Frothy feedlot bloat in cattle: production of extracellular polysaccharides and development of viscosity in cultures of Streptococcus bovis. Streptococcus bovis was cultured in a synthetic medium with three concentrations of sucrose. Initial viscosity of the media was 1.5 centipoise (cp). After incubation for 8 h, the viscosity of the medium with 0.5% sucrose was unchanged, that with 3% sucrose had increased to 8 cp, and that with 6% sucrose to 112 cp. Similar results were found with a rumen fluid medium. A slimy material, responsible for increased viscosity of these cultures, was digested by dextranase. The material appeared as a complex system of intercellular fibers when viewed under the electron microscope after freeze-etching. With proteins and other polymers released from lysed bacteria, this slimy material may contribute directly to increased viscosity and foam formation. In addition to these intercellular fibers, each cell was surrounded by a fibrous capsule that was not digested by dextranase. This capsule stained with lead citrate and uranyl acetate, but not with ruthenium red. The amount of capsular material produced was similar whether the media contained 0.5, 3.0, or 6% sucrose.


Studies on the cellular and free lipopolysaccharides from Branhamella catarrhalis. Cellular and free lipopolysaccharides obtained from Neisseria catarrhalis and Branhamella catarrhalis were found to be essentially identical. Both cellular and free lipopolysaccharides contained core-oligosaccharides of the following composition: D-glucose (4 mol), D-galactose (1 mol), 2-amino-2-deoxy-D-glucose (1 mol), and 3-deoxy-D-manno-octulosonic acid. Aldoheptose and phosphate components were below levels of detection. Several physical methods indicated that all core-oligosaccharide preparations were identical. Lipid A preparations from cellular and free lipopolysaccharides of both organisms were qualitatively and quantitatively similar; they were composed of decanoic acid, dodecanoic acid, 3-hydroxy dodecanoic acid, 2-amino-2-deoxy-D-glucose, phosphate, and ethanolamine. The results tend to justify the transfer of Neisseria catarrhalis to the genus Branhamella.


Effect of calcium and anaerobiosis on the thermostability of Bacillus stearothermophilus. Bacillus stearothermophilus NCA 2184 lost viability and subsequently released cytoplasmic components when suspended in 0.1 M tris(hydroxymethyl)aminomethane (Tris) buffer (pH 7.2) and incubated at 60 degrees C. Cell lysis was prevented by the addition of 10 mM CaCl2 to the Tris-buffer suspension. Cells which were incubated under anaerobic conditions for 20 min in the growth medium before they were collected were stable in the Tris-buffer suspension without added calcium. Anaerobic incubation effected an increase in membrane cardiolipin which appeared to be related to the increase in the thermostability of the cells.


Somatic nuclear division in the sporidia of Ustilago violacea. III. Ultrastructural observations. The paper provides detailed ultrastructural observations on nuclear division in the smut fungus Ustilago violacea and is based on previous light-microscopic work outlining the division in living and stained cells. The division as in many other Basidiomycetes is not intranuclear, but occurs within a partially disrupted membrane. The division takes place after migration of most of the nucleus into the bud cell, after limited breakdown of the nuclear membrane, and after the formation of a spindle between two spindle-pole bodies (SPB). The remaining part of the nucleus containing the nucleolus is left behind in the parent cell and degenerates there. The SPB, as in other Basidiomycetes, is a dome-shaped relatively structureless body, quite distinct from the flat plaques of many Ascomycetes and the elaborat centrioles of Phycomycetes. The SPB divides shortly before migration into the daughter cell and invariably is located at the apex of the migrating nucleus. Nuclear division is completed when the two masses of chromatin clustered about each of the SPB's are separated as the spindle elongates. One daughter neculeus reforms in the bud and the other is reformed in the mother cell. Cells fixed and stained by conventional light-microscopic methods were examined in the light of the electron-microscopic observations to determine whether these procedures induce artefacts. Aceto-orcein and Giemsa when used cold were found to produce relatively artefact-free preparations. However, previous results in which the cells were warmed gently in these stains are now seen to contain artefacts in the form of contracted chromatinic granules often arranged in chains. These artefacts may provide useful information but clearly they must be interpreted cautiously until the nature of the changes induced by heating are known.


Somatic nuclear division in the sporidia of Ustilago violacea. IV. Microtubules and the spindle-pole body. In unbudded cells of the anther smut fungus Ustilago violacea there is a dome-shaped spindle-pole body (SPB) consisting of a core 0.1 mum in diameter surrounded by a ribosome-free region 0.3-0.4 mum in diameter lying in a pocket of the nuclear membrane. After budding the nucleus moves towards the bud and begins to rotate rapidly. At about this stage the SPB divides into two parallel bars each about 0.1-0.15 mum in diameter and 0.3 mum long, separated by a distance of about 0.3 mum. Microtubules associated with the nuclear membrane but not with the SPB are present at the time of nuclear rotation. These microtubules disappear when rotation stops. Microtubules attached to the SPB are found during migration of the chromatinic portion of the nucleus into the bud cell. These microtubules disappear when migration stops and the nuclear membrand begins to break down. The twin SPB bars appear to move into the nucleus through a break in the membrane and begin to move apart forming a spindle about 1 mum long. Chromosomal microtubules (one per kinetochore) were found in several serial sections, and in addition there appeared to be several continuous microtubules present. The separation of the two chromatinic masses appeared to result from elongation of the continuous microtubules to about 3 mum long. Cytoplasmic microtubules and spindle microtubules were both found attached to the SPB as it elongated and one nucleus returned to the mother cell. The paper concludes with a discussion of the SPB as a multifuncitonal control center affecting nuclear migration, spindle formation, membrane breakdown and synthesis, karyogamy, conjugation, budding, chromosomal movement, replication, and disjunction.


Nitrogen fixation associated with grasses in Oregon. Nitrogen fixation associated with both natural grasslands and grain crops of Oregon was studied using the acetylene-reduction assay. A number of the grasses collected has some acetylene-reducing activity. Agrostis tenuis Sibth. had substantially greater activity than any of the other species, with a mean rate estimated at 37 g N2 fixed per hectare per day. Assuming 100 days of activity, about 3 kg of N2 would be fixed per hectare per year. This quantity of nitrogen may be important in the maintenance of this species under natural conditions. Nitrogen-fixing microorganisms were isolated from the root surfaces of some of the grasses. Cultures of Bacillus macerans, Bacillus polymyxa, and Enterobacter cloacoa were isolated from wheat roots as were two cultures which have not been assigned a specific taxonomic classification. Strains of N2-fixing Bacillus species and Gram-negative aerobic bacteria were isolated from Festuca and Agrostis.


Effect of hydroxamic acids on growth and urease activity in Corynebacterium renale. Studies were conducted on the effect of four different hydroxamic acids (HA), hydroxyurea, acetohydroxamic acid, p-flurobenzoylhydroxamic acid and sorbylhydroxamic acid, on the growth and urease activity of Corynebacterium renale. The addition of each of these HA, at concentrations ranging form 10(-3) to 10(-5) M, to medium containing urea as the sole nitrogen source resulted in a lengthened lag period of growth the extent of which depended upon the concentration of each HA tested as well as the structure of the compound; that is, the size and (or) complexity of the side chain attached to the common terminal group of the molecule. However, the maximal growth levels achieved following conclusion of the exponential phase were not affected by the HA. Investigations on the effect of these HA on the urease activity of intact cells as well as cell-free extracts revealed that in each case the enzymatic activity was inhibited by each of the HA tested. The extent of inhibition with the intact cells was aobut one-half of that observed with cell-free extracts. Direct incubation of cell-free extracts as well as intact cells with each of the HA tested was required for maximal inhibition.


Temperature-induced alterations in phospholipids of Fusarium oxysporum f. sp. lycopersici. Ten phospholipids were identified in hyphal membrane preparations of Fusarium oxysporum f. sp. lycopersici when the cells were grown to the late log phase at 15, 25, and 37 degrees C, respectively. The major phospholipids present were phosphatidylcholine (PC) and phosphatidylethanolamine (PE), which together made up about 70% of the total membrane phospholipids. The degree of unsaturation in the acyl group of the phospholipids was inversely related to growth temperature. The polar head group composition was also affected by growth temperature. Cells grown at 15 and 25 degrees C contained the same relative proportions of PC and PE, but when the growth temperature was raised to 37 degrees C, the ratio of PC to PE was doubled. A methylating system capable of converting PE to PC was demonstrated in vitro.


Immediate postnatal decontamination as a means of obtaining axenic animals and human infants. A technique not involving surgery is described for obtaining axenic (germ-free) newborn animals and human infants by decontamination immediately after birth. Three steps are involved: cleansing ther perineal region of the mother with an iodinated bactericidal solution, washing the newborn with the same solution, and after the newborn has been placed in a sterile isolater, administering a single oral dose of an antibiotic mixture previously determined to be active against the fecal and vaginal flora of the mother. All of the newborn obtained by means of this technique, including 13 piglets, 2 lambs, and 4 human infants, were found to be axenic throughout their stay in the isolators. Four piglets obtained by the same technique, but without adminstration of antibiotic mixture, were found not to be anenic. This technique, as compared with methods of surgical delivery of axenic young, embodies a number of advantages. It is harmless to the mother and to the newborn, it is relatively inexpensive, and it obviates the risk of prematurity involved in elective surgical delivery before term.


Halobacterium saccharovorum sp. nov., a carbohydrate-metabolizing, extremely halophilic bacterium. The previously described extremely halophilic bacterium, strain M6, metabolizes a variety of carbohydrates with the production of acid. In addition, the organism produces nitrite (but no gas) from nitrate, is motile, and grows most rapidly at about 50 degrees C. These characteristics distinguish it from all previously described halophilic bacteria in the genus Halobacterium. It is suggested that it be designated as a new species, Halobacterium saccharovorum.


Comparison of biodegradability of crude and fuel oils. Crude and fuel oils were compared for ability to support growth of a mixed population of estuarine bacteria. A total of four oils, two crude and two fuel oils, were examined. It was found that each of the oils supported a unique population of bacteria and yeasts, with respect to generic composition. Low-sulfur, high-saturate, South Louisiana crude oil was found to be highly susceptible to degradation. In contrast, the dense, high-sulfur, high-aromatic, Bunker C fuel oil was strongly refractory to microbial degradation.


Use of a membrane oxygenator for open-heart surgery in infants. Because use of the bubble oxygenator during open-heart surgery is associated with complications such as hemolysis, pulmonary insufficiency and oliguria, a membrane oxygenator was used in conjunction with hypothermia in 37 infants. The main features of the oxygenator are gravitational blood flow, oxygenation into an airless, collapsible blood reservoir, low-flow roller pump flow back to the patient, accurate determination of flows and careful use of a heat exchanger. Gas flow (98% oxygen, 2% carbon dioxide) for the unit of 2 m2 is maintained at 3 to 4 1/min. Specific precautions are taken to ensure absence of bubbles. Three prime solutions are used, the final one having an osmolality of 381 mOsmol and containing 129.9 meq of sodium, 3.8 of potassium and 94.0 of chloride and 2001 mg/dl of glucose. Six patients died, but none of the deaths could be directly  related to the use of the oxygenator. Respiratory complications were minimal, as were other complications. The technique is reliable in oxygenating blood in an tracorporeal circulation, but further familiarity with the membrane oxygenator for use in open-heart surgery in infants is desirable before firm conclusions can be drawn as to its value.


Pericardiectomy for uremic tamponade.

Pericardiectomy for uremic tamponade. Pericardial tamponade developed in 29 patients with uremia. The clinical presentation varied, some patients having no symptoms whereas others sustained circulatory collapse. Pericardial friction rub, elevated central venous pressure and a paradoxical pulse were the most common physical findings. Serial chest radiography and echocardiography were most useful procedures in confirming this diagnosis. Two patients were treated conservatively and died despite repeated pericardiocentesis. The remaining 27 patients underwent partial pericardiectomy. One patient died of cardiorespiratory failure and a second  from brain damage related to cardiac arrest before pericardiectomy. The other 25 patients reported immediate relief of symptoms and no recurrence of pericarditis. Pericardiectomy is the treatment of choice in uremic pericardial tamponade.


A new model for assessment of myocardial function: I. Description and performance norms. Use of a new isometric rabbit-heart model, a modification of Langer's original preparation, has permitted independent assessment of myocardial perfusability in addition to contractility and relaxation. In this model an isolated, paced, interventricular septum contracts against a tension transducer and is perfused from another awake rabbit. Heparinized, diluted arterial blood is warmed and pumped at 1 ml/g-min. Perfusion pressure is measured by transducer. Each preparation serves as its own control. This model was used in determining performance norms for 68 preparations. Contractility was measured by maximum active tension, maximum rate of increase of tension and time to peak tension; relaxation by resting tension, maximum rate of relaxation and relaxation time; and perfusability by mean perfusion pressure and mean conductance. The status of the parabiotic rabbit was closely monitored. These studies have shown that the model is relatively simple, clearly defined and adaptable to a variety of experimental protocols.


Intra-aortic balloon pump assist: adjunct to surgery for left ventricular dysfunction. Intra-aortic balloon pump assist (IABPA) was used intraoperatively and postoperatively in 34 patients with severe left ventricular dysfunction: the mean ejection fraction was 0.29 and all patients had angiographic grade IV left ventricular contractility. There were three groups of patients: 11 patients with acute coronary artery insufficiency--10 of whom survived vein bypass surgery (group 1); 16 patients with crescendo-type unstable angina--of whom 15 survived surgery (group 2); 7 patients with single (6) or multivalvular (1) replacement (combined with vein bypass in 3)--of whom 5 survived (group 3). Overall survival was 88%. The mean duration of 1:1 IABPA was 40 hours. Inotropic support was not required, hemolysis was insignificant and hemostasis remained secure. Two patients required tracheostomy and one required dialysis. One patient had a peripheral embolus in the leg used for IABPA. IABPA improves subendocardial perfusion during induction of anesthesia, during cardiopulmonary bypass and into the postoperative period; left ventricular work is decreased with a concomitant increase in coronary artery and vein graft blood flow. Use of IABPA may also improve survival and lessen morbidity in patients with left ventricular dysfunction due to the beneficial effects on myocardial performance and is thus a valuable adjunct to cardiac surgery in high-risk patients.


Surgical repair of acute ventricular spetal defect complicating myocardical infarction. Ventricular septal defect complicating myocardial infarction was repaired surgically in seven patients between 1965 and 1974. In four, the septal defect had developed in the lower portion of the septum and in three, high in the septum, above the origin of the papillary muscle. Concomitant operations included mitral valve replacement and infarctectomy, in one patient, and triple aortocoronary bypass in another. The commoner low defect was repaired either by amputating the lower portion of the heart or patch-repairing through a left ventriculotomy incision. The higher defects, more difficult to repair, were repaired through a high posterior left ventriculotomy. Complete pre- and postoperative hemodynamic studies were carried out and follow-up information was available for all patients. Recognition of the high defect is essential. Pathologically, the coronary artery lesion is more complicated and extensive and a different surgical approach is necessary. A classification of high and low ventricular septal defects developing after myocardial infarction is recommeneded. The natural history of the disease and the reasonable surgical results support an active surgical approach in both types of postinfarction septal perforation.


Synovial chondrometaplasia: review of world literature and a study of 18 Canadian cases. A retrospective study of synovial chondro-metaplasia in Canada revealed 18 well-documented cases of this condition. Review of these cases together with 137 cases obtained from the literature permitted clarification of the clinical, radiologic and histologic features of the clinical, radiologic and histologic features of the disease. Positive histologic proof of synovial chondrometaplasia is necessary for a true diagnosis. Synovectomy with excision of loose bodies is the treatment of choice in symptomatic cases.


Familial polyposis coli and periampullary carcinoma. An 80-year-old woman with periampullary carcinoma was found, at autopsy, to have polyposis coli. A brief review of the literature indicates that, although the association of Gardner's syndrome with duodenal and pancreatic carcinoma is well established, the patient described in this report is only the second with polyposis coli in whom a periampullary carcinoma developed.


Congenital hip dislocations diagnosed after walking age: results of treatment. The results of treatment of 64 congenital hip dislocations, diagnosed after the children were of walking age, were assessed anatomically, using two criteria--general femoral head shape and the C.E. angle of Wiberg. Results were also related to age at diagnosis and treatment methods. Radiologically 62% of the hips had normal or good results, and of these, 82% were obtained when the diagnosis was made and treatment started before the age of 36 months. In this series no correlation existed between anatomical result and treatment method.


Cigarette smoking and the young: a national survey. Cigarette smoking behaviour among the young was examined in the light of the responses of over 78 000 students to a 1972 questionnaire survey of Canadian schools. As few as 2% (8-year-old girls) and as many as 60% (16 year--old boys) were smoking one or more cigarettes per week. The prevalence of smoking was higher than that reported in earlier studies. Students, particularly girls, were beginning to smoke at progressively earlier ages. Some differences in smoking behaviour were found between regions, language groups and groups of children whose parents did or did not smoke. Recognition of immediate rather than long-term effects of smoking on health was reported as an important consideration in not smoking.


Drug surveillance data in a Canadian hospital. Comparison of results of a Canadian hospital-based drug surveillance program with data from centres in the United States and Israel showed no important difference in the rate of drug exposures or adverse reactions. Drugs for symptomatic relief were frequently used in the Canadian centre. Women received more drugs and had more adverse reactions than men. Life-threatening and potentially fatal reactions were caused by commonly used drugs; autopsy findings may detect previously unsuspected relations between drug events and mechanisms of death. Voluntary reporting and intensive monitoring are both important in the field of adverse drug reactions.


Experience with SI units in biochemistry. Use of Système International d'Unités (SI) for laboratory measurements was instituted Jan. 1, 1975 at two community hospitals. Beforehand, talks were given, pamphlets, conversion tables, new calibration curves and new master record cards were printed, computer cards were reprogrammed and conversion kits were prepared; the total cost was less than $200. After 6 months 16% of the medical staff had stopped converting SI units into conventional units, 78% were still occasionally converting units and 6% were routinely converting units. Changeover had been difficult for 25%, only a nuisance for 49% and easy for 26%. The patients' lives were not endangered by conversion.


Atypical mycobacteria in a tuberculosis hospital. Cultures from 80 out of 1667 patients (4.8%) admitted consecutively to a tuberculosis hospital grew atypical mycobacteria. With four strict criteria it was concluded that the mycobacteria isolated were the cause of the disease in 47 of these patients. The majority of these organisms were resistant to most, and in seven cases to all, of the antituberculous drugs. Ten patients responded poorly to treatment and 14 patients (30%) died, 8 of these from uncontrollable pulmonary infection with the atypical organisms. It is suggested that a recent, simplified classification of mycobacteria proposed by Runyon be adopted.


Evaluation of stroke disability.

Evaluation of stroke disability. The disabilities resulting from a stroke are not well understood from the epidemiologic or functional point of view. The stroke may impair mental status, perception, sensation, communication and motor ability; the total resulting disability is related to the extent of impairment in each of these areas. A complete evaluation in all these areas has to be done to determine the degree of disability before any rehabilitation program is planned. A comprehensive approach to evaluating stroke disability is presented that includes correlating the degree of impairment in each of the above-mentioned areas with the overall functional ability of the patient.


Control of lithium tremor with propranolol. Lithium tremor is an irregular, nonrhythmic tremor of the distal extremities, variable in both intensity and frequency. It is clinically differentiated from essential tremor and tremors due to anxiety and neuroleptics. The pathophysiologic mechanisms are hypothesized to be of perpheral origin. Five patients were successfully treated with propranolol. In general, the dosage of propranolol must be individually adjusted and is usually from 30 to 40 mg daily in divided doses. This blocker of beta-adrenergic receptors remains effective with long-term administration and increases in dosage are not required.


The Canadian Home Fitness Test as a predictor for aerobic capacity. The purpose of this study was to determine if maximum oxygen consumption (Vo(2) max) could be predicted from independent variables measured during the administration of the Canadian Home Fitness Test. Fifty-nine subjects between the ages of 15 and 74 years underwent the fitness test and a progressive exercise treadmill test for the direct determination of volitional Vo(2) max. The results indicated that Vo(2) max could be adequately predicted by the following regression equation: Vo(2) max (ml/kg.min) = 42.5 + 16.6(Vo(2)) - 0.12(W) - 0.12(H) - 0.24(A), where Vo(2) is the average oxygen cost of the last completed exercise stage (in l/min), W is the body weight (in kg), H is the postexercise heart rate (in beats/min) and A is the age (in years).


Management of "psychosomatic" problems in clinical practice. Skilled interviewing and investigation are essential in the diagnosis and treatment of "psychosomatic" illness, the term "psychosomatic" being used in its more colloquial sense to refer to illness characterized by somatic symptoms and related psychopathologic disorders but without organic disease.Treatment of these patients is difficult. They respond best to a psychologically oriented physician who is able and willing to take final responsibility for both physical and psychological care. The hazards of ignoring the psychosocial dimension in patient management are emphasized. Although the family physician generally is the most appropriate therapist, there may be a role for a "liaison physician", a specially trained consultant who is thoroughly familiar with both physical and psychological processes and their interaction.


Locked wards in Canadian mental hospitals: the return to custodialism. In 1975 a survey of the open- and locked-ward practice of 38 of the 44 Canadian public mental hospitals showed that more than one third of the wards are locked 24 hours a day. This survey is the only one known to have been conducted in the last 16 years and the first to have obtained data from all 10 provinces. Hospitals with fewer than 300 beds have a significantly smaller proportion of locked wards than those with more than 600 beds.The custodial, antitherapeutic environment was the most frequently cited disadvantage of the locked ward, and facilitation of the therapeutic milieu was the most commonly cited advantage of the open ward. The most commonly cited problem of the open ward was the inability to protect the community from the dangerous, violent patient. The most frequently cited factor required to open the wards was a higher nursing staff:patient ratio, but it is suggested that this is an erroneous opinion. What is required is the organization and involvement of the patients in meaningful activities throughout the day, hospitals with fewer beds, and better relations with the community to foster public tolerance.National organizations concerned with mental hospital practice have no data on the open- and locked-ward practice in this country. There are pressures, channelled through the political and judicial systems, to lock the wards, and the Law Reform Commission of Canada has recently recommended transferring mentally ill prisoners to mental hospitals.


Exercise London: a disaster exercise involving numerous casualties. A large-scale disaster exercise was conducted to assess how one large community would handle such a situation - particularly, how it would deal with 150 casualties. The planning, undertaken by a subcommittee composed of representatives of all resource groups in the city, took more than a year. The deficiencies of the disaster plan detected during the exercise, which included a lack of trained personnel and various problems of communication, are now being corrected.


Chemotherapy of malignant diffuse mesothelioma. The clinicopathologic features of six pleural and one peritoneal mesothelioma were analyzed. Six patients were treated with either adriamycin or a multiple drug regimen consisting of cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil (COMF). Of those who received COMF, one obtained a complete response lasting 19 months and two had partial responses lasting 3 and 7 months. Adriamycin was administered to five patients. Two obtained a complete response lasting 19 and 7 months. Three had partial responses lasting 2, 6, and 9 months. Grading of response was often difficult requiring serial review of chest x-rays. Survival from diagnosis ranged from 2 to 39 months, with a median of 9 months. We conclude that adriamycin or COMF treatment may offer worthwhile remissions in mesothelioma and that malignant diffuse mesothelioma is more responsive to chemotherapy than previously realized.


Combination chemotherapy with cyclophosphamide, vincristine, and prednisone in advanced non-Hodgkin's lymphomas. From July 1971 to July 1974, 58 patients with advanced non-Hodgkin's lymphomas were treated with cyclophosphamide, vincristine, prednisone (CVP) at Stanford Medical Center. Utilizing the histopathologic criteria of Rappaport el al., response to CVP was found to be significantly better in the nodular (96.6%) and the diffuse lymphocytic (100%) histologies as compared to the diffuse nonlymphocytic lymphomas (47.6%). A pathologically documented complete remission was obtained in 33.9% of patients and all but two remain disease free for periods of 2-28 months. Concurrent bleomycin was administered to 17 patients during CVP therapy and no improvement in response or median survival was noted. Prior radiation therapy delivered to 21 patients did not adversely affect their response to CVP or their survival. Splenectomy in 17 patients prior to CVP did not improve hematologic tolerance to chemotherapy except in those patients with prior radiation therapy, and there was no improvement in response to CVP or survival. CVP is effective in achieving complete remissions and extended disease-free survivals in advanced non-Hodgkin's lymphomas; both a nodular architecture and a diffuse lymphocytic histology are positive determinants for response to chemotherapy and improved median survival.


Diminished bone marrow responsiveness to erythropoietin in myelophthisic anemia. The purpose of this study was to examine a mechanism which might explain the diminished erythropoiesis that occurs when tumor cells invade the bone marrow (myelophthisic anemia). To this end we compared 21 patients with neoplastic bone marrow invasion with seven normal subjects. When erythropoietin was added to bone marrow cell cultures from the normal subjects, the baseline rate of heme synthesis for a specific number of marrow erythroid cells increased 65%. In contrast, in patients with greater than 60% of the marrow replaced by tumor, the marrow cell culture response to erythropoietin was 14% above baseline. A significant inverse correlation was noted between the degree of marrow infiltration with tumor and the stimulation of heme synthesis with erythropoietin. It is proposed that marrow invasion with tumor may result in decreased marrow response to erythropoietin, and hence, diminished red cell production.


Ultrastructure of the basal cell adenoma of parotid gland. Electron microscopic examination of two classical examples of so-called basal cell adenoma of parotid gland disclosed four distinct cellular types: the squamous epithelial cells with tonofilaments and prominent desmosomes predominantly located at the central portion of neoplastic mass; the basally located secretory cells with numerous secretory granules; the occasional intermediate cells with scanty cytoplasmic microfilaments; and the peripherally situated attenuated myoepithelial cells. The neoplastic clusters are surrounded by highly replicated basal laminae with microfibrils in their interstices. This information about its component cells suggests that basal cell adenoma arises from the secretory duct, in particular the intercalated duct, of the parotid gland. The term basal cell adenoma appears appropriate for its designation. It is interesting that the secretory cells and the multilayered basal laminae illustrated in the present study are reportedly seen in adenoid cystic carcinoma of the salivary gland; this finding would suggest a common cellular origin for these two neoplasms.


Adult neuroblastoma. Electron microscopic observations in nine cases. Nine patients, whose ages ranged from 18 to 72, had small round cell neoplasms which were found on electron microscopy to have the ultrastructural features of neuroblastoma. The primary tumor was retroperitoneal in one patient. In another, liver and bone metastases were present and the primary site was not determined. The tumor presented in a peripheral location in the remaining seven patients (leg in two, buttock in one, head and neck in four), and all seven tumors metastasized to regional lymph nodes. One tumor that arose in the nasal cavity displayed olfactory differentiation. Two tumors recurred locally following excision. Although two patients have died from disseminated disease, the prognosis nevertheless appears more favorable than in childhood neuroblastoma. Adequate local excision of a peripheral lesion with close follow-up are indicated.


Chondrosarcoma with dedifferentiated foci. A comparative and ultrastructural study. The light and electron microscopic features of a well-differentiated chondrosarcoma with dedifferentiated foci (CDF) are compared with those of a poorly differentiated chondrosarcoma with spindle cell elements. The differentiation of this lesion from mesenchymal chondrosarcoma and from primitive multipotential primary sarcoma of bone is discussed. Ultrastructurally, the cells of the cartilaginous region of the CDF resembled those of the poorly differentiated chondrosarcoma and of the cartilaginous zones of an extraskeletal mesenchymal chondrosarcoma reported by Fu and Kay, and were characterised by an abundance of dilated endoplasmic reticulum and a scalloped and microvillous cell membrane. The stroma was devoid of mature crossbanded collagen fibers. The dedifferentiated portion was composed of mesenchymal-type cells surrounded by a relatively sparse matrix containing scanty mature collagen fibers; these cells resembled those in the cellular regions of the two previously documented mesenchymal chondrosarcomas but differed from the cartilaginous type cells in the cellular regions of the poorly differentiated chondrosarcoma.


A clinicopathologic and prognostic study of epithelial tumors of the renal pelvis. The aim of the present investigation was to assess the prognosis of epithelial pelvic tumors and evaluate from multivariate analysis the influence of different morphologic and clinical factors on the prognosis. The basic data are derived from the Swedish national series of patients with epithelial renal pelvic tumors diagnosed by histologic examination during 1962-63. Ninety-four of the 102 patients studied had a urothelial pelvic tumor and eight had an epidermoid carcinoma. The corrected 5-year survival rate was 51% in the curatively operated series, 60% among the males and 33% among the females. Infiltration depth was found to be of significant importance for the 5-year survival and thus a strong predictor for prognosis. Furthermore, each tumor grade and tumor structure exerts some influence on the prognosis independent of the infiltration depth. Nine patients had verified, and 16 patients had suspected phenacetin abuse and/or renal papillary necrosis. The survival rate was low and the relative frequency of females was high in this group of patients. These data may indicate a poorer prognosis in patients with phenacetin abuse, and may explain the sex difference in 5-year survival. Thirty-eight per cent of the patients with urothelial tumors of the renal pelvis had a synchronous or asynchronous tumor elsewhere in the urinary tract. The high frequency of local recurrence as well as the high frequency of infiltrating tumors and multiple tumors indicate the necessity for a more extensive operation such as perifascial nephrectomy with total ureterectomy including a cuff of the bladder.


Relationship between serum selenium levels and patients with carcinoma. Serum selenium levels were determined by neutron activation analysis on 110 patients with carcinoma. An attempt was made to correlate the wide range in the serum concentrations of the trace element with the parameters employed in this study. An association was noted between the serum selenium levels and patient survival time, incidence of multiple primary malignancies, rate of recurrence of the primary lesion and the extent of local and disseminated involvement.


Relationships of morphology to clinical presentation in ten cases of early squamous cell carcinoma of the lung. The morphologic changes in 10 patients who were found to have squamous cell carcinoma of the lung before they became evident on chest x ray are discussed. It is suggested that these cases have a long preclinical course as invasive carcinomas that ranges from a microscopic focus of microinvasion (possibly originating from in situ carcinoma in submucosal gland epithelium) to a large concentric carcinoma which may have metastasized to regional lymph nodes. Although the duration of the in situ phase of squamous cell carcinoma of the bronchus in not known, it was evident that the expanse of in situ carcinoma frequently far exceeded that of the invasive carcinoma, and usually extended proximal to the invasive lesion. It is important that the extent of the in situ lesion is determined preoperatively. Finally, multifocal in situ (or invasive) carcinoma was found in at least two of the cases, either synchronously or metachronously.


CEA family syndrome. Abnormal carcinoembryonic antigen (CEA) levels in asymptomatic retinoblastoma family members. Plasma carcinoembryonic antigen (CEA) levels were studied in all available members of 17 families in which a presumed sporadic retinoblastoma had occurred. In 9 of the 17 families, close relatives of the patient had elevated CEA levels in the absence of demonstrable disease; this we have termed the "CEA family syndrome." In two families (Nos. 8 and 17) one or both parents and all of the siblings had elevated CEA levels. To our knowledge, this is the first report of abnormal CEA levels in unaffected family members of patients with nonadenocarcinoma-type malignancies. As follow-up studies of such families become available, detection of the "CEA family syndrome" may prove to be a useful means of locating individuals with inherited premalignant or malignant conditions and may provide a stimulus for additional clinical examination of asymptomatic individuals considered at risk for developing malignancies.


Histiocytic medullary reticulosis with parallel increases in serum acid phosphatase and disease activity. Two months after presenting with autoimmune hemolytic anemia, a 57-year-old man developed increased serum acid phosphatase activity. Subsequently, abnormal histiocytes were found in the bone marrow and blood, and 8 months after the onset of his illness lymph node biopsy led to the diagnosis of histiocytic medullary reticulosis. At that time the level of serum acid phosphatase activity was more than 60 times the upper limit of normal and then paralleled the activity of his disease during temporary responses to chemotherapy, rising to over 90 times normal at the time of his death 1 year after presentation. No prostatic malignancy was demonstrated by biopsies or at autopsy, and electrophoretic studies of the serum enzyme suggested that it was of extraprostatic origin. It is postulated that the acid phosphate present in the serum at levels heretofore described only in metastatic carcinoma of the prostate may have arisen from the abnormal histiocytes.


Bone marrow scanning with 52iron (52Fe). Regeneration and extension of marrow after ablative doses of radiotherapy. Extensively irradiated patients were studied from 0 to 73 months after irradiation by 52Fe bone marrow scanning. Marrow regeneration was observed in most patients after intervals of 12 months or longer. The degree of recovery was not dose-related and the marrow ablative dose was not defined with doses of 4000-5000 rads. Degree of recovery depended more upon the antomic region and/or sequence of fields treated; the last field treated invariably showed poorer regeneration when recovery was uneven. Active erythropoisis expanded into distal inactive erthropoietic sites from 3-12 months after irradiation and then decreased thereafter. Blood count cytopenias were almost always restricted to the first year after irradiation.


Patterns of extension as a guide to radiation therapy in the management of ovarian neoplasms in children. Sixteen cases of childhood malignant ovarian neoplasms of varied histology and stages were reviewed with special reference to the patterns of disease extension within the pelvis and abdomen. All patients had initial surgery elsewhere before referral to Memorial Hospital. Two patients had distant metastases (bone and lung). None of the other 14 girls had disease restricted to the pelvis. The first extension in 11 was to sites within the abdominal cavity as well as to the pelvis and in three to the abdomen without pelvic involvement. Total abdominal irradiation would have been required to encompass all known disease-bearing areas in these 14 girls.


Cancer of the nasal cavity.

Cancer of the nasal cavity. The experience with 40 consecutive cases of cancer of the nasal cavity seen over a period of 15 years is presented. Males outnumbered females in a ratio or 5 to 3. Age ranged from 35 to 88 years, and the median age was 67 years. Epidermoid carcinoma accounted for 78% of the cases. Smoking from early age was a noticeable habit among these patients. The median length of smoking history was 51 years. Most lesions were diagnosed in an advanced stage of the disease, 58% of the cases being T3 lesions. Regional lymph nodes metastases were infrequent; only 12% of the patients presented nodes on admission; another 5% developed metastatic nodes during the follow-up period. An overall 5-year survival of 56% was obtained. The survival of cases with T1N0 lesions was 91%. Radiation therapy was the treatment of choice employed in 85% of the cases. A 5-year survival of 50% was obtained in these patients. Irradiation offers an additional means of salvaging recurrences after surgery. The special characteristics of tumors of the nasal cavity merit the evaluation of such lesions separately from tumors of the paranasal sinuses.


Nasopharyngeal cancer in Bermuda.

Nasopharyngeal cancer in Bermuda. Six cases of nasopharyngeal carcinoma (NPC) were diagnosed in residents of Bermuda in the 7-year period 1966-1972. While epidemiologic study revealed no history of common environmental exposures, two of the six cases occurred in adult sibs from a family in which a third adult sib developed NPC in 1963. These three cases were from a large, possibly in-bred Portuguese family with origins in the Azores Islands. The remaining four cases were all in black children ages 10-15; two of these were first cousins. These observations suggest the possibility that genetic influence may contribute to the etiology of NPC.


Malignant mesothelioma of the tunica vaginalis propria testis in a patient with asbestos exposure. A case report. A case of malignant mesothelioma arising from the tunica vaginalis propria testis is described. The nature of this tumor is evidenced by in situ malignant change of the mesothelial lining as well as by extensive lymphatic and local tissue invasion. This is the first report of a malignant mesothelioma of the tunica vaginalis associated with asbestos exposure and may be epidemiologically as well as clinically important.


Spinal cord compression in malignant lymphoma. Treatment and results. The natural history, treatment, and results of 73 spinal cord compressions caused by malignant lymphomas are analyzed. It is found that the spinal cord compression caused by malignant lymphomas is generally a late manifestation of the illness, although primary or early involvements are occasionally seen. In our study, reticulum cell sarcoma is the most frequently variety followed by Hodgkin's disease and lymphosarcoma. The dorsal spinal cord is the most frequently involved segment and pain, weakness, and paresthesia are cardinal symptoms. Radiation treatment delivered in the early phase of the compression is commonly successful in reversing the neurologic symptoms and a dose above 2500 rads appears to be optimal for local control of disease. The low incidence of cerivcal cord compression in Hodgkin's disease patients may be related to frequent manifestation and irradiation of the neck nodes in these patients. Early detection of disease in the deep seated areas along the spinal cord and irradiation of these areas may prevent progression of tumor to the epidural space.


Metastatic tumors to the bones of the foot. Information on lesions that are metastatic to the bones of the feet is limited. Review of the literature revealed only 17 cases, nine of which were confirmed histologically. Our series involved the clinical records, roentgenograms, and pathologic specimens in eight cases of biopsy-proven metastatic involvement of the bones of the foot. In three additional cases, there was clinical and roentgenographic evidence of metastatic osseous foot lesion but biopsy was not done to provide histiolgic confirmation. Genitourinary malignancies tended to be associated with metastasis to the bones of the feet, the calcaneus being the commonest site of involvement. Although metastatic lesions of the foot are rare, foot pain may be suggestive of an occult carcinoma. Foot pain was the initial presenting complaint in five of our eight cases. The pathogenesis of these distal metastatic lesions remains obscure. Specific problems in management are associated with osseous metastases of the foot.


Adenocarcinoma of the pancreas in childhood. Report of a case and a review of the English language literature. A case of adenocarcinoma of the head of the pancreas in a 13-year-old girl is reported. Some areas simulated an islet cell tumor by light microscopy, but contained numerous eosinophilic granules which were PAS-positive and diastase resistant. Ultrastructurally, the granules were large (960 mum-3000 mum in diameter) and electron-dense, resembling zymogen granules. These granules often showed focal to complete degeneration, occassionally being continuous with a myelin figure. The granules of true islet cell tumors are ultrastructurally distinctive and it is urged, therefore, that all pancreatic neoplasms in children be studied by histochemistry and electron microscopy. Carcinoma of the pancreas in childhood is a rare tumor, often with a rapid clinical course resulting in death. Morphologic separation of cases reported in the English language literature can be made on the basis of acinar differentiation. This feature has been suggested as a peculiarity of childhood pancreatic carcinoma. However, there is a suggestion that this phenomenon occurs in a small percentage of adult tumours as well. More extensive morphologic studies in adult pancreatic cancer may be warranted.


Carcinoma of the pancreas: review of MGH experience from 1963 to 1973. Analysis of surgical failure and implications for radiation therapy. A retrospective study was done of all patients who were seen for definitive treatment of adenocarcinoma of the pancreas at the Massachusetts General Hospital from 1963 to 1973. There were a total of 145 patients. Thirty-one patients were treated with radical surgery, with a 16% operative mortality, a 5-year crude survival rate of 15%, and a local recurrence rate of 50%. Sixty-two patients were treated with biopsy alone, with no 5-year survivors. In addition, there were 35 patients who did not have a radical surgical procedure performed only because of the extent of the local disease. It is proposed that postoperative irradiation may reduce the incidence of local failure after radical surgery, and that preoperative radiation therapy or radiation therapy alone would be an appropriate treatment of those patients in whom the local extent of disease is initially too far advanced to perform radical surgery.


Fulminating parapontine epidermoid carcinoma in a four-year-old boy. An unique case of primary intracranial epidermoid carcinoma in a 4-year-old boy is described. Its parapontine localization and malignant features combined to produce a fulminating clinical course simulating an intra-axial mass lesion. The probable origin of the carcinoma from a benign epidermoid cyst is discussed. A review of the world's literature establishes not only the rarity of cyst-derived intracranial epidermoid carcinoma, but also its unprecedented occurrence in a child.


Management of malignant testicular tumors in children. The result of therapy of 67 cases of children with malignant testicular tumors is presented. The majority of these cases were embryonal carcinoma in which metastases had occurred in the retroperitoneal lymph nodes, lungs, and bones. Long-term survival was obtained in 89% of the cases treated by simple orchiectomy followed by retroperitoneal irradiation. Two cases with metastases benefitted from chemotherapy. The prognosis of embryonal carcinoma of the testis is correlated with the age of the patient and the histologic pattern of the carcinoma; early detection and appropriate treatment are most important for its cure.


Pseudosarcoma and carcinosarcoma of the esophagus. Two cases of polypoid carcinoma with pseudosarcoma and one of so-called carcinosarcoma of the esophagus are presented. The clinical and morphologic characteristics of these tumors are described and the literature is reviewed. It is postulated that pseudosarcomas and so-called carcinosarcomas belong essentially to the same pathologic entity because of their similar morphologic and biologic aspects. The histogenesis of the sarcoma-like elements of these tumors support the theory of epithelial origin on the basis of the sarcoma-like transformation of squamous cell carcinoma and of the presence of epithelial elements in the "sarcomatous" areas.


Intramural squamous cell carcinoma of the esophagus. A case of squamous cell carcinoma arising from an esophageal intramural squamous epithelial cyst is reported. Review of the literature reveals no previous reports of malignant transformation of esophageal cysts, although there have been reports of approximately 64 cases of benign esophageal cysts, and 35 cases of carcinoma arising in esophageal diverticula. In the present case, there was a history of increasing dysphagia for 2 months. Esophagram demonstrated a 4.5-cm concentric narrowing of the proximal esophagus just below the superior esophageal ring. Esophagoscopies revealed an esophageal stricture with intact mucosa, and bronchoscopy showed the lesion to be producing tracheal deviation. Multiple esophageal biopsies revealed mild mucosal hyperplasia with deep submucosal inflammatory changes suggesting an underlying lesion. Despite lack of histologic proof of malignancy, the patient underwent radiation therapy and bleomycin chemotherapy on the basis of the highly suggestive radiographic findings, but died with bilateral bronchopneumonia 6 months after admission. Autopsy demonstrated a 1.5-cm long intramural esophageal squamous epithelial cyst, from which arose a locally invasive squamous cell carcinoma, without mucosal involvement or metastases. There was no demonstrable evidence of any associated esophageal diverticulum.


Primitive neuroectodermal tumor (neuroblastoma) arising in sciatic nerve of a child. A well-documented case of a primitive neuroectodermal tumor (neuroblastoma) arising in the sciatic nerve of a 6-year old boy is presented. After radical surgical excision of the tumor, followed by chemotherapy, the child remained clinically free of disease for 20 months. Tumor then recurred locally followed by widespread dissemination. He expired 2 years postoperatively. The literature on this type of rare and controversial tumor of peripheral nerves is reviewed. Only a very few reported cases are considered fully acceptable. Interest in this subject, and adequate documentation of future reported cases may lead to a better understanding of this class of malignant tumors.


Olfactory neuroblastoma. A clinical analysis of 17 cases. Seventeen patients with olfactory neuroblastoma seen at the Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary from 1941 to 1971 are presented. Data on age, sex, symptoms, physical, and roentgenographic findings, and therapeutic results are evaluated. A system of pretherapy staging is proposed in which for Group A, the tumor is limited to the nasal cavity; in group B, the tumor is localized to the nasal acvity and paranasal sinuses; and in group C, the tumor extends beyond the nasal cavity and paranasal sinuses. Olfactory neuroblastoma is a radioresponsive, and, to a limited extent, radiocurable tumor and varies in aggressiveness. Of 17 patients in this series, 13 or 76% were alive without disease following treatment by surgery, irradiation, and combination of these two methods. Uncontrolled primary lesions with or without metastases accounted for all therapeutic failures. A treatment policy for this disease is presented.


Malignant oncocytoma of the parotid gland. A light and electron microscopic study. A case malignant oncocytoma of the parotid gland occurring in a 91-year-old man is reported. The tumor recurred 10-months and 2 1/2 years after the primary excision. Both primary and recurrent tumors exhibited an infiltrative pattern. The histologic appearance of the original tumor and the recurrent lesion were similar, but there were areas of increased mitotic activity and pleomorphism in the latter. Ultrastructural examination of the recurrent tumor revealed that the cytoplasm was packed with mitochondria. The fine structure was, for the most part, similar to the benign variant reported previously. In the present tumor, however, intercellular spaces were more prominent and a basal lamina was not observed. The malignant oncocytoma occurs both in major and minor salivary glands. The tumor mostly affects the older age group, but the biologic behavior cannot be evaluated fully because of the paucity of cases reported and the lack of follow-up information.


Basal cell adenoma of the parotid gland. Case report with ultrastructural observations. A case of basal cell adenoma of the parotid gland is reported. The tumor was studied by electron microscopy, and fine structural features included numerous desmosomes, large secretory granules, and replication of the basal lamina. Myoepithelial cells were not observed. The observations support the view that the tumor is monomorphic and that it arises from serous cells of the acini or intercalated ducts. The tumor may be the benign homolog of the adenoid cystic carcinoma.


Involved field radiation therapy for early stage Hodgkin's disease in children: preliminary results. Twenty Stage I and II children with Hodgkin's disease were treated with involved field radiation therapy. Twelve patients were Stage I. The histologic types were:nodular sclerosis(seven cases), mixed cellularity (two) and lymphocyte predominant (three). There were eight Stage II patients (six nodular sclerosis and two of mixed cellularity). One Stage I and 4 Stage II patients had class B disease. Involved field irradiation was used in these children after staging laparotomy showed no disease below the diaphragm. Eight of the 20 patients relapsed, five in lymph nodes adjacent to the primary site, two in areas across the diaphragm; the other had both local and distant extension. The median time to relapse after completion of radiation therapy for Stage I and II were 15 and 5 months, respectively. Two of the eight children with recurrent disease are dead. The other six were retreated and are alive and free of disease for periods ranging from 24 to 68 months after original treatment (median, 36 months). Two of the six survivors in this group received irradiation to the site of the recurrent disease only, one was given total nodal irradiation, and three had chemotherapy. The other 12 patients are in continuous first remission. They have been followed for a median time of 26 months. The actuarial relapse-free survival and survival rates at 3 years are 57 and 89%, respectively.


Treatment of Bowen's disease with topical dinitrochlorobenzene and 5-fluorouracil. "Bowen's disease" is a clinical and histologic diagnosis describing the lesions (single or multiple) of cutaneous in situ squamous cell carcinoma. The case of a 54-year-old man with 60 such intra-epidermal carcinomas, and a history of arsenic ingestion, is presented. The patient was sensitized to dinitrochlorobenzene (DNCB), and his lesions were treated with a topical DNCB preparation. All lesions disappeared completely (demonstrated by biopsy of several sites) except for a large (12 X 7 cm) tumor on the flank which partially resolved. Total regression of this lesion was achieved by adding topical 5-fluorouracil (5-FU) therapy. This case demonstrates that the inflammatory reaction induced by DNCB (as evidenced by erythema and by a dense inflammatory cell infiltrate in biopsied areas of treated lesions) can lead to regression of extensive in situ epidermoid carcinoma, and that combined therapy with DNCB and 5-FU can be more effective than DNCB alone. Both agents in appropriate concentrations led to selective destruction of neoplastic tissue with no effect on adjacent normal skin. No systemic toxicity was observed.


Ultrasonic enhancement of nitrogen mustard cytotoxicity in mouse leukemia. Mouse leukemia L1210 cells were exposed to continuous wave 2 MHz, 10 W/cm(2) ultrasound for 10 minutes while suspended in nitrogen mustard solution in vitro. Mice subsequently inoculated with these cells had longer survival times than control animals that received cells exposed to the drug but not ultrasound. Without the drug, ultrasound did not alter survival time. Tracer studies revealed increased cellular accumulation of drug under the influence of ultrasound.


A study of survival in patients with stomach cancer treated by a combination of preoperative intra-arterial infusion therapy and surgery. Since 1968, there have been 62 patients with stomach cancer seen in the First Department of Surgery of Chiba University. Treatment consisted of preoperative intra-arterial chemotherapy and surgery. The chemotherapy entailed continuous infusion for 15 to 20 hours. The survival rates were analyzed with particular emphasis on the degree of serosal invasion of the stomach. The overall survivals at the end of 3 years were 54.2% for the treated patients, and 37.1% for the controls: and at the end of 5 years, 33.3% of the treated patients were living as compared to 29.7% of the control patients. In patients without serosal invasion, the survival rates were higher for those treated than for the controls for the first 2 years. At the end of 3 years, the 39 patients treated for serosal invasion had a survival rate of 46.8% vs. 29% in the controls: and at 5 years, 32.2% of the treated patients vs. 23.7% in the controls. The survival rates for the treated patients with cancerous infiltration of other organs were about the same as those for the corresponding control patients.


Survival of patients with lung cancer treated with vincristine and actinomycin D: An unsuccessful trial. Twenty-five patients with lung cancer were treated with actinomycin-D and vincristine (V-D) with only one objective response (IMD). The survival of these patients was compared retrospectively to a group of 49 consecutive patients treated with radiotherapy only during the same time period. Median survival times for the V-D group and radiotherapy controls were 6.5 and 7.5 months, respectively. It is concluded that V-D did not increase survival in patients with lung cancer and should be dropped from the chemotherapeutic armamentarium in lung cancer.


Ameloblastic sarcoma: pathogenesis and treatment with chemotherapy. A recurrent tumor in a young male demonstrates the progression of an ameloblastic fibroma to an ameloblastic sarcoma. Chemotherapy with Actinomycin D, Vincristine, and Cytoxan produced a complete response without evidence of recurrence 4 years after initiation of chemotherapy. The patient developed an aggressive malignant melanoma 1 year after all chemotherapy was discontinued.


A correlation of DNCB-induced delayed cutaneous hypersensitivity reactions and the course of disease in patients with recurrent breast cancer. Delayed cutaneous hypersensitivity reactions to DNCB were performed before therapy in 84 patients with recurrent breast cancer. Following sensitization, a 100 microgram challenge dose was graded as a strong, weak, or negative reaction. Thirty six patients were rechallenged greater than or equal to 6 months with 109 microgram of DNCB. Patients with a strong delayed cutaneous hypersensitivity reaction to DNCB were characteried by: a significantly higher probability of surviving at 52 and 78 weeks, a longer median length of survival (strong 78 weeks, weak 43 weeks, and negative 35 weeks), and a greater probability of responding to therapy (strong 52%, weak 29%, and negative 23%). It is suggested that patients with histologic grade III tumors with a dense lymphocyte infiltrate had more frequent strong delayed cutaneous hypersensitivity reactions to DNCB than those with few lymphocytes. The correlation of DNCB skin testing with a good prognosis in this group of patients with breast cancer suggests a protective role by the immunologic defense mechanisms and warrants its further evaluation and use in the development of new therapeutic modalities.


The role of immune factors in the survival of circulating tumor cells. The effects of immune serum on the survival of hematogenously disseminated malignant cells were investigated in six murine tumor systems with varying immunogenicity. Blood containing circulating tumor cells demonstrable by bioassay was obtained from donor mice with disseminated tumor. The cellular fraction was isolated by centrifugation and resuspended in immune serum obtained from donor animals bearing the same tumor (Group 1), in immune serum from mice bearing a differing tumor (Group 2), or in normal nonimmune serum (Group 3). The mixed cellular and serum fractions were intravenously inoculated into normal recipient mice which were subsequently scored for the development of pulmonary tumors. Similar incidence (35-50%) of pulmonary tumor deposits were seen in Groups 2 and 3. A significant enhancement in the incidence of lung tumors was present in the Group 1 animals for all tumor systems studies. It was suggested that the observed enhancement resulted from factors present in isologous immune serum but absent from both normal serum and immune serum obtained from hosts bearing heterologous tumors.


Split-course radiotherapy of Hodgkin's disease: local tumor control and normal tissue reactions. One hundred and thirty-six consecutive patients with Stage I-II Hodgkin's disease treated between 1965 and 1969 received a standard tumor dose of 40000 rads to clinically recognized disease using daily fractions of 200 rads given 4 or 5 times per week. Continuous and split-course irradiation, the latter with a 2-2 1/2 week interuption midway through the treatment, were employed in 82 and 54 patients, respectively. "Boost" doses were never given to residual masses at the completion of treatment with either schedule. No loss of therapeutic effectiveness resulted from split-course irradiation, only a single local recurrence having been observed to date. However, patient tolerance with the latter method was  substantially better than with continuous irradiation and resulted in fewer subsequent complications. Furthermore, the low incidence of local recurrence fails to support a practice of administering supplementary irradiation to adenopathy which has not completely resolved after a tumor dose of 40000 rads.


Gonadoblastoma: ultrastructural evidence for testicular origin. A gonadoblastoma arising in the dysgenetic gonad of a virilized 17-year-old Caucasian with a female phenotype and with a 45,X0/46, X-ring-Y genotype was studied by light microscopic histochemistry, electron microscopy, and ultrastructural histochemistry. The gonadoblastoma was composed of nests of cells containg large germ cells and small "granulosa-Sertoli-like cells," and stromal tissue containing "Leydig-like cells." The germ cells were identical to those found in normal fetal gonads and in germ cell tumors. Charcot-Böttcher crystalloids present in the "granulosa-Sertoli-like cells" strongly suggest that they are, in fact, Sertoli cells. Multilayered basal laminae located in the periphery of the tumor nests and in "hyaline bodies" were identical to those surrounding the seminiferous tubules of the adult testis. The "Leydig-like cells" present in the stroma contained occasional dense bodies and crystalloids which characterize the Leydig cells of the fetal testis. Delta 5-3 beta hydroxysteroid dehydrogenase activity was demonstrated in the periphery of lipid droplets and lysosome-like dense bodies of the Leydig cells, and in some Sertoli cells. The findings support the theory that gonadoblastoma arises in a dysgenetic testis rather than in a dysgenetic ovary.


Characterization of an established cell line (SH-3) derived from pleural effusion of patient with breast cancer. Spontaneous emergence of fast-growing cells in prolonged culture of pleural effusion cells obtained from a patient with breast cancer has led to the establishment of a cell line designated as SH-3. By morphological criteria, as revealed by light and electron microscopy, SH-3 cells are epithelial and resumble the poorly differentiated cells of a series of established human tumor cell lines. Their karyotype is hypotetraploid and different from that of HeLa cells. Isoenzyme analysis has shown the presence in the cells of a bone-type alkaline phosphatase and of the fast (A) band of G6PD. The line is free of mycoplasma.


Familial bilateral papillary cystadenoma of the epididymis: report of three cases in siblings. This paper describes an unusual, familial bilateral papillary cystadenoma of the epididymis found in three siblings. The histological characteristics of the tumor were: 1) papillary proliferation of clear cells, consisting of both tall columnar and round ovoid cells, in the efferent duct epithelium; and 2) cystic dilatation of the duct with colloidal material. The present cases were unique in two respects: 1) familial bilateral papillary cystadenomas probably associated with Lindau's disease have not been reported previously: and 2) electron microscopic observations suggested that the tumors originated from the efferent duct.


Malignant peritoneal mesothelioma in an inguinal hernia sac. An instance of malignant peritoneal mesothelioma that appeared to arise from an inguinal hernia sac is reported. This lesion appeared to be different from nodular mesothelial hyperplasia of hernia sacs.


The prediction of lymph node metastases from oral squamous carcinoma. In an attempt to predict which cases of oral and oropharyngeal squamous carcinoma are likely to metastasize to regional lymph nodes a series of 898 cases was grouped according to site, size, grade of histological differentiation, and presence or absence of histologically confirmed regional lymph node metastases. The results were analysed by a logistic multiple regression analysis. They showed that the sites may be divided into three clusters, Cluster 1 consists of tumors of lip, floor of mouth, cheek mucosa, hard palate, and gingiva. These are not significantly different as regards metastasis rate. Cluster 2 consists of tumors of the anterior two-thirds of tongue and has a higher tendency to metastasis than those in Cluster 1. Lesions of the posterior third of tongue and oropharynx form Cluster 3 which exhibits the greatest tendency to metastasis. Sizes of primary lesions are clustered in groups of lesions less than 3 cm, those 3 to less than 4 cm, and those 4 cm or larger, in ascending tendency to metastasis. Well-differentiated and moderately differentiated tumors are not significantly different in their tendency to metastasize and may be reduced to a single cluster, whereas poorly differentiated tumors have a markedly higher metastasis rate. Using these clusters it has been possible to predict the logistically transformed probability of metastasis to a high degree of accuracy (R=0.9398). From this we conclude that if for a given tumor we know to which site, size or differentiation cluster it belongs, we can then estimate its probability of metastasising.


Sarcoma of the prostate.

Sarcoma of the prostate. The experience at the University of Iowa Hospitals with 12 patients having sarcoma of the prostate is described. Although the total number of patients is small, two distinct groups can be identified. The infants, children, and young adults presenting with this malignancy had a very poor survival regardless of the therapy administered. However, the older men have generally done well, surviving several years following therapy for the relief of lower urinary tract obstruction. The longest surviving patient was treated by transurethral prostectomy followed by transperineal instillation of radioactive gold. A program of combination therapy utilizing surgery, external irradiation, and triple chemotherapy is suggested for use in children and young adults with prostatic sarcoma.


The natural history of nodular lymphoma. The clinical and histopathologic characteristics of 65 patients with nodular lymphoma seen at the Massachusetts General Hospital between 1962 and 1972 were reviewed. Five years after diagnosis 54% of these patients were alive, but only 18 percent remained free of disease. Younger patients fared much better (64 percent of those below the age of 50 survived 5 years) than the elderly (only 34 percent of those above the age of 50 survived this long), but histologic subtype by the Rappaport classification was not useful in predicting survival in this series. Individuals with localized disease (80% of those in Stages I and II survived 5 years) experienced better survival than those with dissemination (only 45% of those in Stages III and IV lived this long), but the high relapse rate in Stages I and II indicates that few who presented with localized disease are cured. At the time of death, the histologic pattern had become diffuse in 8 of 18 patients but remained nodular in the other 10. Ten patients treated by total nodal irradiation followed the same survival curve as the remainder treated less radically. It is concluded that nodular lymphoma is an indolent but usually fatal entity: though more than half of our patients survived 5 years, few were cured by the treatments employed.


Primary malignant melanoma of the urinary bladder. A melanin-synthesizing tumor of the urinary bladder was studied by light and electron microscopy. Careful clinical evaluation did not reveal evidence for a primary melanoma elsewhere in the patient. The clinical presentation, course of the disease, and demonstration of melanocytes in the bladder epithelium and malignant melanocytes comprising the tumor by light and electron microscopy indicated that the neoplasm was a primary malignant melanoma arising in the bladder.


Association of renal injury with combined cephalothin-gentamicin therapy among patients severely ill with malignant disease. There is a high incidence of primary renal tubule damage among patients with malignant disease who die following recent treatment with combinations of cephalothin and gentamicin. Administration of this combination of antibiotics appears to make the patient appreciably more susceptible to severe renal injury if an additional, often minor, insult to the renal tubules is superimposed. In the present study, significant blood loss or bacterial infection not promptly controlled by the antibiotic combination were two factors that provided this additional insult to many patients; the renal injury in these patients could not be attributed to bleeding or infection alone. The combination of cephalothin plus gentamicin carries the potential of causing renal tubule injury and places the patient severely ill with malignant disease at risk for renal failure from many clinical complications which are commonly associated with their primary illness.


Craniopharyngiomas: a clinical and pathological review. Two hundred and forty-five cases of craniopharyngiomas were obtained from the files of the AFIP and reviewed statistically with reference to their gross and microscopic appearance and clinical data. The majority of the tumors were cystic and microscopically, cysts were formed by squamous epithelial maturation, by degeneration of the stellate cells at the centers of adamantinomatous nests, or by degeneration of the stroma. Transitional forms were seen between adamantinomatous and squamous epithelium and keratohyaline granules and keratin were present in some cases. Because of this overlap, differentiation between craniopharyngiomas and suprasellar epidermoid cysts often is not possible. Significantly increased acturial survival rates were associated with absence of calcification in plain skull films in adults, negative CSF examination, and tumor size under 3.0 cm.


Malignant ovarian tumors in childhood: prognosis in relation to initial therapy. Twenty-two children with malignant ovarian tumors (12 malignant teratomas, six endodermal sinus tumors, and four embryonal carcinomas) were studied from 1960 through March 1975. Comparison is made between different modalities of therapy, such as surgery alone or surgery in combination with either radiation or chemotherapy. Because of the poor results obtained with the aforementioned treatment methods, a new approach, consisting of more aggressive initial surgery followed immediately by radiation therapy and an intensive chemotherapeutic regimen called the T2 protocol, was begun in 1971 with encouraging results. To date six of ten patients are alive and free of disease with a median observation period of 22+ months. A new grouping defining the extent of disease is also provided. Of the ten patients on the T2 protocol, only one was a Group I; eight were Group III and one was Group IV at the time treatment was initiated. An analysis of the mode of spread, as well as a discussion of the results obtained with previous modalities of therapy in relation to initial grouping and pathology, constitute the background for the proposed treatment.


Characteristics of blacks obtaining Papanicolaou smears. An understanding of the characteristics of women who do not obtain cervical cytology may shed light on procedures which can be instituted by physicians and public health workers to increase use of screening. Of particular interest are women at high risk of cervical cancer. We interviewed a random sample of about 700 blacks living in central Buffalo census tracts in regard to their past use of pelvic examinations as well as circumstances surrounding such use or non-use. We employed only data on screening which was verified in records. We found that there was decreasing use with increasing age and lack of contact with physicians, clinics, or hospitals. The relationship between increasing use and increasing education was found to be a function of the fact that women with more education are likely to be younger. There was clear evidence that making such examinations part of the contact women have with physicians or hospitals for any purpose, including childbirth, would increase the proportions screened.


Particle radiation therapy.

Particle radiation therapy. Particle radiation therapy has the potential for immediate and sustained favorable impact on management of the cancer patient by providing better local tumor control. Scientific knowledge and expertise are immediately available to mount effective clinical studies of fast neurons, protons, and helium ions, and to initiate necessary preliminary studies of pimesons and heavy ions. Meaningful studies will require a long-term commitment of support. The amount of support, although substantial, is not disproportionate to the potential benefit or existing support of other cancer research programs.


Anatomical site and size of 222 early asymptomatic oral squamous cell carcinomas: a continuing prospective study of oral cancer. II. The site and size of 222 asymptomatic, primarily erythroplastic, cancers of the oral mucosa in 161 patients have been prospectively documented. Of 207 intraoral lesions (excluding 15 of the lip), 201 (97.1%) were found in three locations; floor of the mouth (101), ventral or lateral tongue (36), and soft palate complex (64). Of the 101 in the floor of the mouth, 73 occurred in the anterior portion with 33 involving the papilla at exit of Wharton's Duct (submaxillary gland). Of the cancers 84.2% were 2 cm or less and 41.9% were 1 cm or less. Of the lesions 2 cm or less 70.6% were invasive carcinoma. Minimal size does not preclude invasiveness. In view of the apparent predilection of oral carcinoma for particular sites (where there is no obvious agent), rather than random occurrence, the three aforementioned sites are designated as high risk areas which deserve particular scrutiny in an examination of the oral cavity. It is incumbent upon the clinician to biopsy all asymptomatic, persisten (14 days or more) mucosal aberrations in the high risk areas, especially those with erythroplastic components, regardless of size.


Antibody response in patients with acute nonlymphocytic leukemia. Lymphocytotoxic (LCT) and anti-red blood cell (ABO) antibodies were measured serially in adult patients with acute nonlymphocytic leukemia (ANLL) receiving induction chemotherapy. The antigenic stimulus was provided by multiple platelet transfusions, many of which were ABO incompatible. Comparison of pretherapy titers 4-6 weeks into therapy shows that 50% (19/38) of patients became LCT positive (cytotoxicity against greater than 10% of panel of cells) and 54% (19/35) had increases in ABO titers (greater than 2 tube dilution). A total of 66% of patients had significant rises in at least one antibody. ABO and LCT titers tended to vary in parallel although exceptions were noted. The development of anti) remission rate or duration, 3) type of therapy, 4) number of platelet transfusions, 5) time relationship between the antigenic stimulus and the initiation of cytotoxic therapy, and 6) skin test reactivity. Antibody responders tended to have higher pretreatment lymphocyte counts. The ability to develop a secondary antibody response does not appear to be a major prognostic factor in ANLL.


Decreased neutrophil bactericidal activity in acute leukemia of childhood. Neutrophil (PMN) bactericidal activity, phagocytosis, and nitroblue tetrazolium (NBT) reduction were evaluated in 18 children with untreated or relapsing acute leukemia and 20 children in hematologic remission. Half of the patients in relapse demonstrated abnormal PMN bactericidal activity, while remission patients had essentially normal PMN bactericidal activity. Phagocytosis of Staphylococcus aureus was normal in relapse and remission subjects. NBT reduction by PMN's of leukemic patients was significantly lower than that of controls, but there was no correlation between decreased NBT-reductase activity and decreased bactericidal power. Six patients in remission had received intensive chemotherapy for more than 4 years, and all demonstrated normal PMN functions. Among relapse patients with abnormal PMN bactericidal activity 63% eventually developed severe bacterial infections. By comparison, 20% of the relapse patients with normal PMN bactericidal activity subsequently developed severe infections. The PMN dysfunction observed in relapse patients suggests that abnormal PMN bactericidal activity may contribute the increased susceptibility to bacterial infections during leukemic relapse.


Immunochemotherapy in human lung cancer using the streptococcal agent OK-432. Streptococcal agent OK-432 was administered at maintenance levels with conventional inductive chemotherapeutic agents to stage III and IV lung cancer patients. Survival rates were longer in patients treated with OK-432 than in patients treated without OK-432. An enhancement of lymphocyte blastogenic activity and a delayed PPD skin reaction were found in patients treated by OK-432. A low grade fever was present as a side effect of this agent in some patients. The results suggest that OTK-432 may be useful immunotherapeutic agent in combination with induction chemotherapy in reducing host damage in advanced stages of lung cancer.


CEA levels in head and neck cancer.

CEA levels in head and neck cancer. Serum carcinoembryonic antigen (CEA) levels were determined for 439 patients with squamous carcinoma of the head and neck region, 154 healthy smokers, and 122 nonsmokers. Among nonsmokers 95% of the CEA levels did not exceed 5 ng/ml, but among smokers this discriminatory level was 7 ng/ml. Among tumor-bearing patients 36% of the CEA levels exceeded 5 ng/ml but only 17% exceeded 7 ng/ml. Both the incidence and magnitude of CEA elevations correlated with clinical stage of tumor; however, excluding patients with clinically apparent advanced malignancies, the incidence and magnitude of elevations were similar among tumor-bearing patients, tumor-free treated patients, and smokers. Although not predictive of ultimate survival, elevated preoperative CEA levels declined to the range of normals after resection. Similarly, during palliative irradiation for incurable tumors, CEA levels declined with regression of tumor. Irradiation did not nonspecifically elevate CEA levels. The data indicate that in patients with head and neck squamous carcinomas CEA level is not likely to contribute to a determination of prognosis after therapy; however, serial determinations may have adjunctive value in monitoring tumor response.


Malignant lymphoma of the small intestine in multiple family members: association with an immunologic deficiency. Four cases of malignant lymphoma all in male members of a family are described. In three of the affected individuals the primary tumor arose in the small intestine and in the other the site of origin was the retroperitoneum. Immunologic studies were carried out on the two surviving patients and on all other living members of their families. Low levels of immunoglobulins were found in one of the affected boys. During a recurrence of the tumor, the other boy showed temporary partial impairment of cellular immunity as measured by failure to react to delayed hypersensitivity skin tests, although lymphocyte transformation studies were normal. Nine months after treatment was completed his response to skin tests was normal. No immunologic defect was detected in the studies of the non-involved family members. The histologic appearance of the tumors was similar in the tissue sections which were available for review from three of the four patients; the tumor was classified as a malignant lymphoma, diffuse, mixed cell type (lymphocytic and histiocytic).


Glassy cell carcinoma of the cervix.

Glassy cell carcinoma of the cervix. A clinicopathologic analysis of 13 cases of glassy cell carcinoma of the uterine cervix is presented. The glassy cell carcinoma is considered to be a poorly differentiated mixed adenosquamous carcinoma. Its histologic appearance is distinctive, being characterized by cells with a moderate amount of cytoplasm having a ground glass or finely granular appearance, a distinct cell wall that stains with eosin and PAS, and enlarged nuclei with prominent nucleoli. In the present study this tumor was associated with extrapelvic spread in 6/13 cases at diagnosis. Results were poor with either surgery and/or radiotherapy. Only four of 13 patients survived 5 years. The glassy cell carcinoma appears to be a distinct clinicopathologic entity which warrants a place in the classification of carcinoma of the cervix.


Hairy cell leukemia (leukemic reticuloendotheliosis) II. Ultrastructure of the spleen. Seven surgically removed spleens from patients with hairy cell leukemia and hypersplenism were examined ultrastructurally. In all spleens the pulp cords were diffusely and compactly infiltrated by hairy cells. Numerous hairy cells were also evident in the often distended sinuses. The hairy projections were readily visible in electron micrographs and tended to interdigitate to form syncytium-like aggregates. Compression of hairy cells within the cords flattened the projections against the cell bodies and may account for the surface alterations reported by scanning electron microscopic studies. Controversy over the cytogenesis of hairy cells has not been resolved by ultrastructural studies. Although all seven patients had hypersplenism, the hairy cells showed no evidence of phagocytic activity. However, active phagocytosis by cordal macrophages was observed and there is a probable absolute increase in their number contributing to the splenomegaly. The dense infiltrate of hairy cells causes marked widening of the cords and retards the passage of formed elements of the blood through the red pulp. Prolonged sojourn of these elements in a metabolically unfavorable environment results in cellular damage, increased exposure to cordal macrophages, and premature destruction with the evolution of a hypersplenic syndrome.


Spindle cell carcinoma: ultrastructural evidence of squamous origin and collagen production by the tumor cells. Two cases of spindle cell carcinoma (SCC) of the esophagus and skin, respectively, were studied by transmission electron microscopy. The tumor cells were closely associated with collagen fibrils and had abundant rough endoplasmic reticulum with dilated cisternae. Except for their irregular shape and atypical nuclei they resembled actively synthesizing fibroblasts. In addition to these features, some cells contained numerous tonofibrils and occasional well-developed desmosomes. A gradual transition to typical squamous cells was noted in the skin tumor. These findings suggest that the pseudosarcomatous component of SCC originates from mesenchymal metaplasia of squamous cells and that collagen is produced by these metaplastic cells.


Benign vaginal rhabdomyoma: a light and electron microscopic study. A benign vaginal rhabdomyoma from a 49-year-old woman was examined by light and electron microscopy. While many of the ultrastructural features conformed to those noted in previously described rhabdomyomas, certain features are described for the first time. These include attachment plaques between cells enclosed within a common basement membrane, cytoplasmic bodies, and peripheral couplings. Finally, the literature is reviewed and the reported cases of rhabdomyoma are divided into adult and fetal types based upon light microscopic criteria.


Lymphangiomyomatosis: morphogenetic study and ultrastructural confirmation of the histogenesis of the lung lesion. A 34-year old woman underwent a surgical intervention as a result of a retroperitoneal tumor. This tumor was excised and the pathological diagnosis was lymphangiomyoma. Two months later she developed a spontaneous right pneumothorax with a chylous pleural effusion. Roentgenograms showed that the lungs had developed a honeycomb pattern. She was treated surgically and at the same time a biopsy was performed. Sixteen months later she deveoped a left pneumothorax which necessitated additional surgery, and a further biopsy was taken. She died of respiratory insufficiency 2 years after the clinical onset of the symptoms. The pathologic material was studied by both electron and light microscopy in serial sections. The electron-microscopic study proved the muscular nature of this condition. The light microscopic study of the serial sections showed that the lung lesion was due to the proliferation of the muscle cells associated with the lymphatics surrounding the acini.


Thyroid cancer: a study of 573 thyroid tumors and 161 autopsy cases observed over a thirty-year period. Five hundred and seventy-three thyroid tumors from surgical material and 161 autopsy cases were studied as to incidence, types, and precursor changes using the new WHO-classification. In the surgical material 225 tumors were follicular, 145 papillary, 147 anaplastic, 23 squamous cell, and 10 medullary. Twenty-three sarcomas were found. tthe percentage of follicular carcinoma had decreased, whereas that of papillary carcinoma increased and that of anaplastic carcinoma remained constant. In over 50% of anaplastic carcinomas neoplastic follicular structures have been identified. As a rule the more sections are prepared, the more papillary carcinomas and the less sarcomas are diagnosed. Thyroid tumors leading to death were found in 0.33% of 53,134 consecutive autopsies. Anaplastic (52.3%) and follicular (33.5%) carcinoma were most frequently encountered. Metastases of follicular and anaplastic carcinoma were most often found in the lung, pleura, and bones, whereas lymph nodes of the neck, lung, and bones were predominantly involved in cases of the papillary type. Therapy of thyroid carcinoma is total thyroidectomy. The transition of follicular carcinoma to the anaplastic type has to be avoided whenever possible.


Solitary intraparenchymal pulmonary plasmacytoma associated with production of an M-protein: report of a case. A case of a 40-year old man who underwent surgical extirpation of a solitary intraparenchymal pulmonary plasmacytoma is reported. To our knowledge, this is the first reported case associated with the production of an M-protien. The production of protein fell dramatically following removal of the tumor.


Female adnexal tumor of probable Wolffian origin: evidence of a low grade malignancy. A broad ligament tumor with the histologic features of a female adnexal tumor of probable Wolffian origin, as described by Kariminejad and Scully, is reported. Although previous cases were thought to be benign, in the present case, hepatic metastasis occurred 6 years after resection of the primary. Cytologic features by light microscopy were more anaplastic than in the original cases. Ultrastructural findings were not specific for any normal adult or fetal mesonephric tissue previously studied by electron microscopy.


Benign clear cell tumor of lung with necrosis. A case of benign clear cell tumor ("sugar tumor") of the lund with extensive necrosis is reported. Electron microscopic study established the diagnosis by virtue of the characteristic cytoplasmic membrane-bound glycogen. Ultrastructural study may be necessary in cases containing necrosis to differentiate this lesion decisively from metastatic renal cell carcinoma.


Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases. Fifty-eight immature ovarian teratomas were studied. Neoplams with other germ cell elements (endodermal sinus tumor, choriocarcinoma, and dysgerminoma) were excluded so that the clinical and pathologic features of "pure" immature teratomas could be defined and correlated with the prognosis. The primary tumors and their metastatic growths were graded from 0 to 3. Forty were stage I; nine, stage II; and nine, stage III. The size and stage of teratomas were related to survival, but it was the grade of the primary tumor that best determined the likelihood of extraovarian spread, and it was the grade of the metastases that related best to the subsequent course. Actuarial survival was 63% at 5 years and also at 10 years. Regardless of the grade of the primary tumor, only one of six with grade 0 metastases progressed, and that neoplasms may not have been adequately sampled. Two of five neoplasms having grade 1 metastases did not progress, and two of six patients with grade 2 metastatic growths were living after relatively long intervals. All seven patients with grade 3 metastases died with tumor, none surviving more than 2.1 years. Survival of patients with grade 1, 2, and 3 neoplasms was 81, 60, and 30% respectively. The importance of adequate sampling of primary tumor and metastases for estimating prognosis and determining therapy is stressed.


Melanin as a component of cerebral gliomas: the melanotic cerebral ependymoma. Even though melanin is found in certain central nervous system neurons and leptomeningeal melanocytes, gliomas rarely possess melanin. A few rare lethal melanotic medulloblastomas found typically in the cerebellar vermis of children have been described, but neuroglial cells have not been observed to contain this pigment. Since glial elements and the melanotic pigmented layer of the retina are derived from the same ciliated epithelium of the embryonic neural tube, recognition of melanin in a cerebral glioma was predictable. Indeed, melanin was observed in a cystic cerebral ependymal glioma from a 30-year-old woman, supporting the potential of glial cells to produce melanin.


Improved survival in hodgkin's disease.

Improved survival in hodgkin's disease. All patients below the age of 66 whose Hodgkin's disease was treated at the Massachusetts General Hospital between July 1, 1965 and June 30, 1973 were analyzed. The patients were divided into an early group seen before November 1, 1968 and a later group seen after that date. Survival and survival without recurrence were calculated by the actuarial method of Berkson and Gage, and compared with figures obtained from a historical series seen at this institution between 1948 and 1964. In the most recent period (1969-1973), 87% of patients with all stages of Hodgkin's disease were alive five years after diagnosis, a remarkable improvement over the 65% survival of the 1965-1968 group and the 34% survival of the historical series. The excellent survival of the recent group was a result of improved management of patients with advanced disease (Stages III and IV), most plausibly attributed to better appreciation of the extent of disease by surgical staging and to the shift from total nodal irradiation to combination chemotherapy for initial treatment of these patients. Recurrence after irradiation was extremely uncommon in patients in Stage IA and IIA (lymphangiogram-negative, asymptomatic) subjected to aging laparotomy, while similarly staged and irradiated patients in Stages IB and IIB (lymphangiogram-negative, symptomatic) did much less well. Except for the surgically staged patients in Stages IA and IIA, the continuing high relapse rate indicates that five-year survival, even when relapse-free, is not synonymous with cure, and emphasizes the need for caution in predicting the ultimate cure rate with current therapy.


Pediatric Hodgkin's disease. I. Radiographic evaluation. The pretreatment roentgenographic evaluation of 105 consecutive patients less than 16 years of age with Hodgkin's disease was reviewed. The patients were divided into groups aged 1-10 years (37%) and 11-15 years (63%). All patients had chest roentgenograms, of which 36% were abnormal in the younger group and 77% abnormal in the older group. Full-lung tomography was helpful only when the chest film was abnormal or equivocal. Foot lymphography was performed in 103 patients with 20% positive for Hodgkin's disease. Lymphographic-histologic correlation was 98% in the 62 patients undergoing laparotomy. Routine skeletal surveys, as well as examinations of the urinary tract and gastrointestinal tract, were not rewarding.


Pediatric hodgkin's disease. II. Results of therapy. Between 1962 and 1972, 79 previously untreated children, aged 15 years and under, with biopsy-proven Hodgkin's disease were seen, evaluated, and treated at Standford University Medical Center. The 5-year actuarial survival for all patients was 89%; relapse-free survival was 66%. No relapse was seen following aggressive treatment with irradiation and MOPP chemotherapy. In patients who were pathologically staged, no relapse was seen beyond 2 years. Patients with mixed cellularity subtype fared surprisingly well as compared to those with the nodular sclerosing subtype. An analysis of the types of treatment administered and complications of therapy suggests that the major difference between children and adults with Hodgkin's disease is the potential for long-term sequelae resulting from aggressive treatment. In an attempt to maximize the quality of survival, a proposal is made for low-dose radiation and planned MOPP chemotherapy.


Malignant melanoma of the gallbladder: report of three cases and review of the literature. Three cases of primary melanoma of the gallbladder are described to add to the five reported in the literature. As an organ of endodermal origin, the gallbladder appears to share the melanoblastic potentiality possessed by similarly derived organs, and hence, the development of a melanoma within the gallbladder is not unexpected. Presence of melanocytes within the gallbladder mucosa is absolute proof that the tumor is primary. Whether these cells originate from the neural crest and migrate to the gallbladder, or result from local differentiation from preexisting cells remains to be answered.


Prostatic carcinoma: some morphological features affecting prognosis. Morphologic features in 146 cases of prostatic carcinoma were correlated with 5-year survival. Simple probability tests showed a significant prognostic difference of the presence or absence of cell borders, lymphocytic infiltration, pleomorphism of nuclei, and McNeal's typing. Further statistical analysis, with a probability test which was adjusted for the distribution of these factors, showed that only the presence or absence of cell borders and lymphocytic infiltration affected prognosis. It is very important for the pathologist reporting on prostate carcinoma to include mention of these factors in his report because of their prognostic importance. In particular it should be noted that if the tumor has indistinct cell borders and there is no lymphocytic infiltration, then it is likely to have a very poor prognosis.


Risk for breast cancer development determined by mammographic parenchymal pattern. A classification of risk for developing breast cancer has been devised based solely on the appearance of the breast parenchyma by mammography. Four groups of patients were isolated. The study encompassed a five-year period and was done by reviewing the mammograms of all women over the age of 30 who had been examined at Hutzel Hospital, Detroit. The average time of followup would be approximately 2 1/2 years. Four groups had an incidence of developing breast cancer of 0.1, 0.4, 1.7, and 2.2. These parenchymal patterns are described and criteria for their identification are given.