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INTRODUCTION: Stage IV rectal cancer with resectable disease presents challenging issues, as the radical treatment of the whole disease is difficult. Surgery and chemotherapy (CT) play an unquestionable role, but the contribution of pelvic radiotherapy (RT) is not very clear. METHODS: In 2009, we established a prospective treatment protocol that included CT, short-course preoperative radiotherapy (SCRT) with surgery of the primary tumour and all metastatic locations. RESULTS: Forty patients were included. Eight (20%) patients did not receive CT due to significant comorbidities. Radical surgery treatment was possible in 22 (55%) patients. The mean follow-up was 42.81 months (3.63-105.97). Overall survival at 24 and 36 months was 71.4% and 58.2%, respectively. There was good local control of the disease, as 97.2% of pelvic surgeries were R0 and there were no local recurrences. CONCLUSION: In stage IV with resectable metastatic disease, the proposed therapeutic regimen seems very appropriate in well selected patients able to tolerate the treatment. We bet on the role of pelvic RT, due to the good local control of the disease in our series.
Assuntos
Adenocarcinoma/radioterapia , Neoplasias Pélvicas/radioterapia , Cuidados Pré-Operatórios , Radioterapia/métodos , Neoplasias Retais/radioterapia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Pélvicas/secundário , Neoplasias Pélvicas/cirurgia , Prognóstico , Estudos Prospectivos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Taxa de SobrevidaAssuntos
Anestesiologia/organização & administração , COVID-19/epidemiologia , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Pandemias , SARS-CoV-2 , Anestesiologistas/organização & administração , Anestesiologia/estatística & dados numéricos , Conversão de Leitos/estatística & dados numéricos , COVID-19/terapia , Análise Custo-Benefício , Cuidados Críticos/estatística & dados numéricos , Número de Leitos em Hospital/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva , Admissão e Escalonamento de Pessoal , Espanha/epidemiologiaRESUMO
INTRODUCTION: To date, we do not know the best therapeutic scheme in locally advanced rectal cancer when patients are older or have comorbidities. METHODS: In 2009, we established a prospective treatment protocol that included short-course preoperative radiotherapy (RT) with standard surgery +/- chemotherapy in frail patients, mostly older than 80 years or with comorbidities. RESULTS: We included 87 patients; the mean follow-up was 43.5 months (0.66-106.3). Disease-specific survival and disease-free survival at 36 months were 86.3% and 82.8%; at 60 months, they were 78.2% and 78%, respectively, with a local recurrence rate of 2.5%. The rate of late radiotoxicity was 9% in the form of sacral insufficiency fracture and small bowel obstruction with one death. The interval before surgery varied according to the involvement of the mesorectal fascia, but it was less than 2 weeks in 45% of cases. The rate of R0 was 95%. Surgical complications included abdominal wound dehiscence (3.5%), anastomotic leak (2.4%), and reoperations (11.5%). Downstaging was observed in 51% of the cases, regardless of the interval before surgery. DISCUSSION: Therapeutic outcomes in our group of elderly patients and/or patients with comorbidities with neoadjuvant short-course RT are such as those of the general population treated with neoadjuvant RT-chemotherapy, all with acceptable toxicity. Therefore, this treatment scheme, with short-course preoperative RT, would be the most appropriate in this group of patients.
Assuntos
Adenocarcinoma/terapia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Radioterapia Conformacional , Neoplasias Retais/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Comorbidade , Intervalo Livre de Doença , Idoso Fragilizado , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Protectomia , Estudos Prospectivos , Planejamento da Radioterapia Assistida por Computador , Neoplasias Retais/diagnóstico , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Reto/patologia , Reto/efeitos da radiação , Reto/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: In the oncological patient, an COVID-19-Infection, whether symptomatic or asymptomatic, a surgical procedure may carry a higher postoperative morbidity and mortality. The aim of this study was to describe the impact on clinical practice of sequential preoperative screening for COVID-19-infection in deciding whether to proceed or postpone surgery. METHODS: Prospective, cohort study, based on consecutive patients' candidates for an oncological surgical intervention. Sequential preoperative screening for COVID-19-infection: two-time medical history (telematic and face-to-face), PCR and chest CT, 48 h before of surgical intervention. COVID-19-infection was considered positive if the patient had a suggestive medical history and/or PCR-positive and/or CT of pneumonia. RESULTS: Between April 15th and May 4th, 2020, 179 patients were studied, 97 were male (54%), mean (sd) age 66.7 (13,6). Sequential preoperative screening was performed within 48 h before to surgical intervention. The prevalence of preoperative COVID-19-infection was 4.5%, 95%CI:2.3-8.6% (8 patients). Of the operated patients (171), all had a negative medical history, PCR and chest CT. The complications was 14.8% (I-II) and 2.5% (III-IV). There was no mortality. The hospital stay was 3.1 (sd 2.7) days.In the 8 patients with COVID-19-infection, the medical history was suggestive in all of them, 7 presented PCR-positive and 5 had a chest CT suggestive of pneumonia. The surgical intervention was postponed between 15 and 21 days. CONCLUSION: Preoperative screening for COVID-19-infection using medical history and PCR helped the surgeon to decide whether to go ahead or postpone surgery in oncological patients. The chest CT may be useful in unclear cases.
Assuntos
Queixo/inervação , Hipestesia/etiologia , Nervo Mandibular/fisiopatologia , Mieloma Múltiplo/complicações , Síndromes Paraneoplásicas/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vértebras Cervicais/patologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Disartria/etiologia , Disartria/fisiopatologia , Disgeusia/etiologia , Disgeusia/fisiopatologia , Evolução Fatal , Gengiva/inervação , Nervo Glossofaríngeo/fisiopatologia , Humanos , Hipestesia/fisiopatologia , Nervo Hipoglosso/fisiopatologia , Lábio/inervação , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/fisiopatologia , Base do Crânio/patologia , Língua/inervação , Língua/fisiopatologiaRESUMO
OBJECTIVE: To evaluate patients 24 months after deep sclerectomy (DE) with supraciliary implant, and identify any predictive success factors by examination with ultrasound biomicroscopy (UBM) MATERIAL AND METHODS: This study included 26 eyes of 23 patients evaluated by UBM 24 months after a deep sclerectomy with a supraciliary hema implant. RESULTS: There was a significant reduction in intraocular pressure (IOP), changing from a preoperative mean of 25.6 ± 6.4 mmHg to a postoperative mean of 16.2 ± 3.4 mmHg (P<.001). The number of preoperative glaucoma medications also decreased from 2.5 ± 0.6 drugs per patient to 0.5 ± 0.5 (P<.001). No change was observed in the best-corrected visual acuity. The anatomical characteristics of the surgical area, and its relationship with IOP were examined using UBM. There was no correlation between the level of IOP at the time of UBM and the horizontal (r=-.05: P=.71) and vertical diameter (r=-.1; P=.63), the height (r=.28; P=.25) and the volume of intrascleral space (r=-.08; P=.79), the thickness (r=-.07; P=.73) and the length (r=.39; P=.13) of trabeculo-Descemet's membrane (TDM), the presence of filtering bleb (P=.30) and the hypoechoic area in the supraciliary space (P=.24). CONCLUSIONS: The insertion of a hema implant in the supraciliary space is an effective and safe surgery for patients with open angle glaucoma (OAG). No predictive success factors for supraciliary implant were found using the UBM study.
Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma/diagnóstico por imagem , Microscopia Acústica , Esclera/cirurgia , Idoso , Humor Aquoso , Terapia Combinada , Feminino , Seguimentos , Glaucoma/tratamento farmacológico , Glaucoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/uso terapêutico , ReologiaRESUMO
Chronic lymphocytic leukemia (CLL) cells located in proliferation centers are constantly stimulated by accessory cells, which provide them with survival and proliferative signals and mediate chemotherapy resistance. Herein, we designed an experimental strategy with the aim of mimicking the microenvironment found in the proliferative centers to specifically target actively proliferating CLL cells. For this, we co-cultured CLL cells and bone marrow stromal cells with concomitant CD40 and Toll-like receptor 9 stimulation. This co-culture system induced proliferation, cell-cycle entry and marked resistance to treatment with fludarabine and bendamustine. Proliferating CLL cells clustered together showed a typical morphology of activated B cells and expressed survivin protein, a member of the inhibitor of apoptosis family that is mainly expressed by CLL cells in the proliferation centers. With the aim of specifically targeting actively proliferating and chemoresistant CLL cells, we investigated the effects of treatment with YM155, a small-molecule survivin inhibitor. YM155 treatment suppressed the co-culture-induced survivin expression and that was sufficient to inhibit proliferation and effectively induce apoptosis particularly in the proliferative subset of CLL cells. Interestingly, sensitivity to YM155 was independent from common prognostic markers, including 17p13.1 deletion. Altogether, these findings provide a rationale for clinical development of YM155 in CLL.
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Antineoplásicos/química , Resistencia a Medicamentos Antineoplásicos , Proteínas Inibidoras de Apoptose/metabolismo , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Cloridrato de Bendamustina , Células da Medula Óssea/citologia , Antígenos CD40/metabolismo , Ciclo Celular , Proliferação de Células , Técnicas de Cocultura , Feminino , Deleção de Genes , Humanos , Imidazóis/química , Leucócitos Mononucleares/citologia , Masculino , Pessoa de Meia-Idade , Naftoquinonas/química , Compostos de Mostarda Nitrogenada/química , Células Estromais/citologia , Survivina , Receptor Toll-Like 9/metabolismo , Vidarabina/análogos & derivados , Vidarabina/químicaAssuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Idoso , Comorbidade , Esofagoscopia , Humanos , Ligadura , MasculinoRESUMO
Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female genital tract, with myometrial invasion representing an increase in the rate of recurrences and a decrease in survival. We have previously described ETV5 transcription factor associated with myometrial infiltration in human ECs. In this work, we further investigated ETV5 orchestrating downstream effects to confer the tumor the invasive capabilities needed to disseminate in the early stages of EC dissemination. Molecular profiling evidenced ETV5 having a direct role on epithelial-to-mesenchymal transition (EMT). In particular, ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell-cell and cell-substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines. Furthermore, we identified the lipoma-preferred partner protein as a regulatory partner of ETV5, acting as a sensor for extracellular signals promoting tumor invasion. All together, we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Neoplasias do Endométrio/metabolismo , Transição Epitelial-Mesenquimal , Proteínas com Domínio LIM/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Caderinas/metabolismo , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Neoplasias do Endométrio/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Regiões Promotoras Genéticas , Transporte Proteico , Fatores de Transcrição/genética , Transcrição Gênica , Homeobox 1 de Ligação a E-box em Dedo de ZincoRESUMO
p16(Ink4a) is a protein involved in regulation of the cell cycle. Currently, p16(Ink4a) is considered a tumor suppressor protein because of its physiological role and downregulated expression in a large number of tumors. Intriguingly, overexpression of p16(Ink4a) has also been described in several tumors. This review attempts to elucidate when and why p16(Ink4a) overexpression occurs, and to suggest possible implications of p16(Ink4a) in the diagnosis, prognosis and treatment of cancer.
Assuntos
Envelhecimento/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Genes Supressores de Tumor , Neoplasias/genética , HumanosAssuntos
Doadores Vivos , Doadores de Tecidos/ética , Obtenção de Tecidos e Órgãos/ética , Cadáver , Congressos como Assunto , Família , Humanos , Itália , Princípios Morais , Educação de Pacientes como Assunto , Religião e Medicina , Justiça Social , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/normasRESUMO
Uterine lipomas are very uncommon with symptoms that are similar to leiomyomas. Their diagnosis is always histological although some radiological methods may suggest their existence prior to surgery. They are sometimes associated with endometrial pathology, but there are no previous reported cases related to ovarian thecoma. Their prognosis is excellent. Clinical, radiological, morphologic, and immunohistochemical findings are shown which correspond to uterine lipoma associated with endometrial polyps and ovarian thecoma.
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PURPOSE: We evaluate the safety and efficacy of a spinal anesthesia with lidocaine versus a local anesthesia of pudendal block with ropivacaine combined with intravenous sedation in the hemorrhoidectomy procedure and also we compared the short- and long-term efficacy of conventional diathermy versus Ligasure diathermy hemorrhoidectomy. METHODS: Seventy-four patients of grade III or IV hemorrhoids were randomized to conventional diathermy hemorrhoidectomy under spinal (n = 19) or local anesthesia (n = 18) and Ligasure diathermy hemorrhoidectomy under spinal (n = 17) or local anesthesia (n = 20). Time of follow-up was 12 months. RESULTS: Patients operated under local anesthesia had less pain (p < 0.01), less analgesic requirements (p < 0.001), shorter hospital stay (p < 0.01), and less postoperative complications (p < 0.05). A shorter operating time (p < 0.001) and less complications at 4 months postoperatively (p < 0.05) was observed in the Ligasure group, but differences at 12 months were not found. CONCLUSIONS: Hemorrhoidectomy under local anesthesia with pudendal block with ropivacaine and sedation reduced postoperative pain, analgesic requirements, and postoperative complications, and can be performed as day-case procedure. Ligasure diathermy hemorrhoidectomy reduced operating time and was equally effective than conventional diathermy in long-term symptom control.
Assuntos
Diatermia/métodos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Hemorroidas/cirurgia , Adulto , Idoso , Amidas/administração & dosagem , Analgésicos , Raquianestesia/métodos , Anestésicos Locais/administração & dosagem , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Seguimentos , Hemorroidas/complicações , Humanos , Tempo de Internação , Lidocaína/administração & dosagem , Ligadura/efeitos adversos , Ligadura/métodos , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/métodos , Dor Pós-Operatória , Complicações Pós-Operatórias , Ropivacaina , Resultado do Tratamento , Adulto JovemRESUMO
Endometrial carcinoma is the most common gynaecological malignancy in the western world and the most frequent among infiltrating tumours of the female genital tract. Despite the characterisation of molecular events associated with the development of endometrial carcinoma, those associated with the early steps of infiltration and invasion in endometrial cancer are less known. Deep myometrial invasion correlates with more undifferentiated tumours, lymph-vascular invasion, node affectation and decreased global survival. In this review we present an overview of the molecular pathology of myometrial infiltration that defines the initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as a main player of epithelial to mesenchymal transition, as well as modifications on other molecules involved in cell-cell contacts, render cells with a migratory phenotype. In addition, altered signalling pathways and transcription factors associate with myometrial invasion, histologic grade and metastasis.
Assuntos
Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/patologia , Moléculas de Adesão Celular/fisiologia , Neoplasias do Endométrio/genética , Feminino , Expressão Gênica , Humanos , Invasividade NeoplásicaAssuntos
Endometrite/microbiologia , Pós-Menopausa , Tuberculose dos Genitais Femininos/diagnóstico , Hemorragia Uterina/etiologia , Antituberculosos/uso terapêutico , Biópsia por Agulha , Endometrite/tratamento farmacológico , Endométrio/microbiologia , Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Tuberculose dos Genitais Femininos/complicações , Tuberculose dos Genitais Femininos/tratamento farmacológicoRESUMO
AIMS: Rearranged during Transfection (RET)/papillary thyroid carcinoma (PTC) and p53 are two genes involved in the pathogenesis of PTC. It has been suggested that RET/PTC expression is associated with higher rates of local extension and lymph node involvement, whereas p53 mutations are more frequent in poorly differentiated and anaplastic carcinomas. In addition, experimental studies have shown that p53 activity can modify the behaviour of PTC carrying RET/PTC. The aim of this study was to investigate the expression of both RET/PTC and p53 in order to evaluate their usefulness as prognostic factors. METHODS AND RESULTS: Resected specimens of 61 cases of PTC were studied immunohistochemically using a polyclonal antibody to RET and a monoclonal antibody to p53 protein. RET/PTC expression was associated with extrathyroid extension of PTC, at diagnosis (P < 0.05). In contrast, no relationship between p53 immunoreactivity and clinical status was found. In addition, p53 expression was more prevalent among RET/PTC+ patients, and significantly influenced the relationship observed between RET/PTC and extrathyroid extension of the disease. CONCLUSION: Our results suggest that immunohistochemistry for both PTC/RET and p53 could be useful in the clinical evaluation of patients with PTC.
Assuntos
Carcinoma/metabolismo , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/metabolismo , Proteína Supressora de Tumor p53/genética , Adulto , Biomarcadores Tumorais , Carcinoma/diagnóstico , Carcinoma/genética , Feminino , Humanos , Masculino , Prognóstico , Proteínas Proto-Oncogênicas c-ret/biossíntese , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Proteína Supressora de Tumor p53/biossínteseAssuntos
Meningioma/diagnóstico , Mesentério/patologia , Neoplasias de Bainha Neural/diagnóstico , Neoplasias Peritoneais/diagnóstico , Proliferação de Células , Colágeno Tipo IV/análise , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Meningioma/química , Meningioma/ultraestrutura , Mesentério/química , Mesentério/ultraestrutura , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Mucina-1/análise , Neoplasias de Bainha Neural/química , Neoplasias de Bainha Neural/ultraestrutura , Proteínas do Tecido Nervoso/análise , Neoplasias Peritoneais/química , Neoplasias Peritoneais/ultraestrutura , Receptores de Fatores de Crescimento/análise , Receptores de Fator de Crescimento Neural , Vimentina/análiseRESUMO
A dualistic model, which has been established on a morphological basis and that differentiates type I endometrioid from type II non-endometrioid endometrial cancer, is widely accepted. Molecular genetics have provided us with data supporting the dualistic model of endometrial tumorigenesis and with some clues to speculate about the sequence of the molecular alterations defining the tumorigenesis pathways. In type I endometrioid endometrial cancer, PTEN gene silencing, microsatellite instability associated with defects in DNA mismatch repair genes, or mutations in the K-ras gene are the known major alterations defining the progression from normal endometrium to hyperplasia and then on to carcinoma. Recently, cDNA microarray technology for identifying the differences in gene expression patterns between the histological types of endometrial cancer have permitted the identification of differentially expressed genes that could help us to understand differences in the biology and the clinical outcome between histiotypes. Genes involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, or altered genes associated with the initial steps of myometrial infiltration in endometrioid endometrial cancer, represent examples of how useful large genetic screenings can be for understanding the tumorigenesis process and the future directions in the molecular pathogenesis of endometrial cancer.