Publications by authors named "Taijiro Ozawa"

23 Publications

  • Page 1 of 1

An Unusual Presentation of Nasopharyngeal Carcinoma as Lemierre Syndrome.

Am J Case Rep 2019 Feb 28;20:263-267. Epub 2019 Feb 28.

Department of Clinical Engineering, Suzuka University of Medical Science, Suzuka, Mie, Japan.

BACKGROUND Clinical presentation of nasopharyngeal carcinoma (NPC) is correlated with the extent of primary and nodal disease. Hence, depending on the anatomical structures affected, the clinical presentation varies accordingly, ranging from non-specific symptoms of epistaxis, unilateral nasal obstruction, and auditory complaints, to cranial nerve palsies. Nodal metastasis in the neck is a frequent clinical finding in nasopharyngeal carcinoma. CASE REPORT A female was admitted to the hospital because of fever and trismus with painful swelling in the right neck. Computed tomography (CT) revealed a mass in the nasopharynx with heterogeneous enhancement and multiple swollen lymph nodes in the corresponding neck. Initial biopsies of nasopharyngeal mass and lymph node of the neck revealed nonspecific lymphoid hyperplasia; we administered antibiotics with the provisional diagnosis of bacterial infection, including Lemierre syndrome that is typically defined by the constellation of septic internal jugular vein thrombophlebitis, pulmonary and other septic emboli, and sterile site bacterial infection. However, the patient was refractory to antibiotics over a month of treatments. The third biopsy of the throat lesion revealed NPC and bacterial cultures using the biopsy specimen were negative. She received intensity-modulated radiation therapy and chemotherapy for NPC stage II (TNM staging: T2N1M0). She never developed Lemierre syndrome-like symptoms after chemoradiotherapy. CONCLUSIONS We report a unique case of NPC presenting with Lemierre syndrome-like symptoms, including prior sore throat, trismus, painful swollen neck, and high fever. Since these symptoms have not been reported in NPC, we included NPC as a differential diagnosis.
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http://dx.doi.org/10.12659/AJCR.913755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441307PMC
February 2019

The high-sensitivity modified Glasgow prognostic score is superior to the modified Glasgow prognostic score as a prognostic predictor for head and neck cancer.

Oncotarget 2018 Dec 11;9(97):37008-37016. Epub 2018 Dec 11.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Aichi, Japan.

Background: There is increasing evidence that the inflammatory indices of modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) play important roles in predicting the survival in many cancer; however, evidence supporting such an association in head and neck cancer (HNC) is scarce.

Materials And Methods: We evaluated the impact of the mGPS and HS-mGPS on the overall survival (OS) in 129 patients with HNC treated at Aichi Cancer Center Central Hospital from 2012-2013. The mGPS was calculated as follows: mGPS of 0, C-reactive protein (CRP) ≤1.0 mg/dl; 1, CRP >1.0 mg/dl; 2, CRP>1.0 mg/dl and albumin <3.5 mg/dl. Regarding the HS-mGPS, the CRP threshold level was set as 0.3 mg/dl. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models after adjusting for potential confounders.

Results: The prognosis of HNC worsened significantly as both the mGPS and HS-mGPS increased in a univariate analysis. After adjusting for covariates, the HS-mGPS was significantly associated with the OS (adjusted HR for HS-mGPS of 2 compared to an HS-mGPS of 0 [HR] 3.14 [95% CI: 1.23-8.07], P < 0.001), while the mGPS was suggested to be associated with the survival (HR 2.37 [95% CI:0.89-6.33], P = 0.145). Even after stratification by clinical covariates, these associations persisted.

Conclusion: We conclude that the HS-mGPS is useful as an independent prognostic factor in HNC.
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http://dx.doi.org/10.18632/oncotarget.26438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319335PMC
December 2018

Predictive biomarkers for combined chemotherapy with 5-fluorouracil and cisplatin in oro- and hypopharyngeal cancers.

Mol Clin Oncol 2018 Feb 29;8(2):378-386. Epub 2017 Nov 29.

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of The Ryukyus, Nishiharacho, Okinawa 903-0215, Japan.

The present study aimed to identify significant correlations between gene expression and chemotherapy response to 5-fluorouracil (5-FU)/cisplatin in head and neck squamous cell carcinoma (HNSCC), and to identify patients who would benefit from induction chemotherapy for both organ preservation and survival. A total of 64 patients who underwent radical treatment for HNSCC were enrolled. All patients received induction chemotherapy with 5-FU/cisplatin and tumor responses were evaluated. Pretreatment biopsy specimens from all patients were assayed for mRNA expression of thymidylate synthase, dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, tymidine phosphorylase, glutathione S-transferase-pi, p53, RB Transcriptional Corepressor 1, B-cell lymphoma 2 (Bcl-2), Bcl-xL, E2F Transcription Factor 1, epidermal growth factor receptor, human epidermal growth factor receptor 2, phosphoinositide 3-kinase, phosphatase and tensin homolog, vascular endothelial growth factor (VEGF), cyclooxygenase-2, XPA, DNA Damage Recognition And Repair Factor, excision repair cross-complementing 1 (ERCC1), multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein 1, equilibrative nucleoside transporter 1 and β-tubulin by reverse transcription-quantitative polymerase chain reaction, and the association between the expression levels of these genes and patient response to chemotherapy was determined. The complete response (CR) group and non-CR group for induction chemotherapy comprised 32.8 and 67.2% of patients, respectively. The 5-year overall survival rate was significantly higher for the CR group (95%) compared with the non-CR group (57%). According to univariate analysis, chemotherapy response was associated with T-class and mRNA expressions of DPD, ERCC1, XPA, p53, Bcl-2, VEGF and MDR1. Multivariate analysis identified ERCC1 expression and T-class as significant predictors of response to chemotherapy, indicating that a DNA-repair pathway and apoptosis pathway are pivotal mechanisms governing response to chemotherapy. The findings suggest that ERCC1 expression could be a predictive biomarker for chemotherapy response to 5-FU/cisplatin in HNSCC. Assessing mRNA expression is a standard method for these studies, however further investigations examining polymorphisms and mutations in addition to apoptotic responses are required to determine target gene activation in HNSCC.
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http://dx.doi.org/10.3892/mco.2017.1521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774537PMC
February 2018

Renal protective effect of a hydration supplemented with magnesium in patients receiving cisplatin for head and neck cancer.

J Otolaryngol Head Neck Surg 2018 Feb 2;47(1):10. Epub 2018 Feb 2.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusaku, Nagoya, 464-8681, Japan.

Background: Our study analyzes the effect of magnesium supplementation on nephrotoxicity in patients receiving cisplatin for head and neck cancer.

Methods: We retrospectively reviewed the medical records of patients with head and neck cancer who received two doses of cisplatin (80 mg/m2) and 5-fluorouracil (800 mg/m2) 3 weeks apart from August 2008 to October 2012. The regimen prior to 2011 (crystalloid-only) involved the administration of 1000 mL of lactated Ringer's solution on the day prior to cisplatin infusion and 2000 mL of continuous infusion of saline on the day of cisplatin infusion. The regimen after 2011 (magnesium-supplemented) did not involve hydration on the day before cisplatin administration but used 1000 mL of 0.9% saline with magnesium sulfate (20 mEq) administered for 3 hours before cisplatin infusion.

Results: Sixty-five patients were treated with the crystalloid-only regimen and 56 patients with the magnesium-supplemented regimen. The mean creatinine clearance in the magnesium-supplemented group decreased by 4.9 mL/kg/min, whereas that in the crystalloid-only group decreased by 15.0 mL/kg/min after two courses. In multivariate analysis, only magnesium-supplemented hydration was an independent predictive factor for preventing cisplatin-induced nephrotoxicity (odds ratio = 0.157, 95% confidence interval 0.030-0.670, P = 0.0124).

Conclusion: We demonstrated that an intravenous hydration regimen supplemented with magnesium prevented cisplatin-induced nephrotoxicity in patients with head and neck cancer.
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http://dx.doi.org/10.1186/s40463-018-0261-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797413PMC
February 2018

Multicenter Phase 2 Study of Cisplatin and 5-Fluorouracil With Concurrent Radiation Therapy as an Organ Preservation Approach in Patients With Squamous Cell Carcinoma of the Cervical Esophagus.

Int J Radiat Oncol Biol Phys 2016 12 3;96(5):976-984. Epub 2016 Sep 3.

Department of Surgery, National Cancer Center Hospital East, Chiba, Japan.

Purpose: To clarify, in a multicenter, single-arm, phase 2 study (UMIN Clinical Trials Registry no. UMIN000001439), the clinical profile of chemoradiotherapy (CRT) for cervical esophageal cancer.

Patients And Methods: Patients with operable cervical esophageal cancer, excluding candidates for endoscopic resection, were enrolled. Protocol treatment consisted of CRT and adjuvant chemotherapy (CT). First, patients received concurrent CRT with 5-fluorouracil (5-FU) plus cisplatin (CDDP). Chemotherapy consisted of 5-FU at 700 mg/m intravenous on days 1 to 4 and CDDP at 70 mg/m intravenous on day 1, repeated every 4 weeks for 2 cycles. Radiation therapy consisted of 60 Gy in 30 fractions. After completion of CRT, 2 additional cycles of CT with 5-FU (800 mg/m, days 1-5) and CDDP (80 mg/m, day 1) were repeated at a 4-week interval. The primary endpoint was 3-year overall survival.

Results: Thirty patients were enrolled across 8 institutions in Japan, consisting of 26 men and 4 women with a median age of 64.5 years (range, 50-75 years). No grade 4 hematologic toxicity was seen in the CRT phase, and 1 grade 4 thrombocytopenia was seen in the CT phase. Grade 3 nonhematologic acute toxicities in the CRT phase were nausea (10%), mucositis (13.3%), and dysphagia (13.3%). No treatment-related death in either phase occurred. Overall complete response rate was 73%, and 3-year overall and laryngectomy-free survival were 66.5% and 52.5%, respectively. Regarding T4 disease, 3-year overall and laryngectomy-free survival were 58.3% and 38.5%, respectively.

Conclusions: This study, the first prospective study for cervical esophageal cancer, showed that CRT has sufficient efficacy and safety for use as an alternative to surgery for these patients.
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http://dx.doi.org/10.1016/j.ijrobp.2016.08.045DOI Listing
December 2016

Prognostic impact of pathological response to neoadjuvant chemotherapy followed by definitive surgery in sinonasal squamous cell carcinoma.

Head Neck 2016 04 2;38 Suppl 1:E1305-11. Epub 2016 Mar 2.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.

Background: The significance of neoadjuvant chemotherapy followed by definitive surgery for sinonasal squamous cell carcinoma (SCC) was investigated using surgical specimens.

Methods: Surgery was performed in 58 patients, including 43 patients who had received neoadjuvant chemotherapy. The pathological response was classified as grades 0 (no effect), 1 (slight effect), 2 (moderate effect), and 3 (marked effect), and its correlation with prognosis was investigated.

Results: Grade 2 or 3 response was observed in 34.9% of cases that received neoadjuvant chemotherapy. Overall survival (OS), disease-free survival (DFS), locoregional control, and freedom from distant metastasis were significantly better in the effective neoadjuvant chemotherapy group (grades 2 and 3) than in the less effective neoadjuvant chemotherapy group (grades 0 and 1) and the non-neoadjuvant chemotherapy group combined.

Conclusion: Pathological response to neoadjuvant chemotherapy in sinonasal SCC was related to disease prognosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1305-E1311, 2016.
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http://dx.doi.org/10.1002/hed.24217DOI Listing
April 2016

Salvage surgery and microsurgical reconstruction for recurrence of skull base osteosarcoma after carbon ion radiotherapy.

Nagoya J Med Sci 2015 Nov;77(4):667-73

Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Carbon ion radiotherapy has recently emerged as an alternative choice of treatment for malignant tumors of the head and neck. However, it is still in the infant stages and its influence on subsequent salvage surgery remains unclear. Here we report the case of a 43-year-old woman who underwent salvage surgery for left frontal bone osteosarcoma recurrence following carbon ion radiotherapy. Tumor resection was performed with a wide margin including the tissue considered to have been damaged by carbon ion radiotherapy. The dural defect was reconstructed using a fascia lata graft and pedicled galeal pericranial flap. The soft tissue defect was reconstructed using an anterolateral thigh flap anastomosed to the ipsilateral neck interposed by the radial forearm flap. As the patient developed no postoperative wound complications, she was able to initiate adjuvant chemotherapy early. Carbon ion radiotherapy is useful for its focused distribution and strong biological effects. Although the affected field may be limited, its high potency may severely damage adjacent normal tissue and lead to serious postoperative complications. Despite these concerns, satisfactory results were achieved in this case.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664599PMC
November 2015

Role of induction chemotherapy for N3 head and neck squamous cell carcinoma.

Auris Nasus Larynx 2015 Apr 8;42(2):150-5. Epub 2014 Dec 8.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. Electronic address:

Objective: The treatment of head and neck squamous cell carcinoma (HNSCC) with N3 (>6cm) lymph nodes remains difficult, and the best treatment strategy has not been elucidated. The aim of this study was to evaluate the outcomes of various treatment modalities.

Methods: Sixty-nine patients with HNSCC and N3 neck disease treated with definitive therapy in our institute between 1987 and 2013 were included in the analysis. We compared the clinical outcomes of radiotherapy (RT) alone, chemoradiotherapy (CRT) and surgery with or without induction chemotherapy (ICT).

Results: The overall survival (OS) at three years for the patients with N3 neck disease was 41%. The three-year OS rates of patients treated with definitive surgery and definitive CRT were 41% and 48%, respectively. There were no significant differences between these two treatments (P=0.82). The OS of patients who received ICT followed by definitive therapy was significantly better than that of patients who did not (P<0.001). The most common recurrence pattern was distant metastases. The rate of distant metastases was 61% of all treatment failures (20/33).

Conclusion: The high rate of distant metastases in patients with N3 neck disease suggests that prevention of distant metastases can improve survival. Based on this study, we consider that ICT may play an important role in the treatment of N3 neck disease.
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http://dx.doi.org/10.1016/j.anl.2014.10.007DOI Listing
April 2015

Selection of therapeutic treatment with alternating chemoradiotherapy for larynx preservation in laryngeal carcinoma patients.

Jpn J Clin Oncol 2014 Nov 3;44(11):1063-9. Epub 2014 Sep 3.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya.

Objective: We analyzed the efficacy of treatments that included alternating chemoradiotherapy in laryngeal cancer patients.

Methods: Alternating chemoradiotherapy consisted of chemotherapy with 5-fluorouracil (600 mg/m(2)/day) on Days 1-6 and cisplatin (80 mg/m(2)) on Day 7 followed by radiotherapy with 30 Gy. Additional chemoradiotherapy was administered to responders, and laryngectomy was performed in non-responders. The contribution of alternating chemoradiotherapy to laryngeal preservation was compared with that of radiotherapy in patients with T2 disease and with that of laryngectomy in patients with T3/T4 disease.

Results: Analysis of 87 patients was conducted. The 5-year overall survival rate of T2 patients (n = 46) was 88.9% for definitive radiotherapy and 82.5% for alternating chemoradiotherapy. The laryngectomy-free rate in T2 patients was 90.5% for definitive radiotherapy and 80.0% for alternating chemoradiotherapy. In patients with T3/T4 disease (n = 41), the 5-year overall survival rate was 86.9% for alternating chemoradiotherapy and 67.4% for laryngectomy. The laryngectomy-free rate in T3/T4 patients was 91.7% for alternating chemoradiotherapy and 0.0% for laryngectomy.

Conclusions: In advanced carcinoma of the larynx, alternating chemoradiotherapy treatment might enable larynx preservation.
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http://dx.doi.org/10.1093/jjco/hyu131DOI Listing
November 2014

The nodal response to chemoselection predicts the risk of recurrence following definitive chemoradiotherapy for pharyngeal cancer.

Acta Otolaryngol 2014 Aug;134(8):865-71

Department of Head and Neck Surgery, Aichi Cancer Center Hospital , Nagoya , Japan.

Conclusions: The poor response of neck tumors to induction chemotherapy (ICT) as chemoselection is related to a significantly worse prognosis, including higher risks of local recurrence and/or distant metastasis, after definitive chemoradiotherapy (CRT).

Objectives: Neck dissection is frequently performed to treat residual lymph nodes after CRT for the purpose of locoregional control; however, the prognosis of patients with pathologically proven residual neck tumors is poor, and no methods for predicting unfavorable results before CRT have been established. Therefore, in the present study, we focused on the response of lymph nodes to ICT and its relationship with the prognosis among patients treated with chemoselection.

Methods: We retrospectively reviewed a total of 27 oropharyngeal and 24 hypopharyngeal squamous cell carcinoma stage III/IV consecutive patients with cervical lymph node metastasis who exhibited a response of >50% in the primary tumor to ICT followed by concurrent definitive CRT.

Results: The relapse-free survival of the patients who responded (partial response/complete response, PR/CR) to ICT was significantly superior to that of the patients who did not respond (stable disease, SD) to ICT (p = 0.008).
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http://dx.doi.org/10.3109/00016489.2014.894252DOI Listing
August 2014

Prognostic factors and outcomes for salvage surgery in patients with recurrent squamous cell carcinoma of the tongue.

Asia Pac J Clin Oncol 2016 Mar 2;12(1):e141-8. Epub 2013 Aug 2.

Department of Head and Neck Surgery, Aichi Cancer Center.

Aim: Recurrence rates of oral cancer following primary treatment have been reported in the range of 25-48%. However, salvage therapy remains a critical challenge to improving outcomes. Here, we investigated prognostic factors and outcomes for salvage surgery in patients with recurrent oral tongue squamous cell carcinoma (OTSCC).

Methods: We retrospectively reviewed patients who were referred to Aichi Cancer Center, Japan, for the treatment of recurrent OTSCC. All patients included in the present study had undergone salvage surgery. Data to identify the predictive value of prognostic factors were available from 69 patients. Prognostic factors were assessed using Cox's proportional hazards regression analysis. Differences in overall survival between groups of patients were assessed by the log-rank test.

Results: In all, 36 patients (52%) developed second recurrence or died, of which 21 (58%) occurred within 12 months of salvage surgery. Univariate analysis indicated that survival was significantly worse in patients with recurrent stage III or IV tumors, two or more positive cervical lymph nodes, levels IV or V positive cervical lymph nodes, extracapsular spread (ECS) of positive cervical lymph nodes and a disease-free interval from initial treatment of less than 12 months. On multivariate analysis, ECS was an independent prognostic factor for overall survival after salvage surgery.

Conclusion: Neck status at the time of salvage surgery, particularly ECS is a significant prognostic factor for surgical salvage. Survival was also influenced by the stage of the recurrent tumor and disease-free interval, suggesting that the biological features of recurrent tumors might impact on prognosis.
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http://dx.doi.org/10.1111/ajco.12087DOI Listing
March 2016

Impact of positron emission tomography with the use of fluorodeoxyglucose on response to induction chemotherapy in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma.

Acta Otolaryngol 2013 May;133(5):523-30

Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Conclusion: Maximum standardized uptake values (SUVmax) have prognostic value for induction chemotherapy (ICT) response and survival in oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC) patients. Pretreatment positron emission tomography with the use of fluorodeoxyglucose ((18)F-FDG PET) may be an aid in deciding the treatment strategy in OHSCC patients.

Objectives: We investigated the association between pretreatment (18)F-FDG PET and response to ICT and survival in OHSCC patients.

Methods: We conducted a retrospective cohort study of 58 OHSCC patients treated at Aichi Cancer Center Hospital. The predictive impact of SUVmax of the primary tumor site was evaluated using statistical multivariate proportional hazard models.

Results: Thirty-one cases (53%) were located in the oropharynx and 27 (47%) in the hypopharynx. Median SUVmax was 11.6 (range 3.2-23.5), and was significantly higher in the 8 patients with less than stable disease than in the 50 with more than partial response (median SUVmax, 17.3 vs 11.1; p = 0.002). In multivariate analysis, hazard ratios for the medium and high SUVmax groups relative to the low group were 3.07 (95% confidence interval, 0.62-15.29; p = 0.170) and 4.71 (0.97-22.89; p = 0.055), respectively, and the dose-response relationship was statistically significant (p trend = 0.047). A similar tendency was observed on subclassification by oropharynx and hypopharynx.
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http://dx.doi.org/10.3109/00016489.2012.733411DOI Listing
May 2013

Clinical outcome and patterns of recurrence of head and neck squamous cell carcinoma with a limited field of postoperative radiotherapy.

Jpn J Clin Oncol 2013 Jul 9;43(7):719-25. Epub 2013 May 9.

Department of Radiation Oncology, Aichi Cancer Center Hospital, Aichi, Japan.

Background: Postoperative radiotherapy is the standard treatment for head and neck squamous cell carcinoma having high-risk features in surgical specimens. However, its severe toxicity can be a significant problem. This study was undertaken to evaluate the efficacy of our limited-field postoperative radiotherapy with the aim of reducing morbidity by minimizing the radiation field.

Methods: Between 2000 and 2009, 154 patients with head and neck squamous cell carcinoma received limited-field postoperative radiotherapy. The reason for postoperative radiotherapy was close/positive margins in 33 patients and extracapsular extension in 91. The median radiation dose was 50 Gy (30-66.4). The radiation field covered the tumor bed without lymph node regions for close/positive margins and only involved sites of the neck region were irradiated for multiple nodes or extracapsular extension.

Results: With a median follow-up of 43 months for surviving patients, the 3-year overall survival and progression-free survival rates were 53.7 and 42.1%, respectively. The 3-year rates of progression-free survival of the group having major risks (i.e. close/positive margins and/or extracapsular extension) and the group with other risks were 34.7 and 62.8%, respectively (P < 0.01). Thirty-one local recurrences (20%), of which 22 were located out-of-field, and 44 regional recurrences (29%), of which 16 were located out-of-field, developed. Late toxicity of grade 3 or greater developed in only six patients (3.8%).

Conclusions: Although the toxicities associated with limited-field postoperative radiotherapy could be kept to lower levels, the locoregional control rate did not seem to be sufficient. We should arrange the radiation field depending on risk factors.
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http://dx.doi.org/10.1093/jjco/hyt066DOI Listing
July 2013

Neck dissection after chemoradiotherapy for oropharyngeal and hypopharyngeal cancer: the correlation between cervical lymph node metastasis and prognosis.

Int J Clin Oncol 2014 Feb 23;19(1):30-7. Epub 2013 Jan 23.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.

Background: Recently, the role of chemoradiotherapy (CRT) for preserving organs in the treatment of head and neck cancer has been increasing. However, the indication for post-CRT neck dissection (ND) and its surgical extent is still controversial. The purpose of this study was to discuss the indications for post-CRT ND and the proper extent of the surgical procedure.

Methods: We performed a retrospective analysis on N2-3 oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC) patients treated with CRT in our institute from 1995 to 2008, and determined the prognostic impact of post-CRT ND and the distribution of cervical lymph node (CLN) metastasis based on the pathological results of ND.

Results: The patients without pathological CLN metastases had good prognoses, whereas patients with pathological CLN metastases exhibited a significantly high recurrence rate (P = 0.033). Based on the pathological results of ND, performing selective ND at levels II-IV can contain 88 and 85 % of CLN metastasis of the oropharynx and hypopharynx, respectively. In all cases, when pathological CLN metastases were found at level V in ND following CRT, distant metastases developed.

Conclusions: The presence of pathological CLN metastasis affects prognosis, but also a diffuse distribution of CLN metastasis worsens prognosis; that is, the presence of CLN metastasis at level V after CRT appears to be an indicator of distant metastasis. Post-CRT ND may not make sense as a salvage intervention for improving the prognosis in such situations. We concluded that the proper extent of post-CRT ND of OHSCC is selective ND including levels II-IV.
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http://dx.doi.org/10.1007/s10147-013-0518-9DOI Listing
February 2014

[Postoperative chemoradiotherapy with weekly cisplatin for patients at high-risk for recurrence of head and neck squamous cell carcinoma-A phase I/II study].

Gan To Kagaku Ryoho 2012 Oct;39(10):1495-500

Dept. of Head and Neck Surgery, Aichi Cancer Center Hospital, Japan.

A phase I/II study of postoperative chemoradiotherapy with weekly cisplatin for head and neck squamous cell carcinoma was conducted. The eligiblity of patients were the high risk features, i. e., multiple lymph nodes metastasis(2 or more), extracapusular extension of nodal disease(ECE), or the presence of tumor at the surgical section margins(at 5mm or less). The recommended dose of CDDP in a phase I study was 30mg/m2. We performed a phase II study to assess toxicity and tolerability. We assessed 13 patients, 10 of whom were enrolled in a phase II study, and 3 patients in phase I were given the RD. Acute adverse events were rather mild, including grade 1-2 anemia(50%), mucositis(43%)and nausea/vomiting(43%). One patient required administration of CDDP to be discontinued due to grade 1 renal toxicity. The compliance rate was markedly high(85%: 11/13 patients). We consider weekly CDDP of 30mg/m2 to be a safe regimen in the setting of postoperative adjuvant chemoradiotherapy.
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October 2012

Surgical site infection in clean-contaminated head and neck cancer surgery: risk factors and prognosis.

Eur Arch Otorhinolaryngol 2013 Mar 4;270(3):1115-23. Epub 2012 Aug 4.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.

Since new treatment strategies, such as chemoradiotherapy, have been introduced for head and neck cancer, a higher number of unknown factors may be involved in surgical site infection in clean-contaminated head and neck cancer surgery. The aim of the present study was to clarify the risk factors of surgical site infection in clean-contaminated surgery for head and neck cancer and the prognosis of patients with surgical site infection. Participants were 277 consecutive patients with head and neck cancer who underwent clean-contaminated surgery for primary lesions at the Aichi Cancer Center over a 60-month period. A total of 22 putative risk factors were recorded in each patient and statistically analyzed to elucidate surgical site infection related factors. Surgical site infection was observed in 92 (32.1 %) of 277 cases. Univariate analysis indicated that alcohol consumption, T classification, neck dissection, reconstructive procedure, and chemoradiotherapy were significantly associated with surgical site infection. Multiple logistic regression analysis identified two independent risk factors for surgical site infection: reconstructive surgery (p = 0.04; odds ratio (OR) 1.77) and chemoradiotherapy (p = 0.01; OR 1.93). In spite of surgical site infection, the five-year overall survival rate of patients with surgical site infection was not significantly different from those without surgical site infection. Although surgical site infection did not impact the overall survival of patients with surgical procedures, head and neck surgeons should pay attention to patients with previous chemoradiotherapy as well as to those with a high risk of surgical site infection requiring reconstructive surgery.
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http://dx.doi.org/10.1007/s00405-012-2128-yDOI Listing
March 2013

The contribution of neck dissection for residual neck disease after chemoradiotherapy in advanced oropharyngeal and hypopharyngeal squamous cell carcinoma patients.

Int J Clin Oncol 2013 Aug 16;18(4):578-84. Epub 2012 May 16.

Department of Otorhinolaryngology, Head and Neck Surgery, Fukushima Medical University Graduate School of Medicine, Fukushima, Japan.

Background: Planned neck dissection after chemoradiotherapy (CRT) has remained controversial in advanced oro- and hypopharyngeal squamous cell carcinoma (OHSCC) patients. We evaluated the survival contribution of neck dissection (ND) in OHSCC patients with residual nodal disease following CRT.

Methods: We retrospectively evaluated 84 OHSCC patients with N2-3 disease treated at Aichi Cancer Center Hospital between 1995 and 2006. ND after CRT was performed for residual neck disease in 36 patients, but not in 48 patients to achieve a complete response. These two groups were analyzed in terms of both overall survival (OS) and regional control (RC), and surgical complications were evaluated.

Results: The 5-year OS was 76.7 % [95 % confidence interval (CI) 58.8-87.6] for the ND group and 73.9 % (58.6-84.3) for the non-ND group (P = 0.883). The 5-year RC was 91.6 % (76.1-97.2) for the ND group and 81.1 % (65.4-90.2) for the non-ND group (P = 0.252). Stratified by primary tumor site, the 5-year RC was 96.3 % (76.5-99.5) for the ND group, and 78.6 % (58.0-89.9) for the non-ND group (P = 0.072) in oropharyngeal squamous cell carcinoma patients, and 77.8 % (36.5-93.9) for the ND group and 85.9 % (54.0-96.3) for the non-ND group (P = 0.541) in hypopharyngeal squamous cell carcinoma patients. In addition, the complications after ND were tolerable.

Conclusions: We demonstrated that ND was feasible, safe, and correlated with clinical outcomes in OHSCC patients with residual nodal disease after CRT.
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http://dx.doi.org/10.1007/s10147-012-0419-3DOI Listing
August 2013

Follow-up after intraoperative sentinel node biopsy of N0 neck oral cancer patients.

Eur Arch Otorhinolaryngol 2011 Mar 20;268(3):429-35. Epub 2010 Aug 20.

Department of Otorhinolaryngology, Japanese Red Cross Nagoya Daiichi Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, Aichi 453-8511, Japan.

The objective of the study was to evaluate the validity of sentinel node (SN) biopsy in early oral cancer patients focusing on the accuracy of intraoperative diagnoses of SN status, recurrences in follow-up and impact on patient survival. Previously untreated N0 oral cancer patients were candidates for the study. Using a radioisotope method, an intraoperative SN biopsy was performed. Patients with a positive frozen section of SN underwent immediate neck dissection as a single-stage procedure; they were followed in our outpatient clinic. Forty-five cT1-2N0 patients with squamous cell carcinoma were analyzed. There were seven patients with positive SN, five of whom were detected by intraoperative frozen section analysis. The sensitivity, specificity and accuracy of the intraoperative frozen section analysis of SN were 71.4, 100 and 95.6%, respectively. There were 13 recurrences in the course of all patients treated. Those with positive SN showed a tendency toward recurrence. Three patients with negative SN suffered from delayed ipsilateral neck recurrence. These were considered false negatives at a rate of 7.9%. The 5-year overall survival rate of all patients was 91.1%. SN-positive patient survival was significantly poorer than that of SN-negative patients. Positive SN had a negative impact on the survival. SN biopsy was shown to be a valuable method for determining the neck status of early oral cancer patients. The concordance rate of intraoperative multislice frozen section analysis of SN and patient neck status at the time of operation was 95.6%. SN-positive patients exhibited a tendency toward cancer recurrence. There were three cases of false negatives not conforming to the SN concept and their rate was 7.9%. Positive SN had a negative impact on patient survival.
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http://dx.doi.org/10.1007/s00405-010-1364-2DOI Listing
March 2011

Impact of multiple alcohol dehydrogenase gene polymorphisms on risk of upper aerodigestive tract cancers in a Japanese population.

Cancer Epidemiol Biomarkers Prev 2009 Nov 27;18(11):3097-102. Epub 2009 Oct 27.

Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.

Alcohol intake is positively associated with the risk of upper aerodigestive tract (UAT) cancer. The genes that encode alcohol-metabolizing enzymes, primarily alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH), are polymorphic. In Caucasians, significant associations between polymorphisms in ADH1B (rs1229984) and ADH1C (rs698 and rs1693482), and UAT cancer have been observed, despite strong linkage disequilibrium among them. Moreover, UAT cancer was significantly associated with rs1573496 in ADH7, and not with rs1984362 in ADH4. However, little evidence is available concerning ADH4 or ADH7 polymorphisms in Asian populations. We conducted a matched case-control study to clarify the role of ADH polymorphisms in a Japanese population. Cases and controls were 585 patients with UAT cancer and 1,170 noncancer outpatients. Genotyping for ADHs and ALDH2 was done using TaqMan assays. Associations between polymorphisms and UAT cancer were assessed by odds ratios and 95% confidence intervals using conditional logistic regression models that adjusted for age, sex, smoking, drinking, and ALDH2. Adjusted odds ratios were significant for rs4148887 and rs3805322 in ADH4, rs1229984 in ADH1B, rs698 and rs1693482 in ADH1C, and rs284787, rs1154460, and rs3737482 in ADH7. We also observed that ADH7 rs3737482 and ADH4 rs4148887 had independently and statistically significant effects on UAT cancer. The magnitude of effect of these ADH polymorphisms was greater in subjects who were heavy drinkers, heavy smokers, and had esophageal cancer. These findings show that multiple ADH gene polymorphisms were associated with UAT cancer in this Japanese population. Further studies in various ethnicities are required.
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http://dx.doi.org/10.1158/1055-9965.EPI-09-0499DOI Listing
November 2009

[A Phase II study of docetaxel and cisplatin in patients with recurrent or unresectable squamous cell carcinoma of the head and neck].

Gan To Kagaku Ryoho 2009 Aug;36(8):1281-5

Dept. of Head and Neck Surgery, Aichi Cancer Center Hospital.

A Phase I / II study of docetaxel (DOC) and cisplatin (CDDP) combination therapy was conducted. The respective recommended dose (RD) in a phase I study was DOC 60 mg/m(2) and CDDP 80 mg/m(2). We performed a multicenter phase II study to assess the antitumor activity and toxicity of this RD. Patients with recurrent or unresectable squamous cell carcinoma of the head and neck were eligible. For inclusion in this study, patients were required to be >or=20<70 years of age with a Performance Status of 0 to 2. Adequate bone marrow as well as adequate renal and liver function were required. We assessed 22 patients, 13 of whom were enrolled in the phase II study, and 9 patients in phase I were given the RD. Grade 3 or higher neutropenia occurred in 12 patients (55%). There was no episode of febrile neutropenia of more than 3 days or grade 4 neutropenia of more than 3 days receiving G-CSF. Nausea was the most frequent toxicity, but only one patient experienced vomiting of more than grade 3. Pneumonia (grade 3), thrombocytopenia (grade 4) and emphysema (grade 2) were observed. No one achieved a complete response (CR) and 5 achieved a partial response (PR), for an overall response rate of 22.7% (5/22). Stable disease (SD) was seen in 11 and progressive disease (PD) in 6. In 21 of 22 patients, a relapse occurred despite previous treatment. For this population, the response rate was 19.0% (4/21).
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August 2009

[Detection of FDG-PET and FDG-PET/CT in head and neck squamous cell carcinoma].

Nihon Jibiinkoka Gakkai Kaiho 2007 Sep;110(9):629-34

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya.

We evaluated the accuracy of staging in 159 patients with head and neck squamous cell carcinoma (HNSCC) scanned by FDG-PET and 116 patients with the same cancer scanned by FDG-PET/computed tomography (CT). The accuracy was measured by comparing the FDG-PET/FDG-PET/CT findings at the primary tumor site, cervical node sites and distant metastatic sites with the clinical diagnosis. Especially, accuracy at cervical sites was evaluated from the screening point of view. Both examinations yielded an accuracy rate of more than 80% for each site, and a negative predictive value of more than 90% for the cervical sites. For the cervical sites, the positive predictive value (PPV) of FDG-PET was 78% and of FDG-PET/CT was 82%. When one cervical lymph node metastasis was detected by FDG-PET, the PPV was 63%, which appears to be comparatively low. Both examinations showed high accuracy for staging of HNSCC. In the near future, excellent screening examination might become possible with the spread of FDG-PET/CT. However, both examinations do not yield the direct image of the carcinoma itself, but only the status of glucose metabolism in the carcinoma. Care must always be exercised in the interpretation, as there are not a few false negative and false positive cases.
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http://dx.doi.org/10.3950/jibiinkoka.110.629DOI Listing
September 2007

Management of a total parotidectomy defect with a gastrocnemius muscle transfer and vascularized sural nerve grafting.

Ann Plast Surg 2007 Jun;58(6):677-82

Department of Head and Neck Surgery and Reconstructive Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Immediate facial nerve reconstruction is very demanding after total parotidectomy. Under such conditions, we reconstructed facial nerves using vascularized sural nerve with free lateral gastrocnemius muscle flap. The patient was a 14-year-old male diagnosed with mucoepidermoid carcinoma of the right parotid gland. We reconstructed zygomatic, buccal, and mandibular branches of facial nerve using 2 vascularized sural nerves, medial sural cutaneous nerve, and the lateral sural cutaneous nerve. The postoperative course was good, and there was no flap trouble. The reinnervated nerve recovered from 3 months after the operation. In 6 months after operation, almost normal animation was recovered, except for the corners of the patient's mouth. The advantages of this flap are feasible harvesting in the supine position, feasible filling of the dead space, possible harvesting of 2 series of lateral sural cutaneous nerve and median sural cutaneous nerve, and less sacrifice of the donor site. The disadvantage of this method is that the diameter of the pedicle is smaller than that of the medial pedicle. But the diameters of the lateral sural artery and vein are suitable to anastomose the cervical artery and vein. This flap is one of the good options for reconstruction of facial nerves after total parotidectomy.
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http://dx.doi.org/10.1097/01.sap.0000239844.57064.edDOI Listing
June 2007

[A Phase I study of docetaxel and cisplatin for advanced squamous cell carcinoma of the head and neck].

Gan To Kagaku Ryoho 2005 Jul;32(7):977-81

Dept of Head and Neck Surgery, Aichi Cancer Center Hospital.

A Phase I study of docetaxel (DOC) and cisplatin (CDDP) combination therapy was conducted as second-line treatment for advanced squamous cell carcinoma of the head and neck in order to determine the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT) of DOC, and the recommended dose (RD) for this combination therapy. Twenty patients with recurrence for whom failed first-line chemotherapy with CDDP and 5-FU proved in-effective (17 male, 3 female; age range 38-74 years; performance status 0=7, 1 =8, 2=5) were included in this study. DOC at dose level I (40 mg/m2), level II (50 mg/m2), level III (60 mg/m2) and level IV (70 mg/m2) was used, followed by CDDP administration at a fixed dose of 80 mg/m2. Originally, chemotherapy was repeated every 3 weeks. In level I, grade 4 hypokalemia occurred in one patient. No DLT occurred at level II. At level III, one patient experienced grade 4 vomiting. At level IV, grade 2 creatinine clearance decrease occurred in a total of two patients. The maximum tolerated dose in this combination therapy was DOC 70 mg/m2, and CDDP 80 mg/m2. The recommended dose for this combination therapy is DOC 60 mg/m2, and CDDP 80 mg/ m2. A multicenter cooperative phase II study in this RD is recommended.
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July 2005