Luisa F. Martínez de Haro

Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett's esophagus.

ObjectiveTo compare the results of medical treatment and antireflux surgery in patients with Barrett’s esophagus (BE). Summary Background DataThe treatment of choice in BE is still controversial. Some clinical studies suggest that surgery could be more effective than medical treatment in preventing BE from progressing to dysplasia and adenocarcinoma. However, data from prospective comparative studies are necessary to answer this question. MethodsOne hundred one patients were included in a randomized prospective study, 43 with medical treatment and 58 with antireflux surgery. All patients underwent clinical, endoscopic, and histologic assessment. Functional studies were performed in all the operated patients and in a subgroup of patients receiving medical treatment. The median follow-up was 5 years (range 1–18) in the medical treatment group and 6 years (range 1–18) in the surgical treatment group. ResultsSatisfactory clinical results (excellent to good) were achieved in 39 of the 43 patients (91%) undergoing medical treatment and in 53 of the 58 patients (91%) following antireflux surgery. The persistence of added inflammatory lesions was significantly higher in the medical treatment group. The metaplastic segment did not disappear in any case. Postoperative functional studies showed a significant decrease in the median percentage of total time with pH below 4, although 9 of the 58 patients (15%) showed pathologic rates of acid reflux. High-grade dysplasia appeared in 2 of the 43 patients (5%) in the medical treatment group and in 2 of the 58 patients (3%) in the surgical treatment group. In the latter, both patients presented with clinical and pH-metric recurrence. There was no case of malignancy after successful antireflux surgery. ConclusionsThese results show that there are no differences between the two types of treatment with respect to preventing BE from progressing to dysplasia and adenocarcinoma. However, successful antireflux surgery proved to be more efficient than medical treatment in this sense, perhaps because it completely controls acid and biliopancreatic reflux to the esophagus.

Flow cytometric DNA analysis and p53 protein expression show a good correlation with histologic findings in patients with barrett's esophagus

There is a considerable degree of subjectivity and, therefore, substantial interobserver and intraobserver disagreement in the diagnosis and grading of dysplastic lesions in Barretts esophagus (BE). The aim of this study was to evaluate the usefulness of DNA flow cytometry and immunohistochemical staining for p53 protein as objective methods to complement the conventional histologic diagnosis of dysplasia in patients with this disease. The most common problems and the possible advantages of using these procedures are analyzed briefly in this article.

Very Long-term Objective Evaluation of Heller Myotomy Plus Posterior Partial Fundoplication in Patients With Achalasia of the Cardia

Objective:To present the objectively assessed very long-term results of a prospective study of 149 patients with achalasia of the cardia who underwent Heller myotomy and posterior partial fundoplication. Summary Background Data:Very few studies evaluate objectively the very long-term results to analyze whether the effectiveness of Heller myotomy is maintained with the passing of time. Methods:The study group consisted of 149 patients who underwent a Heller myotomy plus a posterior partial fundoplication through a laparotomy. The median follow-up was 6 years (range, 1–27 years). Follow-up period was over 10 years in 53 patients and over 15 in 36. Clinical, radiologic, endoscopic, manometric, and pHmetric evaluations were performed postoperatively. Results:Satisfactory results were higher than 90% up to 5 years. From that time on results gradually decreased to a 75% rate after 15 years (P < 0.001) due to either heartburn or dysphagia. Both the esophageal diameter and the mean resting pressure of the lower esophageal sphincter decreased postoperatively with no significant changes during follow-up. Esophagitis appeared in 11% of the patients (47% of them being asymptomatic) and 24-hour pH monitoring showed pathologic rates of acid reflux in 14% of patients, 58% of them being asymptomatic. Both esophagitis and pathologic rates of reflux appeared in >40% of the patients late in the follow-up. Conclusion:Results after Heller myotomy plus posterior partial fundoplication deteriorate with time, although we achieved a 75% of satisfactory results after >15 years of follow-up. Our study highlights the importance of life long follow-up and the objective assessment of the results.

Intestinal Metaplasia in Patients With Columnar Lined Esophagus is Associated With High Levels of Duodenogastroesophageal Reflux

ObjectiveTo evaluate the rate of duodenogastroesophageal reflux in patients with columnar lined esophagus compared with patients with gastroesophageal reflux disease without columnar lined esophagus, and to analyze whether it is related to the presence of specialized columnar epithelium in the metaplastic segment. Summary Background DataThe carcinomatous degeneration of columnar lined esophagus originates from a specialized columnar epithelium. The appearance of this metaplastic phenomenon is clearly related to severe prolonged gastroesophageal reflux, but only some of these patients finally develop columnar lined esophagus. For this reason other factors have been suggested, particularly the role played by the reflux of duodenal contents into the esophagus. MethodsThe authors studied 15 healthy volunteers (control group), 10 patients with reflux symptoms but without endoscopic lesions, 20 patients with reflux esophagitis without columnar lined esophagus, and 35 patients with columnar lined esophagus (complicated with ulcers or stenosis in 8 cases), of whom 22 had intestinal metaplasia. To assess the reflux of duodenal contents into the esophagus, all the patients underwent Bilitec 2000 and 24-hour esophageal pH monitoring. ResultsThe presence of bilirubin in the material refluxed into the esophagus was greater in the patients with columnar lined esophagus than in the rest of the groups. Likewise, duodenogastroesophageal reflux was greater in the columnar lined esophagus patients who had intestinal metaplasia. ConclusionsDuodenogastroesophageal reflux may play a major role in the development of columnar lined esophagus, especially in patients with intestinal metaplasia.

Barrett’s Esophagus Without Esophageal Stricture Does Not Increase the Rate of Failure of Nissen Fundoplication

ObjectiveTo assess whether the presence of Barrett’s esophagus (BE) modifies the results of Nissen fundoplication. Summary Background DataSome authors consider that BE, whether or not there is associated stricture, significantly increases the failure rate of standard antireflux surgery; they recommend using different and more aggressive surgical procedures in all patients with BE. MethodsOne hundred seventy-seven patients with gastroesophageal reflux disease, without esophageal stricture, were included in a retrospective study. Patients were divided into two groups: those with BE (n = 57) and those without BE (n = 120). Nissen fundoplication was performed in all patients by the same surgical team. Clinical, endoscopic, and functional (manometry and 24-hour pH monitoring) results in the two study groups were compared. ResultsAfter a median follow-up of 5 years (range 1–18) in the BE group and 6 years (range 1–18) in the non-BE group, the rate of clinical recurrence was 8% in the BE group and 10% in the non-BE group, with no statistically significant difference. The rate of pH-metric recurrence was the same in both groups (15%). ConclusionsThe presence of BE without esophageal stricture does not increase the rate of failure of Nissen fundoplication.

DNA Ploidy Status and Proliferative Activity as Markers of Malignant Potential in Barrett's Esophagus: Flow Cytometric Study Using Routinely Paraffin-embedded Tissue

Regular endoscopic surveillance is recommended for patients with Barretts esophagus to detect dysplasia and to diagnose carcinoma while it is in an early and possibly treatable stage. However, there are numerous unknown aspects regarding the natural history of dysplasia in this disease, and there is still a need for more accurate markers of risk of a malignant change. The aim of this study was to investigate the usefulness of DNA flow cytometry in Barretts esophagus to define subgroups of patients showing similar histologic findings but with a different malignancy potential. Routinely formalin-fixed and paraffin-embedded tissues of 43 patients with Barretts esophagus were processed for flow cytometric measurements (ploidy, proliferative index) and the results were compared with the histologic evolution observed in these patients. Only in the group of patients with “indefinite” dysplasia did we find statistically significant differences between the samples from patients with and without progression to more severe lesions (mean proliferative index of stable patients: 5.2% versus 8.3% in patients with progression, p= 0.001, Students t-test). The presence in the flow cytometric analysis of a DNA aneuploid cell line is closely related to the presence of severe histologic alterations (i.e., high-grade dysplasia: p < 0.001, Fishers exact test). Our results suggest that this procedure is at least capable of distinguishing between a real, although incipient, neoplastic process and morphologic changes of a reactive or reparative type. The increment in the tissue proliferative index could be an indicator of an early genomic instability which, with time, will develop into lesions with a more altered DNA content: aneuploidy.

Long-Term Follow-Up of Malignancy Biomarkers in Patients With Barrettʼs Esophagus Undergoing Medical or Surgical Treatment

Objective:This study aims to compare some validated biomarkers of malignancy (Ki-67, p53, and apoptosis) between 2 groups of patients with Barretts esophagus (BE) undergoing randomly medical or surgical treatment. Background:The treatment of choice to prevent the malignant progression of BE remains controversial. Translational studies using biomarkers associated with the metaplasia-tumor pathway could be useful to provide some information in this regard. Methods:The study group consisted of 45 patients: 20 under medical treatment with 40 mg/day of proton pump inhibitors (PPIs) and 25 after Nissen fundoplication (NFP). After a median follow-up of 8 years (range, 5–10 years), the values of Ki-67, p53, and apoptosis were analyzed in all patients before treatment (n = 45) and then 1 year (n = 45), 3 years (n = 45), 5 years (n = 45), and 10 years (n = 25) afterwards in both groups of treatment. These values were also analyzed in 2 subgroups of patients with successful medical and surgical treatment. Results:Both Ki-67 and p53 remained stable after NFP, whereas they increased progressively in patients under PPIs with statistically significant differences between the 2 groups. Conversely, the apoptotic index increased progressively after NFP and decreased in the patients under PPIs with significant differences at 3, 5, and 10 years of follow-up. On comparing the subgroups of successful treatment the same differences were found. Conclusions:Barretts epithelium remains more stable after a long-term follow-up in patients with BE treated surgically than in those under PPIs even in the absence of abnormal rates of acid reflux.

Resultados del cáncer de esófago resecado. Estudio comparativo entre el adenocarcinoma y el carcinoma epidermoide

Resumen Introduccion Algunos autores comunican mejores resultados en la supervivencia a largo plazo de los pacientes con adenocarcinoma (ADC) esofagico que con carcinoma epidermoide (CE). El objetivo de este trabajo ha sido comparar los resultados obtenidos tras reseccion esofagica en los pacientes con ADC y CE de esofago. Pacientes y metodo Se ha realizado un estudio retrospectivo en 231 pacientes con cancer esofagico y reseccion esofagica utilizando la tecnica de Ivor- Lewis en mas del 85% de los casos. Histologicamente, 120 pacientes padecian un ADC, mientras que se resecaron 111 CE. En cuanto a la epidemiologia, el CE mostraba una mayor relacion con el tabaco, el alcohol y los antecedentes de neoplasia laringea, mientras que un mayor numero de pacientes con ADC tenian antecedentes de reflujo gastroesofagico y diagnostico pre/postoperatorio de esofago de Barrett. Resultados La mortalidad postoperatoria fue superior en los pacientes con CE (n = 12; 12%) que en los de ADC (n = 6; 5%), sobre todo por complicaciones pulmonares y fistulas de las anastomosis. La estadificacion postoperatoria segun la clasificacion TNM no mostro diferencias significativas entre ambos grupos. La supervivencia media fue de 15 meses en el ADC y 13 meses en el CE, sin diferencias significativas. La tasa de probabilidad de supervivencia a 1, 3 y 5 anos fue similar en ambos grupos. En el grupo de pacientes con CE sobrevivieron el 66, el 25 y el 21%, respectivamente, mientras que en los pacientes con ADC estaban vivos el 68, el 25, y el 19% en los mismos intervalos de tiempo. Conclusion Aunque el ADC y el CE de esofago son neoplasias de distinta localizacion, epidemiologia y etiopatogenia, los similares resultados del tratamiento quirurgico a corto y largo plazo no justifican un manejo diferente para ambos tipos histologicos.

Standard antireflux operations in patients who have Barrett's esophagus. Current results.

Several therapeutic options exist for patients who have BE, and treatment should be individualized (Fig. 1). The best option in patients who have a high surgical risk or who reject surgery is lifelong conservative treatment, adjusting the PPI dosage with pH-metric controls. In patients who have a low surgical risk the best option is Nissen fundoplication. Only in cases in which esophageal shortening prevents a tension-free fundoplication from being done is a Collis gastroplasty associated with a fundoplication indicated. Other options may be indicated only in exceptional circumstances: (a) duodenal switch, when, after multiple failures with previous surgery, the approach to the esophagogastric junction is extremely difficult; and (b) esophageal resection, when there is a nondilatable esophageal stenosis and in cases in which the histologic study reveals the presence of high-grade dysplasia. Whatever treatment is used, an endoscopic surveillance program is mandatory, since, with the exception of total esophagectomy, no therapeutic option completely eliminates the risk for progression to adenocarcinoma.

[Epiphrenic diverticula: when and how to operate?].

Abstract The majority of epiphrenic diverticula arise due to a peristaltic mechanism caused by an oesophageal motor disturbance that establishes a barrier effect and causes mucosal and submucosal herniation through a weak point in the muscular layer. Intraluminal oesophageal manometry and video-radiology are important in assessing these patients, since they define the characteristics of the functional disorder, as well as the true relationship between the symptoms of the patient and the diverticulum. Surgical treatment is indicated in symptomatic patients, more so if there are respiratory complications. Left posterolateral thoracotomy followed by diverticulotomy, oesophageal cardiomyotomy, and anti-reflux have been considered the surgery technique of choice. Oesophageal myotomy must go beyond, in a proximal direction, the neck of the diverticulum, and, in a distal direction, must progress 1–2 cm into the gastric wall. The laparoscopic approach has won many followers since it has been shown to be both safe and effective as open surgery, adding to the advantages of minimally invasive surgery.