Clinical significance of p53 mutations in adenocarcinoma of the esophagus and cardia.

OBJECTIVE: To compare the frequency and spectrum of p53 gene mutations in adenocarcinomas of the esophagus and cardia and to compare clinical and pathologic features in patients with p53 mutant and nonmutant cancers. SUMMARY BACKGROUND DATA: The p53 gene is commonly mutated in human cancers, and a p53 mutation is reported to be present in more than 50% of esophageal adenocarcinomas. Although many studies have investigated the frequency of p53 protein overexpression in adenocarcinomas of the esophagus or esophagogastric junction, few studies have assessed the frequency and clinical significance of p53 mutations in these tumors. In particular, the prognostic importance of p53 mutation is uncertain. Adenocarcinomas of the esophagus and cardia share many epidemiologic and pathologic features, but it is controversial whether they represent the same tumor. A comparison of the frequency and spectrum of mutations in adenocarcinomas of the esophagus and cardia would test whether these tumors are also similar at the molecular level. METHODS: DNA was isolated from microdissected paraffin-embedded tumor tissues of patients who underwent esophagogastrectomy for adenocarcinoma of the esophagus (n = 19), cardia (esophagogastric junction, n = 12), or subcardia (n = 6). Exons 5 to 8 of the p53 gene were analyzed for the presence of mutations using the polymerase chain reaction with single-strand conformation polymorphism and DNA sequencing of bands showing abnormal mobility. The presence of mutation was confirmed by selective hybridization of a mutant-specific oligonucleotide to DNA isolated from the tumor. RESULTS: p53 mutations were identified in 18 of 37 (48.6%) tumors. Patients with p53 mutant tumors were significantly younger and had a significantly poorer prognosis. There was a similar prevalence of p53 mutations in adenocarcinomas of the esophagus (53%) and cardia (58%). In contrast, mutations were relatively uncommon in subcardia adenocarcinomas (one mutant tumor [17%]). The types of mutations found in the esophageal and the cardia cancers were also similar. CONCLUSIONS: Adenocarcinomas of the esophagus and cardia have a similar frequency and spectrum of p53 gene mutations, suggesting that these tumors have a common pathogenesis. Patients with mutations are younger, have signs of more advanced disease, and have a poorer prognosis than patients without mutations.

Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen.

In the rat model, esophageal adenocarcinoma reproducibly develops following surgically induced duodenal reflux into the esophagus and administration of nitrosamine. In addition, decreasing gastric acid via partial or total gastrectomy increases the prevalence of adenocarcinoma in this model. We questioned whether carcinogen was necessary for cancer development in the gastrectomized model and whether esophageal acidification could reverse the effect of gastrectomy. Three groups of 26 rats each were randomized to a surgical procedure to produce one of the following reflux models: gastroduodenal reflux by esophagojejunostomy, duodenal reflux by total gastrectomy and esophagojejunostomy, or no reflux by Roux-en-Y reconstruction. In a second experiment, 42 rats were operated on to induce duodenal reflux. One week following surgery, they were randomized to receive acidified water (pH 1.8) or tap water. The animals were killed at 24 weeks of age, and the esophagus was evaluated histologically. All animals with reflux had severe esophagitis and 87% developed columnar lining of the distal esophagus. Nearly half (48%) developed adenocarcinoma at the anastomotic site 16 weeks postoperatively and without carcinogen administration. Cancer prevalence did not differ between animals with gastroduodenal or duodenal reflux but tended to be lower in animals receiving acidified water. Duodenoesophageal reflux is carcinogenic in the rat model. Exogenous carcinogen is not necessary for cancer development in gastrectomized rats.

Composition and concentration of bile acid reflux into the esophagus of patients with gastroesophageal reflux disease.

BACKGROUND: Reflux of duodenal contents into the esophagus of patients with gastroesophageal reflux disease has been suggested by pH and bilirubin monitoring but is rarely directly measured. A portable device has been developed and was used to collect and quantitate material refluxed into the esophagus under ambulatory conditions during a prolonged time period. The objective of this study was to use this device to quantitate the composition and concentration of bile acids refluxed into the esophagus of patients with gastroesophageal reflux disease. METHODS: Esophageal aspiration was performed on 43 normal subjects and 37 patients with reflux disease during a 17-hour period. Aspiration was performed through a modified 16F Salem sump tube, positioned 5 cm above the lower esophageal sphincter and connected to a portable, battery powered pump that aspirated continuously at 100 mm Hg pressure. Validation studies showed that minimal amounts of saliva and swallowed liquids were aspirated and that gastric pressure was not altered. Postprandial, upright, and supine collections were performed. Total bile acids were assayed by a standard enzymatic assay; specific conjugated bile acids were analyzed by high-performance liquid chromatography. RESULTS: There was no difference in the total aspiration volume between normal volunteers and patients with gastroesophageal reflux disease, although patients tended to have a higher volume in the supine and postprandial periods. Bile acids could be detected in 58% of normal subjects and 86% of patients (p < 0.003). The mean concentration of bile salt exposure (micromole per liter) was higher in patients during the postprandial and supine periods. The mean bile acid reflux rate (micromole per hour) during all three aspiration periods was significantly higher in patients. On a molar basis the composition of the bile acids was 60% glycocholic acid, 16% glycodeoxycholic acid, and 15% glycochenodeoxycholic acid. Taurocholic, taurodeoxycholic, taurochenodeoxycholic, and glycolithocholic acid constituted the remaining 10%. CONCLUSIONS: Patients with reflux disease have an increased concentration of bile acids in their esophageal aspirates. Most of the exposure occurs during the postprandial and supine periods. A variety of bile acids were detected, most of which were in their glycine conjugated form.

Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease.

OBJECTIVE: The purpose of the study was to test the hypothesis that cardiac mucosa, carditis, and specialized intestinal metaplasia at an endoscopically normal-appearing cardia are manifestations of gastroesophageal reflux disease. SUMMARY BACKGROUND DATA: In the absence of esophageal mucosal injury, the diagnosis of gastroesophageal reflux disease currently rests on 24-hour pH monitoring. Histologic examination of the esophagus is not useful. The recent identification of specialized intestinal metaplasia at the cardia, along with the observation that it occurs in inflamed cardiac mucosa, led the authors to focus on the type and condition of the mucosa at the gastroesophageal junction and its relation to gastroesophageal reflux disease. METHODS: Three hundred thirty-four consecutive patients with symptoms of foregut disease, no evidence of columnar-lined esophagus, and no history of gastric or esophageal surgery were evaluated by 1) endoscopic biopsies above, at, and below the gastroesophageal junction; 2) esophageal motility; and 3) 24-hour esophageal pH monitoring. The patients were divided into groups depending on the histologic presence of cardiac epithelium with and without inflammation or associated intestinal metaplasia. Markers of gastroesophageal reflux disease were compared between groups (i.e., lower esophageal sphincter characteristics, esophageal acid exposure, the presence of endoscopic erosive esophagitis, and hiatal hernia). RESULTS: When cardiac epithelium was found, it was inflamed in 96% of the patients. The presence of cardiac epithelium and carditis was associated with deterioration of lower esophageal sphincter characteristics and increased esophageal acid exposure. Esophagitis occurred more commonly in patients with carditis whose sphincter, on manometry, was structurally defective. Specialized intestinal metaplasia at the cardia was only seen in inflamed cardiac mucosa, and its prevalence increased both with increasing acid exposure and with the presence of esophagitis. CONCLUSION: The findings of cardiac mucosa, carditis, and intestinal metaplasia in an endoscopically normal-appearing gastroesophageal junction are histologic indicators of gastroesophageal reflux disease. These findings may be among the earliest signs of gastroesophageal reflux and contribute to the authors understanding of the pathophysiology of the disease process.

Short-segment Barrett's esophagus: A prevalent complication of gastroesophageal reflux disease with malignant potential.

The significance of finding specialized intestinal epithelium localized to the region of the gastroesophageal junction is unclear. We tested the hypothesis that short segments of specialized intestinal epithelium are a consequence of gastroesophageal reflux disease and are premalignant. Two hundred forty-one patients with reflux symptoms underwent gastroscopy with rigorous biopsy. Barrett's esophagus was diagnosed when specialized intestinal epithelium was present on biopsy. Patients with Barrett's esophagus were subdivided according to the length of Barrett's mucosa: short-segment Barrett's (<3 cm) and extended Barrett's (> or =3 cm). Esophageal function was evaluated by manometry and 24-hour pH monitoring. In another 16 patients with small noncircumferential adenocarcinomas, the endoscopic length of Barrett's mucosa was recorded. Thirty-three patients (14%) had short-segment Barrett's and 37 (15%) had extended Barrett's esophagus. Patients with short-segment Barrett's esophagus had significantly more acid exposure than patients without specialized intestinal epithelium. Eighty-one percent of patients with short-segment Barrett's esophagus had increased esophageal acid exposure as did 100% of those with extended Barrett's esophagus. All lengths of Barrett's mucosa were associated with poor esophageal sphincter function and reduced contraction amplitudes in the distal esophagus. Twelve percent of patients with short-segment Barrett's esophagus had dysplasia. The length of Barrett's mucosa was > or =3 cm in 25% (4 of 16) of patients with early Barrett's adenocarcinoma. Short-segment Barrett's esophagus is commonly associated with gastroesophageal reflux disease. Further, short segments of specialized intestinal epithelium are premalignant in nature.

Barrett's esophagus. The significance of p53 in clinical practice.

OBJECTIVE: The authors provide an updated review the molecular biology of the p53 tumor suppressor gene with reference to its role in the malignant degeneration of Barrett's esophagus. SUMMARY BACKGROUND DATA: Appreciation of the function of the tumor suppressor gene p53 has given new insight into regulation of the cell cycle, and the gene appears to play an important role in many solid tumors. Esophageal adenocarcinoma is increasing in frequency in the western world at an alarming rate and is unique because there is a clear metaplasia (Barrett's mucosa)/ dysplasia/carcinoma sequence. p53 malfunction arises as an early event in this carcinogenic process and has been demonstrated in patients with nondysplastic Barrett's metaplasia. The possible causes of p53 malfunction in this setting are discussed. The most reliable method for the detection of p53 mutations is DNA sequencing. p53 immunohistochemistry appears too insensitive to act as a reliable marker for the presence of a mutation and cannot be used as a reliable marker for the future development of cancer. CONCLUSIONS: High-grade dysplasia within Barrett's mucosa remains the best clinical predictor of adenocarcinoma. The mutational spectrum observed in these tumors should provide clues to their etiology.

Duodenogastric reflux potentiates the injurious effects of gastroesophageal reflux.

Experimental studies have shown that the severity of esophageal mucosal injury in gastroesophageal reflux disease is related to the reflux of both gastric and duodenal juice. The purpose of this study was to determine whether duodenal juice potentiates esophageal injury in patients with reflux disease or, in fact, causes no harm allowing acid and pepsin to do the damage. A total of 148 consecutive patients who had no previous gastric or esophageal surgery underwent endoscopy and biopsy, manometry, and 24-hour esophageal pH and bilirubin monitoring. Esophageal injury was defined by the presence of erosive esophagitis, stricture, or biopsy-proved Barrett's esophagus. Exposure to duodenal juice, identified by the absorbance of bilirubin, was defined as an exposure time exceeding the ninety-fifth percentile measured in 35 volunteers. To separate the effects of gastric and duodenal juice, patients were stratified according to their acid exposure time. One hundred patients had documented acid reflux on pH monitoring, and in 63 of them it was combined with reflux of duodenal juice. Patients with combined reflux (50 of 63) were more likely to have injury than patients without combined reflux (22 of 37; P < 0.05). When the acid exposure time was greater than 10%, patients with injury (n = 40) had a greater exposure to duodenal juice (median exposure time 17.2% vs. 1.1%, P = 0.006) than patients without injury (n = 5), but there was no difference in their acid exposure (16.9% vs. 13.4%). Patients with dysplasia of Barrett's epithelium (n = 9) had a greater exposure to duodenal juice (median exposure time 30.2% vs. 7.2%, P = 0.04) compared to patients without complications (n = 25), whereas acid exposure was the same (16.4% vs. 15%). Duodenal juice adds a noxious component to the refluxed gastric juice and potentiates the injurious effects of gastric juice on the esophageal mucosa.

Gastric juice protects against the development of esophageal adenocarcinoma in the rat.

OBJECTIVE: The authors investigate the effects of gastric juice on tumorigenesis in a rat model of esophageal adenocarcinoma. SUMMARY BACKGROUND DATA: In rats treated with the carcinogen methyl-n-amyl nitrosamine, squamous cancer of the esophagus develops in a time- and dose-dependent manner. When methyl-n-amyl nitrosamine treatment is preceded by an operation to induce reflux of duodenal and gastric juice into the esophagus, there is an increased yield of esophageal tumors, many of which are adenocarcinomas. When only gastric juice refluxes into the esophagus, the tumor yield is less and adenocarcinomas are not found. METHODS: Two hundred seventy 8-week old Sprague-Dawley rats were studied. Twenty unoperated rats served as controls. The remaining rats underwent the following operations: esophagoduodenostomy with gastric and vagal preservation to induce duodenogastroesophageal reflux (n = 48); esophagoduodenostomy with antrectomy and Billroth 1 reconstruction to produce reflux of duodenogastric juice with the exclusion of the antrum (n = 53); esophagoduodenostomy with proximal gastrectomy to induce hypergastrinemia and reflux of duodenogastric juice with exclusion of the body and forestomach (n = 51); esophagoduodenostomy plus total gastrectomy to produce reflux of duodenal juice alone (n = 50); and esophagoduodenostomy with vagal and gastric preservation but with division of the duodenum just beyond the pylorus and reimplantation into the jejunum, 13 cm distal to the esophagoduodenostomy. This produced reflux of duodenal juice with gastric juice diverted downstream, (n = 48). At 10 weeks of age, all rats were given 4 weekly doses of carcinogen (methyl-n-amyl nitrosamine, 25 mg/kg intraperitoneally), and survivors were killed at 36 weeks of age. RESULTS: The prevalence rate of esophageal adenocarcinoma was 30% in rats with duodenogastroesophageal reflux and 87% in rats with reflux of duodenal juice alone. Fifty-six percent of rats with reflux of duodenogastric juice with exclusion of the antrum and 72% of rats with reflux of duodenogastric juice with the exclusion of the body and forestomach developed adenocarcinoma, showing a progression increase in the prevalence of adenocarcinoma as less gastric juice was permitted to reflux with duodenal juice into the esophagus. CONCLUSION: In this rat model, the presence of gastric juice in refluxed duodenal juice against the development of esophageal adenocarcinoma. The protective effect appears to be due to acid secretion from the stomach. Continuous profound acid suppression therapy may be detrimental by encouraging esophageal metaplasia and tumorigenesis in patients with duodenogastroesophageal reflux.

Dysplasia in Barrett's esophagus: diagnosis, surveillance and treatment.

Barrett's esophagus is a premalignant metaplastic change in the lining of the distal esophagus. It represents a peculiar form of healing which occurs in response to chronic gastroesophageal reflux disease. The condition should be considered in all patients undergoing endoscopy for symptoms of reflux disease and is confirmed when any biopsy shows the presence of specialized intestinal metaplasia irrespective of the macroscopic appearance of the distal esophagus. Endoscopic surveillance with multiple biopsy sampling of the esophageal mucosa is indicated for all medically fit patients with Barrett's esophagus. The diagnosis of dysplastic change within this abnormal mucosa requires histological examination of the biopsies by 2 independent but experienced pathologists. Identification of high-grade dysplasia heralds the development of invasive cancer and offers the physician an opportunity to intervene. Despite extensive endoscopic sampling of the esophageal mucosa the differentiation between high-grade dysplasia and invasive adenocarcinoma is unreliable. Esophagectomy remains the treatment of choice for patients with high-grade dysplasia since adenocarcinoma of the esophagus carries such a poor prognosis.

Carcinoembryonic antigen measurements in the management of esophageal cancer: an indicator of subclinical recurrence.

BACKGROUND: Detection of subclinical recurrence after surgical resection of esophageal cancer would allow earlier treatment of recurrent disease and potentially offer a better outcome for rescue therapy. METHODS: The utility of serum carcinoembryonic antigen (CEA) assay was evaluated in the management of patients with esophageal cancer. RESULTS: Serum carcinoembryonic antigen was measured preoperatively in 74 patients. Elevation of the CEA level (> 5 ng/mL) was present in 14 patients (19%). There was no relationship between preoperative CEA elevation and the stage of the tumor or the patients' survival. Eighty-three patients had CEA assay at regular follow-up intervals after resection. Objective evidence of recurrent disease was determined at similar intervals by chest radiography and abdominal and thoracic computed tomography scans. During follow-up, 53 of 83 patients developed recurrence. Postoperative elevation of CEA levels occurred in 32 patients, resulting in a sensitivity of 55% for detecting recurrent disease. Twenty-nine of the 32 patients who developed CEA elevation had objective evidence of metastatic disease. In 13 patients, the rise in CEA levels predated objective evidence of recurrence by a median of 4 months (range 3 to 35), and in 16 patients, it occurred concomitantly. The specificity with which an elevated postoperative CEA level indicated recurrence was high, 90%, with a positive predictive value of 91%. CONCLUSIONS: Postoperative CEA elevation is highly predictive of recurrent disease. In 16% of patients, elevation of CEA was the earliest objective sign of recurrence; such elevation should prompt consideration of adjuvant therapy.

Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re-emphasized.

OBJECTIVE: The author's goal was to determine the role of duodenal components in the development of complications of gastroesophageal reflux disease. SUMMARY AND BACKGROUND DATA: There is a disturbing increase in the prevalence of complications, specifically the development of Barrett's esophagus among patients with gastroesophageal reflux disease. Earlier studies using pH monitoring and aspiration techniques have shown that increased esophageal exposure to fluid with a pH above 7, that is, of potential duodenal origin, may be an important factor in this phenomenon. METHODS: The presence of duodenal content in the esophagus was studied in 53 patients with gastroesophageal reflux disease confirmed by 24-hour pH monitoring. A portable spectrophotometer (Bilitec 2000, Synectics, Inc.) with a fiberoptic probe was used to measure intraluminal bilirubin as a marker for duodenal juice in the esophagus. Normal values for bilirubin monitoring were established for 25 healthy subjects. In a subgroup of 22 patients, a custom-made program was used to correlate simultaneous pH and bilirubin absorbance readings. RESULTS: Fifty-eight percent of patients were found to have increased esophageal exposure to gastric and duodenal juices. The degree of mucosal damage increased when duodenal juice was refluxed into the esophagus, in that patients with Barrett's metaplasia (n = 27) had a significantly higher prevalence of abnormal esophageal bilirubin exposure than did those with erosive esophagitis (n = 10) or with no injury (n = 16). They also had a greater esophageal bilirubin exposure compared with patients without Barrett's changes, with or without esophagitis. The correlation of pH and bilirubin monitoring showed that the majority (87%) of esophageal bilirubin exposure occurred when the pH of the esophagus was between 4 and 7. CONCLUSIONS: Reflux of duodenal juice in gastroesophageal reflux disease is more common than pH studies alone would suggest. The combined reflux of gastric and duodenal juices causes severe esophageal mucosal damage. The vast majority of duodenal reflux occurs at a pH range of 4 to 7, at which bile acids, the major component of duodenal juice, are capable of damaging the esophageal mucosa.

A tailored approach to antireflux surgery.

Tailored surgical antireflux procedures were done in 104 patients during a 7-year period. Presenting symptoms included heartburn in 95 patients (91%), regurgitation in 83 patients (80%), and dysphagia in 61 patients (60%). Evaluation before operation included video barium esophagography, endoscopy, 24-hour esophageal pH monitoring, and esophageal motility studies. On the basis of anatomic and functional findings, the following procedures were performed: 15 laparoscopic and 49 open transabdominal Nissen fundoplications, 23 transthoracic Nissen fundoplications, seven Belsey partial fundoplications, and 10 Collis gastroplasty and Belsey partial fundoplications. The severity of symptoms was assessed before and after operation according to a previously published grading score. Eighty-five of the 104 patients (82%) were able to be contacted for a follow-up evaluation by means of a standardized questionnaire. Median length of follow-up was 4 years, with 40 patients having follow-up beyond 5 years. The tailored operation cured the symptoms of heartburn in 97%, regurgitation in 91%, and dysphagia in 92%. Ninety-eight percent of the patients reported that operation had cured their preoperative symptoms and 93% were satisfied with the outcome of the operation. To obtain optimal results, surgical treatment of gastroesophageal reflux disease should be tailored to the patient's anatomic and functional assessments. For early, uncomplicated disease a transabdominal Nissen fundoplication is done, laparoscopically when expertise exists. Patients with complicated disease should undergo an open antireflux procedure tailored to specific anatomic or functional abnormalities.

Esophageal resection with colon interposition for end-stage achalasia.

OBJECTIVE: To review the potential benefits of esophageal resection with colon interposition in patients with achalasia. DESIGN: Retrospective review. SETTING: University-based tertiary care center. PATIENTS: Nineteen patients (13 men, six women; median age, 44 years; age range, 26 to 77 years) with achalasia and recurrent or persistent dysphagia despite a variety of previous treatments. INTERVENTIONS: Esophageal resection and replacement with colon interposition. MAIN OUTCOME MEASURES: Mortality and morbidity of the procedure, symptomatic outcome, nutritional impact, ability to ingest a meal, and overall patient satisfaction. RESULTS: Follow-up results were available in 15 patients. The procedure accounted for no deaths and complications in four patients. Outcome assessment was done at a median of 6 years (range, 1 to 14 years) after resection. Overall, the symptomatic outcome was excellent to good in 12 patients. Eleven of the 15 patients gained weight (median weight loss, 6.3 kg) after the procedure. Thirteen patients were able to eat three meals daily; seven had the capacity to eat a steak dinner; five, an airline meal; and three, a snack. Nine of the 15 patients enjoyed an unrestricted diet. The speed of ingesting a meal was reduced in that most (11 of 15) were the last to finish when eating in a group. Fourteen of the 15 believed that the operation had cured or improved their preoperative symptoms, and a similar percentage were satisfied with the overall outcome of surgery. Most patients (12 of 15) would have the operation again. CONCLUSIONS: Esophageal replacement for end-stage achalasia can be accomplished with safety and marked improvement of preoperative symptoms. Despite multiple previous therapeutic failures, normal alimentation was restored in the majority of patients, with 93% judging the operation to be highly beneficial, improving their quality of life. Based on this success, guidelines for resection in end-stage achalasia are established.

Does duodenal juice reflux into the esophagus of patients with complicated GERD? Evaluation of a fiberoptic sensor for bilirubin.

BACKGROUND: It is controversial whether duodenal juice can damage esophageal mucosa in patients with gastroesophageal reflux disease (GERD). The issue remains unresolved partly because of difficulties in detecting the presence of duodenal juice in the lower esophagus. OBJECTIVES AND METHODS: This study utilized an in vitro portable spectrophotometer with a fiberoptic probe capable of detecting bile as a marker of duodenal juice. Absorbance/concentration curves were established with known bilirubin concentrations at pH 1.4 and pH 7.7. Esophageal pH and bilirubin absorbance were monitored in vivo over a 24-hour period in 20 healthy volunteers to determine the absorbance threshold for clinical use. The study population consisted of 21 patients with GERD. Four had no mucosal injury, 5 erosive esophagitis, and 12 Barrett's esophagus. RESULTS: The correlation between absorbance and bilirubin concentration was 0.98 and 0.99 for acid and alkaline environments, but bilirubin absorbance was 35% less in an acid environment. Using an absorbance threshold of 0.14, patients with GERD taken in toto had elevated esophageal exposure to bilirubin. No difference was observed in bilirubin exposure between reflux patients without mucosal injury and controls. Highest exposure occurred in patients with Barrett's esophagus. An important observation was that esophageal bilirubin exposure frequently occurred during periods when the esophageal pH was in the normal range. CONCLUSIONS: The fiberoptic probe accurately detects esophageal bilirubin as a marker of duodenal juice. Esophageal exposure to bilirubin is uncommon in normal subjects. Patients with erosive esophagitis and Barrett's metaplasia have increased esophageal exposure to duodenal juice compared to normal subjects. Reflux of duodenal juice into the esophagus can occur when the esophageal pH is within its normal range and is undetectable by pH monitoring alone.

Reasons for conversion from laparoscopic to open cholecystectomy in an urban teaching hospital.

BACKGROUND: Although laparoscopic cholecystectomy has replaced open cholecystectomy for the majority of patients, it is clear that a substantial minority will require laparotomy for safe and successful removal of the gallbladder. PATIENTS AND METHODS: Seven hundred forty-six laparoscopic cholecystectomies performed at LAC+USC Medical Center for January 1991 to May 1993 were retrospectively reviewed. Hospital stay, laboratory values, and complications, as well as the need for and reason for conversion to open cholecystectomy were recorded. There were 661 females and 85 males, with a mean age of 38 years (range 15 to 92). RESULTS: One hundred one (14%) of the 746 patients were converted to open cholecystectomy. Difficult dissection secondary to inflammation or adhesions and the need to treat common-bile-duct stones were the most common reasons for conversion. Patients requiring conversion to open cholecystectomy were more likely to have been admitted through the emergency department (72% versus 46%, P < 0.0001), have had prolonged hospital stays prior to surgery (mean time from admission to surgery 4.4 days versus 2.8 days, P < 0.0001), and to have had a thickened gallbladder wall on preoperative ultrasound (54% versus 20%, P < 0.001). CONCLUSIONS: The most common reasons for conversion to open cholecystectomy are inflammation and adhesions secondary to severe acute and chronic disease and/or the need for clearance of the common bile duct. Patients who were admitted to the emergency department, particularly if they were managed nonoperatively for a period of time and had a preoperative diagnosis of acute cholecystitis, were more likely to require conversion to open cholecystectomy.

Outcome of adenocarcinoma arising in Barrett's esophagus in endoscopically surveyed and nonsurveyed patients.

The value of endoscopic surveillance of Barrett's esophagus and the appropriate management of high-grade dysplasia remain unclear. Seventeen patients who were referred from endoscopic surveillance programs for management of high-grade dysplasia or adenocarcinoma developing in Barrett's esophagus were compared with 35 patients who had a newly recognized Barrett's adenocarcinoma, who had not been in a surveillance program. The referral diagnosis in the surveyed group was adenocarcinoma in six and high-grade dysplasia in 11. After repeat endoscopy with aggressive biopsy, two additional patients with adenocarcinoma were identified. Of the nine patients who underwent esophagectomy for high-grade dysplasia, five had invasive adenocarcinoma in the esophagectomy specimen, which had been missed before the operation, despite the fact that the median number of biopsy specimens obtained per 2 cm of Barrett's mucosa was 7.8 (range 1.5 to 15.0). Overall, 13 patients in the surveyed group had adenocarcinoma, 12 staged early and one staged intermediate by the WNM classification. Surveyed patients were operated on at an earlier stage than the nonsurveyed patients (10 early, 14 intermediate, and 11 late stage tumors; chi 2 = 15.6, p < 0.01). Despite the presence of adenocarcinoma in 13 of the 17 surveyed patients, their survival was significantly better than that of the nonsurveyed group (chi 2 = 5.8, p < 0.05). Patients referred from surveillance programs for Barrett's esophagus have a better outcome and earlier stage tumors than nonsurveyed patients. Inasmuch as multiple biopsy procedures do not exclude the presence of adenocarcinoma, continued surveillance of high-grade dysplasia is dangerous and potentially destructive to surveillance efforts.