A prospective, randomized, controlled trial of covered expandable metal stents in the palliation of malignant esophageal obstruction at the gastroesophageal junction.

OBJECTIVE: Palliation of malignant esophageal obstruction is an important clinical problem. Expandable metal stents are a major advance in therapy, but many stents become obstructed because of tumor ingrowth. The aim of this study was to compare a new, membrane-covered expandable metal stent to conventional prostheses in a randomized controlled trial. METHODS: Sixty-two patients with malignant inoperable esophageal obstruction at the gastroesophageal junction participated in the study. Patients were randomly assigned to covered or uncovered stents. The principal outcome measure was the need for reintervention because of recurrent dysphagia or migration. Secondary endpoints were relief of dysphagia measured by a dysphagia score (grade 0 = no dysphagia, grade 1 = able to eat solid food, grade 2 = semisolids only, grade 3 = liquids only, grade 4 = complete dysphagia) and the rate of complications and functional status. All patients were observed at monthly intervals until death or for 6 months. RESULTS: One week after stenting the dysphagia score improved significantly in both the uncovered (n = 32, 3 +/- 0.1 to 1 +/- 0.1 [means +/- SEMs], p < 0.001) and covered (n = 30, 3 +/- 0.1 to 1 +/- 0.2 [means +/- SEMs], p < 0.001) stents. Obstructing tumor ingrowth was significantly more likely in the uncovered stent group (9/30) than in the covered group (1/32) (p = 0.005). Significant stent migration occurred in 2/30 patients with uncovered stents, as compared with 4/32 patients in the covered group (p = 0.44). Reinterventions for tumor ingrowth were significantly greater in the uncovered stent group (27%), as compared with 0% in the covered group (p = 0.002). Life table analysis showed similar survival in both groups. CONCLUSION: Membrane-covered stents have significantly better palliation than conventional bare metal stents because of decreased rates of tumor ingrowth that necessitate endoscopic reintervention for dysphagia.

Circulating Epstein-Barr virus DNA to monitor lymphoproliferative disease following pediatric liver transplantation.

Epstein-Barr virus (EBV) infection can induce uncontrolled lymphocyte B proliferation in immunosuppressed transplant patients. Monitoring circulating EBV-infected lymphocytes can help in identifying patients at risk of posttransplant lymphoproliferative disease (PTLD). Circulating EBV genome levels were determined in 54 liver transplant pediatric recipients. Ten patients had more than 500 EBV genome/10(5) peripheral blood lymphocytes (PBL) and exhibited clinical manifestations of EBV infection; three developed PTLD. To treat EBV infection, the level of immunosuppression was reduced and acute rejection developed in 4 patients. Three were treated with steroid and one had to be switched from cyclosporine to tacrolimus. Treatment of acute rejection was associated with increases in circulating EBV genome. None of the patients with less than 500 EBV genome/10(5) PBL developed PTLD or EBV infection. Monitoring of EBV DNA is useful in the management of EBV infection and PTLD following pediatric liver transplantation. EBV infection should be treated in ways which do not expose patients to the risk of rejection.

Endoscopic laser ablation of nondysplastic Barrett's epithelium: is it worthwhile?

The clinical value of endoscopic ablation of nondysplastic Barrett's epithelium is controversial. It has been stated that ablation, combined with acid suppression or antireflux surgery, may reduce the risk of adenocarcinoma, thereby obviating the need for endoscopic surveillance in these patients. Eighteen symptomatic patients were enrolled in a prospective study of Nd:YAG laser ablation of Barrett's esophagus followed by treatment with proton pump inhibitors or antireflux surgery. All patients had intestinal metaplasia and no associated dysplasia or carcinoma. Laser treatment was performed with noncontact fibers and a power output of 60 watts. The mean number of treatment sessions was three (range 1 to 5), and the mean energy delivered during each session was 2800 joules (range 600 to 4800 joules). All patients were given a standard dose of omeprazole (40 mg/day) throughout the study period. In two patients a mild distal esophageal stricture occurred and required a single dilatation. Macroscopic and histologic eradication of the specialized columnar epithelium was documented in 8 of 12 patients with tongues of Barrett's metaplasia, in one of four patients with circumferential Barrett's metaplasia, and in two of two patients with short-segment Barrett's esophagus. In five patients (28%) only a partial ablation could be achieved despite repeated laser treatment. Two patients (11%), one with tongues and the other with circumferential Barrett's metaplasia, were considered nonresponders. Adenocarcinoma undermining regenerated squamous epithelium was found, 6 months after eradication, in one patient who underwent esophagogastric resection. Twelve patients agreed to undergo antireflux surgery. Over a mean follow-up period of 14 months (range 4 to 32 months), two patients presented with recurrent Barrett's metaplasia: one at 8 months after successful Nissen fundoplication and the other after 1 year of continuous omeprazole treatment. Progression of Barrett's metaplasia was found in two other patients receiving pharmacologic therapy in whom a partial response to laser treatment had been obtained. In conclusion, Nd:YAG laser therapy of nondysplastic Barrett's esophagus, performed in conjunction with omeprazole treatment and followed by antireflux surgery, allows a partial regression of specialized columnar epithelium in most patients. However, this is a time-consuming procedure that produced only temporary eradication, did not prove effective in reducing cancer risk, and did not obviate the need for endoscopic surveillance.

Endoscopic palliation of oesophageal cancer: results of a prospective comparison of Nd:YAG laser and ethanol injection.

OBJECTIVE: To evaluate the effectiveness of intratumoral alcohol injection compared with Nd:YAG laser in the treatment of unresectable fungating cancers of the oesophagus. DESIGN: Prospective, randomised clinical study. SETTING: University hospital, Italy. SUBJECTS AND INTERVENTIONS: 47 consecutive patients were randomly allocated to have endoscopic Nd:YAG laser treatment (n = 24), or intratumoural injection of 98% alcohol (n = 23). MAIN OUTCOME MEASURES: Morbidity, mortality, dysphagia score, survival. RESULTS: One patient in the laser group needed analgesic support during and after the treatment, whereas 18 (78%) of those treated with alcohol experienced mild pain and most of them required analgesics. An improvement of at least 2 points in the dysphagia score was noted in 21 patients (88%) in the laser group and in 18 in the alcohol group (78%). The mean dysphagia-free intervals between each treatment were 30 and 37 days, respectively. The median survival was 6 months in each group. There were no significant differences in the mean dysphagia scores of patients still alive. There were no complications in the laser group, but one oesophageal perforation occurred during the preliminary dilatation before the second session of alcohol injection. There were no procedure-related deaths. CONCLUSION: The two techniques allowed similar palliation of dysphagia and improvement of quality of life. Intratumoral injection of alcohol is an effective and inexpensive therapeutic option in the palliation of fungating oesophageal lesions.

Duodeno-gastro-esophageal reflux after gastric surgery: surgical therapy and outcome in 42 consecutive patients.

BACKGROUND/AIMS: Duodeno-gastro-esophageal reflux is a common event after gastric surgery and can result in severe symptoms and mucosal injury. Medical therapy is largely ineffective. The most common remedial operation consists of a long isoperistaltic Roux-en-Y limb in order to shunt duodenal contents away from the gastric pouch and the esophagus. METHODOLOGY: Between 1980 and 1996, 42 patients underwent duodenal diversion after gastric surgery. The presence of severe symptoms and/or endoscopic esophagitis unresponsive to medical therapy was considered an indication for surgery. Functional studies were performed in selected patients in an attempt to objectively document the presence of excessive duodeno-gastro-esophageal reflux. A 40-60 cm Roux-en-Y limb was constructed in all patients. RESULTS: There was no post-operative mortality. The median follow-up was 28 months (range: 5-114). Symptoms related to delayed gastric emptying persisted in 5 patients (11.9%). Overall, 32 patients (76%) had a Visick I-II score. Best results (90%) were achieved in patients with previous total gastrectomy. CONCLUSIONS: Roux-en-Y duodenal diversion should be reserved for patients with intractable symptoms and documented reflux, and is mostly effective after total gastrectomy. Patients with a residual stomach are less likely to benefit from the procedure, probably because an underlying motor disorder plays a major role in the pathogenesis of the symptoms than does the reflux of duodenal contents.

Surgical therapy in patients with failed antireflux repairs.

BACKGROUND/AIMS: Failure of antireflux surgery may be due to errors in patient selection, errors in the choice of the operation, or technical errors in the performance of the operation. The purpose of this work was to review a series of patients surgically treated for a failed antireflux procedure over the past two decades. MATERIALS AND METHODS: Seventy patients (62%) out of 113 consecutive individuals presenting with symptoms after one or more operations for gastroesophageal reflux disease underwent reoperation. Five patients had been operated on laparoscopically. The indications for reoperation were based on severity of symptoms and results of objective investigation. Surgical therapy was tailored to the individual patient based on pathophysiological abnormalities and on the results of intraoperative assessment. RESULTS: Reflux symptoms and dysphagia represented the major complaint in 62.8% and 35.7% of patients, respectively. The most common pathophysiological abnormality was an incompetent lower esophageal sphincter. Intraoperative assessment showed a disrupted or misplaced repair in 77% of the patients. The most common reoperation performed was a partial or total fundoplication (54.3%), followed by antrectomy and Roux-en-Y anastomosis (25.7%). There was no mortality. Postoperative morbidity rate was 8.5%. At a median follow-up of 48 months, 87% of patients were scored as Visick 1-2 and 90% declared themselves satisfied with the results of reoperation. CONCLUSIONS: Management of patients with failed antireflux procedures is challenging. However, detailed physiological evaluation and a surgical approach tailored to residual anatomy and function of the foregut can provide excellent results.

Minimally invasive surgery for Zenker diverticulum: analysis of results in 95 consecutive patients.

OBJECTIVE: To assess the effectiveness of transoral stapled diverticulum esophagostomy in relieving symptoms and decreasing outflow resistance at the pharyngoesophageal junction in patients with Zenker diverticulum. DESIGN: Cohort study. From April 1, 1992, until May 31, 1996, the operation was attempted in 95 patients. The median follow-up was 23 months (range, 13-48 months). SETTING: Tertiary care university hospital. PATIENTS: There were 74 men and 21 women, with a median age of 64 years (age range, 37-92 years). All complained of dysphagia and pharyngo-oral regurgitation, and 18 (20%) suffered from recurrent aspiration pneumonia. The median size of the pouch measured by flexible endoscopy was 4 cm (range, 2.5-8 cm). INTERVENTION: The septum between the diverticulum and the esophageal lumen was divided under general anesthesia using a linear endostapler introduced through a Weerda endoscope. In most patients, 2 applications of the endostapler with a modified anvil were used. Operative time averaged 23 minutes. MAIN OUTCOME MEASURES: Morbidity, symptom score, patient's satisfaction, videofluorographic barium transit, hypopharyngeal intrabolus pressure, upper esophageal clearance of radioisotope. RESULTS: A switch to open surgery was required in 3 patients (3.1%), due to difficult exposure of the common wall in 2 cases and a mucosal tear in the other. No postoperative morbidity or mortality was recorded. Oral feeding was started the following day and the median hospital stay was 3 days (range, 2-8 days). Five patients complained of persistent symptoms; 3 of them underwent another endosurgical operation, 1 underwent laser treatment by means of flexible endoscopy, and 1 eventually required open surgery. All patients are asymptomatic at the latest follow-up visit. Postoperative radiologic studies showed free flow of barium in all patients. Manometry showed a significant reduction of hypopharyngeal intrabolus pressure over preoperative values (P=.003). Radionuclide studies showed a significant reduction of upper esophageal residual activity at 1 minute compared with preoperative values (P=.006). CONCLUSIONS: Endosurgical approach to hypopharyngeal diverticula larger than 2 cm is safe and effective. Symptom relief, elimination of the pouch, and decreased outflow resistance at the pharyngoesophageal junction can be obtained without morbidity and with a short hospital stay.

Surgical treatment of the redundant interposed colon after retrosternal esophagoplasty.

Redundancy of the interposed colon used as an esophageal substitute is a common finding in the long-term follow-up of these patients. When symptoms caused by food retention in the colonic loop occur, surgical correction is necessary to improve quality of life and to prevent aspiration. We report a technique to straighten the redundant colon that consists of a side-to-side colocolic anastomosis using a linear stapler. This obviates the need for a redo cologastric anastomosis. Compared with resection of the loop, the operation is quick, safe, and easy to perform, and it may decrease the risk of injury to the marginal vessels of the colon graft.

Preoperative laparoscopy in management of patients with carcinoma of the esophagus and of the esophagogastric junction.

BACKGROUND AND OBJECTIVES: Adequate preoperative staging of patients with esophageal and cardia carcinoma offers the potential for a rational choice of the therapy. The aim of this study was to assess the diagnostic value of laparoscopy compared to ultrasonography (US) and computed tomography (CT) in detecting intra-abdominal metastatic spread. METHODS: Between November 1995 and December 1996, 36 patients with adenocarcinoma of the cardia and 14 patients with squamous cell carcinoma of the lower third of the esophagus were studied with CT scan and US, followed by laparoscopy performed at the same session of planned surgical resection. Mean operative time of laparoscopy was 20 minutes (range 15-55 min). There was no mortality nor morbidity related to the laparoscopic procedure. RESULTS: Laparoscopy lead to a change of the therapeutic approach in five patients (10%): three patients with peritoneal carcinosis undetected at the imaging examinations, and one patient with advanced liver cirrhosis with signs of portal hypertension did not undergo resection; conversely, one patient with a liver hemangioma simulating a metastatic mass at CT/US underwent esophagogastric resection. Laparoscopy showed a higher sensitivity than US and CT in detecting peritoneal metastases (71% vs. 14% vs. 14%, respectively), macroscopic nodal metastases (78% vs. 11% vs. 55%), and liver metastases (86% vs. 71%). CONCLUSIONS: Laparoscopy represents a safe and effective diagnostic procedure in the preoperative staging of esophageal and cardia carcinoma; it provides the potential to avoid unnecessary exploratory laparotomies and to select the most appropriate treatment.

Evaluation of leiomyoma of the esophagus with endoscopic ultrasonography.

Fourteen patients with suspected leiomyoma of the esophagus were studied by endoscopic ultrasonography, computed tomography, endoscopy and barium swallow. The results were correlated with the histology of the resected specimens: in 2 patients with a peduncolated leiomyoma originating from the second echographic layer, endoscopic resection was performed. Endoscopic ultrasonography was superior to other imaging techniques in detection and staging of leiomyoma because it can determine the layer of origin, the direction of the growth and the consistency of the tumor.

Endoscopic ultrasonography for preoperative staging of esophageal carcinoma.

Endoscopic ultrasonography (EUS) is a relatively new diagnostic method to assess the extent and the depth of infiltration of esophageal carcinoma. Since October 1990, EUS was performed in 55 patients presenting with squamous-cell carcinoma of the esophagus, 40 of whom were operated on. The first 23 patients underwent EUS with an Olympus GF-2/EU-M2 echoendoscope with a 7.5-MHz transducer; the last 32 patients underwent EUS with an Olympus GF-3/EU-M3 instrument with a 7.5-12-MHz echoprobe. In 22 patients, the procedure was not completed because of the impossibility of passing through the neoplastic stenosis. The depth of infiltration (T parameter) was correctly defined by EUS in 36 of 40 patients (90%) compared with 50% of computed tomography (CT). The 12-MHz echoprobe yielded a global accuracy in staging T parameter of 94% compared to 82% of 7.5-MHz transducer. The lymph-node involvement (N parameter) was correctly classified by EUS in 20 of 23 patients (87%) compared with 39% by CT. EUS provides a high degree of accuracy in assessing the T and the N parameter in the staging of squamous-cell esophageal carcinoma. The major problem of the instrument is still the frequent impossibility of passing through the neoplastic stenosis.

p53 protein accumulation and p53 gene mutation in esophageal carcinoma. A molecular and immunohistochemical study with clinicopathologic correlations.

BACKGROUND: p53 gene mutation and p53 protein accumulation are common in human cancer. However, their clinical significance is controversial and p53 accumulation may not correlate with gene mutation. The current study investigates the occurrence of p53 alterations in esophageal carcinoma, the correlation between the analyses at the gene and protein level, and their prognostic significance. METHODS: A series of 74 esophageal carcinomas (46 squamous cell carcinomas, 21 Barrett's adenocarcinomas, and 7 undifferentiated carcinomas) was studied by single strand conformation polymorphism (SSCP) analysis and immunohistochemistry (IHC) to detect p53 mutation and accumulation, respectively. RESULTS: p53 mutations in exons 5-8 were detected in 53% of the carcinomas whereas p53 accumulation was observed in 57% of cases. Comparing SSCP and IHC, there were 27 discordant cases (38%). Overall, only 20 tumors (27%) did not display p53 mutation and/or p53 accumulation. No associations were found between p53 aberrations and clinicopathologic parameters, including patients age and gender tumor type, stage, and grade. p53 protein accumulation and p53 gene mutation were not related to patient survival by univariate or multivariate analysis in esophageal carcinomas. CONCLUSIONS: p53 aberrations are very common in esophageal carcinomas. However, p53 gene mutation and p53 protein accumulation have a significant discordance, suggesting that p53 function may be inactivated by mechanisms other than mutation. p53 aberrations do not independently predict prognosis in esophageal tumors.

Improving results of esophageal stenting: a study on 160 consecutive unselected patients.

BACKGROUND AND STUDY AIMS: Esophageal stenting is a valuable treatment in the management of malignant dysphagia. Recently, self-expanding stents have proved effective in reducing morbidity and mortality. The aim of this study was to evaluate the early and late results of esophageal stenting in a series of 160 consecutive unselected patients with unresectable esophageal and cardial carcinoma treated between November 1992 and December 1996. PATIENTS AND METHODS: The procedure was successful in 159 patients (99.4%). A traditional tube was employed in 84 patients (52.5%). Metallic self-expanding stents have been available since June 1993 and were used in 75 selected patients (46.9%). The tumor was located in the cervical, upper, middle and lower thoracic esophagus, and at the gastric cardia in 16, 16, 56, 22 and 34 patients, respectively. In the remaining 15 patients an esophagovisceral anastomosis was involved. Preoperative chemo- and/or radiotherapy were performed in 82 patients (51.3%). RESULTS: Overall hospital morbidity was 11.3% (18/159) and included four dislodgments, four incomplete expansions of a self-expanding stent, two perforations, two incomplete sealings of a malignant respiratory tract fistula, two hemorrhages, two persistent foreign body sensations, one arrhythmia and one aspiration pneumonia. Hospital mortality was 1.3% (2/159) and was recorded in patients who underwent traditional intubation. At discharge, dysphagia was improved at least 2 degrees in 152 patients (96.8%). The overall long-term morbidity was 23.5% (37/157). Mean survival after the procedure was 4.7 months. CONCLUSIONS: Intubation is a safe palliative procedure which can be performed with low morbidity and mortality rates. Self-expanding metallic stents have enhanced the indications and the outcomes of the procedure, resulting in the treatment of strictures where the placement of a traditional tube is difficult or technically impossible.

Primary multiple epithelioid leiomyosarcoma of the liver.

Sarcomas represent only 1-2% of primary malignant tumors of the liver. We report the twenty first case of primary hepatic leiomyosarcoma in the literature. Metastases from gastrointestinal tract, female genital system and lung have to be excluded before confirming diagnosis of a primary neoplasm. Extensive involvement of the liver parenchyma contraindicated surgery, the treatment of choice when the tumor is solitary or multiple but located in one lobe. Chemotherapy, as employed in our patient, is the alternative therapeutic option in inoperable cases, but its role has to be clarified.

Endoscopic management of inveterate esophageal perforations and leaks.

The endoscopic management of four selected patients with inveterate esophageal perforations or leaks is presented. One patient had a perforation of the cervical esophagus following endoscopic removal of a foreign body already treated with surgical drainage; two patients had a leak following diverticulectomy and esophagogastrostomy, respectively, persistent after multiple surgical repairs; the last patient had a spontaneous perforation of the thoracic esophagus persistent after two transthoracic repairs. The mean time elapsed between the diagnosis of perforation and the endoscopic treatment was 19 days. In one patient, transesophageal drainage of a mediastinal abscess was performed. In the other three patients, a stent was placed to seal the leak in combination with gastric and esophageal aspiration. Two of these patients underwent endoscopy in critical condition and could have not been candidates for major surgical procedures. All patients received enteral nutrition. No morbidity or mortality related to the endoscopic procedure was recorded; the treatment was effective in all patients who recovered and resumed oral feeding within 3 weeks. We conclude that endoscopic transesophageal drainage and stenting are effective procedures in the management of patients with inveterate esophageal perforations or leaks.

Surgical therapy of esophageal leiomyoma.

BACKGROUND: Surgical enucleation is the treatment of choice in selected patients with esophageal leiomyoma. The video-thoracoscopic approach can potentially cause less patient discomfort postoperatively and reduce the hospital stay and recovery period. STUDY DESIGN: A retrospective evaluation of 66 patients who underwent surgical therapy for esophageal leiomyoma over a 27-year period was done. The main symptoms were dysphagia in 35 (53 percent) patients, heartburn or regurgitation, or both, in 11 (17 percent) patients, and retrosternal pain in ten (15 percent) patients. Associated esophageal disorders were found in 19 patients (some patients had more than one disorder): hiatal hernia in 15 (23 percent), epiphrenic diverticulum in four (6 percent), and achalasia in three (5 percent). The operation consisted of leiomyoma enucleation in 63 patients, and esophageal resection in three. In six patients, the enucleation was successfully performed by video-thoracoscopy combined with intraoperative esophagoscopy. The muscle layer of the esophagus was approximated in the majority of the patients after tumor enucleation. RESULTS: There was no operative mortality. The incidence of intraoperative esophageal perforation was greater in patients who had previously undergone endoscopic biopsy (p < 0.01). In one patient, a pseudodiverticulum developed after thoracoscopic enucleation, requiring reoperation with approximation of the muscle layer for relief of dysphagia. The length of hospital stay was shorter in patients undergoing the video-assisted operation (p < 0.05). The median follow-up period was 53 months (range, 12 to 248 months). No recurrence of leiomyoma was observed. Overall, seven (11 percent) patients complained of heartburn or epigastric pain, or both, which was responsive to antisecretory drugs, but only three had such symptoms induced by the operation. In two patients the symptoms appeared after combined treatment of an epiphrenic diverticulum, and in one patient after simple leiomyoma enucleation. CONCLUSIONS: Enucleation of esophageal leiomyoma is a safe and effective operation. The video-thoracoscopic approach combined with intraoperative esophagoscopy allows performance of this procedure with the added advantage of shortening hospital stay. The muscle layer of the esophagus should be approximated to avoid decreasing the propulsive activity of the esophageal body. This may improve the long-term outcome of the operation by preserving the acid-clearing mechanism of the esophagus and reducing the incidence of postoperative reflux esophagitis.