Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
Protein Sci ; 33(3): e4898, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38358135

RESUMO

Structural genomics consortia established that protein crystallization is the primary obstacle to structure determination using x-ray crystallography. We previously demonstrated that crystallization propensity is systematically related to primary sequence, and we subsequently performed computational analyses showing that arginine is the most overrepresented amino acid in crystal-packing interfaces in the Protein Data Bank. Given the similar physicochemical characteristics of arginine and lysine, we hypothesized that multiple lysine-to-arginine (KR) substitutions should improve crystallization. To test this hypothesis, we developed software that ranks lysine sites in a target protein based on the redundancy-corrected KR substitution frequency in homologs. This software can be run interactively on the worldwide web at https://www.pxengineering.org/. We demonstrate that three unrelated single-domain proteins can tolerate 5-11 KR substitutions with at most minor destabilization, and, for two of these three proteins, the construct with the largest number of KR substitutions exhibits significantly enhanced crystallization propensity. This approach rapidly produced a 1.9 Å crystal structure of a human protein domain refractory to crystallization with its native sequence. Structures from Bulk KR-substituted domains show the engineered arginine residues frequently make hydrogen-bonds across crystal-packing interfaces. We thus demonstrate that Bulk KR substitution represents a rational and efficient method for probabilistic engineering of protein surface properties to improve crystallization.


Assuntos
Lisina , Proteínas , Humanos , Lisina/química , Cristalização , Proteínas/genética , Aminoácidos/química , Cristalografia por Raios X , Arginina/metabolismo
2.
bioRxiv ; 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37398404

RESUMO

Multiple paralogous ABCF ATPases are encoded in most genomes, but the physiological functions remain unknown for most of them. We herein compare the four Escherichia coli K12 ABCFs - EttA, Uup, YbiT, and YheS - using assays previously employed to demonstrate EttA gates the first step of polypeptide elongation on the ribosome dependent on ATP/ADP ratio. A Δ uup knockout, like Δ ettA , exhibits strongly reduced fitness when growth is restarted from long-term stationary phase, but neither Δ ybiT nor Δ yheS exhibits this phenotype. All four proteins nonetheless functionally interact with ribosomes based on in vitro translation and single-molecule fluorescence resonance energy transfer experiments employing variants harboring glutamate-to-glutamine active-site mutations (EQ 2 ) that trap them in the ATP-bound conformation. These variants all strongly stabilize the same global conformational state of a ribosomal elongation complex harboring deacylated tRNA Val in the P site. However, EQ 2 -Uup uniquely exchanges on/off the ribosome on a second timescale, while EQ 2 -YheS-bound ribosomes uniquely sample alternative global conformations. At sub-micromolar concentrations, EQ 2 -EttA and EQ 2 -YbiT fully inhibit in vitro translation of an mRNA encoding luciferase, while EQ 2 -Uup and EQ 2 -YheS only partially inhibit it at ~10-fold higher concentrations. Moreover, tripeptide synthesis reactions are not inhibited by EQ 2 -Uup or EQ 2 -YheS, while EQ 2 -YbiT inhibits synthesis of both peptide bonds and EQ 2 -EttA specifically traps ribosomes after synthesis of the first peptide bond. These results support the four E. coli ABCF paralogs all having different activities on translating ribosomes, and they suggest that there remains a substantial amount of functionally uncharacterized "dark matter" involved in mRNA translation.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36497840

RESUMO

Sports bras are an essential apparel for active women, but may exert excessive pressure that negatively affects thermoregulation, thermal comfort and wear sensation. This study measures skin temperature changes during short durations of exercise on a treadmill with different bra pressures. The results based on 21 female subjects (age: 27.2 ± 4.5 years old) show that bras with more pressure at the underband or shoulder straps do not cause statistically significant skin temperature changes during exercise (p > 0.05). Nevertheless, compared to the optimal bra fit, significant differences in bra-breast skin temperature are found during running, cooling down and sitting when the bra pressure is increased (p < 0.05), particularly under bra cup (T1) in this study. The FLIR thermal images can visualize the skin temperature changes at abdomen throughout the four activity stages. Subjective sensations of bra thermal comfort, pressure and breast support are assessed. Despite the increased pressure on the shoulders and chest wall, perceptions towards thermal comfort remain unchanged. The perceived pressure comfort and support sensation amongst the 4 bra conditions are comparable. Interestingly, positive sensations of pressure comfort and breast support are perceived with a tight-fitting sports bra during treadmill exercise. High pressures induced by sports bras (>4 kPa) that habitually considered harmful to the human body may not lead to wear discomfort but enhance bra support sensation and a sense of security to the wearers.


Assuntos
Corrida , Temperatura Cutânea , Feminino , Humanos , Adulto Jovem , Adulto , Vestuário , Corrida/fisiologia , Mama , Teste de Esforço , Regulação da Temperatura Corporal
4.
Nature ; 529(7586): 358-363, 2016 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-26760206

RESUMO

Degeneracy in the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, has an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the sequence features influencing protein expression levels in 6,348 experiments using bacteriophage T7 polymerase to synthesize messenger RNA in Escherichia coli. Logistic regression yields a new codon-influence metric that correlates only weakly with genomic codon-usage frequency, but strongly with global physiological protein concentrations and also mRNA concentrations and lifetimes in vivo. Overall, the codon content influences protein expression more strongly than mRNA-folding parameters, although the latter dominate in the initial ~16 codons. Genes redesigned based on our analyses are transcribed with unaltered efficiency but translated with higher efficiency in vitro. The less efficiently translated native sequences show greatly reduced mRNA levels in vivo. Our results suggest that codon content modulates a kinetic competition between protein elongation and mRNA degradation that is a central feature of the physiology and also possibly the regulation of translation in E. coli.


Assuntos
Códon/genética , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/genética , Biossíntese de Proteínas/genética , RNA Bacteriano/metabolismo , RNA Mensageiro/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/biossíntese , Genes Sintéticos/genética , Meia-Vida , Cinética , Modelos Logísticos , Modelos Genéticos , Dados de Sequência Molecular , Razão de Chances , Elongação Traducional da Cadeia Peptídica , Dobramento de RNA , Estabilidade de RNA , RNA Bacteriano/genética , RNA Mensageiro/genética , Transcrição Gênica/genética , Proteínas Virais/metabolismo
5.
World J Surg ; 35(3): 600-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21161656

RESUMO

BACKGROUND: Pharyngo-laryngo-esophagectomy (PLE) has been regarded as a standard treatment for cervical esophageal cancer, but the morbidity and mortality rates associated with PLE are substantial. Chemoradiation (CTRT) is widely used to treat esophageal cancer; however, its role in managing cervical esophageal cancer has not been fully elucidated. It was hypothesized that up-front CTRT could be an effective alternative treatment option to PLE. The purpose of this study was to compare the outcomes of patients with cervical esophageal cancer treated with these two methods. METHODS: Patients with cervical esophageal cancer from 1995 to 2008 were studied. Three main groups were identified: those treated with PLE, those managed with up-front concurrent chemoradiation, and those not suitable for either PLE or chemoradiation but to whom palliative treatment was offered. The demographics, management strategies, and outcomes of these patients were studied and analyzed. RESULTS: A total of 107 patients were studied: 87 (81.3%) were men, and the median age was 64 years (range 17-92 years). There were 62 patients who underwent PLE as the primary treatment, 21 had up-front chemoradiation, and the others had palliative treatment. In the PLE group, curative resection was achieved in 37 (59.7%) patients, 20 of whom had either adjuvant chemoradiation or radiotherapy. The hospital mortality rate was 7.1%. In the chemoradiation group, 10 (47.6%) had tumor down-staging, 6 of whom achieved a clinically complete response. Among the 11 patients with poor response, 5 required salvage PLE for palliation. Chemoradiation-associated morbidities included oral mucositis, bilateral vocal cord palsy, esophageal stricture, carotid artery blowout, and permanent hypothyroidism and hypoparathyroidism. The median survival durations of patients in the PLE and chemoradiation groups were 20 and 25 months respectively (P = 0.39). CONCLUSIONS: Up-front chemoradiation can be an alternative therapeutic strategy to PLE. However, this method is not without drawbacks. A significant proportion also requires salvage surgery. Both PLE and chemoradiation have significant curative as well as palliative role in the management of cervical esophageal cancer and treatment should be individualized.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Cuidados Paliativos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Terapia Combinada , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Cuidados Paliativos/métodos , Faringectomia/métodos , Prognóstico , Radioterapia/métodos , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
6.
Ann Surg Oncol ; 17(8): 2184-92, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20217248

RESUMO

BACKGROUND: Whether the TNM staging system is applicable after neoadjuvant chemoradiation in esophageal cancer is controversial. The aim of this study was to evaluate the prognostic value of histopathological regression of the primary tumor in postchemoradiated patients. MATERIALS AND METHODS: The pretherapeutic and pathological ypTNM stages of patients who have had neoadjuvant chemoradiation followed by esophagectomy were analyzed. The percentage of residual viable cells of the primary tumor (ypV) and other clinicopathological factors were tested for their prognostic value. RESULTS: Of 175 recruited patients, 55 (31.4%) achieved pathological complete response. The median survival of these 55 patients was significantly longer than those with other disease stages (124.8 vs 21.1 months) (P < .001). Gender, ypT, ypN, ypTNM, and ypV stage were significant prognostic factors in univariate analysis. In patients without nodal metastases, the median survival in patients with residual viable cells in the primary tumor (ypV+) was 24.6 months, compared with that of 124.8 months in those with no viable cells (ypV0) (P = .043). In those who had nodal metastases, the median survival of patients with ypV0 and ypV+ were 21.2 months and 17.4 months respectively (P = .37). Cox regression analysis showed that male gender, high percentage of residual viable cells (ypV), and positive nodal status (ypN1) were independent predictors of poor prognosis. CONCLUSIONS: In patients who underwent neoadjuvant chemoradiation therapy, histopathological regression of the primary tumor indicated by percentage of residual viable cells is an important prognostic factor in addition to nodal status and gender.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Sobrevivência Celular , Quimioterapia Adjuvante , Neoplasias Esofágicas/mortalidade , Esofagectomia , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasia Residual , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Radioterapia Adjuvante , Fatores Sexuais , Taxa de Sobrevida , Resultado do Tratamento
7.
J Gastrointest Surg ; 12(10): 1638-45; discussion 1645, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18704592

RESUMO

BACKGROUND: It remains controversial if metastatic cervical lymph nodes in patients with intrathoracic esophageal cancer signify distant metastases and are therefore incurable or if they should be regarded as regional spread with a potential for cure. MATERIAL AND METHODS: Patients with intrathoracic esophageal squamous cell carcinoma managed from 1995 to 2007, in whom metastatic cervical lymph node spread was confirmed by fine needle aspiration cytology, were studied. Treatment strategies and outcome were reviewed. RESULTS: There were 109 patients, of whom 98 were men. Median age was 62 years (range, 34-88). Excluding those who underwent primarily palliative treatments, there were two main groups: 22 who had upfront chemoradiation therapy and subsequent esophagectomy +/- cervical lymphadenectomy and 46 who had chemoradiation only. Significant downstaging occurred in 29 of the 68 patients (42.6%), of whom eight (11.8%) had complete pathological/clinical response. There was no mortality after esophagectomy. Median survival of patients with chemoradiation plus esophagectomy was 34.8 months compared to those with no surgery at 9.9 months, (p < 0.001). Patients with stage IV disease at presentation by virtue of nodal disease survived longer than those with the same stage because of systemic organ metastases: 9.3 vs. 3 months, (p < 0.001). CONCLUSIONS: Prognosis of patients with metastatic cervical nodes was not uniformly dismal. Up to 20% had reasonable survival after chemoradiation and surgical resection. Stage IV disease should be revised to segregate those with nodal and systemic metastases.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Linfonodos/patologia , Neoplasias Torácicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Terapia Combinada , Neoplasias Esofágicas/patologia , Esofagectomia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pescoço , Terapia Neoadjuvante , Prognóstico , Radioterapia Adjuvante , Neoplasias Torácicas/patologia
8.
Ann Surg Oncol ; 15(6): 1750-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18347873

RESUMO

BACKGROUND: The presence of synchronous or antecedent head and neck cancers may complicate management of patients with primary esophageal cancer. METHODS: From January 1982 to December 2004, by means of a prospectively collected database, we compared information from 119 patients with esophageal cancers who had synchronous or antecedent head and neck cancers with information from 1555 patients who only had squamous cell esophageal cancer in a tertiary referral academic hospital. RESULTS: There were far more men and younger patients in those who had head and neck cancers, and multicentric tumors were also more common. Hypopharyngeal tumors were the most frequently encountered head and neck cancer and were found in 36.1% of patients. Resection rates of the primary esophageal cancers were similar in those who had head and neck cancers and in those who only had esophageal cancer (60.7% vs. 61.7% P = .74). Overall postoperative complication rates were not different. Thirty-day mortality rates were 0% and 2.9% for those who did and did not have head and neck tumors, respectively (P = .25). The respective hospital mortality rates were 10.3% and 9.5% (P = .83). Median survival for resectable esophageal cancers was 9.2 months for the former group and 13.4 months for the latter (P = .02). CONCLUSIONS: Esophagectomy rates did not differ when synchronous or antecedent head and neck cancers were present. Similar postoperative morbidity and mortality rates could be achieved. The presence of additional head and neck tumors imparted a worse long-term prognosis.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias Primárias Múltiplas/terapia , Segunda Neoplasia Primária/terapia , Idoso , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/mortalidade , Terapia Combinada , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/mortalidade , Esofagectomia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/mortalidade , Segunda Neoplasia Primária/mortalidade , Prognóstico , Estudos Retrospectivos
9.
J Gastrointest Surg ; 10(9): 1301-11, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17114016

RESUMO

For esophageal cancer, it is not clear if pathologic TNM staging after chemoradiation and resection will have the same prognostic significance compared with patients who undergo resection only. From 1995 to 2004, prospectively collected data from 279 patients with intrathoracic squamous cell cancers were analyzed. Patients were given chemoradiation either as part of a randomized trial comparing neoadjuvant chemoradiation with surgical resection alone, or because of advanced disease at presentation. One hundred seventy patients had surgical resection only (surgery), and 109 had neoadjuvant chemoradiation (CRT plus surgery). In the surgery group, pT1, 2, 3, and 4 disease was found in 15, 17, 104, and 34 patients, respectively; their respective pN1 rates were 13.3%, 29.4%, 57.7%, and 64.7%, P < 0.01. In CRT plus surgery, pT0, T1, 2, 3, and 4 were found in 48, 12, 23, 21, and 5 patients, respectively; their respective pN1 rates were 31.3%, 16.7%, 21.7%, 52.4%, and 20%, P = 0.44. Logistic regression analysis of factors predictive of pN1 showed that pT stage correlated with pN1 status (P = 0.005) in the surgery group, but not for the CRT plus surgery group. Cox regression analysis demonstrated that in the surgery group, pT, pN, and R category, and overall pTNM stage, were independent prognostic factors, whereas pN, R category, and gender were identified as relevant for CRT plus surgery. After chemoradiation, pT and overall pTNM stage groupings were not as clearly prognostic as in patients without prior therapy. Nodal status remains an important prognostic factor.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/diagnóstico , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/diagnóstico , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico
10.
Ann Surg Oncol ; 13(4): 557-64, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16485146

RESUMO

BACKGROUND: The dismal survival associated with esophagectomy for cancer has led to the search for potentially correctable factors responsible for this poor prognosis. Although it is intuitive that technical complications could increase postoperative mortality, the effect on long-term survival is controversial. METHODS: From 1990 to 2002, 434 patients underwent resection for squamous cell carcinoma of the intrathoracic esophagus. Prospectively collected data were reviewed for the presence of technical complications. Patient, tumor, and operative variables, postoperative outcome, and survival were compared between patients with technical complications and those without. Prognostic factors were assessed by multivariate analysis. RESULTS: Technical complications occurred in 98 (22.6%) patients. Patients with technical complications had a higher prevalence of cardiac disease, more proximal tumors, and more cervical anastomoses. Technical complications were associated with an increased rate of pulmonary complications (37.8% vs. 10.7%; P<.001) and increased hospital mortality (9.2% vs. 3.3%; P=.025), but no difference in 30-day mortality (2% vs. 1.2%; P=.6). Poor-prognostic factors for survival included male sex, stage III/IV disease, cirrhosis, proximal tumors, and R1/R2 resection, but not technical complications. CONCLUSIONS: Although immediate postoperative outcome and hospital mortality rates were increased, no effect on long-term survival was seen in patients with complications related to errors in surgical technique.


Assuntos
Anastomose Cirúrgica/efeitos adversos , Perda Sanguínea Cirúrgica , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Obstrução da Saída Gástrica/cirurgia , Complicações Intraoperatórias , Complicações Pós-Operatórias , Reoperação , Deiscência da Ferida Operatória , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
11.
World J Gastroenterol ; 11(23): 3518-22, 2005 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-15962366

RESUMO

AIM: To assess the clinical characteristics of Helicobacter pylori (H pylori) negative duodenal ulcer. METHODS: Patients with an endoscopic diagnosis of duodenal ulcer between 1996 and 2002 were included in the present study. Patients were considered to be negative for H pylori, if both histological examination and rapid urease test of biopsy specimens were negative. A comparison was made between patients with H pylori positive and negative duodenal ulcers. RESULTS: A total of 1 343 patients were studied. Their mean age was 54.7+/-0.5 years. There was a male preponderance (M:F=2.5:1). Three hundred and ninety-eight patients (29.6%) did not have H pylori infection. The annual proportion of patients with H pylori negative duodenal ulcers increased progressively from 1996 to 2002. On multivariate analysis, patients with H pylori negative duodenal ulcer were more likely to be older, have concomitant medical problem, pre-existing malignancy, recent surgery, underlying sepsis, or taken non-steroidal anti-inflammatory drugs. In terms of clinical presentations, patients with H pylori negative duodenal ulcer were more likely to present with bleeding, multiple ulcers and larger ulcers. CONCLUSION: The proportion of patients with H pylori negative duodenal ulcers is on the rise because of a continued drop in incidence of H pylori positive duodenal ulcers in recent years. Such patients have distinct clinical characteristics and it is important to ascertain the H pylori status before starting eradication therapy.


Assuntos
Úlcera Duodenal/microbiologia , Úlcera Duodenal/patologia , Infecções por Helicobacter/complicações , Helicobacter pylori , Progressão da Doença , Úlcera Duodenal/epidemiologia , Feminino , Humanos , Masculino
12.
Arch Surg ; 140(1): 33-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15655203

RESUMO

HYPOTHESIS: A 1-layer, continuous technique for esophageal anastomosis after esophagectomy has been in routine use at the University of Hong Kong Medical Centre since 1996. This study aims to document the results of this method and examine factors that may predispose patients to complications associated with esophageal anastomosis. DESIGN: Retrospective study. SETTING: University academic surgical center. PATIENTS AND METHODS: We studied 218 consecutive patients who had an esophageal anastomosis constructed with a 1-layer, continuous technique. Data were prospectively collected. MAIN OUTCOME MEASURES: Morbidity and mortality rates, anastomotic leaks, stricture, and recurrences. RESULTS: Anastomotic leaks affected 7 patients (3.2%), of whom 3 required surgical reexploration and none died. The hospital mortality rate was 0.9% (2 patients), attributed to myocardial infarction and malignancy. Anastomotic strictures developed in 24 patients (11.1%). Multivariate analysis in those with gastric conduits showed that a cervical anastomosis (intrathoracic vs cervical; odds ratio, 0.27; 95% confidence interval, 0.08-0.87; P = .03) and use of the distal stomach (distal stomach vs whole stomach; odds ratio, 5.25; 95% confidence interval, 1.65-16.66; P = .005) were predictive of benign anastomotic stricture formation. Eleven patients (17.5%) who had a cervical anastomosis developed strictures compared with 13 (8.6%) in those who had intrathoracic anastomoses. Strictures developed in 12 patients (7.4%) with a whole stomach conduit and in 9 patients (19.6%) with a distal stomach conduit. Anastomotic recurrence occurred in 8 patients (3.7%); none had a histologically involved resection margin. CONCLUSIONS: The single-layer, continuous, hand-sewn technique for esophageal anastomosis is safe and effective. Cervical anastomosis and use of the distal stomach were associated with more benign strictures.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esôfago/cirurgia , Estômago/cirurgia , Técnicas de Sutura , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/mortalidade , Esofagectomia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatística como Assunto , Taxa de Sobrevida , Resultado do Tratamento
13.
J Vasc Surg ; 40(6): 1234-7, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15622380

RESUMO

A 67-year-old man with previous total gastrectomy and roux-en-Y esophagojejunostomy had hematemesis 4 weeks after esophagectomy performed because of carcinoma of the esophagus. Investigation showed an aortojejunal fistula with a thoracic aortic pseudoaneurysm. Endovascular stent grafting of the pseudoaneurysm, followed by endoscopic injection of fibrin sealant for the fistula, was performed, and the infection was controlled with broad-spectrum antibiotic agents together with drainage and daily irrigation of the pseudoaneurysm sac. The fistula subsequently healed. The patient remained well 14 months after the procedure; follow-up computed tomograms at 12 months did not show any pseudoaneurysm, and there was no evidence of reopening of the fistula.


Assuntos
Doenças da Aorta/terapia , Implante de Prótese Vascular/métodos , Esofagectomia/efeitos adversos , Adesivo Tecidual de Fibrina/uso terapêutico , Fístula Intestinal/terapia , Idoso , Anastomose Cirúrgica/efeitos adversos , Falso Aneurisma/etiologia , Falso Aneurisma/terapia , Aneurisma da Aorta Torácica/etiologia , Aneurisma da Aorta Torácica/terapia , Doenças da Aorta/etiologia , Drenagem , Endoscopia do Sistema Digestório , Neoplasias Esofágicas/cirurgia , Humanos , Fístula Intestinal/etiologia , Masculino , Stents , Irrigação Terapêutica , Toracotomia , Resultado do Tratamento
14.
Ann Surg ; 240(5): 791-800, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15492560

RESUMO

OBJECTIVE: This study aimed at: (1) documenting the evolution of surgical results of esophagectomy in a high-volume center, (2) identifying predictive factors of pulmonary complications and mortality, and (3) examining whether preoperative chemoradiation therapy would complicate postoperative recovery. SUMMARY BACKGROUND DATA: Pulmonary complications and mortality rate after esophagectomy remain substantial, and factors responsible have not been adequately studied. Neoadjuvant chemoradiation is widely used; it is hypothesized that this may lead to adverse postoperative outcome. METHODS: Prospectively collected data were used to analyze outcome in 421 patients with intrathoracic squamous cell esophageal cancer who underwent resection. Logistic regression analyses determined independent predictors of pulmonary complications and death. Two time periods were compared: period I (January 1990 to June 1995) and period II (July 1995 to December 2001). In the later period, neoadjuvant chemoradiation therapy was introduced. RESULTS: Transthoracic resections were carried out in 83% of patients. Neoadjuvant chemoradiation was given to 42% of patients in period II. Major pulmonary complications occurred in 15.9%, and were primarily responsible for 55% of hospital deaths. Thirty-day and hospital mortality rates were 1.4% and 4.8%, respectively. Logistic regression analysis identified age, operation duration, and proximal tumor location as risk factors for pulmonary complications, whereas advanced age and higher blood loss were predictive of mortality. Chemoradiation did not lead to worse outcome. When period I and II were compared, hospital mortality rate reduced from 7.8% to 1.1%, P = 0.001, with correspondingly less blood loss (median blood loss was 700 ml (range: 200-2700 (period I) and 450 ml (range: 100-7000) (period II), P < 0.01). CONCLUSION: A 1.1% mortality rate was achieved in the last 6 years of the study period. Preoperative chemoradiation did not result in worse outcome. Reduction in mortality rate correlated with decreased blood loss.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Pneumopatias/etiologia , Idoso , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Fatores de Risco , Taxa de Sobrevida
15.
Dis Esophagus ; 17(1): 81-6, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15209747

RESUMO

Conventional pleural cavity drainage after esophagectomy involves one to two large-bore drainage tubes connected to underwater bottles. The purpose of this study is to evaluate the use of a small mobile vacuum drainage system. Out of 173 patients who underwent transthoracic esophagectomy, 167 (97%) had the vacuum drain successfully placed at the end of the operation. Of those, use of the vacuum drain was uneventful for 131 until its removal (78%). Air leaks necessitating connection to underwater drainage occurred in 34 patients (20%), but in 26 of them this was only temporary. Overall success was therefore achieved in 157 patients (94%). Median in-situ placement of the vacuum drain was 4 days, and 85% of patients had their drains removed by the seventh postoperative day. The presence of lung adhesions significantly increased the need for underwater drainage. Postoperative outcomes were no different from a historical cohort with conventional underwater drainage. No drain-related complications were reported. The vacuum drain is an alternative to the conventional, large-bore, chest tube system after transthoracic esophagectomy.


Assuntos
Drenagem/instrumentação , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Derrame Pleural/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Drenagem/métodos , Desenho de Equipamento , Segurança de Equipamentos , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Derrame Pleural/etiologia , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/prevenção & controle , Probabilidade , Estudos Prospectivos , Medição de Risco , Toracotomia/efeitos adversos , Toracotomia/métodos , Resultado do Tratamento
16.
Gastrointest Endosc ; 59(4): 471-4, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15044880

RESUMO

BACKGROUND: Gastric carcinoma is known for its propensity to spread to the peritoneum. This study assessed the value of EUS in the detection of ascites not visible on CT in patients with gastric carcinoma. METHODS: A total of 402 consecutive patients with histopathologically confirmed gastric adenocarcinoma underwent catheter-probe EUS. The accuracy of catheter-probe EUS in the detection of ascites was compared with subsequent findings at laparoscopy or laparotomy. RESULTS: There was a slight predominance of men in the study population (M:F=1.6:1). Mean patient age was 65.4+/-0.7 years. Ascites was noted by catheter-probe EUS in 36 patients (9.0%). There was no procedure-related morbidity or mortality. Ascites and peritoneal seeding subsequently were found in, respectively, 56 (13.9%) and 66 (16.4%) patients. The finding of ascites by EUS was significantly related to the presence of peritoneal seeding (p<0.001). The sensitivity, specificity, and positive and negative predictive values of EUS in the detection of ascites were, respectively, 60.7%, 99.4%, 94.4%, and 94.0%. The positive and negative likelihood ratios were, respectively, 105.0: 95% CI[26, 425] and 0.40: 95% CI[0.29, 0.55]. CONCLUSIONS: EUS is useful for the detection of ascites in patients with gastric carcinoma.


Assuntos
Adenocarcinoma/patologia , Ascite/diagnóstico por imagem , Endossonografia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Gástricas/patologia , Ascite/etiologia , Humanos , Estadiamento de Neoplasias/métodos , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/secundário , Valor Preditivo dos Testes , Estudos Prospectivos
18.
Ann Surg ; 238(3): 339-47; discussion 347-8, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14501500

RESUMO

OBJECTIVE: To identify prognostic factors and reasons for improved survival over time in patients with esophageal cancer. SUMMARY BACKGROUND DATA: Management strategies for esophageal cancer have evolved with time. The impact of chemoradiation in the overall treatment results has not been adequately studied. METHODS: From 1990 to 2000, 399 (62.4%) of 639 patients with intrathoracic squamous cancers underwent resection. Two study periods were analyzed: period I (01/1990-06/1995), and period II (07/1995-12/2000); during period II, chemoradiation was introduced. Prognostic factors were identified by multivariate analysis and the 2 periods compared. RESULTS: Hospital mortality rate after resection decreased from 7.8% to 1.2%, P = 0.002. Five favorable prognostic factors were identified: female gender (female vs. male, HR = 0.66), infracarinal tumor location (infra vs. supra-carinal, HR = 0.63), low pTNM stage (III/IV vs. 0/I/II/T0N1, HR = 1.76), pM0 stage (M1a/b vs. M0, HR = 1.56), and R0 category (R1/2 vs. R0, HR = 2.49). Median survival was 15.8 and 25.6 months in periods I and II, respectively, P = 0.02. More R0 resections were evident in period II, being possible in 63% (period I) and 79% (period II) of patients, P = 0.001. This was attributed to tumor downstaging by chemoradiation and more stringent patient selection for resection in period II. Performing less R1/2 resections in period II coincided with using primary chemoradiation in treating advanced tumors. In patients treated without resection, survival also improved from 3 (period I) to 5.8 months (period II), P < 0.01. CONCLUSIONS: Survival has improved; chemoradiation enabled better patient selection for curative resections and also resulted in more R0 resections by tumor downstaging. This treatment strategy led to overall better outcome for the whole patient cohort, even in those treated by nonsurgical means.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Antineoplásicos/uso terapêutico , Terapia Combinada , Esofagectomia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Seleção de Pacientes , Cuidados Pré-Operatórios , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Taxa de Sobrevida , Fatores de Tempo
19.
Am Surg ; 69(4): 358-61, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12716100

RESUMO

Sentinel lymph node (SLN) biopsy is an evolving treatment approach for patients with operable breast cancer. There have been a number of variations in the biopsy technique. One is the timing of radioisotope injection, which might have a significant influence on the radiation exposure of the personnel in the operating room. The present study aims to compare the one-day with the two-day protocol to see which one is associated with a lower radiation hazard while giving similar results. There were 60 patients recruited; half of them had the SLN biopsy 4 hours after the injection and the other half 24 hours later. Patient characteristics were comparable in both groups. The mean numbers of SLNs found per patient were 1.46 and 1.96 respectively. There was a statistically significant difference in the dosage of radioactivity present in the resected specimen between both groups of patients. However, there were still a number of confounding factors, so the proposed hypothesis of getting less radiation exposure to the medical personnel by using a two-day approach should be further investigated.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela/métodos , Protocolos Clínicos , Feminino , Humanos , Injeções , Pessoa de Meia-Idade , Radioisótopos/administração & dosagem , Cintilografia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA