Radical ilioinguinal lymph node dissection. Treating malignant melanoma.
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Publications and source records attributed to L J Auguste.
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Although Hürthle cell tumors are considered to be variants of follicular neoplasms, they have distinct cytologic and behavioral characteristics. To elucidate the basis for these differences, the expression of 5 oncogenes and growth factors (Pan-ras, N-myc, transforming growth factor-alpha [TGF-alpha], transforming growth factor-beta [TGF-beta], and insulin-like growth factor 1 [IGF-1]) was compared between 12 follicular carcinomas and 8 Hürthle cell carcinomas by immunocytochemistry. The percentage of follicular carcinomas and Hürthle cell carcinomas that stained positively for the different oncogenes was as follows and respectively: Pan-ras 8% versus 63%; TGF-alpha 17% versus 63%; TGF-beta 25% versus 88%; IGF-1 17% versus 88%; and N-myc 17% versus 100%. All these differences were highly significant by the chi 2 test. This difference in the expression of oncogenes between Hürthle cell carcinomas and follicular carcinomas suggests that these two tumors could, in fact, represent separate entities.
Oncogene expression has been found to be a potential marker for aggressive biologic behavior in certain tumors. We studied 21 follicular adenomas and 20 follicular carcinomas by immunocytochemistry utilizing specific monoclonal antibodies against HER-2/neu and c-myc oncogenes. Survival data were obtained from our institution's tumor registry. No expression of the HER-2/neu oncogene was found in the specimens studied. Cytoplasmic staining for c-myc was observed in 3 of 21 adenomas (14%) and 9 of 20 (45%) carcinomas (p < 0.05). The incidence of local, regional, and distant metastases was not significantly different in c-myc (+) and c-myc (-) patients. The c-myc oncogene is expressed more often in malignant than in benign follicular neoplasms of the thyroid, but its expression does not appear to be a good prognostic indicator.
Prostaglandin E2 renders the mucosa of the GI tract more resistant to acute injury by aspirin, acid, bile salts, and stress, whereas leukotrienes promote inflammation and retard healing of ulcers. The relationship of stress ulcer formation to changes in the activities of prostaglandin synthetase and lipoxygenase was evaluated in this study. After a 24 hr fast, 10 rats were stressed by the cold-restraint method for 4 hr and 10 rats were not stressed. Rats were terminated, stomachs were excised, the number of lesions were counted, and the nonulcerated mucosa was assayed for prostaglandin E2 and leukotriene synthesis. The mucosa was minced, washed in buffered saline, and then incubated for 10 min in a 1.3 mM sodium arachidonate solution containing a nonionic detergent (poloxamer 188), NaCl, KCl, KPO4, glutathione, hemin, MgSO4 and Hepes at pH 8.0. An ANOVA was used to compare the groups. Following stress the number of gastric lesions increased from 0.7 +/- 0.6 to 13.5 +/- 2.6, while leukotriene synthesis increased from 173 +/- 20 to 2170 +/- 187 pg/mg/min. A shift in synthesis from prostaglandins to leukotrienes in the mucosa appears to be detrimental to cytoprotection.
A method for the determination of prostaglandin G/H synthase and lipoxygenase activities in tissues was developed and employed with rat gastric mucosa samples. Tissues and microsomes were incubated in a buffer containing nonionic detergent and 1.32 mM arachidonic acid for 10 min. Following extraction with ethyl acetate, the oxidation products of arachidonic acid were derivatized with panacyl bromide. A reversed-phase column and a quaternary mobile phase were used to separate and quantitate the panacyl bromide esters of prostaglandin E2 and leukotriene C4/D4. Prostaglandin G/H synthase and lipoxygenase activities were determined in gastric mucosa and were 371 +/- 66 and 173 +/- pg/mg/min, respectively.
Because melanomas of the upper back, posterior arm, neck, and scalp (BANS) have been shown to be at high risk for recurrence and metastases, a tendency is to carry out wide excision (WE) and elective radical node dissection (RND) for patients with such lesions. To investigate whether this regimen improves the survival rate, we reviewed retrospectively 62 patients with clinical stage I BANS melanoma. Forty-five patients were treated by WE alone and 17 patients were treated by WE and RND (WE + RND). The male:female ratio was 1.5:1 for WE and 1.8:1 for WE + RND. The mean age was 52.9 +/- 15.3 years for WE and 48.2 +/- 12.5 years for WE + RND (p = not significant [NS]). The overall survival rate at 1, 3, and 5 years was 98%, 76%, and 71% for WE and 100%, 88%, and 76% for WE + RND (p = NS). The disease-free survival rate at 1, 3, and 5 years was 91%, 76%, and 71% for WE and 100%, 88%, and 76% for WE + RND (p = NS). In conclusion, WE + RND does not improve survival of patients with stage I BANS melanoma.
Prostaglandin E2 is one of the factors in the maintenance of gastric mucosal integrity and verapamil, a calcium channel blocker, has been shown to reduce gastric mucosal ulcerations during stress. To investigate whether this protective effect of verapamil is mediated via PGE2, four groups of 20 Holtzman rats were given either 1 ml of normal saline (NS) intraperitoneally (ip): 1 mg/kg of indomethacin (I) ip; 2 mg/kg of verapamil (V) ip or I followed by V. Then 10 animals from each group were submitted to stress by the cold-restraint method. After sacrifice, gastric mucosal ulcerations were counted and specimens of nonulcerated mucosa were assayed for PGE2 by HPLC. Stress-induced mucosal ulcerations were associated with a significant decrease in the gastric mucosal levels of PGE2 (from 64.2 to 32.7 pg; P less than 0.05). This effect was magnified by the administration of indomethacin (down to 21.0 pg). Verapamil significantly increased PGE2 levels both in the stressed (48.0 pg) and unstressed (99.9 pg) animals and significantly reduced ulcerogenesis when compared to either NS- or I-treated groups. This effect of verapamil was completely blocked by the administration of indomethacin. In conclusion, verapamil stimulates PGE2 synthesis and its protective effect against stress-induced mucosal damage seems to be mediated by PGE2.
To determine the causes of failures of cervical exploration for primary hyperparathyroidism, we reviewed 892 patients operated on by one surgeon from 1953 to 1990. Twenty-seven patients (3%) remained hypercalcemic or developed hypercalcemia within 6 months of surgery. Of these, five patients had one adenoma removed initially; at reoperation, three patients had a second adenoma that was successfully removed, whereas the other two patients had hyperplasia and required subtotal parathyroidectomies. No enlarged parathyroid glands were identified in 22 patients. Eventually, six patients became normocalcemic spontaneously, seven patients underwent re-exploration with a successful outcome in all but one case, two patients had ectopic hyperparathyroidism associated with carcinoma elsewhere, and seven patients refused reoperation and remain hypercalcemic. The failure rate of surgical exploration for primary hyperparathyroidism can be reduced by systematically exploring all four parathyroid glands. All abnormal parathyroids should be removed with histologic verification. When no abnormal glands are found, localization studies should be performed before re-exploration.
Intraoperative frozen sections fails to diagnose thyroid carcinoma accurately in 16% of cases. In such instances, we recommend that completion thyroidectomy be performed in the patient who has invasive carcinoma, is less than 70 years old, and has a reasonable life expectancy. The procedure should be carried out immediately if the error in diagnosis is discovered within a week; otherwise the procedure should be delayed until 3 to 4 months later. At that time, the recurrent laryngeal nerves and at least two parathyroid glands should be dissected and preserved. A paratracheal lymph node dissection should also be performed and the lower jugular lymph nodes should be sampled. If these jugular lymph nodes are found to be positive, a modified radical neck dissection should be added. The morbidity associated with the completion thyroidectomy is minimal. Postoperatively, a 131I scan of the neck should be carried out and ablative doses of radioactive iodine can be given if the uptake in the thyroid bed is greater than 1.5%. Subsequently, all patients are given thyroid suppressive therapy and are monitored closely. This approach will reduce the local recurrence rate and improve the long-term survival.
An increasing number of patients with primary hyperparathyroidism are found to have two or three enlarged parathyroid glands. Of 865 patients successfully operated on by one surgeon (J.N.A.), multiple enlarged parathyroid glands (adenomas) were found and resected in 33 cases (3.8%), with resulting normocalcemia lasting from 1 to 22 years (mean 5.8). Twenty-nine patients had two adenomas and four had three adenomas. In 28 patients the multiple adenomas were synchronous. Twenty-five patients underwent removal of all of the enlarged parathyroid glands in one operation; in three patients one adenoma was removed, reoperation for persistent hypercalcemia was performed, and a second adenoma was resected with cure. In five patients one adenoma was removed, normocalcemia ensued for 3 to 18 years, and a second (metachronous) adenoma occurred and was resected successfully. Although 10 of 70 enlarged parathyroid glands removed were labeled hyperplasia, cure in all but one of our patients by selective resection of only enlarged parathyroid glands emphasizes the unreliability of histologic criteria in differentiating between parathyroid adenoma and hyperplasia. Based on this study, we support the existence of multiple adenomas and advocate removal of only macroscopically enlarged parathyroid glands in patients with primary hyperparathyroidism.
To evaluate the nutritional benefits of a jejunal pouch vs. esophagojejunostomy following total gastrectomy, we reviewed 24 consecutive cases of total gastrectomy: 14 males and 10 females, 39 to 85 years of age (mean 66.6 y.) undergoing 9 jejunal pouches (JP) and 15 Roux-en-Y esophagojejunostomy (EJ). Indications for surgery included 15 adenocarcinomas, 3 lymphomas, 1 leiomyoma, and 5 hemorrhagic gastritis. The operative mortality was 12.5%. One JP patient was lost to follow-up. The mean survival for EJ was 13.3 months and for JP 36 months. Total gastrectomy resulted in persistent weight loss and hypoalbuminemia, and the creation of a jejunal pouch did not seem to improve significantly the nutritional status following total gastrectomy.
To determine whether starvation increases the susceptibility of the gastric mucosa to stress ulceration and whether this effect is linked to a change in the mucosal level of prostaglandin-E2 (PGE2), 100 Holtzman rats were divided into five groups and deprived of food for 0, 12, 24, 48 and 72 h. Then, ten animals within each group were stressed by cold restraint. At the end of the stress period, all these animals as well as their unstressed counterparts were killed, the number of gastric ulcers were counted, and mucosal levels of PGE2 were assayed. Fasting alone caused no ulcerations but a decrease in mucosal PGE2 during the initial 24 h (p less than .05). However, there was a subsequent increase in mucosal PGE2, possibly related to the release of free fatty acids during starvation. Starvation and stress caused a marked and consistent reduction of the mucosal PGE2 and an increase in the number of mucosal ulcerations directly related to the duration of starvation (p less than .05).
Gastric mucosa of rats and swine was incubated in buffer for 1 min to produce prostaglandins (PGs). After extraction and derivatization with p-(9-anthroyloxy)phenacyl bromide, the prostaglandin esters were determined by high-performance liquid chromatography. A 20-microliter sample was injected into a microparticulate silica gel column with a mobile phase of dichloromethane-acetonitrile-methanol (90:9:1). At a flow-rate of 1.5 ml/min the retention times of the prostaglandin esters were 7.14 min (internal standard), 7.90 min (PGF2), 10.05 min (thromboxane2), 12.26 min (6 alpha-keto-PGF1 alpha) and 13.98 min (PGF2 alpha). In spite of high sensitivity (0.1 ng per sample) for PGE2 and PGF2 alpha, only PGE2 synthesis was observed.
Prostaglandin biosynthesis by gastric mucosa was determined by a 1-min incubation, solvent extraction, and reaction with panacyl bromide. The prostaglandin ester was measured by normal-phase high-performance liquid chromatography. The prostaglandin E2 levels of normal gastric mucosa of rats and swine were 90.6 +/- 31.0 and 79.8 +/- 39.8 pg/min/mg tissue, respectively. This method was sensitive to 40 pg and specific for prostaglandin E2.
To evaluate the effect of arachidonic acid (AA), a prostaglandin precursor, on the mucosal level of PGE2 and its possible protective role against stress ulcerations, 40 Holtzman rats were divided into four groups: Group I intragastrically receiving 1 ml of normal saline (NS); Group II, NS pretreatment followed by stress; Group III, intragastric AA pretreatment without stress; and Group IV, intragastric AA followed by stress. AA was administered as a 120 mM solution in a nonionic detergent, adjusted to a pH of 8.0. Stress was provided by the cold-restraint method. After sacrifice, the number of gastric mucosal ulcerations were counted. Specimens of nonulcerated mucosa were assayed for PGE2 by derivatization with panacyl bromide and by using high-performance liquid chromatography. The animals in Groups I, III, and IV developed no gastric ulcerations and their mucosal prostaglandin E2 remained at a normal level, while those in Group II had a significant reduction of mucosal PGE2 (P less than 0.05) and a significantly increased number of gastric ulcerations (P less than 0.002). These data indicate that stress-induced mucosal ulcerations are associated with significant decreases in the gastric mucosal levels of PGE2. Intragastric administration of arachidonic acid prevents the formation of stress mucosal ulcerations and maintains a normal level of mucosal PGE2.
High-resolution intraoperative ultrasonography was compared with conventional radiographic imaging in the detection of small common bile duct (CBD) stones (less than 5 mm in diameter). Sixteen mongrel dogs had laparotomy and ligation of distal CBD; 1 week to 10 days later, 0-3 gallstones of varying sizes (2-5 mm) were introduced into the dilated CBD (6-16 mm). High-resolution intraoperative ultrasonography of the CBD and a conventional intraoperative cholangiogram were performed to detect the presence and number of stones. The results of these two tests were evaluated independently by two ultrasonographers and two surgeons. There were 21 true-positive and five false-negative readings by sonogram compared with 17 and 9, respectively, by cholangiogram. Sensitivity of the sonogram was 81% and 65.4% by cholangiogram. Score of accuracy was 1.06 and 1.62 by cholangiogram and 0.81 and 0.87 by ultrasound (p less than 0.05). Intraoperative ultrasonography was found to be more sensitive in detecting small CBD stones when compared with intraoperative cholangiogram.
Eighteen cancer patients receiving intensive chemotherapy developed leukopenia, fever, dysphagia, and oropharyngeal soreness. Superficial esophageal ulceration suggestive of esophagitis was demonstrated by radiographic examination in 33% of the patients (5/15). Upper gastrointestinal endoscopy revealed superficial ulceration and white mucosal patches in all patients. There was no morbidity associated with the endoscopic procedures. Sixty-one percent of the patients (11/18) had monilia albicans cultured from the oropharyngeal cavity, and 50% (9/18) had monilia cultured from the esophageal lesions. The evolution of the esophagitis correlated well with the survival of the patients. The monilial esophagitis persisted in six patients who all died within 24 days of systemic moniliasis. After initial improvement five additional patients succumbed; three of them from severe fungal infection. There was resolution of the esophagitis in the remaining seven patients who survived longer. However, two of them had recurrent monilial esophagitis and succumbed to systemic candidiasis. The other five have remained free of esophagitis, their underlying malignancies have remained under control, and so far they have survived an average of one and a half years. Endoscopy is more accurate than radiography in detecting postchemotherapy esophagitis. This complication can be fatal, since it is often followed by systemic candidiasis.
To compare the nutritional effects of two modes of reconstruction after total gastrectomy, a Hunt-Lawrence pouch was constructed in five mongrel dogs, whereas five other dogs had a simple Roux-Y esophagojejunostomy performed. Total body weight, daily food intake, serum albumin values, and intestinal absorption of carbohydrates, fats, and amino acids were evaluated in both groups over a period of 3 months. All values decreased postoperatively when compared with the preoperative values; however, there was no significant difference between the two groups. This study suggests that there is no nutritional benefit from a Hunt-Lawrence pouch over a simple Roux-Y esophagojejunostomy after total gastrectomy.