Publications by authors named "Akihito Watanabe"

42 Publications

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan.

Cancer Med 2021 Jun 15;10(12):3848-3861. Epub 2021 May 15.

Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209601PMC
June 2021

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 Jun 8;26(6):1049-1056. 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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-01900-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134300PMC
June 2021

Evaluation of Pharyngeal Background Mucosa in Patients with Superficial Hypopharyngeal Carcinoma.

Laryngoscope 2021 Mar 17. Epub 2021 Mar 17.

Department of Otolaryngology Head and Neck Surgery, Keiyukai Sapporo Hospital, Sapporo, Japan.

Objectives/hypothesis: Transoral surgery (TOS) has become increasingly popular for patients with superficial hypopharyngeal squamous cell carcinoma (SCC). However, the number of patients in whom metachronous multiple SCC of the head and neck (HNSCC) occurs has also increased. In this study, we investigated whether multiple lugol-voiding lesions (LVLs) in the pharyngeal background mucosa observed during TOS would be a biomarker of metachronous HNSCC.

Study Design: Retrospective study.

Methods: We examined 362 patients who underwent TOS for superficial hypopharyngeal carcinoma. Endoscopic images were reviewed in a blinded fashion by two endoscopists. LVLs in the pharyngeal mucosa were graded as follows: A, no lesions; B, 1 to 4 lesions; and C, ≥5 lesions per endoscopic view.

Results: Cumulative incidence curves of secondary HNSCC in the groups of grades A, B, and C revealed 3-year incidence rates of 14.4%, 18.8%, and 29.3%, respectively (P = .001 for A vs. C and P = .002 for B vs. C). Cumulative incidence curves of third HNSCC in the groups of grades A, B. and C revealed 5-year incidence rates of 3.9%, 9.8%, and 19.6%, respectively (P = .001 for A vs. C and P = .006 for B vs. C). Cumulative incidence curves of fourth HNSCC in the groups of grades A, B, and C revealed 7-year incidence rates of 0%, 2.3%, and 13.2%, respectively (P = .025 for A vs. C and P = .009 for B vs. C).

Conclusions: Multiple LVLs in the pharyngeal mucosa increase the risk of development of metachronous multiple HNSCC.

Level Of Evidence: 3 (nonrandomized, controlled cohort/follow-up study) Laryngoscope, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.29524DOI Listing
March 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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-020-01829-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895797PMC
March 2021

[Efficacy of Neoadjuvant Endocrine Therapy for Prostate Ductal Carcinoma with Large Multiple Cysts Prior to Robot-Assisted Laparoscopic Radical Prostatectomy].

Hinyokika Kiyo 2020 Apr;66(4):127-130

The Department of Urology, Kansai Medical University.

A 71-year-old man with gross hematuria and urinary retention showed a 7×8 cm polycystic mass compressing the prostate on the right ventral side on pelvic magnetic resonance imaging (MRI). The prostate specific antigen (PSA) level was 6.47 ng/ml. Prostate biopsy histopathology was consistent with prostate ductal carcinoma. Considering the difficulty of surgical therapy, endocrine therapy was undertaken prior to surgery for seven months. Almost all of the cyst disappeared ; robot-assisted laparoscopic radical prostatectomy was then successfully performed. Prostate ductal carcinoma is a relatively rare pathology for which radical prostatectomy plays an important role if the disease is localized. However, when ductal carcinoma involves large cysts, surgical treatment may be difficult. This report discusses the usefulness of neoadjuvant endocrine therapy to reduce the size of the cystic lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14989/ActaUrolJap_66_4_127DOI Listing
April 2020

Larynx-preserving hybrid surgery with endoscopic laryngopharyngeal surgery and open surgery for cervical esophageal cancer invading pharynx.

Dis Esophagus 2020 Dec;33(12)

Department of Surgery, Keiyukai Sapporo Hospital, Sapporo, Japan.

Larynx preserving hybrid surgery with endoscopic laryngopharyngeal surgery and open surgery (HELPS) was created for resectable cervical esophageal cancer (CEC) invading the hypopharynx. This study aimed to verify the effectiveness and to evaluate the feasibility of the new HELPS treatment method. Between 2014 and 2018, 19 patients with CEC invading the hypopharynx were treated with HELPS. The postoperative complications and survival rates were reviewed. Postoperative recurrent laryngeal nerve paralysis occurred in four patients. All patients consumed food orally without a feeding tube at the time of the discharge. The median follow-up period was 27 months. The 2- and 3-year overall survival rates were 94.7 and 71.5%, respectively. HELPS, a new surgical treatment method that utilizes endoscopic surgery, is effective, feasible and beneficial for preserving the larynx in patients with CEC even if the tumor invaded the pharynx.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/dote/doaa020DOI Listing
December 2020

Fabrication of Fe-Co Magnetostrictive Fiber Reinforced Plastic Composites and Their Sensor Performance Evaluation.

Materials (Basel) 2018 Mar 9;11(3). Epub 2018 Mar 9.

Department of Materials Processing, Graduate School of Engineering, Tohoku University, Aoba-yama 6-6-02, Sendai 980-8579, Japan.

The inverse magnetostrictive effect is an effective property for energy harvesting; the material needs to have large magnetostriction and ease of mass production. Fe-Co alloys being magnetostrictive materials have favorable characteristics which are high strength, ductility, and excellent workability, allowing easy fabrication of Fe-Co alloy fibers. In this study, we fabricated magnetostrictive polymer composites, in which Fe-Co fibers were woven into polyester fabric, and discussed their sensor performance. Compression and bending tests were carried out to measure the magnetic flux density change, and the effects of magnetization, bias magnetic field, and the location of the fibers on the performance were discussed. It was shown that magnetic flux density change due to compression and bending is related to the magnetization of the Fe-Co fiber and the bias magnetic field. The magnetic flux density change of Fe-Co fiber reinforced plastics was larger than that of the plastics with Terfenol-D particles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma11030406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872985PMC
March 2018

Synopsis of transoral endoscopic laryngopharyngeal surgery for superficial pharyngeal cancers.

Head Neck 2017 09 29;39(9):1779-1787. Epub 2017 Jun 29.

Division of Medical Science, Health Sciences University of Hokkaido, Ishikari-tobetsu, Japan.

Background: Endoscopic laryngopharyngeal surgery (ELPS) was developed for superficial pharyngeal cancers in Japan. In this study, we present our results of ELPS for superficial pharyngeal cancers.

Methods: From November 2009 to December 2015, 258 patients with superficial pharyngeal cancers underwent ELPS. Results, including survival rates, postoperative complications, and vocal function, are reviewed.

Results: The median follow-up period of 258 patients was 31 months. The overall and cause-specific survival rates over 3 years were 85.7% and 100%, respectively. Only 3 patients incurred local recurrences and were successfully salvaged by re-ELPS. Regarding postoperative complications, 4 patients required reoperation because of postoperative bleeding. As for the postoperative quality of life, no patients developed vocal fold paralysis. Every patient was able to consume meals at preoperative levels.

Conclusion: ELPS is a feasible and minimally invasive treatment for superficial pharyngeal cancers with impressive quality of life results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24839DOI Listing
September 2017

MK-801-induced deficits in social recognition in rats: reversal by aripiprazole, but not olanzapine, risperidone, or cannabidiol.

Behav Pharmacol 2015 Dec;26(8 Spec No):748-65

aSchool of Medical Sciences, Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland bGW Research Ltd, Sovereign House, Vision Park, Histon, Cambridgeshire, UK cQs' Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan.

Deficiencies in social activities are hallmarks of numerous brain disorders. With respect to schizophrenia, social withdrawal belongs to the category of negative symptoms and is associated with deficits in the cognitive domain. Here, we used the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) for induction of social withdrawal in rats and assessed the efficacy of several atypical antipsychotics with different pharmacological profiles as putative treatment. In addition, we reasoned that the marijuana constituent cannabidiol (CBD) may provide benefit or could be proposed as an adjunct treatment in combination with antipsychotics. Hooded Lister rats were tested in the three-chamber version for social interaction, with an initial novelty phase, followed after 3 min by a short-term recognition memory phase. No drug treatment affected sociability. However, distinct effects on social recognition were revealed. MK-801 reduced social recognition memory at all doses (>0.03 mg/kg). Predosing with aripiprazole dose-dependently (2 or 10 mg/kg) prevented the memory decline, but doses of 0.1 mg/kg risperidone or 1 mg/kg olanzapine did not. Intriguingly, CBD impaired social recognition memory (12 and 30 mg/kg) but did not rescue the MK-801-induced deficits. When CBD was combined with protective doses of aripiprazole (CBD-aripiprazole at 12 :  or 5 : 2 mg/kg) the benefit of the antipsychotic was lost. At the same time, activity-related changes in behaviour were excluded as underlying reasons for these pharmacological effects. Collectively, the combined activity of aripiprazole on dopamine D2 and serotonin 5HT1A receptors appears to provide a significant advantage over risperidone and olanzapine with respect to the rescue of cognitive deficits reminiscent of schizophrenia. The differential pharmacological properties of CBD, which are seemingly beneficial in human patients, did not back-translate and rescue the MK-801-induced social memory deficit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FBP.0000000000000178DOI Listing
December 2015

Global Trends in Alzheimer Disease Clinical Development: Increasing the Probability of Success.

Clin Ther 2015 Aug 1;37(8):1632-42. Epub 2015 Aug 1.

Global Clinical Development, OPDC, USA, Princeton, New Jersey.

Purpose: Alzheimer disease (AD) is a growing global health and economic issue as elderly populations increase dramatically across the world. Despite the many clinical trials conducted, currently no approved disease-modifying treatment exists. In this commentary, the present status of AD drug development and the grounds for collaborations between government, academia, and industry to accelerate the development of disease-modifying AD therapies are discussed.

Methods: Official government documents, literature, and news releases were surveyed by MEDLINE and website research.

Findings: Currently approved anti-AD drugs provide only short-lived symptomatic improvements, which have no effect on the underlying pathogenic mechanisms or progression of the disease. The failure to approve a disease-modifying drug for AD may be because the progression of AD in the patient populations enrolled in clinical studies was too advanced for drugs to demonstrate cognitive and functional improvements. The US Food and Drug Administration and the European Medicines Agency recently published draft guidance for industry which discusses approaches for conducting clinical studies with patients in early AD stages. For successful clinical trials in early-stage AD, however, it will be necessary to identify biomarkers highly correlated with the clinical onset and the longitudinal progress of AD. In addition, because of the high cost and length of clinical AD studies, support in the form of global initiatives and collaborations between government, industry, and academia is needed.

Implications: In response to this situation, national guidance and international collaborations have been established. Global initiatives are focusing on 2025 as a goal to provide new treatment options, and early signs of success in biomarker and drug development are already emerging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2015.07.006DOI Listing
August 2015

Efficient, effective, safe procedure to identify nonrecurrent inferior laryngeal nerve during thyroid surgery.

Head Neck 2016 Apr 20;38(4):573-7. Epub 2015 Jun 20.

Health Science University of Hokkaido, Ishikari-Tobetsu, Japan.

Background: The nonrecurrent inferior laryngeal nerve (NRILN) is always associated with the aberrant subclavian artery. CT images can detect this vascular anomaly, which predicts an NRILN. The purpose of this study was to report our procedure to identify the NRILN in patients with the aberrant subclavian artery.

Methods: Four of 730 patients undergoing thyroid operation in our hospital were preoperatively diagnosed with aberrant subclavian artery by CT of the neck. To avoid vocal cord paralysis, we approached the vagal nerve first before dissecting the paratracheal region to discover the separation point of the NRILN from the vagal nerve.

Results: The NRILN was identified without difficulty in all 4 patients. No patients showed vocal cord paralysis.

Conclusion: Approaching the vagal nerve first before dissecting the paratracheal region is an efficient, effective, and safe procedure to identify an NRILN in patients who are preoperatively diagnosed as having the aberrant subclavian artery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.23932DOI Listing
April 2016

Lymph node metastasis in t4 maxillary sinus squamous cell carcinoma: incidence and treatment outcome.

Ann Surg Oncol 2014 May 20;21(5):1706-10. Epub 2014 Feb 20.

Department of Otolaryngology - Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan,

Background: The purpose of this study was to evaluate the incidence of lymph node metastasis among patients with T4 maxillary sinus squamous cell carcinoma (MS-SCC) as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC.

Methods: Consecutive series of all patients (n = 128) with previously untreated T4 maxillary sinus SCC between 2006 and 2007 were obtained from 28 institutions belonging to or cooperating in the Head and Neck Cancer Study Group of the Japan Clinical Oncology Group.

Results: Of the 128 patients, 28 (21.9 %) had lymph node metastasis, and six patients (4.7 %) had distant metastasis at diagnosis. Among the 111 patients who were treated with curative intent, 98 had clinically N0 neck disease and did not receive prophylactic neck irradiation. A total of 11 patients (11.2 %) subsequently developed evidence of lymph node metastasis, of whom eight were among the 83 patients with an N0 neck and had not received elective neck treatment. There were 15 patients who received an elective neck dissection as part of the initial treatment, of whom three had pathologically positive for lymph node metastases. Of 11 patients, six patients with nonlateral retropharyngeal lymph node metastasis without primary or distant disease were successfully salvaged.

Conclusions: This study identified the incidence of lymph node metastasis among patients with T4 MS-SCC as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. These results will be of assistance in selecting treatment strategy for T4 MS-SCC in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-014-3544-6DOI Listing
May 2014

[Diagnosis and treatment for head and neck cancer-early detection-].

Authors:
Akihito Watanabe

Nihon Jibiinkoka Gakkai Kaiho 2013 Sep;116(9):1067-9

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3950/jibiinkoka.116.1067DOI Listing
September 2013

Clinical impact of iodine staining for diagnosis of carcinoma in situ in the floor of mouth, and decision of adequate surgical margin.

Auris Nasus Larynx 2012 Apr 31;39(2):193-7. Epub 2011 Aug 31.

Department of Otolaryngology, Keiyukai Sapporo Hospital, Sapporo, Japan.

Objective: The use of iodine staining has been recommended for the early detection of squamous cell carcinoma (SCC) in the upper aerodigestive tract. The purpose was to verify the effectiveness of iodine staining in detecting early squamous cell carcinoma in the floor of mouth.

Methods: Between 1995 and 2005, otolaryngological examinations including the floor of mouth were performed for 2278 esophageal cancer patients as a screening program of high-risk patient group. Iodine staining was applied to a lightly reddish and/or white patch, and/or uneven lesions in the floor of the mouth. Forceps biopsy was performed for demarcated unstained or lightly stained lesions. Three patients with the tumors in the floor of mouth, which were diagnosed as more over T2 level just by visual examination, were excluded from this study. If SCC was found in the specimen, mucosal resection was performed with a safety margin of 2mm from the unstained or lightly stained lesion. The incidence, rate of carcinoma in situ, and prognosis of cancer of the floor of mouth (CFOM) were assessed.

Results: Iodine staining was performed for 72 of 2278 patients (3.2%) according to the presence of suspicious reddish and/or whitish and/or uneven lesions. Of these, unstained or lightly stained areas after iodine staining were recognized in 47 patients and SCC was revealed in 28 of 47 patients. The diagnosis of other 19 patients included inflammatory mucosa (n=11), low grade dysplasia (n=6), and hyperkeratosis (n=2). Sensitivity and specificity of iodine staining for detecting SCC were 100% and 59.6%, respectively. Pathological diagnosis of the 28 patients included squamous cell carcinoma in situ (n=12), microinvasive squamous cell carcinoma (n=15) disease, and focal invasive squamous cell cancer (n=1). Twenty-four of 28 patients were treated with mucosal resection without mandible resection. The other 4 patients did not receive the treatment of CFOM due to concomitant far advanced esophageal cancer. In 24 patients undergoing mucosal resection, no patients developed local recurrence or metastasis to the cervical lymph nodes during an average of 74.2 months of follow-up period (from 7 to 156 months). The 5-year cause-specific survival of these patients was 100%.

Conclusion: The use of iodine staining as a part of otolaryngological examinations may be beneficial for the early detection of CFOM, including carcinoma in situ and micro-invasive SCC. Moreover, it would be very useful to determine an adequate surgical margin for locally mucosal resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2011.08.004DOI Listing
April 2012

Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ⁹-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour.

Psychopharmacology (Berl) 2012 Feb 28;219(3):859-73. Epub 2011 Jul 28.

School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.

Rationale: Phytocannabinoids are useful therapeutics for multiple applications including treatments of constipation, malaria, rheumatism, alleviation of intraocular pressure, emesis, anxiety and some neurological and neurodegenerative disorders. Consistent with these medicinal properties, extracted cannabinoids have recently gained much interest in research, and some are currently in advanced stages of clinical testing. Other constituents of Cannabis sativa, the hemp plant, however, remain relatively unexplored in vivo. These include cannabidiol (CBD), cannabidivarine (CBDV), Δ(9)-tetrahydrocannabivarin (Δ(9)-THCV) and cannabigerol (CBG).

Objectives And Methods: We here determined pharmacokinetic profiles of the above phytocannabinoids after acute single-dose intraperitoneal and oral administration in mice and rats. The pharmacodynamic-pharmacokinetic relationship of CBD (120 mg/kg, ip and oral) was further assessed using a marble burying test in mice.

Results: All phytocannabinoids readily penetrated the blood-brain barrier and solutol, despite producing moderate behavioural anomalies, led to higher brain penetration than cremophor after oral, but not intraperitoneal exposure. In mice, cremophor-based intraperitoneal administration always attained higher plasma and brain concentrations, independent of substance given. In rats, oral administration offered higher brain concentrations for CBD (120 mg/kg) and CBDV (60 mg/kg), but not for Δ(9)-THCV (30 mg/kg) and CBG (120 mg/kg), for which the intraperitoneal route was more effective. CBD inhibited obsessive-compulsive behaviour in a time-dependent manner matching its pharmacokinetic profile.

Conclusions: These data provide important information on the brain and plasma exposure of new phytocannabinoids and guidance for the most efficacious administration route and time points for determination of drug effects under in vivo conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00213-011-2415-0DOI Listing
February 2012

Predictors of cervical lymph node involvement in patients with pharyngeal carcinoma undergoing endoscopic mucosal resection.

Auris Nasus Larynx 2011 Dec 11;38(6):710-7. Epub 2011 Feb 11.

Department of Otolaryngology, Keiyukai Sapporo Hospital, Kita 1-1, Hondori 14-chome, Shiroishi-ku, Sapporo, Japan

Objective: Although detection of pharyngeal carcinoma remaining in the epithelium or subepithelial tissue layer has been difficult by routine examinations, recent advances in endoscopic technology have enabled us to detect these lesions. These patients can receive endoscopic mucosal resection (EMR) and generally have a good prognosis, but some patients have nodal involvement. The purpose was to investigate predictors of nodal involvement in patients with pharyngeal carcinoma undergoing EMR at our hospital.

Study Design: Outcomes research.

Methods: Lymph node involvement, endoscopic morphology, and tumor thickness were investigated in 152 patients treated between 2001 and 2009.

Results: Pathological examination revealed carcinoma in situ (CIS) for 77 patients and subepithelial invasion (SEPI) for 75 patients. There were no patients with muscular invasion. Nodal involvement was found in none of CIS but in 7 of 75 patients (9.3%) with SEPI. In patients with SEPI, the mean tumor thickness was significantly higher in patients with lymph node involvement (1311.4 ± 300.0 μm) than those without involvement (692.6 ± 495.7 μm) (p=0.002). Significant risk factors for nodal involvement included the tumor thickness over 1000 μm (p<0.001) and the presence of venous or lymphatic invasion (p<0.05). Based on analysis in relation to sensitivity and specificity, the tumor thickness over 1000 μm may serve as the most predictive factor for nodal involvement.

Conclusion: Tumor thickness can be a simple predictor for nodal involvement in cases of SEPI. Careful follow-up including neck palpation and annual imaging diagnostics such as computed tomography or ultrasonography are recommended for these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2011.01.001DOI Listing
December 2011

[Treatment of advanced head and neck cancer by TPF].

Gan To Kagaku Ryoho 2010 Jul;37(7):1240-3

Department of Otorhinolaryngology, Head and Neck Surgery, Keiyukai Sapporo Hospital, Sapporo, Hokkaido, Japan

View Article and Find Full Text PDF

Download full-text PDF

Source
July 2010

Narrowband imaging for early detection of malignant tumors and radiation effect after treatment of head and neck cancer.

Arch Otolaryngol Head Neck Surg 2010 Mar;136(3):234-9

Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chang Gung University at Chiayi, Taiwan.

Objectives: To determine the value of narrowband imaging (NBI) screening for the early detection of head and neck squamous cell carcinoma (HNSCC) in patients who have received treatment and to assess the impact of radiotherapy on detection rates.

Design: Cross-sectional study.

Setting: Tertiary referral center.

Patients: From July 1, 2007, through February 28, 2008, a total of 206 patients with HNSCC underwent rhinolarynx videoendoscopic screening performed using conventional white-light and NBI systems during their routine postoperative sessions.

Main Outcome Measure: The rate of detecting malignant tumors, depending on the anatomical site and stage of cancer and the history of radiotherapy after primary treatment.

Results: We identified 68 lesions by endoscopy in conventional white-light and/or NBI mode. Of these, 62 were histopathologically confirmed to be cancerous. The rates of detecting cancerous lesions by white-light and NBI modes were 100% and 97% for oral lesions, 69% and 100% for oropharyngeal lesions (P = .02), and 39% and 100% for hypopharyngeal lesions (P = .001), respectively. No difference was found between the 2 modes with regard to the detection of visible T1 to T4 tumors. However, NBI mode was significantly better than white-light mode for the detection of carcinoma in situ (P < .001).

Conclusion: We found that NBI-assisted endoscopy is highly useful for the detection of precancerous lesions in the oropharyngeal and hypopharyngeal mucosa and is not affected by a history of radiotherapy in patients with HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/archoto.2009.230DOI Listing
March 2010

The value of narrow band imaging for early detection of laryngeal cancer.

Eur Arch Otorhinolaryngol 2009 Jul 4;266(7):1017-23. Epub 2008 Nov 4.

Department of Otolaryngology, Keiyukai Sapporo Hospital, Kita 1-1, Hondori 14-chome, Shiroishi-ku, Sapporo, 003-0027, Japan.

We evaluate the value of laryngoscopy using narrow band imaging (NBI) system in the diagnosis of precancerous and cancerous laryngeal lesions. Thirty-four patients were suspected of having a total of 35 precancerous or cancerous laryngeal lesions among patients receiving conventional white-light laryngoscopy. All 34 patients underwent laryngoscopy with NBI system to determine whether those lesions were malignant before biopsy procedure. The diagnostic criteria of malignancy by NBI view was the presence of demarcated brownish area with scattered brown spots in the lesion. Histopathologic results were retrospectively compared with results of determination of malignancy made by NBI view. Of the 23 lesions histopathologically proved to be malignancies, 21 lesions were classified as malignant by NBI view. Sensitivity and specificity for the diagnosis of malignancy by means of NBI view compared with histopathologic results were 91.3% for sensitivity and 91.6% for specificity. NBI endoscopy seems to be a very promising diagnostic tool in the diagnosis of laryngeal malignant disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00405-008-0835-1DOI Listing
July 2009

The value of narrow band imaging endoscope for early head and neck cancers.

Otolaryngol Head Neck Surg 2008 Apr;138(4):446-51

Department of Otolaryngology, Keiyukai Sapporo Hospital, Sapporo, Japan.

Objectives: To evaluate the diagnostic value of rhinolaryngoscopy using a narrow band imaging (NBI) system in detecting squamous cell carcinoma of the head and neck (SCCHN) in patients with esophageal cancer (EC).

Study Design: Prospective study.

Subjects And Methods: Between January 2006 and December 2006, 667 consecutive EC patients underwent rhinolaryngoscopy screening with both a white light and an NBI system. Sensitivity, specificity, accuracy, and positive/negative predictive values for detecting SCCHNs were calculated and compared.

Results: Forty-five patients (6.7%) of 667 patients had SCCHNs. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for detecting SCCHNs by white light were 51.1 percent, 99.7 percent, 96.4 percent, 92 percent, and 96.6 percent. In contrast, those by NBI were 97.7 percent**, 98.9 percent, 98.8 percent*, 86.3 percent, and 99.8 percent** (*P < 0.01, **P < 0.001 vs white light).

Conclusion: An NBI endoscope significantly improves diagnostic accuracy, sensitivity, and negative predictive value in detecting SCCHN in EC patients. This endoscope would be highly beneficial in detecting superficial SCCHNs in high-risk patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.otohns.2007.12.034DOI Listing
April 2008

[Early detection of recurrent hypopharyngeal cancer after radiotherapy by utilizing narrow-band imaging--report of a case].

Nihon Jibiinkoka Gakkai Kaiho 2007 Oct;110(10):680-2

Department of Otolaryngology, Keiyukai Sapporo Hospital, Sapporo.

Narrow-band Imaging (NBI) is a novel optical technique in which the diagnostic capability of endoscopes in characterizing tissue is enhanced by the use of narrow-bandwidth filters in the video endoscope system. We report a case of early recurrence of hypopharyngeal cancer after radical radiotherapy which was detected by laryngoscopy using NBI. A 66-year-old man with right pyriform sinus cancer was treated by radical radiotherapy in March 2004. Twenty months later, laryngoscopy using NBI revealed an abnormal lesion in the right pyriform sinus, visualized as scattered brownish dots, which highly suggestive of a malignant lesion. After obtaining written informed consent from the patient, endoscopic mucosal resection of the lesion was performed. Histological examination of the resected specimen revealed a squamous cell carcinoma in situ. The patient did not need any additional therapy. Laryngoscopy using NBI appears to have good potential to detect early stage local tumor recurrence after radical radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3950/jibiinkoka.110.680DOI Listing
October 2007

Altered emotional behaviors in the diabetes mellitus OLETF type 1 congenic rat.

Brain Res 2007 Oct 15;1178:114-24. Epub 2007 Aug 15.

Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University, Kanazawa, 920-8640, Japan.

GPR10 is a G-protein-coupled receptor expressed in thalamic and hypothalamic brain regions, including the reticular thalamic nucleus (RTN) and periventricular nucleus (Pev), and the endogenous ligand for this receptor, prolactin-releasing peptide (PrRP), has demonstrated regulatory effects on the stress response. We produced a congenic rat by introducing the Dmo1 allele from the OLETF rat which encodes the amino acid sequences of GPR10 with a truncated NH2-terminus, into the Brown-Norway background. Using receptor autoradiography, we determined a lack of specific [125I]PrRP binding in the RTN and Pev of these mutant rats compared to the control rats. Furthermore, intracerebroventricular injection of PrRP did not induce a significant increase of c-fos-like immunoreactivity in the paraventricular nucleus of the mutant rats compared to the control rats. The mutant rats also displayed a less anxious-like phenotype in three behavioral-based models of anxiety-like behavior (open field, elevated plus maze and defensive withdrawal test). These data show the mutant congenic rat, of which GPR10 neither binds nor responds to PrRP, expresses less anxious-like phenotypes. On the basis of these observations, the GPR10 might be a novel target for the developing new drugs against anxiety and/or other stress-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2007.07.075DOI Listing
October 2007

Head and neck cancer associated with esophageal cancer.

Auris Nasus Larynx 2007 Jun 27;34(2):207-11. Epub 2006 Oct 27.

Department of Otolaryngology, Keiyukai Sapporo Hospital, Sapporo, Japan.

Background: Multiple squamous cell carcinomas (SCCs) frequently arise in the aerodigestive tract. This study aims to clarify the incidence of squamous cell carcinoma of the head and neck (SCCHN) in esophageal cancer (EC) and clinical features of SCCHN.

Method: We reviewed the records of 1118 EC patients treated from May 1995 to December 2001 in our institution. All patients with EC underwent otolaryngological examination and pharyngolaryngoscopy screening before and after its treatment periodically during their follow-up periods. The incidence, site and stage of SCCHNs were analyzed.

Result: A total of 127 patients had associated SCCHNs among all patients with EC (11.4%). Of these, the index antecedent tumor was SCCHN in 49 and EC in 78 patients. One hundred and fifteen patients developed double cancers (SCCHN and EC), 9 patients developed triple cancers (2 SCCHNs and EC) and 3 patients developed fourth cancers (3 SCCHNs and EC). Of 49 patients with the index SCCHN, 30 ECs were detected metachronously after its treatment (Group A) and 20 were synchronously (Group B). Of 78 patients with index EC, 38 SCCHNs were detected synchronously (Group C) and 54 SCCHNs were metachronously (Group D). The stages of 54 SCCHNs in the Group D were 33, 14, 4, 3 (Stages I-IV, respectively), which was significantly earlier than that of 50 SCCHNs in the Groups A and B (p<0.001).

Conclusion: The incidence of SCCHN in our EC patients was 11.4%. Periodic otolaryngological examination and pharyngoscopy screening can detect SCCHNs early in patients with primary EC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2006.07.012DOI Listing
June 2007

[Combination chemotherapy with S-1 and carboplatin for head and neck cancers].

Gan To Kagaku Ryoho 2006 Jun;33 Suppl 1:155-9

Dept. of Otolaryngology, Keiyukai Sapporo Hospital, Japan.

Chemotherapy plays an important role in the treatment of head and neck cancer (HNC) patients with recurrent and/or metastatic unresectable disease. The standard regimen for HNC has been a combination of cisplatin (CDDP) and 5-fluorouracil (5-FU). We planned to develop a new outpatient regimen that could be carried out safely and had an antitumor activity equivalent to the regimen of CDDP plus 5-FU. For this purpose, we selected a combination of S-1 and carboplatin. The overall response rate of 40.9% in this study was almost equivalent to the study previously reported on 5-FU plus CDDP. This regimen of S-1 plus carboplatin has the possibility of yielding tumor responses equivalent to a conventional regimen of 5-FU combined with CDDP in patients with recurrent and/or metastatic head and neck carcinoma as a second-line palliative chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2006

Laryngoscopic detection of pharyngeal carcinoma in situ with narrowband imaging.

Laryngoscope 2006 Apr;116(4):650-4

Department of Otolaryngology, Keiyukai Sapporo Hospital, Sapporo, Japan.

Objectives: Narrowband imaging (NBI) is a novel optical technique that enhances the diagnostic capability of endoscopes in characterizing tissues by using narrow-bandwidth filters in a video endoscope system. The purposes of this study were to verify the effectiveness of the NBI system in conducting endoscopic screening at the oropharynx and the hypopharynx.

Methods: This study was conducted between July 2005 and August 2005. During this period, 217 consecutive patients with esophageal cancer underwent endoscopic screening of the oropharynx and the hypopharynx with the NBI system at the Department of Otolaryngology, Keiyukai Sapporo Hospital.

Results: Among 217 patients, 6 superficial lesions, at the oropharynx (n = 1) and at the hypopharynx (n = 5), were discovered with the NBI system. On conventional electroendoscopic view, four of six lesions could be hardly recognized because of its small diameter measuring 5 mm or less. The NBI view was more beneficial in recognizing the superficial lesions than conventional electroendoscopic view. Endoscopic mucosal resection was performed for all six patients under general anesthesia in the operation room. The histologic examination exhibited a histologically proven squamous cell carcinoma (SCC) in situ. In our series, the NBI system might improve the sensitivity by about twofold over the conventional method.

Conclusion: NBI may play an important role in the diagnosis of SCCs of the oropharynx and hypopharynx.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.mlg.0000204304.38797.34DOI Listing
April 2006

Phase I/II study of S-1 combined with carboplatin in recurrent and/or metastatic head and neck cancer as outpatient chemotherapy.

Head Neck 2006 Jul;28(7):620-5

Department of Otolaryngology, Keiyukai Sapporo Hospital, Kita 1-1, Hondori 14-chome,Shiroishi-ku, Sapporo 003-0027 Japan.

Background: The aims of this study were to determine the recommended dose (RD) in combination chemotherapy of S-1 and carboplatin in recurrent and/or metastatic head and neck cancer (phase I) and to examine response rate and toxicities at RD (phase II).

Methods: S-1 was given orally at a fixed dose of 40, 50, or 60 mg twice daily based on the patient's body surface area for 21 days followed by a 14-day rest. In phase I, carboplatin was given intravenously to a cohort of three patients on day 8 at a dose of 2.5, 3.0, 3.5, or 4.0 area under the curve (AUC) values, depending on the dose-limiting toxicities (DLTs).

Results: In phase I, the RD was estimated as 2.5 AUC. In phase II, thrombocytopenia and leukopenia were most commonly found as hematologic DLTs, which were manageable without hospitalization. The response rate was 40.9%.

Conclusions: This regimen is considered to be active against recurrent and/or metastatic head and neck cancer in an outpatient setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.20379DOI Listing
July 2006

Impact of endoscopic screening on early detection of hypopharyngeal cancer.

Head Neck 2006 Apr;28(4):350-4

Department of Otolaryngology, Keiyukai Sapporo Hospital, Kita 1-1, Hondori 14-chome, Shiroishi-ku, Sapporo 003-0027, Japan.

Background: The aim was to investigate whether periodic pharyngolaryngoscopy screening in high-risk patients with preceding carcinoma of the upper aerodigestive tract can detect early hypopharyngeal cancer and preserve the larynx.

Methods: The records of 122 patients with hypopharyngeal cancer were retrospectively reviewed. Patients were divided into the following two groups: (1) the screening (SCR) group (n = 65), patients whose hypopharyngeal cancer was detected by pharyngolaryngoscopy screening; and (2) the symptom (SYMP) group (n = 57), patients whose cancer was discovered by any symptoms. Patients' demographics and larynx preservation were compared.

Results: The number of patients with clinical stage I to IV disease at diagnosis was 44, 14, three, four for the SCR group, respectively, and six, six, 15, 30 for the SYMP group, which was significantly different (p < .0001). The rate of larynx preservation after radical treatment was 79.4% for the SCR group and 45.4% for the SYMP group (p < .001).

Conclusions: Periodic pharyngolaryngoscopy screening in high-risk patients may contribute to detecting early hypopharyngeal cancer. Early detection of hypopharyngeal cancer may enhance the rate of larynx preservation and improve the quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.20336DOI Listing
April 2006

Secondary amyloidosis and eosinophilia in a patient with uterine leiomyosarcoma.

Jpn J Clin Oncol 2005 Oct 19;35(10):617-21. Epub 2005 Sep 19.

First Department of Internal Medicine, Ehime University School of Medicine, Ehime 791-0295, Japan.

We report a rare case demonstrating the relationship between secondary amyloidosis and uterine leiomyosarcoma. A 59-year-old female with high fever was referred to our hospital. Laboratory tests revealed increased white blood cells, eosinophilia and an accelerated erythrocyte sedimentation rate. Endoscopic examination of the stomach and colon revealed amyloid deposits in their mucosa. The patient showed no symptoms that suggested amyloidosis. No other organs or tissues were surveyed for amyloid deposition. Ga scintigraphy, computed tomography and magnetic resonance imaging suggested necrotic infectious leiomyoma of the uterus, which was considered to be the cause of the fever. The patient underwent total hysterectomy. The histological diagnosis of the mass revealed a low-grade uterine leiomyosarcoma with necrosis. Amyloid deposits in the gastric mucosa disappeared 1 year after the operation. In this case, amyloid deposition was detected by endoscopic biopsy before clinical manifestations. The deposition was reversible and was successfully treated. Thus, it is logical and useful to undertake endoscopic mucosa biopsy to check for amyloid deposition in patients with systemic inflammation, whose serum amyloid A protein level has been high for several months. In addition, peripheral eosinophilia was also detected in this case. Although eosinophilia associated with malignant tumor has been recognized, it is an uncommon occurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyi156DOI Listing
October 2005

[A case of oropharyngeal cancer with multiple bone metastases from prostate cancer that responded to docetaxel, ifosfamide and cisplatin combination therapy].

Gan To Kagaku Ryoho 2005 Jan;32(1):65-7

Dept of Otolaryngology, Keiyukai Sapporo Hospital.

We encountered an oropharyngeal cancer patient with multiple bone metastases from prostate cancer who achieved a partial response to 3 cycles of combination chemotherapy including docetaxel, ifosfamide and cisplatin (DIP). A 72-year-old man was found to have advanced oropharyngeal cancer during hormonal treatment of bone metastases from prostate cancer. Combination chemotherapy was initiated with DIP. After chemotherapy, computed tomography revealed no residual tumor at the oropharyngeal region, but a small ulcer was seen at the base of the tongue by laryngopharyngoscopy. The patient obtained a partial response after 3 cycles of this regimen. During chemotherapy the patient could take oral meals because of no stomatitis. After chemotherapy the patient received radiation therapy (60 Gy/30 f). The oropharyngeal cancer disappeared completely after radiotherapy. It is suggested that combination chemotherapy with DIP is a potential new treatment modality for advanced head and neck cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2005
-->