Inflammatory aspects of experimental aneurysms. Effect of methylprednisolone and cyclosporine.
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Animals↗
Biomedical subjects
G Chejfec
Publications and source records attributed to G Chejfec.
Regulation of Lewis lung carcinoma invasion and metastasis by protein kinase A.
Metastatic Lewis lung carcinoma (LLC-LN7) cells have increased protein kinase A (PKA) activity and are more invasive in vitro than are non-metastatic (LLC-C8) cells. To determine whether PKA mediates the in vitro invasiveness and in vivo metastatic capabilities of these tumor cells, the LLC variants were stably transfected to over-express the C alpha subunit of PKA, and thus to have increased PKA activity, or to express a mutant cAMP-resistant PKA R1 alpha subunit which blocks PKA activation. Wild-type LLC-LN7 tumor cells were invasive in vitro and in vivo, recurred after tumor excision and metastasized to the lungs. However, they lost these properties after transfection to express the mutant R1 alpha that blocks PKA activation. The non-invasive, non-recurring and non-metastatic LLC-C8 cells gained the capacity to invade, to recur following tumor excision and to metastasize when transfected to express the PKA C alpha subunit.
Animals↗
Experimental study of determinants of aneurysmal expansion of the abdominal aorta.
The natural history and the factors determining the expansion of aneurysms have not been elucidated. To study the respective roles of elastolysis, collagenolysis, inflammatory cells, and hypertension in the pathogenesis of aneurysms, two previously described in vivo experimental models were used. An isolated segment of the abdominal aorta was infused with 15 units of pancreatic elastase. The maximal diameter of the aorta was measured before and after infusion and the isolated aorta was excised for classic histologic and immunohistologic studies. Twelve hours after the infusion of elastase the mean diameter of the aorta increased by 30%. The aorta had a cylindric form and only collagen fibers remained. Two and a half days after the infusion the aorta was spherical in shape and the diameter increased by 300% (3.09 +/- 0.08 mm) (p < 0.05). The entire aortic wall was invested by inflammatory cells. Six days after infusion the diameter increased by 421% (4.38 +/- 0.03 mm) (p < 0.05), and immunohistochemical staining showed numerous T lymphocytes and macrophages. Between 6 and 12 days, after perfusion inflammation decreased, the final diameter was 4.23 +/- 0.14 mm (not significant). Sixteen rats had thioglycollate and plasmin infusion, which are nonspecific activators of inflammation. Nine days after infusion the diameter of the aorta had increased by 288%; the elastic fibers of the media were fragmented and rare and the entire aortic wall was invaded by inflammatory cells, predominantly macrophages. The diameter of the aorta increased progressively. Two groups of 17 hypertensive rats (renovascular and spontaneous hypertension) received an aortic infusion of 15 units of pancreatic elastase. Elastolysis overlapped the limits of the infusion and inflammation persisted after 2 weeks. The mean diameter of the aorta (F = 11, p < 0.01) and the mean length of the aneurysms (F = 11.2, p < 0.001) were significantly increased. This study demonstrates that elastolysis and especially collagenolysis are determinants of aneurysmal expansion. Inflammation may be a promoting factor in the degradation of the aortic wall. Hypertension increases the hemodynamic stress to the aorta and activates mural inflammation.
Animals↗
Fecal occult blood testing: a false sense of security?
BACKGROUND: Recent screening studies with fecal occult blood testing (FOBT) report that one of three patients with colorectal cancer (CRC) can be cured of the disease; minimal attention has been given to the two of three patients who despite repeated screening go on to die of silent CRC. We report the known "miss rate" (known false negatives) of our 14-year ongoing program of FOBT that was organized in 1979 to detect early CRC. METHODS: From October 1979 through December 1993, 36,034 FOBT kits were distributed to patients who were without gastrointestinal complaints at Hines Veterans Affairs Hospital. The test was considered positive if at least one result of the six tests was positive and negative if the test result was equivocal. Patients with negative FOBT received a new test kit each year by mail. A positive test was followed by full colonoscopy or an air contrast barium enema if a full colonoscopy was not possible. RESULTS: The overall return rate was 47.8%. CRC was detected in 115 patients: 94 had a favorable and 21 had an unfavorable Duke's C or D or lymphoma prognosis. Of 21 patients 13 (62%) had initially tested FOBT negative (missed lesion). Of the 21 cases of advanced CRC 15 (71.43%) were in the descending, sigmoid, or rectosigmoid colon or rectum. CONCLUSIONS: (1) The majority (82%) of all CRC detected by FOBT screening are diagnosed at a favorable stage. (2) The majority of known advanced CRC (62%) escape early detection with FOBT. (3) Five (62.5%) of eight of the advanced CRC cases discovered on initial FOBT and 10 (76.9%) of 13 of advanced CRC cases missed on initial FOBT but detected in subsequent years were in the left colon and most likely in the range of the flexible sigmoidoscope. (4) FOBT as a sole screening test may provide a false sense of security, especially in patients with advanced left-side CRC.
Aged↗
Clinical features of duodenal somatostatinomas.
BACKGROUND: Duodenal somatostatinomas are rare tumors that are often asymptomatic or present with local symptoms rather than with evidence of excess somatostatin production. To characterize the clinical presentation and management of these neoplasms we reviewed the course of four patients. METHODS: The records of three men and one woman with duodenal somatostatinomas, who were treated between 1988 and 1992, are reviewed. RESULTS: Three of the patients presented with vague gastrointestinal complaints, and one was free of symptoms. No patient had symptoms of somatostatinoma syndrome, nor did any have associated neurofibromatosis. Three patients were diagnosed after biopsy of a submucosal mass during upper endoscopy. Three patients with tumors that measured less than 2 x 2 cm underwent local resection. One patient with a large tumor and liver metastases underwent a Whipple's operation and resection of the liver lesions. Immunohistochemically all tumors predominantly contained somatostatin, although each had traces of other neuropeptides. All tumors contained psammoma bodies. Follow-up periods ranged from 1 to 4 years. CONCLUSIONS: Duodenal somatostatinomas often appear with only local symptoms or are completely asymptomatic. Small tumors may be locally excised. Intraarterial methylene blue injection may help localize very small tumors during operation. Larger tumors, including those with localized metastases, should also be resected when possible.
Aged↗
Adenocarcinomas arising in tongues or short segments of Barrett's esophagus.
The diagnosis of Barrett's esophagus is established when the esophageal mucosa is lined by 2-3 cm of columnar epithelium or when specialized (intestinal type) columnar epithelium of any length is present. Emphasis is frequently placed on long segments of Barrett's because these patients reportedly are at higher risk of developing adenocarcinoma than patients with shorter segments. We present four cases of adenocarcinoma that arose in tongues or short segments (less than 2 cm) of specialized columnar epithelium near the gastroesophageal junction. We emphasize the need for biopsy of minimal appearing abnormalities in this area, and we suggest that histologic subtype, rather than length of involvement, be the major criterion for establishment of Barrett's esophagus.
Adenocarcinoma↗
Correlation of inflammatory infiltrate with the enlargement of experimental aortic aneurysms.
Inflammatory cells often are seen in the walls of human aortic aneurysms, but their significance is uncertain. To investigate their actions an in vivo model of arterial aneurysms was developed in the rat. Fifteen units of hog pancreatic elastase were infused for 2 hours into the isolated abdominal aorta in 26 rats. The vessels were measured in vivo and were excised for conventional histologic and immunohistologic study at selected intervals. In untreated control rats the diameter of the aorta was 1.04 +/- 0.02 mm. Immediately after infusion with elastase the aorta dilated 26% to 1.31 +/- 0.02 mm (p = NS), with no histologically demonstrable remaining elastic lamellae. Two and one half days after infusion the aorta dilated nearly 300% to 3.09 +/- 0.08 mm (p less than 0.05). These vessels exhibited large numbers of activated macrophages and T cells in the media. Three and 4 days after infusion the vessels dilated 388% to 4.04 +/- 0.09 mm and 367% to 3.82 +/- 0.31 mm, respectively. These vessels also exhibited numerous inflammatory cells in the media. Six days after infusion the vessels enlarged 421% to 4.38 +/- 0.03 mm (p less than 0.05), and the infiltrate persisted staining immunohistologically for macrophages, polymorphic neutrophils, and T lymphocytes. Twelve days after infusion the aneurysms remained enlarged but stable at 4.23 +/- 0.14 mm (p = NS). At this time the number of inflammatory cells regressed to control levels. The temporal correlation between inflammatory infiltrate and aneurysmal enlargement suggests that inflammatory cells may participate in the destruction of the aneurysmal vessel wall thereby promoting progressive enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Prevalence of oesophagitis in asthmatics.
The exact relation between gastro-oesophageal reflux and asthma remains poorly understood. To determine whether gastro-oesophageal reflux in asthmatics results in oesophagitis, endoscopy and oesophageal biopsy were performed on 186 consecutive adult asthmatics. The presence or absence of reflux symptoms was not used as a selection criterion for asthmatics. Endoscopy was performed by two endoscopists using predefined criteria. All asthmatics had discrete wheezing and either a previous diagnosis of asthma or documented reversible airways obstruction of at least 20%. The oesophageal mucosa was graded as normal if no erosions or ulcerations were present in the tubular oesophagus; as oesophagitis if a mucosal break with exudate (erosions and/or ulcerations) was present; and as Barrett's if specialised (intestinal) columnar epithelium was present. A hiatal hernia was diagnosed if greater than or equal to 2 cm of gastric mucosa appeared above the diaphragm during endoscopy. Thirty nine per cent of the patients with asthma had oesophagitis or Barrett's oesophagus, or both. There was no difference in the oesophageal mucosal status between asthmatics who required and those who did not require bronchodilators. Fifty eight per cent of asthmatics had a hiatal hernia. It is concluded that oesophagitis is common and independent of the use of bronchodilator therapy in asthmatics.
Adult↗
Spontaneous regression of hepatic pseudotumor.
Inflammatory pseudotumor of the liver is a rare benign lesion that usually has been discovered at laparotomy and treated by hepatic resection. We report a case of hepatic pseudotumor that was treated without surgery and that subsequently spontaneously resolved. Hepatic pseudotumor occur in all age groups, but most commonly in middle-aged adults, with a 3.5:1 male predominance. Presenting symptoms are 1 or 2 months of fever (66%), abdominal pain (51%), and weight loss (21%). Most often, the lesions are solitary encapsulated tumors composed of whorled laminated fibrous stroma and chronic inflammatory infiltrate. Our report provides documentation of spontaneous resolution of a hepatic pseudotumor.
Granuloma, Plasma Cell↗
The importance of hiatal hernia in reflux esophagitis compared with lower esophageal sphincter pressure or smoking.
The characteristics of gastroesophageal reflux disease have not been adequately defined. To determine the influence on the esophageal mucosa of hiatal hernia, lower esophageal sphincter pressure, acid reflux, and cigarettes and alcohol, we studied the reflux parameters, smoking habits, and alcohol consumption of 184 healthy, ambulatory outpatients who received endoscopy as the initial diagnostic procedure for workup of gastroesophageal reflux. Patients received endoscopic and histologic evaluations of the esophageal mucosa, prolonged ambulatory esophageal pH monitoring, and esophageal manometric determinations. Structural analysis was used to test the plausibility of various clinical theories concerning the most important factors contributing to the development of esophagitis. Statistical analyses revealed the following: (a) the lower esophageal sphincter pressure, acid contact time, and frequency of reflux episodes were highly associated with the presence of a hiatal hernia (p less than 0.003 for all parameters); (b) individuals with esophagitis had 16.5 times as many hiatal hernias as found in normal, healthy people; (c) cigarette smoking was not correlated with esophagitis but was significantly associated with increased lower esophageal sphincter pressure (r = 0.18; p less than 0.03); and (d) smoking was also not associated with increased acid contact time or increased frequency of reflux episodes. We conclude that (a) the presence of a hiatal hernia, not the pressure of the lower esophageal sphincter, is the most important predictor of reflux frequency, acid contact time, and esophagitis; (b) a decreased lower esophageal sphincter pressure, as suggested by structural analysis, is unlikely to be the cause of increased reflux episodes or esophagitis; and (c) if smoking and lower esophageal sphincter pressure are factors in the development of esophagitis, they damage the esophageal mucosa by mechanisms other than increased frequency of reflux episodes or increased acid contact time.
Computer Simulation↗
Plasma calcitonin gene-related peptide and atrial natriuretic peptide levels during resection of pheochromocytoma.
Calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) are potent hypotensive agents. To determine if they play a counterregulatory role in catecholamine excess in patients with pheochromocytoma, plasma levels were measured in four patients undergoing resection of sporadically occurring tumors. Each patient was prepared with phenoxybenzamine hydrochloride (Dibenzyline); two patients also received propranolol. Blood was obtained for plasma levels of epinephrine, norepinephrine, CGRP, and ANP at induction of anesthesia, skin incision, tumor manipulation, tumor removal, and 24 hours after operation. Baseline plasma norepinephrine and epinephrine levels were markedly elevated and increased significantly with tumor manipulation and decreased significantly 24 hours after operation. CGRP and ANP levels were slightly elevated throughout but did not change significantly with tumor manipulation or early after tumor resection. Circulating CGRP and ANP do not appear to have an acute counterregulatory role in catecholamine excess in patients with pheochromocytoma but may exert some influence on postoperative hypotension after tumor removal.
Adrenal Gland Neoplasms↗
An immunohistochemical study of benign clear cell ('sugar') tumor of the lung.
Benign clear cell ("sugar") tumor is a rare and most unusual pulmonary neoplasm. Although several reports in the literature have focused on the ultrastructural features of benign clear cell tumor, only a few cases have been formally studied by immunochemistry. Using a broad panel of polyclonal and monoclonal antibodies, five cases were evaluated. In all five cases, there was diffuse immunoreactivity for cathepsin B. Four cases showed immunoreactivity for HMB-45 and for alpha 1-antitrypsin. By two different sources for antivimentin, there was immunoreactivity in four cases (Biogenex, Dublin, Calif) and in two cases (DAKO, Santa Barbara, Calif), respectively. Additional immunoreactivity was present for S100 protein (three cases), HAM-56 (two cases), factor XIIIA (two cases), and neuron-specific enolase (one case). No case expressed immunoreactivity for keratin (AE 1, AE 3, or CAM 5.2), carcinoembryonic antigen, chromogranin, synaptophysin, glial fibrillary acidic protein, or alpha 1-antichymotrypsin. This immunochemical profile suggests that HMB-45, in combination with a variety of immunostains, may serve to distinguish benign clear cell tumor from other clear cell neoplasms.
Adult↗
Antigenic markers of hepatocellular carcinoma.
One hundred thirty-five hepatocellular carcinomas were examined for the presence of antigenic tumor markers by the avidin-biotin-peroxidase complex method. Ninety-seven were from the US and 38 came from Argentina. The following markers were tested: alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg), hepatitis D delta antigen (HD delta Ag), and Mallory's bodies (MB). In the US cases, AFP was present in 43%, AAT in 41%, HBsAg in 17%, and MB in 48%. Both HBcAg and HD delta Ag were absent. In the cases from Argentina, AFP was found in 26% and AAT in 18%. None of the other antigens were seen. Thirteen US tumors expressed three antigens and two four antigens simultaneously. This study reveals in humans a heterogenous expression of antigens by neoplastic hepatocytes with geographic differences, possibly due to multiple factors such as alcohol consumption or prevalence of hepatitis B infection.
Antigens↗
Pulmonary blastoma with neuroendocrine differentiation in cell morules resembling neuroepithelial bodies.
Pulmonary blastoma is an infrequent malignant neoplasm, so called because of its resemblance to fetal lung. The original description outlined the components as variable mixtures of epithelial and stromal elements. More recently, a variant displaying almost exclusively epithelial differentiation has been described. We report our findings in a case of pulmonary blastoma with predominance of epithelial cells, forming tubular structures and large morules. The architectural arrangement of the morules was remarkably similar to normal bronchial neuroepithelial bodies. Moreover, their immunohistochemical profiles were also very similar, including the expression of cytokeratins, chromogranin, neuron-specific enolase, synaptophysin, gastrin, calcitonin, bombesin, somatostatin and serotonin.
Adult↗
Linitis plastica-like carcinoma of the urinary bladder.
Two cases of signet-ring cell adenocarcinoma of the urinary bladder with a linitis plastica pattern of infiltration were studied. Mucin histochemistry indicated the presence of neutral and acid mucopolysaccharides and absence of sulphomucin. Immunocytochemistry of the tumour cells was positive for keratin and carcinoembryonic antigen, but negative for prostatic specific antigen and vimentin. The relevance of these observations to the differentiation and histogenesis of these tumours is discussed.
Adenocarcinoma, Mucinous↗
Islet cell carcinoma of the pancreas.
To define the course of malignant pancreatic islet cell tumors, 20 patients seen over 14 years with these neoplasms were reviewed. The 12 men and 8 women ranged in age from 22 to 76 years, with a mean of 52. Seven functional tumors included three insulinomas, two glucagonomas, one gastrinoma, and one somatostatinoma. One insulinoma was associated with a multiple endocrine neoplasia type I (MEN-I) syndrome. The 13 patients with nonfunctioning tumors had abdominal pain (3), jaundice (2), and steatorrhea (2). Seven had a palpable abdominal mass. Diagnosis of malignancy was based on local invasion (4), distant metastases (15), or both (1). One patient had percutaneous biopsy of a hepatic metastasis. All others had laparotomy for diagnosis and/or treatment. Each patient had a single tumor except the patient with MEN-I syndromes, who had multiple tumors throughout the pancreas. The head was involved in seven patients, the body in seven, and the tail in five. Operations included six curative and three palliative resections, five biliary diversions (two with concomitant enteric bypass), and five biopsies. Palliative resections were done for hormonal or local symptoms such as gastrointestinal (GI) bleeding and pain. Multiple chemotherapeutic agents were used, but the best results were obtained with DTIC (50% response). Four patients had radiation for liver, brain, or bone metastasis, with some improvement. Of five patients who had curative resections, four are alive 15 to 144 months, with a mean of 75 months. One died six years after diagnosis. Of the remaining 15 patients who had liver metastasis, seven patients are alive 8 to 168 months later, with a mean of 87 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma, Islet Cell↗
Adult nesidioblastosis. An unusual cause of fasting hypoglycemia.
Laidlaw coined the term nesidioblastosis in 1938 to characterize the neodifferentiation of the islet cells of Langerhans from pancreatic duct epithelium. It is well recognized in the pediatric population as a frequent cause of persistent neonatal hypoglycemia. However, its occurrence in adults is presumed to be rare and, therefore, it is not appreciated as a cause of hyperinsulinism. Three women, aged 29, 42, and 63, with adult onset hyperinsulinism secondary to nesidioblastosis are reported. All three patients required near-total pancreatectomy. The preoperative findings were consistent with hyperinsulinemic hypoglycemia as with insulinomas. Results of pancreatic imaging studies were normal in two patients and one patient had a pancreatic examination by computerized tomography and magnetic resonance imaging, with false-positive results. Two of the three patients had previously undergone a 50 per cent distal pancreatectomy in which the resected specimens were interpreted as normal in one patient and consistent with nesidioblastosis in the second. Both patients subsequently developed recurrent symptomatic hyperinsulinemic hypoglycemia that persisted despite dosage adjustments in diazoxide therapy. The oldest patient underwent a 95 per cent pancreatectomy at the initial surgical exploration because an insulinoma could not be identified. The other patients underwent a completion 95 per cent pancreatectomy. In both, histochemical examination of each specimen disclosed nesidioblastosis, characterized by clusters of islet cells interspersed throughout the exocrine tissue.
Adult↗
Neuroendocrine tumors of the gastrointestinal tract.
Neoplastic proliferations of neuroendocrine cells (NE) may occur throughout the entire GI tract but affect particularly appendix and ileum ("midgut carcinoids"), rectum ("hindgut carcinoids"), as well as stomach and the duodenum ("foregut carcinoids"). Only more exceptionally, they arise in the esophagus, jejunum and colon. The NE tumors encompass a heterogeneous gross and microscopic structural spectrum, ranging from inconspicuous microproliferations ("mucous membrane nevi") to bulky tumor masses. Their growth patterns are usually characteristic and easily recognized. In doubtful cases their NE differentiation becomes established by a characteristic silver affinity, by the ultrastructurally observed presence of characteristic "endocrine" secretion granules, and by immunohistochemically detectable occurrence of "pan-NE markers" (neuron-specific enolase, chromogranins, and synaptophysin), biogenic amines (mainly serotonin), and neurohormonal peptides. Foregut carcinoids usually contain serotonin, gastrin, and somatostatin, midgut carcinoids often only serotonin and tachykinins, whereas the hindgut carcinoids as a rule are multihormonal with a wide spectrum of hormonal peptides, including even insulin. Most GI NE tumors are found in the appendix (50%) and the ileum (30%). Practically all (98%) of the appendiceal NE tumors are benign. They have recently been proposed as arising from apparently Schwann-cell-related NE cells in the submucosa, whereas the ileal--and probably also all the other non-appendiceal NE tumors--are derived from the totipotential cells in epithelial crypts of the mucosa. Among the ileal NE neoplasms a large number can metastasize and result in a fatal outcome. The ability to metastasize is related to the size and to the multiplicity of the primary tumors at the time of initial diagnosis and, to some extent, to their histopathologic growth pattern. Now, some relationship between the prognosis and the cytochemically assessed nuclear DNA content of the NE tumor cells has also been established; not less than about 1/4 to 1/3 seem to be aneuploid. Almost 90% of the rectal carcinoids are benign. Exceptionally, a highly malignant NE neoplasms can arise from the colon/rectum--as well as from the esophagus--composed of NE cells of small and intermediate size. The NE tumors of the stomach are often composed of ECL (enterochromaffin-cell-like) cells; such ECL cell carcinoids are related to atrophic gastritis with pernicious anemia; experimentally, they can be induced by hypergastrinemia in rats. Duodenal carcinoids often contain psammoma bodies and can be associated with neurofibromatosis.
Appendiceal Neoplasms↗