Javier Regadera

Istituto Nazionale Tumori "Fondazione Pascale", Marano di Napoli, Campania, Italy

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Publications (27)73.6 Total impact

  • Article: Bladder autoaugmentation with protective autologous uterine flap. Experimental study in the rat.
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    ABSTRACT: INTRODUCTION: Enterocystoplasties are associated to complications. We developed a surgical technique for bladder autoaugmentation using autologous uterine flap in the rat, to try and improve the post-surgical evolution. METHODS: 36 female Wistar rats were randomly allocated into following groups: Group 1: Control (n=12) for analytical parameters, Group 2: Sham-operation hysterocystorrhaphy (n=12) and Group 3: Bladder autoaugmentation with autologous uterine flap (n=12). Two weeks after surgery ultrasound examination of the bladder was performed. At 8 weeks and 24 weeks, blood and urine samples were taken. Post-mortem evaluation was performed and urogenital apparatus removed for gross and microscopic examination. The statystical analysis was done using the Kruskall-Wallis and the extension of the Fisher's exact test. Significance was set at 5% (p<0.05). RESULTS: Serum chemistry, blood count and peripheral blood smears, electrolytes and urinary parameters were all within the normal range for the rat. No abnormal findings were observed during ultrasound examination. There was no mortality or other surgical complications. Post-mortem evaluation revealed no dilation of bladder, uterus or upper urinary tract. Uroliths were not observed. Histology of the augmented area demonstrated an excellent union between the bladder and the protective uterine flap. A normal urothelial layer was maintained. CONCLUSIONS: The use of autologous uterine flap to perform bladder autoaugmentation in the rat proved a safe and suitable surgical technique to augment the bladder. The major advantage is the avoidance of the complications observed in other surgical techniques for bladder augmentation, like enterocystoplasties, where gastrointestinal tract epithelium is incorporated into the urinary tract.
    International journal of surgery (London, England) 02/2013;
  • Article: Short and long term fate of human AMSC subcutaneously injected in mice.
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    ABSTRACT: To study the ability of human adipose-derived mesenchymal stem cells (AMSCs) to survive over the short and long term, their biodistribution and their biosafety in vivo in tumor-prone environments. We subcutaneously injected human AMSCs from different human donors into immunodeficient SCID mice over both short- (2 and 4 mo) and long- (17 mo) term in young, and aged tumor-prone mice. Presence of human cells was studied by immunohistochemistry and polymerase chain reaction analysis in all organs of injected mice. Subcutaneously injected AMSCs did not form teratomas at any time point. They did not migrate but remained at the site of injection regardless of animal age, and did not fuse with host cells in any organ examined. AMSCs survived in vivo for at least 17 mo after injection, and differentiated into fibroblasts of the subdermic connective tissue and into mature adipocytes of fat tissue, exclusively at the site of injection. Our results support the assertion that AMSC may be safe candidates for therapy when injected subcutaneously because of their long term inability to form teratomas.
    World journal of stem cells. 06/2011; 3(6):53-62.
  • Article: Liver growth factor treatment restores cell-extracellular matrix balance in resistance arteries and improves left ventricular hypertrophy in SHR.
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    ABSTRACT: Liver growth factor (LGF) is an endogenous albumin-bilirubin complex with antihypertensive effects in spontaneously hypertensive rats (SHR). We assessed the actions of LGF treatment on SHR mesenteric resistance and intramyocardial arteries (MRA and IMA, respectively), heart, and vascular smooth muscle cells (VSMC). SHR and Wistar-Kyoto (WKY) rats treated with vehicle or LGF (4.5 μg LGF/rat, 4 ip injections over 12 days) were used. Intra-arterial blood pressure was measured in anesthetized rats. The heart was weighted and paraffin-embedded. Proliferation, ploidy, and fibronectin deposition were studied in carotid artery-derived VSMC by immunocytochemistry. In MRA, we assessed: 1) geometry and mechanics by pressure myography; 2) function by wire myography; 3) collagen by sirius red staining and polarized light microscopy, and 4) elastin, cell density, nitric oxide (NO), and superoxide anion by confocal microscopy. Heart sections were used to assess cell density and collagen content in IMA. Left ventricular hypertrophy (LVH) regression was assessed by echocardiography. LGF reduced blood pressure only in SHR. LGF in vitro or as treatment normalized the alterations in proliferation and fibronectin in SHR-derived VSMC with no effect on WKY cells. In MRA, LGF treatment normalized collagen, elastin, and VSMC content and passive mechanical properties. In addition, it improved NO availability through reduction of superoxide anion. In IMA, LGF treatment normalized perivascular collagen and VSMC density, improving the wall-to-lumen ratio. Paired experiments demonstrated a partial regression of SHR LVH by LGF treatment. The effective cardiovascular antifibrotic and regenerative actions of LGF support its potential in the treatment of hypertension and its complications.
    AJP Heart and Circulatory Physiology 06/2011; 301(3):H1153-65. · 3.71 Impact Factor
  • Article: Histerocystoplasty: a novel surgical procedure in the rat.
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    ABSTRACT: Enterocystoplasties are associated to complications. To avoid them, different types of tissue templates have been used to augment the bladder and induce native bladder regeneration. A novel surgical technique for bladder reconstruction using autologous uterine tissue was evaluated in a rat model. Forty-two female Wistar rats were randomly allocated into three groups: sham-operation hysterocystorrhaphy (n = 12), hysterocystoplasty (n = 18), and control (n = 12). Two weeks after surgery, ultrasound examination of the bladder was performed. At 2, 4, or 6 mo after surgery, the rats were anesthetized and blood and urine samples were taken. They were then euthanized and post-mortem and histologic examination were performed. Ultrasound examination, analytical parameters and weight control, as well as gross and histologic examination were performed in all the operated animals. The statistical analysis was performed using Kruskal-Wallis and the extension of Fisher's exact tests. Significance was set at 5% (P < 0.05). Serum chemistry, blood count and peripheral blood smears, electrolytes, and urinary parameters were all within the normal range for the rat. Histologic sections of the surgically augmented zone between the bladder and uterine horn demonstrated urothelial epithelization, providing adequate coverage of the transition area in 72.22% of the rats that underwent hysterocystoplasty. The hysterocystoplasty was technically viable in all the cases and proved to be an easy and safe surgical model for bladder reconstruction. All animals were healthy after surgery and all systemic parameters analyzed were within normal physiologic range for the rat.
    Journal of Surgical Research 03/2011; 175(1):157-62. · 2.25 Impact Factor
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    Article: Hypothyroidism enhances tumor invasiveness and metastasis development.
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    ABSTRACT: Whereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development, the relationship between thyroid hormone levels and human cancer is a controversial issue. It has been reported that hypothyroidism might be a possible risk factor for liver and breast cancer in humans, but a lower incidence of breast carcinoma has been also reported in hypothyroid patients In this work we have analyzed the influence of hypothyroidism on tumor progression and metastasis development using xenografts of parental and TRbeta1-expressing human hepatocarcinoma (SK-hep1) and breast cancer cells (MDA-MB-468). In agreement with our previous observations tumor invasiveness and metastasis formation was strongly repressed when TRbeta-expressing cells were injected into euthyroid nude mice. Whereas tumor growth was retarded when cells were inoculated into hypothyroid hosts, tumors had a more mesenchymal phenotype, were more invasive and metastatic growth was enhanced. Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs. These results show that changes in the stromal cells secondary to host hypothyroidism can modulate tumor progression and metastatic growth independently of the presence of TRs on the tumor cells. On the other hand, the finding that hypothyroidism can affect differentially tumor growth and invasiveness can contribute to the explanation of the confounding reports on the influence of thyroidal status in human cancer.
    PLoS ONE 02/2009; 4(7):e6428. · 4.09 Impact Factor
  • Article: Thyroid hormone receptor beta1 acts as a potent suppressor of tumor invasiveness and metastasis.
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    ABSTRACT: Loss of thyroid hormone receptors (TR) is a common feature in some tumors, although their role in tumor progression is currently unknown. We show here that expression of TRbeta1 in hepatocarcinoma and breast cancer cells reduces tumor growth, causes partial mesenchymal-to-epithelial cell transition, and has a striking inhibitory effect on invasiveness, extravasation, and metastasis formation in mice. In cultured cells, TRbeta1 abolishes anchorage-independent growth and migration, blocks responses to epidermal growth factor, insulin-like growth factor-I, and transforming growth factor beta, and regulates expression of genes that play a key role in tumorigenicity and metastatic growth. The receptor disrupts the mitogenic action of growth factors by suppressing activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling pathways that are crucial for cell proliferation and invasiveness. Furthermore, increased aggressiveness of skin tumors is found in genetically modified mice lacking TRs, further demonstrating the role of these receptors as inhibitors of tumor progression. These results define a novel role for the thyroid hormone receptor as a metastasis suppressor gene, providing a starting point for the development of novel therapeutic strategies for the treatment of human cancer.
    Cancer Research 02/2009; 69(2):501-9. · 7.86 Impact Factor
  • Article: [Photodynamic therapy in urology. Biologic and pathologic mechanisms of action].
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    ABSTRACT: Photodynamic Therapy (FDT) is a minimally invasive therapeutic modality extraordinarily useful. In urology, FDT is very useful and may be applied through endoscopes or directly, with excellent results obtained for the diagnosis and treatment of bladder tumors, in the treatment of prostate cancer and its recurrences, and in the treatment of dermatological premalignant lesions and carcinomas of the penis. FDT is founded on the use of photosensitizing products which selectively accumulate in tumor tissues. The irradiation of these tissues with a proper wavelength light (generally in the red region of the visible spectrum lambda > or = 600 nm) produces the formation of oxygen reactive species with cytotoxic effects leading to selective death of neoplastic cells, and tumor regression. The main advantage of FDT is the restriction of cellular damage to the irradiation area, with the associated decrease of secondary effects on healthy tissues near the tumor, on the contrary to what happen with other conventional therapies for some tumors of the urinary tract. Moreover, FDT may be used in combination with radiotherapy and chemotherapy.
    Archivos españoles de urología 11/2008; 61(9):1135-44.
  • Article: Physiological androgen insensitivity of the fetal, neonatal, and early infantile testis is explained by the ontogeny of the androgen receptor expression in Sertoli cells.
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    ABSTRACT: Although gonadotropins and testosterone are high in the fetal/early postnatal periods, Sertoli cells remain immature and spermatogenesis does not progress. We hypothesized that Sertoli cells do not respond to testosterone because they do not express the androgen receptor. The objective of the study was to describe the precise ontogeny of androgen receptor expression in the human testis from fetal life through adulthood. This was an immunohistochemical study on testicular biopsies from fetal, neonatal, prepubertal, pubertal, and adult human testes. Quantification of androgen receptor expression in Sertoli cells was measured. Evaluation of androgen receptor expression in peritubular and interstitial cells as well as anti-Müllerian hormone and inhibin-alpha was also performed. Androgen receptor expression was first observed in the nuclei of few Sertoli cells at the age of 5 months. Labeling was weak in 2-15% of Sertoli cells until 4 yr of age and progressively increased thereafter. High levels of androgen receptor expression were observed in more than 90% from the age of 8 yr through adulthood. Androgen receptor was positive in peritubular cells and variable in interstitial cells. Anti-Müllerian hormone immunolabeling was strong in all Sertoli cells from fetal life throughout prepuberty and weakened progressively as spermatogenesis developed. Inhibin-alpha expression was detected in all Sertoli cells from fetal life through adulthood. A lack of androgen receptor expression could explain a physiological Sertoli cell androgen insensitivity during fetal and early postnatal life, which may serve to protect the testis from precocious Sertoli cell maturation, resulting in proliferation arrest and spermatogenic development.
    Journal of Clinical Endocrinology &amp Metabolism 09/2008; 93(11):4408-12. · 6.50 Impact Factor
  • Article: A murine model of falciparum-malaria by in vivo selection of competent strains in non-myelodepleted mice engrafted with human erythrocytes.
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    ABSTRACT: To counter the global threat caused by Plasmodium falciparum malaria, new drugs and vaccines are urgently needed. However, there are no practical animal models because P. falciparum infects human erythrocytes almost exclusively. Here we describe a reliable falciparum murine model of malaria by generating strains of P. falciparum in vivo that can infect immunodeficient mice engrafted with human erythrocytes. We infected NOD(scid/beta2m-/-) mice engrafted with human erythrocytes with P. falciparum obtained from in vitro cultures. After apparent clearance, we obtained isolates of P. falciparum able to grow in peripheral blood of engrafted NOD(scid/beta2m-/-) mice. Of the isolates obtained, we expanded in vivo and established the isolate Pf3D7(0087/N9) as a reference strain for model development. Pf3D7(0087/N9) caused productive persistent infections in 100% of engrafted mice infected intravenously. The infection caused a relative anemia due to selective elimination of human erythrocytes by a mechanism dependent on parasite density in peripheral blood. Using this model, we implemented and validated a reproducible assay of antimalarial activity useful for drug discovery. Thus, our results demonstrate that P. falciparum contains clones able to grow reproducibly in mice engrafted with human erythrocytes without the use of myeloablative methods.
    PLoS ONE 02/2008; 3(5):e2252. · 4.09 Impact Factor
  • Article: Leydig cell tumor and hyperplasia: a review.
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    ABSTRACT: We describe the role of Leydig cells in normal, hyperplastic and neoplastic testis. Recent acquisitions on etiology and pathobiology of Leydig cell proliferations, unusual microscopic presentations and clinical and morphologic features predictive of malignancy are reported.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 07/2007; 29(3):139-47. · 0.41 Impact Factor
  • Article: [Unilateral essential hematuria: diagnosis, endoscopic treatment, and new diagnostic-therapeutic algorithm].
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    ABSTRACT: To perform a long-term evaluation of 15 patients with unilateral essential hematuria, with the aim of determining the causes of bleeding and the response to endoscopic treatment. To design a diagnostic-therapeutic algorithm for patients with unilateral essential hematuria. We retrospectively review the clinical data of 15 patients with unilateral essential hematuria evaluated by rigid ureterorenoscopy (15 cases), flexible ureteropyelocalycoscopy (15 cases) and percutaneous nephroscopy (3 cases). In 4 patients electric fulguration of the pyelocalicial lesions was carried out. 14 of the 15 patients were successfully treated endoscopically. Only one patient presented recurrence of the hematuria. Mean follow-up time was 64 months (4-168 months). No patient suffered any relevant complication secondary to the endoscopic treatment. The cause of bleeding in patients with unilateral essential hematuria is determined only in a few, but endoscopic treatment is successful in a high percentage of cases. We consider that upper urinary tract endoscopy, mainly flexible ureteropyelocalycoscopy, has strongly impacted the diagnosis and treatment of essential unilateral hematuria. We present a new diagnostic-therapeutic algorithm, based on the usefulness of flexible instrumentation.
    Archivos españoles de urología 04/2007; 60(2):155-64.
  • Article: Primary testicular lesions are associated with testicular germ cell tumors of adult men.
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    ABSTRACT: The present study aims to establish the nature and frequency of testicular lesions in the parenchyma adjacent to testicular germ cell tumors (TGCT) to improve understanding of the factors involved in the development of testicular cancer. Fifty-three cases of TGCT that were fixed in both neutral-buffered formalin and Bouin solution, allowing for the nuclear characterization of Sertoli cells (SCs), were included in this study. In each case, at least 3 sections of different areas of preserved parenchyma surrounding the TGCT were studied. We found Leydig cell hyperplasia, microlithiasis, angiopathy, adenomatous hyperplasia of the rete testis, SC nodules, SC dysgenesis and involution, SC-only tubules, tubular atrophy, adluminal compartment lesions, hypospermatogenesis associated with spermatocyte sloughing, spermatogonial maturation arrest, and hypertrophic and multinucleated spermatogonia. These lesions were found in regions both adjacent and far away from the tumoral mass, and abnormal seminiferous tubules were found intermingled with those showing complete spermatogenesis, suggesting that these lesions are primary and existed before the development of the tumor. Our study suggests that SCs might play a more important role in the development of testicular tumors than previously thought. Our data supports the hypothesis that there is an abnormal differentiation of SCs, caused either by genetic anomalies or by environmental agents during fetal life. This abnormal SC differentiation may cause not only primary spermatogenesis failure and spermatogenesis arrest at different levels, but may also contribute to the poor differentiation of gonocytes into spermatogonia. The abnormal gonocyte differentiation might favor the development of dysplastic germ cells that may later transform into intratubular germ cell neoplasia, unclassified type.
    American Journal of Surgical Pathology 11/2006; 30(10):1260-8. · 4.35 Impact Factor
  • Article: PCPH expression is an early event in the development of testicular germ cell tumors.
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    ABSTRACT: Testicular germ cell tumors (TGCTs) include various malignancies with distinct pathologies that share a common precursor lesion (intratubular germ cell neoplasia, unclassified, ITGCNU, or carcinoma in situ, CIS). TGCTs, as a whole, represent a highly curable tumor paradigm, with high sensitivity to radiotherapy and, especially, to cisplatin-based chemotherapy. However, a percentage of cases display therapeutic resistance, and the molecular mechanisms underlying such resistant phenotype remain to be elucidated. We put forward the notion that expression of oncogenic forms of the PCPH gene, which are known to confer resistance to radiation and chemotherapeutic drugs, including cisplatin, may be expressed in TGCTs, and thus contribute to the development of therapeutic resistance. To begin testing this concept, we studied PCPH expression in human TGCT cell lines and in 54 solid tumors by RT-PCR, western immunoblot and immunohistochemistry. The results demonstrated that: i) PCPH is expressed in TGCT cell lines and tumors, including CIS; ii) its expression levels vary among different TGCT pathologies, being generally higher in well differentiated regions and lower in areas of predominant proliferation; iii) PCPH expression is substantially increased in tumors relative to matched normal testicular tissue; iv) tumor samples express PCPH polypeptides of low molecular mass, consistent with the known size of the PCPH oncoprotein, that are either absent from, or markedly reduced in, matched normal tissue. Collectively, these results positively identify PCPH as a good early molecular marker for testicular neoplasms, and strongly indicate that immunodetection of truncated PCPH polypeptides may be a useful diagnostic tool for TGCT.
    International Journal of Oncology 04/2006; 28(3):595-604. · 2.40 Impact Factor
  • Article: Short-term treatment of spontaneously hypertensive rats with liver growth factor reduces carotid artery fibrosis, improves vascular function, and lowers blood pressure.
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    ABSTRACT: Liver growth factor (LGF), a mitogen for liver cells, reduces fibrosis in a rat model of cirrhosis. The present study assesses the possible vascular antifibrotic and antihypertensive effects of LGF treatment on spontaneously hypertensive rats (SHR). Six-month-old male SHR and normotensive Wistar Kyoto rats (WKY) were treated with LGF (4.5 microg LGF/rat i.p. twice a week for 2 weeks). Haemodynamic parameters were measured in anaesthetized rats. Vascular structure and function were studied in carotid arteries using optical and confocal microscopy, radioimmunoassay for desmosine, and isometric tension recording. LGF reduced systolic and diastolic blood pressure only in SHR. When compared to those of untreated SHR, carotid arteries from LGF-treated SHR showed: 1) a 50% reduction in collagen area and an increase in vascular smooth muscle cell number in the media, 2) no difference in total elastin content, but an increase in size of fenestrae in the internal elastic lamina, and 3) enhanced relaxation to acetylcholine, sodium nitroprusside, and forskolin. These effects were specific for SHR, since no changes were observed in LGF-treated WKY. Short-term treatment with a low dose of LGF induced a large improvement in vascular structure and function and significantly reduced blood pressure in a rat model of essential hypertension. The present results could open future research to explore the vascular effects of this endogenous factor in order to determine its potential as an antifibrotic and antihypertensive agent in humans.
    Cardiovascular Research 03/2006; 69(3):764-71. · 6.06 Impact Factor
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    Article: Paratesticular cysts with benign epithelial proliferations of wolffian origin.
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    ABSTRACT: Paratesticular cysts with benign epithelial proliferations (BEPs) are rare. Only 10 cases were found in a series of 431 paratesticular cysts and were classified as follows: cystadenoma, 5; papilloma, 2; and hamartoma, 3. Four cystadenomas showed multiple papillae lined by CD10+ epithelial cells with hyperchromatic nuclei. The remaining lesion showed areas with a microcystic, glandular, cribriform pattern, with small, benign glands without atypia. Urothelial papilloma presented BEPs with cytokeratin (CK) 7+ and CD10+ and CK20- umbrella-like cells. The mural papilloma was lined by proliferative cylindrical cells exhibiting strong CK7 and CD10 expression. The 3 Wolffian hamartomas were characterized by strongly CD10+ epithelium surrounded by smooth muscle cells. The consistent CD10 expression in BEPs of paratesticular cysts suggests a Wolffian origin. The differential diagnosis of paratesticular cysts with BEP vs metastatic prostatic and primary borderline or malignant tumors is discussed.
    American Journal of Clinical Pathology 09/2005; 124(2):245-51. · 2.60 Impact Factor
  • Article: Granular changes in Sertoli cells in children and pubertal patients.
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    ABSTRACT: To characterize lysosomes and histochemical function of granular Sertoli cells in developmental alterations. Prospective and retrospective study. University hospital and research centers. Nineteen infantile and pubertal patients undergoing testicular biopsy; four rat testes for lysosomal study. CD-68, alpha-1-antitrypsin, vimentin, inhibin alpha subunit, and anti-mullerian hormone antibodies were evaluated. Morphometric measures in seminiferous tubules with and without granular Sertoli cells were obtained. Ultrastructural data of lysosomes in human and rat Sertoli cells were compared. Quantification of mean diameter of seminiferous tubules, tubular fertility index, and germ and Sertoli cell indexes were obtained in human testis. Granular changes in Sertoli cells are due to the accumulation of large amounts of lysosomes. Vimentin immunoexpression in infantile and pubertal granular Sertoli cells was lower than in adjacent nongranular Sertoli cells. Inhibin was negative in granular cells. Anti-mullerian hormone-positive and -negative granular Sertoli cells were present within the same tubules. The presence of early granular changes in Sertoli cells in childhood and pubertal cryptorchidic patients, associated with other developmental alterations, suggests an intense and irreversible dysfunction of phagocytosis in the granular Sertoli cells. These alterations might be considered primary and irreversible anomalies of Sertoli cells, which might be contributing factors in the infertility seen in these patients.
    Fertility and sterility 06/2005; 83(5):1489-99. · 3.97 Impact Factor
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    Article: Malignant mixed tumor of the larynx.
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    ABSTRACT: Malignant mixed tumor of the larynx is a very rare neoplasm; only five cases have been reported, three in the English-language literature. We report the case of a 69-year-old man with a 2-month history of hoarseness and a left laterocervical palpable mass. Total laryngectomy and bilateral radical neck dissection were performed. The tumor involved the glottic and subglottic regions and thyroid cartilage and extended to the anterior side of the larynx. Microscopically, the tumor was composed of three cellular types: epithelial cells, chondrocytes, and spindle cells. The epithelial cells resembled a moderately differentiated adenocarcinoma, the mesenchymal cells resembled a high-grade chondrosarcoma, and the spindle cells had immunohistochemical features of myoepithelial cells. The tumor metastasized to a cervical lymph node, with the three described components. The patient died 11 months after surgery. The lesion in this case was considered to be a malignant mixed tumor. Differences between this tumor and that of laryngeal chondrosarcoma are discussed.
    Head & Neck 03/2005; 27(2):166-70. · 2.40 Impact Factor
  • Article: [Physiopathology of the infertile testicle. Etiopathogenesis of varicocele].
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    ABSTRACT: To review current theories about etiology of varicocele and pathogenic mechanisms leading to a progressive disorder of spermatogenesis in relation to the subfertility or infertility these patients may present with. To evaluate its current anatomical knowledge of the normal venous drain of the testicle and its variations that may condition relapse or failure of the treatment of varicocele. To systematically review pathologic testicular lesions in patients with varicocele. To establish factors that may have prognostic significance on post-treatment fertility. We performed a systematic search in the Medline database for each of the proposed etiological and pathogenic theories on human varicocele. The evaluation of pathologic testicular lesions in patients with varicocele was obtained from the study of testicular biopsies performed at the Hospital La Paz in Madrid over the lost 30 years. Regarding the anatomical theories of varicocele, congenital absence or incompetence of the internal spermatic vein valves, difficult venous drain, augmented hydrostatic pressure of the internal spermatic vein, disorder of the fascial-muscular pump mechanism, and compression of the venous drainage system are considered, among others, potential etiological factors. Regarding possible pathogenic theories of varicocele, we evaluate disorders of testicular thermoregulation, hypoxia, toxic effect of renal and adrenal metabolites, certain endocrine disorders, obstruction of the spermatic tract, disorders of blood flow and epididymal vasculature, oxidative stress, gonadotoxins, apoptosis, and lastly the effect of varicocele on the contralateral testicle. Available data support the idea that etiopathogenesis of varicocele is multifactorial. Many classic etiopathogenic factors related to anatomy, embryology, obstruction, and hyperthermia still prevail in addition to new factors related to oxygen reactive species and apoptosis. However, many pathogenic and physiopathologic aspects of varicocele need to be elucidated yet. As a matter of fact, neither of these data alone may clearly explain the variable effect varicocele has on spermatogenesis and male fertility. So, it is necessary to establish histological criteria with proved prognostic significance that allow us to detect possible progression of testicular lesions after treatment.
    Archivos españoles de urología 12/2004; 57(9):883-904.
  • Article: Xanthogranulomatous funiculitis and orchiepididymitis: report of 2 cases with immunohistochemical study and literature review.
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    ABSTRACT: Two patients with xanthogranulomatous inflammation are described, one with involvement of the spermatic cord and the other with 1 testicle and epididymis affected. To our knowledge, only 12 cases of xanthogranulomatous orchiepididymitis have been reported previously, one of which also presented a xanthogranulomatous funiculitis. Clinically, our patients presented with spermatic cord enlargement (case 1) and chronic orchitis that did not respond to treatment with antibiotics (case 2). Histopathologically, both cases showed extensive xanthogranulomatous inflammation with numerous foamy macrophages that were associated with colonies of microorganisms suggestive of actinomyces in case 1. Additionally, Escherichia coli was cultured from the surgical specimen of case 2. The possible underlying pathology may be diabetes in case 1 and phlebitis associated with chronic orchitis in case 2. Differential diagnoses with other lesions that are rich in macrophages, such as malakoplakia, and those testicular neoplasms without serologic tumor markers are discussed.
    Archives of pathology & laboratory medicine 09/2004; 128(8):911-4. · 2.58 Impact Factor
  • Article: Microlithiasis of the epididymis and the rete testis.
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    ABSTRACT: Testicular microlithiasis is a well-defined clinical and pathologic entity easily diagnosed through testicular echography; however, its association with cancer and infertility is now under debate. Many efforts have been done in recent years to clarify the spectrum of lesions observed in testicular microlithiasis, but no published data as to the existence of a possible microlithiasis of the epididymis and the rete testis have been found. We have observed microlithiasis of the epididymis and the rete testis in surgical (8 epididymis and 6 testis) and autopsy specimens (12 cases). In decreased order of frequency, microliths of the proximal spermatic way were seen in rete testis, epididymal duct, and efferent ducts. Intraluminal, subepithelial, and interstitial microliths were localized along these segments of the spermatic way. Subepithelial microliths were the most frequently found. A granulomatous reaction around the interstitial epididymal microliths, mimicking malacoplakia, was observed in 1 case. The differential diagnosis of microliths includes corpora amilacea, Michaelis-Gutmann bodies, calcium deposits, hyaline globules, and parasites, like the giant kidney worm Dioctophyme renale. In infants and young adults, microlithiasis of the epididymis and the rete testis is frequently associated with alterations in the development of the proximal spermatic way. In elderly adults, it is related to ischemia and obstruction of the spermatic way.
    American Journal of Surgical Pathology 05/2004; 28(4):514-22. · 4.35 Impact Factor