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Biomedical subjects

A R Graham

Publications and source records attributed to A R Graham.

At least 37 records · Page 2Linked to original sources

Catheter ablation of the ventricular septum with radiofrequency energy.

The safety and feasibility of performing catheter ablation of the ventricular septum with radiofrequency energy was assessed in a closed-chest canine model. Radiofrequency energy (750 kHz) was delivered in a bipolar manner via the distal electrodes of two quadripolar catheters positioned across the ventricular septum in 10 dogs at two sites. Each site received from 159 to 823 joules of delivered energy over one to three applications. Four additional dogs underwent unipolar radiofrequency ablation with 331 to 767 joules of delivered energy to each septal site. No significant acute or latent arrhythmias were noted. Dogs were killed at 1 day, and at 1, 2, and 4 weeks after the procedure. Out of a possible 40 potential ablation sites on each side of the septum after bipolar ablation, 21 (53%) discrete endocardial lesions were identified, ranging in size from 4 x 3 x 1.5 to 10 x 8 x 4 mm. When 352 joules or more delivered energy was applied per site, lesions were located at 18 of 28 (64%) possible sites. After unipolar radiofrequency ablation, similarly sized lesions were identified at 15 of 16 (94%) ablation sites. Histologic examination demonstrated well-delineated round or ovoid-shaped lesions with microscopic thrombi overlying two lesions. In conclusion, catheter ablation of the ventricular septum with radiofrequency energy appears capable of safely producing discrete areas of necrosis and may provide an alternative to direct current (DC) energy for catheter ablation of ventricular tachycardia originating from the septum.

Animals↗

Gastrointestinal complications after human transplantation and mechanical heart replacement.

One hundred fifty-three patients underwent 159 heart transplants; 7 of these patients received 8 artificial hearts used as a bridge before implantation. The 1-year survival rate was 81 percent. One hundred forty gastrointestinal complications developed in 70 patients. Thirty-eight operations were required. Twenty-nine were intraabdominal operations. Of these, 22 were elective and 7 were emergency procedures. Five of the seven patients who underwent emergency procedures died, for an overall total mortality rate of 17 percent for major intraabdominal interventions. There were no complications or deaths in patients who underwent elective procedures. Major elective intraabdominal surgical interventions can be safely carried out in heart transplant patients. Repeated physical examination, aggressive use of endoscopy and imaging techniques, sound surgical judgement and a mutual relationship of trust and respect between cardiac and general surgeons are keys to a successful outcome.

Emergencies↗

Ultrastructural morphometric analysis of papillary neoplasms: biological and diagnostic relevance.

Ten papillary adenocarcinomas of thyroid origin (P-Thy), ten papillary adenocarcinomas of ovarian origin (P-Ov), and eight papillary neoplasms of non-thyroid/non-ovarian origin (P-Other) were morphometrically compared using 19 distinct quantitative nuclear and nucleolar parameters as a database for diagnosis. The selected cases consisted of 16 primary and 12 metastatic neoplasms. It was determined that the P-Thy group had a significantly smaller nucleolar area (NuA) and nucleolar perimeter (NuP), and smaller SDs of nuclear area (NA), NuA, and NuP compared with the P-Ov and P-Other groups (P less than .05). The P-Ov group had a significantly smaller SD of NA compared with the P-Other group (P less than .05). The P-Ov group exhibited the greatest variability among the papillary neoplasms. Linear regression analysis indicated that in the P-Thy group alone there was a significant correlation between mean nuclear form factor (4 pi A/P2) and mean NuA (r = -.82; P less than .01), and mean NP and mean NuA (r = +.77; P less than .01). Linear regression analysis also indicated that in the P-Ov group alone, there was a significant correlation between mean NA and mean NuA (r = +.75; P less than .02). Morphometric domains were established using statistically significant sets of variables that distinguished between the groups. The application of three-dimensional computerized cluster analysis techniques indicated that the P-Thy group consistently had the smallest morphometric domains. It was concluded that ultrastructural morphometric analysis of papillary neoplasms has diagnostic potential and reveals interesting biological relationships among distinct nuclear features in the different groups of neoplasms.

Adenocarcinoma, Papillary↗

Determinants of impedance rise during catheter ablation of bovine myocardium with radiofrequency energy.

Recently, radiofrequency (RF) energy has been used as an alternative energy source to direct-current (DC) electricity for catheter ablation of recurrent tachyarrhythmias. Since delivered energy is inversely related to impedance, factors that cause impedance rise during catheter ablation impede the ability to ablate tissue. To elucidate some of the factors responsible for impedance rise during RF (750 kHz) catheter ablation using a constant voltage RF generator, the effects of the following variables on impedance were studied in an in vitro bovine heart model: power setting (10-70 W), pulse duration (10-60 sec), catheter contact pressure (5-120 gm), repeated applications (2-4), and immersion media (saline vs citrated blood). Baseline impedance in blood was twice that of saline (190 vs 80 ohm) and rises in impedances occurred more rapidly in blood for the same energy settings. Increased power settings (greater than or equal to 30 W) and pulse duration (greater than or equal to 30 sec at 20 W) were associated with impedance rises in blood medium. Typically, impedance rises in blood were associated with blood coagulum on the catheter electrodes. Impedance rises in both saline and blood media were also associated with tissue charring and endocardial surface disruption. Once a rise in impedance occurred at the ablation site, repeated applications to the same site resulted in a more rapid rise in impedance. Catheter contact pressure of 80 gm or more also resulted in rapid impedance rise. These data suggest that factors other than set power and duration may also contribute to impedance rises during RF ablation. These findings may have important clinical implications in performing catheter ablation with RF energy.

Animals↗

Chronic incomplete atrioventricular block induced by radiofrequency catheter ablation.

To determine if catheter ablation of the atrioventricular (AV) junction with radiofrequency energy can induce chronic incomplete (first- and second-degree) AV block to avoid the need for a permanent pacemaker, 20 closed-chest dogs were studied. Group 1 (10 dogs) received radiofrequency energy (750 kHz) with a fixed power setting (5 or 10 W) while increasing the pulse duration from 10 to 50 seconds for each application. Group 2 (10 dogs) received energy with a fixed pulse duration (20 or 30 seconds) while increasing the power setting from 5 to 10 W or from 10 to 20 W during each energy delivery. Radiofrequency energy was delivered between a chest-patch electrode and the distal electrode of a regular 7F tripolar His bundle catheter. For each application, the energy delivery was interrupted when 1) the PR interval prolonged (greater than 50%) or 2) second-degree or complete AV block occurred and persisted up to 5 seconds. The ablation procedure ended when there was 1) persistent PR prolongation (greater than 50%) or persistent second-degree AV block (lasting greater than 30 minutes) after ablation, 2) occurrence of two consecutive transient (less than 1 minute) complete AV blocks after each energy delivery, or 3) complete AV block (lasting greater than 2 minutes) after ablation. Of seven dogs in group 1 and five dogs in group 2 in which incomplete AV block was achieved 1 hour after the procedure, six in group 1 and five in group 2 remained in incomplete AV block 2-3 months after ablation. One dog in group 1 progressed into complete AV block. Of the remaining three dogs in group 1 and five dogs in group 2 in which complete AV block was initially achieved 1 hour after ablation, two in group 1 and four in group 2 continued to have complete AV block, whereas one in each group had AV conduction returned to incomplete at 1-2 months of follow-up. Thus, a total of 13 dogs had chronic incomplete AV block induced by radiofrequency catheter ablation. Pathologic examination of the conduction system in two dogs with first-degree AV block, two dogs with second-degree AV block, and one dog with complete AV block showed discrete scars involving the approaches to the AV node and the AV node itself. It is concluded that, in most dogs studied, chronic incomplete AV block could be achieved by careful titration of the dosage of radiofrequency energy and by regulation of the ablation end points.

Animals↗

Comparison of saphenous vein patch, polytetrafluoroethylene patch, and direct arteriotomy closure after carotid endarterectomy. Part I. Perioperative results.

To evaluate the perioperative outcomes and the immediate increases in size after patch closure, 140 carotid endarterectomies were randomized into one of three groups: direct no-patch closure, saphenous vein patch closure, and polytetrafluoroethylene patch closure. Seven patients (4.4%) experienced signs of cerebral ischemia in the immediate postoperative period. In three cases this was transient and reversible. In the other four reexploration was undertaken and carotid thrombosis was corrected by thrombectomy. The condition of one of these patients deteriorated to a permanent stroke, whereas the other patients made a complete recovery. Neurologic complications were more frequent in the no-patch group, but the differences between the groups were not significant. The incidence of perioperative internal carotid stenosis, aneurysmal dilatation, and other morphologic abnormalities was assessed in 131 intravenous digital subtraction angiograms taken before the patient was discharged from the hospital. Eight (17.0%) of the endarterectomies in the no-patch group were narrowed by 30% to 50% diameter stenosis, whereas none of the patched arteries had more than 30% stenosis. In contrast, dilatation of the common or internal carotid artery to more than twice the measured diameter was absent in non-patched arteries but was present in seven (17.0%) saphenous patch closures and four (9.23%) polytetrafluoroethylene patch closures. We conclude that patch closure after carotid endarterectomy is less likely to cause stenosis in the perioperative period. Poly-tetrafluoroethylene patches resist dilatation better than do saphenous vein patches and are less likely to become aneurysmal.

Aged↗

Quantitative light and electron microscopic correlations of nuclear features in papillary thyroid and ovarian carcinomas.

The light microscopic (LM) and electron microscopic (EM) features of nuclear bodies and nucleoli were quantitatively compared in ten papillary carcinomas each of thyroid (PC-Thy) and ovarian (PC-Ovar) origins, along with eight nonthyroid, nonovarian papillary neoplasms from other organs (PN-Oth). In each neoplasm, 100 randomly selected nuclei were scored for the presence of characteristic nuclear bodies; these were defined at the LM level by the presence of a central density surrounded by a clear halo, which corresponded to four distinct quantifiable images at the EM level. Means (+/- standard deviations) of the nucleolar frequency factor, the nucleolar area and the computed total nucleolar area (the product of the nuclear frequency factor and the mean nucleolar area) were assessed for the EM images. The number of nuclear bodies was 11.9 +/- 10.7 for PC-Thy, 5.2 +/- 5.3 for PC-Ovar and 5.9 +/- 7.4 for PN-Oth; the means for PC-Thy and PC-Ovar were significantly different (P less than .03), as were the means for PC-Thy and PN-Oth (P less than .04). The nucleolar frequency factor was 0.60 +/- 0.19 for PC-Thy, 1.19 +/- 0.51 for PC-Ovar and 0.99 +/- 0.22 for PN-Oth; these means were significantly different for PC-Thy versus PC-Ovar (P less than .01) and for PC-Thy versus PN-Oth (P less than .001). The mean nucleolar area was 1.19 +/- 0.45 for PC-Thy, 1.91 +/- 0.92 for PC-Ovar and 1.94 +/- 0.76 for PN-Oth; the means were significantly different for PC-Thy and PC-Ovar (P less than .05) and for PC-Thy and PN-Oth (P less than .05). The computed total nucleolar area was 0.73 +/- 0.41 for PC-Thy, 2.17 +/- 1.09 for PC-Ovar and 1.94 +/- 1.00 for PN-Oth; these means were significantly different for PC-Thy versus PC-Ovar (P less than .001) and for PC-Thy versus PN-Oth (P less than .01). A comparison of the total number of nuclear bodies, as determined by both LM and EM, indicated a significant correlation for the PC-Ovar (P less than .01) and PN-Oth (P less than .001) groups using linear regression analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoma, Papillary↗

Quantitative pathology of coccidioidomycosis in acquired immunodeficiency syndrome.

This study examines the laboratory aspects of diagnosis of coccidioidomycosis in 11 patients with acquired immunodeficiency syndrome (AIDS) and the qualitative and quantitative differences between host responses of AIDS and non-AIDS patients who died with disseminated coccidioidomycosis. Material obtained at bronchoscopy confirmed the diagnosis of pulmonary coccidioidomycosis in 67% (6/9) of the patients. Patients with AIDS had a generally poor granulomatous response and statistically significantly increased numbers of spherules in lung tissue compared with non-AIDS patients. Neither antifungal therapy nor duration of clinical disease influenced the number of organisms present. The findings suggest a parallel between AIDS-associated coccidioidomycosis and other granulomatous diseases such as leprosy and schistosomiasis, in which the type of granuloma formation and organism numbers are influenced by the T-lymphocyte milieu.

Acquired Immunodeficiency Syndrome↗

Prospective randomized trial of polytetrafluoroethylene and Dacron aortic prosthesis. I. Perioperative results.

Over a two year period 80 patients were entered into a prospective randomized trial comparing polytetrafluoroethylene (PTFE) and Dacron infrarenal aortic reconstructions. Fifty-four patients were treated for aneurysm (30 single tubed grafts; 24 bifurcation grafts), and 26 patients were treated for occlusive disease (26 bifurcation grafts). The groups were matched for age, sex and preoperative risk factors. Five patients died after operation (6.3%) including two from hemorrhage, but there were no significant differences in mortality and morbidity between the PTFE and Dacron groups. The volume of blood lost at operation (1930 +/- 1340 ml, all patients); the volume of blood transfused (2.98 +/- 2.43 units); the volume of crystalloids infused (3050 +/- 1390 ml); the intraoperative heparin dosage (67.9 +/- 20.5 mg); the clamp time (71.6 +/- 34.5 min); and the total operating time (228.1 +/- 78.3 min) also showed no significant differences between PTFE and Dacron. The ankle systolic pressure index rose more for PTFE (0.96 +/- 0.24) than for Dacron (0.82 +/- 0.20; P less than 0.002) at the time of discharge. This partially reflects a difference in the index between the groups before operation (PTFE 0.79 +/- 0.30; Dacron 0.72 +/- 0.32), but it may also indicate that PTFE is less thrombogenic than Dacron.

Aged↗

Combined gastrointestinal and abdominal aortic aneurysm operations.

Experience with gastrointestinal surgical conditions in 154 consecutive aneurysm operations at St Vincent's Hospital, Sydney, over 5 years (1982-86) is reported. Seventeen patients (11%) had coincidental gallstones, and six patients had other gastrointestinal conditions. Postoperative gastrointestinal complications occurred in eight patients. The overall in-hospital mortality rate was 7.8%. Four of the 12 deaths were associated with gastrointestinal problems, but these complications first developed after aneurysm surgery in three patients and could not have been avoided by a concurrent operation. The management of gastrointestinal pathology in association with the treatment of abdominal aneurysm is reviewed. The coincidence of these disorders is not sufficiently frequent to allow valid comment on the probability of successful outcomes, but the risks posed by surgically untreated gastrointestinal conditions are low, so that secondary gastrointestinal procedures should be avoided in most aneurysm operations.

Aorta, Abdominal↗

Radiofrequency catheter ablation of the left and right ventricles: anatomic and electrophysiologic observations.

Certain untoward effects associated with the use of direct-current electrical catheter ablation of the ventricular endomyocardium have been noted. We assessed the efficacy and safety of closed-chest catheter ablation of the left and right ventricles using radiofrequency (RF) energy (750 kHz) in six dogs. Mean RF energies between 93 and 123 joules (J) were randomly delivered to three left ventricular (LV) sites via two distal adjacent electrodes (bipolar configuration) using 6-7F USCI tripolar or quadripolar catheters with an interelectrode distance of 5-10 mm. Another 90-143 J were given to two right ventricular (RV) sites in single or multiple divided applications between a distal electrode and an external patch electrode (unipolar configuration). Ventricular arrhythmias were not observed during application of RF energy. Programmed ventricular stimulation before and after the procedure did not induce ventricular tachycardia (VT) or fibrillation except in one dog who had inducible VT prior to ablation. There were no significant changes in LV and RV effective refractory periods after the procedures. Occasional premature ventricular beats and rare episodes of non-sustained VT (3-12 beats) were observed in ambulatory electrocardiographic recordings (13-24 hrs) done immediately after ablation. Dogs were sacrificed after 4-5 days. Pathology showed well-demarcated round or ovoid lesions of varying sizes. Mural thrombus was found in one dog. Microscopic findings consisted of circumscribed areas of coagulation necrosis with a peripheral zone of cellular infiltration. Transmural necrosis without perforation was occasionally seen in the thin RV wall when higher energies were delivered. In conclusion, discrete areas of desiccation injury in the ventricles can be achieved by transcatheter bipolar or unipolar ablation using RF energy. The complications associated with this method appear to be minimal. Further experiments are needed to evaluate its potential for catheter ablation of ventricular tachycardia.

Animals↗

Short- and long-term effects of transcatheter ablation of the coronary sinus by radiofrequency energy.

Catheter ablation of left-sided atrioventricular accessory pathways through the coronary sinus by direct-current shock may be complicated by rupture and thrombosis of the coronary sinus and injury to the coronary arteries. This study examined short and long-term effects of radiofrequency catheter ablation of the coronary sinus in 20 closed-chest dogs to determine whether this technique is feasible for potential interruption of left-sided accessory pathways. Single-pulsed radiofrequency energy (750 kHz, 85-293 J) was delivered to three sites in the distal and middle coronary sinus between the distal (1) or the proximal electrodes (2 or 3) of a standard 6 French quadripolar catheter and a chest-wall patch electrode. Single-pulsed radiofrequency energy (78-293 J) was also applied to two sites near the ostium of the coronary sinus with the proximal (4) or the distal (1) electrode of the same catheter. Coronary artery and levophase coronary sinus angiograms obtained before and immediately after ablation, as well as before killing, showed intact vascular structures in all dogs. Right atrial, pulmonary arterial, and aortic pressures measured in three dogs did not change significantly at the time of energy delivery. No significant changes were found in atrioventricular nodal refractoriness and conduction. None of the dogs had significant rhythm disturbances during and after ablation as evaluated by ambulatory electrocardiographic monitoring and periodic rhythm strips at follow-up. Ten dogs were killed 1-7 days after ablation, three dogs were killed at 4 weeks, three dogs at 6 weeks, two dogs at 8 weeks, and two dogs at 12 weeks. Discrete lesions ranging in size from 3 x 3 to 8 x 10 mm2 in surface area and 0.5-4.5 mm in depth were found in the coronary sinus with most of the lesions extending to the left atrial and left ventricular myocardium. There was neither rupture of the coronary sinus nor occlusion of the coronary arteries. Mural thrombus was found in the coronary sinus on five acute lesions in two dogs, but none was noted on the chronic lesions, which was characterized by chronic granulation tissue and fibrosis. Two dogs in the study during chronic conditions had damage to branches of the underlying coronary artery that showed necrotizing arteritis and arterial sclerosis. Conduction system studies in four dogs showed some chronic inflammatory and fibrotic changes. Similar discrete lesions were found in situ in the coronary sinus of four postmortem human hearts with radiofrequency catheter ablation.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiography↗

Colonic lesion expert system. Performance evaluation.

A computer-based expert system for diagnosing colonic sections as normal, adenoma or adenocarcinoma is described, along with an evaluation of its performance. On the basis of its knowledge base, consisting of the values of diagnostic clues and their associated certainty factors for the possible diagnoses, the system will suggest the diagnosis for new cases presented to it. Using the data provided for 16 diagnostic clues, the system arrived at correct diagnoses for all cases of normal colon, for 49 of 50 cases of adenoma and for 48 of 49 cases of adenocarcinoma. Sample outputs from the expert system are presented and discussed, and the effects of possible alterations in the data base are considered.

Adenocarcinoma↗

Micromorphometry of colonic lesions.

In the formulation of a quantitative component for the knowledge base of a diagnostic expert system, we developed a mathematical model to describe nuclear placement patterns in colon. Glands from normal colon, tubular adenomas, and adenocarcinomas were studied, and a ratio developed of percentage internally displaced nuclei to percentage displacement area. This displacement area represented an inner epithelial zone bounded centrally by the lumen and peripherally by the apical limit of basal nuclei. The mean percentage internally displaced nuclei to percentage displacement area ratio was 0.15 +/- 0.13 for normal glands, 0.75 +/- 0.09 for adenomas, and 1.04 +/- 0.13 for carcinomas. When the percentage internally displaced nuclei to percentage displacement area ratio was plotted against total number of nuclei, there was statistically significant separation of the diagnostic categories at alpha less than or equal to 0.05. Relative nuclear area and its variance were also studied for normal colonic glands, adenomas, and adenocarcinomas. Mean relative nuclear area for cells from normal glands was 284.2, from adenomas 342.4, and from adenocarcinomas 416.4, these being statistically significantly different at alpha less than or equal to 0.05. Variance of relative nuclear area, compared for the three diagnostic categories, was statistically significantly increased only in adenocarcinoma. Quantitation of nuclear placement patterns appears to provide a useful diagnostic clue for the knowledge base of a diagnostic expert system in the discrimination among normal colonic glands, adenomas, and adenocarcinomas.

Adenocarcinoma↗

Transcatheter desiccation of the canine left ventricle using radiofrequency energy: a pilot study.

Catheter ablation of cardiac tissue by means of direct-current electrical energy is associated with several complications. We assessed the efficacy and safety of closed-chest catheter desiccation of the left ventricular myocardium with microbipolar radiofrequency (RF) energy (750 kHz) in five dogs. The unipolar configuration was used with RF energy delivered between the tip electrode of a standard No. 7F tripolar catheter in the left ventricle and an external patch electrode on the left lateral chest wall. A single application with different RF energy settings (100 J, 200 J, and 300 J) was delivered to three individual endocardial sites of the left ventricle. Ventricular tachycardia or fibrillation was not observed during energy application and 24 hours after ablation, as assessed by a Holter recording. There was no damage to the electrode catheter. Dogs were killed on the fifth day. Pathology showed well-delineated ovoid or round-shaped coagulation necrosis at the ablation sites. Microscopic findings consisted of circumscribed areas of necrosis surrounded by a zone of fibroblastic and mononuclear proliferation. In conclusion, catheter ablation of the ventricular myocardium with RF energy is an apparently safe procedure and can effectively produce discrete areas of injury without destruction of surrounding uninvolved myocardium. This method offers potential clinical utility for catheter ablation of refractory sustained ventricular tachycardia.

Animals↗

Congenital heart block and cardiac anomalies in the absence of maternal connective tissue disease.

The association of congenital heart block with maternal connective tissue disease and autoimmunity has been recently reported. Two cases of heart block were diagnosed in utero at 23 and 24 weeks' gestation. Both mothers had extensive workups for connective tissue disease that were negative. Two-dimensional and Doppler echocardiography were performed in utero and both infants had left atrial isomerism, atrioventricular canal defects, and severe hydrops in addition to heart block. Review of the recent literature identifies a subset of congenital heart block in which the mothers have no evidence for connective tissue disease, and the fetus or neonate has complex cardiac malformations and hydrops. The common features in these babies are atrioventricular canal defects and isomerism. No reports of congenital heart disease among the children of mothers with connective tissue disease fit this description. Our recent experience and literature review emphasize the previously known association between congenital heart block and congenital heart disease. This association is especially important in light of the poor prognosis for this group of fetuses and neonates.

Adolescent↗

5-year experience with intravesical therapy of carcinoma in situ: an inquiry into the risks of "conservative" management.

Recent reports of disease progression in patients being treated with intravesical agents for carcinoma in situ of the bladder led us to examine our 5-year experience with 26 consecutive patients with carcinoma in situ treated with intravesical therapy for this lesion. Nine patients with isolated carcinoma in situ and 17 with carcinoma in situ associated with papillary lesions were treated intravesically with a variety of agents in a closely monitored program for a mean of 22 months. All patients wished to exhaust conservative options before accepting cystectomy. Of 26 patients treated 9 (35 per cent) have no evidence of disease with a functional bladder after 27 months, 13 (50 per cent) are treatment failures and 4 (15 per cent) maintain an equivocal status to date. Successful treatment results with each drug were 6 of 24 thiotepa, 0 of 7 mitomycin, 0 of 6 doxorubicin and 3 of 8 bacillus Calmette-Guerin. Treatment failure was associated with disease progression to muscle invasion, adjacent organ invasion or metastases in 7 patients (27 per cent). Significant reduction in bladder capacity after prolonged therapy occurred in 3 patients. Our results suggest that persistent, intensive, "conservative" intravesical therapy in the face of recurrent or persistent disease is associated with substantial patient risk.

Administration, Intravesical↗

The role of immunohistochemistry, electron microscopy, and ultrastructural cytochemistry in the diagnosis of mixed carcinoma-neuroendocrine neoplasms.

We studied four mixed carcinoma-neuroendocrine neoplasms from gastrointestinal tract and pancreas by routine light microscopy (LM), immunohistochemistry (IH), electron microscopy (EM), and ultrastructural cytochemistry (UC). By LM, the individual tumors showed fairly pure neuroendocrine (carcinoid) or epithelial (papillary) patterns, mixed neuroendocrine-carcinoma features and poorly-differentiated tumor in sheets and nests which did not lend itself to morphologic characterization. IH demonstrated mixed expression, within different areas of the same neoplasm, of epithelial antigens (keratins and carcinoembryonic antigen [CEA]) and neuroendocrine markers (neuron-specific enolase [NSE], bombesin and neurohormonal peptides). By EM, each tumor showed ultrastructural features of epithelial and neuroendocrine differentiation which varied substantially in terms of number of cells involved and their distribution; two of the neoplasms showed biphasic differentiation within single cells. The nature of the neurosecretory granules was verified with the uranaffin reaction (UR). This study illustrates the value of combining LM, IH, EM and UC for the identification of mixed carcinoma-neuroendocrine lesions.

Aged↗