Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast.

The prognostic significance of intramammary lymphatic and blood vessel invasion was evaluated in a retrospective series of 221 patients with node-negative carcinoma of the breast treated with modified radical mastectomy. To facilitate identification of lymphatic and blood vessel invasion, the tumors were studied with an immunohistochemical technique using antibodies to endothelial markers. Peritumoral lymphatic and blood vessel invasion (PLBI) (encompassing both lymphatic and blood vessel invasion) was an adverse prognostic indicator independent of menopausal status, tumor size, and other histologic variables. Recurrence of disease and death resulting from carcinoma were significantly higher for patients with PLBI-present (+) tumors compared with patients with PLBI-absent (-) tumors (P less than .0001). The risk of recurrence for patients with PLBI+ tumors was 4.7 times that for their PLBI- counterparts. The presence of intratumoral lymphatic and blood vessel invasion (ILBI) is less important because few examples were found without concomitant PLBI. When PLBI was separated into lymphatic invasion and blood vessel invasion individually, the prognostic significance was retained in both groups. The immunohistochemical approach reduced both false-negative and false-positive observations and identified about 40% of PLBI that would have been missed by routine histologic examination alone. The presence of PLBI appears to be a potentially useful discriminant in predicting the outcome of patients with node-negative carcinoma of the breast.

Benign and malignant tumors in patients with acromegaly.

Growth hormone and its principal mediator insulinlike growth factor I are known promoters of normal growth. To determine whether excessive secretion of growth hormone is associated with an increased occurrence of benign and of malignant tumors, we studied records of 87 patients with acromegaly seen in the Lahey Clinic Medical Center (Burlington, Mass) from 1957 to 1988 and compared the rate of tumor occurrence with a control group of patients with pituitary tumors (198) and with findings from a cancer registry. Patients with acromegaly had a 2.45-fold increased rate of malignant tumors (95% confidence interval, 0.98 to 5.04) compared with findings from the tumor registry. Female patients had a higher rate than male patients. The rate of carcinoma of the thyroid was excessive and previously underscribed, but the rate of carcinoma of the colon was not increased as reported by others. Among benign lesions, goiters, predominantly nodular, were seen in 25% of patients in addition to a large number of mesenchymal lesions.

Barrett's esophagus. Prevalence and incidence of adenocarcinoma.

Between January 1973 and January 1989, 241 patients with Barrett's esophagus were treated at the Lahey Clinic Medical Center, Burlington, Mass. Of these patients, 65 presented with adenocarcinoma in Barrett's esophagus for a prevalence rate of 27%. Of 176 patients followed up for a total of 497 patient-years, adenocarcinoma developed in five patients for an incidence of one per 99 patient-years. The development of adenocarcinoma during endoscopic surveillance 1, 2, 2, 4, and 10 years after the initial diagnosis of Barrett's esophagus emphasizes the importance of long-term endoscopic and histologic surveillance. All five patients had severe dysplasia before adenocarcinoma developed. Yearly endoscopic follow-up examination is recommended for all patients with Barrett's esophagus unless mild dysplastic changes are found, in which case surveillance should be increased. Patients with severe dysplasia who are otherwise acceptable candidates for operation should be advised to have esophageal resection.

Effect of raising endogenous testosterone levels in impotent men with secondary hypogonadism: double blind placebo-controlled trial with clomiphene citrate.

Secondary hypogonadism is not an infrequent abnormality in older patients presenting with the primary complaint of erectile dysfunction. Because of the role of testosterone in mediating sexual desire and erectile function in men, these patients are usually treated with exogenous testosterone, which, while elevating the circulating androgens, suppresses gonadotropins from the hypothalamic-pituitary axis. The response of this form of therapy, although extolled in the lay literature, has usually not been effective in restoring or even improving sexual function. This failure of response could be the result of suppression of gonadotropins or the lack of a cause and effect relationship between sexual function and circulating androgens in this group of patients. Further, because exogenous testosterone can potentially increase the risk of prostate disease, it is important to be sure of the benefit sought, i.e. an increase in sexual function. In an attempt to answer this question, we measured the hormone levels and studied the sexual function in 17 patients with erectile dysfunction who were found to have secondary hypogonadism. This double blind, placebo-controlled, cross-over study consisted of treatment with clomiphene citrate and a placebo for 2 months each. Similar to our previous observations, LH, FSH, and total and free testosterone levels showed a significant elevation in response to clomiphene citrate over the response to placebo. However, sexual function, as monitored by questionnaires and nocturnal penile tumescence and rigidity testing, did not improve except for some limited parameters in younger and healthier men. The results confirmed that there can be a functional secondary hypogonadism in men on an out-patient basis, but correlation of the hormonal status does not universally reverse the associated erectile dysfunction to normal, thus requiring closer scrutiny of claims of cause and effect relationships between hypogonadism and erectile dysfunction.

Occult axillary lymph node metastases in "node-negative" breast carcinoma.

The presence of occult axillary nodal metastases was evaluated in 159 patients with "node-negative" invasive breast carcinoma. Multiple additional levels of the lymph nodes were examined with hematoxylin-eosin staining and keratin immunostaining. Occult nodal metastases were detected in 50 (31%) patients; of these, 28 (17%) were detectable by hematoxylin-eosin stain alone, while the other 22 (14%) consisted of mostly single cells or very small clusters and required immunostaining for detection. The size of the metastatic deposit was < or = 0.2 mn in 31 (19%) patients and greater than 0.2 mm in 19 (12%) patients. Occult nodal metastasis correlated with the presence of peritumoral lymphatic invasion (P = .02) and was seen more frequently with larger tumor size, increased microvasculature, and aneuploidy. As a group occult metastases had no significant prognostic impact. However, patients with metastases measuring greater than 0.2 mm had significantly worse recurrence (P = .02), disease-free survival (P = .04), and overall survival (P = .07) rates; those with metastases detectable by hematoxylin-eosin stain alone also had a less favorable, although not significant, outcome. In contrast, patients with occult metastases that were < or = 0.2 mm or that were detected only by immunostaining had a survival rate comparable to and in fact slightly higher than that of the group without occult metastasis; 23 of these patients were without recurrence after a median follow-up of 11 years. Extension into perinodal soft tissue was an unfavorable feature. In a multivariate analysis peritumoral lymphovascular invasion and increased microvasculature were the most important prognostic parameters, and the presence of occult metastases greater than 0.2 mm was no longer significant. Our data suggest that occult metastases < or = 0.2 mm, especially those consisting of single cells, do not add useful prognostic information, and immunohistochemical studies to detect them are probably unnecessary. Larger metastases and extranodal involvement may have important prognostic value, but in this study they accounted for only 20% of patients who had recurrences or 6% of the total population. This underscores the importance of using more than one prognostic parameter in evaluating breast carcinoma.

Microvessel quantitation and prognosis in invasive breast carcinoma.

The prognostic significance of microvessel quantitation in invasive breast carcinoma was analyzed in a study group that comprised 88 patients with axillary node-negative carcinoma and 32 patients with axillary node-positive carcinoma who had a minimum follow-up period of 9 years. Microvessels were identified by immunohistochemistry using antibodies to endothelial markers, including factor VIII-related antigen and blood group isoantigens (ABH). Factor VIII-related antigen staining provided more consistent results for microvessel quantitation than did staining for ABH isoantigens. The three most vascular areas within a tumor were selected, and the microvessels within a x200 microscopic field of each area were counted by two investigators simultaneously. Node-positive carcinomas demonstrated significantly higher microvessel counts than did node-negative carcinomas (mean +/- SD, 99 +/- 42 and 73 +/- 22, respectively; P less than .001). In node-negative carcinomas, tumors from patients who experienced distant recurrence had higher microvessel counts than did tumors from patients who were disease-free (84 +/- 19 and 70 +/- 22; P = .01). Similarly, in patients with node-positive carcinoma, microvessel counts were considerably higher in tumors from patients who experienced distant recurrence than in patients who did not, although the difference did not reach statistical significance (113 +/- 44 and 93 +/- 34, respectively). Among patients with node-negative carcinoma, those with a microvessel count of less than 84 had a recurrence rate of 20% compared with 57% in patients with counts greater than 84 (P = .003). Microvessel counts were independent of histologic parameters, ploidy status, and S-phase fraction but correlated with peritumoral vascular invasion. Both microvessel counts and vascular invasion were independent prognostic parameters by multivariate analysis. High vessel counts may represent increased tumor angiogenesis and are correlated with tumor aggressiveness. Microvessel quantitation may be an additional prognostic factor that, when used in conjunction with more established parameters, can help in appropriate patient management.

Relationship of hospital size, case volume, and cost for coronary artery bypass surgery: analysis of 12,774 patients operated on in Massachusetts during fiscal years 1995 and 1996.

OBJECTIVE: This study investigates the relationship between the cost of coronary artery bypass graft surgery and both hospital size and case volume. METHODS: Retrospective administrative and cost data were obtained for all 12,774 patients who underwent isolated coronary bypass surgery at 12 Massachusetts hospitals during 1995 and 1996. Hospitals were stratified by number of operating beds into 3 groups (group I, <250 beds; group II, 250-450 beds; group III, >450 beds). Total (diagnosis-related groups 106 + 107) annual coronary bypass cases per hospital varied from 271 to 913 (mean 532). Univariate and multivariable analyses were used to study the relationship between the direct and total cost and a number of patient (age, sex, acuity class, payer) and hospital (bed capacity, annual case volume per diagnosis-related group, cardiothoracic residency) predictor variables. For each hospital, we also studied the relationship between changes in coronary bypass case volume and the corresponding changes in average cost from 1995 to 1996. RESULTS: Scatterplots revealed a broad range of mean direct cost of coronary bypass surgery among hospitals with comparable case volumes. When annual cases were analyzed as continuous variables, there was no linear relationship of case volume with direct or total cost of coronary bypass (r = -0.05 to +0.08) for any diagnosis-related group or year. When hospital bed capacity and case volume were grouped into strata and studied by analysis of variance, there was no evidence of an inverse relationship between these variables and cost. In multivariable analysis, patient acuity class and diagnosis-related group were the most important predictors of cost. Beds and case volume met inclusion criteria for most models but added little to the "explanation" of variability R(2), often less than 1%. Finally, substantial interhospital differences were noted in the magnitude and direction (direct vs inverse) of their 1995 to 1996 change in volume versus change in cost. CONCLUSIONS: Within the range of hospital size and case volume represented in this study, there is no evidence that either variable is related to the cost of performing coronary bypass surgery. Massachusetts hospitals appear to function on different segments of different average cost curves. It is not possible to predict the relative cost of coronary bypass grafting at a given hospital based primarily on volume.

Esophagogastrectomy for carcinoma of the esophagus and cardia: a comparison of findings and results after standard resection in three consecutive eight-year intervals with improved staging criteria.

OBJECTIVE: A review of findings and results after standard resection for carcinoma of the esophagus and cardia without neoadjuvant therapy was done to provide a basis for comparison with current reports of radical resection and neoadjuvant therapy. METHODS: A 24-year experience on one surgical service with 454 operations for carcinoma of the esophagus and cardia was reviewed. A comparison of findings and results in three consecutive 8-year intervals was analyzed, and new staging criteria were developed and compared with those currently favored by the American Joint Committee on Cancer. RESULTS: From January 1, 1970, to January 1, 1994, 454 patients with carcinoma of the esophagus or cardia underwent operation, of whom 408 (90%) had esophagogastrectomy with a 30-day mortality rate of 2.5% and an additional hospital mortality rate of 1.2%. Of the 121 complications (30.7%), 71 (18%) were major and 50 (12.7%) were minor. Cardiovascular complications predominated. The overall 5-year survival was 24.7%, with a 33.7% survival after complete resections in the most recent interval under study. Palliation of dysphagia was achieved in nearly 80% of patients who survived the operation. During the three intervals under review, resectability, mortality, and complication rates remained constant. The percentages of left thoracotomies and transhiatal resections increased, and there was a decrease in thoracoabdominal incisions. The percentages of patients with Barrett's esophagus and stage 0 and I tumors increased. The percentage of complete resections (R0) increased, whereas that for resections with residual microscopic tumor (R1) decreased, and there was no change in the percentage of patients with residual gross tumor after resection (R2). Modified WNM staging criteria are proposed that provide better prognostic stratification of the disease than those currently favored by The American Joint Committee on Cancer. CONCLUSIONS: Standard esophagogastrectomy is applicable in 90% of patients with operable carcinoma of the esophagus or cardia, with consistently low mortality and morbidity rates and satisfactory palliation of dysphagia. The 5-year survival (24.7% overall) remains suboptimal, but the current figure for complete resections (33.7%) is encouraging. There is a need for revision of the current American Joint Committee on Cancer staging criteria.

Flow cytometric and image analyses of colorectal adenocarcinomas. A comparative study with clinical correlations.

Quantitative DNA measurements were performed in 183 colorectal carcinomas by image and flow cytometric analyses of paraffin-embedded tissue. Flow cytometric analysis yielded more diploid tumors compared with image analysis, which identified more tetraploid tumors. Histogram patterns were concordant in 115 tumors (66%); the discordant cases were primarily tumors interpreted as diploid by flow cytometric analysis but were aneuploid or tetraploid by image analysis. Linear regression analysis of DNA indices of concordant samples showed good correlation but only moderate correlation for the entire group. Both techniques revealed more aneuploid tumors in the distal colon and rectum than in the proximal colon. Diploid tumors were associated with a better prognosis; however, tetraploid tumors behaved like aneuploid tumors by flow cytometric analysis but like diploid tumors by image analysis. When stratified by stage, the prognostic value of diploid tumors was seen in stages A and B disease by image analysis only and in stage C disease by flow cytometric analysis only, possibly because of the small cohort size. The S-phase fraction (mean value, 16.8% +/- 9.9%) was higher in aneuploid than in diploid tumors, but no relationship to prognosis was seen. Flow cytometric and image analyses are useful to study ploidy of colorectal carcinoma from archival material. However, important discordant observations reflecting differences in characteristics of the two techniques should be considered, depending on which technique is used.

Achalasia and squamous cell carcinoma of the esophagus: analysis of 241 patients.

Achalasia of the esophagus is presumed by many to be a premalignant lesion leading to an increased risk of squamous cell carcinoma. There is disagreement, however, as to the precise risk of malignant degeneration and there is no consensus as to either the need for close surveillance of achalasia patients or the surveillance technique that should be employed. A review of the available literature on the subject has disclosed a wide range of reported cancer risks in achalasia patients, from zero to 33 times that of the normal population. Cancers, when discovered, are often unresectable and the median survival when they are resectable is low. A personal experience with 241 achalasia patients treated during the past quarter of a century disclosed that 9 had carcinoma, for a prevalence of 3.7%. Carcinoma developed in 3 of these 9 while they were under our observation. This translates into one cancer per 1,138 patient-years of follow-up, an incidence of 88 per 100,000 population, and a risk 14.5 times that of the age-adjusted and sex-adjusted general population. Because of the low postresection survival rate if treatment is delayed until carcinoma of the esophagus becomes symptomatic, closer surveillance of achalasia patients is recommended than has been the case. Because it seems unlikely that close endoscopic surveillance will prove to be cost-effective, periodic (every 2 to 3 years) blind brush biopsy warrants further study as a means of surveillance.

Comparison of results of nocturnal penile tumescence and rigidity in a sleep laboratory versus a portable home monitor.

OBJECTIVES: To validate the results of the home penile tumescence monitor versus the sleep laboratory studies of erectile function. METHODS: We used both methods to study 18 episodes of rigidity and 19 episodes of tumescence in 10 subjects with erectile dysfunction before and after the use of an experimental vasodilating medication. RESULTS: The tumescence measurement in the sleep laboratory compared favorably with the changes in tumescence with the RigiScan portable home monitor: at the base (r = 0.70; P < 0.001), and at the tip (r = 0.84; P < 0.001). In measuring rigidity, the buckling pressure in the sleep laboratory compared favorably with the RigiScan measurements of percent average rigidity at the base (r = 0.56; P = 0.017), at the tip (r = 0.62; P = 0.006), and mean rigidity of the base and tip (r = 0.64; P = 0.004). In a comparison of the buckling pressure with the new RigiScan Plus quantitative program, there was good correlation with the rigidity activity units at the base (r = 0.70; P = 0.001) and at the tip (r = 0.72; P < 0.001). A clinical estimate of penetrable rigidity correlates with the RigiScan base rigidity of 55% to 60% and tip rigidity of about 50%. CONCLUSIONS: The portable home monitor is a viable and cost-effective clinical tool to measure nocturnal penile activity.

Cancer of the esophagus and cardia: does age influence treatment selection and surgical outcomes?

BACKGROUND: Some physicians believe that an aggressive surgical approach for the management of cancer of the esophagus and cardia is unwise in elderly patients because of allegedly higher rates of mortality and morbidity and lower rates of survival than those associated with younger patients. We have long advocated an aggressive surgical approach regardless of the patient's age and have reviewed our experience to determine whether age was a factor influencing treatment and outcomes. STUDY DESIGN: From January 1, 1970 to January 1, 1997, 505 patients with cancer of the esophagus or cardia underwent operations by one surgical team using standard surgical techniques. One hundred forty-seven patients (29.1%) were 70 years of age or older and 358 patients (70.9%) were under 70 years of age. Their records and clinicopathologic features were reviewed and compared. RESULTS: The two groups were similar regarding the location of tumors. Tumor cell types were similar except for adenocarcinomas in Barrett's esophagus, which were less common in the older group (15.6% versus 24%; p=0.046). Surgical procedures were similar, as were the rates of resectability and the percentages of R0 resections. The hospital mortality rate was higher in the elderly patients but not significantly so, and the rates of major and minor complications combined were comparable. The differences in postresection pathologic staging were not significant. Satisfactory palliation of dysphagia was comparable between the groups, as were actuarial 5-year survival rates (24.1% of the elderly patients versus 22.4% of the younger patients). CONCLUSIONS: Age should not be a limiting factor in using an aggressive surgical approach for the management of cancer of the esophagus or cardia in patients aged 70 years or older. Such an approach can be performed as safely as in younger patients, with comparable rates of palliation and survival.

Proposal for improved staging criteria for carcinoma of the esophagus and cardia.

OBJECTIVE: Current staging for carcinoma of the esophagus and cardia remains imprecise. In an effort to improve on presently accepted staging criteria, new and improved criteria were sought. METHODS: A total of 408 specimens resected for carcinoma of the esophagus or cardia between January 1, 1970, and January 1, 1994, were available for analysis. Pathology reports were reviewed, and available histologic slides were examined microscopically. When necessary, paraffin blocks of excised specimens were recut for further pathologic evaluation. On the basis of these findings, tumors were staged according to the criteria of American Joint Committee on Cancer (AJCC). New criteria were established based on the WNM concept and staged accordingly. Survival rates based on these sets of criteria were calculated for each stage, and results were compared. RESULTS: Because our previous studies had shown no advantage provided by the revised AJCC criteria compared with those originally proposed, we modified the WNM system by eliminating the subdivisions of Stage II, reducing the T categories by 1, T3 and T4 having shown no survival differences, and increasing the N categories by 1, depending on the number of nodes involved, e.g. NO = no positive nodes; N1 = 1-4 positive nodes, and N2-5 or more positive nodes. The resulting staging system and 5-year survival rates obtained thereby are as follows: Stage O (TO, is, 1 NO), 88.2%; Stage I (T1N1, T2NO), 50.3%; Stage II (T2N1, T3N0) 22.5%; Stage III (T3N1, any T N2), 10.7%; and Stage IV (M1) 0%. CONCLUSIONS: A new staging scheme for carcinoma of the esophagus and cardia is proposed that provides better prognostic stratification of patients than existing ones.

Ten to 20-year clinical results after short esophagomyotomy without an antireflux procedure (modified Heller operation) for esophageal achalasia.

To determine the long-term clinical results after modified esophagomyotomy without an antireflux procedure for esophageal achalasia, the status of all patients undergoing this operation with a minimum follow-up time of 10 years was reviewed; 81 such patients were operated on between January 1970 and January 1981. Thirteen patients were lost to follow-up review permitting clinical evaluation during the past year of 68 patients (84%) observed for a median of 13.6 years. Fifty-nine patients (87%) were improved by operation; 90% of the patients who underwent a primary procedure were improved, whereas only 73% of patients undergoing reoperation benefited. Kaplan-Meier analysis of the results of all 81 patients disclosed an improvement rate of 98.5% at 5 years, 95.6% at 10 years, 85.8% at 15 years, and 67.3% at 20 years. When the level of improvement or lack thereof was analyzed, the percentage of excellent results decreased from 54% to 32% (P = 0.02). The percentage of good results remained the same, whereas fair or poor results together increased from 20% to 37% (P = 0.05). Neither age, sex, esophageal caliber, duration of symptoms, or previous therapy appeared to influence these results. We conclude that limited esophagomyotomy without an antireflux procedure results in persistent long-term improvement for the patient with esophageal achalasia. The level of improvement, however, decreases with the passage of time, presumably because of persistent disease in the body of the esophagus leading to impaired esophageal emptying in some patients and late reflux esophagitis in other patients owing to poor esophageal clearance.

Reoperation after failed antireflex surgery. Review of 101 cases.

Between January 1970 and July 1994, 101 patients underwent reoperation for a failed antireflux procedure. These patients had previously had 160 upper gastrointestinal tract operations, usually a Nissen fundoplication or one of its modifications (87). The chief reason for failure of the original antireflux procedure was faulty surgical technique (65). An incorrect diagnosis accounted for most of the remaining failure (22). Of patients who had follow-up studies, 80% were improved by reoperation, which consisted of takedown or refashioning of the original wrap in the majority of patients (63). A more radical approach is justified after two failed reoperations. Our current preference is for vagotomy, antrectomy, and Roux-en-Y diversion coupled, when indicated, with resection of the esophagogastric junctional area.

Trabeculectomy with mitomycin C: intermediate-term results.

PURPOSE: This study was performed to provide results 2 to 3 years after trabeculectomy with mitomycin C (MMC). METHODS: A consecutive series of all 68 patients who underwent trabeculectomy with MMC was analyzed using Kaplan-Meier life-table statistics and compared with other published retrospective analyses. RESULTS: At 2- and 3-year follow-up examinations, 59% (95% confidence interval [CI], 44-70%) and 47% (95% CI, 32-61%) of patients, respectively, avoided an intraocular pressure (IOP) of more than 21 mmHg or less than 20% below their preoperative level without glaucoma medication on two consecutive occasions more than 1 month apart after 3 months follow-up (75% [95% CI, 60-84%] and 70% [95% CI, 53-81%], respectively, with medication) and avoided additional glaucoma surgery. Loss of more than three lines of visual acuity on two occasions more than 1 month apart after 3 months follow-up occurred in 28% of patients (> 2 lines in 44%) at 3 years. Nonreversible causes of loss of three lines of acuity occurred in 13% of patients. Complications requiring reoperation occurred in 16% of patients and included hypotony maculopathy (4%) and late bleb leaks (4%). CONCLUSIONS: At the 3-year follow-up evaluation, trabeculectomy with MMC provided an approximately 50% chance of maintaining IOPs less than 21 mmHg and a more than 20% IOP reduction without concomitant use of glaucoma medication, which increased to 70% with the addition of medication. This procedure was associated with an approximately 30% risk of substantial visual loss (approximately 15% nonreversible) and a 15% chance of reoperation for complications.

Cessation of smoking rapidly decreases erectile dysfunction.

OBJECTIVE: To assess the relationship between cessation of smoking and rapid improvement in erectile capacity as well as the effect of nicotine patches on nocturnal penile tumescence and rigidity. METHODS: Nocturnal penile erections were studied in 10 smokers with use of the RigiScan portable home monitor. Two nights were monitored: for the first night, the patients had not stopped smoking; for the second night, the patients had stopped smoking for 24 hours. In addition, four men were monitored after cessation of smoking and wearing nicotine patches for 1 month. RESULTS: Multiple variables studied showed a statistically significant improvement in nocturnal penile tumescence and rigidity in the men who had stopped smoking for 24 hours. Continued improvement was noted in the four men who were monitored while not smoking and wearing nicotine patches for 1 month. CONCLUSION: Stopping cigarette smoking is a factor that rapidly improves penile tumescence and rigidity. Because the improvement continues while the patient is receiving nicotine from transdermal patches, some factor or factors other than the nicotine are responsible for the erectile dysfunction.

Quantitative DNA analysis and proliferation in breast carcinomas. A comparison between image analysis and flow cytometry.

The DNA content and proliferation in 100 invasive breast carcinomas were evaluated by computerized image analysis (IA) and flow cytometry (FCM). For DNA content, image analysis of Feulgen-stained slides of fresh tumor imprints were compared with flow cytometry of propidium iodide-stained disaggregated fresh tumor tissue. The DNA indices obtained by the two methods showed close correlation by linear regression analysis (r = 0.89, p less than .001). There were 44 (44%) diploid and 56 (56%) aneuploid tumors. There was agreement between the two methods in detection of aneuploidy in 81% of tumors. Image analysis required smaller tissue samples, permitted direct visualization and selection of tumor cells, and was more sensitive in detecting tetraploid and highly aneuploid cell populations. In contrast, flow cytometry histograms provided better resolution, and were more effective in detecting multiploid tumors and near-diploid aneuploid tumors. Aneuploidy was significantly related to various adverse prognostic parameters, namely, negative estrogen receptor, high mitotic rate, high histologic and nuclear grades. Proliferation was evaluated by measuring the FCM S phase fraction (SPF), and by image analysis quantitation of immunohistochemical staining using Ki-67 monoclonal antibody. SPF and Ki-67 count showed modest correlation (r = 0.42). Both SPF and Ki-67 count were significantly related to the mitotic rate, histologic and nuclear grades. Our results indicate that the two methods provide comparable results, but offer individual advantages and are complementary techniques in analyzing DNA ploidy and proliferation in breast carcinomas.

Clinical features and prognostic factors associated with adrenocortical carcinoma: Lahey Clinic Medical Center experience.

Adrenocortical carcinoma is a rare tumor associated with a commonly poor prognosis. However, data on the natural history and response to therapy of patients with this malignancy have often been conflicting. Our objective of this retrospective study was to evaluate the clinical course and survival of patients with adrenocortical carcinoma and to identify relevant prognostic factors. Between 1966 and 1996, 31 patients with histologically documented adrenocortical carcinoma were observed at the Lahey Clinic Medical Center. Patient information was obtained from chart review. At the time of diagnosis, 48 per cent of patients had endocrine symptoms with compatible hormonal studies, 19 per cent had involvement of the inferior vena cava by tumor thrombus, and 32 per cent had metastatic disease. The median survival time was 17 months (range, 1-205 months) for the entire group, and the 5-year survival rate was 26 per cent. Age <54 years, absence of metastatic disease at the time of diagnosis, and completeness of surgical resection were associated with better prognosis. Evaluation of survival with the Cox proportional hazards model suggested that age <54 years, absence of metastatic disease, and nonfunctioning tumor status were independently associated with improved survival. The prognosis of patients with adrenocortical carcinoma is poor but appears more favorable in patients <54 years, with localized disease, or nonfunctioning tumor status. Complete tumor resection may be associated with improved survival.

Normal sensation of the human face and neck.

A total of 116 adult volunteers were studied to determine normal values for static two-point discrimination and sensation of pressure of the head and neck. Thirteen regions of the head and neck corresponding to major sensory innervation were examined bilaterally for static two-point discrimination with the Mackinnon-Dellon Disk-Criminator and for sensation of pressure with Semmes-Weinstein monofilaments. Perception of two-point discrimination improved from lateral and posterior areas (17 to 25 mm) to the midline toward the lips (3 to 7 mm). Semmes-Weinstein monofilaments proved inadequate in determining sensitivity to cutaneous pressure because of low thresholds in the face and neck. Static two-point discrimination is a reliably reproducible method for assessing sensation of the face and neck.