Nylon brush improves collection of cervical cytologic specimens.

A prospective, randomized study was performed to compare the efficacy of a combined endocervical and ectocervical nylon brush with the cotton-tipped swab and wooden spatula for obtaining cervical cytologic specimens. Strict objective criteria were used to determine the adequacy of Papanicolaou smears on the basis of the number of cells present. The two methods were equally effective in collecting ectocervical smears. However, 96% of endocervical smears obtained with the nylon brush contained greater than 50 cells, compared with 58% of swab and spatula smears. Only 1.4% of brush samples contained no endocervical cells, versus 19% of swab and spatula smears. The presence of endocervical cells confirms adequate sampling of the transitional zone. Use of the cytologic Papanicolaou brush may result in fewer false negative and inadequate Papanicolaou smears.

Delayed complications from fine-needle biopsies of solid masses of the abdomen.

A prospective study was conducted from 1977 through 1983, to determine the incidence of complications, particularly bleeding, after fine needle biopsy for suspected malignancy of the abdomen and pelvis. Hematocrits before and after the biopsy procedure, medical record follow-up, and review by a coagulation specialist were used to identify bleeders. We performed 395 biopsies on 360 patients. Thirteen percent of the patients had bothersome pain either during or after the biopsy. Hematocrit drops of 3% or more were found in 51 (12.7%) of the patients; nine were determined to be a direct result of the biopsy procedure. Our results and review of the literature suggest that there are complications, including delayed bleeding, yet few are life threatening. We caution, however, that adequate follow-up to identify bleeders is very important in patients having fine-needle biopsies of solid masses of the abdomen.

Cytologic criteria for the diagnosis of pancreatic carcinoma.

Fine-needle aspiration and endoscopic aspiration of pancreatic cells permit the diagnosis of pancreatic carcinoma and avoid the complications and morbidity of pancreatic biopsy. In this study, the accuracy of fine-needle and endoscopic aspiration were compared, and cytologic criteria for pancreatic carcinoma were sought. Pancreatic cytologic preparations from 79 patients, including 39 fine-needle aspirates and 48 endoscopic aspirates, were retrospective reviewed. When compared with definitive tissue diagnosis or clinical course, fine-needle aspiration had a sensitivity for pancreatic carcinoma of 79%. Endoscopic aspiration of pancreatic secretions had a sensitivity of only 33%. There was a single falsely suspicious fine-needle aspirate, but there were no false positive diagnoses when using either collection technic. Seventeen cytologic features were examined to determine cytologic criteria of malignancy. The presence of disoriented or crowded cells in three-dimensional groups, and extreme nuclear enlargement combined with nuclear contour irregularity were the best criteria for pancreatic malignancy.

Quality control in cytopathology. A system for simultaneous monitoring of accuracy and education and for proficiency testing.

Because of its very nature, cytopathology has not lent itself well to quality control. At the University of North Carolina, we practice an internal quality control system based on peer review, interprofessional dialogue and utilization of follow-up information. Recently reported cytology specimens are rescreened and correlated with related surgical specimens. This review is summarized in a weekly conference, at which retrospective accuracy judgments are made for each case under the supervision of the medical director and head cytotechnologist. Diagnostic accuracy is thus monitored. Accuracy is also improved since education is simultaneously monitored. A practical proficiency-testing program built into this system is described.

Barrett's esophagus: clinical, endoscopic, histologic, manometric, and electrical potential difference characteristics.

The clinical, endoscopic, histologic, manometric, and esophageal potential difference characteristics of 20 patients with columnar epithelia lining the lower esophagus (Barrett's esophagus) are presented. Endoscopically, two distinct types were identified: a circumferential-type and an island-type Barrett's esophagus. Patients with these types exhibited similarities in mean age, duration of symptoms, mean lower esophageal sphincter pressure, and frequency of gross esophagitis. Only patients with the circumferential lesion, however, had esophageal strictures or esophageal ulcers. Manometric testing revealed a range of lower esophageal sphincter pressures from 3 to 33 mmHg and qualitative motor abnormalities (i.e., aperistalsis, repetitive waves, tertiary waves) in 3 patients. Histologically, the frequency of epithelial types was junctional greater than specialized columnar greater than atrophic fundic epithelium. More importantly, dysplasia was identified in 2 patients with the circumferential lesion and in 1 patient with the island lesion. Potential difference measurements demonstrated that a high potential difference (greater than -25 mV) was highly specific (92%), but only moderately sensitive (70%) for detecting Barrett's esophagus. Based on these findings, we conclude (a) that there are at least two endoscopically distinct types of Barrett's esophagus involving the lower esophagus--a circumferential type and an island type, (b) that both types are associated with chronic gastroesophageal reflux, with the island type being accompanied by less severe epithelial injury than the circumferential type, and (c) that the identification of dysplasia in the two types suggests that both are unstable lesions requiring continued surveillance with endoscopy and biopsy.

Monolayer culture of human endometrium: methods of culture and identification of cell types.

Monolayer cultures can be established from human endometrial tissue after enzymatic dispersal into isolated glands or single cells. Three cell types that have distinct morphology by light and electron microscopy are observed in the resulting primary cultures. One cell type, an elongated spindle cell, is similar in appearance to fibroblasts derived from other tissues. A second cell type forms colonies of tightly cohesive cells, ranging in shape from oval to polygonal. These cells have typical organelles and junctional complexes characteristic of epithelial cells from the endometrium. The third cell type assumes a pavement-like appearance composed of polygonal cells when viewed by phase contrast microscopy, but lacks distinctive ultrastructural features of epithelial cells. These cells in culture resemble the endometrial stromal cell, the predominant cell type of the human endometrium in vivo. The epithelial cell does not survive subculturing but the other two cell types can be passaged through several generations and can be stored in liquid nitrogen and subsequently returned to culture.

Esophageal potential difference measurements in esophageal disease.

To determine if esophageal transmural electrical potential difference measurements are of use for evaluating esophageal disease, we recorded potential difference in 129 patients with one or more of the following: heartburn, dysphagia, and chest pain. All potential difference studies were performed at the time of esophageal manometry using a Ringer-perfused catheter technique which yields accurate and reproducible results in healthy subjects. In 103 of the 129 patients, esophageal potential difference measurements could be correlated with findings at manometry, endoscopy, and biopsy. The remaining 26 patients had primary esophageal motor disease and were not biopsied. The results of this investigation showed: (a) that 94% of patients with gross endoscopic lesions have an abnormal esophageal potential difference, (b) that an abnormal esophageal potential difference (found in only 1 of 24 patients with normal mucosa) is highly specific for the presence of esophageal mucosal disease, (c) that the type of potential difference abnormality may suggest the nature of the mucosal abnormality, for example high potential difference with Barrett's esophagus and low potential difference with esophagitis or invasive carcinoma, and (d) that while an abnormal esophageal potential difference is highly sensitive for detecting gross esophagitis (38 of 40 patients), it is less sensitive for diagnosing microscopic esophagitis (8 of 16 patients). Based on these findings we conclude that the measurement of esophageal potential difference at the time of manometry can provide additional valuable information about the state of the esophageal mucosa.

Fibroblastic tumor of the urinary bladder after cyclophosphamide therapy.

An unusual fibroblastic tumor occurred in a teenage boy following treatment with cyclophosphamide for Hodgkin's disease. To our knowledge, only one other similar case has been reported. The cellular and structural composition of the tumor resembles that of cyclophosphamide-induced cystitis and therefore suggests a relationship between the two lesions.

Morphologic alterations in early acid-induced epithelial injury of the rabbit esophagus.

To arrive at a basic understanding of the pathogenesis of reflux esophagitis, we developed an acute experimental model in the rabbit for studying the early lesion. Acid was perfused in vivo into the lower esophagus while potential difference was monitored intermittently. At varying degrees of potential difference decline, indicating epithelial injury, the esophageal stratified squamous epithelial tissue was removed for morphologic studies and in vitro electrophysiologic and transport studies. At 50 per cent reduction in potential difference, there was dilation of intercellular spaces, which when correlated with physiologic results of increased permeability indicates increased intercellular water. At 100 per cent reduction in potential difference, cells in the midepithelium were observed to be swollen and ruptured, forming vesicular spaces, midepithelial cleavages, and later early ulceration. Results of functional studies at this stage showed inhibition of sodium transport. The midepithelial site of disruption corresponds to the site of active sodium pumping out of cells in other stratified squamous epithelia. Since sodium is transported by esophageal epithelium and this function was inhibited by acid, we propose that this early morphologic lesion may be the result of damage to the sodium-transporting mechanisms of the epithelium.

Pathophysiology of acute acid injury in rabbit esophageal epithelium.

To increase our understanding of the pathophysiology of reflux esophagitis, we sought the early sequence of changes in mucosal structure and function in acutely acid-damage rabbit esophagus. Using a perfused catheter technique esophageal potential difference (PD) profiles were obtained in anesthetized rabbits before, during, and after perfusion of the lower one-half of the esophagus with phosphate-buffered saline or 80 mM NaCl. When acid perfusion reduced the lower esophageal PD by 40-50% or 80-100% of the initial values, the esophagus was removed, sectioned, and the mucosa studied with light microscopy, transmission electron microscopy, and Ussing chamber technique for evaluation of sodium and mannitol transport. The earlier stage of acid damage (PD 40-50%) was associated with reduced mucosal resistance fom 2,180 +/- 199 to 673 +/- 157 ohm cm2 and increased passive transport of sodium (0.10 +/- 0.06 to 1.82 +/- 0.48 microeq/h.cm2) and mannitol (0.008 +/- 0.003 to 0.051 +/- 0.012 microM/h.cm2) (p less than 0.05). There was no significant change in shirt circuit current (0.35 +/- 0.05 to 0.35 +/- 0.04) or net sodium transport (0.32 +/- 0.06 to 0.37 +/- 0.12) at this stage, and the only morphologic finding was dilated intercellular spaces on electron microscopy. The later stage of acid damage (PD 80-100%) exhibited a further reduction in resistance to 299 +/- 65 ohm.cm2 (p less than 0.05), a finding now accompanied by a reduction in short circuit current (0.35 +/- 0.05 to 0.21 +/- 0.04 microeq/h.cm2) and complete inhibition of net sodium transport (0.32 +/- 0.06 to 0.01 +/- 0.13) (p less than 0.05). Morphologic studies at this time revealed cellular necrosis, edema, and vesicle formation in the stratum spinosum. Both gross mucosal changes and transmural necrosis were notably absent. When esophageal perfusion was performed with a combination of acid (80 mM HCl-80 mM NaCl) and pepsin (100 microgram/ml), the morphologic and physiologic findings were essentially the same as with acid alone; however, the time of perfusion to reach either the 50 or 100% reduction in PD was shortened. The findings in this model can be explained on an initial increase in cellular and/or paracellular permeability followed by inhibition of active sodium transport. The resulting loss of osmolar regulation leads to cell necrosis in the stratum spinosum.

Neurohumoral control of esophageal epithelial electrolyte transport.

The neurohumoral control of epithelial esophageal electrolyte transport was investigated by studying the effect of various hormones and neuroeffector agents on the potential difference (PD) in vivo or on the electrical parameters of electrolyte transport in vitro. The rabbit esophagus, which has no submucosal esophageal glands, demonstrated no effect of pentagastrin, cholecystokinin octapeptide, or synthetic secretin in vivo, and no effect of these hormones or of vasopressin, aldosterone, carbachol, epinephrine, or cAMP in vitro. The rabbit esophagus did respond to metabolic substrates (glucose) in vitro by increasing sodium absorption. In contrast, the opossum esophagus, which contains extensive submucosal glands, had a lower electrical resistance, PD, short-circuit current, and sodium absorption with higher chloride secretion. This esophagus responded to carbachol and epinephrine by sodium and chloride secretion. We believe that only the submucosal glands of the esophagus are under significant neurohumoral control while the sodium transporting function of the stratified squamous epithelium of this organ is important in maintaining its barrier function.

Malignant histiocytosis: a cytochemical and electron microscopic study of an unusual case.

A 25-year-old black female presented with lymphadenopathy, fever and anemia of two months duration. The diagnosis of malignant histiocytosis was made on the basis of histiocytic infiltrations in the sinuses of spleen, liver and lymph nodes and by the demonstration of erythrophagocytosis in bone marrow. Following splenectomy, the patient developed a leukemic phase with as many as 50 X 10(9) abnormal histiocytes/l and bone marrow necrosis. This patient was also atypical because of multiple granulomas in liver, spleen and lymph nodes. Cytochemical and immunofluorescent stains confirmed that the abnormal cells were derived from the monocyte-macrophage series. Electron microscopy was used to further characterize this abnormal cell population. The electron microscopic and cytochemical evidence confirms that the malignant cells in malignant histiocytosis are derived from monocytes.

Clear cell carcinoma of the endometrium.

The clinical data of 22 patients with clear cell adenocarcinoma of the endometrium treated at the University of North Carolina Memorial Hospital are reported. In addition, the data with particular reference to survival, site of recurrence, and treatment are combined with information from two previous reports of clear cell adenocarcinoma of the endometrium to better define survival. It is noted that the patients with clear cell adenocarcinoma of the endometrium were older and had an overall poorer survival than is reported for adenocarcinoma of the endometrium (nonclear cell). Patients with Stage I clear cell carcinoma of the endometrium, however, had a similar five-year survival to Stage I adenocarcinoma of the endometrium. The paper also examines treatment methods and correlates these with site of recurrence as well as survival.

Transmural electrical potential difference in the mammalian esophagus in vivo.

A simple, safe, accurate, and reproducible technique for measuring the transmural electrical potential difference (PD) of the esophagus has been developed. This technique, a modification of those previously used, allows simultaneous correlation of the PD profile with the pressure profile obtained during routine manometry. With this technique, a subcutaneous reference bridge was shown to detect accurately a lumen-negative electrical orientation for the esophageal PD in three species: rabbit, opossum, and man. A characteristic and reproducible PD profile was present for each species. In the rabbit the gastric PD was low,--12 mv, relative to the body of the esophagus,--26 to -29 mv. In contrast, both opossum and man had relatively high gastric PD's ( -36 to -43 mv) when compared to esophageal PD's ( -12 to -25 mv). In the rabbit and opossum, the PD in the lower esophageal sphincter ( -5 to -6 mv) was less than both gastric or esophageal PD's, whereas in human beings the lower esophageal sphincter PD ( -22 mv) was between gastric and esophageal values. In vitro PD measurements and histological studies of opossum esophagus revealed differences in the epithelium which correlated with the different in vivo PD's.

Neonatal and infantile hypoglycemia due to insulin excess: new aspects of diagnosis and surgical management.

Persistent hypoglycemia in the neonate and young infant usually results from inappropriate, excessive secretion of insulin, or a deficiency of one of the hepatic gluco-regulatory enzymes. Hypoglycemia due to hyperinsulinism, whether associated with nesidioblastosis, islet cell hyperplasia, adenoma or normal islets, may have devastating consequences in this age group and demands recognition and effective treatment. Medical management consisting primarily of frequent feeding, the intravenous infusion of glucose and the administration of glucagon, glucocorticoids, epinephrine, and diazoxide is often ineffective and may be punctuated by repeated episodes of hypoglycemia, convulsions, and central nervous system damage. Although subtotal-total pancreatectomy is effective in restoring blood sugar to normal, almost half of the reported patients are mentally retarded. This may be due in part to unwarranted delays in performing pancreatectomy. Experience with 6 patients undergoing subtotal--total pancreatectomy for intractable hypoglycemia supports the contention that this procedure is effective. A euglycemic state was restored in all 6 patients and there was no evidence of residual central nervous system damage. The spleen should be preserved in view of its importance in maintaining normal immunodefense mechanisms.

Congenital insulinoma (nesidioblastoma): ultrastructural evidence for histogenesis from pancreatic ductal epithelium.

An insulinoma removed from a neonate with proved hyperinsulinemia was examined with the electron microscope. The tumor was composed of pancreatic ductal epithelium and beta cells in direct contact and in lobular units. The pattern of the tumor, the morphologic evidence of beta cell-type activity in ductal cells, and the similarity of the arrangement of tumor cells to that observed in islet regeneration after subtotal pancreatectomy in the rat indicate that this tumor originated from ductal epithelium.