SURGICAL TREATMENT OF JUVENILE NASOPHARYNGEAL ANGIOFIBROMA.*} Bruce W. JaFrex, M.D., Baltimore, Md., ALAN M. NauuM, M.D., San Diego, Calif., R, MeLvin Buruer, MD., and PauL H. Warp, M.D., Los Angeles, Calif. ABSTRACT, Twenty-five cases of juvenile nasopharyngeal angiofibroma are reviewed. Surgical removal via a transpalatal approach accompanied by a gingivo- buceal incision and exploration of the pterygomaxillary space to remove Jateral extension is advocated. This procedure is almost uniformly success- ful in eradicating tumors without intracranial extension. Pre-operative estrogen therapy and temporary ligation of the ipsilateral carotid artery in selected cases appears to decrease blood loss at surgery. Pre-operative angiography delineates the nasopharyngeal mass, shows any pterygomaxil- lary space extension, and demonstrates any middle cranial fossa extension. A fairly accurate estimate of the percentages of vascular contribution is also obtained, allowing the surgeon to plan possible vascular control by ligation, Intracranial fossa extension generally greatly increases the oper- ative blood loss and risk, because of probable subtotal resection but is not an absolute contraindication to surgery. ° INTRODUCTION. Juvenile nasopharyngeal angiofibroma (JNA) is a relatively rare, lo- eally expansive, histologically benign tumor of the nasopharynx found pri- marily in adolescent males. Its extensive vascularity is responsible for the *Prosented at the Meeting of the Southern Section of the American Laryngological, Rhino- logical and Otological Society, Inc,, Washington, D. C., January 12, 1973. {From the Department of Surgery/Head and Neck, U.C.L.A. School of Medicine, Los Angeles, Calif, 90024, Dr, Jafek is presently with the Division of, Laryngolory and Otology, Departmen of Surgery, The Johns Hopkins Hospital and_ United States. Public Health Service Hospital, Baltimore, ‘Md. Supported in part by U.S.P.H.S. Grant NB-5295. ‘altor’s Note: This Manuscript recelved In ‘Tum LanyNooscore Office and accepted for pub- Ucation February 6. 1973. ‘Request for. Reprints should be sent to B. W. Jafek, M.D., United States Publle Health Sorv- ee Hospital, 8100 Wyman Park Drive, Baltimore, Md, 21241, 7 107708 JAFEK, ET AL,; JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. patient’s most common presenting symptom of epistaxis. Other symptoms are primarily due to obstruction or erosion, characteristic of any space- occupying mass within the nasopharynx. The etiology. of this turnor is unknown, but numerous theories have been advanced, most speculating on an imbalance of the pituitary-adrenogenital system with neoplastic response of target tissue in the nasopharynx. Ringertz* proposed the central periosteal layer of the bone arising from the embryonal occipital plate and the anterior aspect of the first and second cervical vertebra as the target tissue, while Brunner? mentioned the fascia basalis and Schiff implicated a desmoplastic response of the nasopharyngeal periosteum to an ectopic hamartomatous nidus of vascu- lar tissue, probably of the inferior turbinate type. The nearly exclusive oc- currence of angiofibromas in the adolescent male supports a hormonal im- balance as the responsible etiologic factor, and has led to empirical treat- ment with estrogens and androgens; however, hormonal abnormalities, as. shown by measuring the gonadotropins or 17-ketosteroids have not been demonstrated consistently.#** Forms of therapy reported successful in controlling the tumor are ra- diation, surgery, cryotherapy, electrocoagulation, embolization, hormonal therapy and finally conservative expectant observation with repeated pack- ing until the tumor undergoes “spontaneous regression.’%4:6.5,7,0,0,10,11,12,13, 14,35 16,17,28 Pressman’ asserted that (of these methods) “surgery alone has proven. effective.” He reported that neither he nor anyone he had questioned had ever known of an angiofibroma which spontaneously regressed without therapy after having produced significant hemorrhage. Briant, e¢ al.,* on the other hand, reports a “success rate” with surgery of only 5 percent (one of 19 operations was not followed by additional therapy). Radiation was “successful” (no further therapy required) in 77 percent (17/22) of all cases and in 92 percent (12/18) of patients re- ceiving this as the primary mode of therapy; however, the details of the surgical approach for the patients in this series are not included nor are the methods of follow-up evaluation given (angiography, ete.). Schiff’s excellent report* details the rational for hormone therapy in these tumors, Hayes Martin® was one of the early advocates of this form of therapy but used androgens instead of estrogens as advocated by Schiff. Androgens were later shown to be of limited value.” Preliminary reports of experience using cryotherapy as an adjunct to surgical removal were glowing, but more widespread experience demon- strated little evidence to recommend a combined approach, although some authors continue to favor it.4? Figi* supported electrocoagulation in some cases as an adjunct to radio-JAFEK, ET AL,: JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. | 709 TABLE I. Frequency of Presenting Signs and Symptoms with Nasopharyngeal Angiofibroma. Epistaxis 80 Percent Obstruction. 80 Percent Rhinolalia Clause 24 Percent Conductive Hearing Loss 8 Percent Rhinorrhea 8 Percent Facial Swelling . 8 Percent Neurological Deficits 0 Percent therapy and reported that “all of the patients who have received this ther- apy (radium and/or electrocoagulation) either have been cured or are well on their way to complete recovery”; however, he admitted that in many cases it was not economically possible for the patient to return for later observation. The management of JNA by pre-operative estrogen therapy followed by surgical removal via a transpalatal approach was advocated by Butler, et al.” The pterygomaxillary space was explored and lateral tumor extension removed en bloc. Since his report of eight patients, 14 additional patients have been seen and treated. The purpose of this report is to present a long term (five-year) follow- up on the patients initially treated as well as to detail the authors’ experi- ence with 25 cases seen over a 10-year period. METHODS AND MATERIALS. Twenty-five patients were seen and treated during the period from 1961- 1971 at the UCLA Medical Center. All were males, between the ages of 10-18 with an average age of 14.8 years. None were noted at the time of evaluation or in follow-up to be physiologically immature or sexually un- developed. The presenting complaints are summarized in Table I. Tumor was present in the nasopharynx in all patients on initial exami- nation and extended into the sphenoid (as shown on angiography or at surgery) in 80 percent. Lateral extension into the pterygomaxillary fossa was demonstrated in 76 percent, the right being involved in 40 percent and the left in 86 percent. Middle cranial fossa extension was eventually shown in 20 percent, while the inferior turbinate was involved in-8 per- cent and the septum and soft palate in 4 percent, each. Ulceration of the tumor mass was apparent only in cases where there had been a recent bi- opsy or exposure to secondary inflammation or trauma. Of this series, 52 percent had histologic confirmation of the tumor mass710 JAFEK, ET AL: JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. TABLE Il. Localization of Juvenile Nasopharyngeal Angiofibroma Feeders on Anglography. Vessels Bxternal Internal, Ascending Intern: Carotid ‘Maxillary "Palatine Carolla Ophthalmic Vertebral Right Side 1b 7 2 8 1 1 Left Side 15 4 2 7 1 and 82 percent had undergone at least one previous attempt of surgical removal when seen initially (20 percent had had a biopsy only). TREATMENT TECHNIQUE. Pre-operative carotid angiography was carried out in'84 percent (the exclusions being primarily in the early cases) with additional vertebral studies in 16 percent. Many tumors received vessels from more than one of the major cervical vessels, as shown in Table IJ. The main blood supply was usually from the external carotid or its branches, with occasional contribution from the in- ternal carotid system and rare supply from the vertebrals. Blood supply from the latter two was more common in cases of intracranial extension. Predominate origin from the right and left sides were approximately equal. One early patient became quadraplegic following carotid and vertebral studies, as previously documented,?* the only such complication in over 700 similar studies (AB). A second required emergency tracheotomy following sedation for angiography because of respiratory obstruction due to the mass of the tumor (HE). Nine patients received pre-operative estrogen therapy consisting of Stilbestrol 2.5-5 m. orally three times. daily for two to four weeks pre-op- eratively. The larger dose is currently advocated, when used. The 25 patients underwent 35 separate surgeries, as shown in Table III. Temporary occlusion of the ipsilateral external carotid artery was carried out in 16. Bilateral occlusion was accomplished in four with clipping of the internal maxillary artery in one additional case. Temporary occlusion of the common carotids bilaterally and one vertebral artery under hypoten- sive, hypothermic anesthesia, was utilized in one patient with middle ‘eranial fossa extension and carotid-cavernous fistula, in a heroic attempt at tumor extirpation following failure of other modalities (estrogens, ir- radiation, partial: resection). This terminated fatally (JL). Several patients were anemic due to recent hemorrhage and required pre-operative transfusion.-AqrByiour earyesodo 4 pus tsoqios TeupS1I0 ur sUDNEd 5 419718 ALVIPXVUL [BUILT 'VINI !419j1e PROrv UoMTUIOD ‘OO TeIO;eNG ‘a $3FOL TUT WL ee[ss[estsqforfor|se|eeafez] | fev[seloojoe[re]refed] st] s1[ex|ss[or]za * seme teases |_| xP] [I [a[sle] [aja PEBEEEEE ERE XTX ae Ff x712 JAFEK, ET AL.: JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. Tig. 1. Operative view of palate with Dingman mouth gag in place, Armored endotrachcal tube superior, Incision shown by Black dotted line. The surgical approach is as follows: under general anesthesia, with the patient in the Rose position, a Dingman mouth gag is inserted and the retractors positioned to retract the cheeks (Fig. 1). Hypothermic or hypo- tensive technique are generally considered unnecessary and add further risk to the procedure. The external carotid artery is temporarily occluded with a vascular clamp. Temporary occlusion is preferred to ligation to al- low subsequent arteriography, if needed, as well as to decrease the possi- bility of establishment of collateral circulation from the internal carotid or vertebral system in the event of tumor recurrence. The authors have no experience with embolization of feeder vessels, as recently described by Roberson, et al.,’7 but this technique may prove to be helpful where the highly specialized facilities necessary for this procedure exist. A transpalatal Owens incision is made following injection of the hard palate and greater palatine foramen bilaterally with 1:100,000 Epinephrine, and a horseshoe-shaped flap of palatal mucoperiosteum is elevated posteri- orly to the junction between the hard and soft palate.*° The hard palate is yongeured away near its posterior aspect to allow visualization of the tumor mass (Fig. 2). Xylocaine®-Epinephrine is infiltrated around the tumor, Great care is then taken to incise the mucoperiosteum outside and around the tumor in the nasopharynx, This can be accomplished with a knife or with cuttingJAFEK, ET AL.: JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. 718 Fig. 2. Soft palate and flap retracted posteriorly (p) to visualize tumor mass (1) through hard'palate defect. electrocautery. This tissue is then elevated toward the tumor from all sides, entering the bony defect to continue the elevation and tumor removal. The cryoprobe was used as an adjunct at this point early in the series but soon abandoned as no tumor could be removed whole in the frozen state and after thawing, the freezing had no lasting effect on the bleeding. If no lateral extension has been demonstrated by angiogram or direct visualiza- tion, the tumor is removed at this time. If a lateral extension is present, a gingivobuccal incision is made as de- scribed by Sardana*** and the extension bluntly and sharply dissected free, The smaller extensions can often be pushed into the nasopharynx with the index finger, while larger hourglass pterygomaxillary extensions occasionally necessitate removal of the tumor in two pieces, Rarely a lateral rhinotomy may be necessary to expose anterior-superior tumor ex- tension and to reflect it posteriorly. Once the tumor is entirely freed later- ally and in the nasopharynx, it is removed and examined carefully for evidence suggestive of incomplete removal (Figs. 8 and 4). Piecemeal re- moval is to be avoided, as it may result in increased bleeding and incom- plete tumor removal, The resultant cavity is also carefully inspected for residual occult extensions of the neoplasm. Bleeding points are electro- coagulated, The defect is then packed with Surgicel held in place with a 30 cc..bal-714 JAFEK, ET AL,; JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. Fig, 8, Intact specimen with mucosa-covered pesopharyngeal component (NP), large ptorygo- maxillary extension (prw) and smaller sphenold extension (s). loon catheter brought out through the nose. Over-inflation of this balloon may produce reflex hypotension, which is relieved when some of the fluid is evacuated. The palate and gingivobuccal incisions are. closed in layers as is the neck incision following release of the bulldog clamp. The Foley is removed on the second or third postoperative day, and the patient is allowed to go home on the fifth to tenth day. Tracheotomy is not ordinarily indicated, unless there is evidence of respiratory distress due to obstruction. This occurred in two of the cases. Postoperative broad spectrum antibiotic coverage is given. COMPLICATIONS, During the immediate postoperative period, one patient experienced mild epistaxis without evidence of recurrent tumor. Two had tongue edema which subsided in seven to nine days, necessitating tracheotomy, as men- tioned. This edema was probably due to prolonged pressure from the mouth gag and should be avoided by periodically releasing the gag. There were four small palatal dehiscences, two of which required secondary closure. This complication may be avoided by using a horseshoe Owens incision rather than the earlier Y-incision with a weak trifurcation in the area of the posterior hard palate removal. Two patients had mild transfusion reac-JAFEK, ET AL,: JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. T15 ai if, Ehotgmlcrograph (Hf and 1, x400) shows connective tissue matrix containing vascular gletts ned with a single layer of endothelial cells, ‘The rich vascularity and absence of con- fractile tissue in the walls of these vessels is responsible for the difficulty in controlling the bleeding which may occur spontaneously or operatively. tions. One required secondary revision of an alar stenosis caused by a Foley catheter. _ Many patients experienced moderate to marked rhinolalia aperta, which improved gradually over several months. Most noticed mild to moderate trismus which also gradually resolved. RESULTS, All patients have been seen in follow-up for one to 10 years. Seven pa- tients required more than one procedure, five of whom were subsequently shown to have intracranial extension of tumor, There were five patients with residual tumor following one or more attempts at resection. All of these patients were shown to have intracranial extension on angiography. One of these (HE) remains asymptomatic despite residual tumor demon- strated angiographically five years postoperatively, A second (CV) is asymptomatic, although intracranial extension was shown on the initial angiograms. Postoperative angiography was not obtained, although it is felt that residual tumor may be present. There was one operative mortality ina patient with large bilateral mid- dle cranial fossa extension (JI L).716 JAFEK, ET AL.: JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. Fig. 5. Basal view of bilateral carotid arteriogram during venous phase demonstrates naso- pharyngeal component (NP) with pterygomaxillary extension (PIM). Of the 20 patients without intracranial extension of tumor, all are asymptomatic and free of disease. Two required a second procedure to ac- complish total eradication of the neoplasm. Considering, therefore, only the cases without middle cranial fossa extension, the surgical cure rate is 100 percent in 20 patients. F DISCUSSION. Eleven of our patients (44 percent) had previously undergone adeno- tonsillectomy, one at the age of 14, requiring two units of blood, leading to the diagnosis, This is in contrast to Schiff’s and Tabb’s earlier obser- vations that patients with this neoplasm had rarely undergone adenoidec- tomy” and tends to contradict the theory that adenoidectomy in pre- pubescent males could remove the nidus of vascular tissue that causes the periosteal reaction. Pre-operative carotid angiography including anterior-posterior and later-JAFEK, ET AL.; JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. 17 Fig. 6, Lateral view utilizing subtraction technique of external carotid arterlogram shows large ploryeomaxiliary space extension (erat suppited primarily by the Internal maxillary ar tery’ (ista)s Nasopharyngeal component (NPS ig also seen. al skull views was obtained in 84 percent of the patients reviewed with ad- ditional vertebral studies in 16 percent, ‘as mentioned previously. It is often difficult to determine the site of tumor origin by clinical examina- tion; therefoie, bilateral carotid studies are indicated. A basal skull view was included with the external carotid injection. Blood supply to the tumor was best shown in the lateral and AP views, while the basal view was most helpful in localizing the tumor and demonstrating lateral pterygomaxil- lary extension (Fig. 5). Sources of blood supply can often be predicted quantitatively, indicating which cases can be approached more easily utiliz- ing external carotid artery occlusion. Subtraction technique was helpful in clarifying questionable areas by eliminating the overlying bony struc- tures***4 (Fig. 6). The radioangiographic characteristics have been previ- ously discussed by Rosen, et al.?* Angiographically demonstrated intracranial extension predicts greatly increased operative blood loss and risk, because of the probable subtotal resection of the tumor and may dictate consideration of other modalities, such as irradiation, in life-threatening situations, Thirty-six percent of the patients received pre-operative estrogen ther- apy, consisting of Stilbestrol 2.5-5 mg. orally three times daily for two to four weeks. The larger dose is currently advocated when estrogens are used, Clinically, in some cases, estrogens appear to decrease bleeding and to de- crease the size and increase the solidarity of the tumor mass, although the718 JAFEK, ET AL.: JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. evidénce remains inconclusive on these points. They have been reported to produce an increase in collagen deposition and fibrosis, and, therefore, to decrease tumor vascularity.** Detailed light or electron microscopic comparison studies were not carried out on the tumors in this series to confirm these reports. ° The average blood loss in nine procedures in. which pre-operative estro- gens were used was 1,970 cc., while in 25 procedures not preceded by es- trogen therapy, the average loss was 2,960 cc. This two-unit reduction of blood loss agrees with Conley’s earlier observation in three patients.® Transient nipple enlargement and hyperpigmentation with breast ten- derness was noted in almost all patients. The hormone was discontinued after surgery and brought reversal of these changes. Ligation of the ipsilateral carotid artery has been advocated by some™®"” and felt to be unnecessary by others.*1%?* The average blood loss in our series in 20 procedures (without correlation to the use’of estrogens) in which this was done was 2,490 cc, while in 18 non-ligated cases, the aver- age loss was 3,160 cc, a difference of almost one and one half units. Liga- tion was done only in those cases in which arteriography had shown the major blood supply to the tumor to be from the external carotid system. Several attempts at clinically demonstrating decreased blood flow, by in- cising the tumor mass with and without external carotid ligation, failed to show any decreased blood flow; however, exact measurements of blood flow have not been attempted. Bilateral ligation of the external carotid artery (temporary) in four cases resulted in an average loss of 1,400 cc. and was not accompanied by adverse complications. In seven cases receiving both pre-operative estrogen and ligation of the ipsilateral carotid artery, the average blood loss was 1,960 cc, while in 11 with neither measure, the average loss was 8,370 ce. : The average loss for 11 procedures on patients with proven intracranial extension was 8,390 cc. It is recognized that the cases in these groups were not paired and in no way represent a prospective study of the effects of pre-operative estro- gen therapy or intraoperative ipsilateral external carotid artery ligation; however, it would seem that retrospective review of this series suggests the value of these adjunctive methods in order to decrease operative blood Joss and to allow better tumor visualization, Arteriography is helpful in predicting those cases in which ligation of the artery may prove most ben- eficial. The most important step in the operative procedure is the incision through the basisphenoidal fascia to circumscribe completely the tumorJAFEK, ET AL.: JUVENILE NASOPHARYNGEAL ANGIOFIBROMA, 719 in the nasopharynx. This fascia can be reflected toward the tumor from several sides isolating the feeding vessels and facilitating complete re- moval in one piece without excessive bleeding. The failures were almost uniformly those cases in which the mass was removed piecemeal. The re- moval of sufficient hard palate to visualize the entire nasopharyngeal cir- cumference of the tumor is essential in this respect and resulted in no significant functional impairment in our series. BIBLIOGRAPHY, 1, Rinoenrz, N.: Pathology of Malignant Tumors Arising in Nasal and Paranasal Cavities and Maxilla, Acta Otolaryngologica, Stockholm, Sweden, Suppl. 27:1-405, 1938. 2, Brunner, H.: Nasopharyngeal Fibroma. Ann. Otol., 61:29-68, 1942. 3. Sommrs, M.: Juvenile Nasopharyngeal Angiofibroma. Tae Larynaoscore, 69:981-1016, 1959. . 4, Firzparniox, P, J.: The Nasopharyngeal Angiofibroma. Olin. Radio., 18:62-68, 1967. 5. Conzey, J., pr at.: Nasopharyngeal Angiofibroma in the Juvenile. Surg., Gynec. and Obst., 126:825-837, 1968. 6, Karatay, S.; Karmotootu, S. and Hrozpen, 0.: Significance of Hormones in the Pathogenesis of Nasopharyngeal Angiofibroma. Acta Otolaryngologica, 56:362-369, 1963. 7. Pressman, J. J.; Nasopharyngeal Angiofibroma. Arch, Otol., 76:167-173, 1962. 8. Brianr, T. D, R.; Firzrarnior, P. J., and Boox, H.: The Radiological Treatment of Juvenile Nasopharyngeal Angiofibroma. Ann. Otol., 79:1108-1113, 1970. 9. Martin, H.; Bunion, W. B., and Aners, J. C.: Juvenile Nasopharyngeal Angio- fibroma, Ann, Surg., 127:513-536, 1948. 10. Arosrat, J. V., and Frazetn, B. cer, 18:869-873, 1965. 11, Saurz, M: F. W.; Boxes, R., and Worx, W. Cryosurgical Techniques in Re- moval of Angiofibromas. Tae Lanyncoscors, 74:1071-1080, 1964. 12. Dm Santo, L. W.: Symposium on Malignancy, III, The Curative, Palliative, and re ‘Uses of Cryosurgery in the Head and Neck, Tae Lanynaoscorn, 82: 1282-1291, 9" Juvenile Nasopharyngeal Angiofibroma. Can- 18, Fir, F. A.: Fibromas of the Nasopharynx, Jour. A.M.A., 115:665-672, Aug. 81, 1940. U4, Enmox, J. B.: Juvenile Fibromas of the Nasopharynx, Ann. Otol., 62:277-281, 1955. 16. Jenep, B.; ANnagaro, A., and Banyp, I.: Juvenile Nasopharyngeal Angiofibroma. A Clinical Study of 69 Cases. Acta Radiol., 9:302-310, 1970. Hire Parrenson, C. N.: Juvenile Nasopharyngeal Angiofibroma. Arch. Otol., $1:270-277, 1%, Roserson, G. H., er aL.: Presurgical Internal Maxillary Artery Embolization in Juvenile Angiofibroma. Tre LanyNooscorg, 82:1624-1532, 1972. 18. Acuna, R. T.: The Nasopharyngeal Fibroma and Its Treatment. Arch. Otot., 64: 451-456, 1956, 19. Burien, R. M.; Nanum, A, M., and Hanares, H.: New Surgical Approach to Naso- pharyngeal Angiofibromas. Trans. Amer, Acad. of Ophthal. and Otolaryngol, 71:92-103, Jan-Feb., 1967. 20. Owens, H.: Observations in Treating Seven Cases of Choanal Atresia by the ‘Transpalatine Approach, Tne Lanynaoscorn, 61:304-319, 1951. 21, Canpana, D, S.: Nasopharyngeal Fibroma, Extension Into the Cheek, Arch. Otol., 81:584-588, 1965. . 22, Soumr, M.: Discussion of Paper by Butler, rr at.” Trans. Amer, Acad. of Ophthat, and Otolaryngol. 71:103-104, 1967.720 JAFEK, ET AL.: JUVENILE NASOPHARYNGEAL ANGIOFIBROMA. 23, Hanpousa, A.; Fan, H. and Erw1, A. M.: Nasoy pharyngeal Fibroma: Clinico- pathological Study of 70 Cases..Jour. Laryngol. and Otol., 68:647-666, 1964, 24, Zippeses pes Prantes, B. G.: Subtraktion. Georg Theme, Stuttgart, Germany, 1961. 25. Rosen, L.; Hanarur, W., and Naum, A.: Nasopharyngeal Fibroma. An Angio- graphic Evaluation. Radiol., 36:1084 107, 1966, 26, Wataxe, J., and MacKay, B.: Nasopharyngeal ‘Angiofibroma: Light and Blectron Microscopic Changes After Stilbestrol Therapy. Tue Larynooscore, 80:1109-1121, 1970, 27. Sany, L, L., and Grnats, I, H.: The Blood Supply of the Nasopharyngeal Fibromata, Jour. Laryngol. ‘and Otol, 81:1405- 1408, 1966. 28. Porrmveria, R. J.: The Nasopharyngeal Angiofibroma in the Adolescent Male, Jour, Pediat., 64:260-267, 1964, SECOND INTERNATIONAL CONGRESS ON CLEFT PALATE. The Second International Congress on Cleft Palate will be held in Copenhagen, Denmark, August 26-31, 1973. Dr. P. Fogh-Anderson, DK- 2000, Copenhagen F, Denmark, is Secretary-General of the Society. aah further information, contact Dr. Anderson. CENTENNIAL CONFERENCE ON LARYNGEAL CANCER. The Centennial Conference on Laryngeal Cancer will be held in Toronto, Canada, May 26-31, 1974. The scientific program will feature internationally renowned authori- ties in surgery, radiotherapy and pathology, and will encompass the knowl- edge accumulated on laryngeal cancer since the first laryngectomy a century ago. The aim of the conference is to resolve the differences of opinion as to the treatment of cancer of the larynx, to establish guidelines for research and to contribute to better methods of early diagnosis of the disease. Registration is limited. For further information, please write: Professor D. P, Bryce, Secretary General, 92 College Street, Toronto 2, Ontario, Canada. 5,0,748,9,20,21,12,1,2,8)4