RESUMO
The human endometrium is receptive to the embryo for a specific period of time known as the window of implantation (WOI). During this period, the endometrium shows a specific gene expression profile suitable for endometrial function evaluation. ER Map is a molecular tool able to accurately predict endometrial receptivity status by transcriptomic analysis. In this retrospective study, including 2256 subfertile patients undergoing ART treatment, the clinical value of precise WOI determination is studied in detail. Results obtained when single embryo transfers (sET) were scheduled either within the WOI timeframe as established by ER Map, or deviating from this WOI, are assessed and compared. Data obtained showed that 34.18% (771/2256) of patients had a displaced WOI. Analysis of ART outcomes showed significantly higher pregnancy rates in transfers scheduled within the WOI predicted compared to transfers that deviated more than 12h from this WOI (44.35% vs 23.08%, p < 0.001). The deviation from the WOI had also an impact on the progression of pregnancy, with a significant increase in pregnancy loss (~ twofold) observed in transfers that deviated more than 12h from the WOI predicted. These results indicate that the precise determination of the WOI and personalised embryo transfer can significantly improve clinical outcomes.
Assuntos
Implantação do Embrião/fisiologia , Endométrio/fisiologia , Aborto Espontâneo/fisiopatologia , Adulto , Transferência Embrionária/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Infertilidade Feminina/fisiopatologia , Análise em Microsséries/métodos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Transferência de Embrião Único/métodos , Transcriptoma/fisiologiaRESUMO
PURPOSE: The optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60Gy delivered with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: All consecutive patients that received a definitive CRT>50Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis. RESULTS: A total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60Gy (54-66) and 48Gy (44.8-56) delivered in 30 (27-35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4Gy (IC 95%: 4.8-19.8), the median volumes receiving up to 20Gy (V20) and 30Gy (V30) were 13.5% (3.0-46.0) and 4.6% (0.7-19.8) respectively. The mean dose delivered to the heart was 13.9Gy (IC 95%:0.3-31.3) with a median V40 of 3.3% (0.0-25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9-4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%). CONCLUSION: We demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.
Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Tolerância a Radiação , Radioterapia de Intensidade Modulada/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Estenose Esofágica/etiologia , Feminino , Fluoruracila/administração & dosagem , Coração/efeitos da radiação , Humanos , Leucovorina/administração & dosagem , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Órgãos em Risco/efeitos da radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: In old and frail patients, oncologic anterior skull-base surgery through an endonasal endoscopic approach avoids the morbidity incurred by transfacial and transcranial approaches, sometimes considered unreasonable, although surgery remains the gold standard treatment for sinonasal cancer. OBJECTIVES: To assess the functional and oncologic results of this surgery in over-70 year-olds. MATERIAL AND METHODS: A single-center retrospective study included all patients aged over 70 years at surgery, who underwent endonasal endoscopic oncologic resection and reconstruction of the anterior skull base, between October 2008 and October 2018. RESULTS: Fifteen procedures in 13 patients met the inclusion criteria. Mean hospital stay was 7 days. All resections were considered R0, apart from one case with positive dura-mater margins (6.7%). All patients had complete radio-surgical treatment, in accordance with the REFCOR recommendations. Two cases of meningitis were reported (13.3%). At a median follow-up of 27 months, 4 patients presented local recurrence, 1 of whom also had lung metastases. Two patients died of disease-related or treatment-related causes. CONCLUSION: This technique is a feasible treatment in patients aged over 70 years, providing good functional results, and acceptable oncologic outcome.
Assuntos
Melanoma , Cavidade Nasal , Neoplasias Nasais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Base do Crânio/cirurgia , Cirurgia Endoscópica Transanal/métodos , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estesioneuroblastoma Olfatório/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação , Masculino , Melanoma/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Cuidados Pós-Operatórios/métodos , Estudos RetrospectivosRESUMO
Management of resectable esophageal carcinoma is based on a multimodal treatment associating neo-adjuvant chemoradiation before surgery. This therapeutic sequence allows a disease-free survival rate at 2 years around 45% but remains associated with a high post-operative morbidity. In case of definitive chemoradiotherapy, the dose delivered to the macroscopic disease is a controversial topic since decades and the prognosis of patients treated in this setting at the dose of 50Gy remains poor. This article proposes a review of the main published data and the ongoing studies related to the management of these patients.
Assuntos
Carcinoma/terapia , Quimiorradioterapia Adjuvante/métodos , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante , Humanos , Cuidados Pré-Operatórios/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodosRESUMO
Patients with hepatocellular carcinoma who are on liver transplant waiting list usually require local treatment to limit any risk of tumour growth. Historically percutaneous radiofrequency ablation or transarterial chemoembolization represented the major therapeutic alternatives. Depending on the size, or the topography of the lesion these two techniques may not be feasible. Radiation therapy under stereotactic conditions has recently emerged in the management of localized hepatocellular carcinoma as an alternative to the focused therapies performed to date. We herein report the case of a 43-year-old patient harbouring a complete histological response on explant after liver stereotactic irradiation and discuss its role in the management of hepatocellular carcinoma before liver transplantation.
Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Transplante de Fígado , Radiocirurgia , Adulto , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Contraindicações de Procedimentos , Fracionamento da Dose de Radiação , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias Hepáticas/cirurgia , Radiocirurgia/métodos , Indução de Remissão , Filtros de Veia Cava , Veia Cava Inferior , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico , Trombose Venosa/terapiaRESUMO
PURPOSE: To assess the outcome of locally advanced medullary thyroid carcinoma treated with surgery and adjuvant external beam radiotherapy. PATIENTS AND METHODS: Twenty-nine consecutive patients with non-metastatic medullary thyroid carcinoma treated in our institution between January 1995 and December 2012 were retrospectively evaluated. All underwent curative-intended optimal surgery, followed by external beam radiotherapy because of high risk of locoregional relapse. Twelve patients were stage III, 16 IVa and 1 IVb. Positive surgical margins were present in 11 cases (10 R1 and 1 R2). Median and average preradiotherapy serum calcitonin were 141pg/mL and 699pg/mL, respectively. Fourteen patients received 3D-conformal radiotherapy and 15 received intensity-modulated radiotherapy. Median prescribed dose was 63Gy to the high-risk volumes and 54Gy to the low-risk volumes. Treatment was delivered in 30 fractions. The median gap between surgery and radiotherapy was 1.9months. Median follow-up was 76.4months. RESULTS: Kaplan-Meier estimates of 5-year locoregional relapse-free survival and overall survival were 79 and 96 %, respectively. Among the five locoregional relapses, two were related to a macroscopic metastatic cervical lymph node that was unfortunately not removed during the lymphadenectomy. Eight of ten patients with microscopic positive margins (R1) were controlled regarding the thyroidectomy bed. Eight patients had normal serum calcitonin after external beam radiotherapy, of whom only one developed a locoregional relapse during follow-up. Regarding the 21 patients with persistent positive serum calcitonin after treatment, only ten developed a macroscopic locoregional or distant relapse. One grade III and no grade IV acute morbidity were reported. Fifteen patients reported grade II chronic morbidity and no grade III/IV. CONCLUSION: Maximal surgery followed by adjuvant external beam radiotherapy as a treatment for locally advanced medullary thyroid carcinoma provides a high rate of long-term locoregional control and overall survival with limited toxicity. Postoperative external beam radiotherapy should be considered when patients present features indicating a high risk of locoregional relapse.
Assuntos
Carcinoma Neuroendócrino/terapia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias da Glândula Tireoide/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcitonina/sangue , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Radioterapia Adjuvante , Radioterapia Conformacional , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , TireoidectomiaRESUMO
PURPOSE: Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035). PATIENTS AND METHOD: This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1-T4, M0, N0-N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. RESULTS: From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P=0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P=0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P=1.000 and P=0.5731, respectively). There was no significant difference in local relapse-free survival (P=0.0920) or overall survival (P=0.4575) between patients treated with or without cetuximab. CONCLUSION: Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.
Assuntos
Antineoplásicos/uso terapêutico , Cetuximab/uso terapêutico , Toxidermias/etiologia , Neoplasias de Cabeça e Pescoço/terapia , Mucosite/etiologia , Radioterapia de Intensidade Modulada , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pontuação de Propensão , Estudos ProspectivosRESUMO
PURPOSE: Optimal timing of neck dissection remains debated in the conservative management of patients with locoregionally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The files of 63 patients with radiographic evidence of bulky or necrotic nodal metastases treated by up-front neck dissection and definitive radiotherapy between 2000 and 2012 at two institutions were retrospectively reviewed. RESULTS: The primary site was oropharyngeal, hypopharyngeal or laryngeal in 63%, 21% and 13% cases, respectively. Overall, 83% of the tumours were staged pN2b or more. Extracapsular spread was found in 48 cases (77%). After a 48-month median follow-up, the 3-year locoregional control and overall survival were 88% and 68%, respectively. Only one isolated failure occurred in the dissected neck. CONCLUSION: This combination therapy provides a good locoregional tumour control. It should be considered as an option in laryngeal, hypopharyngeal or oropharyngeal squamous cell carcinomas with bulky or necrotic nodal metastases at presentation.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Esvaziamento Cervical , Terapia Neoadjuvante , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
Current pharmacological treatments of depression and related disorders suffer from major problems, such as a low rate of response, slow onset of therapeutic effects, loss of efficacy over time and serious side effects. Therefore, there is an urgent need to explore new therapeutic approaches that address these issues. Interestingly, the atypical antidepressant tianeptine already meets in part these clinical goals. However, in spite of three decades of basic and clinical investigations, the molecular target of tianeptine, as well as its mechanism of action, remains elusive. Herein, we report the characterization of tianeptine as a µ-opioid receptor (MOR) agonist. Using radioligand binding and cell-based functional assays, including bioluminescence resonance energy transfer-based assays for G-protein activation and cAMP accumulation, we identified tianeptine as an efficacious MOR agonist (K(i Human) of 383±183 nM and EC(50 Human) of 194±70 nM and EC(50 Mouse) of 641±120 nM for G-protein activation). Tianeptine was also a full δ-opioid receptor (DOR) agonist, although with much lower potency (EC(50 Human) of 37.4±11.2 µM and EC(50 Mouse) of 14.5±6.6 µM for G-protein activation). In contrast, tianeptine was inactive at the κ-opioid receptor (KOR, both human and rat). On the basis of these pharmacological data, we propose that activation of MOR (or dual activation of MOR and DOR) could be the initial molecular event responsible for triggering many of the known acute and chronic effects of this agent, including its antidepressant and anxiolytic actions.
Assuntos
Antidepressivos/farmacologia , Receptores Opioides delta/agonistas , Receptores Opioides mu/agonistas , Tiazepinas/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Células HEK293 , Humanos , RatosRESUMO
PURPOSE/OBJECTIVES: To analyze the clinical features, treatment modalities and outcome of patients treated for a localized esthesioneuroblastoma (ENB). MATERIALS AND METHODS: Forty-three consecutive patients with biopsy proven ENB treated at two referral cancer centers between 1998 and 2010 were retrospectively reviewed. RESULTS: Overall, 5 patients had stage A disease, 13 stage B, 16 stage C and 9 stage D according to the modified Kadish classification. Neo-adjuvant chemotherapy was performed in 23 patients leading to a 74 % response rate. Thirty-one patients were treated by surgery. Thirty-nine patients (90.6%) underwent radiation therapy. Twelve patients received bilateral cervical lymph node irradiation (LNI). After a median follow-up of 77 months, the 5-year overall and progression free survival were 65% and 57%. Twelve patients (28%) had a locoregional relapse leading to 10 ENB-related deaths. The major prognostic factor was the modified Kadish stage with a 3-year survival for stage A-B, C and D of 100%, 48% and 22% respectively (p < 0.0001). Two (9%) isolated cervical lymph node relapses occurred among staged B and C patients treated without elective LNI and none after elective or adjuvant LNI. CONCLUSION: The high risk of locoregional failure in ENB justifies the use of multimodal therapy. Induction chemotherapy leads to a high response rate. Elective LNI might prevent regional failure in locally advanced disease.
Assuntos
Estesioneuroblastoma Olfatório/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estesioneuroblastoma Olfatório/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To study quality of life in patients treated for advanced hypopharyngeal or laryngeal cancer, with laryngeal conservation or laryngectomy. PATIENTS AND METHODS: A retrospective 2-center study included 100 patients in remission from squamous cell carcinoma, treated between 1998 and 2009. Seventy patients (24 hypopharynx, 46 larynx) were treated by total (pharyngo-) laryngectomy followed by external radiation therapy, and 30 (13 hypopharynx, 17 larynx) underwent an organ-conservation protocol with concurrent radiochemotherapy or with induction chemotherapy using platin-5FU or taxan-platin-5FU followed by radiation therapy. All patients responded to the quality of life questionnaires (EORTC QLQ-C30 and QLQ-H&N35). RESULTS: Advanced tumor stages IVa and IVb were significantly more frequent in the surgery groups (hypopharynx: 71.6% vs. 45.9%, p=0.01; larynx: 72.4% vs. 37.5%, p<0.01). In pharyngeal cancer, the only significant difference between surgical treatment and laryngeal conservation was for "sensory disorder" (taste and odor), with better results in case of laryngeal conservation (p<0.0001). For the other items, there was a trend for quality of life to appear better in patients with laryngeal conservation (p=NS). In laryngeal cancer, the only significant difference was for "dry mouth", which was significantly less invalidating with surgical treatment (p<0.001). The impairment of the other quality of life items did not differ between surgical and conservative treatment. CONCLUSIONS: Quality of life is impaired in all patients treated for pharyngeal or laryngeal cancer. The type of treatment, surgical or conservative, affects differently various aspects of quality of life.
Assuntos
Neoplasias Hipofaríngeas/psicologia , Neoplasias Laríngeas/psicologia , Qualidade de Vida , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/psicologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Feminino , Nível de Saúde , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/terapia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/terapia , Laringectomia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Faringectomia , Estudos Retrospectivos , Transtornos de Sensação/etiologia , Transtornos de Sensação/psicologia , Inquéritos e Questionários , Xerostomia/etiologia , Xerostomia/psicologiaRESUMO
BACKGROUND: Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil. METHODS: Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts. RESULTS: A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82%; arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively. CONCLUSION: Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Neoplasias Esofágicas/mortalidade , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêuticoRESUMO
PURPOSE: Abdominoperineal resection has a high rate of postoperative morbidity of the perineal wound. This study aimed to determine the effects of perineal colostomy on perineal morbidity after abdominoperineal resection. METHODS: All patients who underwent an abdominoperineal resection for rectal adenocarcinoma between 1993 and 2007 were studied. Two groups were identified and compared who had undergone either an iliac colostomy or a perineal colostomy. RESULTS: The analysis included 110 patients (iliac colostomy group, n = 41; perineal colostomy group, n = 69). There were fewer instances of pelviperineal morbidity (P = .008) and fewer instances of wound dehiscence (P = .02) in the perineal colostomy group, which resulted in a shorter time to healing (35.3 vs 45.1 d, respectively; P = .04). There was no specific postoperative morbidity in any patient and no difference between the 2 groups regarding long-term perineal morbidity. The benefits from perineal colostomy were statistically significant in patients who received radiation therapy in terms of pelviperineal morbidity (P = .01) and healing time (50.8 vs 35.9 days, respectively; P = .02), whereas no difference was found in patients who had not received radiation therapy. CONCLUSION: Perineal colostomy is a safe and functionally acceptable procedure for perineal reconstruction after abdominoperineal resection for rectal adenocarcinoma. In the present study, there was no additional morbidity related to perineal colostomy, and this procedure was associated with a decrease in perineal morbidity and healing time compared with primary perineal closure, in particular, after radiotherapy treatment.
Assuntos
Adenocarcinoma/cirurgia , Colostomia/métodos , Períneo/cirurgia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Idoso , Distribuição de Qui-Quadrado , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Períneo/patologia , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
G-protein-coupled receptors (GPCRs) are key players in the precise tuning of intercellullar communication. In the brain, both major neurotransmitters, glutamate and GABA, act on specific GPCRs [the metabotropic glutamate (mGlu) and GABA(B) receptors] to modulate synaptic transmission. These receptors are encoded by the largest gene family, and have been found to associate into both homo- and hetero-oligomers, which increases the complexity of this cell communication system. Here we show that dimerization is required for mGlu and GABA(B) receptors to function, since the activation process requires a relative movement between the subunits to occur. We will also show that, in contrast to the mGlu receptors, which form strict dimers, the GABA(B) receptors assemble into larger complexes, both in transfected cells and in the brain, resulting in a decreased G-protein coupling efficacy. We propose that GABA(B) receptor oligomerization offers a way to increase the possibility of modulating receptor signalling and activity, allowing the same receptor protein to have specific properties in neurons at different locations.
Assuntos
Receptores de GABA-B/química , Receptores de GABA-B/fisiologia , Receptores de Glutamato Metabotrópico/química , Receptores de Glutamato Metabotrópico/fisiologia , Animais , Dimerização , Humanos , Receptores de GABA-B/classificação , Receptores de GABA-B/metabolismo , Receptores de Glutamato Metabotrópico/classificação , Receptores de Glutamato Metabotrópico/metabolismoRESUMO
OBJECTIVES: To evaluate the neck control after prior surgical management of patients with squamous cell carcinoma of the oral cavity and to quantify the ratio of patients among whom neck dissection did not have a real therapeutic value. To discuss the usefulness of the sentinel node biopsy in this group of patients. METHOD: Retrospective analysis of patients with epidermoid carcinoma of the oral cavity who had systematically a neck dissection. RESULTS: Thirty-nine files of patients have been processed. We found 45% patients classified pN0 (among whom about one half where classified pT4). With a mean follow-up of 19 months, we did not find any cervical lymph node relapse. Five patients died (13.5%) without any cervical disease. CONCLUSION: The systematic cervical lymph node dissection remains the most effective means to obtain the neck control of squamous cell cancers of the oral cavity. It however was applied without therapeutic value for 45% of the patients of this series. The validation of the sentinel node concept as a method of cervical staging should make it possible to avoid this surgical procedure in more than one third of the cases.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Bucais/cirurgia , Boca/cirurgia , Esvaziamento Cervical/métodos , Periodicidade , Carcinoma de Células Escamosas/patologia , Humanos , Pessoa de Meia-Idade , Boca/patologia , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVE: Vertical transmission (VT) is the main route of human immunodeficiency virus (HIV) infection in children. Since the publication of PACTG 076 study in 1994, several preventive methods against the vertical transmission of the HIV have been developed. In this study, we compare the clinical and epidemiological profile of HIV-infected pregnant women and the VT rate in the years 1994 and 2004. PATIENTS AND METHOD: We looked at maternal, obstetric and pediatric variables of HIV-infected women and their children, born in 1994 and 2004, who were followed in Hospital La Paz. RESULTS: We included 40 mother-infant couples in 1994 and 35 couples in 2004. The HIV vertical transmission rate was 35% in 1994 and 0% in 2004. We did not find changes in Hepatitis C virus (HCV) vertical transmission. In 1994, HIV-infected mothers had a more advanced HIV-disease and the major route of HIV-transmission was the intravenous drug use. Vaginal delivery was more frequent and rupture of membranes was longer than in 2004. The main route of maternal HIV infection in 2004 was sexual contact. In this same year, the use of combination antiretroviral therapy, even during pregnancy, was generalized, the elective cesarean section was the most frequent form of delivery, and every newborn received zidovudine. CONCLUSIONS: In the last decade, there have been important epidemiological changes in HIV-infected mothers in our society. The administration of antiretroviral therapy during pregnancy and to the newborn, as well as other obstetric strategies, can prevent HIV vertical transmission. Nevertheless, we did not find any change in the risk of HCV vertical transmission.
Assuntos
Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno/efeitos adversos , Cesárea/estatística & dados numéricos , Estudos Transversais , Parto Obstétrico/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Emigração e Imigração/estatística & dados numéricos , Feminino , Infecções por HIV/congênito , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Hepatite C/epidemiologia , Hepatite C/transmissão , Hospitais Universitários/estatística & dados numéricos , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Retrospectivos , Risco , Comportamento Sexual , Espanha/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Zidovudina/uso terapêuticoRESUMO
BACKGROUND: The value of ultra-low coloanal anastomosis (CAA) for rectal cancer is dependent on the oncological and functional results. The aim of this comparative study was to evaluate the long-term oncological outcome of CAA with or without intersphincteric resection (ISR) for low-lying rectal tumours. METHODS: The study population comprised consecutive patients with low rectal cancer who underwent CAA in a single institution between 1977 and 2004. Patients were divided into two groups according to whether or not a partial ISR had been performed. Cox multivariate models were used for survival analysis. RESULTS: Some 278 patients underwent CAA with curative intent; 173 had ISR and 105 had CAA without ISR. Mean follow-up was 66.8 months. The 5-year actuarial rate for local recurrence, regardless of tumour stage, was 10.6 per cent in the ISR group versus 6.7 per cent for CAA alone (P = 0.405), and the 5-year actuarial overall survival rate was 86.1 and 80.0 per cent respectively (P = 0.318). Cox multivariable analysis revealed that resection of the anal canal was not a prognostic factor for local or metastatic recurrence. CONCLUSION: Sphincter-preserving surgery appears to be oncologically adequate for very low-lying rectal tumours.
Assuntos
Adenocarcinoma/cirurgia , Bolsas Cólicas , Proctocolectomia Restauradora/métodos , Neoplasias Retais/cirurgia , Adenocarcinoma/mortalidade , Idoso , Anastomose Cirúrgica/métodos , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Recidiva Local de Neoplasia , Neoplasias Retais/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Wound anthracnose, caused by Colletotrichum musae, and early ripening are the main problems affecting the quality of export bananas (Musa AAA Cavendish) from the Caribbean. These problems generally concern bananas grown in lowland plantations during the rainy season. Three experiments were carried out to study the influence of the physiological age of bananas, calculated on the basis of mean daily temperature sums, on their susceptibility to anthracnose. Stressful growing conditions, especially soil flooding, slowed fruit growth but had no direct effect on fruit susceptibility to C. musae or on the green life. However, fruit that had accumulated lower temperature sums were less susceptible to wound anthracnose. By varying the source-sink ratio, we show that bananas of the same grade but different physiological ages had markedly different susceptibility to C. musae. Bananas with the same temperature sum accumulation but grown in different soil-climate conditions had different levels of susceptibility. Fruit grown in cooler, highland areas were less susceptible to C. musae than fruit of the same physiological age from lowland plantations. Our results suggest that temperature sum accumulation rate is a critical factor affecting the susceptibility of bananas to the pathogen.
RESUMO
This article reviews the concept of selectivity in peritumoral microscopic disease to be included in the Clinical Target Volume (CTV) for elective treatment for oral cavity and oropharyngeal squamous cell carcinoma, using the local tumoral spread. The objective of the present article is to present a procedure for the delineation of the target volumes, required for an appropriate application of 3-DCRT and IMRT for head and neck cancers. These propositions are for the delineation of microscopic peritumoral target volumes when external beam irradiation is required. CTVs are illustrated on CT sections.