Early enteral nutrition and mobilization following head and neck surgery with free flap reconstruction.

BACKGROUND: Perioperative management methods that reduce surgery-associated invasiveness and improve the quality of postoperative recovery are being promoted as enhanced recovery after surgery programs in various areas. Early enteral nutrition and mobilization are essential elements for enhanced recovery after surgery; however, their safety and feasibility are unclear in head and neck surgery with free tissue transfer reconstruction. This study aimed to clarify these uncertainties. METHODS: This is a retrospective before-after study. From 2018 to 2022, 187 and 173 patients received conventional management on or before April 2020 and early management on or after May 2020, respectively. The conventional management and early management groups received enteral nutrition and mobilization on postoperative days 2 and 1, respectively. The primary outcome for safety assessment was the incidence of complications. The secondary outcome was the compliance rate of conventional management or early management for feasibility assessment and the length of hospital stay. RESULTS: The clinical tumour-node-metastasis stage and American Society of Anesthesiologists physical status showed significant differences between the groups. In multivariable analysis, the early management group demonstrated a significantly lower incidence of treatment-required complication classified Clavien-Dindo Grade 2 and above (odds ratio = 0.57; 95% confidence interval = 0.31-0.92) and lower wound infection (odds ratio = 0.53; 95% confidence interval = 0.31-0.92). The early management group had lower compliance rate than the conventional management group; however, no statistically significant difference was observed (79.8% vs. 85.0%, P = 0.21). CONCLUSION: Early management is safe and feasible following head and neck surgery with free tissue transfer reconstruction. It could reduce the complication rate and is considered a useful postoperative management method.

Reconstruction techniques using free jejunal transfer for total pharyngolaryngectomy with total glossectomy.

BACKGROUND: Total pharyngolaryngectomy is sometimes combined with total glossectomy for advanced hypopharyngeal or cervical esophageal cancers involving the tongue base. The optimal reconstruction method for total pharyngolaryngectomy with total glossectomy has not been established due to a considerable diameter mismatch between the floor of mouth and the esophageal stump. This report describes two reconstruction methods using free jejunal transfer. METHODS: Five consecutive patients who underwent total pharyngolaryngectomy with total glossectomy were included, with a mean age of 67.0 (range 55-75) years. Primary tumors included tongue, hypopharyngeal, cervical esophagus, and laryngeal cancers. The mean defect size was 17.0 (16-19) × 6.8 (6-7) cm. Surgical techniques involved either a simple incision or a two-segment method to address the size mismatch between the jejunum and the floor of mouth. In the simple incision method, a longitudinal cut was made to the antimesenteric or paramesenteric border of a jejunum wall to expand the orifice. In the two-segment method, a jejunal graft was separated into two segments to reconstruct the floor of mouth and the cervical esophagus, and these segments were connected with a longitudinal incision to the cervical esophageal segment to form a funnel-shaped conduit. RESULTS: Of the five patients, three underwent the simple incision method and two the two-segment method. Postoperative pharyngoesophagography showed a smooth passage for all patients. Postoperative courses were uneventful except for one flap loss due to arterial thrombosis. Four patients achieved oral feeding, while one became gastric-tube dependent. At a mean follow-up of 22.1 (4-39) months, one patient required tube feeding, two tolerated full liquid, and two consumed a soft diet. CONCLUSIONS: Both the simple incision and two-segment methods achieved satisfactory swallowing function. The choice between these reconstruction methods may depend on the extent of resection of the posterior pharyngeal wall.

Factors affecting polyglycolic acid sheet engraftment success for covering mucosal defects from head and neck surgery.

BACKGROUND: Polyglycolic acid (PGA) sheets have been used with fibrin glue to cover extensive mucosal defects in oral and pharyngeal surgery; however, the sheets can fall off before wound healing is completed. Hence, prolonged fasting is often recommended in such patients. However, there are few studies on the factors that shape PGA sheet engraftment. We studied sheet engraftment rates considering these factors. METHODS: All consecutive cases of oral surgery in 2013-21 in which the defect was covered with fibrin glue and Neoveil® or Neoveil Nano® PGA sheets were identified. The loss of all sheets was defined as an engraftment failure. Multiple logistic regression analysis was conducted to identify whether the PGA-sheet type, application site, defect size and postoperative fasting duration predicted engraftment. RESULTS: Overall, 137 patients were identified (mean age, 73 years; 57% male). The surgeries were conducted with Neoveil® in 66% of the patients; the most common site was the buccal mucosa (25%), and the mean defect size and fasting duration were 709 mm2 and 4 days, respectively. The engraftment rate was 76%. Neoveil Nano® PGA sheets were associated with a 2.8-fold better engraftment rate than Neoveil® (univariate: 87 vs. 70%, P = 0.032; multivariate: 95% confidence intervals = 1.067-7.410, P = 0.036). Other variables, including fasting duration, were not predictive of engraftment. CONCLUSIONS: This is the largest case series of patients with head and neck cancer who underwent fibrin glue-PGA sheet defect coverage. The fasting duration did not influence engraftment. Therefore, early oral intake is not contraindicated in such patients.

Post-operative progress of arm abduction function and rate of lymph node metastasis around the region of the accessory nerve: a multicentre prospective observational study.

OBJECTIVE: Although neck dissection is an essential technique in the surgical treatment of head and neck carcinoma, arm abduction disorders occurring after neck dissection reduce the patient's quality of life. METHODS: We prospectively evaluated the rate of lymph node metastasis in Levels IIB and V in head and neck cancer patients who underwent neck dissection at eight centres in Japan. In addition, post-operative arm abduction disability was classified according to functional assessment values at 1 month post-operatively, and the rate of maintained function at 6 and 12 months was evaluated. RESULTS: Lymph node metastasis occurred in Level IIB in 12 of 242 cases (4.9%) and in Level V in 5 cases (2.1%) during the 12-month post-operative course. In patients with preservation of the ipsilateral accessory nerve, arm abduction function was maintained in 142 of 209 patients (67.9%) at 12 months after surgery. Post-operative radiotherapy and Level V dissection had no statistically significant effect on the recovery of arm abduction function. Level V dissection caused a temporary loss of abduction function post-operatively. A higher arm abduction test score at 1 month post-operatively was associated with a higher rate of subsequent ability to maintain arm abduction function. CONCLUSIONS: In patients classified as cN0, metastatic rate at Levels IIB and V was low. In this cohort, omitting Level V dissection may be an option in strategies aimed at maintaining arm abduction function.

Potential efficacy of local therapy for progressive lesions after nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: In recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), local therapy (LT) such as surgery or radiotherapy can be treatment options for improved survival or quality of life. To date, however, few reports have addressed the efficacy of LT for sites of disease progression after immune checkpoint inhibitors, including other cancers. METHODS: We conducted a retrospective analysis of patients with R/M SCCHN originating from the oral cavity, oropharynx, hypopharynx, and larynx and treated with nivolumab. We extracted patients undergoing salvage LT or palliative radiotherapy (RT) to the selected progressive lesion at any time after initiation of nivolumab. RESULTS: Twenty-four patients received LT. Salvage LT was performed in 9 (37.5%) patients, including surgery and definitive RT in 5 and 4 patients, respectively. Palliative RT was performed in 15 (62.5%) patients. LT was provided in 10 (41.7%) patients for oligoprogressive disease. Twelve (50.0%) patients received subsequent systemic therapy immediately after LT. Classification based on patient treatment divided the population into four subgroups with different prognoses (salvage LT followed by subsequent systemic therapy [n = 3], salvage LT alone [n = 6], palliative RT followed by subsequent systemic therapy [n = 9], and palliative RT alone [n = 6]). Median OS in this order was 24.5, 9.0, 7.3, and 2.4 months (p = 0.001). All patients in the salvage LT followed by subsequent systemic therapy group continued nivolumab. CONCLUSION: In R/M SCCHN patients who have received nivolumab, salvage LT for the selected progressive lesion with continuation of nivolumab potentially provides an excellent survival prognosis.

Establishment of a monoclonal antibody against glycosylated CD271 specific for cancer cells in immunohistochemistry.

Various proteins are highly expressed in cancer (e.g., epidermal growth factor receptor); however, the majority are also expressed in normal cells, although they may differ in expression intensity. Recently, we reported that CD271 (nerve growth factor receptor), a glycosylated protein, increases malignant behavior of cancer, particularly stemlike phenotypes in squamous cell carcinoma (SCC). CD271 is expressed in SCC and in normal epithelial basal cells. Glycosylation alterations generally occur in cancer cells; therefore, we attempted to establish a cancer-specific anti-glycosylated CD271 antibody. We purified recombinant glycosylated CD271 protein, immunized mice with the protein, and screened hybridomas using an ELISA assay with cancer cell lines. We established a clone G4B1 against CD271 which is glycosylated with O-glycan and sialic acid. The G4B1 antibody reacted with the CD271 protein expressed in esophageal cancer, but not in normal esophageal basal cells. This specificity was confirmed in hypopharyngeal and cervical cancers. G4B1 antibody recognized the fetal esophageal epithelium and Barrett's esophagus, which possess stem cell-like characteristics. In conclusion, G4B1 antibody could be useful for precise identification of dysplasia and cancer cells in SCC.

Management of elderly patients with head and neck cancer.

There are no established guidelines for managing older patients with head and neck cancer. Most clinical trials that define current standard therapy included few elderly patients. On the other hand, there is great variability in patients' comorbidities, physical functions, cognitive function, familial and financial background and values. The key point appears to be appropriate geriatric assessment, clarifying the patients' outcomes and a multidisciplinary team approach, including the treatment decision-making policy. Although these processes should be scientific in nature, the evidence for the treatment of elderly head and neck patients is very limited. This review summarizes the evidence available regarding the management of geriatric assessment, each treatment modality and the multidisciplinary team approach for older patients with head and neck cancers.

The characteristics of missed pharyngeal and laryngeal cancers at gastrointestinal endoscopy.

OBJECTIVES: Understanding the miss rate and characteristics of missed pharyngeal and laryngeal cancers during upper gastrointestinal endoscopy may aid in reducing the endoscopic miss rate of this cancer type. However, little is known regarding the miss rate and characteristics of such cancers. Therefore, the aim of this study was to investigate the upper gastrointestinal endoscopic miss rate of oro-hypopharyngeal and laryngeal cancers, the characteristics of the missed cancers, and risk factors associated with the missed cancers. METHODS: Patients who underwent upper gastrointestinal endoscopy and were pathologically diagnosed with oro-hypopharyngeal and laryngeal squamous cell carcinoma from January 2019 to November 2020 at our institution were retrospectively evaluated. Missed cancers were defined as those diagnosed within 15 months after a negative upper gastrointestinal endoscopy. RESULTS: A total of 240 lesions were finally included. Eighty-five lesions were classified as missed cancers, and 155 lesions as non-missed cancers. The upper gastrointestinal endoscopic miss rate for oro-hypopharyngeal and laryngeal cancers was 35.4%. Multivariate analysis revealed that a tumor size of <13 mm (odds ratio: 1.96, P=0.026), tumors located on the anterior surface of the epiglottis/valleculae (odds ratio: 2.98, P=0.045) and inside of the pyriform sinus (odds ratio: 2.28, P=0.046) were associated with missed cancers. CONCLUSIONS: This study revealed a high miss rate of oro-hypopharyngeal and laryngeal cancers during endoscopic observations. High-quality upper gastrointestinal endoscopic observation and awareness of missed cancer may help reduce this rate.

Systemic therapy for salivary gland malignancy: current status and future perspectives.

Salivary gland malignancies are rare neoplasms that have a broad histological spectrum and a variety of biologic behaviors. Salivary gland malignancies are known as chemo-resistant tumors, which render optimal treatment challenging. This review summarizes the role of systemic therapy for salivary gland malignancies. To date, the advantage of adding concurrent chemotherapy has remained undefined for both postoperative and inoperable locally advanced salivary gland malignancy patients undergoing radiotherapy. For recurrent/metastatic disease, local and/or systemic treatment options should be discussed in a multidisciplinary setting with consideration to both patient needs and tumor factors. For symptomatic patients or those who may compromise organ function, palliative systemic therapy can be a reasonable option based on the results of phase II studies. Platinum combination regimens as first-line therapy have been widely accepted. Personalized therapies have become established options, particularly for androgen receptor-positive, HER2-positive and NTRK fusion-positive salivary gland malignancies (i.e. androgen receptor and HER2 in salivary duct carcinoma and NTRK3 in secretory carcinoma). For patients with adenoid cystic carcinoma, multi-targeted tyrosine kinase inhibitors have also been developed. Anti-PD1 checkpoint inhibitors have shown limited activity to date. Investigation of active systemic treatments for salivary gland malignancy remains a significant unmet need. Future directions might include a more comprehensive genomic screening approach (usually next-generation sequencing-based) and combination strategies using immune checkpoint inhibitors. These are rare malignancies that require ongoing effort in the conduct of high-quality clinical trials.

Human papillomavirus-related oropharyngeal carcinoma.

It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recognized as carcinoma with clinical presentations different from nonrelated head and neck carcinoma. Twenty years after and with the revision of the tumor-node-metastasis classification in 2017, various clinical trials focused on human papillomavirus-related oropharyngeal carcinoma to improve the prognosis and quality of life of patients with this disease. However, the incidence of human papillomavirus-related cancers is increasing, which is expected to be particularly prominent in Japan, where human papillomavirus vaccination is not widely available. In this review, we describe the current status of clinical trials (mainly focused on initial surgery and radiation dose reduction) for, primary and secondary prevention of, and the present status of human papillomavirus-related oropharyngeal carcinoma in Japan.

Discovery of a chemical compound that suppresses expression of BEX2, a dormant cancer stem cell-related protein.

Cancer stem cells (CSCs) are believed to cause cancer metastasis and recurrence. BEX2 (brain expressed X-linked gene 2) is a CSC-related gene that is expressed in dormant CSCs in cholangiocarcinoma and induces resistance against chemotherapy. The aim of the present study was to identify small compounds that have activity to inhibit BEX2 expression and result in the attenuation of CSC-related phenotypes. We screened 9600 small chemical compounds in high-throughput screening using cholangiocarcinoma cell line HuCCT1 expressing BEX2 protein fused with NanoLuc, and identified a compound, BMPP (1, 3-Benzenediol, [4-(4-methoxyphenyl)-1H-pyrazol-3-yl]). BMPP was found to exert decreasing effects on BEX2 protein expression and G0 phase population of the tumor cells, and increasing effects on ATP levels and chemotherapeutic sensitivity of the cells. These findings indicate that BMPP is a valuable chemical compound for reducing dormant CSC-related phenotypes. Thus, the identification of BMPP as a potential CSC suppressor provides scope for the development of novel therapeutic modalities for the treatment of cancers with BEX2 overexpressing CSCs.

Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck.

In order to maximize the benefit of induction chemotherapy, practice based on a comprehensive interpretation of a large number of clinical trials, as in this review, is essential. The standard treatment for locally advanced squamous cell carcinoma of the head and neck is surgery or chemoradiation. However, induction chemotherapy followed by (chemo) radiotherapy may be used in some circumstances. Although many clinical trials of induction chemotherapy have been conducted, a rationale other than to preserve the larynx is still controversial. Selection of this modality should therefore be made with care. The current standard regimen for induction chemotherapy is docetaxel, cisplatin and 5-FU, but concerns remain about toxicity, cost and the duration of treatment. Regarding treatment after induction chemotherapy, it is also unclear whether radiation alone or chemoradiation is the better option. Furthermore, there is no answer as to what drugs should be used in combination with radiation therapy after induction chemotherapy. Several new induction chemotherapy treatment developments are currently underway, and future developments are expected. This review article summarizes the current position of induction chemotherapy for head and neck squamous cell carcinoma, based on the evidence produced to date, and discusses the future prospects for this treatment.

Preoperative prognostic nutritional index as a method to predict postoperative complications after major head and neck surgery with free tissue transfer reconstruction.

BACKGROUND: Head and neck (H&N) cancer patients are often malnourished and have diminished immunity. H&N surgery with free tissue transfer reconstruction (HNS-FTTR) is associated with a relatively high incidence of postoperative complications. METHODS: Associations between possible risk factors and postoperative Clavien-Dindo (C-D) grades ≥ II and ≥ IIIa wound healing- or infection-related complications, postoperative overall complications and prolonged hospital stay were investigated in 188 patients who underwent HNS-FTTR during 2014-2018. The preoperative prognostic nutritional index (PNI) was calculated using the serum albumin level and total lymphocyte count. RESULTS: C-D ≥ II and ≥ IIIa complications were seen in 66 (35.1%) and 37 (19.7%) patients, respectively. Multivariate analysis showed that (i) previous irradiation was significantly associated with C-D ≥ II wound healing- or infection-related complications and prolonged hospital stays [odds ratio (OR) 3.096 and 3.328; P = 0.007 and 0.008, respectively]; and (ii) operation time of ≥9 h 20 min was a significant risk factor for C-D ≥ IIIa wound healing- or infection-related complications, and C-D ≥ IIIa overall complications (OR 2.987 and 2.257; P = 0.021 and 0.047, respectively). (3) Only preoperative PNI ≤ 40 was associated with all occurrences of C-D ≥ II and ≥ IIIa wound healing- or infection-related complications, C-D ≥ II and ≥ IIIa overall complications, and prolonged hospital stays (OR 3.078, 2.918, 2.627, 3.132 and 3.116; P = 0.020, 0.046, 0.036, 0.023 and 0.025, respectively). CONCLUSIONS: PNI, easily calculated, was the lone risk factor significantly predicting all C-D ≥ II and ≥ IIIa postoperative wound healing- or infection-related complications, C-D ≥ II and ≥ IIIa postoperative overall complications and prolonged hospital stay after HNS-FTTR.

Immunotherapy for squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment and evades immune responses through multiple resistance mechanisms. A breakthrough in cancer immunotherapy employing immune checkpoint inhibitors has evolved into a number of clinical trials with antibodies against programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for patients with squamous cell carcinoma of the head and neck. CheckMate141 and KEYNOTE-048 were practice-changing randomized phase 3 trials for patients with platinum-refractory and platinum-sensitive recurrent or metastatic squamous cell carcinoma of the head and neck, respectively. Furthermore, many combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors and immune accelerators are currently under investigation. Thus, the treatment strategy of recurrent or metastatic squamous cell carcinoma of the head and neck is becoming more heterogeneous and complicated in the new era of individualized medicine. Ongoing trials are investigating immunotherapeutic approaches in the curative setting for locoregionally advanced disease. This review article summarizes knowledge of the role of the immune system in the development and progression of squamous cell carcinoma of the head and neck, and provides a comprehensive overview on the development of immunotherapeutic approaches in both recurrent/metastatic and locoregionally advanced diseases.

Surgical management around the paratracheal area of hypopharyngeal cancer.

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.

Nutritional support dependence after curative chemoradiotherapy in head and neck cancer: supplementary analysis of a phase II trial (JCOG0706S1).

OBJECTIVES: To explore the risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months in patients with unresectable locally advanced head and neck carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706 (UMIN000001272). METHODS: Forty-five patients received radiation therapy for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. Risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months were analyzed using Cox regression models and logistic regression models, respectively, with consideration to patient laboratory data just before chemoradiotherapy. Radiation fields were reviewed to analyze the relationship between the extent of the irradiated field and functional outcome. RESULTS: With a median follow-up period of 3.5 years, 3-year laryngo-esophageal dysfunction-free survival was 48.9%. For laryngo-esophageal dysfunction-free survival, hazards ratio of 2.35 in patients with nutritional support at registration (vs. without nutritional support; 95% confidence interval 0.96-5.76). For nutritional support dependence over 12 months, odds ratio was 6.77 in patients with hemoglobin less than the median of 13.4 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.24-36.85) and was 6.00 in patients with albumin less than the median of 3.9 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.11-32.54). Primary sites in disease-free patients with nutritional support dependence over 12 months were the oropharynx (N = 2) or hypopharynx (N = 1), and all pharyngeal constrictor muscles were included in irradiated fields with a curative dose. CONCLUSIONS: This supplementary analysis showed that pretreatment severe dysphagia requiring nutritional support, anemia and hypoalbuminemia might have a negative prognostic impact on long-term functional outcomes after curative chemoradiotherapy in head and neck cancer.

Clinical impact of cachexia in unresectable locally advanced head and neck cancer: supplementary analysis of a phase II trial (JCOG0706-S2).

OBJECTIVES: To evaluate the clinical impact of cachexia, defined by the combination of albumin and C-reactive protein levels, in patients with unresectable locally advanced head and neck squamous cell carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706. METHODS: Forty-five patients received radiation for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. The present analysis was conducted in 44 patients with available data. The association between treatment efficacy and cachexia was investigated. Pretreatment cachexia was defined as a serum albumin level of less than 3.5 mg/dl and C-reactive protein level of more than 0.5 mg/dl. RESULTS: Among the 44 patients, 5 patients had cachexia. On comparison with the cachexic and non-cachexic patients, the percentage of clinical complete remission (20% vs 72%), time to treatment failure at 3 years, (20% vs 53%) and proportion of treatment completion (20% vs 79%) were statistically worse in the cachexic patients, while overall survival, progression-free survival and local progression-free survival at 3 years tended to be worse in cachexic patients. CONCLUSIONS: This supplementary analysis from a prospective study suggests that a pretreatment status of cancer cachexia is a prognostic factor for treatment outcomes and compliance in patients with locally advanced head and neck squamous cell carcinomas treated with chemoradiotherapy, and a candidate stratification factor in future prospective trials in this population.

A review of head and neck cancer staging system in the TNM classification of malignant tumors (eighth edition).

A number of major modifications were made to the classification of head and neck carcinomas in the eighth edition of the American Joint Committee on Cancer, Cancer Staging Manual and Union for International Cancer Control TNM classification of Malignant Tumors. These modifications were aimed at improving the prognosis prediction accuracy of the system. In this article, we review the new edition of the TNM classification system. Among the several changes in the new system, a separate algorithm for p16-positive oropharyngeal carcinoma was included, as were new chapters on 'Head and Neck Skin Carcinoma' and 'Unknown Primary Carcinoma-Cervical Nodes.' Changes to Tumor (T) classification were made by introducing the depth of invasion of oral carcinoma, whereas changes to Node (N) classification were made by adding extra-nodal extension. It is believed that these changes will help improve the accuracy of the system in the prediction of prognosis. However, it is necessary to verify their validity through further clinical research.

[Current Status and Future Prospects of Minimally Invasive and Function-Preserving Surgery].

The keywords of surgical treatment in the 21st century are "minimally invasive" and "function preserved". "Laryngeal function" is important in the head and neck region. The goal of laryngeal function preservation surgery is to be able to talk on "telephone" (vocalization function), to be able to "eat out" (chewing/swallowing function), "bath to shoulder" (nasal respiration function). Minimally invasive surgery and function-preserving surgery for head and neck cancer have been developed mainly for transoral surgery. In Japan, oral endoscopic surgery is the main surgical method. Transoral videolaryngoscopic surgery(TOVS)and endoscopic laryngo-pharyngeal surgery(ELPS)developed in Japan are widely performed. On the other hand, transoral robotic surgery(TORS)is commonly performed overseas, and insurance adaptation is expected in Japan in the future. Open surgery is available for invasive cancer cases that transoral surgery is inappropriate. Because it is deeper and wider resection, it is necessary to understand the method of setting appropriate resection area and swallowing improvement surgery. Then you can increase options for function-preserving surgery by open surgery for patients. Advances in imaging equipment present a very fine organizational structure on a large screen. The expanded surgical field will allow for highprecision surgery and minimize postoperative functional damage. We are not bound by existing concepts but we must seek next generation surgery that incorporates evolved technology.

Retrospective observational study of occult cervical lymph-node metastasis in T1N0 tongue cancer.

Objective: Delayed neck metastasis is the most significant prognostic factor for early tongue cancer. The main strategies for controlling cervical lymph nodes in Japan are elective neck dissection or watchful waiting. Elective neck dissection offers significantly better survival, but adversely impacts patient quality of life; consequently, here we investigated how to identify high-risk patients warranting elective neck dissection. Methods: We retrospectively evaluated 67 patients with T1N0 oral tongue squamous cell carcinoma who underwent primary treatment in our department from April 2001 to March 2015. All the patients underwent watchful waiting alone for neck management. We investigated the rates of occult neck metastasis, prognosis and circumstances of recurrence, and associations with pathological tumor thickness, depth and muscle invasion by the primary tumor. Correlation between the thickness in pathological specimens and that at magnetic resonance imaging was additionally investigated. Results: Neck recurrence was evident in 20 patients, of which 19 developed within 1 year. Therefore, the rate of occult neck metastasis was 29.9%. Patients with muscle invasion, tumor thickness ≥2 mm or tumor depth ≥2 mm on surgical specimens were significantly more likely to develop delayed neck metastasis. Prognosis was significantly worse for patients with muscle invasion or tumor thickness ≥2 mm. Thickness using magnetic resonance imaging was well correlated with pathological thickness. Conclusions: Patients with tumors ≥2 mm in thickness or muscle invasion developed neck metastasis, suggesting that elective neck dissection may be warranted for patients with these findings. For preoperative assessment of the need for elective neck dissection, magnetic resonance imaging would be a potential modality for T1N0 tongue cancer.