Etiology of hyperparathyroidism and bone disease during chronic hemodialysis. II. Factors affecting serum immunoreactive parathyroid hormone.

Plasma concentration of immunoreactive parathyroid hormone (IPTH) was measured in 18 patients who had been on a hemodialysis program for longer than 6 months. A negative correlation was found between the predialysis plasma concentration of IPTH and the mean concentration of calcium in the dialysate previously used: plasma concentrations of IPTH were higher in patients dialyzed against a calcium concentration between 4.9 and 5.6 mg/100 ml than in patients dialyzed against a calcium concentration of 6.0 mg/100 ml or more. Plasma concentrations of IPTH also were higher in patients with bone disease than in patients without bone disease. Furthermore, a positive correlation was found between predialysis plasma concentrations of IPTH and calcium, and between mean predialysis concentration of IPTH and phosphate. To obviate the possibility that individual differences in susceptibility could have accounted for the observed effects of plasma phosphate and of dialysate calcium, a 2 x 2 factorial study was conducted in seven of these patients to examine the independent effects of perturbation of each of these factors. It was observed that plasma concentration of IPTH was lowest with the combination of high dialysate calcium and low plasma phosphate, highest with the combination of low dialysate calcium and high plasma phosphate, and intermediate with the two other combinations. It is concluded that both dialysate calcium and plasma phosphate are important determinants of parathyroid function in these patients.

U.S. centralized cancer patient data system for uniform communication among cancer centers.

The evolution of the Centralized Cancer Patient Data System, a cooperative venture of the 21 comprehensive cancer centers in the United States, and its structure at the end of 3 years of data collection are described. Functions of the data system are detailed in terms of input and output. It is concluded that the short-run objective of establishing a data system to provide high-quality patient data that ae 21 comprehensive cancer centers in the United States, and its structure at the end of 3 years of data collection are described. Functions of the data system are detailed in terms of input and output. It is concluded that the short-run objective of establishing a data system to provide high-quality patient data that ae 21 comprehensive cancer centers in the United States, and its structure at the end of 3 years of data collection are described. Functions of the data system are detailed in terms of input and output. It is concluded that the short-run objective of establishing a data system to provide high-quality patient data that are comparable among cancer centers has been largely accomplished. Moreover, the very process of setting up the national data system has benefited the participating centers by upgrading their individual cancer registries. For the future, the goal is to realize the research potential of this new cooperative data collection mechanism, as well as the accumulating data themselves. Progress toward the long-term goal is just beginning.

Prognostic variables in osteosarcoma: a multi-institutional study.

This is a report of a multi-institutional study of all patients with osteosarcoma who were seen at 13 comprehensive cancer centers from July 1, 1977, to December 31, 1982. Follow-up extended to 9 years; a minimum of 3 years was obtained for greater than 90% of the patients. All patients with osteosarcoma were considered, but only those with tissue confirmation who had had at least part of their first course of treatment at one of the 13 institutions were included. There were 543 patients. In a search for prognostic indicators, 38 patient characteristics, three treatment categories, and an institutional variable were studied. A combination of nine of these constituted the best indicator of survival. They were morphology (two parts), site of primary cancer (two parts), spread of tumor, grade and size of tumor, duration of symptoms, weight loss of greater than 4.5 kg (10 lb), swelling at primary site, and lytic appearance. Unexpectedly, treatment was not one of the indicators of survival. A prognostic score was developed in which the coefficients were obtained from the Cox regression (step-down) method. Each patient had a score (S) and an observed survival time that together provided the expected risk of death for that patient. Although this was not a randomized study, treatments were compared before and after adjusting for characteristics identified as prognostic. Three treatments differed little: surgery alone, surgery plus chemotherapy and/or radiotherapy, and chemotherapy and/or radiotherapy followed in 1-4 months by surgery. Patients with amputations and those with resections had similar death rates, but the observed progression rates differed widely. However, when the rates were adjusted for prognostic characteristics, the difference disappeared. Complete surgery (if osteosarcoma existed within surgical margins) was no better than incomplete surgery (if osteosarcoma existed beyond surgical margins) with respect to death but, as would be expected, complete surgery was much better with respect to disease progression.

Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up.

BACKGROUND: The Mayo Lung Project (MLP) was a randomized, controlled clinical trial of lung cancer screening that was conducted in 9211 male smokers between 1971 and 1983. The intervention arm was offered chest x-ray and sputum cytology every 4 months for 6 years; the usual-care arm was advised at trial entry to receive the same tests annually. No lung cancer mortality benefit was evident at the end of the study. We have extended follow-up through 1996. METHODS: A National Death Index-PLUS search was used to assign vital status and date and cause of death for 6523 participants with unknown information. The median survival for lung cancer patients diagnosed before July 1, 1983, was calculated by use of Kaplan-Meier estimates. Survival curves were compared with the log-rank test. RESULTS: The median follow-up time was 20.5 years. Lung cancer mortality was 4.4 (95% confidence interval [CI] = 3.9-4.9) deaths per 1000 person-years in the intervention arm and 3.9 (95% CI = 3.5-4.4) in the usual-care arm (two-sided P: for difference =.09). For participants diagnosed with lung cancer before July 1, 1983, survival was better in the intervention arm (two-sided P: =.0039). The median survival for patients with resected early-stage disease was 16.0 years in the intervention arm versus 5.0 years in the usual-care arm. CONCLUSIONS: Extended follow-up of MLP participants did not reveal a lung cancer mortality reduction for the intervention arm. Similar mortality but better survival for individuals in the intervention arm indicates that some lesions with limited clinical relevance may have been identified in the intervention arm.

A controlled pilot study of high-dose methotrexate as postsurgical adjuvant treatment for primary osteosarcoma.

Thirty-eight patients whose primary extremity or limb girdle osteosarcomas had been completely excised (37 amputations, one limb sparing procedure) were allocated at random to two treatment groups receiving respectively regular follow-up examinations plus a high-dose methotrexate (HDMTX) regimen or regular follow-up without primary adjuvant chemotherapy. Although the vincristine, HDMTX, leucovorin regimen was generally quite tolerable when given at three-week intervals for one year and most of the chemotherapy patients followed the planned HDMTX dose escalations from 3 to 6 to 7.5 g/m2, delayed methotrexate excretion limited dosage escalations in 25%. An estimated 52% of the 38 patients were surviving five years after randomization and an estimated 42% remained continuously relapse-free after five years. No significant differences between the outcomes of the 20 treated and the 18 untreated patients were apparent; however, power to detect differences was low. Furthermore, no significant differences in postmetastasis survival were apparent between the 12 treated and 10 untreated patients who relapsed. Approximately 20% of these failing patients appear to have been salvaged for long-term survival. This pilot study of HDMTX confirms the continuing need for controlled clinical trials in determining the therapeutic value of adjuvant chemotherapy programs for patients with primary osteosarcoma.

Abnormalities of endogenous glucagon and insulin in unstable diabetes.

The responses of glucagon, growth hormone, and insulin secretion to the oral administration of glucose and to the intravenous infusion of saline, arginine, and insulin were measured in seven patients who had stable diabetes, eight who had unstable diabetes, and seven healthy volunteers. Hyperglycemia suppressed secretion of glucagon in normal subjects but not in diabetics. The oral glucose and arginine infusion tests demonstrated partial preservation of insulin-secretory ability in stable diabetics and its virxual absence in unstable diabetics. Glucagon responses to arginine infusion were similar in all three groups. In response to hypoglycemia induced by insulin infusion, the concentrations of plasma glucagon increased in normal subjects and, to a lesser extent, in stable diabetics but increased in only two of the unstable diabetics. The impairment in glucagon response during hypoglycemia in diabetics correlated positively with the degree of diabetic instability and insulin deficiency during glucose and arginine testing. The severity of the insulin deficiency also correlated with the degree of diabetic instability. These findings support the hypothesis that inherent abnormalities of insulin and glucagon secretion may account for many of the clinical characteristics of unstable and stable diabetic patients.

Forearm and finger hemodynamics, blood pressure control, and lipid changes in patients with diabetic hypertension treated with atenolol and prazosin.

Hypertension and diabetes mellitus frequently coexist and are independent risk factors for reduced peripheral perfusion. Antihypertensive medications that reduce blood pressure and improve peripheral perfusion would have advantages in diabetic patients with hypertension. In a randomized, two-placebo period, single-blind, two-way crossover study, we determined finger and forearm blood flow, lipid levels, and blood pressure control in 19 diabetic patients with hypertension, with each atenolol or prazosin and placebo period of 4 weeks' duration. Both drugs reduced blood pressure (sitting: 157/95 to 142/84 mm Hg, atenolol; 155/95 to 138/82 mm Hg, prazosin; standing: 154/94 to 144/84 mm Hg, atenolol; 154/94 to 133/81 mm Hg, prazosin). Lipid levels did not change except that low-density lipoprotein levels fell from 148 to 127 mg/dl with prazosin. Atenolol did not change forearm or finger blood flow or vascular resistance. Prazosin increased blood flow and reduced vascular resistance in both finger and forearm. In conclusion, prazosin has a potentially more appropriate hemodynamic profile than has atenolol in diabetic patients with hypertension.

Forearm and finger hemodynamics, blood pressure control, and lipid changes in diabetic hypertensive patients treated with atenolol and prazosin. A brief report.

Hypertension and diabetes mellitus frequently coexist and are independent risk factors for reduced peripheral perfusion. Antihypertensive medications that reduce blood pressure and improve peripheral perfusion would have advantages in diabetic hypertensive patients. In a randomized, two-placebo-period, single-blind, two-way, crossover study, finger and forearm blood flow, lipid levels, and blood pressure control were determined in 19 diabetic hypertensive patients given prazosin and atenolol, with each drug and placebo period lasting four weeks. Both drugs reduced blood pressure (sitting, 157/95 to 142/84 mm Hg for atenolol and 155/95 to 138/82 mm Hg for prazosin; standing, 154/94 to 144/84 mm Hg for atenolol and 154/94 to 133/81 mm Hg for prazosin). Lipid levels did not change, except that low-density lipoprotein levels decreased from 148 to 127 mg/dl with prazosin. Atenolol did not change forearm or finger blood flow or vascular resistance. Prazosin increased blood flow and reduced vascular resistance in both finger and forearm. In conclusion, prazosin demonstrated a potentially more appropriate hemodynamic profile than atenolol in diabetic hypertensive patients in this study.

Cardiac death in mucocutaneous lymph node syndrome.

A 12 year old boy had 4 symptom-free years after hospitalization for acute febrile mucocutaneous lymph node syndrome before he died suddenly from extensive myocardial infarction. Current evidence suggests that many patients with this syndrome have coronary artery disease and that those with significant cardiac findings should be studied with coronary angiography. Serial studies are recommended because of the danger of sudden death.

Abnormal cardiovascular regulation in the mitral valve prolapse syndrome.

Studies of patients with mitral valve prolapse syndrome have suggested autonomic nervous system dysfunction, but a precise definition of mechanisms is lacking. We measured supine and standing heart rate, blood pressure, cardiac output, oxygen consumption, plasma catecholamines, and blood volume in 23 symptomatic women with both echocardiographic and phonographic signs of MVP and in 17 normal control subjects. An analysis of the results revealed 2 distinct subgroups of patients: those with normal heart rates but increased vasoconstriction (Group I, n = 10) and those with orthostatic tachycardia (Group II, n = 13). Group II patients had heart rates at rest supine of 97 +/- 3 compared with 79 +/- 2 in Group I patients and 78 +/- 8 in control subjects. Estimated total blood volumes were lowest in Group I patients, intermediate in Group II patients, and highest in control subjects (p less than 0.05). Other measurements at rest supine were similar in patients and controls. After standing for 5 minutes, patients had a higher mean plasma epinephrine value, diastolic blood pressure (81 +/- 2 versus 74 +/- 3 mm Hg, p less than 0.05), and peripheral resistance (1,878 +/- 114 versus 1,414 +/- 92, dynes s cm-5, p less than 0.01), wider arteriovenous oxygen difference (6.7 +/- 0.4 versus 5.3 +/- 0.5 vol%), and lower stroke volume index (26 +/- 2 versus 33 +/- 2 ml/m2, p less than 0.01) than did the control subjects. Cardiac output was normal in Group II patients but reduced in Group I patients, who demonstrated marked vasoconstriction. No patient had evidence of a "hyperkinetic" circulatory state. A cycle of decreased forward stroke volume, vasoconstriction, and blood volume contraction appears to be present in at least some symptomatic patients with MVP.

Who responds to sugar pills?

Among 288 cancer patients undergoing controlled trials of oral analgesics there were 112 who received 50% or greater pain relief from placebo formulations. Patients who responded to placebo had a greater response rate to active drugs. They also had a higher incidence of central nervous system side effects to placebo. Patient groups showing as increased placebo response included those with a high level of education, farmers, those with a professional occupation, women working outside the home, and patients who were widowed, separated, or divorced. Those resistant to placebo were patients with a low educational level, unskilled workers, housewives, married women without children, and smokers. It is theorized that placebo response is a type of autohypnosis phenomenon resulting from exaggerated oral-dependency needs. Particularly vulnerable to placebo effect is the very self-sufficient individual with heavy responsibilities who is thrust into the unaccustomed dependency of disabling illness.

Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome.

We performed a retrospective study of 859 patients with papillary thyroid cancer, who had received their primary treatment at the Mayo Clinic during the period 1946 through 1970. The maximal follow-up was 39 years. All but 2 patients underwent a thyroid operation; 319 (37%) had metastatic cervical nodes. Of the 800 patients without distant metastatic lesions on initial examination who underwent a potentially curative surgical procedure, postoperatively 7% had nodal metastatic lesions, 6% had a local tumor recurrence, and 5% had a distant metastatic lesion. In patients who had intrathyroidal tumors initially, postoperative local recurrences or distant metastatic lesions resulted in a 10-year cancer mortality of 17 and 41%, respectively; in those with extrathyroidal tumors, postoperative recurrences were associated with significantly higher death rates. Death from thyroid cancer was highly associated with the following factors: age more than 50 years, male sex, tumor size, tumor grade, initial extent of disease, and absence of Hashimoto's disease. Earlier studies of Mayo patients treated between 1926 and 1960 described no deaths due to thyroid cancer in patients with occult tumors (1.5 cm or less). Four such patients were identified among our 859 patients; all had been examined and treated after 1961. To date, 56 (6.5%) of the 859 patients have died as a result of papillary thyroid cancer. In this study, in which 16% of patients underwent total thyroidectomy and 3% had radioiodine ablation, the overall mortality observed at 30 years was only 3% above that expected.

Cholecystectomy and gastric ulcer--an etiologic relationship?

To determine whether cholecystectomy might be a factor predisposing to gastric ulceration, we evaluated the frequency of prior cholecystectomy in the 181 residents of Rochester, Minnesota, who had gastric ulcer diagnosed at the Mayo Clinic during the 10-year-period from 1966 to 1975. This frequency was similar to that in a control population from the same city, matched for age, sex, and time of registration at the Mayo Clinic. This was also true for subgroups of benign gastric ulcer. However, the frequency of prior cholecystectomy was higher in patients with type 1 ulcer than in those with type 2 or 3 ulcer, probably as a result of the relative predominance of older women in the type 1 ulcer group. These data do not support the hypothesis that cholecystectomy may be harmful in predisposing to gastric ulceration.

Trends and variability in survival from osteosarcoma.

Survival of patients with primary osteosarcoma who received traditional surgical management has been very poor. Several studies have reported the percentage of patients alive 3 years after first treatment to be between 20 and 25%. In a study of such patients first treated at the Mayo Clinic between Jan. 1, 1963, and July 1, 1974, the survival noted in the first few years was typical of that of other reports, about 25%. However, by 1972 through mid-1974, the 3-year survival had become 50%. This improvement was not the result of adjuvant treatment or any basic change in type of patient treated, yet it is similar to that reported in connection with some of the new adjuvant therapies used in trials depending on historical controls. Our results cast doubt on findings made in the absence of concurrent, randomly selected controls.

Hemoccult stool tests: false-negative results due to storage of specimens.

Stoll samples mixed with 0 to 38 mg of hemoglobin per gram of stool were tested for occult blood by the Hemoccult (HO) method when fresh and after storage for 1 to 14 days. The intensity of the HO reaction in fresh stool samples was directly related to the hemoglobin concentration, and approximately 8 mg/g was required for a positive reaction. After samples had been stored on HO cards for 4 days, the intensity of the HO reaction was decidedly less in all. Except at the highest concentrations studied, all became HO-negative or trace within 8 days. In contrast, samples of most concentrations that were stored in tightly capped containers prior to preparation of HO cards maintained a positive reaction intensity for 1 week. Nevertheless, the intensity of the HO reaction decreased significantly (P less than 0.01) with each method of storage. No false-positives were induced by storage during this portion of our study. Samples from 100 stool specimens sent to the clinical laboratory for determination of occult blood were also smeared on separate HO cards for testing immediately and after 4, 7, or 10 days of storage. Only one positive HO reaction was observed on an HO card prepared from a specimen initially classified as HO-negative. In contrast, up to 40% of the stored HO cards prepared from specimens initially classified as HO-positive were HO-negative when analyzed 4 days later.

Lymphadenectomy in the management of stage I malignant melanoma: a prospective randomized study.

A prospective randomized study was initiated at our institution in 1972 to determine the efficacy of routine elective lymphadenectomy in localized (stage I) melanoma. Included in the study were 171 patients, 62 of whom had no lymphadenectomy, 55 of whom had delayed lymphadenectomy, and 54 of whom had immediate lymphadenectomy. No significant difference was found among the three treatment groups with respect to survival or metastasis-free survival. Multifactorial analysis indicated that the level of invasion and the thickness of the lesion were the most important prognostic factors, followed by age (60 years or older), site (legs), and tumor type (nodular). A prognostic index based on these variables was highly predictive of metastasis or death. Even when this score was considered, no significant variation was noted among the three treatment groups. More subsequent complications of melanoma, however, occurred in the group with no lymphadenectomy--36 in this group but only 19 in each of the other treatment groups. This finding was not statistically significant but does indicate that a few additional problems may be associated with leaving regional nodes intact. Further studies are needed, and indeed are being conducted, to determine whether elective lymphadenectomy improves survival sufficiently to offset the costs and the complications associated with this approach.

The primary surgical treatment of carcinoma of the breast: a changing trend toward modified radical mastectomy.

To study the effectiveness of a trend at the Mayo Clinic toward modifying the standard radical mastectomy, the 5-year survival of 873 women treated surgically for breast cancer from 1965 through 1968 was evaluated. The observed survival of 534 patients treated by the standard radical mastectomy was 85% when nodes were negative and 56% when nodes were positive. For 339 patients treated by the modified radical mastectomy, the observed survival was 80% and 48% when axillary nodes were negative and positive, respectively. In order to accomplish a more significant analysis of cancer risk and results of the two operative procedures, a relatively homogeneous group of 541 patients was established from the total group. In this homogeneous group, the observed survival of 336 patients treated by the standard radical mastectomy was 86% when nodes were negative and 66% when nodes were positive. For 205 patients treated by the modified radical mastectomy, the observed survival was 84% and 66% when axillary nodes were negative and positive, respectively. When patients were further analyzed and compared according to the extent of axillary-node involvement, age at the time of treatment, grade, size, location, and histopathologic type of tumor, and the use of postoperative irradiation, survival was essentially the same, irrespective of the type of mastectomy performed.

Invasive Hürthle cell carcinoma of the thyroid: natural history and management.

Debate surrounds the natural history and appropriate management of Hürthle cell neoplasms of the thyroid. Some of the uncertainty stems from difficulty in the differentiation of benign from malignant lesions. We report the presentation, management, and outcome of patients with invasive Hürthle cell carcinoma who were examined at this institution between 1946 and 1971. We believe that our review allows us to make reasonable recommendations concerning the management of patients with this type of carcinoma.

Anaplastic carcinoma of the thyroid: a clinicopathologic study of 82 cases.

Anaplastic carcinoma of the thyroid accounts for about 10% to 15% of all thyroid carcinomas in the United States. Its lethality is evidenced by a 5-year survival rate of 3.6% and a median survival of 4 months. Rapid growth of a thyroid mass, frequently in a preexisting goiter, is the most common manifestation; the diagnosis should be considered and expeditiously pursued in all patients who present with this finding. Relatively favorable prognostic features seem to be unilateral tumors, a tumor diameter of less than 5 cm, no invasion of adjacent tissue, and absence of nodal involvement. For resectable lesions, thyroid lobectomy with wide margins of adjacent soft tissue on the side of the tumor seems to constitute a safe, appropriately aggressive surgical approach. Total thyroidectomy and radical neck dissection results in an increased complication rate and has no advantage over a more conservative approach. Radiotherapy, chemotherapy, immunotherapy, and combination radiotherapy and chemotherapy need further evaluation.

Trends and variability in survival among patients with osteosarcoma: a 7-year update.

This report is an update of a 1978 article on osteosarcoma in Mayo Clinic patients. It includes additional follow-up on previously reported cases and incorporates new cases treated since the time of that original study. From 1963 through 1981, 336 patients with classic, previously untreated osteosarcoma received their first definitive treatment at our institution. Survival of these patients was studied in detail. The most significant result was that survival in the 1960s was much worse than that in the 1970s. The first evidence of improvement in survival was noted in 1969; subsequently, further improvement occurred but was not consistent. This finding prevailed with respect to duration of survival to death, survival to detection of metastasis, and survival from occurrence of metastasis to death. On the basis of detailed regression analysis, several variables had independent prognostic value. From these findings, a prognostic score was developed, which was based on the number of the following unfavorable characteristics: age younger than 10 years, male sex, tumor diameter more than 15 cm, cell type osteoblastic or chondroblastic, duration of symptoms 2 months or less, and involvement of the femur or humerus. Patients with five or six of these unfavorable characteristics had a very poor survival; in contrast, patients with only one or two characteristics had a good outcome. Even when these scores were fairly constant, however, the calendar period had a strong influence on survival. Likewise, when treatment was considered and adjustments by score were made, no significant differences could be found between those patients treated by amputation only and those treated by amputation supplemented with chemotherapy or radiotherapy.