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Biomedical subjects

D B Skinner

Publications and source records attributed to D B Skinner.

At least 37 records · Page 2Linked to original sources

Flow cytometric DNA analysis of squamous cell carcinoma of the esophagus.

Although an abnormal amount of cellular DNA content is known to occur in squamous cell carcinoma of the esophagus, the significance and clinical relevance of this finding have yet to be elucidated. Paraffin-embedded blocks from 77 patients with squamous cell carcinoma of the esophagus were dewaxed and made into a suspension by mechanical mincing and enzymatic digestion. The nuclei were stained with propidium iodide, and the DNA content evaluated with flow cytometric study. The DNA index (DI) and the coefficient of variation were determined and the results were compared with other pathologic prognostic features. DNA aneuploidy was identified in 70.1% of the specimens and found to correlate significantly with both histologic grading (P less than 0.025) and the incidence of postoperative recurrence (P less than 0.05). Although the 5-year survival was slightly better in the euploid group than in the aneuploid group (28.8% and 19.1%, respectively), this difference was not statistically significant (P greater than 0.1). There was no correlation of the DI with the extent of wall penetration by the tumor, the incidence of lymph node metastases, or the surgical staging, features previously shown to correlate with prognosis in patients with esophageal carcinoma.

Carcinoma, Squamous Cell↗

Expression of ras oncogene p21 protein in esophageal squamous cell carcinoma.

In order to investigate the value of ras oncogene expression as a prognostic indicator in esophageal squamous cell carcinoma, we evaluated the level of ras oncogene protein product (p21) in 52 specimens resected between 1977 and 1986. All patients were followed until death or for at least 2 years. Pathology slides and archival paraffin blocks were retrieved for confirmation of the original diagnosis, study of histopathologic features, and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution of antibody giving definitive staining using the avidin-biotin peroxidase method. Ras oncogene was expressed in 88.5% of the specimens. We did not find a significant correlation between ras expression and any of a variety of clinical and histopathologic prognostic parameters. Although patients' median survival after resection of specimens with ras oncogene expression was less than half the median survival after removal of tumors without such expression, this difference was not statistically significant. Further prospective investigations are needed to assess the role of ras oncogene evaluation in clinical practice.

Adult↗

Adenocarcinoma in Barrett's esophagus.

Adenocarcinoma arising in association with the columnar-lined esophagus is now recognized with increasing frequency. The incidence of malignant degeneration in Barrett's esophagus, its etiology, and pathogenesis are all issues of ongoing debate. The role of gastroesophageal reflux in driving the malignant change remains unproven. Surgical resection is the treatment of choice; however, prognosis is generally poor. Surveillance of patients with non-malignant Barrett's esophagus permits detection of early lesions where resection results in excellent long-term survival.

Adenocarcinoma↗

Indications for esophagectomy in nonmalignant Barrett's esophagus: a 10-year experience.

Between 1978 and 1988, 88 patients were referred for the surgical treatment of nonmalignant Barrett's esophagus. Nineteen patients required esophageal resection. Male/female ratio was 13:6; age range was 13 to 84 years (mean age, 49.8 years; median age, 40 years). Preoperative studies demonstrated strictures in 11 patients and ulcers in 7. Penetrating Barrett's ulcer resistant to treatment was the indication for resection in 5 patients. Ulcers penetrated to the pericardium (1 patient), pulmonary vein (1), lung (1), and mediastinum (2). Other indications for resection included undilatable strictures (2), previous operations (4), high-grade dysplasia (3), parietal cells lining the esophagus (1), patient's refusal of long-term surveillance (2), and the inability to exclude adenocarcinoma preoperatively (2). Reconstruction was achieved by colon interposition (15) or esophagogastrostomy (4), with one postoperative death. Mean follow-up was 41 months and was 100% complete. Of the 18 patients, 3 have occasional regurgitation but none have any dysphagia or weight loss. Esophageal resection is indicated in a select group of patients with Barrett's esophagus. Absolute indications include a deep penetrating ulcer confirmed intraoperatively, high-grade dysplasia, strong suspicion of cancer, and multiple previous operations. Relative indications include strictures not responding to dilation and young patients refusing long-term surveillance.

Adolescent↗

Chronic respiratory symptoms and occult gastroesophageal reflux. A prospective clinical study and results of surgical therapy.

Seventy-seven patients with a primary complaint of persistent cough, wheezing, and/or recurrent pneumonia were evaluated for the presence of occult gastroesophageal reflux disease. Fifty-four patients (70%) had increased esophageal acid exposure on 24-hour pH monitoring of the distal esophagus. In 28% of these patients the respiratory symptoms were thought to be due to aspiration because they occurred during or within 3 minutes after a reflux episode. In the other patients, the respiratory symptoms were either induced by or were unrelated to reflux episodes. The number of respiratory symptoms reported by the patients with increased esophageal acid exposure was directly related to the presence of a nonspecific esophageal motility abnormality (p less than 0.05). This suggested that a motility disorder contributes to aspiration by promoting the aboral flow of refluxed gastric juice. Seventeen patients with increased esophageal acid exposure had an antireflux operation to relieve their respiratory complaints. Patients whose respiratory symptoms induced reflux episodes were not helped by the procedure. Of the other patients, symptoms were abolished by the procedure only in those with normal esophageal motility. It is concluded that the majority of patients suffering from chronic unexplained respiratory symptoms have occult gastroesophageal reflux disease, but only a minority of them are helped by surgery. Carefully performed esophageal function studies are needed to select those patients who will benefit from a surgical antireflux procedure.

Adult↗

En bloc esophagectomy: the first 100 patients.

Between 1969 and 1984, 251 patients with carcinoma of the esophagus were evaluated. One hundred and eleven patients underwent en bloc esophagectomy. The technique of operation is described. Hospital mortality was 11% (12/111). Complications occurred in 49 patients. There have been no recurrences of cancer more than 3 years after operation. Absolute survival at 5 years is 55%, 29%, 15%, and 8% for W1N0, W1N1, W2N0, and W1/W2N2, respectively. En-bloc resection could be accomplished for esophageal carcinoma with an acceptable mortality and morbidity. The operation is potentially curative in a small subset of patients with unfavorable prognostic factors.

Adult↗

Pathophysiology of gastroesophageal reflux.

The factors controlling competence of the gastroesophageal junction have been carefully analyzed over the last decade. Although the presence of an anatomic sphincter guarding the lower esophagus has not been confirmed in humans, a manometrically defined high-pressure zone is present in the lower esophagus. The magnitude of sphincter pressure correlates well with the incidence of pathologic gastroesophageal reflux. Another important determinant of cardial competence is the length of intra-abdominal esophagus. The interaction of length and pressure in maintaining competence is demonstrated by several clinical and experimental studies. Twenty percent of refluxors have normal components of cardial competence. Several physical factors, namely components of Laplace's law, may govern control of reflux especially after antireflux repairs. The occurrence of esophagitis as a complication of gastroesophageal reflux is determined by the ability of the esophageal body to rid itself of an acid load as well as by factors that delay gastric emptying.

Animals↗

Surgical and endoscopic palliation of esophageal carcinoma.

We reviewed the records of 732 patients with advanced esophageal carcinoma to determine the efficacy of palliative therapy. Palliative resection was performed in 156 patients. Hospital mortality was 9.6%, 1-year survival was 29.1%, and median survival was 7.8 months. Excellent or good palliative results were obtained in 78% of operative survivors. Bypass procedures were performed in 49 patients: hospital mortality was 20.4%, with a median survival of 6.2 months. Excellent or good palliative results were obtained in 71% of operative survivors. Intubation of the tumor was performed in 254 patients. Thirty-day mortality was 10.2%, and median survival was 4.0 months. No patient received excellent palliation. Neodymium:yttrium-aluminum-garnet laser therapy or photodynamic therapy was performed in 50 patients. No procedure-related deaths were recorded, and median survival was 4.1 months. Excellent or good results were obtained in 83% of patients. Lesser procedures were performed in 106 patients, and 117 had only staging examinations. Although surgical palliation of esophageal cancer with resection or bypass provides good results, the cost is high. Improvements in palliative results require reduction in operative mortality, increased accuracy of preoperative staging, continuing use of laser therapy, and increased use of chemotherapy alone or in combination with radiotherapy and operation.

Adult↗

Choices in treating carcinoma of the esophagus.

A number of treatment regimens are now available for patients with esophageal carcinoma. They include several surgical procedures, chemotherapy and radiotherapy programs, either separate or combined, laser treatments, intubation and other palliative methods. Some of these programs are rigorous and are intended to be curative, others are purely palliative. Thus, each patient needs to be assessed by careful staging to select the most appropriate treatment. Analysis demonstrates that the factors principally and independently influencing prognosis are the depth of malignant penetration through the esophageal wall and the number of involved lymph nodes in addition to distal metastases. Modern staging techniques should be used to identify these prognostic factors preoperatively and at surgery before final decisions about treatment are made.

Carcinoma↗

Treatment of carcinoma of the proximal esophagus.

Selection of therapy for carcinoma of the proximal esophagus is controversial. We reviewed our experience with 41 patients with carcinoma of the esophagus within 24 centimeters of the incisor teeth to address this issue. Thirty-seven patients had squamous cell carcinoma, three had adenocarcinoma and one patient had a mucoepidermoid carcinoma. Seventeen patients underwent surgical therapy, which consisted of a resection in 15, colonic bypass in one patient and extracorporeal bypass in one. Ten patients underwent postoperative radiation therapy. Radiation therapy was the primary treatment in 23 patients and chemotherapy alone in one patient. The three month mortality rate was similar for patients with tumor resection and for those receiving radiation therapy as the primary treatment. Median survival time for patients undergoing resection and adjuvant radiation therapy was 12 months and seven months for those receiving only irradiation. Statistical analyses were not performed because patients with radiation only had more advanced disease, invalidating comparison. In terms of palliation, ten of the patients who had radiation therapy could eat solid food, seven could only swallow liquids and six had persistent, complete obstruction. All 12 of the survivors who had a resection were able to eat solid food. Although the one month mortality rate is higher for those treated surgically than with radiation therapy, the three month mortality rates are similar. Surgical treatment provides better palliation and a reasonable survival time and is preferred for patients with resectable disease who are physiologically fit enough to undergo operation. A benefit of postoperative adjuvant radiation therapy is undefined but probably present.

Adenocarcinoma↗

Surgical management of esophageal strictures.

The cases of 50 consecutive patients requiring operative treatment for esophageal strictures were reviewed to evaluate results and develop principles of management. Forty-eight had gastroesophageal reflux disease and 2 had chronic lye strictures. Of the patients with gastroesophageal reflux disease, 21 had a Barrett's esophagus. Esophageal dilations had been performed in 29 patients, 12 of whom also had undergone previous surgical procedures. Preoperative dilations by our group were used to determine further intervention. Patients with dilatable strictures were randomized to either a Nissen or a Belsey operation. In this group, there were no operative deaths, and excellent or good clinical results were obtained in 28 of 34 (82%) patients, with no significant differences noted in the outcomes between the two operations. Patients with undilatable strictures, Barrett's ulcer, or mucosal dysplasia underwent resection plus colon interposition (N = 12) or resection plus gastric interposition (N = 4). Two of the patients in the Nissen operation group later required resection and colon interposition, bringing that total to 14. Resection plus colon interposition resulted in excellent or good results in 71% of patients, with a 7% operative mortality. These results suggest that a standard transthoracic antireflux procedure can be performed with a low risk when strictures are dilatable. Excellent or good results were obtained in 82% of patients, which is equivalent to results for more complex operations. There was no significant difference in the outcome for the transthoracic Nissen procedure compared with the Belsey procedure. In addition, when required, resection plus colon interposition provided excellent or good results in 71% of the patients.

Anastomosis, Surgical↗

Surgical treatment of achalasia: results with esophagomyotomy and Belsey repair.

To address the controversy regarding the choice of operation for achalasia, the cases of 57 patients having operation, 38 for the first time (Group 1) and 19 with a previous procedure (Group 2), were reviewed. Surgical emphasis was on hiatal dissection to maximize exposure and use of the Belsey fundoplication to achieve cardiac competence without obstruction. Operative mortality was 1 (1.8%) of 57 patients. In group 1, 21 of the 38 had prior pneumatic dilations. All were treated with esophagomyotomy and a Belsey fundoplication. Clinical results are excellent or good in 30 (88%) of the 34 patients for whom follow-up is available, and are similar in patients with and without prior dilation. Lower esophageal sphincter (LES) pressure decreased from 22.3 to 7.7 mm Hg (p less than 0.001), and pH testing shows no reflux in any of 13 patients. In Group 2, previous operations were esophagomyotomy in 13, esophagomyotomy plus a Nissen fundoplication in 3, and a Nissen fundoplication only in 3. The initial operation failed because of inadequate myotomy in 6 patients, an obstructive Nissen fundoplication in 6, and reflux esophagitis in 7. In these 7 patients, acid reflux testing documented reflux due to cardiac incompetence and delayed clearance. Reoperations included takedown of a Nissen fundoplication in 6, esophagomyotomy and Belsey procedure in 15, Belsey procedure in 1, and resection plus colon interposition in 2. Clinical results are excellent or good in 12 (75%) of the patients with follow-up. These conclusions can be drawn. (1) Esophagomyotomy and Belsey fundoplication lowers LES pressure and provides good results with low risk, even after pneumatic dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pleuro-peritoneal shunting. Alternative therapy for pleural effusions.

Pleural effusions are resistant to standard therapy, which causes discomfort and can require prolonged hospitalization. As an alternative, pleuroperitoneal shunting for pleural effusions of various etiologies was evaluated. We implanted 36 shunts in 29 patients. Two patients had bilateral shunts and five had shunt revisions. The effusion was related to a malignancy in 22 patients, postoperative chylothorax in two patients, and other causes in five patients. Therapeutic thoracentesis had been attempted in 28 patients, and eight had had chest tube placement previously with attempted sclerosis. Seven patients had a trapped lung syndrome. There was no operative mortality. All patients were deemed ready for discharge from the hospital if they had recovered from the operation within 48 hours. Five patients had poor results, either because of a moribund status or their refusal or inability to pump the shunt. Of the remaining 24 patients, four had good results with temporary improvement, and excellent results were achieved in 20 patients (83.3%), who experienced symptomatic relief and stabilization or regression of pleural effusion until the time of their death. Patients with chylothorax experienced complete resolution. The 14 patients with malignant effusions had a median survival of 4 months, and there were no instances of peritoneal tumor seeding. In conclusion, pleuroperitoneal shunting is an alternative therapy for pleural effusions that requires a limited hospitalization only, is associated with minimal and short-term discomfort, achieves excellent results in properly selected patients, and is the only viable therapy when lung expansion cannot be achieved.

Adult↗

Composition of the refluxed material determines the degree of reflux esophagitis in the dog.

To evaluate the influence of the composition of refluxed material in the pathogenesis of esophagitis, a dog model was used to allow esophageal reflux of gastric secretions, duodenal pancreaticobiliary secretions, and a combination of both. Control dogs had only an esophageal incision. Incompetence of the cardia was established in five other groups by transecting the distal sphincter and creating a hiatal hernia. Two groups received moderate or maximal histamine stimulation of gastric secretion. A gastrojejunostomy, pyloromyotomy, and duodenal closure distal to the papilla were added in the other three groups, creating duodenogastric reflux; two were stimulated with histamine and one had a truncal vagotomy and no histamine. Radiologic, manometric, and pH studies showed that incompetence of the cardia was obtained. The dogs were killed 4 wk postoperatively and evaluated for gross and microscopic evidence of esophagitis. Erosive esophagitis was found only in dogs with reflux of gastric juice following maximal acid stimulation. Microscopic reflux changes in esophageal mucosa were seen in all groups; again, changes were most pronounced in dogs with maximal gastric stimulation. The combination of duodenogastric reflux and moderate gastric stimulation produced more significant alterations in microscopic reflux criteria than did moderate gastric stimulation alone. Our conclusions are as follows: In a dog model of gastroesophageal reflux of various combinations of gastric and duodenal secretory components, erosive esophagitis occurred only with maximal gastric stimulation in the absence of duodenogastric reflux. All reflux combinations, however, produced some degree of microscopic changes, suggesting they could eventually cause gross changes with a lengthened experimental time span.

Animals↗

Selective operative approach for diagnosis and treatment of anterior mediastinal masses.

We retrospectively reviewed the records of 41 patients with an isolated anterior mediastinal mass to identify whether the traditional surgical approach of resection for both diagnosis and therapy is the optimal approach to these tumors. In addition to plain chest radiographs, clinical evaluation included computed tomography (CT) in 23 and gallium scintigraphy in 23. The initial intervention was attempted excisional therapy in 16 and mediastinoscopy for biopsy in 25. Pathological diagnoses included lymphoma (13), thymoma (11), germ cell tumor (6), carcinoid (2), bronchogenic carcinoma (2), and other benign processes (7). Based on histological findings, nonoperative therapy was the most appropriate treatment in 61%. The clinical selection of the surgical approach was not aided by patient age, symptoms, or findings on CT. The gallium scan was positive in 13 of 15 patients for whom nonoperative therapy was appropriate, and was normal in 7 of 8 for whom excision was indicated. Mediastinoscopy is useful in the diagnosis of anterior mediastinal masses, and may eliminate unnecessary thoracotomy, especially when a gallium scan is positive.

Adolescent↗