High dosage pre-operative radiation and surgery for carcinoma of the larynx and laryngopharynx. A 14-year program

A carefully planned clinical program of combined pre-operative radiation and surgery has been conducted by the Department of Otolaryngology at The Mount Sinai Hospital for the past 14 years in an effort to improve the survival rates for advanced cancer of the larynx and laryngopharynx. The Combined Therapy Program, introduced in 1958, encompassed three separate but interdependent phases. The first stage consisted of a strict protocol of 5,500 rads of Cobalt 60 teletherapy administered over a five to six-week period. The second stage involved a rest period of three to six weeks to allow for proper healing of radiation reactions. The third stage comprised the radical procedure which included a wide field laryn-gectomy, ipsilateral hemithyroidectomy and radical neck dissection. Whenever indicated, a contralateral neck dissection was performed as soon as feasible. The protocol described above was applied only to those patients who fit all the criteria that categorized them as having advanced cancer of the larynx and laryngopharynx. In this study all patients had a biopsy proven diagnosis of squamous cell carcinoma. A very careful statistical analysis has been made of the survival experience of this series of cases. The three and five-year survival rates have been computed by the actuarial method,¹ which when compared to the direct method, adds more reliability to the results. The direct method removes those cases not treated at least three and five years ago in computing three and five-year survival rates, while the actuarial procedure includes all cases in the computation of survival rates. Between November, 1958, and March 1, 1972, 64 patients had been treated by combined therapy. According to the American Classification² the 64 cases are composed of 20 Stage II (T₂N₀ excluded), 12 Stage III and 32 Stage IV cases. According to the actuarial method the absolute survival rates for all cases were 77 percent and 59 percent for three and five years respectively. The corresponding determinate rates were 88 percent and 86 percent. Analyzing the results according to stages, the three-year determinate rates ranged from 100 percent for Stage II to 79 percent for Stage IV. The corresponding absolute rates ranged from 89 percent to 70 percent. The five-year determinate rates ranged from 100 percent to 74 percent, while the absolute five-year survival rates ranged from 50 percent for Stage II to 66 percent for Stage IV. This apparent reversal is far from being statistically significant because of considerable sampling error. The complications seen in patients treated with combined therapy have been essentially the same as those patients who undergo radical surgery without pre-operative radiation. Several preventive measures have been utilized during surgery, and it is to be emphasized that there have been no deaths related to complications, and all patients ultimately healed completely. The important controversy which exists in the- combined method of therapy concerns the question of using low dosage pre-operative radiation in the order of 1,000 to 3,000 rads or high dosages of radiation. It is our contention that serial section studies of biopsied laryngeal specimens labelled with tritiated thymidine tend to disprove the claims made favoring the value of low dosage radiation. The in vitro tritiated thymidine studies demonstrated that active DNA synthesis was observed in cancer cells in an appreciable number following dosages of 3,500 and also 5,500 rads.³ A further significant factor to be considered, we believe, is the effect of high dose pre-operative radiation on the incidence of cervical recurrence. In this series, 44 patients had clinically palpable nodes pre-operatively. There were six patients who developed local cervical recurrence, a rate of 14 percent. In conclusion, our statistics seem to indicate that our combined method of therapy has improved the survival rates of patients with advanced cancer of the larynx and laryngopharynx.     

Recurrent meningitis secondary to idiopathic oval window csf leak

Bacterial meningitis remains a life-threatening infection even in the present antibiotic era; thus, any abnormality which predisposes a patient to a recurrence of this serious disease, must be identified and corrected. This report describes the history of a 12-year-old boy with a profound neurosensory hearing loss, a related absence of vestibular function and a Monclini-type of temporal bone dysplasia who developed recurrent episodes of meningitis which were due to an idiopathic cerebrospinal fluid otorrhea. Even though the meningitis was labyrinthogenic in origin, the patient did not experience the associated symptoms of hearing loss and/or vertigo since the affected inner ear was clinically unreactive. By surgically exploring the middle ear, the presence of a cerebrospinal fluid otorrhea was confirmed. The leak was observed to be coming from a defect in the stapes footplate, and it was controlled by firmly packing the inner ear vestibule with muscle. A remarkable similarity exists between the patient described above and the 15 previously reported cases of meningitis due to a spontaneous cerebrospinal fluid otorrhea. Generally, the problem occurred in young children, the average age being 6.4 years; male and female were equally afflicted. All 15 previously reported cases had a severe neurosensory hearing loss which was unilateral in 10 individuals and bilateral in the other five. In 11 of the case reports, the vestibular function was evaluated, and the labyrinth was noted to be unreactive in the affected ear. An associated congenital abnormality of the inner ear was described in 11 of the patients reviewed. Anatomically, in 13 cases, the leak was observed to be coming from the oval window area. Other affected sites included one report of a fissure of the promontory and one report of a defect in the roof of the eustachian tube. Multiple surgical procedures were required in 11 of the 15 patients in order to identify the exact source of the otorrhea and to seal it permanently. In three cases, the successful procedure was a middle ear exploration with stapedectomy and packing of the inner ear vestibule. Overall, a total of 36 operations was performed in the 15 patients reviewed. In conclusion, when the physician is confronted by a case of meningitis in a patient with a unilateral or bilateral total loss of hearing and vestibular function, the possible presence of an idiopathic cerebrospinal fluid leak should be considered, especially if radiographic studies demonstrate a temporal bone dysplasia. In these selected cases, if the etiology of the meningitis is obscure, a middle ear exploration should be performed both for diagnostic purposes as a means to ascertain definitely the presence of a leak and for therapeutic purposes to seal it effectively.     

Characterization of a carboxyterminal peptide fragment of the human choriogonadotropin beta-subunit excreted in the urine of a woman with choriocarcinoma.

We have observed low-molecular weight carboxyterminal fragments of the human choriogonadotropin (hCG) beta-subunit in the urines of several women with choriocarcinoma, and we have characterized one fragment in detail. Its apparent molecular weight by gel chromatography on Sephadex G-100 was 14,200. The fragment was not adsorbed to concanavalin A-Sepharose, indicating that it lacked the asparagine-linked carbohydrate groups of intact hCG beta. It was active in radioimmunoassays (RIA) using antisera either to the hCG beta carboxyterminal peptide (CTP) or to the desialylated hCG beta CTP (hCG beta as-CTP), indicating the presence of not only the hCG beta carboxyterminus but also desialylated O-serine-linked carbohydrate side chains on the fragment. It lacked luteinizing hormone/choriogonadotropin radioreceptor activity and hCG beta conformational immunoreactivity (SB6 RIA). On Sephadex G-100 gel chromatography, the elution profiles of this fragment and the hCG beta as-CTP(115-145) prepared by trypsin digestion of as-hCG were essentially indistinguishable (apparent molecular weights 14,200 and 14,000, respectively). The immunological characteristics of the fragment in both hCG beta CTP and hCG beta as-CTP RIA were indistinguishable from those of the hCG beta as-CTP(115-145) glycopeptide. Carboxyterminal fragments of hCG beta were evident in urine specimens obtained from 10 of 11 patients with choriocarcinoma but not in those obtained from normal subjects who were given an intravenous infusion of highly purified hCG. Of six pregnant women, only the one at term excreted carboxyterminal fragments of hCG beta and then only in trace amounts. We conclude that hCG beta carboxyterminal fragments, including one that is indistinguishable from the tryptic glycopeptide hCG beta as-CTP(115-145), can occur naturally in the urine of patients with choriocarcinoma.     

Physical Therapy and Complementary and Alternative Medicine: An Educational Tool for Enhancing Integration

In an outpatient rehabilitation setting, both patients’ use and therapists’ knowledge of complementary and alternative medicine (CAM) varies widely. Based on this observation and a recognition of CAM as an emerging practice area for rehabilitation professionals, it was felt that a thorough and consistent approach to the education and orientation of physical therapists to the world of CAM and integrative care was needed. This special interest paper will describe one center’s approach, development, and use of a unique and comprehensive training manual designed to provide both a structured and standardized approach for educating physical therapists about CAM and related therapeutic modalities. This innovative teaching tool allows for multiple methods of content delivery within a multidisciplinary format and can be used for those who practice currently or desire to practice in an integrative care environment.