Radiotherapy of T1 glottic cancer with 6 MeV X rays.

We treated 154 patients with T1 glottic carcinoma with 6 MeV X rays through 16 cm2 parallel-opposing open fields on a free set-up delivering a median dose of 67 Gy in 6 2/3 weeks. Observed and relative 5-year survival rates for all patients were 87% and 100%, respectively. The local control rate at 5 years was 89%. Of 18 patients who clinically had local recurrence, 17 were salvaged by a secondary treatment. There were no complications requiring medical or surgical attention. A tendency toward increasing local control rates with increasing total doses was observed in the range between 57.5 Gy and 72.5. No significant correlation was found between local control rates and field size, daily dose, or the technique used. A tendency toward a lower local control rate was noted for patients whose anterior commissures were grossly involved; however, it is not known if this could be attributed to the use of 6 MeV X rays. The results are comparable to those obtained with 60Co as reported in the literature. It is concluded that 6 MeV X rays on a free set-up delivering 65-70 Gy in 6 1/2-7 weeks can be used satisfactorily for the treatment of early glottic carcinoma.

Stage I-II carcinoma of the anterior two-thirds of the tongue treated with different modalities: a retrospective analysis of 244 patients.

Treatment results of 244 patients with stage I-II cancer of the mobile tongue were analyzed according to the modalities employed (implantation, surgery, cryosurgery and intraoral irradiation). Overall local control rates at three years were 90 +/- 3% for implant, 89 +/- 7% for cryosurgery, and 84 +/- 9% for surgery. Local control rates in stage II patients treated with intraoral electron irradiation, however, were only 50 +/- 13%. Five-year survival rates were 72 +/- 3% with no significant differences observed in patients with either stage I or stage II regardless of treatment modality. Sixty percent (29/48) of the patients with local recurrences were salvaged by the second treatment. Since the local control and survival achieved by these modalities were similar, with the exception of patients with stage II treated by intraoral electron irradiation, we recommend interstitial implantation with iridium, intraoral electron irradiation or surgery for patients with T1 tumors, and iridium implantation or surgery for patients with T2 tumors. For those with superficial lesions measuring 5 mm or less in thickness, cryosurgery is being offered as an alternative. The patient can choose the treatment modality taking into account his/her age, sex and profession.

A new concept and technique for reconstruction of the lower pharyngeal space using the free jejunal graft.

OBJECTIVE: To report on a new concept and simple operative procedure to conform the diameter of the oral end of free jejunal grafts to that of pharyngeal defects for reconstruction of the lower pharyngeal space. DESIGN AND METHODS: A preliminary study showed that the jejunum is supplied by a highly vascular network and that longitudinal paramesenteric incisions can be made without disturbing the blood supply of the jejunum. We then developed the following operative procedure. The position of the highest point of the pharyngeal defect and the site of the recipient vessels are determined. The free jejunal graft is positioned with its mesentery in correspondence with the location of the recipient vessels. The position of a longitudinal incision 180 degrees to the highest point of the defect is then determined. After the oral border of the jejunum is opened with scissors, a pharyngojejunal end-to-end anastomosis is performed. PATIENTS: Eighteen patients with defects of the lower pharyngeal space after cancer treatment. RESULTS: We transferred jejunal grafts in 18 patients using this operative procedure. In 7 of these patients, paramesenteric incisions were made. The lengths of the incisions ranged from 2 to 8 cm. Transfer was successful in all 18 patients. Postoperative leakage occurred in 1 patient in whom an antimesenteric incision had been made; however, a fistula did not develop. CONCLUSIONS: Our method allows defects of the lower pharyngeal space to be reconstructed with end-to-end anastomosis of free jejunal grafts regardless of the location of the defect or of recipient vessels. This method is simple and appropriate for correcting large pharyngeal defects.

Versatility of the free anterolateral thigh flap for reconstruction of head and neck defects.

OBJECTIVE: The anterolateral thigh flap has many advantages in head and neck reconstruction. However, it has not yet come into widespread use because of the anatomic variations of its perforators. Herein, we describe a safe operative technique related to the patterns of the perforators and discuss its wide versatility. SETTING: A national cancer center hospital. PATIENTS: Thirty-eight anterolateral thigh flaps were transferred. Confirmation and dissection of the flap pedicle were simultaneously performed with tumor resection. The design and elevation of the flap were carried out immediately after the tumor resection was completed. RESULTS: From the study of the anatomic variations of the perforators, septocutaneous patterns were recognized in 10 cases (26.3%) and musculocutaneous patterns in 28 cases (73.7%). All flaps were easily and safely elevated with our techniques. Thirty-six flaps survived. Partial necrosis was noted owing to excessive thinning procedure in one patient and total necrosis was noted owing to venous thrombosis at the anastomosis part in another patient. CONCLUSIONS: We found that the anterolateral thigh flap has numerous advantages. It is possible to perform the flap elevation and the tumor resection simultaneously. The flap is generally thin and is suitable for reconstruction of intraoral defects. Combined flaps with neighboring tissues and other, distant flaps can be used. Furthermore, since our technique minimizes the problems of confirmation and dissection of the perforators, we conclude that this flap can be successfully used to repair a variety of large defects of the head and neck.

Postoperative complications and functional results after total glossectomy with microvascular reconstruction.

Microsurgical reconstruction after total glossectomy can greatly improve quality of life; however, postoperative functional results are often unstable, and the effectiveness of total glossectomy remains questionable. To determine the problems of reconstruction after total glossectomy with laryngeal preservation and to examine the functional results of swallowing and speech, 30 patients who had undergone total glossectomy and reconstruction with free flaps were reviewed for this study. The patients ranged in age from 20 to 73 years, and 23 of the 30 had undergone reconstruction with a rectus abdominis musculocutaneous flap. Wider and thicker flaps were designed and transferred and were sutured to suspend the larynx. To maintain physiologic swallowing function after surgery, the extent of laryngeal suspension and cricopharyngeal myotomy was limited. Of the 30 patients, 21 (70 percent) could be decannulated with laryngeal preservation; 20 of these 21 could tolerate a normal/soft/pureed diet, and 1 was limited to a fluid diet. Speech was intelligible in 16 of the 19 patients evaluated. In 9 of the 30 patients, laryngeal function could not be preserved. In four of these nine patients, additional resection combined with total glossectomy caused severe aspiration and recurrent pneumonia. Two patients with preoperative cerebral dysfunction were also poor candidates for laryngeal preservation. Additionally, the transferred flap's lack of bulk in the oral cavity and the advanced age (73 years) of one patient and the poor motivation of another may have contributed to postoperative aspiration. Aspiration occurred in one patient because of local recurrence of a tumor. The presence of preoperative cerebral dysfunction (p = 0.025), resection of the epiglottis (p = 0.005), and postoperative orocutaneous fistulas (p = 0.04) were significantly associated with the failure of laryngeal preservation. However, because of the difficulty of enrolling a sufficient number of patients in the study and the inherent limitations of retrospective studies, multivariate analysis in this study showed that no factors, such as patient age, flap volume, and the type of neck dissection, were significant predictors of laryngeal preservation. Although prospective studies are necessary, the function of individual patients must be assessed so that the study experiences discussed here can be applied to subsequent patients.

Comparison of innervated and noninnervated free flaps in oral reconstruction.

Thirteen patients who had undergone ablative surgery for advanced squamous cell carcinoma in which more than half of the tongue had been resected underwent reconstruction in which the cutaneous nerve of a free flap was anastomosed to the stump of the transected lingual nerve. Eight of the patients underwent reconstruction with an innervated anterolateral thigh flap and five patients underwent reconstruction with an innervated rectus abdominis musculocutaneous flap. Sensory recovery of the flap at least 6 months postoperatively was compared in these 13 patients and in 16 additional patients who received noninnervated versions of the same flaps for the same defect. The degree of sensory recovery of innervated thigh flaps was significantly greater than that of noninnervated ones in all modalities and that of innervated rectus abdominis flaps was also greater than that of noninnervated flaps, except for hot and cold perception. These results indicate that sensory regrowth occurs in most areas through the surgically created pathways. However, results of Semmes-Weinstein testing showed that recovery did not reach the level of protective sensation in either type of innervated flap. Although these findings must be followed by additional objective and functional tests and the need for sensory reeducation should be considered, this simple operative procedure can improve postoperative intraoral function and should be attempted whenever possible after ablative surgery.

Lymphoscintigraphy of head-and-neck cancer.

To achieve the visualization of regional lymph nodes by lymphoscintigraphy, 21 patients with head-and-neck cancer were studied with the aid of 99mTc-labeled rhenium sulfur colloid (99mTc Re). Four injection sites were selected; the injections were given into the subcutaneous tissue of the parietal area of 11 patients, into the submucosa of the retromolar area of 6 patients, into the subcutaneous tissue of the postauricular area of 2 patients, and into the thyroid glands of 2 patients. Lymphoscintigraphy was done three hours after the injection. The cervical regions were visible in 85.7% of the patients on the affected side and in 90.5% on the healthy side. The visualization comprised the following regions: submental, submandibular, deep cervical, accessory, and supraclavicular regions. In total, 102 nodes were visualized on the affected side (average 4.8 per patient) and 110 nodes in the healthy side (average 5.5). Histologically, 15 of 21 patients had lymph nodes metastases and 6 did not. Of these 21 patients, 66.7% (14/21) had confirmed lymph node metastases in the visualized regions. This technique appears to be a relatively easy and efficient method of imaging the regional lymph nodes in head-and-neck cancer both before treatment and after neck surgery.

Comparative evaluation in pharyngo-oesophageal reconstruction: radial forearm flap compared with jejunal flap. A 10-year experience.

We reviewed 109 consecutive patients with cancer of the hypopharynx or cervical oesophagus who underwent free flap transfer for immediate reconstruction after total pharyngolaryngo-oesophagectomy. The free flaps used were either free jejunal (n = 70) or radial forearm flaps (n = 39). Significantly more fistulas (3/70 compared with 15/39, p < 0.0001) and strictures (6/64 compared with 13/33, p = 0.0008) developed in the radial forearm than the jejunal flap group. However, functional donor site morbidity was minimal and there were no cases of total flap necrosis in the forearm flap group. We consider that the free jejunal flap should be the first choice for total reconstruction of pharyngo-oesophageal defects. However, the forearm flap is suitable for elderly, high risk patients, because it is less invasive and has minimal donor site morbidity, which facilitates early recovery.

Closure of large pharyngo-oesophageal fistulas with free flap transfer after resections for cancer.

Postoperative salivary fistulas still remain a serious and potentially lethal problem in head and neck reconstruction particularly if the fistula is large and involving one half or more of the circumference of the pharyngo-oesophagus. Pedicled flaps have traditionally been the flaps of choice for closure of these fistulas, but the results are often disappointing. During the period 1982 to 1995, we have used either a radial forearm free flap or a jejunal free flap to close large and complex pharyngo-oesophageal fistulas after resection for cancer in 15 patients. Although two patients developed major fistulas that required additional operations for closure, successful closure was achieved in all but one case: the success rate was therefore 14/15 (93%). We consider that jejunal flaps are suitable for circumferential pharyngo-oesophageal reconstruction and forearm flaps for non-circumferential defects.

[A 74-year-old man with urinary incontinence, right leg weakness and multiple cranial nerve palsies].

We report a 74-year-old man with a lung cancer, who developed right leg weakness, neurogenic bladder, and multiple cranial nerve palsies. The patient was well until December of 1992, when he was 74-year-old, when he noted transient double vision; in February of 1993, he noted numb sensation and weakness in his right leg. Later in the same month, he developed overflow incontinence of urine and weakness in his right face. He also noted deafness in his left ear (he had a marked loss of hearing in his right ear since childhood because of otitis media). His weakness in his right leg had progressed, and he was admitted to our service on March 19, 1993. On admission, he was afebrile and BP was 130/50 mmHg. General physical examination was unremarkable. On neurologic examination, he was alert and oriented to all spheres; no dementia was noted nor were detected aphasia, apraxia, and agnosia. His optic fundi were unremarkable; ocular movement appeared normal, however, he complained of diplopia in far vision. Sensation of the face was intact. He had right facial palsy of peripheral type; he was unable to close his right eye, and Bell's phenomenon was observed on attempted eye closure. On the left side, he had facial spasm. He had marked bilateral deafness. He had no dysarthria or dysphagia. The remaining of the cranial nerves were intact. Motor wise, he was unable to stand or walk alone; weakness did not appear to account for his difficulty in gait; manual muscle testing revealed 4/5 weakness in his tibialis anterior muscle, 1/5 in the peroneus longus, 0/5 in his extensor hallucis longus and extensor digitorum longus, all on the right side. Brachioradial and quadriceps femoris reflexes were increased to 3/4; plantar response was equivocal on the right side, and flexor on the left. Sensory examination revealed loss of touch and pain sensation in the L5 and S1 distributions in his right leg: vibration and position sensations were also diminished in his right foot. He had overflow urinary incontinence with loss of bladder sensation. Marked nuchal stiffness was noted, however, no Kernig's sign or eye ball tenderness was present. Pertinent laboratory findings were as allows; WBC 8,100/microliters, Ht 42.5%, platelet 326,000/microliters, TP 6.8 g/dl, BUN 16 mg/dl, creatinine 0.54 mg/dl, glucose 95 mg/dl, Na 136 mEq/l, K 4.4 mEq/l, Cl 100 mEq/l; liver profile was normal; CEA 436.6 ng/ml, CA19-93 U/ml; urinalysis was normal.(ABSTRACT TRUNCATED AT 400 WORDS)

[Surgical treatment of differentiated thyroid cancer with tracheal invasion].

Thirty patients with tracheal invasion of differentiated thyroid cancer underwent partial resection of the tracheal wall between 1978 and 1996 at National Cancer Center Hospital. In most cases, the defect in the tracheal wall was reconstructed secondarily using a local flap. This method was easy in comparison with end-to-end anastomosis of the trachea following circumferential resection of the wall. Partial resection of the tracheal wall proved to be a effective treatment for thyroid cancer invasion of the tracheal, because of low incidence of local recurrence. When the defect of the tracheal wall was too large to be reconstructed using a local flap, hydroxylapatite was employed and good results were obtained.

Possible function and some properties of the CcpA protein of Bacillus subtilis.

The ccpA mutations alsA1 (alsA1 is allelic to ccpA) and ccpA::Tn917 completely abolished catabolite repression of gluconate kinase and sorbitol dehydrogenase synthesis in Bacillus subtilis, whereas they only partially affected the catabolite repression of inositol dehydrogenase, histidase and xylose isomerase synthesis. The alsA1 mutation also partially affected catabolite repression of sporulation. Analysis of revertants from the alsA1 mutant by direct sequencing indicated that this mutation comprises a base substitution of guanine at nucleotide -14 to adenine within the Shine-Dalgarno sequence of the ccpA gene (ccpA translation starts at nucleotide +1). A 1.37 kb EcoRI fragment carrying the ccpA gene was cloned into Escherichia coli plasmid pUC19 and B. subtilis plasmid pUB110, resulting in plasmids pCCPA19 and pCCPA110, respectively. The ccpA gene carried in pCCPA110 complemented the alsA1 mutation. Western blotting revealed that the level of the CcpA protein in B. subtilis cells, which seemed to be constitutively synthesized, was approximately 10 times lower for the alsA1 mutant than for the wild-type. The CcpA protein synthesized by either E. coli cells bearing pCCPA19 or B. subtilis cells bearing pCCPA110 was purified to over 90% homogeneity; the latter cells were grown in the presence of glucose. The molecular mass of the protein purified from E. coli was 74 kDa, suggesting that this protein exists as a dimer because its subunit molecular mass was 38 kDa as determined by SDS-PAGE. Gel retardation analysis indicated that the purified CcpA protein in both cases did not bind to the cis sequence for catabolite repression of the gnt operon, but it bound non-specifically to DNA.

Multiple primary cancers in patients with squamous cell carcinoma of the oral cavity.

During the 27 years between 1962 and 1988, 984 patients visited the National Cancer Center Hospital for previously untreated squamous cell carcinoma of the oral cavity and lip. The records of all these 984 patients were reviewed to determine the incidence of additional primary carcinoma. 1) One hundred and thirty-five additional carcinomas developed in 111 patients (11.2%) during 5,689.2 person-years of observation. The incidence of additional primary carcinoma was 23.7 per 1,000 person-years. 2) The cumulative rate of additional primary carcinoma during the first five years of observation showed a tendency to increase in the most recently treated patients (from 1980 to 1988). 3) The observed-to-expected ratio (O/E ratio) for all sites was 2.77 and this is significantly high (P less than 0.01). The calculation of the O/E ratio for each site revealed significantly high risks in the oral cavity and pharynx, esophagus and skin. The O/E ratio for the oral cavity and pharynx was extremely high (79.45). 4) The O/E ratio for all sites in each year of follow-up was the highest in the first year, stayed nearly constant from the second to 14th years, and decreased gradually afterwards. Significantly high risk was observed until the 13th year of follow-up. Patients with oral squamous cell carcinoma must be under frequent and regular examination for almost 15 years.

Molecular phylogeny of parasitic zygomycota (Dimargaritales, zoopagales) based on nuclear small subunit ribosomal DNA sequences.

We analyzed sequence data of the 18S rDNA gene from representatives of nine mycoparasitic or zooparasitic genera to infer the phylogenetic relationships of these fungi within the Zygomycota. Phylogenetic analyses identified a novel monophyletic clade consisting of the Zoopagales, Kickxellales, Spiromyces, and Harpellales. Analyses also identified a monophyletic mycoparasitic-zooparasitic Zoopagales clade in which Syncephalis, Thamnocephalis, and Rhopalomyces form a sister group to a Piptocephalis-Kuzuhaea clade. Although monophyly of the mycoparasitic Dimargaritales received strong bootstrap and decay index support, phylogenetic relationships of this order could not be resolved because of the unusually high rate of base substitutions within the 18S rDNA gene. Overall, the 18S gene tree topology is weak, as reflected by low bootstrap and decay index support for virtually all internal nodes uniting ordinal and superordinal taxa. Nevertheless, the 18S rDNA phylogeny is mostly consistent with traditional phenotypic-based classification schemes of the Fungi.

[Quality of life in treated head and neck cancer patients].

Sixty-Seven patients with head and neck cancer have been studied with respect to their quality of life after their treatment. The Grogono Woodgate index was used to evaluate their quality of life, the quality of life of patients treated for laryngeal cancer was excellent, even if they underwent total laryngectomy. On the contrary, however, patients who had hypopharyngeal cancer and had undergone a pharyngolaryngoesophagectomy had the lowest indices. As for patients with an oral cancer, their indices were high if the cancer was being controlled by radiotherapy.

Malignant tumors of the nasal cavity: review of a 60-case series.

Sixty cases of primary malignant tumor of the nasal cavity treated in our hospital between 1962 and 1993 were reviewed. Males were affected 2.8 times more frequently than females. The age at the first consultation ranged from 11 to 92 years, with a mean of 55.1 years. The peak distribution was seen in the 6th decade. Twenty-six cases were epithelial malignancies (squamous cell carcinoma 15; adenocarcinoma 3; adenoid cystic carcinoma 3; undifferentiated carcinoma 3; mucoepidermoid carcinoma 1; malignant mixed tumor 1), while 34 cases were non-epithelial malignancies (malignant melanoma 14; malignant lymphoma 14; plasmacytoma 3; olfactory neuroblastoma 2; rhabdomyosarcoma 1). The most common symptom on presentation was nasal obstruction (66.7%), followed by epistaxis (55.0%). The first recurrence was local in 19 patients, whereas cervical lymph node metastasis occurred in three patients, bone metastasis in two, intraperitoneal metastasis in two, and brain metastasis in one. The overall five-year cumulative survival rate was 48.0%. The five-year survival rates for squamous cell carcinoma, malignant melanoma, and malignant lymphoma were 57.0%, 31.0%, and 40.0%, respectively.

p53 expression in multicentric squamous cell carcinoma and surrounding squamous epithelium of the upper aerodigestive tract. Immunohistochemical analysis of 95 lesions.

BACKGROUND: It is now well documented that patients with squamous cell carcinoma of the upper aerodigestive tract frequently develop additional squamous cell carcinoma in the same field. METHODS: p53 expression in 95 patients with multicentric squamous cell carcinoma and in squamous epithelia surrounding multicentric squamous cell carcinomas of the upper aerodigestive tract in 20 patients was examined by immunohistochemistry. In addition, p53 expression in 129 patients with supposedly unicentric squamous cell carcinoma and in squamous epithelia surrounding unicentric squamous cell carcinoma in 22 patients was also examined by immunohistochemistry. RESULTS: Among the 95 patients with multicentric squamous cell carcinoma, 62 (65%) had a clearly positive reaction for p53 protein, whereas 56 (43%) of 129 patients with unicentric squamous cell carcinoma had a positive reaction for p53 protein. The frequency of positive nuclear p53 staining in multicentric squamous cell carcinoma appeared higher than that in unicentric squamous cell carcinoma. However, there was no significant difference between the two groups. Among the nondysplastic squamous epithelia surrounding multicentric squamous cell carcinomas in 20 patients, 12 (60%) were p53 positive, whereas only five (22%) of 22 patients with nondysplastic squamous epithelia surrounding unicentric squamous cell carcinomas were positive. The difference between the two groups was significant (P < 0.05). CONCLUSIONS: The present results suggest that nuclear accumulation of p53 in the squamous epithelium surrounding multicentric squamous cell carcinoma is probably due to heavier exposure and increased susceptibility to mutagens of the affected individuals, although this remains to be verified.

Reconstruction of the cervical esophagus with a free inferior rectus abdominis flap.

An inferior rectus abdominis flap was transferred in an 83-year-old female patient with a cervical esophageal carcinoma. This flap can be a good option for pharyngoesophageal reconstruction when it is desirable to avoid laparotomy and to shorten the operating time in an elderly or high-risk patient.

Laryngeal metastasis from a pulmonary papillary adenocarcinoma: a case report.

Metastases to the larynx from distant primaries are very rare. The present article reports a case of metastatic papillary adenocarcinoma of the larynx of lung origin. The patient was a 59-year-old female non-smoker, who had a history of adenocarcinoma of the right lung. For the laryngeal tumor, we performed a partial laryngectomy following biopsy. The tumor of the larynx was a papillary adenocarcinoma resembling the lung tumor, both demonstrating positive immunohistochemical staining for pulmonary surfactant apoprotein. The findings emphatically indicated the laryngeal tumor to be metastasis from the primary papillary adenocarcinoma of the lung. The present case report presents the clinical findings, course of disease and histopathological findings with brief reviews of the literature.

[An evaluation of excisional biopsy for tongue carcinoma].

An evaluation of excisional biopsy for tongue carcinoma (T1, T2) as a surgical treatment was performed. Forty-seven patients who received excisional biopsy among 394 patients with tongue carcinoma (T1, T2) treated in National Cancer Center Hospital during 24 years were examined. These patients were divided into following three groups: group a) patients treated with excisional biopsy only, group b) those treated with excisional biopsy and cryosurgery, group c) those treated with excisional biopsy and radiotherapy. We examined local control rate of these groups, degree of differentiation in histopathological examination, and median cancer free surgical margin. From these we obtained following results: 1) There was no significance in local control rate among these three groups (group a 77%, group b 84%, group c 45%) 2) There were no local recurrences in the patients with cancer free margin of 5 mm or more except when the histopathology showed perineural invasion, lymphatic vessel invasion, and/or deep invasion to the muscle. 3) Even if we had cancer positive surgical margin with excisional biopsy, we could obtain high local control rate (75%) with additional cryosurgery. We conclude that excisional biopsy for tongue carcinoma (T1, T2) is a good method for primary therapy.