Local and systemic production of proinflammatory chemokines in the pathogenesis of HAM/TSP.

BACKGROUND: HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is related with high proviral load, high proinflammatory cytokine levels, and passage of infected cell from the blood to the central nervous system. We aimed to evaluate the participation of chemokines and adhesion molecules in HAM/TSP pathogenesis. METHODS: CXCL9, CXCL10, sICAM-1, and sVCAM-1 were determined by ELISA in serum and cerebrospinal fluid (CSF) of HTLV-1 infected individuals. The frequency and median fluorescence intensity (MFI) of lymphocytes and monocytes expressing ligands of adhesion molecules (CD11a and CD49d) and a chemokine receptor (CXCR3) were analyzed by flow cytometry. RESULTS: The levels of CXCL9 and CXCL10 in serum of definite HAM/TSP were higher than in serum of probable HAM/TSP and HTLV-1 carriers. Considering the production of chemokines by patients with definite HAM/TSP, CXCL9 levels were higher in serum than in CSF, and CXCL10 production was higher in CSF than in serum. Levels of adhesion molecules in serum and CSF of HTLV-1 infected individuals did not differ. The MFI of CD11a on CD4+, CD8+ and CD14+ cells was lower in definite HAM/TSP than in HTLV-1 carriers and did not differ from probable HAM/TSP and healthy subjects (HS). The frequency of lymphocytes expressing CXCR3 was lower in definite HAM/TSP than in cells of probable HAM/TSP and did not differ from carrier and HS. CONCLUSION: These data point to the participation of proinflammatory chemokines, especially CXCL10, in the pathogenesis of definite HAM/TSP.

Immunological and viral features in patients with overactive bladder associated with human T-cell lymphotropic virus type 1 infection.

The majority of patients infected with human T-cell lymphotropic virus-type 1 (HTLV-1) are considered carriers, but a high frequency of urinary symptoms of overactive bladder, common in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) have been documented in these patients. The aim of this study was to determine if immunological and viral factors that are seen in HAM/TSP are also observed in these patients. Participants were classified as HTLV-1 carriers (n = 45), HTLV-1 patients suffering from overactive bladder (n = 45) and HAM/TSP (n = 45). Cells from HTLV-1 overactive bladder patients produced spontaneously more proinflammatory cytokines than carriers. TNF-α and IL-17 levels were similar in HAM/TSP and HTLV-1 overactive bladder patients. High proviral load was found in patients with overactive bladder and HAM/TSP and correlated with proinflammatory cytokines. In contrast with findings in patients with HAM/TSP, serum levels of Th1 chemokines were similar in HTLV-1 overactive bladder and carriers. Exogenous addition of regulatory cytokines decreased spontaneous IFN-γ production in cell cultures from HTLV-1 overactive bladder patients. The results show that HTLV-1 overactive bladder and HAM/TSP patients have in common some immunological features as well as similar proviral load profile. The data show that HTLV-1 overactive bladder patients are still able to down regulate their inflammatory immune response. In addition, these patients express levels of chemokines similar to carriers, which may explain why they have yet to develop the same degree of spinal cord damage as seen in patients with HAM/TSP. These patients present symptoms of overactive bladder, which may be an early sign of HAM/TSP.

Osteogenic sarcoma of the maxillary region in a Mexican mestizo population.

BACKGROUND AND OBJECTIVES: This study analyzed maxillary osteosarcoma in a mestizo population, with particular emphasis on the type of treatment and disease-free and overall survival. METHODS: This is a retrospective study including all mestizo patients with osteosarcoma of the maxilla seen in a single cancer institution in Mexico during a 20-year period. RESULTS: There were 21 patients. Age ranged from 16 to 76 years (mean, 37.5 y). Mean evolution time to diagnosis was 13 months, with a mean tumor size of 7 × 6 cm2. Surgery was the initial treatment in 19 patients, 17 of whom received adjuvant treatment. Disease-free survival according to surgical margin and overall survival were not statistically significant. Disease-free survival was 29% at 5 years, and overall survival was 50% and 25% at 5 and 10 years, respectively. CONCLUSIONS: Osteosarcomas of the maxilla are infrequent lesions that merit early diagnosis and proper treatment because of their rapid evolution. Treatment is currently based on a well-planned surgery with free surgical margins plus adjuvant radiotherapy and/or chemotherapy.

Laser resection of liposarcoma of the hypopharynx.

Liposarcomas represent between 15 and 18% of all sarcomas with the most common site being the extremities and retroperitoneum. Liposarcomas of the head and neck are rare, with an estimated incidence representing 3 to 5.6% of all liposarcomas. Liposarcomas most commonly present in the soft tissues of the neck. Primary liposarcoma of the hypopharynx (piriform sinus) is extremely rare. The symptoms presented are principally dysphagia, dyspnea, dysphonia, airway obstruction and sensation of a foreign body. Treatment of choice is surgery, and the literature describes the performance of lateral pharyngotomy, simple excision and even total laryngectomy. We present the case of a 23-year-old patient who was diagnosed 7 years prior with liposarcoma of the piriform sinus. The patient underwent surgery using a cervical approach. The tumor recurred 4 years postoperatively and the patient was again surgically intervened using the same approach. He presented to our Institute with 3 months evolution of dysphonia. Nasofibrolaryngoscopy and imaging studies were performed. Surgical treatment was decided upon with CO2 laser using suspension microlaryngoscopy, obtaining excellent results. Some of the advantages of this approach are low morbidity because of the avoidance of performing a tracheostomy, rapid return to oral feeding without necessity of a feeding tube, and reduction in hospitalization days. Disadvantage includes difficulty in evaluating margins.

Pentoxifylline down modulate in vitro T cell responses and attenuate pathology in Leishmania and HTLV-I infections.

Tumor necrosis factor-alpha (TNF-alpha) is known to have numerous biological properties relating to inflammation. This cytokine participates in the tissue damage of chronic inflammatory, autoimmune and infectious diseases. Pentoxifylline is a methylxanthine that inhibits phosphodiesterase IV, which inhibits the degradation of the cAMP and prostanoids. The increased intracellular concentration of the cAMP leads to a negative regulation of NF-kappaB and NF-AT transcription factors and suppresses TNF-alpha production. This review describes studies that support evidences that TNF-alpha is involved in the pathogenesis of HTLV-1 associated myelopathy and of cutaneous and mucosal leishmaniasis. Additionally, it demonstrates the effect of pentoxifylline in vitro in inhibiting TNF-alpha and IFN-gamma spontaneous production in PBMC from HTLV-1-infected patients, as well as its in vivo effect in inhibiting TNF-alpha in sera from mucosal leishmaniasis patients. Moreover, we review the results of clinical studies from the last 10 years using pentoxifylline to treat HTLV-1 associated myelopathy and cutaneous and mucosal leishmaniasis.

Macroglossia caused by adenoid cystic carcinoma. Case report.

A 33-year-old woman sought medical care at our institution for macroglossia. She had been treated before with tracheostomy and gastrostomy due to an adenoid cystic carcinoma (ACC) of the mobile tongue, in clinical stage IVC. She was subjected to total glossectomy with larynx preservation, modified radical dissection of the right neck and of the left supraomohyoid muscle, as well as reconstruction using a free flap from the rectus abdominus. The histological report described a 15x11 cm solid type ACC of the mobile tongue (grade III), with infiltration to adjacent soft tissues, vascular and lymphatic vessels, as well as two metastatic lymph nodes in the right neck dissection. One month after surgery, bone and bilateral pulmonary tumor activity became evident. In advanced-stage tumors, treatment must be individualized, and when accompanied by severe deterioration of the quality of life, surgery is recommended independently from the extension, provided that a good reconstruction is accomplished.

Carotid body tumour resection with LigaSure device.

OBJECTIVE: We carried out this study in patients who underwent resection of carotid body tumour (CBT). Shamblin's classification system was used as well as the modified Shamblin classification. We sought to determine whether surgical time and bleeding could be reduced with the use of the LigaSure system. METHODS: A prospective study was carried out in patients with CBT. RESULTS: A decrease in both time and bleeding was shown, although only overall time showed statistical significance. Cases were classified as Shamblin I, II and III in two, six, and four cases, respectively, and after surgical treatment were classified as modified Shamblin I, II, IIIa and IIIb in two, one, and six cases, respectively, by infiltration to the carotid. There was nerve damage in four cases, and there were three carotid resections. CONCLUSIONS: Use of LigaSure decreased bleeding and surgical time in CBTs. Lesions of the artery are mainly caused by infiltration or by muscular hypotrophy of the artery, which frequently requires vascular reconstruction. Nerve injury continues to be an important postoperative complication, which may result in a reduction in the quality of life for the patient. The rates of nerve injury as a result of surgery were unchanged.

Adenoid cystic carcinoma of the tongue--clinicopathological study and survival analysis.

BACKGROUND: To review the demographic data of a series of adenoid cystic carcinoma (ACC) of the tongue, as well as to analyze c-kit expression, histopathologic patterns, prognostic factors, evolution, recurrences and/or persistence and survival. METHODS: Retrospective study from 1986 to 2006, which reviews a database of 68 patients with diagnosis of head and neck ACC. RESULTS: We found eight cases of ACC of the tongue (11.7% of all head and neck ACCs). There were 7 female (87.5%) and 1 male (12.5%) patients, with an average age of 51 years (range 33 to 67 years). Seven patients were surgically treated, three of which required adjuvant treatment. Only one female patient did not accept treatment. Average follow-up time was 5.3 years. Metastases developed in 37% of cases during the follow-up period. Histopathologically, the cribriform pattern predominated (6/8 cases). All cases presented perineural invasion, and one patient also presented vascular invasion. c-kit positivity was observed in all cases. Global survival in the seven treated cases was 51% and 34% at 5 and 10 years, respectively, while the disease-free period was of 64% at 3 years and 42% at 10 years. CONCLUSION: ACC of the tongue is a rare neoplasm, in which early diagnosis is important because these are slowly-growing tumors that produce diffuse invasion. As the role of c-kit could not be assessed in this series, surgery continues to be the cornerstone of treatment and radiotherapy is indicated when surgical margins are compromised. Metastatic disease is still hard to handle because of the lack of adequate therapies for these tumors. Hence, survival has not changed in the last years.

[Supracricoid partial laryngectomy as salvage for recurrent carcinoma of the larynx initially treated by vertical partial hemilaryngectomy. Case report]. / Laringectomía parcial supracricoidea de rescate por recurrencia de carcinoma laríngeo tratado inicialmente con hemilaringectomía parcial vertical. Informe de caso.

OBJECTIVE: We undertook this study to report the possibility of salvage of vertical partial hemilaryngectomy with imbrication laryngoplasty (PVHLIL) to supracricoid partial laryngectomy (SCPL) with cricohyoidoepiglottopexy (CHEP) in a patient with recurrent glottic carcinoma. CLINICAL CASE: A 68-year-old patient with recurrent glottic squamous cell carcinoma (T1aN0) was treated with imbricated partial laryngectomy. Transoperative histopathological report demonstrated vocal cord free surgical margins anterior at 1 cm and 0.4 cm posterior. The patient was evaluated trimonthly and at 16-month follow-up presented with tumor activity on the posterior third of the left false vocal cord, close to the arytenoids, which still conserved mobility. Biopsy was performed and confirmed recurrence of squamous cell carcinoma. SCPL with CHEP was performed with a satisfactory postoperative evolution with tracheotomy decannulation at day 7. Physiological phonation and retirement of nasogastric tube were accomplished at day 15, as well as reinitiation of oral feeding. Histopathological report showed a moderately differentiated squamous cell carcinoma. Functional evaluation with PVHLIL is a clear voice alteration; however, patients do not require permanent tracheostomy, and a close to normal biopsicosocial integration after SCPL + CHEP is possible. CONCLUSIONS: PVHLIL is an excellent treatment option for selected glottic tumors staged T1 or T2. Close follow-up must be given to allow the possibility of organ conservation either with radiotherapy or surgery. When recurrence occurs, SCPL + CHEP must be considered according to the established criteria for this procedure. Total laryngectomy must be considered as the last option, with the only purpose being a normal quality of life.

[Reconstruction of the floor of the mouth with double free flap: report of three cases]. / Reconstrucción con doble colgajo libre del piso anterior de la boca. Informe de tres casos.

BACKGROUND: We undertook this study to describe three cases of reconstruction of the floor of the mouth with two simultaneous free flaps. METHODS: Three patients with cancer of the anterior floor of the mouth were subjected to segmental resection of the mandible and resection of the floor of the mouth with subsequent reconstruction using two simultaneous osseous and fasciocutaneous free flaps. RESULTS: All patients had a satisfactory evolution. Two patients underwent adjuvant radiotherapy, one due to the initial clinical stage and the other due to positive surgical margins. The third patient had neoadjuvant postoperative radiotherapy and concomitant chemoradiotherapy. CONCLUSIONS: If a tumor involves osseous structures of the anterior floor of the mouth, it is best to perform surgery with wide margins with segmental resection of the mandible. Surgical technique is the decision of the surgeon: how many and which types of flaps will be used for reconstruction of the anterior floor of mouth. When there is necrosis of a free flap in the head and neck region, attempt with another free flap is recommended.

Modulation of T cell responses in HTLV-1 carriers and in patients with myelopathy associated with HTLV-1.

OBJECTIVE: Human T lymphotropic virus-type 1 (HTLV-1) activates the immune system leading to a persistent and exacerbated T-cell response with increased production of IFN-gamma and TNF-alpha. Overproduction of pro-inflammatory cytokines is correlated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although some HTLV-1 carriers also show high levels of these cytokines. In this study, the ability of regulatory cytokines and cytokine antagonists to inhibit spontaneous IFN-gamma production was investigated. METHOD: IFN-gamma levels were measured by ELISA before and after addition of cytokines or anti-cytokines. RESULTS: Addition of IL-10 significantly reduced spontaneous IFN-gamma synthesis in cell cultures from HTLV-1 carriers, while no differences were observed in HAM/TSP patients. There was also a tendency to decreased IFN-gamma levels in cell cultures from HTLV-1 carriers with exogenous addition of TGF-beta. In paired analysis, neutralization of IL-2 significantly decreased IFN-gamma production in HTLV-1 carriers but not in HAM/TSP patients. Neutralization of IL-15 was less effective than neutralization of IL-2 in modulating IFN-gamma production. In HTLV-1 carriers, anti-IL-2 and simultaneous addition of anti-IL-2 and anti-IL-15 decreased IFN-gamma synthesis by 46 and 64%, respectively, whereas in patients with HAM/TSP simultaneous neutralization of both anti-cytokines only decrease IFN-gamma levels by 27%. CONCLUSIONS: Although a large proportion of HTLV-1 carriers produced high levels of pro-inflammatory cytokines similar to those observed in HAM/TSP patients, immune response can be downregulated by cytokines or cytokine antagonists in most HTLV-1 carriers. This modulation can be an important step in the prevention of tissue damage and progression from the HTLV-1 carrier state to HAM/TSP.

Reconstrucción con doble colgajo libre del piso anterior de la boca: informe de tres casos / Reconstruction of the floor of the mouth with double free flap: report of three cases

BACKGROUND: We undertook this study to describe three cases of reconstruction of the floor of the mouth with two simultaneous free flaps. METHODS: Three patients with cancer of the anterior floor of the mouth were subjected to segmental resection of the mandible and resection of the floor of the mouth with subsequent reconstruction using two simultaneous osseous and fasciocutaneous free flaps. RESULTS: All patients had a satisfactory evolution. Two patients underwent adjuvant radiotherapy, one due to the initial clinical stage and the other due to positive surgical margins. The third patient had neoadjuvant postoperative radiotherapy and concomitant chemoradiotherapy. CONCLUSIONS: If a tumor involves osseous structures of the anterior floor of the mouth, it is best to perform surgery with wide margins with segmental resection of the mandible. Surgical technique is the decision of the surgeon: how many and which types of flaps will be used for reconstruction of the anterior floor of mouth. When there is necrosis of a free flap in the head and neck region, attempt with another free flap is recommended.

Laringectomía parcial supracricoidea de rescate por recurrencia de carcinoma laríngeo tratado inicialmente con hemilaringectomía parcial vertical: informe de caso / Supracricoid partial laryngectomy as salvage for recurrent carcinoma of the larynx initially treated by vertical partial hemilaryngectomy: case report

OBJECTIVE: We undertook this study to report the possibility of salvage of vertical partial hemilaryngectomy with imbrication laryngoplasty (PVHLIL) to supracricoid partial laryngectomy (SCPL) with cricohyoidoepiglottopexy (CHEP) in a patient with recurrent glottic carcinoma. CLINICAL CASE: A 68-year-old patient with recurrent glottic squamous cell carcinoma (T1aN0) was treated with imbricated partial laryngectomy. Transoperative histopathological report demonstrated vocal cord free surgical margins anterior at 1 cm and 0.4 cm posterior. The patient was evaluated trimonthly and at 16-month follow-up presented with tumor activity on the posterior third of the left false vocal cord, close to the arytenoids, which still conserved mobility. Biopsy was performed and confirmed recurrence of squamous cell carcinoma. SCPL with CHEP was performed with a satisfactory postoperative evolution with tracheotomy decannulation at day 7. Physiological phonation and retirement of nasogastric tube were accomplished at day 15, as well as reinitiation of oral feeding. Histopathological report showed a moderately differentiated squamous cell carcinoma. Functional evaluation with PVHLIL is a clear voice alteration; however, patients do not require permanent tracheostomy, and a close to normal biopsicosocial integration after SCPL + CHEP is possible. CONCLUSIONS: PVHLIL is an excellent treatment option for selected glottic tumors staged T1 or T2. Close follow-up must be given to allow the possibility of organ conservation either with radiotherapy or surgery. When recurrence occurs, SCPL + CHEP must be considered according to the established criteria for this procedure. Total laryngectomy must be considered as the last option, with the only purpose being a normal quality of life.

Efeito de drogas inibidoras de TNF-a em células mononucleares do sangue periférico de pacientes infectados pelo HTLV-I / Effect of drugs inhibiting TNF-a in peripheral blood mononuclear cells of patients infected by HTLV-I

O Retovírus HTLV-I é o agente etiológico da Mielopatia Associada ao HTLV-I/Paraparesia Espástica Tropical (HAM/TSP), Leucemia de Células T do Adulto (ATL) e outras doenças sistêmicas mediadas pela resposta imune. A infecção pelo HTLV-I induz uma elevada proliferação espontânea das células T do perfil de citocinas com predominância das pró-inflamatórias. Nos indivíduos com HAM/TSP o TNF-a encontra-se elevado e envolvido na lesão tecidual. O surgimento de drogas inibidoras da síntese de TNF-a traz a possibilidade de uma terapêutica, buscando reduzir a inflamação e lesão tecidual. O objetivo deste estudo foi avaliar o poder inibidor destas drogas na produção de TNF-a em PBMC de indivíduos infectados com HTLV-I. PBMC de 37 indivíduos foram avaliados: assintomáticos (n=11), subclínicos (n=7) e com mielopatia (n=19). Foram utilizadas quatro drogas inibidoras da síntese de TNF-a: Pentoxifilina, Forskolin, Rolipram e Talidomida, as quais agem em diferentes etapas da síntese desta citocina. As concentrações espontâneas de TNF-a e IFN-y e com as drogas inibidoras foram avaliados nos sobrenadantes das culturas de PBMC através da técnica de ELISA e os resultados comparados entre os grupos usando o teste Mann-Whitney. A produção espontânea de TNF-a foi mais elevada no grupo com HAM/TSP quando comparado ao assintomático e a diferença estatisticamente significante (p = 0.001). A produção espontânea de IFN-y também foi mais alta no grupo com HAM/TSP quando comparados aos assintomáticos e a diferença estatisticamente significante (p = 0.017). Para avaliação das drogas inibidoras de TNF-a, utilizamos PBMC de indivíduos com de TNF-a e IFN-y espontâneos maiores que 5 pg/ml e os resultados comparados pelo teste estatístico Wilcoxon signed ranks. Pentoxifilina foi utilizada nas doses de 50 e 200 μM. A inibição da produção de TNF-a com 50 μM foi de 71 ± 26% (p = 0.003) e de IFN-y com 50 μM foi de 46 ± 24% (p = 0.001). Forskolin foi utilizado nas doses...