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Biomedical subjects

Y Inuyama

Publications and source records attributed to Y Inuyama.

At least 91 records · Page 5Linked to original sources

Simultaneous carboplatin and radiotherapy for all stages of head and neck squamous cell carcinoma.

The study investigated the toxicity and efficiency of the concomitant administration of radiotherapy and carboplatin to patients with head and neck carcinomas. Sixty-three patients with head and neck squamous cell carcinomas, other than nasopharyngeal cancer and Stage I (UICC) laryngeal cancers, were treated by external radiotherapy and four courses of carboplatin at a dose of 100 mg/m2 per week. In two patients, only three courses were possible due to renal toxicity. In the other 61 patients, toxicities were self-limiting and no patient required interruption of carboplatin administration. No patient required discontinuation of radiotherapy because of acute toxicity. Of 61 evaluable patients, a complete response (CR) was obtained in 11.5% and a partial response (PR) in 60.7% at 40 Gy. In 41 patients treated to 65 Gy (including two patients with maxillary sinus carcinoma, who were treated by debulking surgery), CR was obtained in 76.9% and CR+PR was 100% at the end of treatment. The actuarial survival rate of the 63 patients at 2 years was 69.2%, with a median follow-up period of 24.4 months. One of 12 patients who received salvage surgery after radical radiotherapy has died due to poor wound healing after the surgery. The schedule was safe, providing a weekly check of serum samples was possible. It is likely that the rate of local control and vocal cord preservation in laryngeal tumours might improve if concurrent carboplatin is used. Careful follow-up is required to determine the long-term effect of concomitant carboplatin administration.

Adult↗

[Clinical study of subglottic carcinoma].

Recently, therapy for laryngeal carcinoma has been becoming established, particularly in the early stage. The prognosis of laryngeal carcinoma is said to be better than that of other head and neck carcinomas. Laryngeal carcinoma is divided into 3 subtypes, supraglottic, glottic and subglottic, according to origin. We analyzed the subglottic carcinomas diagnosed and treated in our department between 1972 and 1990. During that period we treated 515 cases of laryngeal carcinoma, 204 cases of the supraglottic type, 284 cases of the glottic type, and 27 cases (5.2%) of the subglottic type. The 5-year survival rate in subglottic carcinoma was 44% (T1: 83%, T2:55%, T3: 17%, T4: 0%), worse than in the other types of laryngeal carcinoma. We think that there were 2 main reasons for the worse prognosis. The first was their high rate of local recurrence after radiation therapy particularly in the early stage. Although 15 T1 and T2 patients who received full dose (65Gy) radiotherapy had a complete response, 8 patients developed local recurrence. The results of the salvage operation were good in T1 cases, but were followed by death because of metastasis or second recurrence in 2 of the 3 T2 patients. The second reason for the worse prognosis appeared to be metastasis in the advanced cases. Five (50%) T3 and T4 patients developed metastasis to the lung, mediastinum and cervical lymph nodes, resulting in death. Thus, we believe that the main therapy for subglottic carcinoma, except T1, should be surgery to obtain a better outcome, and that adjuvant chemotherapy after irradiation or neck (paratracheal) dissection with total laryngectomy should be performed in advanced cases.

Adult↗

[Effect of oak pollen on patients with birch pollinosis].

The author reviewed 53 cases of birch pollinosis treated in our ENT-clinic between 1990 and 1991. Of interest is the fact that many of these patients complained of typical symptoms in and after June, when birch pollen has usually disappeared. We considered this discrepancy to be attributable to the effects of grass pollen, one of the common causal agents in this period. However, only a few patients tested positive for grass pollinosis. We therefore postulated that cross-reactivity between birch and oak pollen accounted for this phenomenon, because both trees belong to same order, Fagales. A strong correlation between RAST scores for birch and oak pollen was detected, and the oak pollen RAST score was significantly reduced by birch pollen extract in an inhibition test. These findings demonstrated actual cross-reactivity between birch and oak pollen. Birch pollinosis patients in Sapporo therefore have allergic symptoms from March to July.

Cross Reactions↗

[Antineutrophil cytoplasmic antibody (C-ANCA) levels in relation to the treatment of Wegener's granulomatosis].

We assessed the clinical significance of cANCA in relation to the diagnosis and follow-up of Wegener's granulomatosis patients using NephroScholor C-ANC, the ELISA kit for the detection of cANCA. The NephroScholor C-ANC test for cANCA was revealed to be useful for the diagnosis of Wegener's granulomatosis, but slightly less sensitive than the indirect immunofluorescence assay using human neutrophils, which has been in widespread use for the detection of ANCAs. With NephroScholor C-ANC, the cANCA titer can be estimated conveniently and expressed quantitatively. When conventional immunosuppressive therapy with prednisolone and cyclophosphamide was applied, the patients' symptoms subsided as the cANCA titer decreased, and thus it also seemed useful for the follow-up of Wegener's granulomatosis patients. However, a rising ANCA titer during the course of the disease was not always correlated with the occurrence of a relapse as previously reported. Based on these findings, it is not recommended that treatment be changed immediately because of elevation of the ANCA titer alone, and it never seemed too late to increase immunosuppressive therapy, even after a clinical exacerbation was observed. Several treatments other than the conventional immunosuppressive therapy have often been applied for our patients, especially in the limited type of this disease, and these treatments, including sulfamethoxazole-trimethoprim alone, low-dose prednisolone alone, and cyclophosphamide alone, have often been useful. We conclude that the choice of therapy must depend on the severity or the condition of the individual patient, and this therapeutic policy should reduce unnecessary side effects of potentially toxic drugs.

Adult↗

Salvage chemotherapy with PEM and long-CF regimen in CDDP refractory advanced head and neck cancer.

With the aim of increasing complete response rates and improving survival in cisplatin (CDDP)-based combinations (CDDP + 5-fluorouracil (5FU) and/or CDDP+methotrexate (MTX)+bleomycin (BLM) of refractory advanced head and neck cancer, we scheduled 21 patients to receive PEM and Long CF, PEM regimens consisting of CDDP (P) Etoposide (Etop) (E) and mitomycin-C (MMC) (M) (CDDP 60 mg/m2/2 hr. infusion on day 1; Etop 40 mg/m2/1 hr. infusion on day 1, 2, 3; MMC 7 mg/m2 iv bolus on day 1). Of 12 patients evaluable for response, 2 CR, 3 PR were realized, with an overall response rate of 42%. Myelosuppression was the major side effect, and thrombocytopenia (8% greater than WHO grade III) was the dose-limiting toxicity. Long CF consisted of CDDP (C) and 5FU (F) (CDDP 8 mg/m2/2 hr. infusion on day 1-5, 8-12, 15-19, 22-26; 5FU 300 mg/m2/24 hr. infusion or tegaful.uracil (UFT-E) 400 mg/m2 P.O. on day 1-28. Of 8 patients evaluable for response, 3 PR were realized, with an overall response rate of 38%. N&V and leukopenia were the major side effects. These adverse reactions were all transient. We concluded that these two regimens produced beneficial effects in patients with advanced recurrent head and neck cancer which had already been treated with CDDP-based combinations.

Aged↗

[Head and neck cancer].

The purpose of this paper is to discuss the recent advances of cancer chemotherapy for head and neck cancer from the viewpoint of survival, focusing on 1) neo-adjuvant chemotherapy, 2) concurrent radiotherapy and chemotherapy, 3) adjuvant chemotherapy, and 4) chemotherapy for palliation. Although neo-adjuvant chemotherapy did not increase survival, it produced a higher rate of organ preservation in some sites such as the larynx and maxilla. Concurrent radiotherapy and chemotherapy form the most promising primary chemotherapy approach to prolong survival of patients with locally advanced resectable and unresectable disease. It is the only systemic approach consistently shown to improve local-regional control and survival in randomized trials. The lack of impact on distant relapse rates, however, suggests that concurrent chemotherapy and radiotherapy should be followed by adjuvant chemotherapy. No survival benefit is evident in adjuvant chemotherapy trials, but some randomized trials including ours produced a significant reduction in the distant relapse rate. As for chemotherapy for palliation, the 5- and 10-year survival were 3.8% and 2.5%, respectively, in patients with local-regional diseases who received chemotherapy for palliation, according to our results. In the patients with distant relapse, the median survival was 10 months, ranging from 2 to 53 months.

Antineoplastic Combined Chemotherapy Protocols↗

Jun and Fos related gene products bind to and modulate the GPE I, a strong enhancer element of the rat glutathione transferase P gene.

The rat glutathione transferase P gene has a strong enhancer element, termed GPE I, which is composed of a dyad of palindromicly oriented TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive element (TRE)-like sequences. TRE is a binding sequence of the transcription factor AP-1, which consists of several closely related proteins belonging to the Jun and Fos family. The gel retardation experiments show that all the heterodimers formed between the Jun and Fos related gene products bind to the GPE I as well as to the TRE. In spite of the fact that the GPE I has a stronger activity than the TRE, the binding affinities of these heterodimers to the GPE I are much lower than to the TRE. Co-transfection studies of the reporter construct containing the GPE I and expression constructs of each of the Jun and Fos family cDNAs indicate that FosB and delta FosB repress transcription through the GPE I enhancer. These results suggests that some of Jun/Fos family may regulate the rat GST-P gene expression through the GPE I in vivo.

Animals↗

Nature of the fine fibrils of the basilar membrane in the cochlea.

Fine fibrils in the basilar membranes of mouse and guinea-pig cochleae were examined by transmission electron microscopy. The fibrils were 10 nm in diameter and ran straight without branching. The fibrils appeared as two parallel lines in longitudinal sections, and round or polygonal in cross-sections, displaying tubular structures with a lumen. They were similar in ultrastructural details to the elastin-associated and elastin-independent microfibrils of Low (1962) in the subcutaneous tissue. It is concluded that the fibrils in the basilar membrane are the microfibrils.

Animals↗

The significance of herpes viral latency in the spiral ganglia.

To better understand the pathogenesis of idiopathic sudden hearing loss (ISHL), the possibility of latent virus infection in the spiral ganglion cell was considered. Only few spiral ganglion cells showed positive viral antigen after systemic guinea pig-specific cytomegalovirus (GPCMV) inoculation indicating the absence of hearing loss but the possibility of a subsequent latent infection. By using a modern molecular biological technique we have detected the herpes simplex virus type-1 (HSV-1) DNA in human spiral ganglia. The concept of establishing viral latency in the spiral ganglion cells with periods of reactivation fits with the clinical picture seen in ISHL, even though the mechanism of reactivation still remains unclear.

Adult↗

Acute measles infection in the hamster cochlea.

Measles virus has been implicated in sudden sensorineural hearing loss (SNHL) in adults as well as in children. Furthermore, sensorineural hearing loss following live measles virus vaccination has been reported. As of yet, however, there has been only few reports on human temporal bone pathology due to measles, and on experimental animal models of measles infection. This study was undertaken to examine acute measles infection in adult hamster cochlea morphologically and immunohistochemically for precise understanding of this viral infection. Atrophy of the stria vascularis, loss of the organ of Corti, "rolled-up" tectorial membrane, and cell infiltration with a positive immunofluorescent reaction primarily within the scale media indicating endolymphatic labyrinthitis were the principal findings. These results were generally consistent with previous ones on human temporal bone pathology not only due to measles but also to SNHL. We consider measles virus to be one of the possible pathogens, even if low in frequency, causing profound and irreversible hearing loss, including SNHL. Completion of measles vaccination without complication and selective or mass revaccination may be necessary to prevent such hearing loss.

Acute Disease↗

[An ELISA for the detection of anti-neutrophil cytoplasmic antibodies using the cytoplasmic alpha-fraction--clinical use for the diagnosis of Wegener granulomatosis and for monitoring its activity].

Anti-neutrophil cytoplasmic antibodies (ANCA) have been reported to be a disease-specific marker for Wegener's granulomatosis (WG). In the present study we developed an enzyme-linked immunosorbent assay (ELISA) for detecting and quantifying ANCA. The cytoplasmic alpha-fraction of neutrophils obtained from healthy human donors was used as an antigen. The alpha-fraction was purified from supernatants of homogenized neutrophils by sucrose gradient centrifugation. Peroxidase conjugated rabbit anti-human IgG was used as a secondary antibody. Diluted sera from 13 patients with WG, 15 with Sjögren syndrome, 1 with polymorphic reticulosis, 3 with relapsing polychondritis, 4 with other collagen diseases, 4 with sinusitis and 18 healthy donors were examined. It was concluded that this ELISA was sufficiently specific and sensitive for WG, and the ELISA units correlated individually with the ANCA titers as determined by an indirect immunofluorescence technique. This ELISA provides precise ANCA quantitation and will be useful for the diagnosis of WG and for monitoring its activity.

Antibodies, Antineutrophil Cytoplasmic↗

[A tinnitus case with an implanted electrical tinnitus suppressor].

An electrical tinnitus suppressor, which was developed at Hokkaido University, was implanted in a female tinnitus patient. She had suffered from bilateral chronic otitis media and her bilateral hearing was seriously impaired. The electrical tinnitus suppressor consists of a stimulator, a coil inside the plastic hearing aid case and an implanted coil in the mastoid. The auditory nerve is stimulated at home twice. Using the system, her hearing ability and emotion improved in addition to tinnitus suppression. Her hearing level and tinnitus also improved in the ear contralateral to the stimulated side.

Cochlear Implants↗

[Four cases of olfactory neuroblastoma treated with craniofacial surgery].

We report 4 cases of olfactory neuroblastoma with anterior cranial fossa extension treated by craniofacial surgery. Three patients have been alive and well for 4 years, 1 year and 11 months after the initial treatment without major surgical complications but one patient died of local recurrence 11 months after treatment. Multidisciplinary surgery for olfactory neuroblastoma with intracranial extension permits radical tumor excision and reconstruction of the anterior skull base. This one-stage procedure combining neurosurgery and plastic surgery with pre or post-operative radiotherapy is considered to be essential for eradicating this tumor.

Adult↗

[Multidisciplinary treatment for organ/function preservation in head and neck cancer].

Neo-adjuvant chemotherapy (NAC) improved quality of life for surviving patients by providing effective organ/function preservation. Regrettably, however, many randomized trials did not show that NAC significantly improved survival. Many design limitations of these trials make it impossible to draw definitive conclusion. So neo-adjuvant trials should investigate the issue of optimal number of chemotherapy cycles on response (clinical/histologic) and on survival. Future work also should study the integration of biologic response modifiers, differentiation agents, other cytotoxic agents and irradiation into primary therapy. Concomitant chemoradiotherapy is the only approach in this category that has shown potential by increasing survival in randomized studies. This survival benefit has appeared in trials in both resectable and unresectable head and neck squamous cell carcinoma. Recent data from numerous phase II study trials supported the promise of concurrent cisplatin (including carboplatin) and radiotherapy. All the positive single-agent concomitant trials used suboptimal doses of active drugs like BLM, MTX etc, and full doses of relatively inactive drugs like MMC. This indicates that chemotherapy enhances radiotherapy. Recent date from numerous phase II trials now support the promise of concurrent cisplatin (or carboplatin)/radiotherapy. The lack of overlapping toxicities allows optimal administration of both modalities. Concomitant multi-agent chemoradiotherapy began as a result of positive studies with concomitant single-agent chemoradiotherapy. But, this combined therapy increased acute toxicity. Nevertheless, early results from the randomized trials are encouraging, with survival favoring the concomitant arm. The future trials will be required more patients, longer follow-ups and careful assessments of toxicity and quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

[Current status of clinical trials on pre- and postoperative chemotherapy for head and neck cancer].

The purpose of this paper is to discuss the current status and issues of clinical trials in pre- and post-operative chemotherapy for head and neck cancer, focusing on 1) neo-adjuvant chemotherapy, 2) concurrent radiotherapy and chemotherapy, and 3) adjuvant chemotherapy. Although neo-adjuvant chemotherapy did not increase survival, it produced a higher rate of organ preservation in some sites such as the larynx and maxilla. Concurrent radiotherapy and chemotherapy is the most promising primary chemotherapy approach to prolong survival of patients with locally advanced resectable and unresectable disease. It is the only systemic approach consistently shown to improve local-regional control and survival in randomized trials. No survival benefit is evident in trials of adjuvant chemotherapy, the third major treatment category, but some randomized trials produced a significant reduction in distant relapse rate. Based on the results obtained so far, future clinical trials should be continued to search for more effective programs in the systemic control of advanced head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Chromium-induced carcinoma in the nasal region. A report of four cases.

The carcinogenicity of chromium is well established in chromium-induced lung cancer. As of yet, however, there have been only few reports of head-and-neck cancer induced by chromium. We report four cases of carcinoma in the nasal region which seemed to be induced by chromium. All patients have worked at the same chromate factory for 19 to 32 years. The first patient has suffered from squamous cell carcinoma of the left nasal cavity, starting 11 years after his retirement. He received radiotherapy followed by surgery. A malignant fibrous histiocytoma occurred in his left upper gingiva in a previously irradiated region, 7 years after the previous treatment. Surgery and chemotherapy for palliation failed to control the tumour, and he eventually expired. The other three patients underwent lobectomy for lung cancer. In cases 2 and 3, the tumour occurred in the left nasal cavity six and ten years, respectively, each after the lobectomy. In case 4, the tumour arose from the nasopharynx 15 years after the lobectomy. These patients are alive and well without any sign of tumour. The presented cases seem to be induced by long-term exposure to chromium. We conclude that regular physical examination of chromate workers is mandatory for the early detection not only of lung cancer but also of head-and-neck cancer.

Aged↗

[A prospective randomized trial of adjuvant chemotherapy with UFT for head and neck carcinoma. Head and Neck UFT Study Group].

A prospective randomized trial was performed in 67 institutions for the purpose to evaluate the efficacy of adjuvant chemotherapy after radical treatment of head and neck carcinoma. A comparison was made between the following two groups; one-year oral administration of UFT, 300 mg/day, after radical treatment (UFT group); and a non-treatment group. Patients were classified under the following three categories; 1) stage II-IV, receiving radical surgery; 2) stage II, receiving radical radiotherapy; and 3) nasopharyngeal cancer. The numbers of cases were 424, 111 and 25, respectively, and they were randomized into two groups. The numbers of eligible cases were 398, 105 and 25, respectively. Statistical analysis was performed in the cases receiving radical surgery and in those receiving radical radiotherapy. As the results, in cases receiving radical surgery no significant difference was observed in 3-year survival rates (77.9% for UFT group vs 72.9% for non-treatment group) or 3-year relapse-free rates (73.4% for UFT group vs 66.2% for non-treatment group) between the two groups. However, the distant relapse rate was significantly lower in the UFT group than in the non-treatment group (7.9% vs 14.6%; p = 0.034). In the cases receiving radical radiotherapy, no significant differences was observed in either 3-year survival rates or 3-year relapse-free rates. Thus it was suggested that UFT maintenance therapy might suppress the distant metastasis after radical surgery. We considered a further confirmative trial for patients at high risk of distant metastasis after radical surgery to be advisable.

Administration, Oral↗

Thyroplasty type I with ceramic shim.

To improve hoarseness or misswallowing caused by unilateral recurrent laryngeal nerve paralysis, medialization of paralyzed vocal cord has frequently been performed. This method includes such techniques as injection method, insertion method, and arytenoid adduction, each presenting its merits and demerits. The insertion method which can be done while monitoring the patient's voice seems advantageous in that the technique is easy to perform and generally guarantees the voice improvement. Among insertion methods, Isshiki thyroplasty type I is the one most representative as well as popularized. However, since a silicone shim is inserted in this operation, it may be accompanied by the risks of carcinogenicity, foreign body reaction, and induction of collagen disease of silicone. Therefore we planned to use a ceramic as a safe substitute instead of silicone. There has been no article reporting the use of ceramic in this type of surgery. We used a fibrin glue to fix the ceramic shim and for hemostasis, which was found very useful. Hitherto, 2 cases of unilateral recurrent laryngeal nerve paralysis underwent Isshiki thyroplasty type I using ceramic shim with satisfactory results.

Aged↗