Reef environments shape microbial partners in a highly connected coral population.

Evidence is mounting that composition of microorganisms within a host can play an essential role in total holobiont health. In corals, for instance, studies have identified algal and bacterial taxa that can significantly influence coral host function and these communities depend on environmental context. However, few studies have linked host genetics to algal and microbial partners across environments within a single coral population. Here, using 2b-RAD sequencing of corals and metabarcoding of their associated algal (ITS2) and bacterial (16S) communities, we show evidence that reef zones (locales that differ in proximity to shore and other environmental characteristics) structure algal and bacterial communities at different scales in a highly connected coral population (Acropora hyacinthus) in French Polynesia. Fore reef (FR) algal communities in Mo'orea were more diverse than back reef (BR) communities, suggesting that these BR conditions constrain diversity. Interestingly, in FR corals, host genetic diversity correlated with bacterial diversity, which could imply genotype by genotype interactions between these holobiont members. Our results illuminate that local reef conditions play an important role in shaping unique host-microbial partner combinations, which may have fitness consequences for dispersive coral populations arriving in novel environments.

Manifest Anxiety Scale for evaluation of effects of granisetron in chemotherapy with CDDP and 5FU for head and neck cancer.

The level of anxiety was examined before treatment by means of the Manifest Anxiety Scale (MAS) in 41 patients with squamous cell carcinoma of the head and neck. They received 5 days of neoadjuvant chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5FU). Granisetron (KYT) was administered daily from day 1 to day 5. Nausea, vomiting, appetite, and well-being were assessed during and after chemotherapy. The relation between the effects of KYT and anxiety was studied. Seventeen patients were proven to have anxiety and were compared with the other 24 patients. In patients with anxiety, the percentage well-being was significantly lower on days 1 and 2 (P=0.008, 0.001). The rate of freedom from nausea was significantly lower from day 4 to day 9 for anxiety patients (P=0.010-0.050). The percentage of anxiety patients without loss of appetite was significantly lower from day 6 to 9 (p=0.001-0.020). The rate of freedom from vomiting was significantly lower on days 4, 5 and 7 for anxiety patients (P=0.024, 0.024, 0.014). The results indicate that the effect of KYT was significantly lower from day 3 to day 7 for anxiety patients (P=0.008-0.045). The anxiety group had significantly poorer well-being at the beginning of chemotherapy, and were not responsive to KYT in the delayed phase. Our results prove that anxiety patients show delayed emesis, and the administration of KYT is considered insufficient. It may be important to co-administer a tranquilizer to any patient who exhibit anxiety as defined by the MAS, in order to reduce delayed emesis.

Influence of the light schedule on the toxic interaction between propranolol and disopyramide in chick embryos.

The effect of the light schedule on toxic interactions between propranolol and disopyramide were studied in chick embryos. Fertilized eggs of White Leghorns were incubated under dark conditions and investigated, on two occasions, under light conditions or under dark conditions. Propranolol, with and without disopyramide, was injected into the air sac of fertilized eggs on the 16th day of incubation. Electrocardiograms (ECGs) were recorded 0 to 60 min after the injection. After the injection of propranolol with disopyramide, the heart rate was significantly decreased compared with the injection of propranolol alone under light conditions. In addition, this toxic interaction between propranolol and disopyramide was more severe under dark conditions than under light conditions. These findings indicate that manipulation of the light schedule has a marked influence on the toxic interaction between propranolol and disopyramide in chick embryos.

The effect of fosfomycin on glycopeptide antibiotic-induced nephrotoxicity in rats.

The effect of coadministration of fosfomycin (FOM) on glycopeptide antibiotic-induced nephrotoxicity for 3 days was investigated in rats. To induce nephrotoxicity in a short time, gentamicin (GM) was also coadministered. In the present study, FOM decreased glycopeptide antibiotic-induced nephrotoxicity as shown by reduced urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) as well as fewer histopathological signs of nephrotoxicity in the groups treated with the combination of glycopeptide and FOM as compared with a glycopeptide alone. In addition, the higher the dose of FOM, the more it decreased urinary NAG levels, suggesting that the role of FOM in alleviating nephrotoxicity is dose dependent. The accumulation of teicoplanin and vancomycin was significantly lower in the renal cortex of rats treated with the combination of glycopeptide antibiotics and FOM as compared with glycopeptide antibiotics alone (P < 0.05). In conclusion, the concomitant administration of FOM and glycopeptide antibiotics may help to achieve a chemotherapeutic strategy that reduces the nephrotoxic effects of glycopeptide antibiotics.

UFT plus carboplatin for head and neck cancer.

Cisplatin plus fluorouracil (5-FU) is widely accepted as neoadjuvant and adjuvant chemotherapy in the treatment of head and neck squamous cell carcinoma; UFT is also an active agent against this disease. In the first retrospective study, we examined the efficacy of UFT as adjuvant chemotherapy in patients with maxillary cancer. The 5-year survival rate of those treated with UFT vs those not treated was 71.4% vs 23.8%, respectively. In the second study we developed the carboplatin plus UFT regimen--as a modification of cisplatin plus 5-FU--and studied its efficacy and toxicity in patients with advanced head and neck squamous cell carcinoma. These patients received UFT plus carboplatin. The objective response rate was 53.1%; grade > or = 3 leukopenia, anemia, and thrombocytopenia were rare. These findings suggest that UFT plus carboplatin in the outpatient setting is feasible for patients with head and neck squamous cell carcinoma.

[A randomized crossover comparison of azasetron alone and azasetron plus dexamethasone for the prevention of nausea and vomiting by chemotherapy including cisplatin].

A randomized crossover study between azasetron alone and azasetron combined with dexamethasone was performed to investigate the prevention of nausea and vomiting due to chemotherapy including cisplatin in patients with advanced head and neck carcinoma. The results indicated that the combination therapy with dexamethasone was more effective than azasetron alone in preventing nausea on days 1 through 5 after the administration of cisplatin and was significantly superior to azasetron alone on days 2 and 3. In addition, complete response (no vomiting) and the antiemetic and antinausea efficacy of combination therapy with dexamethasone on day 2 was significantly superior compared to azasetron alone. No adverse effect from either antiemetic therapy was observed in this study.

Role of CD44 variant exon 6 in invasion of head and neck squamous cell carcinoma.

OBJECTIVES: To determine the correlation between the expression of CD44 variant exon 6 (v6) and the clinicopathological features of head and neck squamous cell carcinomas (HNSCCs), and to study the role of CD44v6 in cell invasion using a human HNSCC cell line (HSC-2). DESIGN: The expression of CD44v6 was evaluated using immunohistochemical analysis in paraffin-embedded tissue specimens from 89 primary lesions. The concentration of CD44v6 protein in 37 cryopreserved tumor specimens was evaluated using the enzyme-linked immunosorbent assay. The HSC-2 cells were treated with 2F10, a monoclonal antibody against CD44v6. The effects of 2F10 on HSC-2 cell proliferation, migration, and invasion potential were evaluated. RESULTS: The down-regulation of CD44v6 expression or the concentration of cancer tissue significantly correlated with a lower degree of pathohistological differentiation and a higher rate of cervical metastasis. The invasion of HSC-2 cells into type I collagen gel and the expression of CD44v6 were decreased in invading cells released from the upper layer. Furthermore, the treatment of HSC-2 cells with 2F10 significantly enhanced cell invasion. However, 2F10 did not affect either the proliferation or migration properties of HSC-2 cells. CONCLUSIONS: The down-regulation of CD44v6 expression may be useful as a biological marker for the degree of malignancy in HNSCCs. We assume that the loss or dysfunction of CD44v6 is involved in the acquisition of invasion ability in HSC-2 cells. In addition, the potential existence of a CD44v6-mediated signal transduction pathway may play a role in inhibiting the invasion in HNSCCs.

Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma.

Three different membrane-type matrix metalloproteinases (MT-MMPs) activate in vitro the latent form of matrix metalloproteinase-2 (MMP-2), which is one of the key proteinases in invasion and metastasis of various cancers. We examined the mRNA expression of MT1, 2, and 3-MMPs and MMP-2 in cell lines of head and neck squamous cell carcinoma (HNSCC) and quantitated the relative expression levels in human HNSCC tissues by Northern blotting. The tissue localization of MT1-MMP and MMP-2 was determined by immunohistochemistry and in situ hybridization. Their implications in clinicopathologic factors were statistically evaluated. All cell lines examined consistently expressed MT1-MMP and MMP-2, but not MT2, 3-MMP. In the clinical specimens, there was a significant correlation in coexpression of messenger of RNA (P = .0005) and colocalization by immunohistochemistry (P < .0001) for MT1-MMP and MMP-2. Relative mRNA expression levels of MT1-MMP and MMP-2 in the carcinoma tissues were significantly higher than those of the control tissues (P = .0045 and P = .0122, respectively). Both mRNA expression level and immunopositivity of MT1-MMP significantly correlated with lymph node metastasis (P = .0081 and P = .0193, respectively), which was confirmed by multivariate logistic regression analysis. Immunoreaction of MT1-MMP and its mRNA expression were observed in both carcinoma cells and stromal cells. The localization of MMP-2 closely corresponded to that of MT1-MMP. These observations suggest that MT1-MMP possesses a role as a determinant of lymph node metastasis in HNSCC, and that concurrent expression of MT1-MMP and MMP-2 are involved in progression of HNSCC.

Granulocyte-macrophage colony-stimulating factor upregulates matrix metalloproteinase-2 (MMP-2) and membrane type-1 MMP (MT1-MMP) in human head and neck cancer cells.

Matrix metalloproteinase-2 (MMP-2) and membrane type 1-MMP (MT1-MMP) play an important role in the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC), but the mechanism of their regulation is not clearly understood. Recently, granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be associated with cancer invasion and metastasis. We hypothesized that GM-CSF may upregulate MMP-2 and/or MT1-MMP expression in HNSCC cells, and may thereby influence their ability to invade and metastasize. We studied the effects of GM-CSF on the production of MMP-2 and MT1-MMP in HNSCC cell lines SAS and HSC-2. Gelatin zymography of conditioned media derived from HNSCC cells revealed a major band of 68 kDa, which was characterized as proMMP-2. GM-CSF stimulated the production of proMMP-2 in both cell lines in a dose-dependent manner. Treatment with 50 ng/ml GM-CSF for 24 h increased the proMMP-2 activity 3.4-fold in SAS cells and 2.3-fold in HSC-2 cells compared with untreated controls. Northern blot analyses demonstrated that GM-CSF led to elevated mRNA levels of MMP-2 and MT1-MMP in both cell lines. The results identify GM-CSF as a regulator of MMP-2 and MT1-MMP expression in certain types of HNSCC, and suggest that GM-CSF may contribute to the invasiveness of HNSCC through the regulation of MMP-2 and MT1-MMP expression.

Clinicopathological significance of expression of CD44 variants in head and neck squamous cell carcinoma.

Splice variants of the cell surface glycoprotein CD44 have been reported to be associated with the progression of various human tumors. The aim of this study is to determine the correlation between the expression of CD44 isoforms, especially CD44 variant 2 (CD44v2), and the clinicopathological features of head and neck squamous cell carcinomas (HNSCCs). The expression of CD44 isoforms was evaluated immunohistochemically in paraffin-embedded tissues from 89 primary lesions, using monoclonal antibodies against CD44 standard (CD44st), CD44 variant 6 (CD44v6) and CD44v2. Cancer tissues from 89 (100%), 85 (95.5%) and 59 (66.3%) patients showed positive immunoreactivity for CD44st, CD44v6 and CD44v2, respectively. A significant correlation was observed between the down-regulation of CD44v2 and poorer differentiation of the tumor cells (P = 0.02). We could not find any significant correlation between the expression of CD44v2 and T stage or N stage (lymph node status). However, the rate of positive cervical lymph node metastasis tended to increase with reduced expression of CD44v2 (P = 0.08). Down-regulation of CD44v2 expression was correlated with shorter overall survival (P = 0.01). Furthermore, Cox's multivariate analysis revealed that only CD44v2 expression and lymph node status were independent prognostic factors. These findings suggest that down-regulation of CD44v2 expression may be one of the biological markers for the degree of malignancy in HNSCCs.

Nephrotoxicity of teicoplanin in rats.

Teicoplanin, a glycopeptide antibiotic, is marketed in a number of European countries and has recently been put on the market in Japan. The spectrum of antibacterial activity of teicoplanin is equivalent or superior to that of vancomycin. The aim of the present study is to examine the nephrotoxicity of teicoplanin compared with vancomycin in rats. Wistar male rats, housed in a light-controlled room at room temperature for 1 week, were used. They were injected with either 15 or 50 mg/kg/day of teicoplanin or 50 or 200 mg/kg/day of vancomycin at 13:00 daily for 14 days. The rats were randomly assigned to groups of five rats each and were housed individually in metabolic cages to collect urine. Urine samples were collected 24 hours prior to the drug treatment and every 24 hours thereafter for 14 days. N-Acetyl-beta-D-glucosaminidase (NAG) activity was determined in the supernatant and expressed in international units per total urine collected for 24 hours. The group which was given vancomycin 200 mg/kg/day had significantly elevated urinary NAG levels compared with the other groups (p < 0.05). No significant differences were observed in the NAG levels in urine among the remaining three groups. These results suggest that the nephrotoxicity of teicoplanin may be only one-fourth that of vancomycin in rats. It appears that by extrapolating the dose amount required for the treatment in humans to rats, the high dose of teicoplanin was set at 50 mg/kg/day and that of vancomycin, 200 mg/kg/day. The recommended dose for teicoplanin will probably be 200 mg/day compared to 2 g/day of vancomycin. If the teicoplanin dose is only one-tenth that of the vancomycin dose, then teicoplanin should be better tolerated than vancomycin in terms of nephrotoxicity.

[Low-dose CDDP and 5-FU for head and neck cancer patients].

Combination chemotherapy with CDDP and 5-FU is one of the most effective regimens for head and neck cancer. Recent studies have focused on biochemical modulation in the combination of CDDP and 5-FU. We studied the difference in effectiveness and adverse effects between two CDDP administration schedules for CDDP-5-FU combination chemotherapy. For regimen A, CDDP was administered on 5 consecutive days from day 1 to day 5, with a daily dose of 16 mg/m2. For regimen B, CDDP was administered at 80 mg/m2 on day 1. 5-FU was administered at 600 mg/m2/day in a continuous drip infusion for 120 hours from day 1 to day 5 for regimens A and B. Twenty-seven patients with head and neck squamous cell carcinoma were included in this study, and received either regimen A or B. Thirteen patients were given regimen A and 14 regimen B. With regimen A, 3 patients showed CR and the response rate was 76.9%. With regimen B, 3 patients showed CR and the response rate was 64.3%. The rates of efficacy were not different between regimen A and B. In contrast, a difference was seen with organ toxicity. Regimen B was more toxic for renal function than regimen A, while regimen A showed greater toxicity to bone marrow function. Acute nausea and vomiting were observed more frequently with regimen B. The difference in organs and symptoms of adverse effects, according to the schedule of CDDP administration would seem to be important in the treatment of head and neck cancer patients. The schedule of CDDP administration should be adjusted depending on the renal and bone marrow functions of the patients. Because multiple infusion of CDDP proved to be efficacious, low-dose CDDP and 5-FU will have a role for patients with head and neck squamous cell carcinoma. We also introduce other reports on the efficacy of low-dose CDDP and 5-FU.

[Statistical analysis of localized non-Hodgkin's lymphomas of the head and neck--multivariate analysis of prognostic factors and evaluation of therapeutic modalities].

Prognostic factors and treatment outcome of 48 patients with Stage I (29) or II (19) non-Hodgkin's lymphoma of the head and neck were analyzed retrospectively. There were 26 males and 22 females, aged from 15 to 89 years old, with an average age of 57. The primary lesion was located in Waldeyer's ring in 25 patients, the nasal cavity and paranasal sinuses in 13, cervical lymph nodes in 8, and others in 2. Histologically, 2 had low grade lymphoma, 42 had intermediate grade disease, and 1 had high grade disease. The patients were treated with radiation alone (5 patients), chemotherapy according to a cyclophosphamide, doxorubicin, vincristine, prednisone- (CHOP) regimen (8 patients), or a combination of both treatments (35 patients). In univariate analyses, an unfavorable prognosis was associated with age > or = 60, Stage I disease, and extralymphatic lesion. Multivariate analysis showed that an extralymphatic lesion was a significant independent risk factor for death (p = 0.0093). The overall five-year survival rate was 73.5%. Differences in the treatment was not reflected in the outcome. Our results suggest that a combination of chemotherapy (CHOP) and radiation is an appropriate treatment for lymphatic stage I and II non-Hodgkin's lymphoma of the head and neck. However, more intensive therapy is necessary for patients with extralymphatic head and neck NHL.

Protective effects of sodium-L-ascorbyl-2 phosphate on the development of UVB-induced damage in cultured mouse skin.

The protective effect of sodium-L-ascorbyl-2 phosphate (As-2P), a stable form of ascorbic acid (AsA), against photodamage induced by a single dose of UVB exposure (290-320 nm, Max 312 nm) was investigated using cultured mouse skin. When the cultured skin was treated with various As-2P concentrations, the cutaneous AsA level increased in proportion to the As-2P concentration. After 3 h of incubation, the AsA level in the cultured skin treated with 2, 20 and 100 mM As-2P increased 1.03-, 2.17- and 6.27-fold, respectively, compared with that of the control skin. These results suggest that As-2P was transported into the cultured mouse skin where it was converted to AsA. After 3 h, the cutaneous AsA level in irradiated (20 kJ/m2) skin was depleted to a half of that in the control skin. However, the level in skin pretreated with 20 mM As-2P was maintained within normal limits, even after 24 h. Pretreatment with 20 mM As-2P significantly prevented such photodamage as sunburn cell formation, DNA fragmentation and lipid peroxidation, which were caused by a single dose of UVB irradiation. These results suggest that the protective effect of 20 mM As-2P on UVB-induced cutaneous damage is due to the maintenance of a normal As level by conversion of As-2P to As in skin tissue.

Postadministration protective effect of magnesium-L-ascorbyl-phosphate on the development of UVB-induced cutaneous damage in mice.

The effects of stable vitamin C, magnesium-L-ascorbyl-2-phosphate (MAP), administered after acute and chronic exposure to UVB irradiation were investigated using hairless mice. Intraperitoneal administration of 100 mg/kg of MAP immediately after acute exposure to 15 kJ/m2 of UVB significantly prevented increases of UVB-induced lipid peroxidation in skin and sialic acid in serum, an inflammation marker. Administration of 50 mg/kg of MAP immediately after each exposure significantly delayed skin tumor formation and hyperplasia induced by chronic exposure to 2 kJ/m2 of UVB. Intraperitoneal administration of 200 mg/kg of MAP produced an increase in ascorbic acid (As) levels in the serum, liver and skin within 15 min. Serum As levels quickly returned to normal, but hepatic and cutaneous levels remained elevated before returning to normal after 24 h, suggesting that MAP was converted to As in the serum and in those tissues. Ultraviolet B-induced hydroxyl radical generation in murine skin homogenates was scavenged by As-Na addition, which was directly detected by electron spin resonance (ESR). These results suggest that postadministration of MAP delays progression of skin damage induced by UVB irradiation. It is presumed that MAP, once converted to As, exhibits such inhibitory effects by scavenging hydroxyl and lipid radicals generated as a direct or indirect result of UVB exposure.

Protective effect of ceftriaxone against the nephrotoxicity of isepamicin administered once daily in rats.

The protective effect of ceftriaxone on isepamicin-induced nephrotoxicity was investigated. For 14 d, Wistar rats were administered either ceftriaxone 100 mg/kg intraperitoneally, isepamicin 300 mg/kg subcutaneously, or ceftriaxone isepamicin in combination. The animals given 300 mg/kg of isepamicin showed a significant increase in urine NAG (N-acetyl-beta-D-glucosaminidase) levels as compared with the control animals which received saline (p<0.01). However, the increase in NAG level was markedly less when isepamicin was administered in combination with ceftriaxone (p<0.01). Ceftriaxone alone had no effect on urine NAG activity. Serum creatinine levels were significantly higher in animals treated with isepamicin alone than in control animals (p<0.01) or animals receiving the isepamicin ceftriaxone combination (p<0.01). After 14 d of treatment, ceftriaxone had not accumulated in renal tissue, but it did reduce the renal intracortical accumulation of isepamicin (p<0.01). Histopathologically, ceftriaxone induced very few cellular alterations and considerably reduced the manifestation of typical signs of isepamicin nephrotoxicity. This investigation demonstrates that ceftriaxone protects animals against isepamicin-induced nephrotoxicity.

[Result of treatment of squamous cell carcinoma of the tongue and floor of the mouth].

A statistical analysis was performed on 40 patients with squamous cell carcinoma of the tongue and mouth floor, which could be followed for 6 months or more after initial treatment in the Department of Otorhinolaryngology, School of Medicine, Keio University during the 14 years from 1983 to 1996. The 5-year survival rate determined by the Kaplan-Meier method for each stage was 100% for Stage I, 77.8% for Stage II, 60.0% for Stage III and 44.4% for Stage IV. Thirteen suffered a relapse after initial treatment and patients with relapses among them have all survived after the subsequent salvage surgery. In contrast, in nine patients with cervical relapse, however, the 5-year survival rate was 11.1% with an unfavorable prognosis. This confirmed that suppressing cervical relapses is important for treating tongue and floor mouth cancers. The treatment strategy in our department is characteristic of positive enforcement of prophylactic neck dissection in the surgery and introduction of neoadjuvant chemotherapy (NAC) in the chemotherapy. Prophylactic neck dissection was performed in the 17 patients and no relapse was observed on the side of prophylactic neck dissection. NAC was performed on 26 patients in consideration of suppressed minute metastases and preserved function and 24 determinable cases were statistically analyzed. Among patients who had received NAC, the oral function was successfully preserved without surgical intervention in six patients both patients who showed complete response (CR) and four out of 14 patients who had a partial response (PR) following NAC. This may indicate that the oral function could be preserved in those patients who exhibited CR following NAC, but that preservation could be difficult in patients who exhibited PR. In addition, concerning the accumulated 5-year survival rate in relation to the effect of NAC, responders (CR + PR) accounted for 90.9% and non-responders (no change + progressive disease following NAC) for 15.0% with a very good outcome noted in the responder group. These figures suggest that responders may have a significantly good prognosis in the multivariant analysis including additional background factors before treatment as well. Accordingly, the present therapeutic measures for non-responders must be reexamined and performed more carefully and accurately as compared with those for responders.

[Statistical analysis of oropharyngeal squamous cell carcinoma--multivariate analysis of prognostic factors and evaluation of therapeutic modalities].

Ninety-one cases of oropharyngeal squamous cell carcinoma initially treated at Keio University Hospital between July 1981 and June 1996 were reviewed retrospectively. There were 83 males and 8 females, aged from 29 to 83 years old, with an average age of 62.7. The primary lesion was located in the lateral wall in 52 patients (57.1%), the superior wall in 23 (25.3%), the anterior wall in 14 (15.4%) and the posterior wall in 2 (2.2%). Double cancer was detected in 21 patients (23.1%). The patients were divided into two groups according to the initial main treatment of the primary lesion without regard to chemotherapy: 72 patients (79.1%) who received curative radiotherapy with or without salvage surgery, and 14 patients (15.4%) who underwent curative surgery with or without preoperative and/or postoperative radiation. The remaining 5 patients were treated by chemotherapy alone. Prior to the above treatments 50 patients (54.9%) received neoadjuvant chemotherapy (NAC). Survival distributions were estimated by the Kaplan-Meier method as univariate analysis, and compared by the generalized Wilcoxon test. The overall five-year cumulative survival rate was 55.6%. The five-year survival rates according to stage (UICC classification, 1987) were as follows: stage I (11 cases), 70.7%; stage II (12 cases), 63. 6%; stage III (30 cases), 52.3%; and stage IV (38 cases), 52.5%. Significant clinicopathological variables that influenced survival were: (1) T stage (p = 0.0075); (2) age (p = 0.0274); and (3) location of primary lesion (p = 0.0400). The results of multivariate analysis by Cox's proportional hazards model identified T stage as a significant independent prognostic factor. Evaluation of the therapeutic modalities led to the following conclusions. (1) Differences in the initial treatments of the primary lesion were not reflected in the outcome. (2) Salvage surgery for residual or recurrent tumor contributed to improving the survival. The superior wall type, in particular, seemed to be a good indication for salvage surgery. (3) Although the limitations of radiotherapy are not defined clearly, we have to determine the indications for radical resection of tumors resistant to radiotherapy with reconstruction. (4) The response rate of NAC reached 85.4%, but there were no significant differences in survival between the group that underwent NAC and the other group in any other subset analyses. (5) Among the patients who underwent NAC, the responder (CR + PR) group showed a better five-year survival rate (61.3%) than the non-responder (NC + PD) group (42.9%), but the difference was not significant.

Adjuvant chemotherapy with oral tegaful and uracil for maxillary sinus carcinoma.

We have applied tegaful and uracil (UFT) treatment as adjuvant chemotherapy to patients after the completion of primary therapy. UFT was given per os at a dose of 300 or 400 mg/day for more than 1 year. A retrospective study was conducted on 15 patients, assessed as the UFT-treated group, and 24 patients assessed as the UFT-nontreated group. The 5-year survival rate in patients treated or not treated with UFT was 76.6 and 22.6%, respectively. Among those who underwent surgery in combination with other therapy, the 5-year survival rate was 74.1% with UFT and 27.3% without UFT. In patients receiving chemotherapy plus radiotherapy alone, the 5-year survival rate was 80.0% with UFT and 19.2% without UFT. In 23 patients with proven effects of neoadjuvant chemotherapy comprising 18 PR cases and 5 CR cases, a comparison was made between 10 patients treated with UFT and 13 patients not treated with UFT. As a result, the 5-year survival was 76.2 and 17.9%, respectively. In the patients with T3 disease, who occupied the majority, the 5-year survival rate was 71.4 and 23.8%, respectively. Adjuvant chemotherapy with UFT tends to show a substantial significant difference particularly in patients who were successfully treated with radiotherapy plus chemotherapy as the primary treatment. UFT was clearly shown to have a statistically significant effect, despite a small population. The findings of the present investigation point to the value of conducting further study to ascertain the effect of UFT by a randomized trial in a larger population.