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Background: Transoral videolaryngoscopic surgery (TOVS) is widely used in Japan, and conventional two‐dimensional (2D) endoscopic methods have been established. Three‐dimensional (3D) endoscopic surgery offers superior distance perception because it provides stereoscopic views. Recently, we have developed 3D endoscopy for TOVS (3D TOVS). Methods: This study included 46 patients with pharyngeal cancer who underwent 3D TOVS. The perioperative complications and survival curves were retrospectively analyzed. Results: One patient with oropharyngeal cancer who underwent neck dissection and transoral resection simultaneously experienced postoperative hemorrhage of the neck. Another patient with oropharyngeal cancer underwent hemostasis for postoperative pharyngeal hemorrhage. There was one case of aspiration pneumonia. One patient developed cervical lymph node recurrence; however, there was no local recurrence or primary mortality. The 2‐year overall survival, disease‐specific survival, local control rates, locoregional control rate, and invasive disease‐free survival were 90.9%, 100%, 100%, 97.4%, and 79.9%, respectively. Conclusions: Three‐dimensional endoscopy can be safely applied to TOVS. [ABSTRACT FROM AUTHOR]

The status of human papilloma virus (HPV) and p16 overexpression for nasal vestibule squamous cell carcinoma (NVSCC) is unclear. The purpose of this retrospective study was to analyze the presence of HPV and the role of p16 overexpression as a surrogate marker in cases of NVSCC. Retrospective analysis was performed on patients who were diagnosed and treated for NVSCC at the University of Tokyo Hospital, Japan. p16 immunohistochemistry was considered positive with at least moderate staining intensity and diffuse staining (≥75% of tumor cells), according to the 8th edition of the American Joint Commission on Cancer. HPV-DNA testing was performed using multiplex polymerase chain reaction. Five patients were included in the study. Ages ranged from 55 to 78 years; there were two men and three women; two had T2N0, and three had T4aN0. Surgery was performed in one case, surgery plus radiation therapy (RT) in one case, and chemoradiation therapy (CRT) in three cases. Four of the five tumors showed p16 overexpression. One of five cases had an HPV-16 genotype. The mean follow-up period was 73 months, and all the patients survived. One patient with p16-negative carcinoma had local recurrence and underwent salvage surgery. Of the four patients with p16-positive carcinoma, one with CRT and one with surgery plus RT, each had delayed cervical lymph node metastasis, which was salvaged with neck dissection subsequent RT. In NVSCC, four of the five cases were p16-positive, and one was high-risk HPV infection. [ABSTRACT FROM AUTHOR]

Background: Although total laryngectomy is the standard treatment for advanced laryngeal cancer, the significance of elective neck dissection (END) for N0 laryngeal cancer remains unclear in Japan, which is an aging society. Methods: We conducted a retrospective nationwide observational study on patients with T3–T4N0 laryngeal squamous cell carcinoma treated with curative total laryngectomy from 2011 to 2018 in Japan. Results: A total of 1,218 patients were analyzed. The median patient age was 72 years, with 735 cases of T3N0 and 483 cases of T4N0. END was performed on the affected side in 850 patients (70%) and on the contralateral side in 502 patients (41.2%). END on the affected side was omitted in patients aged > 80 years (40.4%) and in patients with an advanced performance status. The occult lymph-node metastasis rate did not differ by age (18.8%–19.6%); it tended to increase chronologically from 2011 (11.1%) and was higher in cT4a (22.5%) and pT4a (24.3%) cases. In this study, coherent clinical information and follow-up data were available for 252 patients. Both univariate and multivariate analyses showed no significant prognostic factors for overall survival or recurrence-free survival for either affected or contralateral END. Older age and subglottic location were poor prognostic factors, but death due to factors other than laryngeal cancer could not be ignored in older patients. Conclusion: Omission of END during laryngectomy for T3–T4N0 laryngeal cancer is acceptable for older patients who want their operation to be completed in a short time. [ABSTRACT FROM AUTHOR]

Background D3 lymph node dissection is recommended for patients with advanced sigmoid and rectal cancer in Japan. This trial aimed to investigate the feasibility of indocyanine green (ICG) as a tracer to increase the nodal harvest during D3 lymph node dissection in patients with sigmoid and rectal cancer. Methods This prospective randomized clinical trial was performed between May 2021 and April 2022. The inclusion criteria were patients with stage I–III sigmoid or rectal cancer eligible for laparoscopic resection. Patients were 1: 1 randomized to either the ICG group (endoscopic ICG injection at the tumour site and intraoperative imaging to guide dissection) or the control group (routine laparoscopic white-light imaging). All patients were treated with D3 dissection, and the primary outcome was the number of harvested lymph nodes at the D3 level. Results Out of 210 patients screened, a total of 66 patients were enrolled and randomized. Patients in the two groups presented similar ages and clinical stages (ICG group versus control group, median age of 58.0 versus 58.5 years; stage III 36.4 per cent versus 36.4 per cent, whereas the rate of rectal cancer was 27.3 per cent versus 48.5 per cent respectively). ICG imaging was helpful for completely dissecting D3 lymph nodes and could identify a median of more than 2 (range 1–6) D3 lymph nodes neglected by routine laparoscopic white-light imaging during surgery. The median number of D3 lymph nodes harvested in the ICG group was significantly higher than that in the control group (7.0 versus 5.0, P = 0.003); however, there was no significant difference in the median numbers of positive D1, D2, and D3 lymph nodes between the two groups. Conclusion ICG is safe and feasible to guide D3 lymph node dissection and can increase the number of harvested D3 lymph nodes in patients with sigmoid and rectal cancer. Registration number: NCT04848311 (http://www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Objective: The localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC).Methods: This prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin. All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0.Results: SN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis. After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC.Conclusion: SLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III). [ABSTRACT FROM AUTHOR]

Objectives: The management of patients with cervical metastasis in head and neck cancer of unknown primary (HNCUP) remains controversial. This current multicenter retrospective study investigated the treatment outcomes of patients with HNCUP. Methods: The study included patients who were treated curatively at 12 institutions in Japan from January 2006 to December 2015. Results: Eighty patients with HNCUP were included. The median follow-up period was 34 months. The three-year overall survival (OS), disease-specific survival (DSS), regional relapse-free survival (RRFS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS) rates were 72.5%, 80.3%, 74.0%, 89.7%, and 86.9%, respectively. Nodal status was a significant factor for OS, DSS, RRFS, and DMFS; and extracapsular extension (ECE) was significant for OS and DSS. There was a distinct difference between the survival rates of patients with N1-2a and N2b-3 disease. RT was a significant positive factor for LPFS (3-year LPFS, RT 93.0% vs. no RT 83.0%, p=.043). Conclusions: For N2a as well as N1 disease without ECE, a single treatment modality, including ND or RT alone is acceptable. When ND alone is performed, thorough monitoring should be continued during follow-up to identify the emergence of the primary lesion. [ABSTRACT FROM AUTHOR]

Objectives: After tuberculous pleurisy, lymphadenitis arising from cervical lesion is the second most common form of extrapulmonary tuberculosis. It is generally treated with antituberculosis agents, but some patients resist chemotherapy. In such cases, surgical resection is often considered as an alternative treatment. This study aims to evaluate the therapeutic outcome of cervical tuberculous lymphadenitis and the future course of treatment of this disease.Methods: We retrospectively reviewed the clinical charts of patients diagnosed at the Tokyo Metropolitan Tama Medical Center between 2009 and 2015 and identified 38 cases of cervical tuberculous lymphadenitis. Precisely 798 patients were registered for primary tuberculosis at our institution during the same period.Results: Patient ages ranged from 21 to 85 years (average: 58.9 years), and the male-to-female ratio was 1:1.2. The range of tuberculosis progression was as follows: 30 (78.9%) in only the cervical lymph node, 3 in the other (axillary, mediastinal, and abdominal) lymph nodes, 1 in the lung and vertebrae lumbales, 2 in the lung, and 1 in the pleural membrane. All 38 patients were initially treated with antituberculous drugs at the Department of Pulmonary Medicine based on guidelines for tuberculosis cases in Japan. In seven cases, the antituberculous drugs were replaced due to side effects. Four cases involved a single drug-resistant strain, and one case involved a double drug-resistant strain. Thirty-three (86.8%) cases were cured by chemotherapy alone. The three patients resistant to chemotherapy were successfully treated through neck dissection. Thirty-six cases (94.7%) were cured by chemotherapy or chemotherapy and surgery.Conclusion: Local therapy could prove effective in cervical tuberculous lymphadenitis patients who exhibit an inadequate response to drugs. The role of neck dissection in cervical tuberculous lymphadenitis remains an important consideration. [ABSTRACT FROM AUTHOR]

Conclusion: The outcome of this treatment was good, indicating that it is safe and effective. A favorable outcome was obtained, especially in patients with T3, N0-1, and N2a-b cancer, while outcome remained unfavorable in patients with T4a and N2c cancer. Consideration should be given to the need for intensity-modulated radiation therapy (IMRT) and maintenance therapy. Objective: To improve the survival and functional organ preservation rates in patients with lateral oropharyngeal squamous cell carcinoma. Methods: The primary site was treated conservatively by neoadjuvant chemotherapy and/or concurrent chemoradiation therapy. Chemotherapy was administered by superselective intra-arterial infusion and cervical lymph node metastasis was treated by radical neck dissection. Results: Among 71 patients, the 5- and 10-year overall survival rates were 85.1% and 63.5%, respectively; and the 5- and 10-year functional organ preservation rates were 61.0% and 51.6%, respectively. The outcomes were especially good in patients with T3 N0-1, and N2a-b cancer. All patients with N2c cancer had poor outcomes. [ABSTRACT FROM AUTHOR]

Conclusion: The results of this study accord with those of past reports about the prevalence of level V metastasis in head and neck squamous cell carcinoma (HNSCC) cases. Because of the low rate of level V metastasis, and from the viewpoint of standard postoperative radiotherapy, selective neck dissection without level V dissection may be possible in cases without clinical evidence of level V metastasis on both the ipsilateral and contralateral sides. In addition, degree of pathological differentiation and pN stage >N2b are suggested risk factors for level V metastasis. Objectives: The most frequent complication of any type of neck dissection in HNSCC cases with level V metastasis is shoulder dysfunction secondary to traction or ischemic injury to the spinal accessory nerve (SAN). The purpose of this study was to examine procedures to preserve the SAN and avoid level V dissection and shoulder dysfunction due to SAN injury. This study investigated the prevalence of level V metastasis and its associated risk factors at various primary sites in patients with HNSCC. Methods: Clinical and pathological data were retrospectively reviewed for 162 patients with HNSCC, including those with clinically negative neck (cN0) and clinically positive neck (cN+) in whom level V neck dissection was performed. The prevalence of pathological metastasis to level V lymph nodes on both the ipsilateral and contralateral sides was investigated. Several potentially predictive risk factors for level V metastasis, such as age, sex, primary site, T stage, N stage, degree of pathological differentiation, and lymph node status of levels I-IV, were also evaluated. Statistical analysis was performed using Fisher's exact test. Results: In total, 301 neck dissections (ipsilateral side, n = 162; contralateral side, n = 139) were performed in this study. The most common primary site was the oral cavity ( n = 51), followed by the larynx ( n = 48), hypopharynx ( n = 39), and oropharynx ( n = 24). On the ipsilateral side, the overall incidence of pathologically positive neck (pN+) was 63.6% (103/162). The overall prevalence of level V metastasis was 7.4% (12/162), 6.8% (11/162) on the ipsilateral side, and 1.4% (2/139) on the contralateral side. Isolated level V metastasis and bilateral level V metastasis was observed in three patients and one patient, respectively. Metastasis to level V and other levels was observed in eight patients (8/96, 8.3%), and level V involvement on the ipsilateral side alone was observed only in three patients (3/66, 4.5%). There were two cases in which level V was involved when the other levels were also involved (2/22, 9.1%), and there was no case in which the other levels were not involved on the contralateral side. A statistically significant association was found between level V metastasis and pN stage >N2b ( p = 0.0035), degree of pathological differentiation ( p = 0.0305) on the ipsilateral side, status of neck levels I-IV ( p = 0.001), and the number of positive neck levels ( p < 0.0001) on the contralateral side. [ABSTRACT FROM AUTHOR]

Conclusion: The occult metastasis rate for T2 oral cancer can be reduced by ultrasonography (US). Also, the late metastasis rate is considered to be reduced by combining US with frozen section biopsy (FSB) during supraomohyoid neck dissection (SOHND). Objectives: Early oral cancer has been reported to show occult metastases in 15-53% of patients, but the criteria or methods for the diagnosis of cervical lymph node metastasis are unclear in many studies, and there is no clear definition of occult metastasis. In patients with T2 oral cancer, the diagnosis of lymph node metastasis by US and its pathological diagnosis (pN) after neck dissection were compared to evaluate the usefulness and limitations of US, occult metastasis rate, significance of SOHND as preventive neck dissection, and use of FSB. Methods: A total of 73 patients with T2 oral cancer were investigated retrospectively. Modified radical neck dissection (MRND) was performed in N++ patients, and SOHND was carried out in N0 patients. FSB was performed in all patients undergoing SOHND. US and pN diagnoses were compared. Results: The occult metastasis rate was 18% when occult metastases were limited to those detected by SOHND and 22% when late nodal recurrences were also included. [ABSTRACT FROM AUTHOR]

Terminology for neck dissection is quite complicated because a large number of nonradical neck dissections were created by different surgeons, each of whom named their operational method in their own words in an attempt to preserve functions that were usually lost by radical neck dissection. This complication is still causing serious confusion among head and neck surgeons throughout the world, although there have been many proposals for standardization. Japan Neck Dissection Study Group created in 2005 and updated in 2009 a new classification and nomenclature system that is easy to understand, compatible with Japanese classifications of other carcinomas, and easily interchangeable with other neck dissection terminology proposals. Based on the Classification of Regional Lymph Nodes in Japan, published by the Japan Society of Clinical Oncology, our new system divides cervical lymph nodes into four basic regions and other regions. Each of the four basic regions is further divided into several subregions. Each region, subregion, or principal nonlymphatic structure has its own symbol consisting of one alphabetical letter, two alphabetical letters, or one alphabetical letter plus one numeral. Each neck dissection operation is designated by a combination of these symbols. Neck dissections are classified into two groups, total neck dissection and selective neck dissection, according to the extent of resection of the cervical lymph nodes. We simply hope that this new system will contribute to resolving the confusion over the terminology used for neck dissection, not only in Japan but throughout the world. [ABSTRACT FROM AUTHOR]

Because there are few exchanges of doctors and surgical techniques among leading Japanese hospitals, neck dissections in Japan have become so highly diverse that the uniformity and comparability of nonradical neck dissections have become questionable. The Japan Neck Dissection Study Group (JNDSG) was organized in 2002 and includes 22 leading Japanese hospitals as members. To enhance exchanges among member hospitals and standardize nonradical neck dissections, JNDSG planned and conducted a prospective study, in which surgeons from participating hospitals were directed to observe neck dissections conducted by surgeons in other hospitals. To standardize the observation method, JNDSG created a specialized form consisting of 79 questions regarding details of neck dissection. A total of 235 patients were enrolled between February 18, 2004 and November 22, 2006. Of the 79 questions, difference among participating hospitals was confirmed in 13 details and strongly suspected in 7 details. To standardize these 20 details, JNDSG established a manual, “Standard Surgical Maneuvers for Each Detail of Neck Dissection,” based on the discussion about the optimal procedures concerning each detail. As the study proceeded from the first to the second stage, the intensity of difference among the hospitals decreased in 11 details and increased in 6 details. Because there were more details showing decreased intensity, this study was concluded to have contributed to some extent to the standardization of nonradical neck dissections in Japan. Although standardization of a surgical procedure in a multi-institutional setting is a very rare undertaking, this study achieved noteworthy success. [ABSTRACT FROM AUTHOR]

Background: The spinal accessory nerve (SAN) has several anatomical variations, which may be a pitfall in neck dissection (ND). These include the trapezius muscle branch (TB), which stems from the common trunk before entering the sternocleidomastoid muscle (SCM)., Aims/objectives: To investigate the prevalence of this variation and suggest a protocol for preventing unexpected injury of the TB in ND., Materials and Methods: We conducted a retrospective cohort study for 93 patients who had undergone neck dissection (117 sides) without resection of the SCM nor SAN. We recorded the division of the TB after and before penetration of the SCM by the common trunk (penetrating type TB [PTB]) and non-penetrating type TB [NPTB], respectively)., Results: Among NDs, PTB and NPTB were observed in 61 (52%) and 56 (48%) sides, respectively. In the subgroup of 24 cases with bilateral ND, PTB/PTB, NPTB/NPTB, and NPTB/PTB were observed in eight (33%), nine (38%), and seven (29%) cases, respectively. The prevalence of PTB/NPTB did not differ according to age, sex, or laterality., Conclusions and Significance: NPTB is a common anatomical variation. The presence or absence of a branch from the common trunk must be initially checked to avoid unexpected damage to the TB.

Background: Free flap failure secondary to internal jugular vein thrombosis (IJVT) is a significant complication after head and neck reconstructive surgery. A consensus has not yet been reached among reconstructive surgeons regarding the treatment of IJVT., Methods: We retrospectively evaluated the incidence of IJVT in 118 patients who underwent free flap reconstruction at Hyogo Cancer Center, Akashi, Japan. The occurrence of IJVT-related flap circulation crisis and pulmonary thromboembolism (PTE) was studied. This study was approved by the institutional ethics committee, and written informed consent was obtained from each patient., Results: From 118 patients who underwent head and neck reconstructive surgery, we included 116 internal jugular veins (IJVs) preserved after neck dissection in the present study. IJVT was confirmed in 25 (21.6%) IJVs from 23 patients. One patient (0.8%) developed venous congestion due to IJVT, which resulted in total flap necrosis. Two patients (1.7%) exhibited PTE associated with IJVT. They were treated with direct oral anticoagulants for 3 months and were discharged without any sequelae., Conclusion: Our results suggest that IJVT after head and neck reconstructive surgery caused not only flap circulation crisis but also PTE. Reconstructive surgeons should be aware of the potential risks due to serious complications associated with IJVT., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified., Methods: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists., Results: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy., Conclusions: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.

Objective: Salivary gland carcinoma is rare among head and neck cancers. Sublingual gland carcinoma, a type of salivary gland carcinoma, is even rarer; therefore, the number of cases at a single institute is too small for sufficient evaluation of tumor characteristics. We conducted a multicenter, retrospective analysis of sublingual gland carcinomas in patients who visited 12 institutions associated with the Kyoto Hospital and Affiliated Facilities Head and Neck Clinical Oncology Group., Methods: Thirteen previously untreated patients who visited the institutions between 2006 and 2015 were enrolled. The overall survival (OS) and disease-free survival (DFS) rates for all patients and by disease stage were analyzed. Statistical analyses were performed for all patients with respect to disease stage., Results: Eight of thirteen patients were diagnosed with adenoid cystic carcinoma on pathological study. A significant difference in OS rate was observed between patients with Stage I-III and Stage IV disease; however, the difference in DFS rate by disease stage was not significant., Conclusion: Stage IV disease was identified as a poor prognostic factor in patients with sublingual gland carcinoma. However, even patients with Stage I-III disease experienced relatively short DFS. Distant metastasis is a serious problem among patients with sublingual gland carcinoma., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to retrospectively describe the characteristics and outcomes of patients with oral squamous cell carcinoma and level IV/V metastasis and to compare patients who underwent no postoperative therapy with those who underwent postoperative radiotherapy (RT) and concomitant chemoradiotherapy (CCRT)., Methods: We evaluated 669 patients. Clinicopathological data, postoperative therapy, and clinical course were investigated., Results: Sixty-one patients (9.1%) developed level IV/V metastasis. The 3-year cumulative overall survival rates of patients with and without level IV/V metastasis were 47.3% and 64.3%, respectively. Tongue tumors, pN2 or N3 classification, and moderate or poor differentiation were significantly associated with the development of level IV/V metastasis. The surgery+RT/CCRT group was associated with better 3-year cumulative disease-specific survival and overall survival rates than the surgery only group., Conclusion: Adjuvant therapy (RT alone or CCRT) after surgery is recommended for patients with level IV/V metastasis., (© 2019 Wiley Periodicals, Inc.)

Objective: We aimed to clarify the suitable surgical management around the paratracheal area of patients who undergo total pharyngolaryngectomy based on the pathological results of hypopharyngeal cancer., Methods: The study was conducted under a multicenter, retrospective observational design in Japan. We analyzed histopathological paratracheal lymph node metastasis and thyroid invasion, and recurrence around the paratracheal area for 184 patients who underwent initial surgery among 280 participants., Results: There were significant differences in the frequency of metastasis to paratracheal lymph nodes as cN advances (P = 0.0344) and cT advances (P = 0.00028). By subsite, the paratracheal lymph node metastasis ratio was 22/130 patients (16.9%) in piriform sinus (PS), 8/32 (25.0%) in PW, 5/22 (22.7%) in PC and 10/17 (58.8%) in cervical esophagus (Ce+). The ratio of cases with bilateral paratracheal metastasis tended to be higher in cN2c, posterior wall (PW) and postcricoid (PC). Invasion to the thyroid was histopathologically confirmed in 16/184 patients (8.7%). Invasion from the primary lesion was in 15 patients., Conclusion: This study indicates that it is better for patients with advanced hypopharyngeal cancer at minimum undergo ipsilateral paratracheal lymph node dissection. Tumor subsite of PW, PC or cN2c disease or disease extending to the Ce+ should be treated with bilateral paratracheal neck dissection. In order to more reliably perform paratracheal dissection, there is also an option to resect the thyroid lobe in the range of dissection. Preservation of the thyroid gland can be considered if invasion into the thyroid gland has been clearly ruled out., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

For stage I/II tongue cancer patients, it is controversial whether prophylactic neck dissection should be performed with partial glossectomy. Based on the evidence of the primary tumor's depth of invasion as a predictive factor of occult lymph node metastases and a prognostic factor of disease-free survival, randomized phase III trial was initiated in November 2017 to evaluate the omission value for prophylactic neck dissection for stage I/II tongue cancer with 3-10 mm of depth of invasion. In 5 years, 440 patients will be accrued from 28 institutions. The primary end point of the study is the overall survival, whereas the secondary end points are relapse-free survival, local relapse-free survival, proportion of unresectable relapse and of cervical lymph node relapse, post-operative function (paralysis of the accessory and facial nerves and subjective symptoms) and adverse events. This trial has been registered with the UMIN Clinical Trials Registry (registration number: UMIN000030098; http://www.umin.ac.jp/ctr/index.htm).

Disseminated carcinomatosis of the bone marrow (DCBM) is characterized by diffuse metastasis to bone marrow and sudden mortality. To the best of our knowledge, no studies to date have reported progression of oral squamous cell carcinoma to DCBM. Herein, we report a case of squamous cell carcinoma in the maxillary gingiva suspected of progressing to DCBM. A 64-year-old woman presented with white lesions on the left maxillary gingiva. The lesions were diagnosed as squamous cell carcinoma (T2, N0, M0), and partial maxillectomy performed. Two years and 5 months after surgery, metastasis was noted in the left cervical lymph node and left radical neck dissection carried out. The subsequent diagnosis was right cervical lymph node metastasis and multiple bone metastases. The patient also presented with thrombocytopenia, anemia, and elevated levels of alkaline phosphatase, probably due to metastatic bone disease. Although various antitumor therapies were administered, the patient died 6 months after diagnosis of multiple bone metastases.

Objectives: Unlike glottic cancer, supraglottic cancer often presents with neck metastases. This different might be attributable to the location of the primary lesion. This study aimed to clarify the relationships between the sublocation of T1-2 supraglottic cancer, human papillomavirus (HPV) infection, neck metastasis, and prognosis of supraglottic cancer., Methods: This retrospective clinical study investigated 55 Japanese patients with T1-2 supraglottic cancer treated between 1994 and 2015., Results: Of 55 patients with T1-2 supraglottic cancer, neck metastasis was present at initial diagnosis in 14 patients (25.5%). Presence of neck metastasis was the only factor associated with worse prognosis of T1-2 supraglottic cancer (p=0.004). In multivariate analysis, age <70years (p=0.033) and sublocation of the primary lesion in the superior epilaryngeal portion (p=0.017) were significantly associated with presence of neck metastasis in multivariate analysis. Twelve (27.9%) of 43 patients showed positive results for human papillomavirus infection. However, human papillomavirus infection was not associated with prognosis, presence of neck metastasis, or primary lesion sublocation in T1-2 supraglottic cancer., Conclusion: Relatively young patients with supraglottic cancer at the superior epilaryngeal portion are more likely to show neck metastasis. Human papillomavirus infection was not associated with frequency of neck metastasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

Many authors have studied variation in the maxillary artery but there have been inconsistencies between reported observations. The present research aimed to examine the courses and branching patterns of the trunk and branches of the maxillary artery in a large sample of Japanese adult cadavers. The course of the maxillary artery should be reclassified into seven groups as a clear relationship was found between the origin of the middle meningeal artery and the course of the maxillary artery. This indicates that conventional theory about the formation of the maxillary artery, which was considered to be a direct derivative of the stapedial artery, might be inaccurate. Many variations in the origin of the inferior alveolar artery were found. Notably, the inferior alveolar artery origin from the external carotid artery and a double origin of the inferior alveolar artery was also observed. Thus, the maxillary artery might be derived from a combination of both the external carotid and stapedial arteries.

Background: Anaplastic thyroid carcinoma (ATC) accounts for only 1 to 2% of all thyroid carcinomas, but it is one of the most lethal neoplasms in humans. To date, most findings about ATC have been derived from single-institution studies with limited numbers of cohorts. To obtain further insights into this "orphan disease," we have established a multicenter registry, the ATC Research Consortium of Japan (ATCCJ). We analyzed prognostic factors and treatment outcomes using the large cohort database of the ATCCJ., Methods: Most of the Japanese centers involved in the treatment of thyroid cancer were invited to join the ATCCJ and have provided information on ATC patients treated between 1995 and 2008. The database includes 677 cases from 38 registered institutions. Survival curves were determined using Kaplan-Meier methods and were compared using the log-rank test. Cox's proportional hazards model was used for multivariate analysis., Results: Clinical varieties of ATC were classified into four types: common type (n = 547); incidental type (n = 29); anaplastic transformation at the neck (n = 95); anaplastic transformation at a distant site (n = 6). The incidental type followed by anaplastic transformation at the neck showed better outcomes than the other types. Anaplastic transformation at a distant site showed the worst outcomes. The 6-month and 1-year cause-specific survival (CSS) rates for common-type ATC were 36 and 18%, respectively. In all, 84 (15%) achieved long-term (>1 year) survival. Multivariate analysis identified age ≥70 years, presence of acute symptoms, leukocytosis (white blood cell count ≥10,000/mm(3)), large tumor >5 cm, T4b tumor, and distant metastasis as significant risk factors for lower survival. CSS rates also differed significantly depending on UICC stages, with 6-month CSSs of 60% for stage IVA, 45% for IVB, and 19% for IVC. For 36 of 69 (52%) stage IVA patients who underwent radical surgery, adjuvant therapies, including radiation therapy (RTX) and chemotherapy (CTX) did not show additional benefit statistically. Conversely, among 242 stage IVB patients, 80 (33%) underwent radical surgery. For those patients, therapies combining RTX with CTX significantly improved CSS., Conclusions: Long-term survival is possible for selected patients with ATC. To determine the treatment strategy, UICC stage (disease extent) and other prognostic factors (e.g., biologic malignancy grade) should be considered.

Background: Medullary thyroid carcinoma (MTC) accounts only for 1.4% of all thyroid malignancies in Japan. Since 1996, we have performed hemithyroidectomy, instead of total thyroidectomy, for sporadic nonhereditary MTC when the primary lesion is located in only one lobe. Regarding lymph node dissection, modified radical neck dissection (MND) at least ipsilateral to the tumor has been routinely performed, even if there is no clinically apparent metastasis. We investigated the clinical outcomes of MTC patients in our department., Methods: A series of 118 patients with MTC who underwent initial surgery between 1975 and 2005 were enrolled in this study. The RET gene mutations were analyzed for all patients and 46 had germline RET gene mutations. Of those 46 patients, 26 were diagnosed as MEN 2A and 2 were diagnosed as MEN 2B. Postoperative follow-up periods averaged 141 months., Results: Of 115 patients who did not have distant metastasis at surgery and who underwent locally curative surgery, 78 (67.8%) were biochemically cured. All patients without pathological lymph node metastasis were biochemically cured, and 44.8% of patients with node metastasis were also biochemically cured. The 10-year and 20-year disease-free survival rates were 89.0% and 82.5%, respectively. None of the patients who did not show lymph node metastasis and only 2 (2.6%) of 78 patients who were biochemically cured showed clinically apparent carcinoma recurrence. The 10-year and 20-year cause-specific survival rates were 96.6% and 91.7%, respectively. Lymph node metastasis, tumor size>4 cm, extrathyroid and extranodal tumor extensions significantly affected cause-specific survival of patients., Conclusions: Clinical outcomes of MTC patients in our series were better than those in Western countries, a result that might have resulted in part because of our routine MND regardless of whether clinically apparent node metastasis was detected.

According to our previous data on papillary thyroid cancer (PTC), recurrences are related to lymph node ratio (number of metastatic lymph nodes/number of dissected nodes) and lymphatic spread of PTC is more symmetrical than previously thought. Therefore, neck dissection should be performed symmetrically. Our basic procedure for clinically evident PTC is total thyroidectomy with central neck dissection. For the cases with jugular chain adenopathy and/or T3, T4 tumor, bilateral lateral neck dissection should be added. Surgical clearance of malignant tissue is important for curability. For micro PTC (T<1 cm), lobectomy with ipsilateral central neck dissection or careful observation are proposed. Meticulous maneuver of parathyroid glands and recurrent laryngeal nerves is essential for above-mentioned procedure.

The incidence of thyroid cancer clinically detected is increasing, mainly due to the technical progress in thyroid sonography. There are many problems and questions regarding the management of patients with thyroid tumors, including how to distinct thyroid follicular cancer from adenoma (no definite method is available except for the histological examination of the tissue specimen at surgery), how to treat patients with unproved thyroid tumor (thyroidectomy or observation ?), how to define "poorly differentiated thyroid cancer" (different definition between WHO and Japan) and how to treat patients with differentiated thyroid cancer (total thyroidectomy or subtotal thyroidectomy, with or without prophylactic neck dissection, with or without postoperative remnant ablation by radioactive iodine, with or without postoperative TSH suppression by thyroid hormone, thyroidectomy or observation for micro-carcinoma). Several guidelines for management of thyroid tumors have recently been published from western thyroid associations. Their basic policy how to manage differentiated thyroid cancer is considerably different from, at least, the traditional treatment in Japan. An evidence-based guideline should be published soon in

Staging nasopharyngeal carcinoma (NPC) by the UICC 4th-edition TNM classification system (the old system) did not give an accurate prognosis because of the uneven distribution of patients in each stage. This system was revised in 1997 (the new system). To evaluate the performance of the new system, 35 patients with NPC who had been staged by the old system were restaged according to the new system. Restaging of the patients resulted in an overall "downstaging." Differences in the overall survival rates of the early group (stages I, II, III), stage IVA, stage IVB, and stage IVC patients were statistically significant (75%, 48%, 74%, and 0%. respectively; p = .01). T4 was a significant factor of poor outcome (hazard rate, 2.932; 95% CI, 1.667 to 8.545), whereas N3 was not (hazard rate, 0.858; 95% CI, 0.281 to 2.618). The new staging system is more useful than the old system.

Most hereditary medullary thyroid carcinomas (MTC) occur in association with multiple endocrine neoplasia (MEN) type 2 syndromes. Since Farndon et al. reported two kindreds, that is collections of relatives, with familial non-MEN MTC in 1986, only five kindreds with this disorder have been reported in the English literature. In this paper, we describe a rare Japanese kindred with familial non-MEN MTC, confirming the existence of this distinct clinical entity in Japan. A 42-year-old woman underwent a left hemithyroidectomy with modified neck dissection (MND) under a diagnosis of sporadic MTC at 28 years of age. She developed lymph node metastasis in the right neck region 7 years after the initial surgery, and underwent MND and right hemithyroidectomy. Although no findings of MTC were histologically confirmed in the resected right thyroid lobe, C-cell hyperplasia was observed. Hereditary MTC was strongly suspected, but we could not confirm specific manifestations associated with MEN type 2 in any family members. However, 7 years later, a paternal aunt and cousin were diagnosed with MTC. Other family members were evaluated by ultrasonography and calcium-pentagastrin provocation testing, and three additional patients with MTC across two generations were found. None of these patients had any extrathyroidal manifestations associated with MEN type 2, and the entity of familial non-MEN MTC was confirmed.

In contrast to Caucasians, the Japanese population has a relatively high incidence of malignant melanoma in the oral cavity, but its classification and treatment has not been established up to now. We present here the detailed clinical and histological features of 14 cases of oral melanoma. In 13 of the 14 patients, the lesions exhibited three phases: a nodular phase consisting of spindle-shaped or epithelioid tumor cells in the submucosa, a pigmented plaque phase consisting of preinvasive tumor cell nests in the lower epithelial layers, and a macular phase consisting of proliferation of dendritic melanocytes without apparent atypia or simple hyperpigmentation in the basal cell layer. The macroscopic and microscopic findings of 13 melanomas corresponded to those of acral lentiginous melanoma of the skin, while the one lesion showing no radial growth phase was classified as nodular melanoma. We devised a new treatment plan for oral melanoma in 1980, which includes surgical excision via an intraoral approach, therapeutic neck dissection, and adjuvant immunochemotherapy. Out of 11 patients treated in this manner, nine had a good outcome without major cosmetic and functional morbidity. This suggests that the prognosis of oral melanoma is not so poor as reported previously if adequate therapy is provided.