Surgical correction of the Wolff-Parkinson-White syndrome in the closed heart using cryosurgery: a simplified approach.

The conventional operation for ablation of accessory atrioventricular (AV) pathways in the Wolff-Parkinson-White syndrome requires an endocardial approach to the AV groove and necessitates the use of cardiopulmonary bypass and induced cardiac arrest. The feasibility of creating transmural atrial fibrosis at the level of the AV anulus in the closed heart in dogs without damaging the vascular contents of the AV fat pad was demonstrated. This was done by dissecting the fat pad from the atrium and applying a cryoprobe to the exposed atrial-anular region after retraction of the fat pad. The technique was then applied to successfully ablate 12 left parietal wall accessory pathways in 11 patients with the Wolff-Parkinson-White syndrome. This simplified approach to any parietal wall accessory pathway does not require cardiopulmonary bypass or induced cardiac arrest and may broaden the indications for this operation.

Cryosurgical modification of the atrioventricular node: a closed heart approach in the dog.

Intraoperative modification of the atrioventricular (AV) node to prolong refractoriness could be an alternative to His bundle ablation in patients with refractory supraventricular arrhythmias. It was postulated that a cryosurgical lesion at the posterior interatrial septum in the closed heart could achieve this. An electrophysiologic study was performed in anesthetized dogs. The AV fat pad was mobilized to expose the posteroseptal region. A cryoprobe cooled to 0 to -10 degrees C was moved in the exposed region until reversible AV block indicated proximity of the AV node. The probe was then cooled to -70 degrees C for 30 seconds. Four weeks later, five dogs had a favorable result with a mean prolongation of Wenckebach cycle length of 45 +/- 7% (p less than 0.05). Two dogs had complete heart block. Decreased (one dog) or increased (one dog) duration of freezing resulted in no change and complete heart block, respectively. Histologic examination verified partial damage to the AV node with preservation of the His bundle. Thus, controlled cryoinjury to modify AV node function is feasible in the closed heart; preservation of AV conduction provides an advantage over His bundle ablation.

The respiratory effects of cobalt.

We studied seven subjects with certain manifestations of cobalt-induced lung disease. All worked with cobalt and were involved in either the production or use of hard metal. The mode of presentation varied from an acute hypersensitivity pneumonitis that cleared completely when exposure ceased to progressive severe interstitial fibrosis of the lungs. In one subject reexposure was followed by a recurrence of the symptoms. All subjects showed restrictive ventilatory impairment and a reduction of their diffusing capacity. The radiologic appearances varied greatly. While two subjects had clear roentgenograms with small lung volumes, others had a micronodular pattern or small blotchy nodular infiltrates, and one had diffuse reticulonodulation as is seen in cryptogenic fibrosing alveolitis. The pathologic appearances varied between desquamative interstitial pneumonia and overt mural fibrosis of the alveoli. Six of the seven patients had multinucleated giant cells in their biopsy specimens or bronchoalveolar lavage fluid.

Hemodynamic modification of aortic atherosclerosis. Effects of propranolol vs hydralazine in hypertensive hyperlipidemic rabbits.

According to hemodynamic theories of atherogenesis, atherosclerotic plaques are a reaction to endothelial damage caused by arterial flow disturbances such as turbulence. Earlier studies showed that hydralazine increased, whereas propranolol decreased, the product of heart rate X blood velocity, a predictor of arterial flow disturbances, and that hydralazine aggravated, whereas propranolol decreased turbulence in the region of carotid artery stenosis. This study was done to test the hypothesis that drugs which reduce arterial flow disturbances may be more effective in preventing atherosclerosis, than antihypertensive drugs which worsen arterial flow disturbances. Eighty-three New Zealand white rabbits were made hypertensive by a one-kidney Goldblatt procedure, and were fed a 1% cholesterol diet. Untreated hypertensive (P less than 0.01) and hydralazine-treated hypertensive rabbits (P less than 0.05) had significantly more atherosclerosis than did the normotensive controls; propranolol-treated rabbits did not differ significantly from the normotensive controls. Analysis of covariance showed that propranolol-treated rabbits had significantly less atherosclerosis than hydralazine-treated rabbits with blood pressure (P less than 0.04) or heart rate (P less than 0.006) as the covariates.

Antiulcer agents. 3. Structure-activity-toxicity relationships of substituted imidazo[1,2-a]pyridines and a related imidazo[1,2-a]pyrazine.

Investigation of the interrelationship between structure, antiulcer activity, and toxicology screening data derived from a series of compounds selected from structure-activity studies directed toward identifying a successor to 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1), has identified 3-(cyanomethyl)-2,7-dimethyl-8-(phenylmethoxy)imidazo[1,2 -a]pyridine (5), 3-amino-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine (6), and 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine (7). These analogues exhibit a combination of antisecretory and cytoprotective activity in animal models, while eliminating the adverse effects of the prototype 1. One of these, 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine, Sch 32651 (7), has a profile meeting all criteria.

Development of endometriosis from embryonic duct remnants.

Among 18 cases of endometriosis involving ovaries and fallopian tubes, we identified three cases with foci of endometriosis adjacent to the embryonic duct remnants in the fallopian tube. The serial sections of the blocks of tissue containing areas of interest showed segments of embryonic duct remnants with changes suggestive of gradual transformation to endometrial glands. The early changes consisted of replacement of the muscular coat surrounding the epithelium of embryonic duct remnants by the endometrial stroma with positive immunoreactivities for estrogen receptor. Subsequently there were changes of the embryonic duct remnant epithelium into endometrial epithelium with diffuse immunoreactivities for estrogen receptor. The significance of this transformation as a mechanism of development of endometriosis is discussed.

Absence of serum prostate-specific antigen and loss of tissue immunoreactive prostatic markers in advanced prostatic adenocarcinoma after hormonal therapy: a report of two cases.

We report two cases of advanced prostatic adenocarcinoma (PA) showing complete loss of three tissue immunoreactive prostatic markers, ie, prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and Leu-7 (CD57), with absence of elevated serum PSA level, despite tumor progression after hormonal therapy with or without radiotherapy. The pretreatment serum PAP in the first case and serum PAP and PSA in the second case were elevated. In both cases, the prostatic adenocarcinoma in the initial transurethral resection specimens showed positive immunoreactivity with three prostatic markers. After treatment, in both cases, the serum PSA were undetectable, and tumor cell immunostaining for three prostatic markers was negative. In addition, the posttreatment tumors in both cases showed increased number of tumor cells with neuroendocrine differentiation in comparison those in the pretreatment tumors. Although early PA without elevated serum level of PSA is common, advanced PA with absence of elevated serum PSA, associated with presence of tissue immunoreactive prostatic markers are rare. This is the first report of advanced prostatic adenocarcinomas showing loss of tumor cell prostate-specific markers with absence of elevated serum PSA level after hormonal therapy despite tumor progression.

Pattern of distribution of intraductal and infiltrating ductal carcinoma: a three-dimensional study using serial coronal giant sections of the breast.

The purpose of this study was to establish the 3-dimensional (3D) structure of the breast tissue and to study the distribution and relationship between the intraductal and infiltrating components of ductal carcinoma and other proliferative epithelial lesions of the breast. Thirty mastectomy specimens with infiltrating carcinoma less than 3.0 cm in diameter were serially cut in the coronal plane. Each giant section was divided into small sections for routine processing. Using Photoshop (Adobe) and PowerPoint (Microsoft) software programs, the routinely stained sections were scanned and assembled to reestablish complete giant sections of the breast and subsequently the 3D structure. Intraductal and infiltrating ductal carcinomas, epithelial hyperplasia with atypia, and marked epithelial hyperplasia without atypia were mostly confined to a single duct (27 cases), resulting in an increase in size of the involved breast segment. Three remaining cases included a case of Paget's disease with tumor appearing to spread from one duct system to another system through the epidermis and two cases with multiple separate foci of carcinomas located in different quadrants and accompanied by ductal spread in different lactiferous ducts. Both intraductal and infiltrating carcinomas were often located in the superficial segments (near the subcutaneous tissue) (28 cases). The infiltrating components were often located adjacent to area of pure intraductal carcinoma and were often peripheral (nearer the chest wall than the nipple). Intraductal carcinomas showed a "fanned out" pattern of distribution, frequently extended toward the nipple (with involvement of the nipple or subareolar tissue in 7 cases), and occasionally were seen in the breast tissue peripheral to the infiltrating carcinoma. Multiple ducts with intraductal carcinoma could be seen to be connected with each other with serial sections. However, in at least 6 cases, foci of intraductal carcinomas were separated from each other by segments of duct with benign epithelium. Breast carcinoma often arise from the breast segment close to the subcutaneous tissue. Infiltrating carcinoma lesser than 3.0 cm in diameter is usually located adjacent to the area of pure intraductal. The pattern of spread of intraductal carcinoma has a pyramid-like shape, with the summit toward and occasionally extending up to the nipple. These findings should be considered in the surgical strategy for segmental resections of breast carcinomas.

Angiosarcoma of the chest wall.

Angiosarcoma is a rare and highly malignant tumor of vascular origin. The causative factors include trauma, radiation, foreign bodies, thorium dioxide, and viral infections. We report a case of angiosarcoma occurring in a thoracotomy incision 17 years after operation for stage I lung cancer.

Glomus tumor of the trachea.

Extracutaneous glomus tumors are uncommon and rarely occur in the trachea. We describe a 73-year-old man with a glomus tumor of the trachea who presented with cough, dyspnea, chest pain, and hemoptysis. A curative segmental tracheal resection with primary reconstruction was performed with no recurrence at 6-year follow-up. The clinicopathologic features of this unusual neoplasm are discussed with a review of the literature.

Surgical repair of Wolff-Parkinson-White syndrome: a new closed-heart technique.

The conventional operation for ablation of accessory pathways in Wolff-Parkinson-White (WPW) syndrome requires an endocardial approach and necessitates cardiopulmonary bypass and hypothermic cardiac arrest. Cryosurgical ablation of these pathways from the epicardial surface has been described but limited to superficial accessory pathways. We report a new closed-heart technique combining dissection of the atrioventricular (AV) pad and cryosurgery. Six patients with WPW syndrome underwent operation for ablation of accessory pathways associated with disabling tachyarrhythmia refractory to medical management. All pathways were located in the left lateral AV sulcus as determined by preoperative and intraoperative electrophysiological assessment. The heart was exposed through a median sternotomy. The AV fat pad and its vascular contents were dissected away from the atrium at the site of the pathway. A small segment of the ventricle adjacent to the sulcus was exposed. The fat pad was retracted to avoid cryoinjury to the coronary vessels. A cryoprobe, 1.5 cm in diameter, was applied to the exposed AV junction (-60 degrees C for 2 minutes) to create transmural fibrosis. After ablation of the pathway was verified, the chest was closed. All 6 patients have remained free from preexcitation during short-term follow-up. This simplified technique is applicable to patients with free wall accessory pathways. This group constitutes the majority of symptomatic patients with WPW syndrome at our institution.

Cystic disease of the lungs.

Cystic disease of the lung should be considered in the differential diagnosis of any patient presenting with respiratory symptoms. The most important aids available to the thoracic surgeon for the evaluation of cystic disease are history, physical examination, and chest radiograph. Confirmation of diagnosis often requires computed tomography, pulmonary and thoracic aortic angiography, and upper gastrointestinal barium series.

Adenomatoid tumor of the genital tract: evidence of mesenchymal cell origin.

The objective of this study was to re-examine the histogenesis of adenomatoid tumors. This benign neoplasm is characterized by gland-like structures with a pseudodinfiltrative pattern, usually involving fibromuscular tissue at a certain distance from an overlying surface mesothelium. Twenty cases of adenomatoid tumors and four cases of reactive submesothelial lesions, characterized by marked proliferation of subserosal mesenchymal cells, were reviewed. Nineteen of twenty adenomatoid tumors, including lesions with ill-defined borders, showed no connection with surface mesothelium. At the periphery of small tumors, isolated glands, clusters of epithelioid cells and single epithelioid, and spindled cells showing no connection to adjacent glands or cell clusters were identified. The tumor cells shared features with reactive subserosal stromal cells including an infiltrative pattern and histochemical and immunohistochemical properties. The differences between adenomatoid tumors and reactive submesothelial tissue are quantitative in nature: predominant amount of spindled cells in reactive submesothelial lesions, and predominant amount of gland-like structures in adenomatoid tumors. It is proposed that adenomatoid tumors arise from pluripotent mesenchymal cells that differentiate toward submesothelial cells and eventually mesothelial cells. This differentiation is probably induced by the adjacent submesothelial cells.

Immunohistochemical study of papillary thyroid carcinoma and possible papillary thyroid carcinoma-related benign thyroid nodules.

Recent immunohistochemical studies have identified different antisera that have various degrees of sensitivity and specificity for papillary thyroid carcinoma (PTC). In this study, we performed immunostaining for CK, EMA, HBME, CD57 and CD15 in PTC, and benign thyroid nodular lesions to compare the sensitivity and the specificity of these antisera for PTC. In addition, we studied the patterns of immunostaining of these antisera in benign nodular thyroid lesions displaying a fine chromatin pattern, foci of cells with nuclear grooves, and optically clear nuclei. Fifty-five PTC (composed of 30 papillary variants and 25 follicular variants), 5 follicular carcinomas, 30 follicular adenomas, and 20 thyroid nodular lesions (5 papillary variants and 15 follicular variants) were submitted for immunostaining with CK, EMA, HBME, CD57, and CD15. CK and HBME showed the highest sensitivity and specificity for PTC when an arbitrary cutoff of more than 10% positive cells was considered as positive diagnostic immunostaining for these sera. The other antisera were less sensitive and less specific. One case of PTC showed negative HBME but positive CD15, whereas three papillary variants and two follicular variants of benign thyroid nodules revealed a positive diagnostic HBME immunostaining for PTC and negative CK immunostaining. Any combination of positive diagnostic immunostaining with CK+ HBME, CK+ CD57 or CK+ CD15 has a sensitivity of 95% and specificity of 90% for PTC. Thyroid nodules with a diffuse or focal fine chromatin pattern and focal areas with nuclear grooves or optically clear nuclei displayed immunoreactivity ranging from 0% to 50% of cells. Three of five follicular carcinomas showed negative reactivity for HBME, CD57, and CD15. A combination of immunostaining with CK, HBME and CD57 (or CD15) is a sensitive and specific test for PTC. This panel can be used to rule out thyroid nodules posing a diagnostic problem with PTC. Follicular adenoma and nodules of the thyroid, with a fine chromatin pattern and focal nuclear grooves or optically clear nuclei, displayed an intermediate range of reactivity between reactive thyroid tissue and PTC.

Incidental prostatic adenocarcinomas and putative premalignant lesions in TURP specimens collected before and after the introduction of prostrate-specific antigen screening.

BACKGROUND: Since the introduction of prostate-specific antigen (PSA) screening for the detection of prostatic adenocarcinoma (PCA), there has been an increase in the incidence of stage T1c PCA. The purpose of this study was to compare the frequency of incidental PCA found in transurethral resection of prostate (TURP) specimens for a 14-month period during 1989-1990 (before PSA screening was available) with the incidence of PCA for a 32-month period during 1997-1999 (after PSA screening became available). DESIGN: Consecutive TURP specimens from the 2 time periods were reviewed to identify incidental PCA, prostatic intraepithelial neoplasia (PIN), and atypical adenomatous hyperplasia (AAH). Cases of TURP for palliative treatment of known advanced PCA were excluded from the study. All TURP specimens were fixed in 10% buffered formalin and were processed according to the same protocol. RESULTS: We reviewed 533 and 449 TURP specimens for the time periods 1989-1990 and 1997-1999, respectively. Comparison of the results for these 2 time periods revealed that the combined prevalence of T1a and T1b PCA decreased over time from 12.9% to 8.0% (P =.06) with the introduction of PSA screening. A new group of T1c PCA was established in the post-PSA screening period of 1997-1999. There were no statistically significant differences in the incidences of T1a PCA, PIN, and AAH in TURP specimens for the 2 time periods. CONCLUSION: The decreased incidence of T1b PCA in TURP specimens for the 1997-1999 period represents a shift in PCA staging. Some PCAs previously staged as T1b are now staged as T2 carcinomas, as a result of PSA screening and earlier clinical detection. The introduction of PSA screening has had no influence on the incidence of T1a PCA, PIN, or AAH in TURP specimens.

Infiltrating papillary thyroid carcinoma: review of 134 cases of papillary carcinoma.

BACKGROUND: Papillary thyroid carcinomas (PTCs) are diagnosed mainly by the features of nuclei of the neoplastic cells. Theoretically, by similarity to other types of carcinoma, infiltrative tumor growth likely distinguishes the thyroid neoplastic lesions with potential of metastasis from those without this capability. METHODS: One hundred thirty-four cases of PTC, consisting of 41 encapsulated tumors and 93 nonencapsulated tumors, were examined for the presence of infiltrating PTC (IPTC), defined by tumor cells infiltrating a desmoplastic or sclerotic stroma. RESULTS: Encapsulated tumors with focal or extensive IPTC and nonencapsulated tumors with focal or extensive IPTC were associated with rates of lymph node metastases of 28%, 42%, 36%, and 65%, respectively. The tall cell variant of PTC was associated with a higher rate of metastasis. There was a small group of tumors without identifiable IPTC, designated as PTC without identifiable infiltrating carcinoma, which included six encapsulated tumors with areas of sclerosis in the capsule and three nonencapsulated tumors consisting of neoplastic cells with optically clear nuclei, nuclear grooves, and intranuclear inclusions in over two thirds of the cell population. Of these lesions, one case developed lymph node metastases. Papillary thyroid tumors without areas of IPTC and exhibiting the nuclear changes described, but in less than two thirds of the tumor cells, did not develop lymph node metastases. CONCLUSIONS: Infiltrating tumor growth is an indicator of malignant behavior in most thyroid papillary neoplastic lesions. The extent of IPTC is likely proportional to the rate of lymph node metastases.

Unusual immunostaining pattern of chromogranin in normal urothelium and in transitional cell neoplasms.

We report an unusual pattern of immunostaining for chromogranin A in 24 transitional cell carcinomas (TCC). Positive immunostaining was seen with chromogranin A antisera in 10 of 16 urinary bladder TCC, neither of 2 prostatic TCC, 3 of 3 ureteral TCC and 2 of 3 metastatic TCC. This staining was demonstrated within the cytoplasm of transitional cells at all levels of the neoplastic epithelium, including cells near the basement membrane and at the free surface (umbrella cells). In 5 of 7 cases there was also immunoreactivity of the non-neoplastic urothelium. Immunostaining with neuron-specific enolase and synaptophysin was negative in all of these cases and no neuro-secretory granules were identified in 7 cases examined by electron microscopy. This pattern of immunostaining is probably due to reactivity with chromogranins or certain chromogranin-like proteins in the transitional cells, particularly in the umbrella cells.

Basaloid carcinoma of the lung with bronchiolo-alveolar cell differentiation. A case report.

AIMS: We report a case of pulmonary basaloid carcinoma with bronchiolo-alveolar cell differentiation. PATIENTS AND RESULTS: A 75 year-old presented with a tumor measured 2.0 cm and was located in the periphery of the left upper lobe. Histologically, the lesion consisted of nests of basaloid cells, and lumina and clefts lined by tumor cells with features of mucous cells or type II pneumocytes or with mixed features. CONCLUSIONS: Previously reported basaloid carcinomas of the upper aero-digestive tract and lung have been purported to have an aggressive behavior. The tumor in the present study had features of a histopathological low grade tumor including a low mitotic rate, no tumor necrosis and a growth pattern at the periphery similar to that of bronchiolo-alveolar carcinoma.

Papillary thyroid carcinoma and related thyroid neoplastic lesions: a light microscopic study with emphasis on nuclear changes.

A total of 187 thyroid lesions consisting of 2 cases of Grave's disease, 21 cases of multinodular goiter, 40 follicular adenomas and 124 low-grade papillary thyroid carcinomas were studied to identify intermediate neoplastic lesions in the spectrum of nuclear changes between benign reactive thyroid follicles and low-grade thyroid papillary carcinoma. The lesions were examined and classified on the basis of the following nuclear features: fine chromatin seen in the thyroid papillary carcinomas and coarse chromatin seen in follicular carcinomas. Cases with Hürthle cell changes were excluded from the study. Cases with nuclei containing coarse chromatin were classified in the group of follicular adenomas with a coarse chromatin pattern. The neoplastic thyroid lesions containing fine chromatin showed a spectrum of nuclear changes ranging between reactive follicular lesions and papillary thyroid carcinoma with lymph node metastasis. Such lesions were classified as follicular adenomas with a fine chromatin pattern. The nuclei of these lesions were graded into mild to marked "nuclear atypia with a fine chromatin pattern". The degree of atypia depended on the degree and extent of nuclear changes. Encapsulated follicular adenomas with a fine chromatin pattern and with mild atypia (11 cases), moderate atypia (13 cases), marked atypia (27 cases), and encapsulated or nonencapsulated papillary thyroid carcinoma were characterized by uniform nuclei; with mild, moderate and marked nuclear atypia in less than 2/3 of the cell population and marked nuclear atypia in more than 2/3 of the cell population; and measuring 5.4-6.3, 6.0-7.2, 6.3-9 and 7.2-10 microns in diameter, respectively. Follow-up of cases of papillary thyroid carcinoma fulfilling the above criteria showed lymph node metastasis in 33% of cases, whereas follicular adenomas with a fine chromatin pattern, including cases originally diagnosed as papillary carcinoma, showed no evidence of lymph node or distant metastasis in a follow-up period of 30 months to 15 years. In the thyroid tissue surrounding papillary thyroid carcinoma or encapsulated follicular adenoma with a fine chromatin pattern and marked atypia, adenomatous nodules with a fine chromatin pattern and with low-grade nuclear atypia were identified. The adenomatous nodules with a fine chromatin pattern and with mild, moderate and marked atypia showed architectural, cytoplasmic and nuclear features similar to those of follicular adenoma with a fine chromatin pattern of the same grade. Of interest, a large number of cases of follicular adenoma with a fine chromatin pattern had areas with features of follicular adenoma with a coarse chromatin pattern.

Ret oncogene protein expression in papillary thyroid carcinoma and related lesions.

BACKGROUND: Activation of Ret oncogenes, particularly Ret/PTC, has been identified in papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the immunostaining pattern of Ret oncogene protein in PTC and nodular non-PTC lesions with a fine chromatin pattern. MATERIALS AND METHODS: Ninety-three PTC and 139 nodular non-PTC lesions were microscopically reviewed to identify the nuclear changes of "limited nuclear features of PTC" (focal nuclear grooves, nuclear inclusions or optically clear nuclei) and areas of infiltrating carcinoma (IC) and were submitted for immunostaining with Ret oncogene protein antiserum. RESULTS: Immunoreactivity for Ret protein ranged from negative in follicular adenoma (FA) with a coarse chromatin pattern, to negative or weak reactivity in FA with a fine chromatin pattern, to strong reactivity in PTC with areas of infiltrating carcinoma (IC). In FA with fine chromatin, FA and follicular carcinoma (FC) containing an admixture of areas of coarse and fine chromatin, areas with nuclear changes with "limited nuclear features of PTC" displayed varying degrees of immunoreactivity. The intensity of immunostaining varied with the degree of nuclear change. The noninvasive component of PTC with IC usually showed more extensive and stronger reactivity than PTC without IC. PTCs with and without IC were associated with a rate of lymph node metastasis of 48% and 3%, respectively. CONCLUSIONS: The expression of Ret oncogenes (Ret/PTC, other unknown variants or wild type) is focally or extensively present in all PTC with IC. The degree of immunoreactivity is likely to be proportional to the potential for lymph node metastasis of PTC. In the context of this study and due to the specificity of Ret oncogenes, it is likely that nodular non-PTC lesions with a fine chromatin pattern and focal positive reactivity for Ret oncogene represent PTC-related lesions.