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1.
Strahlenther Onkol ; 190(12): 1133-40, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25015426

RESUMEN

PURPOSE: The purpose of this article is to report the outcome of neoadjuvant radiochemotherapy (N-RCT) + surgery in patients with squamous cell carcinoma of the esophagus at a single institution. METHODS: We retrospectively reviewed data from patients who were referred to our department for N-RCT. From 1988­2011, 103 patients were treated with N-RCT with cisplatin and/or 5-fluorouracil (5-FU). Group 1: (n = 55) from 1988­2006 with 39.6­40 Gy and 5-FU with (n = 17) or without cisplatin (n = 38). Group 2: from 2003­2010 with 44­45 Gy and 5-FU with (n = 40) or without cisplatin (n = 8). All patients underwent radical resection with reconstruction according to tumor location and 2-field lymph node dissection. The degree of histomorphologic regression was defined as grade 1a (pCR, 0 % residual tumor), grade 1b (pSTR, < 10 % residual tumor), grade 2 (10­50 % residual tumor), and grade 3 (> 50 % residual tumor). RESULTS: Median follow-up time from the start of N-RCT was 100 months (range 2­213 months). The median overall survival (OS) for the whole cohort was 42 months and the 5-year OS was 45 ± 5 %. In the multivariate analysis, worse ECOG performance status (p < 0.001), weight loss > 10 % before the start of the N-RCT (p = 0.025), higher pT category (p = 0.001), and grade 2/3 pathologic remission (p < 0.001) were significantly associated with a poor OS. PCR and pSTR rates for group 1 were 36 % and 18 % compared to 53 % and 22 % for group 2 (p = 0.011). There was a tendency for a better outcome in group 2 patients without statistical significance. The 5-year OS, disease-free survival and recurrent-free survival were 36 ± 7 %, 35 ± 6, and 36 ± 7 % for group 1 and 55 ± 7, 49 ± 7, and 53 ± 7 in group 2 (p = 0.117, p = 0.124, and p = 0.087). There was no significant difference between the two groups considering the postoperative morbidity and mortality. CONCLUSION: Higher radiation doses and more use of simultaneous cisplatin lead to higher pathologic response rates to N-RCT and may be associated with better survival outcomes. Prospective controlled trials are needed to assess the true value of intensified N-RCT regimens.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Quimioradioterapia Adyuvante/métodos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Tasa de Supervivencia , Cisplatino/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Estudios Longitudinales , Masculino , Dosificación Radioterapéutica , Estudios Retrospectivos , Resultado del Tratamiento
2.
Clin Gastroenterol Hepatol ; 9(3): 202-10, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21172455

RESUMEN

BACKGROUND & AIMS: There is controversy about the best way to treat esophageal anastomotic leakage. We evaluated the effects of treatment with self-expanding metal stents in patients with esophageal anastomotic leakage after esophagectomy or gastrectomy for cancer. METHODS: We investigated outcomes and procedure-related complications of 115 patients who received endoscopic stents for anastomotic leakage after esophagectomy or gastrectomy at a university hospital from 2004 to 2009. We also performed a systematic literature review on stent therapy and compared outcomes with that of other treatment regimens for esophageal anastomotic leakage. RESULTS: Among the 115 patients who received stents, the in-hospital mortality rate was 9% and complete anastomotic healing was achieved in 70% (95% confidence interval [CI], 64%-76%). Stent dislocation occurred in 53% of the patients (95% CI, 43%-62%), in all patients with esophagocolonostomy, in 61% with esophagojejunostomy, and in 49% with esophagogastrostomy. Three percent of patients (95% CI, 1%-5%) needed laparotomy to remove dislocated stents. Elective endoscopic stent removal was performed in 80% of the patients after a median of 54 days (range 17-427 d); 12% of these patients developed symptomatic anastomotic strictures after stent removal. CONCLUSIONS: Anastomoses completely heal in 70% of patients that receive endoscopic stents for anastomotic leakage after esophagectomy or gastrectomy. Stent therapy should be used in the management of patients with adequately perfused esophageal anastomotic leakage. However, stent dislocation remains a common problem after surgery.


Asunto(s)
Fuga Anastomótica/cirugía , Endoscopía/métodos , Stents/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/efectos adversos , Esofagectomía/efectos adversos , Gastrectomía/efectos adversos , Hospitales Universitarios , Humanos , Persona de Mediana Edad , Resultado del Tratamiento
3.
Neurogastroenterol Motil ; 33(8): e14164, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33960578

RESUMEN

BACKGROUND: Acetylcholine is the main excitatory neurotransmitter in the enteric nervous system (ENS) in all animal models examined so far. However, data for the human ENS is scarce. METHODS: We used neuroimaging using voltage and calcium dyes, Ussing chamber, and immunohistochemistry to study fast synaptic neurotransmission in submucosal plexus neurons of the human gut. KEY RESULTS: Electrical stimulation of intraganglionic fiber tracts led to fast excitatory postsynaptic potentials (fEPSPs) in 29 submucosal neurons which were all blocked by the nicotinic antagonist hexamethonium. The nicotinic agonist DMPP mimicked the effects of electrical stimulation and had excitatory effects on 56 of 73 neurons. The unselective NMDA antagonist MK-801 blocked fEPSPs in 14 out of 22 neurons as well as nicotine evoked spike discharge. In contrast, the application of NMDA showed only weak effects on excitability or calcium transients. This agreed with the finding that the specific NMDA antagonist D-APV reduced fEPSPs in only 1 out of 40 neurons. Application of AMPA or kainite had no effect in 41 neurons or evoked spike discharge in only one out of 41 neurons, respectively. Immunohistochemistry showed that 98.7 ± 2.4% of all submucosal neurons (n = 6 preparations, 1003 neurons) stained positive for the nicotinic receptor (α1 , α2 or α3 -subunit). Hexamethonium (200 µM) reduced nerve-evoked chloride secretion by 34.3 ± 18.6% (n = 14 patients), whereas D-APV had no effect. CONCLUSION & INFERENCE: Acetylcholine is the most important mediator of fast excitatory postsynaptic transmission in human submucous plexus neurons whereas glutamatergic fEPSPs were rarely encountered.


Asunto(s)
Neuronas/fisiología , Plexo Submucoso/fisiología , Transmisión Sináptica/fisiología , Acetilcolina/farmacología , Anciano , Estimulación Eléctrica , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen , Neuronas/efectos de los fármacos , Plexo Submucoso/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos
4.
Chirurg ; 92(6): 559-566, 2021 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-34009441

RESUMEN

BACKGROUND: During the first wave of the COVID-19 pandemic, the downregulation of all elective interventions during the period from 15 March 2020 to 15 May 2020 in Germany led to a decrease in operations. The impact on the number of specific operations in visceral surgery is so far unknown. METHODS: This retrospective study included 301 patients who underwent a cholecystectomy or appendectomy at a university hospital or a primary care facility between 15 March 2020 and 15 May 2020 (vs. 2018 and 2019). The number of cases and the clinical outcomes were analyzed. RESULTS: The suspension of elective surgery resulted in a significant reduction in elective cholecystectomy and emergency appendectomy. At the University Hospital the number of appendectomies decreased by 33% from 24 in 2018 to 16 in 2020 and the number of cholecystectomies declined by 57% from 30 in 2018 to 13 in 2020. At the primary care hospital, the number of appendectomy patients decreased by 48% from 23 in 2018 to 12 in 2020 and the number of cholecystectomies increased from the year 2018 to 2019 and subsequently declined by 30% in 2020. The duration of surgery, length of hospital stay and clinical course of patients did not significantly differ from the previous year time periods. CONCLUSIONS: During the first wave of the COVID-19 pandemic, the lockdown resulted in a significant reduction in frequently carried out visceral surgical interventions. In order to maintain the optimal medical care for the total population, current options for surgical and conservative treatment must be weighed against each other depending on the numbers of local infections and the individual comorbidities of the patients.


Asunto(s)
COVID-19 , Pandemias , Apendicectomía , Control de Enfermedades Transmisibles , Alemania , Humanos , Atención Primaria de Salud , Estudios Retrospectivos , SARS-CoV-2
5.
Langenbecks Arch Surg ; 395(4): 347-50, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20300770

RESUMEN

INTRODUCTION: For the better understanding of the pathophysiological events occurring in the sequence inflammation-metaplasia-carcinoma in esophageal adenocarcinoma, an animal model would be desirable. In the past, several rat models have been used yielding conflicting results. Some demonstrated a sequence similar to the human situation whereas others failed to initiate true esophageal adenocarcinoma or even Barrett's metaplasia. For the study of the molecular events involved in the carcinogenesis of Barrett's carcinoma, a mouse model would be much more promising since most of the genetically altered animals are mice. However, as of now no such model exists, in the past predominately due to the high mortality involved with the surgical procedure to create a mixed duodenogastric reflux. METHODS: Forty BALB-C mice weighing between 22 and 25 g underwent an esophagojejunostomy. The animals were sacrificed at 3, 4, and 5 months. Pathological evaluation was performed with HE staining. RESULTS: Overall mortality was 17%. However, mortality within the first ten animals was 30%. Reasons were technical problems with the anastomosis, opening of the pleural cavity, or bleeding events. All animals had a severe esophagitis regardless of the time. Intestinal metaplasia could be found in 60% of the animals after 4 months and esophageal adenocarcinoma in 55% after 5 months. One animal showed multiple lung metastases. CONCLUSION: After a certain learning curve esophagojejunostomy is feasible in mice with an acceptable mortality rate and leads to esophageal adenocarcinoma.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Esofágicas/cirugía , Esófago/cirugía , Yeyuno/cirugía , Anastomosis Quirúrgica , Animales , Modelos Animales de Enfermedad , Estudios de Factibilidad , Ratones , Ratones Endogámicos BALB C
6.
Sci Rep ; 10(1): 13791, 2020 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-32796868

RESUMEN

The pig is commonly believed to be a relevant model for human gut functions-however, there are only a few comparative studies and none on neural control mechanisms. To address this lack we identified as one central aspect mechanosensitive enteric neurons (MEN) in porcine and human colon. We used neuroimaging techniques to record responses to tensile or compressive forces in submucous neurons. Compression and stretch caused Ca-transients and immediate spike discharge in 5-11% of porcine and 15-24% of human enteric neurons. The majority of these MEN exclusively responded to either stimulus quality but about 9% responded to both. Most of the MEN expressed choline acetyltransferase and substance P; nitric oxide synthase-positive MEN primarily occurred in distal colon. The findings reveal common features of MEN in human and pig colon which we interpret as a result of species-independent evolutionary conservation rather than a specific functional proximity between the two species.


Asunto(s)
Colon/citología , Mucosa Intestinal/citología , Neuronas/citología , Estrés Mecánico , Adulto , Anciano , Anciano de 80 o más Años , Animales , Calcio/metabolismo , Células Cultivadas , Colina O-Acetiltransferasa/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Neuronas/fisiología , Óxido Nítrico Sintasa/metabolismo , Especificidad de la Especie , Sustancia P/metabolismo , Porcinos
7.
Neurogastroenterol Motil ; 32(2): e13748, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31612595

RESUMEN

BACKGROUND: Herbal medicinal products with a broad activity spectrum may be promising alternatives to treat functional gastrointestinal disorders (FGD). Menthacarin® is a drug with a fixed combination of peppermint and caraway oils, which is clinically used to treat FGD-associated symptoms. MATERIALS: We studied the effects of peppermint and caraway oils on contractile and secretory activity in 255 human small and large intestinal preparations derived from surgical resections (73 patients). Motility was recorded in circular smooth muscle strips and secretion with the Ussing chamber-voltage clamp technique. Electrical field stimulation evoked nerve induced contractile responses. KEY RESULTS: Peppermint and caraway oil concentrations dependently inhibited muscle contractility as indicated by sustained muscle relaxation and decrease in phasic contractility. These effects occurred in small and large intestinal preparations with IC50 values ranging between 17 and 90 µg/mL for peppermint oil and between 7 and 127 µg/mL for caraway oil. Neither peppermint nor caraway oil influenced the nerve evoked contractile response. The inhibition of contractile activity, but not the muscle relaxation, was prevented by the L-type calcium channel activator Bay K8644 but not by the neurotoxin tetrodotoxin. Both peppermint oil and caraway oil increased epithelial secretion, which remained in tetrodotoxin. CONCLUSION & INTERFERENCE: The findings revealed a strong muscle inhibitory and pro-secretory action of peppermint and caraway oils at clinically relevant concentrations. Both actions were nerve-independent. The inhibition of contractility was mediated by inhibition of L-type calcium channels. The effects on muscle and epithelial activity may contribute to the beneficial effects observed in patients with FGD.


Asunto(s)
Intestinos/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Aceites de Plantas/farmacología , Humanos , Mentha piperita , Técnicas de Cultivo de Órganos
9.
Clin Gastroenterol Hepatol ; 6(1): 53-61, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18166477

RESUMEN

BACKGROUND & AIMS: Neoadjuvant chemoradiotherapy has become a standard treatment of locally advanced rectal carcinomas, even though the responsiveness varies from complete response to resistance. The aim of the study was to evaluate the capacity of gene expression signatures to identify responders and nonresponders pretherapeutically. METHODS: By using microarray technology we generated gene expression profiles of 43 biopsy specimens of locally advanced rectal carcinomas. The transcription profile then was compared with histopathologic response and used to identify a set of genes discriminating responders from nonresponders. RESULTS: We identified a gene expression signature of 42 genes, mostly encoding proteins that either play a role in the nucleus, such as the transcription factor ETS2, or are associated with transport function, such as the solute carrier SLC35E1, or the regulation of apoptosis, such as caspase-1. In leave-one-out cross-validation the correct classification of a responder was 71%, the specificity of the analysis for a correct classification of a nonresponder was 86%. By applying an additional statistical method of 200 successive splittings into training and test data sets we generated an individual prediction accuracy measure for each predicted response. CONCLUSIONS: Our study shows that pretherapeutic prediction of response of rectal carcinomas to neoadjuvant chemoradiotherapy is feasible, and may represent a new valuable and practical tool of therapeutic stratification.


Asunto(s)
Carcinoma/genética , Carcinoma/terapia , Perfilación de la Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias del Recto/genética , Neoplasias del Recto/terapia , Adulto , Anciano , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Valor Predictivo de las Pruebas , Recto/patología , Sensibilidad y Especificidad , Factores de Transcripción/genética
10.
J Nucl Med ; 57(3): 367-71, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26585062

RESUMEN

UNLABELLED: In prostate cancer (PC) patients, the differentiation between lung metastases and lesions of different origin, for example, primary lung cancer, is a common clinical question. Herein, we investigated the use of Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ((68)Ga-PSMA-HBED-CC) for this purpose. METHODS: PC patients (n = 1,889) undergoing (68)Ga-PSMA PET/CT or PET/MR scans were evaluated retrospectively for suggestive lung lesions. For up to 5 lesions per patient, location, CT diameter, CT morphology, and SUVmax were determined. The standard for classification was either histopathologic evaluation or, in the case of PC metastases, responsivity to antihormone therapy. A comparison of the different classes was executed by Student t test. Prostate-specific antigen and prostate-specific membrane antigen (PSMA) immunohistochemistry were performed if histologic samples were available; (68)Ga-PSMA autoradiography was performed on an exemplary case of PET-positive lung cancer. RESULTS: Eighty-nine lesions in 45 patients were identified, of which 76 were classified as PC (39 proven, 37 highly probable), 7 as primary lung cancer, and 2 as activated tuberculosis; 4 lesions remained unclear. The mean SUVmax was 4.4 ± 3.9 for PC metastases and 5.6 ± 1.6 for primary lung cancer (P = 0.408). Additionally, substantial differences in SUVmax intraindividually were detected. The 2 tuberculous lesions showed an SUVmax of 7.8 and 2.5. Using immunohistochemistry, we could demonstrate PSMA expression in the neovasculature of several PSMA PET-positive lung cancers as well as in tuberculous lesions from our histologic database. CONCLUSION: Quantitative (SUV) analysis of (68)Ga-PSMA PET was not able to discriminate reliably between pulmonary metastases and primary lung cancer in PC patients. The reason for the unexpectedly high tracer uptake in non-PC lesions is not completely clear. PSMA expression in neovasculature provides a possible explanation for this finding; however, other contributing factors, such as tracer binding to proteins other than PSMA, cannot be excluded at present.


Asunto(s)
Ácido Edético/análogos & derivados , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/etiología , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/patología , Radiofármacos/farmacocinética , Anciano , Anciano de 80 o más Años , Autorradiografía , Diagnóstico Diferencial , Ácido Edético/síntesis química , Ácido Edético/farmacocinética , Radioisótopos de Galio , Humanos , Procesamiento de Imagen Asistido por Computador , Enfermedades Pulmonares/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos/síntesis química , Estudios Retrospectivos , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico por imagen
11.
Tumori ; 101(3): 263-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25908044

RESUMEN

AIMS AND BACKGROUND: The primary objective was to assess the different reasons for refusal of surgical resection (SR) in patients with esophageal squamous cell cancer (ESCC), who were initially planned for neoadjuvant radiochemotherapy (N-RCT) + SR, but SR was not performed after N-RCT. METHODS AND STUDY DESIGN: From 1988 to 2011, 311 patients with ESCC were treated with N-RCT in a tertiary referral center for esophageal diseases. Fifty-three patients were analyzed who received RCT with 40-45 Gy and concomitant chemotherapy in neoadjuvant intention, but in whom the treatment was stopped or switched to definitive RCT due to progression, patient decision, or new findings. RESULTS: The reasons for refusal of SR for these 53 patients were as follows: (1) patients' or physicians' preference for the planned treatment was changed during the N-RCT, such that RCT was continued to a curative dose without a break (group 1, n = 23, 44%); (2) patients were restaged after 4 weeks, and the tumor board decided to continue RCT because R0 resection was unlikely and/or patients were medically unfit (group 2, n = 15, 28%); (3) patients refused continuation of any treatment (group 3, n = 15, 28%). Refusal of SR was significantly more likely in patients with longitudinal tumor dimension >8 cm and those with an Eastern Cooperative Oncology Group performance status score of 2. Median follow-up time from the start of N-RCT was 57 months (range 1-137 months). The survival rates at 2 and 5 years were 36 ± 7% and 27 ± 7%, respectively. Group 1 had significantly longer survival. CONCLUSIONS: The planned N-RCT+SR could not be completed in a considerable number of patients in a tertiary referral center. More strict selection criteria for multimodality treatment including SR could spare some of these patients an incomplete treatment and probably lead to increased utilization of definitive RCT.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/terapia , Quimioradioterapia Adyuvante , Neoplasias Esofágicas/terapia , Esofagectomía , Terapia Neoadyuvante/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Quimioradioterapia Adyuvante/métodos , Cisplatino/administración & dosificación , Contraindicaciones , Toma de Decisiones , Supervivencia sin Enfermedad , Neoplasias Esofágicas/patología , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Radioterapia Conformacional , Estudios Retrospectivos , Resultado del Tratamiento , Negativa del Paciente al Tratamiento , Pérdida de Peso
12.
Ann Thorac Surg ; 73(1): 302-4, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11834036

RESUMEN

Perforating benign ulcer is a very rare complication of Barrett's esophagus. This report presents the management of a patient with a Barrett's ulcer that penetrated into the left mainstem bronchus resulting in a life-threatening bronchial esophageal fistula. This rare complication was successfully managed by using a staged surgical approach, which combined the principles used for treating benign esophagorespiratory fistulas and perforating Barrett's ulcers.


Asunto(s)
Esófago de Barrett/complicaciones , Fístula Bronquial/etiología , Fístula Esofágica/etiología , Perforación Intestinal/complicaciones , Úlcera Péptica/complicaciones , Anciano , Fístula Bronquial/diagnóstico , Fístula Bronquial/cirugía , Fístula Esofágica/diagnóstico , Fístula Esofágica/cirugía , Humanos , Masculino
13.
Mol Carcinog ; 45(10): 786-94, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16921482

RESUMEN

Expression of TGF-beta1, a major member of the TGF-beta superfamily and important promoter of tumor growth, was investigated in a series of primary resected esophageal (Barrett's) adenocarcinomas to establish its potential clinical significance and prognostic relevance in this entity. A series of 123 primary resected adenocarcinomas of the distal esophagus, arising in association with Barrett's esophagus, and corresponding normal squamous epithelium (n = 12) and non-malignant Barrett's mucosa (n = 11), were investigated by means of quantitative RT-PCR for expression of TGF-beta1, using paraffin embedded tissue samples. Gene expression levels were correlated with clinical parameters and overall survival. TGF-beta1 mRNA was expressed in all tumors, but relative gene expression levels varied largely among different tumors. The relative gene expression was significantly higher in tumor tissue compared to squamous epithelium (P = 0.005) and Barrett's mucosa (P=0.002), expressing only low amounts of TGF-beta1. Relative overexpression of the TGF-beta1 gene was associated with advanced UICC stage (III/IV vs. I/II; P = 0.009), depth of tumor infiltration (pT3 vs. pT1/2; P < 0.001), nodal involvement (pN1 vs. pN0; P = 0.006), and lymphatic vessel invasion (L1 vs. L0; P = 0.011). On univariate survival analysis, TGF-beta1 overexpression had a significant negative impact on survival (log rank test; P = 0.0255). However, the prognostic impact was not independent from other strong predictors of survival (pT, pN) on multivariate survival analysis. Our data show that TGF-beta1 overexpression is associated with advanced stage of esophageal adenocarcinoma and implies a negative impact on survival. The TGF-beta pathway may be a potential target for molecular therapies of advanced tumors of this entity.


Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/patología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica/genética , Factor de Crecimiento Transformador beta/genética , Adulto , Anciano , Anciano de 80 o más Años , Esófago de Barrett/genética , Esófago de Barrett/patología , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , Factor de Crecimiento Transformador beta1
14.
Ann Surg ; 241(1): 63-8, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15621992

RESUMEN

SUMMARY BACKGROUND DATA: Duodenogastric-esophageal reflux disease is directly linked to Barrett's esophagus and to the development of esophageal adenocarcinoma. Despite this link, little is known about the mutagenic potential of refluxed material on the esophageal mucosa. We hypothesize that the reflux of gastric and duodenal content causes mutations in esophageal mucosa in vivo. METHODS: Seven Sprague Dawley/Big Blue F1 lacI transgenic rats underwent esophagoduodenostomy (ED) to surgically create duodeno-gastric-esophageal reflux. Fourteen nonoperated rats served as negative (n = 7) and as positive (n = 7/methyl-N-amyl-nitrosamine [MNAN] intraperitoneally) controls. The animals were killed 16 weeks after operation or injection, the entire esophageal mucosa was harvested, and mutation frequency was determined through standard Big Blue Mutagenesis Assay. RESULTS: Gross esophagitis was evident in all operated animals. The frequency of lacI mutations in esophageal mucosal cells of animals with ED was significantly higher, nearly 1.5-fold, than that of nonoperated animals. Nitrosamine administration resulted in a nearly 20-fold increase of lacI mutation frequency. Thirteen mutations were successfully sequenced, 46% occurred at CpG dinucleotide sites and 61% were either C to T or G to A transitions. CONCLUSIONS: The data provide preliminary evidence of the mutagenic potential of bile reflux on esophageal epithelium. The specific mutations are markedly higher than would be expected by chance and are similar to that found in p53 mutations of human esophageal adenocarcinoma, providing a link to human esophageal cancer.


Asunto(s)
Adenocarcinoma/genética , Reflujo Duodenogástrico/genética , Neoplasias Esofágicas/genética , Esofagitis/genética , Esófago/patología , Adenocarcinoma/patología , Animales , Animales Modificados Genéticamente , Reflujo Duodenogástrico/complicaciones , Reflujo Duodenogástrico/patología , Neoplasias Esofágicas/patología , Esofagitis/etiología , Esofagitis/patología , Mucosa Intestinal/patología , Operón Lac/genética , Ratones , Modelos Animales , Mutación , Ratas , Ratas Endogámicas F344 , Ratas Sprague-Dawley
15.
Eur Radiol ; 14(7): 1188-95, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15083335

RESUMEN

The use of multiplanar reconstructions (MPRs) generated from multislice spiral CT (MSCT) data sets in the preoperative assessment of vascular invasion in pancreatic cancer was evaluated. Forty patients underwent biphasic high-resolution MSCT prior to surgery for pancreatic head cancer. Image reconstruction included thin-slice axial, sagittal and coronal MPRs as well as an MPR perpendicular to the course of a major peripancreatic vessel in proximity to the tumor. CT criteria for vascular invasion were: (1) circumferential involvement >180 degrees and (2) vessel narrowing. Imaging findings of 52 vessels were correlated with surgical and histopathological reports. Regarding the CT criterion circumferential involvement, vascular invasion was demonstrated on axial MPRs with a sensitivity and specificity of 58 and 97%. For the assessment with coronal and sagittal MPRs sensitivity was only 47%. Vascular invasion was recognized best on perpendicular MPRs with a sensitivity, specificity and accuracy of 74, 97 and 88%, respectively. Vessel narrowing was a less reliable CT criterion for vascular invasion, mainly due to the lower specificity of 91% obtained with each available MPR. Thin-slice MPRs oriented perpendicularly to a possibly invaded vessel exactly depict the grade of circumferential involvement and thus have the capability to improve the assessment of vascular invasion in pancreatic cancer.


Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Venas Mesentéricas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Vena Porta/diagnóstico por imagen , Tomografía Computarizada Espiral , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Venas Mesentéricas/patología , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Pancreáticas/patología , Vena Porta/patología , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
16.
World J Surg ; 28(7): 675-9, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15175900

RESUMEN

Angiogenesis is essential for tumor growth and metastasis. An association between microvessel density, a measure of tumor angiogenesis, and conventional prognostic variables has been shown for many tumor entities. For Barrett's carcinoma, the results are controversial. Immature vessels formed in tumors are structurally and functionally different from those in mature vessels. The relation between mature and immature vessels as a prognostic factor for Barrett's carcinoma has not been assessed. Specimens from 45 R0-resected Barrett's carcinomas were immunostained for vascular endothelial growth factor (VEGF), CD 31, and smooth muscle alpha-actin to discriminate between mature and immature vessels. VEGF staining was evaluated quantitatively by measuring optical density with a new computer-based program and expressed as a percentage of the staining (juvenile placental tissue) on control slides. The neovascularization coefficient (i.e., the relation between mature and immature vessels) was estimated with an interactive analytic computer program. The median survival of the study group was 45.7 months. The neovascularization coefficient correlated with the histopathologic classification ( p < 0.001). Survival time in patients with a low neovascularization coefficient was significantly better than the survival time in patients with a high neovascularization coefficient ( p = 0.021). VEGF expression did not correlate with clinicopathologic data ( p > 0.05) or with patient survival ( p > 0.05). The tumors with a high neovascularization coefficient did not have significantly elevated VEGF expression. Based on a strong quantitative computer evaluation program, the present study indicates that neovascularization has an important impact on the survival of patients with Barrett's carcinoma. However, VEGF does not appear to be the vascular growth factor stimulating neovascularization in Barrett's carcinoma patients.


Asunto(s)
Adenocarcinoma/metabolismo , Esófago de Barrett/complicaciones , Neoplasias Esofágicas/metabolismo , Neovascularización Patológica , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/etiología , Adenocarcinoma/mortalidad , Anciano , Neoplasias Esofágicas/irrigación sanguínea , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/mortalidad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia
17.
Ann Surg ; 235(3): 346-54, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11882756

RESUMEN

OBJECTIVE: To quantitate and characterize the motility abnormalities present in patients with epiphrenic diverticula and to assess the outcome of surgical treatment undertaken according to these abnormalities. SUMMARY BACKGROUND DATA: The concept that epiphrenic diverticula are complications of esophageal motility disorders rather than primary anatomic abnormalities is gradually becoming accepted. The inconsistency in identifying motility abnormalities in patients with epiphrenic diverticula is a major obstacle to the general acceptance of this concept. METHODS: The study population consisted of 21 consecutive patients with epiphrenic diverticula. All patients underwent videoesophagography, upper gastrointestinal endoscopy, and esophageal motility studies. The diverticula ranged in size from 3 to 10 cm and were predominantly right-sided. Seventeen patients underwent transthoracic diverticulectomy or diverticulopexy with esophageal myotomy and an antireflux procedure. The length of the myotomy was determined by the extent of the motility abnormality. Transhiatal esophagectomy was performed in one patient with multiple diverticula. Two patients declined surgical treatment and another patient died of aspiration before surgery. Symptomatic outcome was assessed via a questionnaire at a median of 24 months after surgery. RESULTS: The primary symptoms were dysphagia in 5 (24%) patients, dysphagia and regurgitation in 11 (52%) patients, and pulmonary symptoms in 5 (24%) patients. The median duration of the primary symptoms was 10 years. Esophageal motility abnormalities were identified in all patients. An esophageal motor disorder was diagnosed only by 24-hour ambulatory motility testing in one patient, and 24-hour ambulatory motility testing clarified the motility diagnosis in five other patients. The most common underlying disorder was achalasia, which was detected in nine (43%) patients. A hypertensive lower esophageal sphincter was diagnosed in three patients, diffuse esophageal spasm in five, "nutcracker" esophagus in two, and a nonspecific motor disorder in two patients. One patient had an intraoperative myocardial infarction and died. Two patients had persistent mild dysphagia after surgery. The remaining patients had complete relief of their primary symptoms. CONCLUSIONS: There is a high prevalence of named motility disorders in patients with epiphrenic diverticula, and this condition is associated with the potential for lethal aspiration. Twenty-four-hour ambulatory motility testing can be helpful if the results of the stationary examination are normal or indefinite. Resection of the diverticula and a surgical myotomy of the manometrically defined abnormal segment results in relief of symptoms and protection from aspiration.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Divertículo Esofágico/etiología , Divertículo Esofágico/cirugía , Trastornos de la Motilidad Esofágica/complicaciones , Anciano , Anciano de 80 o más Años , Divertículo Esofágico/fisiopatología , Trastornos de la Motilidad Esofágica/fisiopatología , Femenino , Humanos , Masculino , Manometría , Persona de Mediana Edad
18.
Dig Dis Sci ; 48(6): 1057-61, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12822862

RESUMEN

The purpose of this study was to evaluate the interindividual and intraindividual variability of slow motorized pull-through lower esophageal sphincter (LES) manometry compared to standard station pull-through LES manometry to measure LES overall length, abdominal length, and pressure and to report normal values for the slow motorized pull-through method. The slow motorized pull-through had significantly smaller coefficient of variation, indicating closer agreement between different examiners in analyzing a given tracing. The correlation coefficients for each parameter in normal subjects and symptomatic patients was significantly higher when using slow motorized pull-through for both patients and normal subjects for all three parameters. The 5th percentile of normal values obtained from 41 volunteers for LES overall length, abdominal length, and pressure was 2.7 cm, 1.4 cm, 5.1 mm Hg, respectively. The results indicate that the slow motorized pull-through method is more reproducible than the standard station pull-through method both between different observers and when the same examiner measures the same tracing on two different occasions.


Asunto(s)
Unión Esofagogástrica/fisiopatología , Manometría/métodos , Adulto , Femenino , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/fisiopatología , Humanos , Masculino , Variaciones Dependientes del Observador , Valores de Referencia
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