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1.
Lett Appl Microbiol ; 57(1): 3-10, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23551112

RESUMO

UNLABELLED: Two bacteriophages, isolated from faeces, were assayed as biocontrol agents of pathogenic Escherichia coli during milk fermentation. Phage DT1 was tested on the strain E. coli DH5α, one enteropathogenic E. coli (EPEC) strain and one Shiga toxigenic E. coli O157:H7 (STEC) strain. Phage DT6 was tested on two STEC strains (O157:H7 and non-O157). One additional assay was performed by using a cocktail of both phages against the O157:H7 STEC strain. Streptococcus thermophilus 10-C, the strain used as lactic starter, reached 10(9)  CFU ml(-1) after 4 h, while pH values fell to 4·5 after 8 h, regardless of the presence of E. coli strains and/or phages. In absence of phages, E. coli strains reached 4-6 log CFU ml(-1) at 5-6 h. Escherichia coli DH5α and O157:H7 STEC strains were rapidly and completely inactivated by phage DT1 and phage cocktail, respectively, while O157:H7 STEC was completely inactivated either by DT1 or by DT6, after 8 h. The EPEC strain was not detected at 1 h (<10 CFU ml(-1) ) but grew afterwards, though at lower rates than without phage. For non-O157:H7 STEC, reductions lower than 1 log CFU ml(-1) were observed for all sampling times. Phages DT1 and DT6, either individually or as a cocktail, effectively reduce O157:H7 STEC counts during milk fermentation, without compromising the starter culture performance. SIGNIFICANCE AND IMPACT OF THE STUDY: Coliphages DT1 and DT6, isolated from faeces and selected on the basis of their host range, showed to be valuable tools for the control of pathogenic Escherichia coli during milk fermentation, without compromising the starter culture performance. Both phages, either individually or as a cocktail, may function as an extra safety barrier beyond traditional pasteurization, effectively reducing O157:H7 Shiga toxin-producing Escherichia coli (STEC) counts during early growth, thus avoiding Shiga toxin production and accumulation.


Assuntos
Agentes de Controle Biológico , Colífagos , Escherichia coli O157/virologia , Fezes/virologia , Leite/microbiologia , Escherichia coli Shiga Toxigênica/virologia , Animais , Bovinos , Escherichia coli O157/crescimento & desenvolvimento , Fermentação , Escherichia coli Shiga Toxigênica/crescimento & desenvolvimento , Streptococcus thermophilus/crescimento & desenvolvimento
2.
Ann Oncol ; 23(3): 664-670, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21652581

RESUMO

BACKGROUND: Based on a phase I study showing the feasibility of combining of oxaliplatin, cisplatin, and 5-fluorouracil (5-FU) (OCF) with radiation therapy (RT) in esophageal cancer, the efficacy of this regimen in esophageal, gastroesophageal (GE), and gastric (G) cancer was assessed in this phase II multicenter study. PATIENTS AND METHODS: Patients with resectable tumors were eligible. Treatment included two cycles of oxaliplatin 85 mg/m(2), cisplatin 55 mg/m(2), and continuously infused 5-FU 3 g/m(2) in 96 h and concurrent RT (45 Gy), followed by surgery after 6-8 weeks. Primary end point was complete pathologic response (pCR). RESULTS: Forty-one patients were enrolled. Tumor location was esophagus 39% (squamous 10/adenocarcinoma 6), GE junction 32%, and stomach 29%. G3-G4 adverse events included asthenia (27%) and neutropenia (14%). One toxic death occurred. Thirty-one patients (75.6%) underwent surgery (R0 in 94%). Pathologic response was achieved in 58% of patients, with pCR in 50% and 16% of esophageal and GE/G cancer, respectively. pCR was achieved in 67% of squamous cell carcinoma. Survival: median follow-up, 50.4 months; median progression-free survival and overall survival were 23.2 and 28.4 months, respectively. CONCLUSION: Preoperative OCF plus RT showed an acceptable toxicity and promising activity especially in squamous cell esophageal cancer.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante/métodos , Neoplasias Gástricas/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Neoplasias Gástricas/patologia
3.
Clin Transl Oncol ; 23(9): 1857-1865, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33792839

RESUMO

BACKGROUND: To demonstrate whether extensive intraoperative peritoneal lavage (EIPL) could yield better results in overall survival and less recurrence, regardless of peritoneal cytology, compared to standard peritoneal lavage (SPL). METHODS: A prospective randomised multicenter study including 94 patients (47 per arm) to detect a 20% difference in 3-year overall survival in patients with locally advanced tumours without peritoneal carcinomatosis. Three samples of peritoneal fluid were obtained (at the beginning, the end of procedure and after the assigned peritoneal lavage). Clinicopathological and surgical data were analysed by group. Postoperative complications, location of recurrence and surgical approach were evaluated. Overall survival was calculated by the Kaplan-Meier method and the uni/multivariate analysis for prognostic factors was carried out using Cox regression analysis. RESULTS: A total of 86 patients were analysed (4 excluded per group). No statistical differences were observed in clinicopathological or surgical data between groups, considering both groups well-balanced for analysis. Overall survival at 3 years was 64.3% for SPL vs. 62.3% for EIPL (p 0.421). Only three patients had at least one positive peritoneal cytology (1:2). There were no differences regarding postoperative complications (SPL: 37.2% vs. EIPL: 32.5%, p 0.65) or between location of recurrence and number of recurrences. The number of recurrences did not differ between surgical approaches, but locoregional and peritoneal recurrences were fewer with the laparoscopic approach (p 0.048). CONCLUSIONS: The regular use of extensive peritoneal lavage in patients with locally advanced gastric cancer, regardless of peritoneal cytology, has not been effective as prophylaxis of peritoneal recurrence or better survival.


Assuntos
Cuidados Intraoperatórios/mortalidade , Recidiva Local de Neoplasia/mortalidade , Lavagem Peritoneal/métodos , Neoplasias Peritoneais/mortalidade , Neoplasias Gástricas/mortalidade , Idoso , Análise de Variância , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/secundário , Lavagem Peritoneal/mortalidade , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/prevenção & controle , Neoplasias Peritoneais/secundário , Estudos Prospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
4.
Eur J Surg Oncol ; 47(12): 3081-3087, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33933340

RESUMO

BACKGROUND: Although the number of nationwide clinical registries in upper gastrointestinal cancer is increasing, few of them perform regular clinical audits. The Spanish EURECCA Esophagogastric Cancer Registry (SEEGCR) was launched in 2013. The aim of this study was to assess the reliability of the data in terms of completeness and accuracy. METHODS: Patients who were registered (2014-2017) in the online SEEGCR and underwent esophagectomy or gastrectomy with curative intent were selected for auditing. Independent teams of surgeons visited each center between July 2018 and December 2019 and checked the reliability of data entered into the registry. Completeness was established by comparing the cases reported in the registry with those provided by the Medical Documentation Service of each center. Twenty percent of randomly selected cases per hospital were checked during on-site visits for testing the accuracy of data (27 items per patient file). Correlation between the quality of the data and the hospital volume was also assessed. RESULTS: Some 1839 patients from 19 centers were included in the registry. The mean completeness rate in the whole series was 97.8% (range 82.8-100%). For the accuracy, 462 (25.1%) cases were checked. Out of 12,312 items, 10,905 were available for verification, resulting in a perfect agreement of 95% (87.1-98.7%). There were 509 (4.7%) incorrect and 35 (0.3%) missing entries. No correlation between hospital volume and the rate of completeness and accuracy was observed. CONCLUSIONS: Our results indicate that the SEEGCR contains reliable data.


Assuntos
Confiabilidade dos Dados , Neoplasias Esofágicas/cirurgia , Sistema de Registros/normas , Neoplasias Gástricas/cirurgia , Esofagectomia , Feminino , Gastrectomia , Humanos , Masculino , Espanha
5.
Dan Med Bull ; 56(2): 89-91, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19486621

RESUMO

INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. TRIAL DESIGN: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Laparoscopia , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Seleção de Pacientes , Projetos de Pesquisa
6.
Artigo em Inglês | MEDLINE | ID: mdl-18609003

RESUMO

Rectal cancer was initially considered a contraindication for the laparoscopic approach to low rectal resection due to the greater difficulty of deep pelvic dissection, but several studies have demonstrated its potential clinical advantages. The currently accepted technique for this intervention includes total mesorectal excision, which entails complete dissection of the mesorectum followed by low transection of the rectum. The laparoscopic approach provides good visualization and magnification of the operative field, but transection of the rectum may be more difficult. This is illustrated by the conversion rate of around 15% in most series, mainly due to technical difficulties. Contour placement may overcome these difficulties. Two key points support the interest in the use of devices with the features of the Contour. First, the current feeling and evidence indicate that with presently available laparoscopic devices, the section of the low rectum in selected patients (males and mid-third rectal tumors) is often difficult. Secondly, although the Contour device was designed for open surgery, surgeons have the intuitive perception that it perfectly accomplishes the functions an ideal laparoscopic stapler should include. There is clearly a need for more appropriate laparoscopic instruments for low rectal transection. The Contour device could be considered a prototype because it meets the surgeon's requirements when operating on the low rectum, providing one shot, simultaneous sewing and cutting function and a symmetric rectum section. However, a number of technical modifications would enhance the utility of the instrument in this setting.


Assuntos
Laparoscopia/métodos , Neoplasias Retais/cirurgia , Grampeadores Cirúrgicos , Anastomose Cirúrgica/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Masculino , Reto/patologia , Reto/cirurgia , Fatores Sexuais , Grampeamento Cirúrgico
7.
Surg Endosc ; 21(5): 719-23, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17242987

RESUMO

BACKGROUND: As a result of the high success rate associated with the laparoscopic approach for achalasia, surgery for the disease has become the treatment of choice in recent years. With the greater number of patients undergoing surgery, surgeons may encounter other upper gastroesophageal illnesses associated with achalasia, and these may require evaluation for simultaneous surgical treatment. This study aimed to evaluate the incidence of gastroesophageal diseases associated with achalasia, and to determine the possibility for simultaneous management using the laparoscopic approach. METHODS: From January 1999 to May 2006, 81 patients were referred from the Service of Gastroenterology to the Service of General and Digestive Surgery as candidates for the surgical management of achalasia. Data for this group were recorded prospectively in laparoscopic surgery databases at the Hospital Sant Pau and the Hospital de Igualada. A total of 78 patients underwent laparoscopic Heller myotomy with gastric fundoplication. RESULTS: In 8 of 81 patients, nine additional gastroesophageal diseases (11.1%) were found: three cases of pseudoachalasia (3.7%), three cases of paraesophageal hiatal hernia (3.7%), two cases of esophageal diverticulum (2.5%), and one case of gastric volvulus (1.2%). Pseudoachalasia was diagnosed for three patients. The diagnosis was made preoperatively for one of these patients. For the other two patients, an adenocarcinoma arising from the gastroesophageal junction was diagnosed during the laparoscopy. In three cases, a paraesophageal hiatal hernia was found and treated by laparoscopic Heller myotomy, sac excision, hiatal closure, and posterior fundoplication. Esophageal diverticulectomy was performed for one patient. Another patient presented with an organoaxial gastric volvulus associated with achalasia, for which laparoscopic Heller myotomy, posterior fundoplication, and anterior gastropexy were performed. The median follow-up period was 39 months, with no recurrence. CONCLUSIONS: Despite their infrequency, several gastroesophageal diseases may be found in association with achalasia. Laparoscopic surgery may be useful for the diagnosis and/or treatment of both diseases.


Assuntos
Acalasia Esofágica/complicações , Acalasia Esofágica/cirurgia , Gastroenteropatias/etiologia , Laparoscopia , Trato Gastrointestinal Superior , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adolescente , Adulto , Idoso , Procedimentos Cirúrgicos do Sistema Digestório , Divertículo Esofágico/diagnóstico por imagem , Divertículo Esofágico/etiologia , Divertículo Esofágico/cirurgia , Acalasia Esofágica/diagnóstico por imagem , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico , Junção Esofagogástrica , Feminino , Fundoplicatura , Hérnia Hiatal/diagnóstico por imagem , Hérnia Hiatal/etiologia , Hérnia Hiatal/cirurgia , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Radiografia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Volvo Gástrico/etiologia , Volvo Gástrico/cirurgia
8.
Nat Biotechnol ; 18(7): 723-7, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10888838

RESUMO

Rapid advances are being made in the engineering of replication-competent viruses to treat cancer. Adenovirus is a mildly pathogenic human virus that propagates prolifically in epithelial cells, the origin of most human cancers. While virologists have revealed many details about its molecular interactions with the cell, applied scientists have developed powerful technologies to genetically modify or regulate every viral protein. In tandem, the limited success of nonreplicative adenoviral vectors in cancer gene therapy has brought the old concept of adenovirus oncolysis back into the spotlight. Major efforts have been directed toward achieving selective replication by the deletion of viral functions dispensable in tumor cells or by the regulation of viral genes with tumor-specific promoters. However, the predicted replication selectivity has not been realized because of incomplete knowledge of the complex virus-cell interactions and the leakiness of cellular promoters in the viral genome. Capsid modifications are being developed to achieve tumor targeting and enhance infectivity. Cellular and viral functions that confer greater oncolytic potency are also being elucidated. Ultimately, the interplay of the virus with the immune system will likely dictate the success of this approach as a cancer therapy.


Assuntos
Adenoviridae/genética , Adenoviridae/fisiologia , Terapia Genética/métodos , Neoplasias/terapia , Animais , Vetores Genéticos , Humanos , Modelos Biológicos , Neoplasias/imunologia
9.
Surg Endosc ; 20(2): 316-21, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16247573

RESUMO

BACKGROUND: Several studies have shown that laparoscopic surgery (LS) minimizes surgical trauma and the immune function is better preserved. Another major advantage of LS is the lower incidence of septic complications. However, several in vitro studies have shown that CO(2) severely impairs macrophage physiology. In theory, this would reduce the ability to respond to peritoneal contamination. However, there is some controversy in view of the evidence of a better preserved peritoneal response to sepsis. This study analyzed the early response of the peritoneum to contamination in a CO(2) ambience. METHODS: A total of 192 CD-1 mice were distributed in three groups: group 1, laparotomy (LAP, n = 64); group 2, CO(2) laparoscopy (CO(2)-LC, n = 64); and group 3, wall lift laparoscopy (WL-LC, n = 64). Mice in each group were randomized to receive 1 ml of Escherichia coli suspension (1 x 10(4) colony-forming units/ml) or saline. Peritoneal fluid was obtained at 1.5, 3, 6, and 12 h after surgery. Monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and prostaglandin E(2) (PGE(2)) were measured. RESULTS: MCP-1 levels were significantly greater and higher earlier in group 2 (CO(2)-LC) than in group 1 (LAP) (p < 0.007). Simultaneously, the increment in the traction group (WL-LC, group 3) was significantly higher (p < 0.002) than after laparotomy, with no differences in group 2 (CO(2)-LC). When a contamination was added to the laparotomy subgroup, there was a significant increase compared to the group without contamination (p < 0.5). MCP-1 modifications after contamination in the LAP group were statistically significant and appeared later than in the WL-LC (p < 0.002) and CO(2)-LC groups (p < 0.02). For IL-6, the three models presented a significant increase in the noncontaminated groups. This occurred significantly later in the LAP group. Simultaneously, the increase in IL-6 occurred earlier and was significantly higher in the WL-LC group compared to the LAP group (p < 0.003), without differences between CO(2)-LC and wall lift groups. Significant differences between contaminated and noncontaminated subgroups were only observed in the LC-CO(2) groups. When contaminated, the traction model sustained a higher and earlier rise in IL-6 levels compared to the LAP and LC-CO(2) groups (p < 0.001). For PGE(2), The three models showed a significant increase in PGE(2) levels in the noncontaminated groups. However, there were no significant differences between them. In the contaminated groups, there was no statistical difference between the groups. CONCLUSION: Despite a transient impairment of the immediate peritoneal response to a septic challenge, the degree of injury with LS is lower than that with open surgery, and abdominal infection can therefore be better controlled.


Assuntos
Abdome/cirurgia , Infecções por Escherichia coli/metabolismo , Laparoscopia/efeitos adversos , Peritônio/metabolismo , Infecção da Ferida Cirúrgica/metabolismo , Animais , Líquido Ascítico/metabolismo , Dióxido de Carbono , Quimiocina CCL2/metabolismo , Dinoprostona/metabolismo , Interleucina-6/metabolismo , Laparotomia/efeitos adversos , Camundongos , Camundongos Endogâmicos , Pneumoperitônio Artificial , Fatores de Tempo
10.
Surg Endosc ; 20(8): 1208-13, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16865623

RESUMO

BACKGROUND: Laparoscopic splenectomy (LS) offers better short-term results than open surgery for the treatment of immune thrombocytopenic purpura (ITP), but long-term follow-up is required to ensure its efficacy. The remission rate after splenectomy ranges from 49 to 86% and the factors that predict a successful response to surgical management have not been clearly defined. The goal of this study was to determine the preoperative factors that predict a successful outcome following LS. METHODS: From February 1993 to December 2003, LS was consecutively performed in a series of 119 nonselected patients diagnosed with ITP (34 men and 85 women; mean age, 41 years), and clinical results were prospectively recorded. Postoperative follow-up was based on clinical records, follow-up data provided by the referring hematologist, and a phone interview with the patient and/or relative. Univariate and multivariate analyses were performed for clinical preoperative variables to identify predictive factors of success following LS. RESULTS: Over a mean period of 33 months, 103 patients (84%) were available for follow-up with a remission rate of 89% (92 patients, 77 with complete remission with platelet count > 150,000). Eleven patients did not respond to surgery (platelet count < 50,000). Mortality during follow-up was 2.5% (two cases not related to hematological pathology and one case without response to splenectomy). Preoperative clinical variables evaluated to identify predictive factors of response to surgery were sex, age, treatment (corticoids alone or associated with Ig or chemotherapy), other immune pathology, duration of disease, and preoperative platelet count. In a subgroup of 52 patients, we also evaluated the type of autoantibodies and corticoid doses required to maintain a platelet count > 50,000. Multivariate analysis showed that none of the variables evaluated could be considered as predictive factors of response to LS due to the high standard error. CONCLUSION: Long-term clinical results show that LS is a safe and effective therapy for ITP. However, a higher number of nonresponders is needed to determine which variables predict response to LS for ITP.


Assuntos
Doenças do Sistema Imunitário/cirurgia , Laparoscopia , Púrpura Trombocitopênica/cirurgia , Esplenectomia , Adolescente , Adulto , Idoso , Feminino , Humanos , Doenças do Sistema Imunitário/sangue , Doenças do Sistema Imunitário/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos , Púrpura Trombocitopênica/sangue , Púrpura Trombocitopênica/mortalidade , Indução de Remissão , Resultado do Tratamento
11.
Oncogene ; 18(8): 1589-95, 1999 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-10102629

RESUMO

In order to test if the carboxyl terminal polypeptide of the Retinoblastoma (Rb) tumor suppressor protein, could be used to suppress the growth factor-independent growth phenotype of p210bcr-abl positive myeloid cells, we introduced a truncated form of the 3' end of the Rb cDNA encoding its last 173 amino acid residues (Rb C-box) which localize into the cytoplasm where the p210bcr-abl transforming protein is found, into myeloid cells (32D) which depends on the p210bcr-abl protein for IL3 growth factor-independent growth (32D-p210). The expression of the plasmid vectors carrying the Rb C-box cDNAs was shown to inhibit the abl tyrosine specific protein kinase activity of the p210(bcr-abl) oncoprotein and to suppress the IL3-independent growth phenotype of the 32D-p210 cells. The Rb C-box polypeptides did not suppress the growth of the untransfected 32D parental cell line in methylcellulose in the presence of IL3-conditioned medium. These results suggest that the cytoplasmic localization of the p210(bcr-abl) allows it to escape the effect of intranuclear proteins such as Rb which negatively regulate the p145(c-abl) kinase.


Assuntos
Transformação Celular Neoplásica/genética , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Fragmentos de Peptídeos/fisiologia , Proteína do Retinoblastoma/fisiologia , Animais , Ensaio de Unidades Formadoras de Colônias , DNA Complementar/genética , Genes do Retinoblastoma , Humanos , Interleucina-3/farmacologia , Proteínas Recombinantes de Fusão/fisiologia , Tetraciclina/farmacologia , Transcrição Gênica/efeitos dos fármacos , Transfecção
12.
Thromb Haemost ; 82(2): 562-71, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10605752

RESUMO

To achieve efficient delivery and sustained expression of the human factor VIII cDNA in vivo, a minimal-adenoviral (mini-Ad) vector system was developed. The system is composed of a mini-Ad vector with essential cis-elements (less than 1 kb) of the viral genome, an E1-deleted ancillary Ad with packaging attenuation, and an E1-complementing production cell line. Based on this system, MiniAdFVIII was generated to deliver a 27 kb expression cassette consisting of a full-length human factor VIII cDNA flanked by human albumin promoter and genomic sequences. The MiniAdFVIII vector mediated expression of functional human factor VIII in HepG2 and 293 cells. A single-dose intravenous injection of 10(11) viral particles in hemophilic mice of MiniAdFVIII produced a sustained high-level expression of human factor VIII (at 100-800 ng/ml up to 369 days) which corrected the FVIII-deficient phenotype. Safety studies of MiniAdFVIII showed that there were no significant toxic effects in mice and dogs after single intravessel doses of up to 3 x 10(11) and 6 x 10(12) viral particles, respectively. Studies for developing the MiniAdFVIII vector with a site-specific integration mechanism and progress in the development of a human factor VIII-tolerized mouse model for pre-clinical studies of MiniAdFVIII are reported. Further pre-clinical studies and product development of MiniAdFVIII for clinical trials are also discussed.


Assuntos
Adenoviridae/genética , Fator VIII/genética , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos , Hemofilia A/terapia , Animais , Modelos Animais de Doenças , Cães , Humanos , Camundongos
13.
Arch Surg ; 133(3): 272-4; discussion 275, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9517739

RESUMO

BACKGROUND: Current treatment of malignant melanoma of the leg includes ilioinguinal lymphadenectomy (IIL). Standard open IIL (open IIL) includes sectioning of the inguinal ligament to gain access to the iliac nodes. Extraperitoneal laparoscopic IIL (lap IIL) is a feasible, less aggressive approach. It can be combined with standard superficial lymphadenectomy for treatment of malignant melanoma. DESIGN: Comparative, prospective, nonrandomized series. SETTING: Tertiary care center. PATIENTS: Twelve consecutive, unselected patients with malignant melanoma treated with lap IIL (group 1) were compared with 10 consecutive, unselected patients with malignant melanoma on whom open IIL was performed (group 2). INTERVENTIONS: Standard open IIL and laparoscopic extraperitoneal iliac lymphadenectomy (lap IIL) plus superficial groin lymphadenectomy. MAIN OUTCOME MEASURES: Operative time, intraoperative complications, requirements of analgesia, total volume of lymphatic drainage, number of lymph nodes retrieved, immediate morbidity, hospital stay, and long-term morbidity were evaluated. RESULTS: Operative time was significantly longer for the lap IIL group (group 1) than for the open IIL group (group 2) (177+/-44 vs 140+/-18 minutes, respectively; P<.05), but no patients in group 1 needed conversion to open surgery or developed related complications. Overall lymphatic drainage was significantly lower in group 1 than in group 2 (615+/-518 mL vs 1393+/-793 mL, repectively; P<.01). The number of doses of analgesics (13+/-8 vs 31+/-22, P<.03) and length of postoperative stay (7.3+/-3.3 vs 13+/-5 days, P<.006) were also significantly lower in the laparoscopic group. The overall number of lymph nodes retrieved was similar in both groups (10.2+/-4.6 vs 10+/-3, P=.9). One patient developed a groin hernia of 6 m after open IIL. CONCLUSIONS: Laparoscopically assisted IIL offers a less aggressive approach than open IIL and entails less pain and a shorter hospital stay, as we observed in 2 groups with similar oncological results (mainly, a similar number of lymph nodes retrieved) who were treated with one procedure or the other. Further research should be done to confirm these preliminary advantages in a prospective randomized trial with long-term follow-up.


Assuntos
Laparoscopia , Perna (Membro) , Excisão de Linfonodo/métodos , Melanoma/cirurgia , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Feminino , Virilha , Humanos , Masculino , Pessoa de Meia-Idade , Peritônio , Estudos Prospectivos , Resultado do Tratamento
14.
Arch Surg ; 133(1): 56-60, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9438760

RESUMO

OBJECTIVE: To document the existence of residual splenic function after laparoscopic splenectomy in a series of 48 patients. DESIGN: A noncomparative descriptive case series. SETTING: A tertiary care center. PATIENTS: A series of 9 patients without clinical improvement after laparoscopic splenectomy of 48 consecutive patients undergoing laparoscopic splenectomy for several hematologic disorders after a mean follow-up of 16 months (range, 1-40 months). INTERVENTIONS: A computed tomographic scan and technetium Tc 99m sodium pertechnetate heat-damaged red blood cell scintigraphy were performed for patients with partial (platelet count <100x10(9)/L) or total (platelet count <50x10(9)/L) failure of improvement. MAIN OUTCOME MEASURE: Evidence of residual splenic tissue by image diagnosis. RESULTS: The condition of 9 of the 48 patients failed to improve after laparoscopic splenectomy. Six patients experienced a total failure of improvement and 3 experienced a partial failure of improvement (1 patient had human immunodeficiency virus-related thrombocytopenia and 8 had idiopathic thrombocytopenic purpura). Three patients had residual splenic function, which was revealed by scintigraphy. The results of a computed tomographic scan showed an accessory spleen in one patient and splenic implants in splenic fossa in another patient. CONCLUSION: Laparoscopic splenectomy has a promising role in the management of hematologic diseases requiring splenectomy, but it requires exquisite care to avoid parenchymal rupture and cell spillage and to avoid leaving accessory spleens, which can lead to the failure of surgical treatment.


Assuntos
Laparoscopia , Baço/anormalidades , Baço/fisiologia , Esplenectomia/métodos , Adolescente , Adulto , Feminino , Seguimentos , Doenças Hematológicas/fisiopatologia , Doenças Hematológicas/cirurgia , Humanos , Masculino , Período Pós-Operatório , Resultado do Tratamento
15.
Surg Endosc ; 15(8): 833-6, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11443462

RESUMO

BACKGROUND: Most of the published animal studies that have evaluated tumor growth and port site metastases in laparoscopy have utilized a cell suspension model and thus cannot be compared to the clinical situation. Although solid tumor models have been developed, there has been no experimental model that establishes an orthotopic tumor in the rectum, reflecting the clinical situation of a solid colonic cancer. METHODS: Tumor cells (colon adenocarcinoma DHD/K1/TRb) were administered intraperitoneally in rats, which were used as solid tumor donors. A 20-mg piece of solid tumor from the donor was placed in a submucosal blister created in the rectum wall of the study rats. The approach to the submucosal blister was made through the mucosa after contralateral enterotomy. In order to validate the model, this intervention was performed in 10 cases (group A). After 10 days of intervention, the rats were submitted to resection of the rectum and histological examination of the specimen. In another 10 rats (group B), manipulation of the tumor was performed after 10 days to cause tumor cell spillage. The likelihood of tumor dissemination was investigated in this group 20 days after this intervention. RESULTS: Group A developed solid tumors in seven of 10 cases (70%). All of the tumors were localized between the muscular and the mucosal layer, with preservation of the serosa and without affecting the enterotomy. In all of the rats in group B, macroscopic tumor was observed in the upper rectum (100%) 10 days after its induction. Twenty days after tumor manipulation, nine rats had local tumor dissemination; two of them also had general tumor dissemination in the abdominal cavity. CONCLUSIONS: We established a novel solid colonic tumor model in rats for the investigation of intraoperative tumor cell spillage during resection of the colon and the development of port site metastases.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Modelos Animais de Doenças , Laparoscopia/efeitos adversos , Inoculação de Neoplasia , Adenocarcinoma/secundário , Animais , Mucosa Intestinal , Masculino , Recidiva Local de Neoplasia/patologia , Transplante de Neoplasias/métodos , Punções/efeitos adversos , Ratos , Reto , Células Tumorais Cultivadas/transplante
16.
Surg Endosc ; 18(8): 1283-7, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15457387

RESUMO

BACKGROUND: Laparoscopic splenectomy (LS) has been demonstrated as an effective and safe treatment for hematological disorders requiring spleen removal, especially in cases of normal-sized spleens. However, although results are promising, long-term outcome data are lacking. We reviewed our clinical experience with LS in a series of 255 cases, with particular attention to the long-term outcome related to the disease process requiring LS. METHODS: From February 1993 to October 2003, LS was attempted in 255 patients (100 males and 155 females with a mean age of 45 +/- 19 years) and clinical information was recorded in a prospective database. Indications for splenectomy included idiopathic thrombocytopenic purpura (ITP) (n = 115), HIV-ITP (n = 9), Evans syndrome (n = 6), autoimmune hemolytic anemia (AIHA) (n = 13), hereditary spherocytosis (HS) (n = 19), hematologic malignancy (n = 66), thrombotic thrombocytopenic purpura (n = 1), and others (n = 26). Long-term postoperative follow-up evaluation was obtained through clinical notes, follow-up visits by the referring hematologist, and by phone interviews both with patients and with the referring hematologist. RESULTS: A total of 186 patients (73%) were available for a mean follow-up of 35 months (range, 1-104). Of the ITP patients, 87 (76%) were followed up, with a remission rate of 89% (complete remission in 75%). A similar remission rate was observed in ITP-HIV; in patients available for follow-up (78%), complete remission was achieved in 83%. In Evans, complete remission was achieved in all patients available for follow-up (67%). Clinical response for hemolytic disease ranged between 70% for AIHA and 100% for HS. In the malignant group, the late mortality rate was 22%. The mortality rate in the miscellaneous group was 5%. No cases of splenectomy-related sepsis occurred during follow-up. CONCLUSIONS: LS offers advantages for all types of splenic diseases requiring surgery. It provides not only good clinical short-term outcome but also satisfactory long-term hematological results.


Assuntos
Doenças Hematológicas/cirurgia , Laparoscopia/métodos , Esplenectomia/métodos , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento
17.
Surg Endosc ; 18(7): 1045-50, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15156380

RESUMO

BACKGROUND: Initial experience with the laparoscopic repair of paraesophageal and type III mixed hiatal hernias showed that it is safe and feasible, with excellent immediate and short-term results. However, after a longer follow-up, a recurrence rate of < or =40% has been demonstrated. Data related to the outcome of paraesophageal hernia repair and the recurrence rate are still lacking. Quality-of-life scores may offer a better means of assessing the impact of surgical treatment on the overall health status of patients. Therefore, we performed prospective evaluation of anatomic and/or symptomatic recurrences after paraesophageal or large hiatal hernia repair. In addition, we investigated the correlation between recurrence and the patient's quality of life. METHODS: All patients after who had undergone repair of paraesophageal of mixed hiatal hernia were identified prospectively from a database consisting of all patients who had had laparoscopic operations for gastroesophageal pathology at our hospital between February 1998 and December 2002. The preoperative symptoms were taken from patients' clinical files. In March 2003, all patients with > or =6 months of follow-up had a barium swallow and were examined for radiological and clinical signs of recurrence. Thereafter, the patients' quality of life after surgery was evaluated using three standard questionnaires (Short Form 36 [SF-36], Glasgow Dyspepsia Severity Score [GDSS], and Gastrointestinal Quality of Life Index [GIQLI]. RESULT: During the study period, 46 patients had been operated on. The mean age was 63 years (range, 28-93). Thirty seven of them had a follow-up of > or =6 months. Eight patients (21%) had postoperative gastrointestinal symptoms. Barium swallow was performed in 30 patients (81%) and showed a recurrence in six of them (20%). According to SF-36 and GDSS, the patients' postoperative quality of life reached normal values and did not differ significantly from the standard values for the Spanish population of similar age and with similar comorbidities. Successfully operated patients reached a GIQLI value comparable to the standard population. However, symptomatic patients had significantly lower GIQLI scores than the asymptomatic or the Rx-recurrent group. CONCLUSION: The laparoscopic treatment of large paraesophageal and mixed hiatal hernias is not only feasible and safe but also offers a good quality of life on a midterm basis. However, the anatomic and functional recurrence rate is high. The next step is to identify the subset of patients who are at risk of failure and to establish technical alternatives that would ensure the durability of the repair.


Assuntos
Fundoplicatura/estatística & dados numéricos , Hérnia Hiatal/cirurgia , Laparoscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Dispepsia/epidemiologia , Dispepsia/etiologia , Estudos de Viabilidade , Feminino , Seguimentos , Fundoplicatura/métodos , Hérnia Hiatal/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Radiografia , Recidiva , Índice de Gravidade de Doença , Espanha/epidemiologia , Inquéritos e Questionários , Resultado do Tratamento
18.
Surg Endosc ; 16(3): 426-30, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11928021

RESUMO

BACKGROUND: Laparoscopic splenectomy (LS) is considerably more difficult to perform when the spleen is enlarged. The new technique of hand-assisted designed technique aimed to assist laparoscopic surgery allows the surgeon to insert his or her hand into the abdomen while maintaining the pneumoperitoneum, thus recovering the tactile sensation lost in conventional laparoscopic surgery. OBJECT: In this study, we compared the immediate results of conventional LS and hand-assisted LS (HALS) in cases of splenomegaly. METHODS: Between February 1993 and August 2001, 200 LS were attempted at two university hospitals. In 56 cases, splenomegaly (final spleen weight >700 g) was observed clinically or detected on radiological examination. We compared the first 36 patients operated on by conventional LS (group I) with the last consecutive 20 patients, who underwent HALS (group II). The study parameters were operative time, conversion rate, transfusion rate, morbidity and length of hospital stay. RESULTS: The groups were comparable in terms of age (58 +/- 13 [ranges, l9-82] vs 58 +/- 16 years [range, 44-84] (ns), diagnosis, and spleen weight (1425 +/- 884 [range, 700-3400]) vs 1753 +/- 1124 g [range, 720-4500] (ns). HALS was associated with less morbidity (36% vs 10%) (ns), a shorter operative time (177 +/- 52 [range, 95-300]) vs 135 +/- 53 min [range, 85-270] (p <0.009), and a shorter hospital stay (6.3 +/- 3.3 [range, 3-14]) vs 4 +/- 1.2 [range, 2-7] days (p <0.05). CONCLUSION: In cases of splenomegaly, HALS assisted laparoscopic surgery significantly facilitates the surgical maneuvers during LS while maintaining the advantages of a purely laparoscopic approach.


Assuntos
Laparoscopia/métodos , Esplenectomia/métodos , Esplenomegalia/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Surg Endosc ; 14(1): 22-6, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10653230

RESUMO

BACKGROUND: The incidence of colorectal carcinoma increases in the elderly. Regardless of age as an isolated factor, postoperative complications represent the main factor in increasing hospital mortality. METHODS: The aim of this study was to compare the short-term results (first 30 postoperative days) after laparoscopically assisted colectomy (LAC) and open segmental colectomy (OC) in colorectal carcinoma between two groups of patients, older than 70 and younger than 70 years of age. In the study from November 1993 to June 1998, 255 patients were evaluated to participate. RESULTS: Peristalsis, oral intake, and discharge from the hospital occurred earlier in LAC than in OC treated patients, in the two age groups. The mean operative time was significantly longer in the LAC than in the OC patients in the two age groups. No differences were observed in morbidity between LAC and OC in the group younger than 70 years of age. However, the overall morbidity was significantly lower in the LAC group in patients older than 70 years. One patient in the LAC group older than 70 years died. CONCLUSION: These results suggest that laparoscopically assisted colectomy may be particularly indicated in elderly patients.


Assuntos
Colectomia , Neoplasias Colorretais/cirurgia , Laparoscopia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Colectomia/efeitos adversos , Feminino , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos
20.
Int Surg ; 81(1): 1-5, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8803695

RESUMO

After the spread of laparoscopic cholecystectomy, minimally invasive surgery has been applied to other organs such as the pancreas. Diagnostic laparoscopy is a very useful tool which provides information in conjunction with other instruments such as ultrasonography and computed tomography in the study of pancreatic cancer. Laparoscopic ultrasonography improves the sensibility and specificity of laparoscopy alone in predicting resectability. Although experimental cases of pancreatic resection have been described, the majority of patients require palliative treatment. Surgical bypass has a high morbidity rate and nonoperative biliary decompression has become an established treatment for relieving jaundice. However, these techniques are associated with a high rate of recurrent obstruction. Laparoscopic cholecystojejunostomy gives the advantage of definitive bypass with shorter hospital stay, and a gastrojejunostomy can also be performed when duodenal obstruction occurs. Relief of pain is possible with a thoracoscopic splanchnicectomy, which offers good results. Internal drainage for pseudocysts is another new application of laparoscopic surgery which gives excellent results.


Assuntos
Cuidados Paliativos , Pancreatopatias/diagnóstico , Neoplasias Pancreáticas/cirurgia , Pseudocisto Pancreático/cirurgia , Idoso , Gastroenterostomia/métodos , Gastrostomia/métodos , Humanos , Laparoscopia , Pessoa de Meia-Idade , Ultrassonografia/métodos
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