Clinical outcomes of head and neck mucosal melanoma treated with surgery: a single-center study in Japan.

BACKGROUND: Head and neck mucosal melanomas are rare malignancies. Although the prognosis is poor owing to the high incidence of distant metastases, locoregional control remains important. It is difficult to obtain results in a large cohort because of its rarity. This study aimed to elucidate the survival outcomes of patients with head and neck mucosal melanoma treated with surgery in Japan. METHODS: Patients with head and neck mucosal melanoma who were surgically treated between 2007 and 2021 at the National Cancer Center Hospital were retrospectively analyzed. RESULTS: A total of 47 patients were included in this study. The 5-year overall survival, disease-specific survival, locoregional control and relapse-free survival rates were 42%, 50%, 79% and 13%, respectively. The disease-specific survival of the oral mucosal melanoma group was significantly better than that of the sinonasal mucosal melanoma group (5-year disease-specific survival rate: 70% versus 37%, respectively; P = 0.04). Multivariate analyses revealed that sinonasal mucosal melanoma were independently significant adverse prognostic factor, for overall survival and disease-specific survival. Patients with oral mucosal melanoma patients had a higher incidence of lymph node metastasis than those with sinonasal mucosal melanoma patients (P < 0.0001). CONCLUSION: This study demonstrated the survival outcomes of the largest cohort of patients with head and neck mucosal melanomas treated surgically at a single institution within the past 20 years in Japan. We found that survival outcomes and incidence of nodal metastases varied by site.

Clinical and pathological features of second primary neoplasms arising in head and neck reconstructive skin flaps.

The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is increasing because of the increase in head and neck flap reconstruction and cancer survival. Prognosis, optimal treatment, and their clinicopathological-genetic features are under debate and are difficult to diagnose. We retrospectively reviewed SNAFs based on a single center's experience over 20 years. Medical records and specimens of 21 patients with SNAF who underwent biopsies between April 2000 and April 2020 at our institute were retrospectively analyzed. Definite squamous cell carcinoma and the remaining neoplastic lesions were subclassified as flap cancer (FC) and precancerous lesions (PLs), respectively. Immunohistochemical studies focused on p53 and p16. TP53 sequencing was conducted using next-generation sequencing. Seven and 14 patients had definite FC and PL, respectively. The mean number of biopsies/latency intervals was 2.0 times/114 months and 2.5 times/108 months for FC and PL, respectively. All lesions were grossly exophytic and accompanied by inflamed stroma. In FC and PL, the incidences of altered p53 types were 43% and 29%, respectively, and those of positive p16 stains were 57% and 64%, respectively. Mutation of TP53 in FC and PL were 17% and 29%, respectively. All except one patient with FC under long-term immunosuppressive therapy survived in this study. SNAFs are grossly exophytic tumors with an inflammatory background and show a relatively low altered p53 and TP53 rate and a high p16 positivity rate. They are slow-growing neoplasms with good prognoses. Diagnosis is often difficult; therefore, repeated or excisional biopsy of the lesion may be desirable.

Comparison of Survival Outcomes Between Larynx-Preserving Open Partial Pharyngectomy and Radiotherapy or Chemoradiotherapy in Patients with Hypopharyngeal Squamous Cell Carcinoma: A Single-Center Retrospective Analysis with Inverse Probability of Treatment Weighting Adjustments.

BACKGROUND: There is a group of hypopharyngeal squamous cell carcinoma (HPSCC) patients for whom larynx-preserving open partial pharyngectomy (PP) and radiotherapy/chemoradiotherapy (RT/CRT) are indicated. We aimed to retrospectively evaluate the survival difference as there is no evidence directly comparing the two therapies. METHODS: This study evaluated HPSCC patients who were initially treated by PP or RT/CRT at our institution between January 2007 and October 2019. Overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival (LFS), and local relapse-free survival (LRFS) were evaluated. The main analyses were performed with inverse probability of treatment weighting (IPTW) adjustments. Sensitivity analyses compared hazard ratios (HRs) obtained with three models: unadjusted, multivariate Cox regression, and propensity score-adjusted. RESULTS: Overall, 198 patients were enrolled; 63 and 135 underwent PP and RT/CRT, respectively. IPTW-adjusted 5-year OS, DSS, LFS, and LRFS rates in the PP and RT/CRT groups were 84.3% and 61.9% (p = 0.019), 84.9% and 75.8% (p = 0.168), 94.8% and 90.0% (p = 0.010), and 75.9% and 74.1% (p = 0.789), respectively. In the IPTW-adjusted regression analysis, PP was associated with a significant benefit regarding OS (HR 0.48, 95% confidence interval [CI] 0.26-0.90) and LFS (HR 0.17, 95% CI 0.04-0.77). The results obtained with the three models in the sensitivity analyses were qualitatively similar to those of the IPTW-adjusted models. CONCLUSION: Despite the risk of bias related to unadjusted factors, our results suggest that PP is associated with significantly better OS and LFS compared with RT/CRT for HPSCC.

Preoperative steroid for enhancing patients' recovery after head and neck cancer surgery with free tissue transfer reconstruction: protocol for a phase III, placebo-controlled, randomised, double-blind study (J-SUPPORT 2022, PreSte-HN Study).

INTRODUCTION: There is no established methodology for the perioperative management of head and neck cancer surgery and free tissue transfer reconstruction (HNS-FTR). A single dose of corticosteroid administered immediately before surgery has been shown to reduce postoperative pain and nausea/vomiting after some types of surgery. However, the efficacy of this strategy has not been demonstrated in HNS-FTR, and the increased risk of infectious complications associated with its use cannot be ruled out. This phase III, placebo-controlled, randomised, double-blind, comparative, multicentre study seeks to determine if preoperative administration of corticosteroid hormone has an adjunctive effect in terms of reducing pain and nausea/vomiting after surgery and improving the quality of postoperative recovery. METHODS AND ANALYSIS: Using the minimisation method, patients undergoing HNS-FTR are currently being recruited and randomly assigned to a study arm at a 1:1 allocation rate. The study treatment arm consists of 8.0 mg of dexamethasone phosphate dissolved in 100 mL of saline administered as a single dose by intravenous infusion. These treatments will be administered in a double-blind fashion. All patients will receive perioperative care according to the common multicentre enhanced recovery after surgery programme. The primary endpoint is the quality of postoperative recovery, as determined by the area under the curve (AUC) for total score on the Japanese version of the Quality of Recovery Score (QOR-40J) on postoperative days 2 and 4. The point estimate and CI for the difference in the AUC between the groups on postoperative days 2 and 4 will be calculated. ETHICS AND DISSEMINATION: The study will be performed in accordance with the Declaration of Helsinki and Japan's Clinical Trials Act. The study protocol was approved by the Certified Review Board of National Cancer Center Hospital East (Reference K2021004). TRIAL REGISTRATION NUMBER: The study was registered in the Japan Registry of Clinical Trials (jRCTs031210593; V.3.0, November 2021, available at https://jrct.niph.go.jp/en-latest-detail/jRCTs031210593).

Survival Impact of Lingual Lymph Node Metastases in Tongue Cancer: An Analysis Regarding Anatomical Subsites.

BACKGROUND/AIM: Lingual lymph node (LLN) metastasis from tongue cancer occurs at four subsites. However, subsite-related prognosis is unknown. This study aimed to analyze the association between LLN metastases and disease-specific survival (DSS) with respect to these four anatomic subsites. PATIENTS AND METHODS: Patients with tongue cancer treated between January 2010 and April 2018 at our institute were reviewed. The four subgroups of LLNs were median, anterior lateral, posterior lateral, and parahyoid. DSS was evaluated. RESULTS: LLN metastases occurred in 16 of the 128 cases; six and 10 cases were identified during initial and salvage therapy, respectively. Zero, four, three, and nine cases were median, anterior lateral, posterior lateral, and parahyoid LLN metastases, respectively. The 5-year DSS of patients with LLN metastasis was significantly poor on univariate analysis; parahyoid LLN metastasis showed the worst prognosis. Multivariate analysis indicated that only advanced nodal stage and lymphovascular invasion were significant survival factors. CONCLUSION: Parahyoid LLNs may require the most caution in tongue cancer. The significance of LLN metastases alone for survival was not confirmed on multivariate analysis.

BCOR-CCNB3 sarcoma arising in the pharynx.

Reports on BCOR-CCNB3 sarcoma in the head and neck region are scarce, given their unknown etiology. An 18-year-old male patient presented a rapidly enlarging tumor extending from the right nasopharynx to the oropharynx. Histological examination showed a spindle cell sarcoma with BCOR-CCNB3 fusion detected by fluorescence in situ hybridization, and BCOR-CCNB3 was diagnosed. After three courses of alternating VDC-IE therapy, the patient underwent tumor resection based on the original tumor range with a minimal margin, using the mandibular swing technique. Radiation therapy (50.4 Gy) was administered postoperatively, followed by three additional courses of alternating VDC-IE therapy. The patient survived and showed no evidence of disease at 12 months postoperatively. BCOR-CCNB3 sarcoma is a chemotherapy-sensitive sarcoma, and conservative resection with a minimal margin that does not interfere with the treatment flow is preferable.

Transnasal photoimmunotherapy with cetuximab sarotalocan sodium: Outcomes on the local recurrence of nasopharyngeal squamous cell carcinoma.

Photoimmunotherapy for head and neck cancer (HNC-PIT) is a newly developed locoregional treatment targeting the epidermal growth factor. This treatment consists in administering cetuximab sarotalocan sodium that conjugates cetuximab with the dye IRdye700DX, which is activated by near-infrared ray illumination at 690 nm. HNC-PIT has been conditionally approved in Japan in September 2020 for the treatment of unresectable locally advanced or unresectable locoregionally recurrent HNC. However, its outcomes on the local recurrence of the nasopharyngeal squamous cell carcinoma (NPSCC) remain undetermined. In this report, we assessed the effects of HNC-PIT assisted by transnasal endoscopy on the local recurrence of NPSCC. A 77-year-old male presented with a local recurrence of NPSCC. The initial diagnosis revealed a squamous cell carcinoma, T2N2M0 stage III, positive for Epstein-Barr virus-encoded small RNA by in situ hybridization, which was treated with concurrent chemoradiotherapy (CRT). However, local recurrence was detected 14 months after CRT. We performed HNC-PIT under transnasal endoscopy. Seven months have passed since the HNC-PIT treatment, and the patient is alive without delayed adverse events and evidence of recurrence. Local recurrence of NPSCC, which is difficult to treat with minimally invasive surgery, is considered a potential candidate for HNC-PIT.

Comparison of survival outcomes between adolescent and young adults and older adults with tongue squamous cell carcinoma: a nationwide database study using the head and neck cancer registry of Japan.

BACKGROUND: This study aimed to evaluate the prognostic outcome for adolescent and young adult (AYA) generation patients with tongue squamous cell carcinoma (TSCC). METHODS: Data were obtained from the Head and Neck Cancer Registry of Japan, and patients who were newly diagnosed with TSCC from 2011 to 2014 were extracted. We compared the clinical parameter and survival of the ≤ 39 years old (AYA) patient group with the 40-79 (non-AYA) group. Propensity score matching (PSM) was used for survival analyses. RESULTS: Our cohort included 2221 patients with TSCC. AYA and non-AYA groups consisted of 258 and 1963 patients, respectively. The AYA group has a larger proportion of females than the non-AYA group (P < 0.001). Following PSM, both overall and disease-specific survival of the AYA group was significantly longer than those of the non-AYA group (P = 0.009 and P = 0.04, respectively). CONCLUSION: We demonstrated the survival superiority of AYA patients with TSCC compared to older adult patients. Therefore, our study results may reduce this anxiety by providing patients with appropriate information of prognosis for AYA patients with TSCC.

Olfactory Preservation in Craniofacial Resection of Tumor Invading Hemianterior Skull Base: Operative Video.

In traditional craniofacial resection of tumors invading the anterior skull base, the bilateral olfactory apparatus is resected. Recently, transnasal endoscopy has been used for olfactory preservation in resections of unilateral low-grade malignancies. However, for tumors that invade the orbita or for high-grade malignancies, the transnasal endoscopic skull base surgery has been controversial. This video demonstrates the surgical techniques of olfactory preservation during craniofacial resection of a high-grade malignancy invading the hemianterior skull base and orbita. We present the case of a 32-year-old woman with osteosarcoma in the right ethmoid sinus. The tumor invaded the ipsilateral cribriform plate, dura menta, and orbital periosteum; however, the nasal septum and crista galli were intact ( Fig. 1A, B ). Because the tumor was a high-grade malignancy and the orbita had been invaded, we performed craniofacial resection instead of endoscopic resection ( Fig. C2A ). We drilled into the right side of the crista galli, midline of the cribriform plate, and perpendicular plate of the ethmoid bone via craniotomy. As a result, we accessed the nasal cavity directly ( Fig. 2B ). To preserve the nasal septum, we detached the remaining right septal mucosa through the transfacial approach ( Fig. 2C ). Because of the high risk of cerebrospinal fluid leakage as a result of previous irradiation, we performed vascularized free flap reconstruction of the skull base instead of pericranial flap. Postoperative computed tomography revealed no evidence of tumor ( Fig. 1C, D ). The patient's sense of smell returned after 1 postoperative day, and she was discharged on the postoperative day 14. The link to the video can be found at: https://youtu.be/XzPABYwzkjs .

Surgical technique for superselective neck dissection under local anesthesia in recurrent head and neck cancer.

The aim of this paper is to describe a safe and effective surgical technique for neck dissection under local anesthesia. An increasing number of patients cannot undergo general anesthesia due to systemic complication arising from old age. Moreover, the long-term survival of patients with recurrent or metastatic cancer due to advances in chemotherapy has increased the necessity of neck dissection under local anesthesia. Appropriate pain control and selection of medical devices are important factors for success of the surgery under local anesthesia. In addition to the usual subcutaneous infiltration anesthesia for pain control, nerve blocks for each cervical nerve encountered during surgery are extremely effective. Since muscle relaxants are not available, sharp devices such as knife or scissors, instead of electric scalpel, should be used to prevent unexpected muscle contractions caused by electric current. This video presents well-proven techniques and technical tips for superselective neck dissection under local anesthesia.

Carotid artery ligation via sternotomy as a palliative surgery: Case report of advanced intramediastinal malignant soft tissue tumor.

Under extreme conditions and in palliative settings, shared decision making with the patient is vital; narrative decisions beyond evidence could be considered. If there is a chance of symptom palliation, extended surgery should not be avoided merely because of the limited life expectancy.

Metastasis to the lateral lingual lymph node located behind the submandibular gland: A case of squamous cell carcinoma of the tongue.

Inconsistency in the definition of LLNs may be a hurdle in ensuring the accuracy of the evidence. Refinements in the classification of LLNs, based on the fascial anatomy and lymphatic vessels, are warranted.

Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence.

OBJECTIVES: This study aims to evaluate whether the accumulation of TP53 mutations is associated with clinical outcome by comparing full-coverage TP53 deep sequencing of the initial and recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Medical records and surgical specimens of 400 patients with HNSCC surgically treated with curative intent, of which 95 patients developed local or locoregional recurrence, were reviewed. Of these patients, 63 were eligible for genomic analysis. Full-coverage TP53 deep sequencing of 126 paired initial and recurrent tumor samples was examined using next-generation sequencing (NGS). Temporal changes in the mutation status, molecular characterization, and clinical outcome were compared. Fisher's exact test, Kaplan-Meier method, log-rank test, and Cox regression models were used for statistical analysis. RESULTS: Of the recurrent tumors, 22% harbored accumulation of TP53 mutations, and 16% lost the original mutation. The accumulation of TP53 mutations was significantly more frequent in oral cancer than in pharyngeal or laryngeal cancer (33% vs. 7%, p = 0.016). Two-year post-recurrence survival (PRS) was associated with TP53 status for recurrent tumors, but not for initial tumors. The TP53 status for recurrent tumors was an independent risk factor in multivariate analysis (hazard ratio, 5.76; 95% confidence interval, 1.86-17.8; p = 0.0023). CONCLUSION: Approximately one-third of the recurrent HNSCC cases showed a different TP53 status from the initial tumor. Temporal changes in the mutation status differed by primary site. Full-coverage TP53 deep sequencing of recurrent tumors was useful in predicting post-recurrence prognosis.

Uniform infection screening allowed safe head and neck surgery during the coronavirus disease 2019 pandemic in Japan.

BACKGROUND: The purpose of this study was to determine whether a uniform infection screening protocol could be used to safely perform head and neck cancer surgery during the coronavirus disease 2019 pandemic and clarify how surgical treatment changed compared with the pre-pandemic period. MATERIALS AND METHODS: During the unprecedented coronavirus disease 2019 pandemic in Tokyo, we continued providing head and neck cancer care, guided by our own uniform screening protocol. In this study, medical records of 208 patients with head and neck malignancy, who underwent surgical treatment at our hospital during the first and second wave of pandemic for each 2-month period (first wave: 30 March 2020-30 May 2020, second wave: 14 July 2020-14 September 2020) and the 2-month pre-pandemic period (30 October 2019-30 December 2020), were analysed. RESULTS: A total of 133 patients were admitted for surgical treatment and all, except six patients with emergency tracheostomy, were screened according to the protocol. As a result, all 127 patients received surgical treatment as planned, and all 1247 medical staff members involved in the surgeries were uninfected by severe acute respiratory syndrome coronavirus 2. During the first wave of pandemic, 20% reduction of head and neck surgery was requited; however, restrictions of surgery were not necessary during the second wave. Surgical procedure, length of hospitalization, postoperative complications and number of medical staff were unchanged compared with pre-pandemic period. CONCLUSION: Our data indicate that continuation of head and neck anticancer surgical treatment in an epidemic area during the coronavirus disease 2019 pandemic were safe and feasible, if adequate and strict preventive measures are vigorously and successfully carried out.

Risk Factors for Delayed Surgical Recovery and Massive Bleeding in Skull Base Surgery.

BACKGROUND: To determine factors that delay surgical recovery and increase intraoperative hemorrhage in skull base surgery. METHODS: Factors related to delayed postoperative recovery were retrospectively reviewed in 33 patients who underwent open skull base surgery. Early and late recovery phases were assessed as "days required to walk around the ward (DWW)" and "length of hospital stay (LHS)," respectively. Intraoperative blood loss was cal-culated every hour and analyzed in 4 steps, i.e., craniotomy and intracranial manipulation, cranial fossa osteotomy, extracranial osteotomy, and reconstruction. RESULTS: More than 4,000 mL of blood loss (B = 2.7392, Exp[B] = 15.4744; 95% CI 1.1828-202.4417) and comorbidi-ty (B = 2.3978, Exp[B]) = 10.9987; 95% CI 1.3534-98.3810) significantly prolonged the DWW; the occurrence of postoperative complications significantly delayed the LHS (p = 0.0316). Tumor invasion to the hard palate, the maxillary sinus, the pterygopalatine fossa, the base of the pterygoid process, the sphenoid sinus, the middle cranial fossa, and the cavernous sinus and a long operation time (>13 h) were associated with increased total hemorrhage. The optimal cut-off hemorrhage volume associated with total massive blood loss in craniotomy and intracranial manipulation (AUC = 0.8364), cranial fossa osteotomy (AUC = 0.8000), and extracranial osteotomy (AUC = 0.8545) was 1,111, 750, and 913 mL, respectively. Persistent infection (6%) and neuropsychiatric disorder (6%) are direct causes of delayed LHS. CONCLUSION: Blood loss, comorbidity, and postoperative complications were risk factors for delayed surgical recovery. Meticulous preoperative planning, intraoperative surefire hemostasis, and perioperative holistic management are prerequisites for safe skull base surgery.

An anatomical study of the anterior wall of the hypopharyngeal and the cervical esophageal junction.

OBJECTIVE: The upper esophageal sphincter plays a significant role by forming a physical barrier at the junction of the hypopharynx and the cervical esophagus. As few studies have focused on the ventral aspect of this junction, the contribution of the anterior wall of the cervical esophagus to upper esophageal sphincter function remains unknown. The purpose of this study was to examine the muscle fibers' arrangement at the junction, especially of those forming its anterior wall. METHODS: Thirteen specimens from 13 Japanese cadavers were analyzed. Six specimens were dissected macroscopically, while the remaining seven were examined histologically. RESULTS: The outer longitudinal layer of the proximal esophagus was well-developed anterolaterally. The uppermost fibers of the inner circular layer of the esophagus ascended longitudinally. The anterolateral part of the outer longitudinal layer and the uppermost region of the inner circular layer were continuous with the median tendinous band, in turn reaching superior to the cricoid cartilage. Histological analysis showed that the tendinous band was also continuous with the superior part of the perichondrium of the cricoid cartilage and with the aponeurosis of the transverse and oblique arytenoids. CONCLUSION: The well-developed anterolateral region of the outer longitudinal layer and the uppermost fibers of the inner circular layer were continuous with the median tendinous band, which reached superior to the cricoid cartilage. The contraction of the proximal esophagus may result in protrusion of the anteromedian esophageal wall into the lumen, thereby supporting the closure of the upper esophageal sphincter.

Medial lingual lymph node metastasis in carcinoma of the tongue.

Lingual lymph node metastases are rarely seen in carcinoma of the tongue, and these nodes are not removed during neck dissection. Lingual lymph nodes are classified into medial and lateral groups, and metastasis to the former is extremely rare. A 55-year-old male with squamous cell carcinoma of the tongue, (stage T4aN0M0), underwent hemiglossectomy with neck dissection and free flap reconstruction. The lingual septum had a mass, 8 mm in size, which was diagnosed as medial lingual lymph node metastasis on histopathology. The patient developed multiple distant metastases and died of disease 18 months after the initial surgery. The presence of medial lymph node metastasis could result in contralateral neck metastases and worsen prognosis. Such cases may warrant more intensive therapy than recommended by current guidelines.

Deep cervical fascia as an anatomical landmark of lingual lymph nodes: An anatomic and histologic study.

OBJECTIVES: We aimed to discuss the definition of lingual lymph nodes based on the deep cervical fascia anatomy. METHODS: A total of 11 cadavers were histopathologically evaluated. Specimens were dissected into serial stepwise cross-sections. The deep cervical fascia and lymph nodes were evaluated by staining the cross-sections with Elastica van Gieson and hematoxylin and eosin stains, respectively. The gross anatomy of the deep cervical fascia was evaluated in 1 cadaver after bilateral dissection. RESULTS: A single severely degenerated medial lingual lymph node (MLLN) was identified in the lingual septum of 1 cadaver. A single lateral lingual lymph node (LLLN) was identified in 1 cadaver, between the genioglossus and the hyoglossus. The superficial layer of deep cervical fascia (SLDF) was found to split into two layers encapsulating the submandibular gland. The deeper portion of this fascia was in close contiguity with the hyoglossus and formed the boundary between the mouth and the neck. The SLDF was found to be discontinuous with the area between the sublingual space and the submandibular gland. CONCLUSIONS: The SLDF could serve as an anatomical landmark for lingual lymph nodes, since it is considered to be the demarcating boundary during neck dissection. When lymph nodes that are located deeper than the SLDF were defined as lingual lymph nodes, 1 MLLN and 1 LLLN were identified.

Prediction of the depth of invasion in superficial pharyngeal cancer: Microvessel morphological evaluation with narrowband imaging.

BACKGROUND: Magnifying endoscopy with narrowband imaging (ME-NBI) is useful in predicting the invasion depth by examining the microvascular status of tumor surfaces. This retrospective study aimed to determine its efficacy in pharyngeal cancer. METHODS: Between April 2016 and March 2018, 59 lesions from 46 patients who underwent transoral resection were retrospectively analyzed. Using ME-NBI, microvascular status was classified into B1, B2, or B3, based on the classification of the Japan Esophageal Society. RESULTS: A significant correlation was observed between microvascular status and invasion depth (P = .011). Mean thickness of lesions with B1, B2, and B3 vessels were 563, 1364, and 2825 µm, respectively (P = .006). In previously treated lesions, a significant correlation was observed between microvascular status and invasion depth (P = .012). CONCLUSIONS: ME-NBI is useful in predicting the invasion depth and thickness of pharyngeal tumors, even in patients with previously treated lesions.