Biomedical subjects
Publications and source records attributed to M E Johns.
Molecular analysis of surgical margins may provide greater accuracy in predicting local recurrence. The high frequency of associated p53 mutations implicates tobacco in the molecular progression that eventuates in head and neck squamous cell carcinoma.
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Warthin's tumor previously has been thought to occur much more commonly in men than in women and rarely in African Americans. One hundred thirty-two cases of Warthin's tumor treated at The Johns Hopkins Hospital from 1952 to 1992 were retrospectively reviewed. There were 90 (68%) men and 42 (32%) women, with an overall man-to-woman ratio of 2.2:1. The number and percentage of women with Warthin's tumor increased over each consecutive decade: 1952 to 1962, 5 (21%); 1963 to 1972, 6 (29%); 1973 to 1982, 11 (31%); and 1983 to 1992, 20 (39%). A positive smoking history was found in 88% of the men and in 89% of the women with a Warthin's tumor. Eleven (8%) African Americans and 1 (0.75%) Asian American were diagnosed to have a Warthin's tumor. Also, the incidence of African Americans with a Warthin's tumor increased over each decade: 0 (0%), 1 (4.8%), 2 (5.5%), and 8 (16%). This study's results indicate a progressive increase in the occurrence of this tumor in women and in African Americans and a higher overall incidence in African Americans than previously reported.
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Pathologic evidence of gastroesophageal reflux demonstrated by either Barrett's esophagus or esophagitis was present in 33% of patients undergoing laryngopharynoesophagectomy, while secondary esophageal squamous cell carcinomas were present in 25% of the specimens. Overall, 54% of all the patients undergoing laryngopharyngoesophagectomy had esophageal disease. This incidence of reflux and secondary esophageal malignant neoplasia is higher than in the general population. Careful assessment of the patient's preoperative history for gastroesophageal reflux, contrast swallowing studies, and esophagoscopies correctly diagnosed most but not all of the esophageal lesions found on pathologic examination. Interestingly, all of the esophageal carcinomas removed in the laryngopharyngoesophagectomy specimens were small and sometimes not evident clinically. Although gastroesophageal reflux has been postulated as an additional etiologic agent in the development of laryngeal carcinoma, all the patients in our study had heavy alcohol and tobacco consumption, and therefore reflux could not be evaluated separately as a risk factor.
From 1975 to 1987, 87 patients with carcinomas of the major salivary glands (70 parotid and 17 submandibular) were treated at our institution by either surgery or surgery followed by postoperative radiotherapy (RT). Surgical procedures included superficial (24%) or total (56%) parotidectomies and submandibular gland resection (20%). Postoperative RT usually began 2 to 4 weeks following surgery. Using 4 MV photons or, infrequently, 60Co, the majority of patients received 6000 cGy in 6 weeks to the parotid region (ranged from 4500 to 7000 cGy). Determinant actuarial survival was 74% at 5 years and 71% at 10 years. For patients with previously untreated disease, 5 of 19 (26%) treated by surgery alone experienced local recurrence, whereas only 2 of 50 (4%) recurred locally following surgery plus postoperative RT (p = 0.01). For patients presenting with recurrent disease, 4/4 (100%) failed locally following surgery as opposed to 3/14 (21%) following surgery plus postoperative RT (p = 0.01). The determinant 5-year actuarial survival for patients receiving postoperative RT was 75% versus 59% for surgery alone. Results were analyzed by multivariate methods using determinant survival or recurrence as endpoints. Five important prognostic factors were identified. (a) Facial nerve paresis was predictive of poor outcome (p less than 0.001) with 3-year relapse free survival of 13%. (b) Undifferentiated histology was associated with decreased survival (p = 0.002). (c) Male sex was associated with poor outcome (p = 0.008). (d) Skin invasion resulted in decreased survival (p = 0.012). (e) Radiotherapy was associated with improved survival (p = 0.014). In addition, postoperative RT was effective in preventing local recurrence (p less than 0.001). The data demonstrate the efficacy of postoperative RT in improving survival and local control for patients with carcinomas of the major salivary glands.
A retrospective analysis was made of the data on 60 patients with stage T1 glottic carcinoma (43 T1a, 17 T1b) who received radiation therapy and 17 patients with T1a disease who underwent laser excision as the primary treatment modality. Patients who received radiation therapy achieved 3- and 5-year actuarial local control rates of 92% and 89% for T1a and 77% and 77% for T1b disease, respectively. In patients who underwent laser excision (all with T1a disease), the 3-year local control rate was 77%. Of the 42 evaluable irradiated T1a patients, 31 (74%) had a normal to near-normal voice, eight (19%) had mild or intermittent hoarseness, and three (7%) had persistent hoarseness. Of the 13 evaluable patients in the laser-excision group, four (31%) had a normal to near-normal voice, five (38%) had mild or intermittent hoarseness, and four (31%) had persistent hoarseness. The difference in the quality of voice between these two groups is statistically significant (P = .012), although the ultimate local control rate after salvage therapy for irradiated patients (97%) was similar to that for laser-excision patients (94%).
Both academic and economic goals must be served by the academic health center. In response to ongoing stresses on medicine, the Johns Hopkins School of Medicine and the Johns Hopkins Hospital rapidly developed and implemented an expanded system of medical care. Vertical integration included provision of both acute and chronic care facilities and both primary and specialty care, as well as insurance products, in particular a health maintenance organization. Horizontal integration was accomplished by acquisition of or affiliation with other hospitals. The realignment of medical resources and patients shifted the locus of medical education somewhat, from the traditional hospital setting to the ambulatory care setting (in which many students and residents will eventually practice anyway). In addition, many physicians in the new settings are not traditional Johns Hopkins faculty members. Results of educational efforts in these altered circumstances so far have been mixed, partly because the capacity of the individual center to train students and residents is necessarily limited, and the fragmentation of the system makes inevitable problems of quality control and management. These issues are being worked out. The drain on faculty resources for research imposed by the need to expand clinical practice has been offset by a system of awards for research to faculty members. Efforts are being made to sustain the excellence of the traditional Johns Hopkins faculty's reputation while assuring doctors newly affiliated with the Hopkins system that they are no less important to the system. Opportunities to learn and to teach more economical medicine while retaining quality are discussed.
Bilateral enlargement of the parotid glands has been noted in five patients who are seropositive for antibody to the human immunodeficiency virus. A characteristic cystic appearance has been noted in these lesions on clinical and radiographic examination. A benign lymphoepithelial infiltrate with cystic degeneration is found in parotid specimens from these patients. The presence of human immunodeficiency virus ribonucleic acid in inflammatory cells infiltrating the parotid specimen was confirmed by an in situ hybridization technique. The clinical manifestations of sicca syndrome were not present nor were opportunistic infections diagnostic for the acquired immunodeficiency syndrome.
The diagnosis of salivary gland tumors is complicated by their relative infrequency, the limited amount of pretreatment information usually available, and the wide range of biologic behaviors seen with different histopathologic types. Most salivary gland neoplasms originate in the parotid, 10-15% arise from the submandibular glands, and the rest occur in the sublingual and minor salivary glands. The probability of a salivary gland neoplasm being malignant is inversely proportional to the size of the gland. The authors discuss two major theories of histogenesis, itemize the various benign and malignant varieties of tumor, discuss the presentation and prognosis for each type, and present a list of factors that influence survival. They also discuss the newest staging system.
The authors base their treatment of salivary gland malignancies on the size of the primary and the histopathologic diagnosis. Group 1 includes smaller tumors in the T1 and T2 classification with cell types that are associated with slow growth. A parotidectomy is usually sufficient therapy for tumors in this group. Group 2 contains T1 and 2 tumors with more aggressive behavior. Total parotidectomy is indicated here, with postoperative radiotherapy. T3 tumors and patients with nodal metastasis or recurrent tumors make up group 3. Radical parotidectomy with sacrifice of the facial nerve is usually required for a sufficient tumor-free margin in these patients, and postop radiotherapy is also necessary. Group 4 includes T4 lesions. Extent of disease dictates magnitude of excision and amount of postop radiotherapy.
Head and neck cancer (H&N CA) patients have known depression of cell-mediated immunity. There is suggestive evidence that prostaglandin (PGE2)-secreting cells may be a major factor. The authors have sought to determine the role of PGE2-releasing monocytes-macrophages in this immune depression by determining the effects of adherent cell depletion and by measuring the effects of indomethacin, a PGE2 synthetase inhibitor, on selected tests of lymphocyte function. Lymphocyte stimulation with phytohemagglutinin (PHA) (T-cell stimulant) and Staph phage lysate (SPL) (B-cell stimulant) was done in the presence of varying concentrations of indomethacin; the effect of adherent cell depletion also was determined. The study population included 45 patients with localized or locoregional squamous CA of the H&N and 40 controls. Results included the following: (1) lymphocyte stimulation responses to PHA and SPL were generally depressed in the CA patients versus controls; (2) incubation with indomethacin produced bivalent effects in both controls and CA patients, depending on the concentration of indomethacin and lymphocyte stimulant; incubation with optimum concentrations of indomethacin generally produced augmented responses in both study groups whereas high concentrations of indomethacin were suppressive; (3) the immune potentiating effects were not observed in older patients with advanced disease; and (4) removal of adherent leukocytes (mainly monocytes) also restored depressed lymphocyte responses. Although other factors also are operative, our data suggest that PGE2-secreting monocytes-macrophages may have a major role in the immune depression of H&N CA patients. Age and host effects of the cancer and the malnutrition common to these patients probably are involved also, although their singular contribution has not been measured. This depression is largely reversible by a PGE2 synthesis inhibitor, indomethacin, which suggests the potential value of in vivo administration of indomethacin to H&N CA patients as an adjunct.
Of 293 patients who underwent computed tomography (CT), surgery, and pathologic examination for chronic sinusitis, 25 had a diagnosis of fungal sinusitis at pathologic examination. Of these, 22 had foci of increased attenuation at CT (in four patients the mean representative CT number [Hounsfied unit] was 122.2 HU [SD, 8.2 HU]), and three did not. Of the 22, 19 patients (76%) met the CT criterion of this study (there was a 12% false-positive and a 12% false-negative diagnostic rate). Six of the 19 patients and one additional patient underwent magnetic resonance (MR) imaging, and all demonstrated remarkably hypointense signal characteristics on T2-weighted images. The findings at MR imaging therefore appear more characteristic of fungal sinusitis than the findings at CT. Furnace atomic absorption spectrometry showed increased concentrations of iron and manganese in mycetoma compared with their concentrations in bacterially infected mucus. This finding and the presence of calcium in the fungal concretion may explain the hypointense T2-weighted signal on MR images.
The exposure obtained using the degloving approach is superb and the absence of resultant facial scar or deformity provides a dramatic new addition to the otolaryngologist's surgical repertoire. The advantages of the degloving technique in exposure of the midface, nasal cavities, paranasal sinuses, nasopharynx, skull base, and clivus have led to its increasing importance in the otolaryngology literature. Within 2 years of the technique's introduction in our department, it had been used 48 times for a wide variety of problems, including inverting papilloma, juvenile angiofibroma, chordoma and selected cases of fungal disease of the sinuses. This article describes the procedure, reports the results from a panel of 48 patients, and discusses potential complications. The authors' experience with this procedure indicates that it should become a procedure of choice for management of inverting papilloma and juvenile angiofibroma, as well as a major alternative method in many other circumstances.
Magnetic resonance studies frequently demonstrate increased T2-weighted signal in the nasal area. To further evaluate this phenomenon, several MRI examinations of the nasal cavity were performed within an 8- to 12-hour period. The study demonstrated that changes alternated from side to side and were interrupted by the administration of topical vasoconstriction, confirming imaging of the normal nasal cycle. Changes were also observed within the ethmoid sinuses. Signal intensity on T2-weighted images during the congested phase was similar to inflammatory mucosa. Occasionally, these changes make interpretation of the extent of pathology difficult in patients with sinus disease, and raise the possibility of inflammatory pathology in asymptomatic patients. Awareness of MRI imaging of nasal cycle should reduce the likelihood of diagnostic errors and provides another method for study of this physiologic phenomenon.