis rat recipients. Nonoperated hearts were also studied. Enzyme activities were determined for phosphofructokinase, pyruvate kinase, and lactate dehydrogenase. There were no alterations in the control group compared to nonoperated hearts. However, the rejection cohort of hearts showed decreased glycolytic enzymes. Although lactate dehydrogenase maintained similar levels compared to the control group, phosphofructokinase showed only 50% activity, and pyruvate kinase showed less than 10% of the activity compared with controls. These results suggested that metabolic alterations in rejected hearts differ from other cardiomyopathies.

Location of phosphoglycerate mutase in rat skeletal muscle. An immunocytochemical and biochemical study.

The subcellular distribution of phosphoglycerate mutase was studied by immunogold techniques. With the aid of highly affinity-purified anti-phosphoglycerate mutase antibodies, the enzyme was found in both cytosol and nucleus of rat skeletal muscle. No evidence of interaction with contractile proteins was observed in cytosol. Nuclear location was also confirmed biochemically using purified nuclear preparations from rat skeletal muscle. Only one immunoreactive nuclear band was observed by Western blot experiments and corresponded to that of phosphoglycerate mutase mobility. Activity measurements from nuclear extracts showed that 25% of total specific activity is found in the nuclei.

Isolation and sequencing of a cDNA encoding the B isozyme of rat phosphoglycerate mutase.

Phosphoglycerate mutase consists of two kinds of different subunits, M and B. We previously sequenced a rat cDNA encoding the type-M subunit. Here, we report the sequence of the type-B subunit-encoding cDNA. This cDNA has 1754 bp and contains a long 3'-untranslated region of 897 bp.