Patricio Burdiles

Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients.

Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis.

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.

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.

Conservative Management of Anastomotic Leaks after 557 Open Gastric Bypasses

Background: One of the most serious complications after gastric bypass is an anastomotic leak. In a prospective surgical protocol for the management of this complication, the authors determined the incidence of anastomotic leaks Methods: From August 1999 to January 2005, 557 patients with morbid obesity were submitted to laparotomic resectional gastric bypass. In all patients a left drain was placed during surgery. All patients had a radiological study with liquid barium sulphate on the 5th postoperative day. After the occurrence of an anastomotic leak, the daily output of the leak was carefully measured. Results: 12 patients developed an anastomotic leak at the gastrojejunostomy. All were managed medically, with antibiotics if necessary, enteral or parenteral feeding and frequent control by imaging procedures. In 8 patients, the left drain was maintained in situ up to 43 days after surgery. In 4 patients, the drain had been removed between the 5th and 8th days after surgery after a normal radiologic study, but had to be inserted under radiological control 2-3 weeks after the gastric bypass. Daily output increased significantly the second week after surgery, and the leak closed at a mean of 30 days after surgery. One patient of the 12 (8%) died 32 days after surgery from septic shock, without any abdominal collection secondary to the leak. Conclusion: The occurrence of an anastomotic leak is nearly 2% after gastric bypass. The majority of them can be managed medically, without the need for a reoperation, due to the fact that there is no acid production in the small gastric pouch and there is no intestinal reflux due to the long Roux loop.

Treatment of Common Bile Duct Injuries during Laparoscopic Cholecystectomy: Endoscopic and Surgical Management

Abstract. The increase of laparoscopic cholecystectomy has resulted in an increase of bile duct injuries. The purpose of this article is to define the types of injury, their occurrence and frequency, and their management by endoscopic and surgical techniques. Three investigations were included in the present study. 1. A 3-year retrospective study among 29 hospitals with 25,007 laparoscopic cholecystectomies. 2. An 8-year prospective study at our institution of 6488 patients. 3. A prospective endoscopic study of 94 patients with injuries and strictures of the common bile duct (CBD) after laparoscopic cholecystectomy. A special classification for bile duct injuries was developed. Among 25,007 patients from 29 hospitals, a total of 74 lesions were detected with an incidence of 0.29%. At our institution, 20 cases were seen (0.29%) with type I, II, and III injuries. The 94 cases managed by endoscopic procedure were submitted to endoscopic retrograde cholangiopancreatography (ERCP) and papillotomy, with placement of several stents 5 to 10 F during 8 months. The results of this procedure have been excellent to good in 76% of the cases up to 3 years of follow-up. According to our previous and present experience, bile duct injuries after laparoscopic procedure are two times higher than after open procedure. The best treatment is the prevention of these injuries by careful surgical technique. If they occur, the best moment to repair them is during surgery. If they are noticed after the operation, endoscopic or surgical procedures can be employed.

Effect of gastric bypass on Barrett's esophagus and intestinal metaplasia of the cardia in patients with morbid obesity.

Gastric bypass in patients with morbid obesity should be an excellent antireflux procedure, because no acid is produced at the small gastric pouch and no duodenal reflux is present, due to the long Roux-en-Y limb. Five hundred fifty-seven patients with morbid obesity submitted to resectional gastric bypass, and routine preoperative upper endoscopy with biopsy samples demonstrated 12 patients with Barrett’s esophagus (2.1%) and three patients with intestinal metaplasia of the cardia (CIM). An endoscopic procedure was repeated twice after surgery, producing seven patients with short-segment Barrett’s esophagus (BE) and five patients with long-segment BE. Body mass index (BMI) decreased significantly, from 43.2 kg/m2 to 29.4 kg/m2 2 years after surgery. Symptoms of reflux esophagitis, which were present in 14 of the 15 patients, disappeared in all patients 1 year after surgery. Preoperative erosive esophagitis and peptic ulcer of the esophagus healed in all patients. There was regression from intestinal metaplasia to cardiac mucosa in four patients (57%) with short-segment BE, and in one patient (20%) with long-segment BE. Two (67%) of three cases with CIM had regression to cardiac mucosa. There was no progression to low- or high-grade dysplasia. Gastric bypass in patients with Barrett’s esophagus and morbid obesity is an excellent antireflux operation, proved by the disappearance of symptoms and the healing of endoscopic esophagitis or peptic ulcer in all patients, which is followed by an important regression to cardiac mucosa that is length-dependent and time-dependent.

Latest results (12-21 years) of a prospective randomized study comparing Billroth II and Roux-en-Y anastomosis after a partial gastrectomy plus vagotomy in patients with duodenal ulcers.

Introduction:After a partial resection of the stomach, the continuity of the gastrointestinal tract can be restored either by a Billroth II gastrojejunal anastomosis or a Roux-en-Y gastrojejunostomy. Each procedure has its advantages and disadvantages. Objective:To determine through a prospective and random clinical trial, the clinical outcome and the endoscopic and histologic alterations of the distal esophagus and the gastric remnant in patients who received a partial distal gastrectomy due to duodenal ulcers and a Billroth II or Roux-en-Y reconstruction. Material and Methods:In this prospective random trial, a total of 75 patients with duodenal ulcers were included. A bilateral selective vagotomy and partial distal gastrectomy were performed in all patients. A Billroth II or Roux-en-Y 60-cm-long loop was randomly used for reconstruction of the gastrointestinal tract. During the latest follow-up clinical evaluation, upper endoscopy and biopsy samples from the distal esophagus and gastric remnant were obtained. Results:There was 1 operative mortality and 6 patients had some morbidity. The average follow-up period was 15.5 years (range, 11–21). Patients with Roux-en-Y gastrojejunostomy were significantly more asymptomatic and had greater Visick I grading than patients with Billroth II reconstruction (P < 0.001). In the distal esophagus, endoscopic findings were normal in 90% of the Roux-en-Y group, but only in 51% of the Billroth II group (P < 0.0009). Nearly 25% of the latter group had the appearance of a short-segment Barrett esophagus compared with 3% of the Roux-en-Y group (P < 0.0001). The gastric remnant endoscopic findings were normal in 100% of the Roux-en-Y group and in 18% of the Billroth II group (P < 0.02). Histologic analyses showed similar proportions of normal fundic mucosa and chronic active fundic gastritis. However, chronic atrophic fundic gastritis and intestinal metaplasia were significantly more frequent after Billroth II reconstruction (P < 0.008). Helicobacter pylorus was present in a similar proportion of patients. Conclusions:This prospective and random study showed that Roux-en-Y gastrojejunostomy is significantly better than a Billroth II reconstruction in patients with duodenal ulcers, through subjective and objective endoscopic and histologic evaluations during the latest follow-up evaluation.

Clinical, endoscopic, and functional studies in 408 patients with Barrett's esophagus, compared to 174 cases of intestinal metaplasia of the cardia

OBJECTIVE:The pathophysiology of gastroesophageal reflux disease (GERD) has been studied extensively in patients with long-segment Barretts esophagus (LSBE), but few reports have explored GERD pathophysiology in patients who have short-segment Barretts esophagus (SSBE) or intestinal metaplasia at the cardia (IMC). We aimed to compare clinical, endoscopic, histological, and functional features in patients with LSBE, SSBE, and IMC.METHODS:We identified 582 patients who had intestinal metaplasia at the squamocolumnar junction in the distal esophagus and divided them into three groups based on the extent of columnar-lined esophagus observed endoscopically: 1) patients with IMC who had no columnar-lined esophagus (i.e., the squamocolumnar and gastroesophageal junctions coincided), 2) patients with LSBE who had >3 cm of columnar-lined esophagus, and 3) patients with SSBE who had <3 cm of columnar-lined esophagus. All patients had esophageal manometric evaluation, and 24-h esophageal pH monitoring was performed to determine the extent of acid and bile (bilirubin) reflux.RESULTS:There were 174 patients with IMC, 155 with LSBE, and 25 with SSBE. Compared to patients with LSBE and SSBE, patients with IMC had significantly lower frequencies of GERD symptoms, hiatal hernia, and erosive esophagitis; significantly higher lower esophageal sphincter pressures; and significantly shorter durations of acid and bile reflux. Between patients with SSBE and LSBE, significant differences were found in the frequency of hiatal hernia and duration of acid reflux (both greater in the patients with LSBE). Also, dysplasia was significantly more frequent in patients with LSBE than in those with SSBE or IMC.CONCLUSION:GERD symptoms, signs, and physiological abnormalities are found more often in patients with Barretts esophagus than in those with IMC, and the duration of acid reflux in patients with LSBE is greater than that in patients with SSBE. These findings suggest that the extent of intestinal metaplasia in the esophagus is related directly to the severity of underlying GERD.

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.