Glycoproteins distinguishing non-small cell from small cell human lung carcinoma recognized by monoclonal antibody 43-9F.

Cell lines derived from human squamous lung carcinoma release large amounts of a soluble glycoprotein into the culture media, having very high molecular weight (greater than 2 X 10(6] and mucin-like properties. A monoclonal antibody called 43-9F has been generated that recognizes a carbohydrate epitope on the glycoconjugate. The epitope is also present on a diverse set of smaller glycoproteins (Mr 50,000-200,000) distributed primarily on the surface of the squamous lung carcinoma cells. A sensitive assay using the 43-9F antibody in a dot blot procedure has been devised that is able to detect an amount of antigen less than that possessed by a single squamous lung carcinoma cell. This assay, and also conventional immunofluorescence and immunohistochemical assay procedures, have been used to screen different normal cells, normal tissues, cancer cells, and tumor biopsy specimens for the antigen. In the normal lung the 43-9F antigen is found only on cells of some of the seromucous glands. In the normal digestive system it is associated in certain organs only with a limited population of mucosal epithelial cells. Other organ systems lack any reactive cells. The cells of most human non-small cell lung carcinomas and their released glycoconjugates have large amounts of the 43-9F epitope, while small cell lung carcinomas and the glycoconjugates released by small cell lung cancer cells lack the epitope. The oligosaccharide recognized by the 43-9F antibody may therefore provide a useful marker to distinguish the different lung carcinomas and for investigating the different cells of origin of these tumors.

Thymectomy as immunosuppression in uremic patients.

Five uremic patients awaiting renal transplantation underwent transcervical thymectomy in an evaluation of the immunosuppressive effect of removal of the thymus in such transplantations. A number of immunological parameters, including lymphocyte transformation tests, were followed in these patients for up to 30 weeks after thymectomy. The number of B lymphocytes in the blood, stem cells in bone marrow, and T lymphocytes in lymph nodes decreased, whereas IgG, IgA, and IgM in four cases and C3 complement in all five cases increased. Blood leucocyte and lymphocyte counts did not show any characteristic changes. The T cell response of circulating lymphocytes was determined after stimulation with mitogens, specific antigens, and allogeneic cells in mixed lymphocyte culture, and showed a large increase. Thymectomy of uremic patients results in a considerable increase in immunocompetence in the first 30 weeks, indicating that it is not suitable as an immunosuppressive treatment.

Resection of acquired tracheal stenosis in childhood.

In a series of 74 tracheal resections, six were performed in boys aged 2 to 13 years. One patient was intubated shortly after operation because of bulbar paralysis with swallowing difficulties. He died 5 months later of traumatic hydrocephalus. Another patient was reintubated because of an accompanying nondiagnosed glottis stenosis which later was treated successfully. Four patients have been followed up from 4 to 10 years. In these patients tracheoscopy and x-ray examination have shown that the anastomosis has grown at the same rate as the rest of the trachea. It is concluded that operation can be performed in children at any age provided that swallowing is normal and accompanying laryngeal stenosis is excluded.

Does achalasia predispose to cancer of the esophagus?

In a follow-up study of 147 patients with achalasia of the esophagus treated by myotomy, 146 patients were traced (58 female and 88 male patients aged 4 to 83 years [median, 46 years]). The living persons were contacted in writing or by telephone. The mean follow-up time after the operation was 23.2 years (range, 6 to 41 years). The cause of death was established for 71 patients. There were three postoperative deaths and two deaths following recurrence. In comparison with the Danish population, the 66 remaining patients were found to have a relatively higher cancer mortality (33.8 percent). Contrary to the expected less than one, ten of 23 patients who died of cancer had a malignant tumor in the esophagus. The mortality rate after 30 years was 66.1 percent, 11.9 percent of the deaths caused by esophageal cancer. It is concluded that there is a connection between achalasia and cancer of the esophagus that ought to be considered in the treatment and follow-up of patients with achalasia.

Arterial line filtration protects brain microcirculation during cardiopulmonary bypass in the pig.

Microemboli in the brain may inhibit brain function during cardiopulmonary bypass, and in a previous study in pigs of normothermic nonpulsatile bypass we reported a significant decrease in cerebral glucose consumption secondary to interruption of the capillary flow, possibly caused by microemboli. In the present study we measured the regional cerebral glucose consumption and the regional capillary diffusion capacity (that is, the number of perfused capillaries) in 10 different brain regions in two separate groups of animals with and without an arterial filter during normothermic cardiopulmonary bypass. Inclusion of a 40 micron arterial filter in the bypass circuit increased the regional brain glucose consumption 27% (median; range -12% to 145%) and regional capillary diffusion capacity increased 123% (median; range 36% to 829%). No change in brain histologic features, the cerebrovascular permeability to serum proteins, or cerebral water content was observed. The arterial filter probably protects the cerebral microcirculation and prevents the decrease in cerebral glucose consumption otherwise seen during bypass.

Brain microvascular function during cardiopulmonary bypass.

Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass.

Regulatory peptides in the lower esophageal sphincter of man.

Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.

Brain histology, blood-brain barrier and brain water after normothermic and hypothermic cardiopulmonary bypass in pigs.

The effect of hypothermia during cardiopulmonary bypass (CPB) on cerebral histopathology, blood-brain barrier permeability to serum proteins and water content was evaluated. Pigs were subjected to non-pulsatile CPB for 2 h at either normothermia or hypothermia, and a group of anaesthetised pigs served as normothermic controls. The histopathology was assessed on paraffin embedded sections. The permeability of the cerebral vessels was studied by immunocytochemical demonstration of extravasated serum proteins. The cerebral water content was assessed by specific gravity measurements. The histological studies demonstrated hydropic degeneration of the brain parenchyma and perivascular swelling of the astrocytic endfeet throughout both white and gray matter in the normothermic CPB group. Similar changes were not encountered during hypothermic CPB, which suggests a beneficial effect of decreased temperatures on brain tissue during CPB. Neither normothermic nor hypothermic CPB induced significant changes in the cerebrovascular permeability or in the specific gravities.

Brain damage following low flow cardiopulmonary bypass in pigs.

Reduction of pump flow during cardiopulmonary bypass (CPB) reduces the formation of microemboli and trauma to the blood components, reduces both rewarming of the heart and the noncoronary collateral flow, and improves surgical exposure. Recent studies indicate that a reduction in pump flow, even at normothermia, does not increase the incidence of postoperative cerebral dysfunction. We examined the cerebral consequences of 2 h of normothermic CPB in pigs carried out at pump flows of either 70 ml/kg per min or 50 ml/kg per min, and compared the results with those of a nonperfused control group. We measured the regional cerebral glucose metabolism and the regional capillary diffusion capacity simultaneously in ten different brain regions. Brain morphology, the blood-brain barrier permeability to serum proteins and the regional cerebral water content were also determined in the same animals. Glucose metabolism decreased significantly in both CPB groups (P < 0.001), and significant differences were found between the capillary diffusion capacities of the three groups (P < 0.05), with decreases in eight out of ten brain regions examined in the 50 ml/kg per min group. The results indicate that a reduction of pump flows from 70 ml/kg per min to 50 ml/kg per min is deleterious to the brain, and that a pump flow of 70 ml/kg per min itself has an injurious effect, when normothermic CPB is carried out for 2 h without the use of vasoactive drugs to maintain the blood pressure. Mean arterial blood pressure (MAP) rather than pump flow seemed to determine the adequacy of the cerebral perfusion.

[Does achalasia predispose to cancer of the esophagus?]. / Disponerer achalasia til esophaguscancer?

In a follow-up study of 147 patients with achalasia of the esophagus treated by myotomy, 146 patients were traced (58 female and 88 male patients aged 4 to 83 years; median 46 years). The living persons were contacted in writing or by telephone. The mean follow-up time after the operation was 23.2 years (range, six to 41 years). The cause of death was established for 71 patients. There were three postoperative deaths and two deaths following recurrence. In comparison with the Danish population, the 66 remaining patients were found to have a relatively higher cancer mortality (34.9% percent). Contrary to the expected less than one, ten of 23 patients who died of cancer had a malignant tumor in the esophagus. The mortality rate after 30 years was 66.1 percent, 11.9 percent of the deaths caused by esophageal cancer. It is concluded that there is a connection between achalasia and cancer of the esophagus that ought to be considered in the treatment and follow-up of patients with achalasia.

[Surgical treatment of cancer of the cardia and the esophagus]. / Kirurgisk behandling af cancer cardiae og cancer esophagi.

During the period 1977 to 1989, 379 patients with cancer cardiac and cancer esophagi were admitted. The ages ranged from 18-88 years with an average of 65 years. The treatment concept was basically unchanged during the study period. Resection as described by Ivor Lewis was employed as palliative or curative treatment when resection was considered possible. Intubation of the esophagus was employed when no other treatment was considered possible. Resection was employed in 251 patients, eight of these emergencies on account of perforation or haemorrhage. Bypass operations were employed in five patients, intubations in 63 and no surgical treatment was undertaken in 60 patients. The all over operative mortality for resections was 11.2% and for elective operations 9.9%. The operative mortality increased with the TNM stage of the tumour and was 3.2% for stages I + II, 8.2% for stage III and 24.4% for stage IV. The complication ration was 42%. 15% of the patients submitted to resection required reoperation. Anastomotic leaks were encountered in 18 patients and nine of these died. Pulmonary complications were the most frequent and resulted in ten early postoperative deaths. The mortality connected with intubations was 15%. The over all five-year survival rate after resections was 10.4%. In stages I + II this was 42% and 8% in stage III. None of the patients in stage IV survived for two years. The longest survival after intubation was less than one year.