Publications by authors named "Hitoshi Hirakawa"

59 Publications

Effectiveness of nivolumab affected by prior cetuximab use and neck dissection in Japanese patients with recurrent or metastatic head and neck cancer: results from a retrospective observational study in a real-world setting.

Int J Clin Oncol 2021 Apr 8. Epub 2021 Apr 8.

Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita15 Nishi7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.

Background: To examine the effect of prior use of cetuximab and neck dissection on the effectiveness of nivolumab, we conducted a large-scale subgroup analysis in Japanese patients with recurrent/metastatic head and neck cancer.

Methods: Data on the effectiveness of nivolumab were extracted from patient medical records. All patients were analyzed for effectiveness by prior cetuximab use. In the analyses for prior neck dissection, only patients with locally advanced disease were included.

Results: Of 256 patients analyzed, 155 had received prior cetuximab. Nineteen of 50 patients with local recurrence underwent neck dissection. The objective response rate was 14.7 vs 17.2% (p = 0.6116), median progression-free survival was 2.0 vs 3.1 months (p = 0.0261), and median overall survival was 8.4 vs 12 months (p = 0.0548) with vs without prior cetuximab use, respectively. The objective response rate was 23.1 vs 25.9% (p = 0.8455), median progression-free survival was 1.8 vs 3.0 months (p = 0.6650), and median overall survival was 9.1 vs 9.9 months (p = 0.5289) with vs without neck dissection, respectively.

Conclusions: These findings support the use of nivolumab for patients with recurrent/metastatic head and neck cancer regardless of prior cetuximab use or neck dissection history.

Trial Registration Number: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436).
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http://dx.doi.org/10.1007/s10147-021-01900-4DOI Listing
April 2021

Coordinated Expression of HPV-6 Genes with Predominant E4 and E5 Expression in Laryngeal Papilloma.

Microorganisms 2021 Mar 3;9(3). Epub 2021 Mar 3.

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

Laryngeal papilloma (LP) associated with human papillomavirus (HPV)-6 or -11 infection shows aggressive growth. However, the detailed molecular mechanism of virus-driven tumorigenesis has not been uncovered fully. HPV-6 viral gene expression and dynamic alterations were investigated with in situ localization of viral DNA and RNA in 13 patients with HPV-6-infected laryngeal papilloma. The average viral load was 4.80 × 10 ± 1.86 × 10 copies/ng DNA. , , and mRNAs accounted for 96% of the expression of 9 mRNAs. The alteration of viral DNA load during recurrence paralleled the mRNA expression levels, and the expression of all mRNAs showed a similar curve. , , and were expressed in the middle to upper part of the epithelium and were co-expressed in the same cells. E4 immunohistochemistry demonstrated an extensively positive reaction in the upper cell layer in accordance with mRNA expression. These results suggest that individual viral genes are coordinately expressed for viral replication, virus release, and immunosurveillance avoidance. The newly developed E4-specific monoclonal antibody can be applied to further functional studies and clinical applications such as targeted molecular therapies.
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http://dx.doi.org/10.3390/microorganisms9030520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998961PMC
March 2021

Different Indocyanine Green Fluorescence Patterns of Two Skin Metastases of Hypopharyngeal Squamous Carcinoma: A Case Report.

Photodiagnosis Photodyn Ther 2021 Feb 12:102211. Epub 2021 Feb 12.

Department of Radiology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan.

Background: Skin metastasis of squamous cell carcinoma of the head and neck is a rare disease. Although the lesion is usually detected by physical examination, ultrasound imaging, computed tomography, and positron emission tomography, some problems remain, such as technical difficulty, objectivity, and radiation exposure. Recently, indocyanine green fluorescence angiography (ICG-FA) has been used to discover superficial tumors. However, the optimum timing of ICG injection and fluorescence patterns of skin tumors in ICG-FA are still unknown.

Case Presentation: We encountered a 60-year-old man with hypopharyngeal squamous cell carcinoma. The patient underwent concurrent chemotherapy, radiotherapy, and surgery. However, during these treatments, the patient had two nodules in the skin of the right upper limb. Thus, the patient underwent ICG-FA. The two skin metastatic nodules showed different fluorescence patterns. One lesion showed high fluorescence intensity during ICG-FA. However, the fluorescence intensity of a small part of the other lesion exceeded that of the surrounding tissue only for a short time.

Conclusion: We suggest that ICG-FA is effective for detecting skin metastases, and with further studies on the various fluorescence patterns of skin tumors, this technique will become more efficient.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102211DOI Listing
February 2021

Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma.

BMC Cancer 2021 Jan 22;21(1):87. Epub 2021 Jan 22.

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan.

Background: Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway, especially raptor and rictor, in HPV-related head and neck cancer is still unclear. The aim of the present study was to elucidate the role of the mTOR pathway in HPV-related oropharyngeal squamous cell carcinoma (OPSCC).

Methods: The present study involved two strategies. The first was to investigate the activity of mTOR and mTOR-related complexes in high-risk HPV-positive (UM-SCC47 and CaSki) and HPV-negative (SCC-4 and SAS) cancer cell lines. The second was to elucidate mTOR complex expression in 80 oropharyngeal cancer tissues and to examine the relationship between mTOR complex expression and survival in patients with OPSCC.

Results: The UM-SCC47 and CaSki cell lines showed high gene and protein expression of raptor. They also exhibited G1/S and G2/M phase cell cycle arrest following 24 h incubation with 6 μM temsirolimus, a rapamycin analog, and temsirolimus administration inhibited their growth. HPV-related OPSCC samples showed high gene and protein expression of raptor and rictor compared with HPV-unrelated OPSCC. In addition, HPV-related OPSCC patients with high raptor and rictor expression tended to have a worse prognosis than those with low or medium expression.

Conclusions: These results suggest that raptor and rictor have important roles in HPV-related OPSCC and that temsirolimus is a potential therapeutic agent for patients with HPV-related OPSCC. This is the first report to reveal the overexpression of raptor and rictor in HPV-related OPSCC.
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http://dx.doi.org/10.1186/s12885-021-07794-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821513PMC
January 2021

Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study.

Int J Clin Oncol 2021 Mar 21;26(3):494-506. Epub 2020 Nov 21.

Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita15 Nishi7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.

Background: To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice.

Methods: This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records.

Results: Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1-27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2-12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141.

Conclusions: The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141.

Trial Registration Number: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436).
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http://dx.doi.org/10.1007/s10147-020-01829-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895797PMC
March 2021

Incidentally Detected Microcarcinoma of Thyroid in Surgical Specimens of the Goiter in Pediatric Patient: A Case Report.

Tokai J Exp Clin Med 2020 Sep 20;45(3):144-147. Epub 2020 Sep 20.

Department of Pediatric Surgery, Tokai University Hachioji Hospital, 1838 Ishikawa-machi, Hachioji, Tokyo 192-0032, Japan.

A 14 year-old girl with a previous medical history of cholecystic polyps was referred to our department with throat discomfort during swallowing. The cervical ultrasound and magnetic resonance imaging revealed a massive polycystic formation with a diameter of 45 × 24 × 31 mm consistent with a right lobe goiter. However, there were no findings for suspected malignancy. Hemithyroidectomy was performed and the specimen was sent for histopathological assessment. Hematoxylin-eosin staining of the right lower nodule showed variably-sized follicles consistent with adenomatous goiter. The right upper nodule showed a growth of relatively compact sized follicles with a thick fibrous capsule. A satellite nodule lying outside of the tumor capsule was consistent with minimally invasive follicular thyroid microcarcinoma. We observed her without any additional treatment and no recurrence is seen at present.
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September 2020

Brain Activity in Patients With Unilateral Vocal Fold Paralysis Detected by Functional Magnetic Resonance Imaging.

J Voice 2020 Aug 30. Epub 2020 Aug 30.

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan. Electronic address:

Objectives: Understanding brain activity in response to unilateral vocal fold paralysis is essential to determine the neural compensatory mechanism underlying adaptation to voice disorders and to develop novel and improved rehabilitation programs for these disorders. We aimed to clarify brain activity during phonation (prolonged vowel, |i:|) in patients with chronic left vocal fold paralysis (LVFP) and compare with that in normal controls.

Study Design: Case-control study.

Methods: This functional magnetic resonance imaging (fMRI) study of an event-related task comprised 12 individuals with LVFP of more than 6 months duration and 12 healthy controls. The experimental task alternated phonation (prolonged vowel, |i:|) and no phonation (rest) conditions. The functional images obtained were single-shot gradient-echo echo-planar imaging. The volumes were acquired parallel to the anterior-posterior commissure plane and were sensitive to BOLD contrast. Data sets were processed and statistically analyzed using Statistical Parametric Mapping 8 software. Within-group analyses were conducted by applying the one-sample t test (P < 0.001, uncorrected). A random-effects analysis was used for group comparison.

Results: The LVFP group showed significantly higher brain activity in the right premotor areas, left parietal lobule, right primary somatosensory areas, and bilateral supplementary motor area and lower brain activity in the auditory-related areas of the superior temporal gyrus. There were no significant correlations of the percent signal change on fMRI with disease duration, maximum phonation time, or age.

Conclusion: Patients with chronic unilateral vocal fold paralysis have stronger activity during voluntary phonation in various central networks. More detailed information on the central nervous system regions related to voluntary phonation from early to chronic phase is needed to understand the compensatory mechanisms in vocal fold paralysis and to establish an effective rehabilitation program. This is the first report to investigate brain activity in chronic unilateral vocal fold paralysis.
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http://dx.doi.org/10.1016/j.jvoice.2020.08.008DOI Listing
August 2020

Measurement of stapes footplate thickness in otosclerosis by ultra-high-resolution computed tomography.

Acta Otolaryngol 2020 Nov 23;140(11):899-903. Epub 2020 Jul 23.

Department of Radiology, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Japan.

Background: Ultra-high-resolution computed tomography (U-HRCT) utilizes a 1024 × 1024 matrix with 0.25-mm section thickness, offering better spatial resolution than conventional multi-detector row CT to detect anatomic data for otologic surgery.

Aims: We examined stapes footplate thickness using U-HRCT in relation to stapedotomy to predict the difficulty of the surgical procedure.

Materials And Methods: Subjects were 12 otosclerosis patients and 25 controls who underwent diagnostic U-HRCT. A profile curve (Hounsfield units) was used to measure stapes footplate thickness along a perpendicular line across the stapes footplate in a plane parallel to the lateral semicircular canal.

Results: Footplate thickness was smaller at the midpoint than just before the anterior crus and just after the posterior crus. Interobserver variability was lowest at the midpoint, where foot plate thickness was significantly greater in the affected ear in otosclerosis patients compared with controls (0.60 ± 0.09 mm vs 0.46 ± 0.04 mm;  < .001). Otosclerosis patients were detected using U-HRCT with a high area under the curve. Difficulty in the stapes opening procedure correlated with stapes footplate thickness.

Conclusions: Footplate thickness on U-HRCT correlated with temporal bone anatomy and corresponded to surgical difficulty. U-HRCT-derived anatomic data is useful for evaluating the stapes.
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http://dx.doi.org/10.1080/00016489.2020.1788225DOI Listing
November 2020

Induction Chemotherapy in Hypopharyngeal Cancer: Influence of DNA Repair Gene Polymorphisms.

Anticancer Res 2020 Jun;40(6):3277-3285

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Background/aim: The aim was to clarify whether DNA repair gene polymorphisms can be used to predict response to cisplatin, 5-fluorouracil, and docetaxel (TPF) as induction chemotherapy (ICT) in Japanese patients with hypopharyngeal cancer (HPC).

Materials And Methods: DNA repair gene polymorphisms (rs3212986, rs1799793, rs13181, and rs25487) were analyzed in 117 HPC patients and 125 control subjects by PCR-restriction fragment length polymorphism. Forty-one HPC patients who received TPF-based ICT, followed by surgery or chemoradiotherapy/radiotherapy were analyzed for ICT response, laryngeal preservation, and survival outcome.

Results: ICT responders (29 cases) had significantly better overall survival than ICT non-responders (12 cases; 86.0% vs. 37.0%, respectively, p<0.01 by log-rank test) and better laryngeal preservation rates. The DNA repair gene polymorphisms were not related to ICT response.

Conclusion: ICT is beneficial for chemoselection of HPC patients, but a role for DNA repair gene polymorphisms in ICT response was not confirmed.
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http://dx.doi.org/10.21873/anticanres.14310DOI Listing
June 2020

ERCC1 C8092A polymorphism predicts fair survival outcome in Japanese patients with pharyngo-laryngeal squamous cell carcinoma.

Eur Arch Otorhinolaryngol 2020 Feb 20;277(2):601-610. Epub 2019 Nov 20.

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan.

Purpose: To evaluate the prognostic significance of DNA excision repair gene polymorphisms, excision repair cross-complementation group 1 (ERCC1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) polymorphisms were investigated in Japanese patients with head and neck squamous cell carcinoma (HNSCC).

Methods: A total of 225 consecutive patients with HNSCC who underwent surgery or chemoradiotherapy/radiotherapy (CRT/RT) with curative intent as primary treatment from 2006 to 2017 were recruited. ERCC1 C8092A and XRCC1 Arg399Gln polymorphisms in DNA extracted from individual blood samples were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Cumulative survival was estimated by Kaplan-Meier analysis with a log-rank test and Cox proportional hazards model stratified by treatment arm, adjusting for clinical prognostic factors.

Results: Multivariate analysis showed that carriers with the ERCC1 8092 (C/A+A/A) genotype (hazard ratio, 3.56; 95% confidence interval, 1.22-7.39; p = 0.02) had significantly worse survival than those with ERCC1 8092 C/C who received CRT/RT. Conversely, the XRCC1 Arg399Gln polymorphism did not influence survival in patients who received CRT/RT as well as surgery.

Conclusion: The ERCC1 C8092A polymorphism might be an independent predictor of response to CRT and survival outcome in patients with HNSCC. This is the first report to investigate the role of DNA excision repair gene polymorphisms in patients with head and neck cancer in a Japanese population.
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http://dx.doi.org/10.1007/s00405-019-05731-yDOI Listing
February 2020

Hypopharyngeal cancer risk in Japanese: Genetic polymorphisms related to the metabolism of alcohol- and tobacco-associated carcinogens.

J Cancer Res Ther 2019 Jul-Sep;15(3):556-563

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Background: Several studies have investigated hypopharyngeal cancer (HC) risk in combination with xenobiotic metabolism-related genetic polymorphisms and the burden of alcohol consumption and smoking in European countries but not in East Asian countries.

Patients And Methods: This hospital-based case-control study involved 61 male patients with HC and 71 male cancer-free controls. Information on age, body mass index, and alcohol and cigarette consumption was obtained from medical records, a self-completion questionnaire, and a thorough interview by an otolaryngologist. Alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), cytochrome P450 A1 (CYP1A1) MspI, CYP1A1 Ile462Val, glutathione S-transferase (GST) M1, GSTT1, and GSTP1 gene polymorphisms were determined by polymerase chain reaction-based methods. Univariate and multivariate analyses were performed by adjustment for age by the Mantel-Haenszel method.

Results: The burden of alcohol and cigarette consumption significantly increased the risk of HC and showed a synergistic effect. ADH1B*1/*1 (odds ratio [OR] 7.34) and ALDH2 *1/*2 (OR 13.22) were significant risk factors for HC. Individuals with ADH1B*1/*1 or ALDH2 *1/*2 who consumed alcohol were more susceptible to HC. However, polymorphisms of CYP1A1 gene and GSTs were not significant cancer risk factors in patients with HC.

Conclusions: ADH1B*1/*1 and ALDH2 *1/*2 were significant risk factors for HC, while polymorphism of CYP1A1 gene and GSTs was not a significant risk factor for HC. These polymorphisms determined the effects of alcohol and cigarette smoke in addition to burden of alcohol and cigarettes intake on the risk of HC.
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http://dx.doi.org/10.4103/jcrt.JCRT_980_17DOI Listing
November 2019

High-risk type human papillomavirus infection and p16 expression in laryngeal cancer.

Infect Agent Cancer 2019 5;14. Epub 2019 Mar 5.

1Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215 Japan.

Background: Oropharyngeal cancers associated with high-risk type human papillomavirus (HR-HPV) infection have better prognosis than virus negative cancers. Similarly, the HPV status in laryngeal cancer (LC) may be associated with better outcome.

Methods: Samples from 88 patients with LC were investigated using the polymerase chain reaction (PCR) and p16 immunohistochemistry for HR-HPV analysis. The cut-off point for p16 overexpression was diffuse (≥75%) tumor expression with at least moderate (+ 2/3) staining intensity.

Results: The 5-year cumulative survival (CS) rate was 80.7% in all patients with LC. According to a combination of HR-HPV DNA status and p16 overexpression, subjects with LC were divided into four groups: HR-HPV DNA-positive/p16 overexpression-positive ( = 5, 5.7%; CS = 100%), HR-HPV DNA-positive/p16 overexpression-negative ( = 11, 12.5%; CS =81.8%), HR-HPV DNA-negative/p16 overexpression-positive ( = 0), and HR-HPV DNA-negative/p16 overexpression-negative ( = 72, 81.8%; CS = 79.5%). HR-HPV DNA-positive/p16-positive cases tended to have integrated HPV infection and high viral load, compared with HR-HPV DNA-positive/p16 overexpression-negative cases.

Conclusions: LC patients with HPV infection and high levels of p16 expression might have an improved survival outcome; however, it is necessary to recruit additional LC cases with HPV infection to determine the definitive characteristics of HPV-mediated LC and estimate survival outcome. These results may contribute to the development of a useful method for selecting patients with a potentially fair response to treatment and ensure laryngeal preservation.
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http://dx.doi.org/10.1186/s13027-019-0224-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402092PMC
March 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

Staging and prognosis of oropharyngeal carcinoma according to the 8th Edition of the American Joint Committee on Cancer Staging Manual in human papillomavirus infection.

Eur Arch Otorhinolaryngol 2019 Mar 29;276(3):827-836. Epub 2018 Dec 29.

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

Purpose: The aim of this study was to evaluate the 8th edition of the American Joint Committee on Cancer Staging Manual: Head and Neck Section on oropharyngeal squamous cell cancer (OPSCC) and to clarify the relationship between p16 overexpression and the presence of human papillomavirus (HPV) DNA using fresh frozen samples.

Methods: Samples from 100 OPSCC patients were analyzed using polymerase chain reaction (PCR) and p16 immunohistochemistry.

Results: Five-year overall survival (OS) was 73.0%, 93.9%, and 62.2% in all, p16-positive (n = 34), and p16-negative (n = 66) cases, respectively. OS tended to be better aligned with stage in the 8th edition than in the 7th edition. The 5-year OS was 96.0% in never or light smokers (< 40 pack-years), and 87.5% in heavy smokers (≥ 40 pack-years) in the p16-positive group, respectively (p = 0.027). HPV infection was found in 100% of p16-positive and 21.2% of p16-negative cases. The p16-positive cases had higher viral load and integrated physical status than the p16-negative cases. Although 1 case with p16 overexpression showed no PCR amplification using consensus primers, PCR amplification was detected using HPV 16 E6-specific primers.

Conclusions: The 8th edition predicts OPSCC prognosis more accurately than the 7th edition and p16-overexpression is an excellent surrogate marker for detecting HPV infection. Although high-risk-type HPV infection was observed in p16-negative cases, it showed no significant effect in survival outcome.
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http://dx.doi.org/10.1007/s00405-018-05263-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411679PMC
March 2019

Detection of human papillomavirus in branchial cleft cysts.

Oncol Lett 2018 Aug 30;16(2):1571-1578. Epub 2018 May 30.

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

High-risk human papillomavirus (HPV) DNA has been reported to be present in branchial cleft cysts, but further information is required to clarify the role of HPV infection in branchial cleft cysts. The presence of HPV, the viral load and the physical statuses in samples from six patients with branchial cleft cysts were investigated using the polymerase chain reaction (PCR), quantitative PCR, hybridization (ISH) using HPV DNA probes and p16 immunohistochemical analysis. High-risk type HPV-16 DNA was identified in four of the six branchial cleft cysts analyzed. Of the HPV-positive branchial cleft cysts, three exhibited mixed-type integration of HPV. HPV DNA was distributed among the basal-to-granular layers of the cystic wall in ISH analysis, and p16 was weakly expressed in the nuclei and cytoplasm of the same layers in patients with integration. ISH revealed that one patient with episomal-type infection exhibited HPV DNA in the cyst wall and did not express p16. Two patients without evidence of HPV infection exhibited weak p16 expression in the superficial cyst-lining cells of branchial cleft cysts. These results indicate that infection with high-risk HPV types may be common in branchial cleft cysts. In addition, p16 is not a reliable surrogate marker for HPV infection in branchial cleft cysts.
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http://dx.doi.org/10.3892/ol.2018.8827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036516PMC
August 2018

Prospective randomized investigation implementing immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids during the perioperative period for head and neck carcinomas.

Jpn J Clin Oncol 2018 Apr;48(4):356-361

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

Objectives: The purpose of this study is to evaluate whether a nutritional supplement with a high blend ratio of ω-3 fatty acids can minimize weight loss and attenuate increases in inflammatory marker levels during the perioperative period in patients undergoing surgery for head and neck carcinoma.

Methods: Patients with ≥5% weight loss within 6 months were considered as targets for aggressive nutritional intervention. Among these patients, those with head and neck squamous cell carcinoma, who underwent major invasive surgery with free flap reconstruction were included in the present study. The patients were randomized into two groups: the 'nutritional supplementation group' and the 'non-intervention group'. The nutritional supplementation group received two packs of Prosure® (an eicosapentaenoic acid [EPA]-enriched oral nutritional supplement) per day for 28 days during the perioperative period.

Results: Compliance with the Prosure® dosage was very good at 6277/6720 ml (average) before surgery (93%) and 5229/6720 ml after surgery (78%), and a significant increase in EPA concentration was shown in the group that received Prosure® (P < 0.0001: Welch's t-test). However, 28 days of nutritional supplementation did not lead to further weight change or changes in the inflammatory marker levels of patients were already showing cachexia (based on weight loss). Interestingly, no further change in the mean weight was noted in these patients. The incidence of postoperative complications did not differ between the two groups.

Conclusion: In this trial, immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids from 2 weeks before surgery until 2 weeks after surgery was not effective for maintaining the nutritional status of head and neck carcinoma patients.
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http://dx.doi.org/10.1093/jjco/hyy008DOI Listing
April 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

Prognostic importance of pathological response to neoadjuvant chemotherapy followed by definitive surgery in advanced oral squamous cell carcinoma.

Jpn J Clin Oncol 2017 Nov;47(11):1038-1046

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Okinawa.

Objective: The clinical importance of neoadjuvant chemotherapy (NAC) followed by definitive surgery was retrospectively investigated in clinical Stage III/IV oral squamous cell carcinoma (OSCC).

Methods: Surgery was performed for OSCC in 164 patients, including 72 patients who had received NAC (two cycles of cisplatin and fluorouracil) prior to surgery from January 2004 to December 2014. The clinical characteristics and survival parameters of the groups that received and did not receive NAC were evaluated. The pathological response was classified as Grade 0 (no effect), 1a (very slight effect), 1b (slight effect), 2 (moderate effect) or 3 (marked effect), and its correlation with prognosis was investigated.

Results: There were no statistical differences in survival indicators between patients who received NAC and those who did not (overall survival, P = 0.75). The proportion of patients who received NAC in the effective NAC group (Grades 1b, 2, and 3) was 52.8%. After a median follow-up of 35 months, overall survival (P = 0.01), disease-free survival (P = 0.002), locoregional disease-free survival (P = 0.003), and distant disease-free survival (P = 0.01) were significantly better in the effective NAC group than in the less effective NAC group (Grades 0 and 1a).

Conclusion: Although NAC had a limited effect on disease prognosis in OSCC, the pathological response to NAC could be an important prognostic indicator for advanced OSCC.
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http://dx.doi.org/10.1093/jjco/hyx097DOI Listing
November 2017

Surgical Treatment of Inguinal Hernia with Prolapsed Ovary in Young Girls: Emergency Surgery or Elective Surgery.

Tokai J Exp Clin Med 2017 Jul 20;42(2):89-95. Epub 2017 Jul 20.

Department of Surgery, Pediatric Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Objective: Inguinal ovarian hernias are common in young girls. Many articles in medical literature recommend early surgery for inguinal ovarian hernia because of the risk of torsion of the prolapsed ovary. However, since many irreducible herniated ovaries in newborn infants and during early infancy undergo spontaneous reduction by the age of 9 months, the policy at our institute is to obtain informed consent from the patient's family and then wait to perform surgery until after 9 months of age. In the present study, we assessed the indications for surgery for inguinal ovarian hernia in newborn infants and during early infancy.

Methods: Between 2003 and 2011, a total of 673 girls with inguinal hernias (age at the time of onset of symptoms: mean, 42.5 months; median, 39 months) were brought to our outpatient clinic for consultation. We reviewed their age at the time of the onset of hernia symptoms and their age at the time of surgery, their history of surgery, and their history of inguinal ovarian hernia using information obtained from their medical records.

Results: Among the 673 outpatients, 71 patients (mean/median age at the time of onset of symptoms: 11.2/1.5 months) were diagnosed as having an inguinal ovarian hernia at the time of diagnosis. Among these patients, surgery was performed for 58 patients (mean/median age at the time of surgery: 21.3/11 months). Of these patients, the ovary had already spontaneously reduced into the abdomen in 35 cases (mean/median age at the time of surgery: 24.1/12months), whereas the ovaries were on the wall of the hernia sac in 22 cases (mean/median age at the time of surgery: 17.3/10 months). In one case, a testis instead of an ovary was observed in the hernia sac at the time of surgery. Surgeries were performed in 611 of the 673 patients (mean/median age at the time of surgery: 54/50 months). In 35 cases (mean/median age at the time of surgery: 21.6/10 months), the ovary was still on the hernia sac wall at the time of surgery, but an inguinal ovarian hernia had not been diagnosed before surgery in 13 of these cases. A severe complication occurred in only one case, in which a hernia sac that contained a fallopian tube and ovary was ligated. None of the cases exhibited torsion of the ovary within the inguinal canal.

Conclusion: Since the ovary can be expected to undergo spontaneous reduction into the abdomen by late infancy in many young patients with inguinal ovarian hernias, patients with inguinal ovarian hernias can be treated by elective surgery at the most convenient age, after 9 months of age.
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July 2017

Protein-losing Enteropathy Caused by Spontaneous Reduction of Intussusception with Meckel's Diverticulum.

Tokai J Exp Clin Med 2017 Apr 20;42(1):10-12. Epub 2017 Apr 20.

Department of Pediatric Surgery, Tokai University Hachioji Hospital, 1838 Ishikawa-machi, Hachioji, Tokyo 192-0032, Japan.

Protein-losing enteropathy (PLE) is a relatively rare condition. In this article, we report the case of a 6-year-old boy diagnosed with PLE who developed intussusception, in whom at operation Meckel's diverticulum was identified in his intestine. Spontaneous reduction of intussusception is thought to relate to the mechanism of PLE.
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April 2017

Lymphoepithelial carcinoma in parotid gland related to EBV infection: A case report.

Auris Nasus Larynx 2018 Feb 27;45(1):170-174. Epub 2017 Jan 27.

Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Japan.

Lymphoepithelial carcinoma commonly occurs at the nasopharynx and rarely occurs at other sites in the head and neck region. It is well known to occur at limited patients of local area as Asia or Arctic Circle. Related to this point, it is pointed out that this tumor has strong relation with Epstein-Barr Virus (EBV) infection. In this time, we experienced to treat lymphoepithelial carcinoma with metastatic cervical lymph nodes occurring at parotid gland. The morbidity ratio of this tumor is less than one percent of all parotid gland tumors. Moreover, we proved the infection of EBV to tumor cell by in situ hybridization (ISH). Incidentally, because it is considered that this tumor has well sensitivity against irradiation or anti-tumor drugs, prognosis of this tumor is better than that of other head and neck tumors with different pathological type. Actually, we tried to perform chemotherapy twice in (Nedaplatin (CDGP) 60mg/m×day 2 and 5-FU 600mg/m×day 5) and to irradiate about 70Gy dose against parotid gland and cervical lymph nodes. It could not find local recurrence or metastasis as of now after five years from treatment.
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http://dx.doi.org/10.1016/j.anl.2016.12.010DOI Listing
February 2018

Quality of life and functional status of terminally ill head and neck cancer patients: a nation-wide, prospective observational study at tertiary cancer centers in Japan.

Jpn J Clin Oncol 2017 Jan 27;47(1):47-53. Epub 2016 Sep 27.

Department of Palliative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo.

Background: Little is known about quality of life and functional status of patients with terminally ill head and neck cancers.

Methods: We conducted a multicenter, prospective, observational study to examine quality of life and functional status in terminally ill head and neck cancer patients.

Results: Of the 100 patients meeting inclusion criteria, 72 were observed until death. There was no significant difference in the quality of life score between baseline and Week 3. Forty patients (54.9%) could speak and 22 patients (30.5%) could have oral intake upon study entry. Fifty-three patients (74.6%) received enteral nutrition. Twenty-six patients (36.6%) required dressing changes for fungating tumors. The route of nutritional intake (nasogastric tube vs. percutaneous gastric tube) might be predictive for the duration of hospital stay (64 vs. 21 days, P = 0.0372).

Conclusion: There was no significant relationship between quality of life and functional status seen in this study. Feeding tube type could have the most impact on quality of life.
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http://dx.doi.org/10.1093/jjco/hyw138DOI Listing
January 2017

Sentinel node biopsy for oral cancer: A prospective multicenter Phase II trial.

Auris Nasus Larynx 2017 Jun 3;44(3):319-326. Epub 2016 Aug 3.

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

Objective: A recent study identified a survival benefit with prophylactic neck dissection (ND) at the time of primary surgery as compared with watchful waiting followed by therapeutic neck dissection for nodal relapse, in patients with cN0 oral squamous cell carcinoma (OSCC). Alternative management of cN0 neck cancer is recommended to minimize the adverse effects of ND, indicating the need for sentinel node biopsy (SNB) and limited neck dissection. We conducted a multicenter Phase II study to examine the feasibility of SNB for clinically N0 OSCC.

Methods: Previously untreated N0 OSCC patients (n=57) with clinical late-T2 or T3 tumors were enrolled across 10 institutions. SNB navigated with multislice frozen section analysis of sentinel nodes (SNs) and SNB supported sentinel node lymphatic basin dissection (SN basin dissection) were performed in a one-stage procedure. The endpoint was to investigate the rate of false-negative metastases after SN basin dissection and SNB alone.

Results: Most tumors were late-T2 lesions (n=50; 87.7%). SNs were identified in all patients. A total of 196 SNs were detected. Among these SNs, 35 (17.8%) were positive for metastasis (9 in level I, 12 in level II, 12 in level III, 1 in level V and 2 in the contralateral region of the neck). The false-negative rate of SNB supported by SN basin dissection and SNB alone was 4.5% and 9.1%, respectively. The concordance of the SN status in intraoperative frozen sections with the permanent histopathology was 97.4% (191/196). The sensitivity and specificity of intraoperative pathological evaluation were 85.7% (30/35) and 100% (30/30), respectively. The 3-year overall survival (OS) and disease-free survival was 89.5% and 82.5%, respectively. The OS of SN-negative patients was significantly longer than that of SN-positive patients (P=0.047).

Conclusion: The current study verified that SN basin dissection was a useful back-up procedure for SNB performed as a one-stage procedure, showing a low false-negative rate. SNB alone is an appropriate staging method for patients with clinical N0 staging, and a reliable procedure to determine the appropriate levels for neck dissection.
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http://dx.doi.org/10.1016/j.anl.2016.07.008DOI Listing
June 2017

Impact of total lesion glycolysis measured by F-FDG-PET/CT on overall survival and distant metastasis in hypopharyngeal cancer.

Oncol Lett 2016 Aug 23;12(2):1493-1500. Epub 2016 Jun 23.

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

The present study investigated the possible correlation between F-2-fluorodeoxyglucose (F-FDG)-uptake parameters and clinicopathological parameters in hypopharyngeal squamous cell carcinoma (HPSCC). A total of 53 patients, newly diagnosed with HPSCC, received pretreatment F-FDG-positron emission tomography/computed tomography (PET/CT). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) were calculated as F-FDG-uptake parameters of the primary tumor. Tumor thickness, depth of invasion and pathological tumor volume were pathologically measured. Upon univariate survival analysis, SUVmax ≥28.5, SUVpeak ≥19, MTV ≥12 and TLG ≥42 were significantly associated with a shorter overall survival (OS) time, and MTV ≥12 and TLG ≥42 were significantly associated with a shorter distant metastasis-free survival (DMFS) time. Upon multivariate analysis with adjustment for clinical T category and treatment group, patients with SUVmax ≥28.5 exhibited a significantly shorter OS time, while TLG ≥42 was significantly correlated with shorter OS and DMFS times. Upon simple regression analysis, TLG was found to be significantly associated with tumor thickness and depth of invasion, while MTV was found to be closely associated with pathological tumor volume. In conclusion, pretreatment F-FDG-PET/CT is likely to provide valuable prognostic parameters in HPSCC.
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http://dx.doi.org/10.3892/ol.2016.4765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950179PMC
August 2016

Treatment results of alternating chemoradiotherapy with early assessment for advanced laryngeal cancer: A multi-institutional phase II study.

Auris Nasus Larynx 2017 Feb 18;44(1):104-110. Epub 2016 Jul 18.

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

Objective: To evaluate the efficacy and safety of alternating chemoradiotherapy (ACRT) with early assessment of advanced laryngeal cancer.

Methods: Patients with stage III or IV glottic or supraglottic squamous cell carcinoma were enrolled. ACRT consisted of two cycles of chemotherapy involving 5-fluorouracil and cisplatin (weeks 1 and 6) and radiotherapy (RT; weeks 2 and 7) administered alternately. An early assessment was performed after one cycle of chemotherapy and RT. Patients with a partial response (PR) or a complete response at early assessment continued ACRT. Patients with stable disease (SD) or progressive disease at early assessment discontinued ACRT and underwent salvage surgery. After completion of ACRT, patients who had residual primary tumor and lymph metastasis underwent salvage surgery.

Results: Twenty-eight patients were enrolled in this trial. Median follow-up was 60.0 months. After each cycle of chemotherapy and RT, 24 of the 28 patients (85.7%) were assessed as having a PR at early assessment and continued ACRT, and 4 of 28 patients (14.3%) who were assessed as having SD at early assessment discontinued ACRT and underwent salvage surgery. The estimated 5-year local control and 5-year survival rates were 49.0% and 77.4%, respectively. Larynx preservation was achieved in 17 patients. The estimated 5-year laryngeal preservation rate was 59.4%. Major toxicity included nausea, stomatitis, dermatitis, dysphagia and hemoglobin toxicity. Grade 3 or 4 stomatitis occurred in three patients (10.7%).

Conclusion: The clinical results of ACRT with early assessment of advanced laryngeal cancer patients showed sufficient efficacy and safety.
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http://dx.doi.org/10.1016/j.anl.2016.05.003DOI Listing
February 2017

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

Retrospective analysis of the clinical efficacy of definitive chemoradiotherapy for patients with hypopharyngeal cancer.

Jpn J Clin Oncol 2016 Apr 29;46(4):344-9. Epub 2016 Jan 29.

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

Objective: A retrospective analysis was performed to evaluate the clinical efficacy of definitive chemoradiotherapy including intensity-modulated radiotherapy for patients with hypopharyngeal cancer.

Methods: Previously untreated 204 patients with hypopharyngeal cancer were treated with definitive chemoradiotherapy. Of note, 66-70 Gy was delivered to the primary and involved nodes and 36-54 Gy was delivered to the prophylactic lymph node using standard fractionated radiotherapy. One hundred and forty-six patients received induction chemotherapy as a larynx preservation strategy, followed by definitive radiotherapy with or without concurrent chemotherapy. Intensity-modulated radiotherapy was also performed after 2006.

Results: The median follow-up time of this cohort was 43.4 months (range; 6.9-151.0). The 3-year overall survival, progression-free survival and larynx preservation survival rates were 78.8% (95% confidence interval; 73.0-85.0), 58.4% (95% confidence interval; 51.8-65.9) and 67.5% (95% confidence interval; 61.0-74.7), respectively. Multivariate analyses identified the following significant prognostic factors: an advanced age, the T category and N category for overall survival, the T category and N category for progression-free survival and the T category for larynx preservation survival. Acute toxicities of Grade 3 or higher were observed in 47 patients (23.0%). Two patients (1.0%) had Grade 4 pharyngeal edema. Suspicious treatment-related death due to lethal pharyngeal hemorrhage occurred in 1 (0.4%) patient. The rates of Grade 2 xerostomia in patients treated with intensity-modulated radiotherapy were 28.1, 17.4 and 9.5% at 6 months, 1 and 2 years after the completion of radiotherapy, respectively.

Conclusions: The efficacy and safety of definitive chemoradiotherapy are considered feasible with sufficient laryngeal preservation.
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http://dx.doi.org/10.1093/jjco/hyv216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886140PMC
April 2016

Lymph node density is a prognostic factor in patients with major salivary gland carcinoma.

Oncol Lett 2015 Dec 19;10(6):3523-3528. Epub 2015 Oct 19.

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

Lymph node density (LND) has been reported to be a significant predictor of survival in patients with oral and other carcinomas exhibiting positive lymph nodes. The present study investigated whether the LND is associated with overall survival in subjects with major salivary gland carcinoma. A total of 78 patients newly diagnosed with major salivary gland carcinoma underwent primary tumor resection and neck dissection without preoperative treatment. Of these 78 patients, 32 with pathologically positive lymph nodes were enrolled in the present study. The LND was calculated as the ratio of the number of positive lymph nodes to the number of total lymph nodes. The survival rate was analyzed according to the Kaplan-Meier method. A univariate survival analysis was performed using the log-rank test, and a multivariate survival analysis was performed using the Cox proportional hazards model. An LND of ≥0.38 was found to significantly correlate with a shorter overall survival time in univariate analysis (P=0.017). In multivariate survival analysis, after adjusting for anatomical location (parotid gland/others), an LND of ≥0.38 was identified to be associated with a significantly shorter overall survival time. These results suggest that the LND functions as a prognostic factor in cases of major salivary gland carcinoma.
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http://dx.doi.org/10.3892/ol.2015.3814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665639PMC
December 2015