Three-dimensional endoscopic ultrasound of the esophagus

Background: The aim of this study was to develop a technique for three-dimensional endoscopic ultrasound of the esophagus based on standard ultrasonic images. Methods: Endoscopic ultrasound was performed in five esophageal cancer patients using a high-resolution miniprobe (360°, 12.5 MHz). For acquisition of three-dimensional data sets, the miniprobe was attached to a stepping motor that enabled ECG-triggered withdrawal of the transducer. Three-dimensional images were reconstructed from serial transverse sections on a PC-based 3D work station. Results: Twelve volume scans were obtained in five patients with esophageal cancer. The system enabled the acquisition of accurate three-dimensional ultrasound data within 30– 50 s. Computed image processing allowed us to display the data in transverse, longitudinal, and oblique sections, or as a 3D reconstruction. Three-dimensional imaging provided accurate visualization of the tumor and surrounding structures in all cases. The tumor stage was determined correctly in four of five patients. Longitudinal scan planes and 3D views improved the assessment of longitudinal tumor infiltration and the spatial relation of the tumor to relevant mediastinal structures. Conclusion: This study shows that three-dimensional endoscopic ultrasound of the esophagus is technically feasible. The technique allows the assessment of local tumor spread in previously unattainable scan planes and 3D views. This promising preliminary experience should encourage further exploration of this method.     

Inhibition by halothane,but not by isoflurane,of oxidative response to opsonized zymosan in whole blood

In an attempt to clarify some apparent discrepancies in reports of the effects of anesthetic agents upon granulocyte function, we studied the effects of halothane and isoflurane, using techniques that allowed us to perform the assays in whole blood and in sealed vials to prevent volatile gas evolution; assay gas concentrations were measured, rather than inferred. Chemiluminescence, superoxide production, and hydrogen peroxide production were assessed after presentation of opsonized zymosan as a phagocytic stimulus. Incubation with halothane led to a highly statistically significant dose-related inhibition of Chemiluminescence (maximum 66%), H₂O₂ production (67%) and ·O ₂ ^– production (61%), within the concentration range observed in blood from patients undergoing general anesthesia. In contrast, the presence of isoflurane led to no statistically significant changes in any of the functions measured. Cells harvested from patients undergoing elective halothane anesthesia showed the same functional inhibition, but for quantitative differences likely due to the inability to control for dilution effects in clinical samples. It has been suggested that halothane anesthesia may be associated with excess mortality in septic patients; although the results we report are readily reversible, their presence during a prolonged anesthesia could be harmful in a patient who is not immunologically normal and/or who is already infected. Careful clinical trials will be necessary to determine if isoflurane is a superior agent in this context.     

Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases

Comparative genomic hybridization (CGH) was used to screen 54 advanced colon carcinomas. i.e., 24 primary tumors and 30 metastases, for chromosomal alterations. Using a sensitive statistical method for the determination of DNA imbalances and histograms for analysis of the incidence of changes, we identified the DNA over-representation of chromosome 20q as the most common alteration being present in 100% of cases. High incidence deletions were observed on 18q21-18q23 (96%), 4q27-4q28 (96%), 4p14 (87%), 5q21 (81%), 1p21-1p22 (72%), 21q21 (74%), 6q16 (72%), 3p12 (66%), 8p24-8p21 (66%), 9p21 (64%), 11q22 (64%), and 14q13-14q21 (64%). Further frequent over-representation was found on 7q12-7q11.2 (75%), 16p11-16p12 (70%), 19p13 (70%), 9q34 (67%), 19q13 (67%), 13q34 (64%), 13q13 (64%), 17q21 (59%), 22q11 (61%), 8q24 (57%), and 1q21 (57%). Pronounced DNA gains and losses being defined as regions in which the ratio profiles exceeded the values of 1.5 and 0.5, respectively, frequently colocalized with peaks of incidence curve. The use of difference histograms for the comparison of tumor subgroups as well as case-by-case histogram for the analysis of 15 paired tumor samples identified several of the above alterations as relevant for tumor progression and metastasis formation. The study identified additional loci and delineates more precisely those that have been previously reported. For comparative purposes, we have made our primary data (ratio profiles, clinicopathological parameters, histograms) available at the interactive web site http://amba.charite.de/cgh, where the incidence of changes can be determined at individual loci and additional parameters can be applied for the analysis of our CGH results.     

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Near-infrared fluorescent dyes for enhanced contrast in optical mammography: phantom experiments

Optical mammography with near-infrared (NIR) light using time-domain, frequency-domain, or continuous-wave techniques is a novel imaging modality to locate human breast tumors. By investigating excised specimens of normal and diseased mamma tissue we were able to demonstrate that differences in their scattering properties are a poor predictive parameter for normal and diseased mamma tissue. This paper describes the application of a NIR dye to improve the differentiation between breast tumors and normal tissue in a rat model. The NIR dye furnished a high tumor-to-tissue contrast ratio (6:1) in fluorescence images. Furthermore, this dye was used to develop liquid scattering phantoms with absorbing and fluorescent inhomogeneities. Using frequency-domain and time-domain instrumentation these inhomogeneities were localized at sufficient contrast by their increased absorption and fluorescence. Contrast between inhomogeneities and surrounding medium could be improved by combining fluorescence and transmittance images.     

Reconstruction after gastrectomy and quality of life

To evaluate quality of life and functional results following surgery for gastric cancer we studied 104 patients with no evidence of disease at a minimum of 12 months postoperatively. Patients were treated with total gastrectomy and jejunal pouch reconstruction according to Hunt-Lawrence-Rodino (n=59) or simple esophagojejunostomy (n=24) and distal subtotal gastrectomy (n=21). No significant differences were found between total gastrectomy with pouch reconstruction and distal gastric resection with respect to dumping or heartburn, whereas patients with total gastrectomy and restoration with esophagojejunostomy suffered from both. The latter group of patients also had reduced nutritional status. Although there is a lack of a proper definition of quality of life, all instruments applied to its measurement indicated improved results for patients with pouch reconstruction and those after distal gastrectomy, but we could not state any significant differences. We conclude that in terms of postoperative functional results as well as quality of life distal gastric resection has no advantage over total gastrectomy with pouch reconstruction; hence a reduction of surgical radicality in an attempt to improve postoperative results is not justified. Pouch reconstruction should be considered the treatment of choice for reconstruction after total gastrectomy.

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Resumen Con miras a evaluar la calidad de la vida y los resultados funcionales luego de cirugía por cáncer gástrico, estudiamos 104 pacientes que se encontraban libres de enfermedad a un mínimo de 12 meses postoperatorios. Los pacientes fueron tratados con gastrectomía total y reconstrucción con una bolsa yeyunal de tipo Hunt-Lawrence-Rodino (n=59) o simple esofagoyeyunostomía (n=24) y gastrectomía subtotal distal (n=21). No se encontraron diferencias significantivas entre los pacientes sometidos a gastrectomía total con reconstrucción con bolsa yeyunal y los sometidos a resección distal con respecto a dumping o pirosis, en tanto que los pacientes sometidos a gastrectomía total y restauración mediante esofagoyeyunostomía exhibieron ambos síntomas. Además, los últimos desarrollaron deterioro de su estado nutricional. Aparte de la falta de una adecuada definición de calidad de la vida, todos los parámetros aplicados para su medición demostraron mejores resultados en los casos de gastrectomía total con reconstrucción con bolsa yeyunal y en los casos de gastrectomía distal, pero sin que pudiéramos hallar diferencias significativas. Nuestra conclusión es que en términos de los resultados funcionales postoperatorios así como de calidad de la vida, la resección gástrica distal no tiene ventaja sobre la operación con reconstrucción con bolsa yeyunal y que no se justifica una reducción de la radicalidad quirúrgica con el objeto de mejorar los resultados postoperatorios. La reconstrucción con bolsa yeyunal debe ser considerada como el procedimiento de elección en la gastrectomía total.

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Résumé Afin d'évaluer la qualité de vie et les résultats fonctionnels après chirurgie pour cancer gastrique, nous avons étudié 104 patients qui semblaient guéris à 12 mois. Les patients ont eu soit une gastrectomic totale suivie ou de la confection d'un néogastre jéjunal selon le procédé de Hunt-Lawrence-Rodino (n=59) ou une simple anastomose oesojéjunale (n=24), soit d'une gastrectomie distale subtotale (n=21). Il n'y avait aucune différence significantive entre la gastrectomie totale suivie de reconstruction par néogastre et la gastrectomie distale subtotale en ce qui concerne le dumping syndrome ou le reflux, alors que les patients qui avaient eu une gastrectomie totale suivie d'anastomose oesojéjunale avaient les deux. Chez ces derniers, on a également noté une certaine malnutrition. En dépit du manque de définition précise de la qualité de vie, tous les moyens utilisés pour la mesurer ont indiqué um meilleur résultat pour les patients ayant eu une reconstruction avec néogastre par rapport à la gastrectomie distale, sans toutefois atteindre la signification statistique. Nous concluons qu'en terme de résultats fonctionnels postopératoires ainsi que de la qualité de vie, la gastrectomie distale ne présente aucun avantage par rapport à la gastrectomie totale suivie de néogastre, et une réduction dans l'importance de l'intervention pour améliorer les résultats fonctionnels n'est pas justifiée. La confection d'un néogastre doit être la méthode de reconstruction de choix après gastrectomie totale.

     

Leukocyte activation by isolated hyperthermic liver and limb perfusion due to malignancy

Fourteen patients with liver tumor malignancy and sixteen patients with malignant melanoma localized to one limb were studied regarding leukocyte activation with the release of polymorphonuclear neutrophilic (PMN) elastase and of neopterin and formation of cytokines (TNF- and Il-6) during the surgical treatment. Patients undergoing liver resection (n=10), abdominal hysterectomy (n=10), or hip replacement surgery (n=10) served as control groups. Isolated hyperthermic liver perfusion was performed with cytostatic-containing perfusate (melphalan and cisplatinum). Patients with recurrent malignant melanoma confined to one limb underwent isolated hyperthermic limb perfusion with cytostatic-containing perfusate (melphalan). Blood samples for determination of PMN elastase, neopterin, TNF-, and IL-6 were drawn from the patients preoperatively, 1 minute before the start of the perfusion, 60 and 120 minutes after the start of the perfusion, and 24 hours postoperatively. Samples from the perfusate were drawn 60 minutes after the start of the perfusion. High concentrations of plasma PMN clastase were found both in patients undergoing liver and limb perfusion and in patients undergoing liver resection surgery. Elevated concentrations of Il-6 were found in the patients undergoing liver perfusion and in patients undergoing liver resection. In none of the patients were there increased concentrations of neopterin or TNF-. The perfusate contained high concentrations of PMN elastase, neopterin, and IL-6. This study also demonstrated that major surgery leads to elevated concentrations of PMN elastase and IL-6. An increase of PMN elastase and IL-6 was seen in response to perfusion and to surgical trauma.

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Resumen Catorce pacientes con tumores malignos del hígado y 16 pacientes con melanoma maligno localizado en una extremidad fueron estudiados en relación con la activación de leucocitos con liberación de elastasa de PMN y de neopterina y la formación de citocinas (FNT- e IL-6) en el curso del tratamiento quirúrgico. Pacientes sometidos a resección del hígado (n=10), histerectomía abdominal (n=10) y reemplazo de cadera (n=10) sirvieron como grupos control. Se realizó perfusión hipertérmica aislada del hígado con perfusato citostácico (melfalán y cisplatino). Los pacientes con melanoma maligno recurrente confinado a una extremidad fueron sometidos a perfusión hipertérmica aislada de la extremidad con perfusato citostácico (melfalán). Se tomaron muestras de sangre para determinación preoperatoria de elastasa de PMN, neopterina, FNT- e IL-6, un minuto antes de comenzar la perfusión, 60 y 120 minutos después del comienzo de la perfusión y 24 horas después de la operación. Se tomaron muestras del perfusato a los 60 minutos luego del comienzo de la perfusión. Se encontraron altas concentraciones de elastasa de PMN tanto en los pacientes sometidos a perfusión hepática o de la extremidad, como en los pacientes sometidos a resección hepática. Se encontraron concentraciones elevadas de IL-6 en los pacientes sometidos a perfusión hepática y en los pacientes sometidos a resección del hígado. En ningún paciente se encontraron concentraciones aumentadas de neopterina o de FNT-. El perfusato contenía altas concentraciones de elastasa de PMN, neopterina e IL-6. Se encontró un aumento en la elastasa de PMN y en la IL-6 en respuesta a la perfusión y al trauma quirúrgico.

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Résumé Quatorze patients ayant une tumeur maligne du foie et 16 patients ayant un mélanome malin localisé à une extrémité ont été étudiés en ce qui concerne l'activation des leucocytes associée à un relargage d'élastase PMN et de néoptérine ainsi que la formation de cytokinines (TNF- et IL-6) pendant le traitement chirurgical. Trente patients avant eu soit une résection hépatique (n=10), soit une hystérectomie abdominale (n=10) ou une prothèse de hanche (n=10) ont servi de témoins. On a perfusé le foie avec un perfusât de cytostatiques (mélphalane et cis-platine). Les patients ayant un mélanome malin d'une extrémité ont eu une perfusion isolée hyperthermique avec une perfusion de cytostatique (mélphanane). Des échantillons du sang ont été retirés pour déterminer les taux d'élastase PMN, de la néoptérine, du TNF-, et de l'IL-6 en préopératoire, une minute avant le début de la perfusion, 60 et 120 minutes après le début de la perfusion, et 24 heures postopératoirement. Des échantillons ont été retirés 60 minutes après le début de la perfusion. Des concentration élevées d'élastase PMN ont été retrouvées à la fois chez les patients ayant une perfusion hépatique et de l'extrémité et chez les patients ayant eu une résection du foie. Des concentration élevées en IL-6 ont été retrouvées chez le patient ayant une perfusion du foie et chez le patient ayant une résection hépatique. Les concentrations en néoptérine et en TNF- n'étaient pas élevées. Le liquide de perfusion contenait des concentrations élevées en élastase PMN, néoptérine et en IL-6. Cette étude démontre aussi que la chirurgie majeure est associée avec des concentrations élevées en PMN elastase et IL-6. Une augmentation en PMN-élastase et en IL-6 a été retrouvée en réponse à la perfusion et au traumatisme chirurgical.