Biomedical subjects
Publications and source records attributed to G W Clark.
The purpose of this article is to discuss the operative challenges posed by the advanced laparoscopic approach to a patient with situs inversus. The patient is a morbidly obese woman who has multiple co-morbidities related to her weight and who presented for bariatric surgery. A laparoscopic gastric by-pass was successfully performed. Situs inversus totalis is not a contraindication for laparoscopic surgery.
BACKGROUND: Women who suffer from morbid obesity are often infertile. If these women are able to become pregnant, they are considered high risk because of the hypertension, diabetes and other associated risk factors. Following the pregnancy is difficult due to limitations of the physical examinations. More costly ultrasound examinations are needed at a higher frequency. Bariatric surgery reduces the woman's weight and the incidence of obesity related co-morbidities. The number of pregnancies and rate of complications during those pregnancies in our post-bariatirc surgical patients were evaluated. METHOD: Our group has been doing bariatric surgery since the early 1980s. We have over 2000 active patients on our current newsletter mailing list. The patients also have a series of networks through support groups. The patients are informed to contact us when they become pregnant so we may assist the obstetrician with their care. Through these various means, we have been able to identify 41 women in our patient population who have become pregnant. Using personal interview, questionnaire, and review of perinatal records, pregnancy-related risks and complications were studied. RESULTS: With over a 95% follow-up rate on the patients identified as having been pregnant following surgery, we found less risk of gestational diabetes, macrosomia, and cesarean section than associated with obesity. There were no patients with clinically significant anemia. CONCLUSION: Since the patients had an operation that restricts their food intake, some basic precautions should be taken when they become pregnant. With this in mind, our patients have done well with their pregnancies. The post-surgical group had fewer pregnancy-related complications than did an internally controlled group that were morbidly obese during their previous pregnancies.
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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.
Oesophageal cancer is one of the most lethal carcinomas, with 5-year survival rates of less than 5%. This is due to a combination of factors including late presentation, associated cardiac and respiratory disease, and the technical difficulties of resectional surgery. The outcome for patients with oesophageal cancer has changed little in recent years, perpetuating a pervading attitude of pessimism in the surgical community. The epidemiology of oesophageal cancer is changing with the increasing incidence of adenocarcinoma. Most of these tumours arise in the setting of Barrett's oesophagus and chronic gastro-oesophageal reflux disease. Survival following surgery for oesophageal cancer is determined by several independent factors, most notably the pathological stage of the disease and the patients physiological status. However, in patients with limited disease, in particular patients with less than five lymph node metastases, the extent of the nodal dissection positively impacts survival. This article reviews the changing epidemiology of oesophageal cancer, focusing on the need for early diagnosis and the selection of patients for surgery. It places emphasis on the importance of integrating surgical therapy in a multidisciplinary team approach to the management of such patients.
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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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.
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.