Department of Otolaryngology, Kurume University School of Medicine, Kurume, Japan

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THE KURUME MEDICAL JOURNAL Vol. 16, No. 3, 1969 PATHOLOGICAL STUDIES RELATING TO NEOPLASMS OF THE HYPOPHARYNX AND THE CERVICAL ESOPHAGUS IKUICHIRO HIROTO, YASUSHI NOMURA, KUSUO SUEYOSHI, SHIGENOBU MITSUHASHI, AKINORI ICHIKAWA AND HIROYOSHI KUROKAWA Department of Otolaryngology, Kurume University School of Medicine, Kurume, Japan (Received for publication June 4, 1969) Pharyngolaryngoesophagectomy is the most radical surgical procedure for carcinoma of both the hypopharynx and the cervical esophagus. CLASSIFICATION Seventy-seven cases of these diseases came under our surgical care for nineteen years since 1950 (Table 1). In the international classification of cancer, the hypopharynx belongs to "Head and Neck Sites" and the cervical esophagus to "Alimentary Canal" as a region of the esophagus. However, in the majority of our cases of pharyngolaryngoesophagectomy, the tumor was located at the boundary between the pharynx and the esophagus, namely pharyngoesophagus, extending to the both sites. Therefore, it may be more convenient to classify the sites of the tumor as shown in this table and to refer these diseases to one category, that is "hypopharyngoesophageal carcinoma". TABLE 1 Sites of Tumors (1950-1968) 127

128 HIROTO, I., ET AL. RESULTS OF SURGERY The prognosis of this disease is notoriously poor and our results are no exception. The results of pharyngolaryngectomy or pharyngolaryngoesophagectomy are shown in Table 2 and Figure 1. Fifty of them have died; a half of them within one year and more than 90% within 3 years after surgery. The death was caused by local recurrence of carcinoma in 60%, and by pulmonary metastasis in 15%. The results of surgery with respect to the site are presented in Table 3. Many of these cases were treated only by surgery without preoperative irradiation. Five year survival ratio was 44% in the tumor of hypopharynx, 33% in that of pharyngoesophagus, and 0% in cervical esophagus. The lower the tumor was located, the worse the prognosis was. As shown on the previous slide, 75% of unlucky cases died of local recurrence or lung metastasis. In order to improve the poor results of surgery for this disease, we have to study the cases of recurrence carefully as well as to investigate the excised specimens. RESULTS OF PHARYNGOLARYNGOESOPHAGECTOMY. (1950 `1965) Fig. 1 TABLE 2 Results of Pharyngolaryngoesophagectomy (1950-1968)

NEOPLASMS OF HYPOPHARYNX AND CERVICAL ESOPHAGUS 129 TABLE 3 Results of Surgery with Respect to Site (1950-1965) REASONS FOR FAILURE The site of recurrence of tumors after surgery is indicated in Table 4. On this table, it is remarkable that 1) the recurrence in the mesopharynx was found more often than in the cervical esophagus. This indicates that the tumor should be dissected more carefully at the upper margin than at the lower, 2) the recurrence in the paratracheal lymphnodes was noticed in cases of the tumor in any location, especially often in the cervical esophagus carcinoma. The recurrent tumor in the deep or superficial cervical lymphatic chain can be excised successfully again, but the recurrence in the paratracheal nodes is difficult to be controlled. The dissection of paratracheal nodes should be done completely and very carefully in the first surgery. TABLE 4 Causes of Death due to Recurrence PATHO-ANATOMICAL OBSERVATIONS Twenty-nine specimens were studied from the stand point of clinical pathology. Histologically, the material consisted of 26 specimens of differentiated squamous cell carcinoma and only 3 of undifferentiated. It indicates that Bleomycin, a new anticancer drug, is useful for this carcinoma, because of its special efficiency to the differentiated squamous cell carcinoma. The preoperative application of Bleomycin may be profitable in controlling the tumor as well as the lung metastasis. The Figure 2 shows the longitudinal extent of the tumor in each specimen as vertical lines. The upper margin of the tumor was found at the

130 HIROTO, I, ET AL. EXTENT OF TUMOR IN 29 SPECIMENS. Fig. 2 level of the superior margin of the epiglottis in the most upward extended case and the lower margin was at the fifth tracheal cartilage or below, in the most downward extended case, the carcinoma is mostly located around the inferior border of the cricoid cartilage, the region of the pharyngoesophagus, extending to both pharynx and esophagus. In all the 25 cases in which the thyroid gland was removed with the tumor, adhesion was so firm that separation of the thyroid gland from the tumor was very difficult. Invasion of the carcinoma into the thyroid gland was histologically demonstrated in 9 of 25 cases, that is one third of the cases. Some surgeons perform total thyroidectomy regardless of possible postoperative tetany, but I prefer to excise only one lobe of the thyroid gland on the more involved side and conserve the other if possible. The larynx or trachea was involved in 6 of 29 cases; that is one fifth of all the cases. The mucous membrane of the hypopharynx and the cervical esophagus was involved almost all around the circumference in more than 70% of the specimens. The invasion of carcinoma into the muscle layer was also observed in the similar ratio; however, there was no case in which the tumor had destroyed the entire Fig. 3

NEOPLASMS OF HYPOPHARYNX AND CERVICAL ESOPHAGUS 131 muscle layers. These findings may suggest that the carcinoma extends easily to the inner layer of the musculature, but, thereafter, it spreads more rapidly along the surface of the tube than invades the deeper musculature. It may be subject to the anatomy of the lymphatic system. The lymphatic system in the hypopharynx and the cervical esophagus consists of three lymphatic networks; two in the mucous membrane and one in the submmucous coat as shown in Fig. 3. The superficial and the deep mucosal networks has dense meshes elongated longitudinally along the tube. The submucosal network has coarse meshes spread in the submucous coat. These lymphatic networks are connected with each other. In the muscle layer of the hypopharynx and the cervical esophagus, no lymphatic network exists. Collecting lymphatic vessels from these networks run through the muscle layer directly to the cervical lymphnode. The estimate of carcinomatous expansion under the mucous membrane is very important in making dicision of the level for dividing the tumor from the normal part. In 25 cases, who came under our observation submucosal extension was more expansive at the upper margin of the tumor than the lower; that is, it was measured 11 mm upward on average (from 20 mm to 3 mm) and 5 mm downward (from 10 mm to 2 mm). According to these figures, dissection must be done 2 or 2.5 cm above, and 1 or 1.5 cm below the visible tumor (Fig. 4). Fig. 4 The cervical lymphatic system consists of the deep cervical lymphatics along the jugular vein, the superficial cervical lymphatics along the accessory nerve and the paratracheal lymphatics along the recurrent laryngeal nerve. The regional lymphnodes of the cervical esophagus are the paratracheal nodes. The cervical esophagus sends its lymph either via paratracheal nodes or directly into the inferior nodes of the deep cervical chain (Fig. 5). The lymph from the hypopharynx usually f lowa direct into the superior nodes of the deep cervical chain. However, if these superior lymph nodes are clogged by a metastatic carcinoma,

132 HIROTO, I., ET AL. Fig. 5 flow into the paratracheal lymph nodes may take place in the form of the socalled paradoxical metastasis, which has to be fully taken into consideration. The site and size of the paratracheal lymphnodes in normal subject showed large individual variations as illustrated in this slide. The majority of the normal nodes was 5 mm or smaller in diameter. Then, the lymph nodes larger than 5 mm in diameter must be excised as pathologic, with suspected metastasis. A dead space remains in the upper mediastinum after excision of the paratracheal lymphnodes with adjacent tissues. It is desirable to fill the dead space with pedicle grafts of sternohyoid and sternothyroid muscles. DISCUSSION AND CONCLUSION Table 5 shows a comparison of our results of pharyngolaryngoesophagectomy for the first 10 years and for the latest 6 years. The results in the latter is remarkable better than in the former; that is, improved by about 20% in 3 year survival ratio and by about 15% in 5 year survival ratio. The main surgical procedure was the same in both periods; but, in the latter period, the surgery was carried out under consideration of above mentioned clinico-pathological findings and the neckdissection was also performed more completely than in the earlier period. I mentioned a new chemotherapeutics, " Bleomycin " which is very effective to the differentiated squamous cell carcinoma. The results of pharyngolaryngoesophagectomy will be surely improved by the combination with The Result TABLE 5 of Pharyngolaryngoesophagectomy

NEOPLASMS OF HYPOPHARYNX AND CERVICAL ESOPHAGUS 133 the preoperative application of Bleomycin as well as the irradiation. I expect now a brilliant future in the treatment of this disease. REFERENCES 1) ALONSO, JUSTO M. Surgical treatment of the Retrocricoid cancer. Acta oto-laryng. (Stockh.) 60, 283-286, 1965. 2) COLEMAN, FRANK PHILIP and BRAWNER, DONALD L.: Carcinoma of the cervical esophagus. Arch. Surg. 62, 102-111, 1951. 3) FEMENIC, B. and SUBOTIC, R.: Certain problems in the surgical treatment of postcricoid carcinoma. Laryngoscope. 72, 1346-1350, 1962. 4) FENDEL, K., TEICHERT, H. and FUNK, G.: Die Behandlungsergebnisse Zanges beim Larynx- nud Hypopharynx- Karzinom in Jena 1932-1955. Z. Laryng. Rhinol. 41, 318-328, 1962. 5) GRIMES, ORVILLE F. and STEPHENS, H. BRODIE: The surgical treatment of carcinoma of the hypopharynx, larynx, and upper esophagus. J. Thorac. Surg. 24, 246-255, 1952. 6) HARRISON, D. F. N.: Pharyngo-esophageal replacement in post-cricoid esophageal carcinoma. Ann. Otol. (St. Louis) 73, 1026-1041, 1964, 7) HARRISON, D. F. N.: Surgical management of cancer of the hypopharynx and cervical oesophagus. Brit. J. Surg., 56, 96-103, 1969. 8) HIROTO, IKUICHIRO: Hypopharyngoesophageal carcinoma, its surgical treatment. Kurume med. J. 10, 162-172, 1963. 9) LEDERMAN, M.: Cancer of the pharynx; a study based on 2417 cases with special reference to radiation treatment. J. Laryng. 81, 151-172, 1967, 10) RAVEN: Cancer of the pharynx, larynx and oesophagus and its surgical treatment. Butterworth, 1958.