Owen Korn

Long-term results of classic antireflux surgery in 152 patients with Barrett's esophagus : Clinical, radiologic, endoscopic, manometric, and acid reflux test analysis before and late after operation

BACKGROUND The classic surgical procedure for patients with Barretts esophagus (BE) has been either Nissen fundoplication or posterior gastropexy with calibration of the cardia. METHODS The purpose of our study was to determine late subjective and objective results of these classic surgical techniques in a large number of patients with BE. A total of 152 patients were included in this prospective protocol. RESULTS There was 1 death (0.7%) after operation. The late follow-up of 100 months demonstrated a high percentage of failures among patients with noncomplicated BE (54%) and an even higher figure in patients with complicated BE (64%). In 15 patients low grade dysplasia appeared at 8 years of follow-up and an adenocarcinoma in 4 patients. Twenty-four-hour pH monitoring demonstrated a decrease in acid reflux into the esophagus, and Bilitec studies also demonstrated a decrease of duodenoesophageal reflux, but in all cases with a higher value than the normal limit. CONCLUSIONS Classic antireflux surgery in patients with BE results in a high percentage of failures at very late follow-up because it cannot completely avoid acid and duodenal reflux into the esophagus.

Very late results of esophagomyotomy for patients with achalasia: clinical, endoscopic, histologic, manometric, and acid reflux studies in 67 patients for a mean follow-up of 190 months.

Introduction:Laparoscopic esophagomyotomy is the preferred approach to patients with achalasia of the esophagus, However, there are very few long-term follow-up studies (>10 years) in these patients. Objective:To perform a very late subjective and objective follow-up in a group of 67 patients submitted to esophagomyotomy plus a partial antireflux surgery (Dors technique). Material and Methods:In a prospective study that lasted 30 years, 67 patients submitted to surgery were divided into 3 groups: group I followed for 80 to 119 months (15 patients); group II, with follow-up of 120 to 239 months (35 patients); and group III, with follow-up more than 240 months (17 patients). They were submitted to clinical questionnaire, endoscopic evaluation, histologic analysis, radiologic studies, manometric determinations, and 24-hour pH studies late after surgery. Results:Three patients developed a squamous cell esophageal carcinoma 5, 7, and 15 years after surgery. At the late follow-up, Visick III and IV were seen in 7%, 23%, and 35%, according to the length of follow-up of each group. Endoscopic examination revealed a progressive nonsignificant deterioration of esophageal mucosa, histologic analysis distal to squamous-columnar junction showed a significant decrease of fundic mucosa in patients of group III, with increase of intestinal metaplasia, although not significant time. Lower esophageal sphincter showed a significant decrease of resting pressure 1 year after surgery, which remained similar at the late control. There was no return to peristaltic activity. Acid reflux measured by 24-hour pH studies revealed a progressive increase, and the follow-up was longer. Nine patients developed Barrett esophagus: 6 of them a short-segment and 3 a long-segment Barrett esophagus. Final clinical results in all 67 patients demonstrated excellent or good results in 73% of the cases, development of epidermoid carcinoma in 4.5%, and failures in 22.4% of the patients, mainly due to reflux esophagitis. Incomplete myotomy was seen in only 1 case. Conclusion:In patients with achalasia submitted to esophagomyotomy and Dors antireflux procedure, there is a progressive clinical deterioration of initially good results if a very long follow-up is performed (23 years after surgery), mainly due to an increase in pathologic acid reflux disease and the development of short- or long-segment Barrett esophagus.

Enhancement in liver SREBP-1c/PPAR-α ratio and steatosis in obese patients: Correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion

Sterol receptor element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) mRNA expression was assessed in liver as signaling mechanisms associated with steatosis in obese patients. Liver SREBP-1c and PPAR-alpha mRNA (RT-PCR), fatty acid synthase (FAS) and carnitine palmitoyltransferase-1a (CPT-1a) mRNA (real-time RT-PCR), and n-3 long-chain polyunsaturated fatty acid (LCPUFA)(GLC) contents, plasma adiponectin levels (RIA), and insulin resistance (IR) evolution (HOMA) were evaluated in 11 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 8 non-obese subjects who underwent laparoscopic cholecystectomy (controls). Liver SREBP-1c and FAS mRNA levels were 33% and 70% higher than control values (P<0.05), respectively, whereas those of PPAR-alpha and CPT-1a were 16% and 65% lower (P<0.05), respectively, with a significant 62% enhancement in the SREBP-1c/PPAR-alpha ratio. Liver n-3 LCPUFA levels were 53% lower in obese patients who also showed IR and hipoadiponectinemia over controls (P<0.05). IR negatively correlated with both the hepatic content of n-3 LCPUFA (r=-0.55; P<0.01) and the plasma levels of adiponectin (r=-0.62; P<0.005). Liver SREBP-1c/PPAR-alpha ratio and n-3 LCPUFA showed a negative correlation (r=-0.48; P<0.02) and positive associations with either HOMA (r=0.75; P<0.0001) or serum insulin levels (r=0.69; P<0.001). In conclusion, liver up-regulation of SREBP-1c and down-regulation of PPAR-alpha occur in obese patients, with enhancement in the SREBP-1c/PPAR-alpha ratio associated with n-3 LCPUFA depletion and IR, a condition that may favor lipogenesis over FA oxidation thereby leading to steatosis.

Open transthoracic or transhiatal esophagectomy versus minimally invasive esophagectomy in terms of morbidity, mortality and survival.

BackgroundSurgical treatment of esophageal cancer is associated with a high rate of morbidity and mortality even in specialized centers. Minimally invasive surgery has been proposed to decrease these complications.MethodsThe authors present their results regarding postoperative complications and the survival rate at 3 years, comparing the classic open procedures (transthoracic or transhiatal esophagectomy) with minimally invasive surgery. Surgical procedures were performed according to procedures published elsewhere.ResultsThe study enrolled 166 patients who underwent surgery between 1990 and 2003. Open transthoracic surgery was performed for 60 patients. In this group of patients, postoperative mortality was observed in 11% of the cases. Major, minor, and late complications were observed in 61.6% of the patients, and the 3-year survival rate was 30% for this group. Open transhiatal surgery was performed for 59 patients. The morbidity, mortality, and 3-year rate were almost the same as for the transthoracic surgery group. For the 47 patients submitted to minimally invasive procedures (thoracoscopic and laparoscopic), the complications and mortality rates were significantly reduced (38.2% and 6.4%, respectively). For the patients submitted to minimally invasive surgery, the 3-year survival rate was 45.4%. It is important to clarify that the patients submitted to minimally invasive surgery manifested early stages of the diseases, and that this the reason why the morbimortality and survival rates were better.ConclusionsThe transthoracic and transhiatal open approaches have similar early and late results. Minimally invasive surgery is an option for patients with esophageal carcinoma, with reported results similar to those for open surgery. This approach is indicated mainly for selected patients with early stages of the disease.

Liver NF‐κB and AP‐1 DNA Binding in Obese Patients

Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and in the progression from steatosis to nonalcoholic steatohepatitis (NASH). Our aim was to assess nuclear factor‐κB (NF‐κB) and activating protein‐1 (AP‐1) activation and Toll‐like receptor 4 (TLR4) expression as signaling mechanisms related to liver injury in obese NAFLD patients, and examined potential correlations among them, oxidative stress, and IR. Liver NF‐κB and AP‐1 (electromobility shift assay (EMSA)), TLR4 expression (western blot), ferric reducing ability of plasma (FRAP), and IR evolution (HOMA) were evaluated in 17 obese patients who underwent subtotal gastrectomy with gastro‐jejunal anastomosis in Roux‐en‐Y and 10 nonobese subjects who underwent laparoscopic cholecystectomy (controls). Liver NF‐κB and AP‐1 DNA binding were markedly increased in NASH patients (n = 9; P < 0.05) compared to controls, without significant changes in NAFLD patients with steatosis (n = 8), whereas TLR4 expression was comparable between groups. Hepatic NF‐κB activation was positively correlated with that of AP‐1 (r = 0.79; P < 0.0001); both liver NF‐κB and AP‐1 DNA binding were inversely associated with FRAP (r = −0.43 and r = −0.40, respectively; P < 0.05) and directly correlated with HOMA (r = 0.66 and r = 0.62, respectively, P < 0.001). Data presented show enhanced liver activation of the proinflammatory transcription factors NF‐κB and AP‐1 in obese patients with NASH, parameters that are significantly associated to oxidative stress and IR.

Gastroesophageal reflux disease after sleeve gastrectomy.

Gastroesophageal reflux disease is commonly present in obese patients. 1–3 In patients undergoing gastric bypass, the incidence of GERD is as high as 50% to 100%. Therefore, it is very important to evaluate preoperatively the presence of reflux symptoms and endoscopic esophagitis to choose the best treatment of both pathologic conditions: GERD and obesity. There are publications reporting the strategy for treating concomitant hiatal hernia or GERD disease and bariatric procedures for obese patients. Laparoscopic sleeve gastrectomy (LSG) is a frequently used alternative procedure for surgical treatment of obesity. This technique modifies the anatomy of the esophagogastric junction (EGJ) converting it in a straight tubular segment and partially sectioning the sling fibers that may affect the lower esophageal sphincter (LES) mechanism. Consequently, some patients present reflux symptoms associated with endoscopic esophagitis and therefore PPÍs treatment must be indicated. After SG LES incompetence is present in 85% of patients and thus could promote pathologic reflux. However, others have suggested that reflux esophagitis improves after SG; therefore it is a very controversial point. There are very few data regarding GERD or hiatal hernia after SG including endoscopic objective evaluation of reflux. In this paper, we present our experience regarding the frequency of gastroesophageal reflux disease after SG and review the available literature concerning this point.

Dysplasia and Adenocarcinoma After Classic Antireflux Surgery in Patients With Barrett’s Esophagus: The Need for Long-Term Subjective and Objective Follow-Up

ObjectiveTo assess the clinical, endoscopic, and functional results in a group of patients with Barrett’s esophagus undergoing classic antireflux surgery in whom dysplasia and adenocarcinoma were found at a late objective follow-up. Summary Background DataThere have been isolated reports of patients with Barrett’s esophagus undergoing antireflux surgery who show dysplasia or even adenocarcinoma on follow-up. MethodsOf 161 patients undergoing surgery, dysplasia developed in 17 (10.5%) at late follow-up and adenocarcinoma developed in 4 (2.5%). These 21 patients represent the group assessed and were compared with 126 surgical patients with long-segment Barrett’s in whom dysplasia did not develop. They were evaluated by clinical questionnaire, multiple endoscopic procedures and biopsy specimens, 24-hour pH studies, and 24-hour bilirubin monitoring. ResultsOf the 17 patients with dysplasia, 3 were asymptomatic at the time that dysplastic changes appeared; all patients with adenocarcinoma had symptoms. Two patients (12%) in the dysplasia group had short-segment Barrett’s; all patients with adenocarcinoma had long-segment Barrett’s. Manometric studies revealed an incompetent lower esophageal sphincter in 70% of the dysplasia group, similar to nondysplasia patients with recurrence, and in 100% of the adenocarcinoma group. The 24-hour pH study showed pathologic acid reflux in 94% of the patients with dysplasia, similar to patients with recurrence without dysplasia, whereas bilirubin monitoring showed duodenal abnormal reflux in 86% of the patients. Among patients with dysplasia, three different histologic patterns were identified. All patients with adenocarcinoma had initially intestinal metaplasia, with appearance of this tumor 6 to 8 years after surgery. ConclusionsPatients with Barrett’s esophagus who undergo antireflux surgery need close and long-term endoscopic and histologic surveillance because dysplasia or even adenocarcinoma can appear at late follow-up. Metaplastic changes from fundic to cardiac mucosa and then to intestinal metaplasia and later to dysplasia or adenocarcinoma can clearly be documented. There were no significant differences in terms of clinical, endoscopic, manometric, 24-hour pH, and bilirubin monitoring studies between patients with recurrence of symptoms without dysplastic changes, and patients with dysplasia. Therefore, the high-risk group for the development of dysplasia is mainly the group with failed antireflux surgery.

A new physiologic approach for the surgical treatment of patients with Barrett's esophagus: technical considerations and results in 65 patients.

OBJECTIVE To determine the results of a new surgical procedure for patients with Barretts esophagus. SUMMARY BACKGROUND DATA In addition to pathologic acid reflux into the esophagus in patients with severe gastroesophageal reflux and Barretts esophagus, increased duodenoesophegeal reflux has been implicated. The purpose of this study was to establish the effect of a new bile diversion procedure in these patients. METHODS Sixty-five patients with Barretts esophagus were included in this study. A complete clinical, radiologic, endoscopic, and bioptic evaluation was performed before and after surgery. Besides esophageal manometry, 24-hour pH studies and a Bilitec test were performed. After surgery, gastric emptying of solids, gastric acid secretion, and serum gastrin were determined. All patients underwent highly selective vagotomy, antireflux procedure (posterior gastropexy with cardial calibration or fundoplication), and duodenal switch procedure, with a Roux-en-Y anastomosis 60 cm in length. RESULTS No deaths occurred. Morbidity occurred in 14% of the patients. A significant improvement in symptoms, endoscopic findings, and radiologic evaluation was achieved. Lower esophageal sphincter pressure increased significantly (p < 0.0001), as did abdominal length and total length of the sphincter (p < 0.0001). The presence of an incompetent sphincter decreased from 87.3% to 20.9% (p < 0.0001). Three of seven patients with dysplasia showed disappearance of this dysplasia. Serum gastrin and gastric emptying of solids after surgery remained normal. Basal and peak acid output values were low. Twenty-four hour pH studies showed a mean value of 24.8% before surgery, which decreased to 4.8% after surgery (p < 0.0001). The determination of the percentage time with bilirubin in the esophagus was 23% before surgery; this decreased to 0.7% after surgery (p < 0.0001). Late results showed Visick I and II gradation in 90% of the patients and grade III and IV in 10% of the patients. CONCLUSIONS This physiologic approach to the surgical treatment of patients with Barretts esophagus produces a permanent decrease of acid secretion (and avoids anastomotic ulcer), decreases significantly acid reflux into the esophagus, and abolishes duodenoesophageal reflux permanently. Significant clinical improvement occurs, and dysplastic changes at Barretts epithelium disappear in almost 50% of the patients.

Adenocarcinoma appearing very late after antireflux surgery for Barrett's esophagus: Long-term follow-up, review of the literature, and addition of six patients

Antireflux surgery is supposed to prevent the development of adenocarcinoma in patients with Barrett’s esophagus. The purpose of this study was to determine the prevalence of adenocarcinoma late after antireflux surgery. A total of 161 patients with long-segment Barrett’s esophagus had antireflux surgery and were followed for a mean of 148 months (range 54 to 268 months) Clinical, endoscopic, histologic, and functional studies were performed. Of the original 161 patients, 147(91.3%) completed long-term follow-up. Six patients (4.1%) developed adenocarcinoma 4,5,6,9,17, and 18 years, respectively, after surgery. Five were men. Two of them were asymptomatic for 12 and 17 years. Three of them had extralong-segment Barrett’s esophagus. Five underwent manometric evaluation with only one showing an incompetent lower esophageal sphincter. In two cases, 24-hour pH studies showed massive acid reflux. Two patients had early adenocarcinoma, whereas four had advanced carcinoma. Adenocarcinoma in long-segment Barrett’s esophagus seems to develop mainly in patients with recurrence of pathologic reflux, especially among men. A review of the English language literature during the last 2 3 years found 25 articles dealing with Barrett’s esophagus and antireflux surgery. Most of these reports had only a few patients with short-term follow-up (<60 months). To determine the true prevalence of this complication, a long-term objective follow-up is necessary.

Early and late results of the acid suppression and duodenal diversion operation in patients with Barrett's esophagus: Analysis of 210 cases

The usual surgical treatment for patients with Barrett’s esophagus (BE) is a classic Nissen fundoplication or posterior gastropexy with cardial calibration. However, some surgical reports as well as our experience suggest that the rate of failure of the Nissen fundoplication or Hill’s posterior gastropexy in patients with BE is significantly higher than in those with reflux esophagitis without BE, probably due in part to the persistence of duodenal reflux into the esophagus. Our aim was to determine the late subjective and objective results of an operation consisting in “acid suppression” (vagotomy-partial gastrectomy) and “duodenal diversion” (Roux-en-Y anastomosis) as a primary surgical procedure for patients with BE. Altogether, 210 patients were subjected to this technique. It consisted in a primary operation in 142 patients and revision surgery in 68. They underwent complete clinical, radiologic, endoscopic, histologic, and manometric studies. In some cases 24-hour pH studies, Bilitec studies, gastric emptying, and gastric acid secretion evaluations were performed. There were two deaths (0.95%), and postoperative morbidity was low (5.3%). The late mean follow-up (58 months) for 146 patients who completed a follow-up longer than 24 months showed Visick I and II grades in 91.1% of the cases. In 14.9% of the cases 24-hour pH monitoring showed excessive acid reflux 1 year after surgery. No dysplasia or adenocarcinoma has appeared up to now. Functional studies showed significant alleviation of lower esophageal sphincter (LES) incompetence, with abolition of duodenal reflux into the esophagus. Gastric emptying of solids was normal, and basal and peak gastric acid output remained at a low level 8 to 10 years after surgery. In patients with BE, with severe damage of the LES and esophageal peristalsis, the “suppression diversion” operation completely abolishes the reflux of injurious components of the refluxate and improves sphincter competence. This effect is permanent and avoids the appearance of dysplasia or adenocarcinoma.RésuméLe traitement habituel des patients ayant un oesophage de Barrett (OB) consiste en une fundoplicature classique selon Nissen ou en une gastropexie postérieure avec calibration du cardia. Cependant, certaines publications, comme notre expérience, suggèrent que le taux d’échec de la fundoplicature complète selon Nissen ou de la gastropexie postérieure selon Hill est significativement plus élevé en cas d’OB qu’en cas de reflux en l’absence d’OB, probablement en raison de la persistance du reflux duodénal dans l’œsophage. Afin de déterminer les résultats tardifs subjectifs et objectifs d’une opération qui consiste en une suppression de l’acidité (vagotomie, gastrectomie partielle) associée à un diversion duodénale (anastomose en Y), on a étudié les résultats chez 210 patients ayant eu cette intervention: de première intervention pour 142 patients et comme chirurgie revisioneile dans 68 cas. Tous les patients ont eu une étude clinique, radiologique, histologique et manométrique complète. Dans certains cas, on a réalisé des études de pH de 24 heures, une étude Bilitec, une étude de la vidange gastrique ou une évaluation de la sécrétion. Deux patients sont décédés (0.95%). La morbidité postopératoire a été très basse (5.3%). Dans 146 cas où le suivi a été supérieur à 24 mois, avec un suivi moyen à distance de 58 mois, 91% des patients avaient des scores Visick I et II. Cependant, dans 14.9% des cas, la pH-métrie des 24 heures a montré un reflux acide excessif un an après la chirurgie. On n’a observé aucun cas de dysplasie ou d’anénocarcinome jusqu’à présent. Les études fonctionnelles ont montré une amélioration significative dans l’incompétence du sphincter inférieur de l’œsophage. La vidange gastrique pour les solides était normale, alors que les taux de débit acide de base et maximal étaient très bas 8 et 10 ans après chirurgie. Chez un patient présentant un OB, avec des lésions sévères du sphincter inférieur de lœophage et une modification du péristaltisme oesophagien, l’intervention “suppression/diversion” abolit complètement le reflux de composants agressifs et améliore la compétence sphinctérienne. Cet effet est permanent et évite l’apparition de dysplasie ou d’adénocarcinome.ResumenEl tratamiento quirúrgico habitual del esófago de Barrett es la fundoplicación a lo Nissen o una gastropexia posterior, con calibración del cardias a lo Hill. Sin embargo, algunas publicaciones y nuestra propia experiencia demuestran que en pacientes con Barrett estas técnicas se acompañan de un gran porcentaje de fracasos, que no se observan en pacientes con reflujo esofágico sin enfermedad de Barrett. Para evaluar los resultados tradíos, 210 pacientes con enfermedad de Barrett fueron sometidos a una operación “supresora de la acidez” consistente en: una vagotomía con gastrectomía parcial acompañada de transección duodenal y reconstrucción mediante una anastomosis en Y de Roux. En 142 casos esta técnica constituyó el tratamiento inicial; 62 pacientes fueron sometidos a dicha intervención por fracaso de las operaciones clásicas ya mencionadas. Todas los enfermos habían sido estudiados por completo no sólo desde el punto de vista clínico, radiológico y endoscópico sino también, por lo que al estudio histológico y manométrico se refiere. En algunos casos se realizaron: pHmetría de 24 horas, estudios de Bilitec, de vaciamiento gástrico y de acidez gástrica. Registramos dos muertes (0.95%). La morbilidad postoperatoria fue escasa (5.3%). El seguimiento medio a largo plazo fue de 58 meses; de 146 pacientes, con un seguimiento superior a los 24 meses, el 92.2% se clasificaron como pertenecientes al grado Vlsick I y II. Sin embargo, el 14.9% de los casos en los que se estudió duante 24 horas la pHmetría, mostraron al año de la intervención quirúrgica un reflujo ácido excesivo. Hasta la actualidad no se ha registrado ningún caso de displasia o adenocarcinoma. Los estudios funcionales revelan una significativa mejoría del incompetente esfinter esofágico inferior con abolición del reflujo duodeno-esofágico. El vaciamiento gástrico para sólidos fue normal y la acidez gástrica máxima se mantuvo muy baja a los 8–10 años de la operación. En pacientes con enfermedad de Barrett la técnica quirúrgica propuesta por los autores abole por completo el reflujo y los deletéreos efectos de los distintos componentes del mismo, mejorando la competencia del esfinter. Estos resultados son permanentes sin que la operación induzca al desarrollo de displasias o adenocarcinomas.