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G W Clark

Publications and source records attributed to G W Clark.

At least 19 recordsLinked to original sources

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.

Adenocarcinoma

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.

Adult

Surgical management of Barrett's esophagus.

Barrett's esophagus is a premalignant metaplastic change in the lining of the distal esophagus. It represents a peculiar form of healing which can occur at any time in patients with reflux esophagitis. Ninety percent of patients with Barrett's esophagus have a mechanically defective lower esophageal sphincter and 93% have abnormal esophageal acid exposure on 24 hour esophageal pH monitoring. Barrett's esophagus 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 appearances of the distal esophagus. An anti-reflux procedure is indicated for patients with Barrett's esophagus since it is highly effective in controlling reflux symptoms, healing the associated esophagitis, prevents repetitive injury of the Barrett's epithelium, and is more effective than medical therapy in the long term. Annual endoscopic surveillance with multiple biopsy sampling of the esophageal mucosa is indicated after the antireflux repair. Identification of high grade dysplasia heralds the development of invasive cancer and offers the surgeon 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. Barrett's adenocarcinoma can be cured by en bloc esophagectomy in selected patients with early disease.

Adenocarcinoma

Biopsy of upper gastrointestinal tract lesions. Indications and clinical significance.

Endoscopic biopsy is an integral part of the investigation of foregut disease. This article discusses the indications for obtaining biopsies in lesions of the esophagus and stomach and for interpretation of brush cytology, fine needle aspiration, and interoperative tissue biopsy in foregut malignancies. New concepts in the diagnosis of Barrett's esophagus are proposed and appropriate management strategies of this condition are examined in depth.

Adenocarcinoma

Selection of patients for curative or palliative resection of esophageal cancer based on preoperative endoscopic ultrasonography.

OBJECTIVE: To assess the accuracy of pretreatment staging and the potential of using endosonographic findings to select patients for curative or palliative resection by comparing the preoperative endosonographic and computed tomographic (CT) findings with the histology of the surgical specimen. METHODS: Forty-two patients referred to our clinic with esophageal carcinoma underwent preoperative upper endoscopy with biopsy, endosonography, thoracic CT, and abdominal CT. Based on endoscopic ultrasonographic findings, patients with early-stage disease underwent en-bloc esophagogastrectomy, whereas those with advanced disease had a palliative transhiatal esophagectomy. Exceptions included patients with poor physiologic reserve who were treated by the transhiatal route. RESULTS: In eight patients, we were unable to pass the ultrasonographic endoscope. Seven of these eight had transmural tumors with nodal involvement on histologic study. Tumor length, based on endosonographic measurements, was correctly predicted in 34 patients (85%). Extent of wall penetration was accurately predicted in 26 (76%) of the 34, and regional lymph node status was accurately predicted in 28 (82%) of the 34. Of the patients with sonographic wall penetration, 80% had histologic evidence of one or more positive nodes. Using the WNM staging system, endoscopic ultrasonography correctly staged the cancer in 68% of the patients. Three patients were treated with an inappropriate procedure. CONCLUSION: Endosonography is a reliable method for the preoperative staging and selection of patients for curative or palliative resection. Endosonographic wall penetration appears to be a critical factor in determining tumor spread.

Adult

Is Barrett's metaplasia the source of adenocarcinomas of the cardia?

OBJECTIVE: To investigate the prevalence of Barrett's esophagus in patients with adenocarcinomas located at the gastroesophageal junction. DESIGN: A case series of patients who underwent esophagogastrectomy for adenocarcinoma was retrospectively reviewed. Tumors were grouped by location as esophageal, cardiac, and subcardiac, and the prevalence of specialized intestinal metaplasia in the histological specimens was determined. SETTING: A university department of surgery that specializes in esophageal diseases. PATIENTS: One hundred patients with adenocarcinoma of the esophagus, cardia, or proximal stomach. MAIN OUTCOME: Cardiac adenocarcinomas were associated with Barrett's esophagus in 42% of the patients. RESULTS: Specialized intestinal metaplasia was identified in the histological sections from the resected specimen in 42% (13/31) of cardiac adenocarcinomas and in 79% (38/48) of esophageal adenocarcinomas but in only 5% (1/21) of subcardiac adenocarcinomas. The preoperative endoscopic biopsy results concurred with the final diagnosis of Barrett's esophagus in 33 of the 38 esophageal tumors, six of the 13 cardiac tumors, and the one subcardiac tumor but failed to detect specialized intestinal metaplasia in 54% (7/13) of cardiac tumors. Cardiac tumors were associated with shorter lengths of Barrett's mucosa than esophageal tumors (2.7 +/- 1.8 cm vs 7.4 +/- 3.4 cm, P < .01). The Barrett's metaplasia was dysplastic in 36 of the 38 esophageal tumors, 10 of the 13 cardiac tumors, but not in the subcardiac tumor. CONCLUSIONS: Adenocarcinomas located at the gastroesophageal junction were associated with Barrett's metaplasia in nearly one half of the patients. The length of the Barrett segment tends to be short and may be missed during endoscopy. The presence of high-grade dysplasia within Barrett's mucosa supports a barrett's origin for half of the adenocarcinomas arising at this location.

Adenocarcinoma

Effect of gastroduodenal juice and dietary fat on the development of Barrett's esophagus and esophageal neoplasia: an experimental rat model.

BACKGROUND: Reflux of duodenal content into the lower esophagus of rats enhances the formation of nitrosamine-induced esophageal cancer and results in the induction of adenocarcinoma. We investigated the extent of the mucosal injury that was produced when the lower esophagus of rats was exposed to the reflux of gastroduodenal juice in the presence or absence of a carcinogen and tested the hypothesis that induction of esophageal cancer in this model would be influenced by the intake of dietary fat. METHODS: Esophagoduodenostomy with gastric preservation was performed in 165 Sprague-Dawley rats in order to expose the lower esophagus to the reflux of gastroduodenal juice. Postoperatively selected groups of rats were treated with the carcinogen methyl-n-amylnitrosamine (MNAN). Subsequently, rats were fed diets of differing fat and calorie content for 20 weeks until they were put to death. RESULTS: Refluxed gastroduodenal juice, in the absence of MNAN, induced esophageal inflammatory changes (diffuse papillomatosis and hyperkeratosis) in 38 of 39 rats (97%), specialized columnar metaplasia (Barrett's esophagus) in four of 39 (10%), dysplasia in three of 39 (8%), and squamous cell carcinoma in one of 39 (3%). Diet did not influence the incidence of neoplasia in the absence of MNAN treatment. In rats treated with MNAN, refluxed gastroduodenal juice induced inflammation in 110 of 111 rats (99%), columnar metaplasia in 14 of 111 (13%), and cancer in 63 of 111 (57%). Fifty-eight percent of esophageal tumors were squamous cell carcinoma and 42% were adenocarcinoma. The highest incidence of tumors was observed in rats fed the semipurified high-fat diet (24 of 29; 83%) compared with rats fed the semipurified control diet (13 of 29; 45%), semipurified, calorie-restricted diet (15 of 27; 55%), and chow diet (11 of 26; 42%), p < 0.05. CONCLUSIONS: Reflux of gastroduodenal content into the lower esophagus of rats can induce both Barrett's metaplasia and neoplasia. Addition of a carcinogen increases the tumor yield and results in a proportion of the lesions being adenocarcinoma. This carcinogenic process is promoted by a diet with a high fat content.

Adenocarcinoma

Nodal metastasis and sites of recurrence after en bloc esophagectomy for adenocarcinoma.

The operative specimens from 43 patients undergoing en bloc esophagectomy for adenocarcinoma of the lower esophagus or cardia were analyzed. Depth of invasion of the tumor and extent and location of lymph node metastases were determined. Postoperative recurrence was identified from positive findings on successive 3-month computed tomographic scans. Positive nodes occurred in 33% (2/6) of intramucosal tumors, 67% (6/9) of intramural tumors, and 89% (25/28) of transmural tumors (p < 0.01). Commonly involved nodes were those in the lesser curve of the stomach (42%), parahiatal nodes (35%), paraesophageal nodes (28%), and celiac nodes (21%). Excluding perioperative deaths, follow-up was complete for 38 patients. Twenty patients had recurrence. Fifteen patients (40%, 15/38) had nodal recurrence: cervical, 7.9% (3/38); superior mediastinal, 21% (8/38); and abdominal, 24% (9/38) (retropancreatic in 7 and retrocrural in 2). Of 5 patients with nodal recurrence alone, 3 (60%) had recurrence at sites outside the margins of resection. Patients with four metastatic nodes or less had a survival advantage over those with more than four (p < 0.05). There was no difference in survival according to location of nodal metastases. Two (22.2%) of 9 patients with celiac node metastases survived longer than 4 years. Adenocarcinoma of the lower esophagus and cardia spreads widely to mediastinal and abdominal nodes, and death can occur from nodal disease. Rates of lymph node metastases increase with the depth of the primary tumor. Patients with lymphatic metastases can be cured particularly if there are fewer than four nodes involved. Curative surgical therapy necessitates wide lymph node resection to ensure removal of all metastatic nodes.

Adenocarcinoma

Motility in the Hunt-Lawrence pouch after total gastrectomy.

PURPOSE: The aim of this study was to evaluate motility patterns of the Hunt-Lawrence pouch and the jejunal limb of patients reconstructed with a pouch after total gastrectomy, and to compare the findings in symptomatic patients to those without symptoms after the operation. PATIENTS AND METHODS: Thirty-three patients who had undergone post-gastrectomy pouch reconstruction were studied using a water-perfused motility system. In 21, the pouch was connected by a Roux-en-Y, and, in 12, by a jejunal interposition. Twenty-eight patients were asymptomatic, including 17 connected by a Roux-en-Y and 11 by a jejunal interposition. Five patients were by a jejunal interposition. Five patients were symptomatic, including 4 connected by Roux-en-Y Y and 1 by jejunal interposition. A control group consisted of 5 healthy volunteers who had not undergone operation. RESULTS: The motility phases in the pouch and jejunal limb of asymptomatic patients were of shorter duration than those of controls, and they followed a random sequence instead of a normal progression from phase I to II to III. Motility features were similar in the pouch and the jejunal limb. Orthograde propagation of phase III-like activity was reduced and may contribute to the pouch storage function. Four of the 5 symptomatic patients showed highly abnormal motility with hypomotile or obstructive patterns. The technique of connecting the pouch--jejunal interposition of Roux-en-Y--did not affect the motility findings. CONCLUSIONS: The altered motility occurs after a Hunt-Lawrence pouch reconstruction in asymptomatic patients. Symptoms after gastrectomy are associated with further disturbed motility that can be differentiated from the motility changes in asymptomatic patients.

Adult

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.

Adenocarcinoma

Comparison of an intravenous bolus of famotidine and Mylanta II for the control of gastric pH in critically ill patients.

The effects of the intravenous bolus administration of famotidine versus the administration of Mylanta II liquid every 2 hours on the pH of the gastric antrum, body, and fundus for 24 hours were compared in 10 critically ill patients admitted to the intensive care unit with isolated cranial trauma. Patients received 30 mL of Mylanta II every 2 hours via nasogastric tube for 24 hours, followed by administration of 20 mg of intravenous bolus famotidine every 12 hours for the subsequent 24-hour period. pH of the gastric antrum, body, and fundus was monitored continuously using a three antimony pH electrode/nasogastric tube assembly. Gastric pH data were analyzed for the percentage of time pH was less than 4 and median pH for the antrum, body, and fundus for each 24-hour period. The percentage of time pH was less than 4 was significantly less in the antrum and body of the stomach during famotidine therapy (8.9% +/- 3.6% and 24.9% +/- 6.9%, respectively) compared with Mylanta II (39.1% +/- 6.7% and 57.6% +/- 8.5%, respectively, both p < 0.005), but was not significantly different in the fundus (famotidine: 25.3% +/- 7.8%; Mylanta II: 28.3% +/- 6.5%). Median gastric pH for 24 hours was significantly greater in the antrum and body of the stomach during famotidine therapy (7.8 +/- 0.2 and 6.8 +/- 0.6, respectively) compared with Mylanta II (4.5 +/- 0.6 and 3.7 +/- 0.9, respectively, p < 0.005 and p < 0.01, respectively), but was not significantly different in the fundus (famotidine: 5.9 +/- 0.8; Mylanta II: 5.4 +/- 0.7). The data indicate that an intravenous bolus of famotidine every 12 hours is more effective than Mylanta II liquid every 2 hours administered via a nasogastric tube in maintaining gastric pH above 4 in critically ill patients. Famotidine produces a uniform increase in gastric pH throughout the stomach, whereas Mylanta II controls only proximal gastric pH, probably related to fundic pooling of antacid in the supine position.

Adult

Metabolism of carcinogenic nitrosamines in the rat and human esophagus and induction of esophageal adenocarcinoma in rats.

The mechanism is discussed by which certain nitrosamines induce esophageal papillomas and squamous cancer in rats, and some evidence is presented for the view that nitrosamines also induce the same cancer in humans, especially in China and South Africa. Studies on the metabolism of nitrosamines by cytochrome P450 isozymes in rat and human esophagus, including the activation reactions of formaldehyde and pentaldehyde formation from methyl-n-amylnitrosamine (MNAN), are reviewed. These reactions are catalyzed by microsomes from the rat and human esophagus, probably because these microsomes contain specific cytochrome P450 isozymes. Evidence is reviewed for the occurrence of nitrosamines related to MNAN in fungus-infected corn. The incidence of esophageal adenocarcinoma is rising in Western countries. The precursor lesion, Barrett's esophagus, is associated with colon cancer, suggesting a role for bile salts in the induction of the esophageal tumor. Studies are described in which rats were subjected to esophago-duodenostomy (joining the duodenum to the esophagus) and then treated with nitrosamines that normally induce esophageal squamous cancer. Adenocarcinomas of the lower esophagus were induced as well as Barrett's esophagus (under one set of conditions). Feeding a high-fat diet with this system increased the incidence of esophageal adenocarcinoma. This tumor was not induced when the operation was changed to esophago-gastroplasty (widening the lower esophageal sphincter). These results support a role of reflux of duodenal contents (including bile and pancreatic juice) rather than of gastric contents in the etiology of human esophageal adenocarcinoma.

Adenocarcinoma

Effect of duodenal switch procedure on gastric acid production, intragastric pH, gastric emptying, and gastrointestinal hormones.

The duodenal switch operation preserves the pylorus and the proximal 3 to 7 cm of duodenum in continuity with the stomach while diverting pancreaticobiliary secretions. We compared it with the Roux-en-Y without vagotomy or antrectomy in 12 dogs with innervated gastric pouches. Acid secretion was inhibited between tests using ranitidine in the Roux-en-Y group only, but two of the six dogs still developed stomal ulcers and the remainder showed stomal hyperemia. This may be due to a significant increase in gastric acid output after Roux-en-Y, but gastric emptying and plasma gastrin, cholecystokinin, secretin, gastric inhibitory polypeptide, peptide YY, and neurotensin were similar after both procedures. In 12 patients and a further 6 dogs, the duodenal switch caused no significant change in the intragastric pH environment as assessed by intragastric pH monitoring. The duodenal switch is a suitable procedure for pancreaticobiliary diversion.

Anastomosis, Roux-en-Y

Migratory birds of central Washington as reservoirs of Campylobacter jejuni.

Migratory ducks, Canada geese, and sandhill crane from the Pacific North American Flyway have been screened for Campylobacter spp. Samples (298) from these birds were examined and the incidence of Campylobacter spp. in the samples were as follows: sandhill crane (Grus canadensis tabida), 81%; ducks (Aythya collaris, Anas carolinensis, Aythya americana, and Anas platyrhynchos), 73%; and Canada geese (Branta canadensis), 5%. All isolates were identified as Campylobacter jejuni. To our knowledge this is the first report of the isolation of C. jejuni from sandhill crane. The high frequency of isolation in both the sandhill crane and migratory ducks indicated that these bird populations may play a significant role in the dissemination of the bacterium. Because of their migratory habits, these birds may be particularly important in spreading C. jejuni to remote areas.

Animals

Seasonal occurrence of Campylobacter spp. in surface waters and their correlation with standard indicator bacteria.

Campylobacter jejuni, Campylobacter coli, and a Campylobacter-like organism were isolated from a number of natural water sources in central Washington, including ponds, lakes, and small mountain streams at elevations ranging from 1,460 to 5,400 feet (ca. 445 to 1,646 m) above sea level. At the two sites where extensive sampling was done, the bacteria were recovered throughout the year. Generally, the recovery rates were highest in the fall and winter months and lowest during the spring and summer months. Campylobacter density did not show significant correlation with microbiological (plate counts of fecal and total coliforms, fecal streptococci, and heterotrophic bacteria) or physical (water temperature, pH, and conductivity) parameters.

Campylobacter

Small rodents and other mammals associated with mountain meadows as reservoirs of Giardia spp. and Campylobacter spp.

Sixty-five percent (469 of 722) of the fecal samples collected from small rodents in the central Washington Cascade mountains were positive for Giardia spp. Trapping studies showed that microtines of the genus Microtus were heavily infected with the parasite. Morphologically the cysts and trophozoites were of the Giardia duodenalis type. Small-rodent populations appear to maintain their infection throughout the year. Our data suggest that there is no difference in the percentage of positive animals in areas receiving a lot of human use as opposed to animals in those areas receiving very little or no human use. Giardia spp. were also found in elk and beaver fecal samples. Campylobacter spp. were recovered infrequently from the small rodents inhabiting alpine meadows. Of 551 specimens cultured, less than 1% were positive for the bacterium, and the isolates were identified as Campylobacter coli. Water voles were susceptible to a human isolate of Campylobacter jejuni and shed the bacterium for several weeks. C. jejuni was also isolated from a bear fecal sample collected from a protected watershed. Our studies indicate that microtines and possibly other small rodents inhabiting mountain meadows have a potential to act as a reservoir for both Giardia spp. and Campylobacter spp. Because these animals may carry human pathogens, they should be included in animal surveys designed to assess the health risks associated with mountain watersheds.

Animals