Results of radical radiation therapy in clinical stage I, technically operable non-small cell lung cancer.

From 1970 to 1983, 1,646 lung cancer patients were referred for treatment to the Hunter Radiation Therapy Center, Yale-New Haven Hospital. Forty-three patients had clinical Stage I non-small cell lung cancer felt to be surgically resectable but were treated with radical radiation therapy either for medical reasons (37 patients) or because the patient refused surgery (six patients). This group of clinical Stage I lung cancer patients is understaged by modern criteria since the majority of patients did not have thoracic CT scans and staging was based on fairly limited clinical and radiographic studies. The histological diagnosis was squamous cell carcinoma in 53% of the Stage I patients, adenocarcinoma in 25%, and other non-small cell histologies in 22%. All patients were treated with megavoltage irradiation and the mediastinum was treated in 88% of the patients. Eleven patients were treated with a continuous course (CC) and 32 patients received split course (SC) therapy based on physician preference. The CC consisted of a median fraction size of 200 cGy to a total median dose of 5900 cGy in 6-7 weeks. The SC used a median fraction site of 275 cGy to a total median dose of 5400 cGy over a 6-week period with a 2-week rest in the middle of treatment. The actuarial survival rate of the 43 clinical Stage I patients was 36% at 3 years and 21% at 5 years. Intrathoracic failures occurred in 39% of the patients. Despite the fact that the CC group was similar to the SC group in terms of age, histology, and tumor extent, the CC patients had a lower thoracic failure rate (2/11) versus 15/32), a longer median survival (51.6 months versus 27 months), and a better actuarial 5-year survival rate (45% versus 12%) when compared to the SC patients. Using Cox regression analysis to compare survival curves, the CC group had a significantly better survival compared to the SC group (p = .04).

Conservative surgery and radiation therapy in breast carcinoma: local recurrence and prognostic implications.

Conservative surgery with radiation therapy has been used with increasing frequency at Yale-New Haven Hospital since the late 1960's, resulting in a minimum evaluable follow-up time of 5 years on 278 patients treated prior to 1982. The radiation therapy technique generally encompassed treatment to the breast and regional lymph nodes of 4600 cGy with an electron beam boost to the tumor bed of 6400 cGy. Axillary dissection was performed in 19%, adjuvant chemotherapy in 7.3%, and adjuvant hormonal therapy in 5.7%; 65% were clinical Stage I and 35% were clinical Stage II. As of July 1987, with a minimum evaluable follow-up of 5 years and a median follow-up of 7.46 years, the actuarial 5- and 10-year survival for all 278 patients was 83% and 67%, respectively. The breast recurrence-free rate was 91% at 5 years and 80% at 10 years. Whereas the 5-year survival was significantly greater for clinical Stage I patients (91% vs 68%, p = .01), the breast recurrence-free rates did not significantly differ between clinical Stage I & II (93% vs 88%). There were 31 patients who failed in the breast alone as the first site of failure; 67% were at or near the primary site whereas 33% were distinctly removed from the primary site. Salvage mastectomy was performed in 25 patients, repeat wedge resection in two patients, and biopsy only in four patients. Axillary nodes were positive in five (33%) of 15 evaluable patients undergoing axillary dissection at the time of recurrence. The 5-year actuarial survival following local recurrence for the 31 patients was 48% at a mean follow-up of 5.06 years. The local recurrences were further subclassified into localized breast recurrences (LBR), defined clinically as greater than 3 cm and/or with dermal involvement. The 22 patients experiencing localized breast recurrences tended to occur later (median time to recurrence 4.3 years) than the nine patients experiencing a diffuse breast recurrence (median time to recurrence 2.9 years). At last follow-up, three (14%) of the 22 localized breast recurrences had subsequently failed distantly and none had subsequent local failure, whereas four (44%) of nine diffuse breast recurrences had subsequent distant failure and five (55%) of the nine diffuse breast recurrences experienced further local disease. The 5-year actuarial survival following salvage treatment was 90% for the localized breast recurrences and only 13% for the diffuse breast recurrences.

Dirhythmic breathing.

Four patients with severe chronic obstructive lung disease and recent respiratory failure are described in whom two distinct simultaneous respiratory rhythms were identified, one at 8 to 13 breaths per minute and the other at 39 to 65 per minute. Magnetometer measurements of thoracoabdominal motion together with simultaneous electromyograms of multiple inspiratory muscles suggested that both rhythms were the result of coordinated action of several inspiratory muscles. We suggest that this phenomenon, which we have called dirhythmic breathing, results from the conflicting influence upon respiratory centers and motoneurons of two or more stimuli, some favoring rapid shallow breaths and others slow deep breaths.

A rabbit lung model for testing reaction to inhaled dental restorative particles.

A study was designed to test the outcome of the deposition of particles of plastic composite dental restorative material in rabbit lungs. Grinding and polishing these restorations in situ produces some particles in the 0.5- to 10-microns size range that easily enter and remain in human lungs and are associated with industrial lung disease. Dental restorative plastic material was ground in the laboratory, suspended in saline solution, and injected transtracheally into four New Zealand white rabbits. Two control rabbits were similarly injected with saline solution transtracheally. Twenty-four hours later, the rabbits were injected with 1 mCi of 67Ga citrate intravenously and subsequently reanesthetized for scanning. Baseline scans were obtained in the six animals prior to the injection of the test particles. Positive gallium scans were obtained 72 h after the administration of particulate material in the four test rabbits. The gallium scans of the control rabbits remained no different from baseline. The study was repeated one month later. The animals were killed seven days after the last gallium scan. Light microscopy and transmission electron microscopy of the lungs of the test animals showed foci of chronic inflammation around particles of the restorative material. Particles were in vacuoles within alveolar macrophages and also free in interstitium. Control animals had normal histologic conditions. Silver amalgam and gold dental restorations have years of clinical use but the new plastic composite restorative materials are rapidly being introduced into human clinical dental practice. Normal use involves polymerization, grinding, and polishing of the material within the mouth. The chronic inflammation in the lungs of rabbits indicates a need to test dental restorative material for lung biocompatibility before further, extensive clinical use.

Conservative surgery with radiation therapy in clinical stage I and II breast cancer. Results of a 20-year experience.

Conservative surgery and radiation therapy have been increasingly utilized at Yale-New Haven (Conn) Hospital since the 1960s. This analysis represents our experience from 1962 to 1982, with a total of 281 patients having a minimum assessable follow-up of five years and a median follow-up of 7.4 years. Five- and ten-year actuarial survivals were 83% and 67%, respectively. The actuarial breast recurrence-free rate was 91% at five years and 80% at ten years. Of 31 patients having recurrences in the breast alone, the actuarial five-year survival following recurrence was 48%. Twenty-eight (90%) of these 31 recurrences were salvageable with mastectomy or repeated wedge resection. Patients experiencing an early breast recurrence (less than three years) following initial treatment had a poorer prognosis than patients having recurrences later.

Fevers of unknown origin in patients requiring mechanical ventilation: an odontogenic problem?

Patients who are on continuous monitors and mechanical ventilators, and who are receiving medical care in an intensive care setting, do not meet the usual expectations for dental care. Two examples of odontogenic contribution to fevers of unknown origin are presented in the context of treatment of continuously monitored patients with mechanically supported respiration. It is intended that these cases show the need for active dental consultation and participation by dentists in the care of the patient who is chronically ill and who cannot be brought to the traditional dental care setting.

Right atrial myxosarcoma in a dog.

A case of right atrial myxosarcoma is described in a Staffordshire bull terrier with a history of weight loss, exercise intolerance and collapse. The diagnosis of an intracavitary cardiac tumour was made on echocardiography. The dog was euthanased. Secondary spread to the lungs and lymph nodes was present. Myxoma is one of the rare intracavitary cardiac tumours and this case is believed to be the 1st report of its more malignant form in the dog.

Surgical problems in patients on ventilators.

Patients on ventilators for respiratory failure due to pulmonary disease may develop three major complications requiring general surgical evaluation: gastrointestinal (GI) bleeding, paralytic ileus, and mesenteric vascular insufficiency. GI bleeding from acute hemorrhagic gastritis (stress ulceration) can be avoided by aggressive medical therapy consisting of volume replacement, antacids, nutrition, and treatment of the precipitating causes. When conservative therapy fails, surgery will be needed to control bleeding. Intestinal ileus is of uncertain etiology. Initially, it is treated conservatively. Rarely, when the patient develops peritoneal irritation or a cecal diameter of greater tha 9 cm, surgery is indicated. Mesenteric vascular insufficiency of the nonocclusive type occurs in elderly individuals with heart disease, who develop a low cardiac output syndrome. Therapy must consist of avoiding a low flow state with proper fluid management, cardiorespiratory care, and drug therapy. Surgical intervention is indicated when physical examination and laboratory data point to a loss of intestinal viability.

Relative contributions of rib cage and abdomen to breathing in normal subjects.

By use of the method of Konno and Mead and the respiratory magnetometer, the partition of respired gas volumes into rib cage and diaphragm-abdomen components was accomplished in 81 normal subjects including 32 young and middle-aged men, 29 young and middle-aged women, and 20 elderly men. Studied were isovolume maneuvers and the relaxation configuration over the inspiratory capacity range, quiet tidal breathing, increased amplitudes of slow breathing, rapid inspirations and expirations, and both quiet and forceful phonation. No major differences were noted between men and women or between the young and the elderly during any respiratory acts. During quiet breathing most normal subjects are abdominal breathers when supine and thoracic breathers when upright. Rapid respiratory maneuvers were accomplished mostly through rib cage displacement suggesting that rib cage muscles are capable of more rapid action than diaphragm and abdominal muscles. Data from deep breathing and rapid maneuvers supported the view that abdominal and rib cage muscles often act to optimize the mechanical (length-tension) advantage of the diaphragm.

Compliances of human rib cage and diaphragm-abdomen pathways in relaxed versus paralyzed states.

The respiratory magnetometer method of Konno and Mead was used to measure separately the rib cage and the diaphragm-abdomen components of the total respiratory system compliance in 11 subjects with normal respiratory systems. Measurements made in the awake, relaxed state by the method of Heaf and Prime were compared with similar measurements made in the anesthetized, paralyzed state by the supersyringe method. The rib cage component was greater in the paralyzed than the relaxed state in 9 of 11 subjects, but the diaphragm-abdomen component was greater in the relaxed than the paralyzed state in 8 of 11 subjects. We believe that these differences can be explained by respiratory muscle activity in the presumed relaxed state. The fraction of the tidal volume attributable to rib cage displacement compared to abdominal displacement was greater during mechanical ventilation in the paralyzed state than during awake, spontaneous breathing. This can be explained by the different distribution of inflating forces produced by diaphragmatic contraction compared to positive airway and alveolar pressure, in particular by the very different patterns of diaphragmatic displacement in the 2 states.

Thoracoabdominal motion in chronic obstructive pulmonary disease.

Studies of thoracoabdominal motion using the respiratory magnetometer were performed in 30 patients with chronic obstructive pulmonary disease. Volume equivalency of thoracic and abdominal deflections was established by using the concepts and methods developed by Konno and Mead. Twenty patients were ambulatory, although disabled, and 10 were in acute respiratory failure and were studied in a respiratory intensive care unit. Five of 20 ambulatory patients and 8 of 10 patients in acute respiratory failure showed inward abdominal motion coincident with outward rib cage motion during inspiration, suggesting ineffective diaphragmatic function. This pattern of thoracoabdominal motion was identical to that seen in 2 high quadriplegics with diaphragmatic paralysis when they were breathing entirely with their neck muscles. Inspiratory ascent of the diaphragm was confirmed fluoroscopically in 3 of the 5 ambulatory patients. Patients showing this pattern were generally severely disabled and had the largest residual volumes. Two abnormal patterns of thoracoabdominal motion were observed during the performance of maximal voluntary ventilation in the ambulatory patients. The first, seen in 9 of 20 patients, was characterized by reciprocal or paradoxical motion of rib cage and abdomen, with increase in rib cage volume associated with decrease in abdominal volume during inspiration. The second pattern, seen in 5 of 20 patients, showed complete disorganization of rib cage and abdominal motion, with no consistent or reproducible pattern. Thus, a significant proportion of patients with disabling chronic obstructive pulmonary disease show abnormalities in thoracoabdominal motion that are observable with the respiratory magnetometer and ofter by simple inspection. Most of these abnormalities suggest malfunction of respiratory muscles, particularly the diaphragm.

Prolongation of the half-life of lactate after maximal exercise in patients with hepatic dysfunction.

Decreased hepatic clearance of exogenous sodium lactate has previously been demonstrated in patients with hepatic dysfunction. The purpose of this study was to obtain a more precise understanding of the rate of metabolic normalization or decrease of endogenously produced lactate in patients with hepatic cirrhosis. The differential kinetics of lactate metabolism are of clinical interest. Male volunteer patients with hepatic cirrhosis (n = 7), who had survived acute hospitalization, were compared to healthy age-matched males with normal liver function (n = 7). After arterial cannulation, bicycle ergometry was performed at a workload of 25 watts (W); the load was increased by increments of 25 W at 2-min intervals to maximum aerobic capacity. Lactate was measured in arterial blood before, at 4-min intervals during, and on a minimum of 11 occasions in the 30 to 70 min after exercise. The time interval during which lactate declined linearly to half its maximal concentration (Lt50) was graphically computed. The Lt50 was 34.8 +/- 4.5 min (mean +/- SEM) in the experimental group and 14.1 +/- 1.3 min in the control subjects (p less than .005). Lactate disappears from the bloodstream almost three times more slowly in patients with hepatic cirrhosis. The implication for interpretation of changes in lactate during circulatory shock in the presence of liver dysfunction is addressed.