Esophagoscopy was started by Adolf Kussmaul (1868). A brass tube, 47 cm in length and 1.3 cm in diameter, was inserted into the esophagus by a sword-swallowing entertainer, and Dr. Kussmaul observed the esophagus with Desormeaux's light source. After that, Killian, Bruenings, and Jackson further developed esophagoscopy with their own instruments. According to questionnaires in 229 hospitals in Japan, the Jackson-type of rigid scope was still used in 76% in 1965. The flexible esophagofiberscope was developed from American Cytoscope Makers, Inc. by Philip A. LoPresti (1964). In Japan, the esophagofiberscope was developed by the Olympus company and the Machida company after 1965. The push button system on the control unit of the Olympus EF was an excellent device for the manipulation of the instrument in the esophagus. The imaging and angulation mechanisms of the fiberscope have improved rapidly, and, moreover, a small-sized esophagofiberscope (EF-P₂, EF-P₃) has been developed. These became safer and easier to use in screening examinations of the esophagus. Later, esophago-gastro-duodenal fiberscope (panendoscope for upper G1 examination) was developed by LoPresti P.A. (1971) for use in emergency endoscopy of the upper G1 bleeding. At almost the same time, a long gastrointestinal fiberscope (GIF-D) was produced by Olympus for export. This was a forward-viewing fiberscope, 1100 mm in length and 13 mm in diameter with an angulation mechanism accomodating four directions. Later still, a small-sized panendoscope (GIF-P₂), 9 mm in diameter with 200° angulation at its distal portion, was also developed by Olympus. It was used for routine screening-examinations of the esophagus, stomach and duodenum and had no blind areas. Endoscopic iodine (Lugol) staining came into use for the fine examination of the esophagus. Based on Schiller's test (1933) for the diagnosis of cervical cancer of the uterus, Voegeli (1966), Rywlin (1970), Brodmerkel (1971) and Nothmann (1972) applied iodine (Lugol) staining in auxiliary diagnostic procedures of esophageal diseases, in particular, for the definite diagnosis of esophagogastric junction in reflux esophagitis and of early esophageal cancer. Since 1974, Japanese doctors have used endoscopic iodine staining of the esophagus. With this technique, the detection of mucosal cancer of the esophagus has become easier and the number of mucosal cancers of the esophagus detected has increased year by year. Since 1987, the minimally invasive treatment, that is, endoscopic mucosal resection (EMR) has been performed for mucosal cancer of the esophagus. Three typical procedures of EMR, i.e. the 2-channel method (Momma), the EEMR-tube method (Makuuchi) and the EMR-cap method (Inoue), are widely performed. Absolute indication for EMR of the esophagus is considered to be as follows: (1) m₁, m₂ cancer, (2) less than 3×3 cm or less than a third of the circumference of the esophagus, (3) less than 3 lesions, and (4) no lymph node metastasis. However, the enlargement of the EMR can be considered due to the recent remarkable advancements in these techniques. In conclusion, I talked about the rigid esophagoscope, flexible esophagofiberscope, long esophagogastroduodenal fiberscope, endoscopic iodine staining and EMR procedures as the historical progresses of esophagoscopic examination.

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Pneumonia is a common cause of death in older people. Antimicrobial drugs do not prevent pneumonia and, because of increasingly resistant organisms, their value in curing infection might become even more limited. Establishing new strategies to prevent pneumonia through consideration of the mechanisms of this devastating illness is essential. The purpose of this review is to discuss how pneumonia develops in the elderly and to suggest preventive strategies that may reduce the incidence of pneumonia among them. Aspiration of oropharyngeal bacterial pathogens into the lower respiratory tract is one of the most important risk factors for pneumonia; impairments in swallowing and the cough reflex among older adults (e.g., related to cerebrovascular disease) increase the risk for the development of pneumonia. Thus, strategies to reduce the volume and pathogenicity of aspirated material should be pursued. For example, since both swallowing and the cough reflex are mediated by the endogenous substance P, pharmacologic therapy using angiotensin converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in a lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine (and, of course, prevention of cerebral vascular disease, which can result in basal ganglia strokes) could also affect the incidence of pneumonia. Thus, promising pharmacologic treatments for preventing pneumonia in the elderly and other proven strategies, e.g., infection control and cerebrovascular disease prevention, might lessen the incidence of pneumonia.

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It is well known that multiple primary cancers frequently occur in the upper aerodigestive tract. In this study, we evaluated the incidence of multiple primary cancer of the upper aerodigestive tract and patient survival. From January 1995 to September 2001, 285 patients with head & neck cancer, 136 patients with esophageal cancer and 652 patients with lung cancer underwent surgical resection and/or chemoradiotherapy at our institute. Multiple primary cancers were found in 12 patients: head & neck and esophagus cancer in 6, head & neck and lung cancer in 2, and lung and esophagus cancer in 4. All of the patients were male, heavy smokers, and drinkers. Synchronous multiple cancer was found in one patient and metachronous multiple cancer in 11. The second cancer was found at a mean interval of 4 years (range: 0-10 years) after the onset of the first cancer. In two patients, an early-stage cancer was found in the esophagus and hypopharynx by screening fiberscopy. Ten patients complained of symptoms due to their second cancer. The TNM stage of the second cancer was I or II in 7 patients, and III or IV in 5 patients. The 5 year survival rate was 100% in patients with cancer of the head & neck and lung, 65% in patients with cancer of the head & neck and esophagus, and 50% in patients with cancer of the lung and esophagus after the first cancer treatment. In conclusion, the prognosis for patients with multiple primary cancers in the upper aerodigestive tract is determined in part by the presence or absence of esophageal cancer. It is important that esophageal cancer be found in its early stages.

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We studied the clinical features and surgical outcomes of multiple primary malignancies originating from head, neck and esophagus in resected cases of lung carcinoma as compared with multiple primary malignancies in other organs and non-multiple primary lung carcinoma cases. One hundred twenty-eight lung carcinoma cases out of 1279 resected cases with lung carcinoma presented other malignancies in other organs at our clinic from 1985 to 1999. The multiple-organ carcinomas consisted of 14 cases involving head and neck, 12 cases involving esophagus, 24 cases involving stomach, 33 cases involving colon, 17 cases involving hepatoportal organs, 28 cases involving genitourinary organs, 6 cases involving breast, 3 cases involving thyroid gland, 3 cases involving lymph and other organs, including 117 cases of double (91.4%), 10 cases of triple (7.8%), and a case of quadruple (0.8%) carcinoma. Forty cases were subsequent to lung carcinoma, 66 cases were prior to lung carcinoma, and 22 cases were synchronous within 6 months. The smoking index of the cases in the A group (which included head, neck and esophagus malignancies) was significantly higher than that of the B group (which included other multiple malignant cases) or the C group (which included non-multiple primary lung carcinoma cases). The means of the smoking index for these groups were: 1031, 693, and 714 repsectively, p=0.0174, p=0.0192. Moreover, as for histology, the number of cases with squamous cell carcinoma was significantly higher than that with adenocarcinoma in the A group, as compared to the B and C groups (squamous cell carcinoma: adenocarcinomas=18:5, 32:61, and 394:648 respectively, p<0.0001, p<0.0001). Multiple malignancies, including lung carcinoma, have tended to increase in the past few years. The development of multiple malignancies in lung carcinoma patients including head, neck or esophagus carcinoma, may be significantly related to smoking status.

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Our biological and experimental findings on double esophageal carcinomas were reported. First, endoscopic screening and Lugol's staining of the esophagus was performed for head and neck cancer patients after treatment of primary lesions. Unstained lesions were found in 17 cases (29%), of which 7 cases (41%) revealed a positive p53 of biopsy samples in immunohistochemical staining. Moreover, 10 (24%) of the 41 normal stained cases revealed a positive p53 in samples biopsied from the middle esophagus. On the other hand, the microsatellite instability (MSI) of dysplastic lesions coexisting with esophageal carcinomas was investigated. Twenty-one (78%) of 24 dysplastic lesions of mutator phenotype esophageal carcinoma revealed a positive MSI, whereas only 5 (29%) of 17 dysplastic lesions of non-mutator phenotype esophageal carcinoma did so. These facts suggest that certain biological markers might predict secondary carcinomas in the esophagus and head and neck. Second, an epidemiologic study showed a high incidence of esophageal carcinoma after gastrectomy. The esophagus after gastrectomy was exposed to a more alkaline circumstance due to the reflux of duodenal juice, especially pancreatic juice, to the esophagus, which these seemed to cause the carcinogenesis in our patients. Therefore, preventive procedures against reflux esophagitis after gastrectomy should contribute to not only QOL but also to the prevention of secondary esophageal carcinoma.

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The clinical aspects of esophageal cancer associated with other primary cancers were discussed.
Patients and Method: Among 263 patients who had curative resections for esophageal cancer at our department between 1986 and 1998, 53 patients (20.2%) had primary cancer in other organs. The clinicopathologic factors, therapeutic strategies, and outcomes were studied in these patients.
Results: Other primary cancers were found symchronously in 23 patients and metachronously in 30. Other primary cancers were found in the following organs: stomach in 21 patients, head and neck in 16, liver in 3, colon in 3, lung in 3, breast in 3, kidney in 2, prostate in 2, and uterus in 2. Leukemia developed in 1 patient. There wes no difference in the clinicopathologic factors between patients with and without other primary cancer. Among 18 patients in whom gastric cancer was found synchronously or antecedent to esophageal cancer, reconstruction was performed with preserved stomach after curative resection for gastric cancer in 4 patients. For the other 14 patients, reconstruction using jejunum or colon was performed in 8 and 6 patients, respectively. Cancer was found in the stomach used as esophageal substitute in 3 patients. The cancer was curatively treated with endoscopic mucosal resection in 1 of these patients and with gastrectomy with jejunal reconstruction in 1 patient. The other patient at high risk is on TS-1 and has survived cancer free for 2 years. The head and neck cancers were treated with surgery in 7 patients and chemoradiotherapy in 9. The survival rate was 44% and 40% in the patients with and also other primary cancer, respectively, at 5 years after esophagectomy. The most significant factor in the multivariate analysis for prognosis was lymph node metastasis of esophageal cancer.
Conclusions: Other primary cancers were found in 20% of our patients with esophageal cancer. Association of gastric cancer, which was most common, required an organ other than the stomach for reconstruction. Because the association of other primary cancers did not reduce the survival rate for esophageal cancer, radical treatment for each malignancy is essential for a good outcome.

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Between 1985 and 2000, 128 esophageal cancer patients underwent esophagectomy with resulting vocal cord paralysis (VCP). They were disease free at least 1 year after surgery. They were divided into Group A (63 patients operated on between 1985 and 1993) and Group B (65 patients operated on between 1994 and 2000). In 1993, we revised our surgical techniques in removing the recurrent nerve lymphatic chains in order to reduce postoperative VCP. Thus, we could compare these two groups of patients. Only two patients (3.1%) of Group B complained of severe hoarseness 1 year after surgery, as compared to 18 patients (28.6%) in Group A. Of the 108 patients who did not complain of severe hoarseness, the mean duration of their difficulty in talking was 3.3 months for Group B and 6.0 months for Group A. The incidence of the persistent VCP 1 year after surgery significantly decreased from 57.1% in Group A to 24.6% in Group B, mainly owing to a recovery from left recurrent nerve palsy. In the group of patients with severe hoarseness 1 year after surgery, daily activity and percentage of ideal body weight at 1 year had deteriorated. Severe hoarseness, therefore, does not seem to be an inevitable consequence of esophagectomy for cancer but rather to surgical maneuver and a poor nutritional state. From the viewpoint of quality of life, the permanent nerve paralysis caused by esophageal cancer surgery is worrisome and a factor in the deterioration of daily activity until it is adequately treated.

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Injection therapy to the vocal cords was performed for 87 patients with unilateral paralysis after esophagectomy. A bronchoscope was inserted transnasaly and atelocollagen was injected using a needle with a 4 mm-length tip. Injection was performed within 7 days after esophagectomy in 27 patients, within 14 days in 21 patients and within 30 days in 19 patients. As complications, 3 patients had nasal bleeding, 2 had laryngeal edema and 3 had fever. None of the 17 patients who recovered from their paralysis had any late complication in vocal cord function. Of the 48 patients who received injection within 14 days, 6 patients had pneumonia but none needed intubation, tracheostomy or mechanical ventilation. Injection therapy to the vocal cords using a bronchoscope was therefore useful to prevent pulmonary complications in patients with unilateral paralysis after esophagectomy.

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The authors examined 601 patients with recurrent laryngeal nerve paralysis (RLNP) between October 1976 and June 2001 at the Ehime University Hospital and Kumamoto University Hospital. The number of male patients was 1.3 times greater than that of female patients. Their ages ranged between 2 months and 87 years, with patients in their sixties and seventies being most frequent. RLNP patients whose problem was related to surgery totaled 27.3% in the first 10 years, while between 1986 and 1997, they totaled 50.6% and between October 1998 and June 2001 occupied 47.0%. Thus, RLNP problems related to surgery showed an increasing tendency. Thyroid surgery, intubation, and surgeries for esophageal cancer, cardiovascular diseases and lung cancer were the major frequent etiologies of RLNP related surgery, in this order. Even when these diseases were successfully treated, RLNP sometimes persisted to cause severe hoarseness, resulting in a deterioration in the patient's quality of life. The authors performed phonosurgical treatments such as arytenoid adduction and type I thyroplasty for 71 RLNP patients Although the phonatory functions of these patients improved after the treatment, nearly half of them did not reach a normal range of phonatory function. Three of the 38 patients who underwent arytenoid adduction had postoperative dyspnea and received a tracheostomy. Local edema and insufficient abdution of the vocal fold on the healthy side seemed to be a cause of dyspnea in one patient. The other two both had a history of esophagectomy and reconstruction with a gastric tube. The causes of their sudden dyspnea was considered to be laryngospasms resulting from the regurgitation of gastric juice.

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Since adjuvant disease related to silicone was reported, the indication of intrafold silicone injection for the patients with unilateral recurrent laryngeal nerve paralysis (ULRLNP) has been re-considered. In particular, the autologous fat injection technique has been reported as a safe method, and this procedure is now carried out frequently in Japan. In the present study, we compared the results of sillicone injection in 349 cases with the results of fat injection in 18 cases and found that postoperative voice function was excellent in both methods. In addition, no patients suffered from adjuvant disease in either group. Although intrafold autologous fat injection is a less invasive and safe alternative method for patients with ULRLNP, this procedure is not practical in thin patients. Our results indicate that percutaneous intrafold silicone injection is a usuful therapy for ULRLNP terminal patients, such as those with esophageal or lung cancer.

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In our department, 55 patients with bilateral vocal cord paralysis accounted for 9.8% of all cases of vocal cord paralysis between 1988 and 2000. The cause of the paralysis was non-surgical in 38 patients (idiopathic in 12, intracranial or nervous diseases in 8, trauma in 5, esophagus cancer in 4, lung cancer in 3, thyroid cancer in 2 and others), whereas the paralysis in 17 patients was due to surgical operations (esophageal surgery in 7, endotracheal intubation in 4, cardiovascular surgery in 2 and others). As for treatment, we performed a lateralization of the vocal cord (Ejnell's operation) in 8 patients, and a tracheostomy in 26 patients.
Recently, we performed a new technique for the lateralization of the vocal cord using an endo-extralaryngeal needle carrier developed by Lichtenberger and obtained good results. The advantages of this technique, in addition to the advantage of the Ejnell's operation, are as follows: (1) it is easy to arrange a thread in the proper position because the needle is inserted into the larynx via a direct laryngoscope with a microscope. (2) There is little invasion, because the thyroid cartilage is not exposed. Thus, this technique will continue to be very useful for lateralization of the vocal cord.

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The therapeutic effects of IGF-I gene transfer into denervated rat laryngeal muscle and GDNF gene transfer into rat nucleus ambiguus after vagal avulsion were investigated. Four weeks after IGF-I gene transfer, IGF-I transfected animals had a significant improvement in muscle fiber diameter and motor endplate morphology. GDNF transfected animals had a significantly larger number of surviving motor neurons in nucleus ambiguus two and four weeks after GDNF gene transfer. These results indicate that gene therapy for laryngeal paralysis may provide tremendous opportunity for augmentation of current surgical treatment modalities by preventing or reversing muscle atrophy and motor neuron death.

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