Complications including dysphagia following transoral non-robotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

OBJECTIVE: Transoral surgery is a minimally invasive treatment but may cause severe dysphagia at a lower rate than chemoradiotherapy. METHODS: We compared clinical information, surgical complications, and swallowing function in patients who underwent transoral nonrobotic surgery for laryngo-pharyngeal squamous cell carcinoma between 2015 and 2021 in a multicenter retrospective study. RESULTS: Six hundred and forty patients were included. Postoperative bleeding was observed in 20 cases (3.1%), and the risk factor was advanced T category. Postoperative laryngeal edema was observed in 13 cases (2.0%), and the risk factors were prior radiotherapy, advanced T stage, and concurrent neck dissection in patients with resected HPC. Dysphagia requiring nutritional support was observed in 29 cases (4.5%) at 1 month postoperatively and in 19 cases (3.0%) at 1 year postoperatively, respectively. The risk factors for long-term dysphagia were prior radiotherapy and advanced T category. Short-term risk factors for dysphagia were prior radiotherapy, advanced T category, and concurrent neck dissection, while long-term risk factors for dysphagia were only prior radiotherapy and advanced T category. CONCLUSION: Prior radiotherapy, advanced T stage, and concurrent neck dissection increased the incidence of postoperative laryngeal edema and short-term dysphagia, but concurrent neck dissection did not affect long-term dysphagia. Such features should be considered when considering the indication for transoral surgery and postoperative management.

Mucosal melanoma of the head and neck: a retrospective analysis of 34 cases in Japan.

PURPOSE: Mucosal melanoma of the head and neck (MMHN) is a rare condition. This study aimed to investigate oncological outcomes of surgical intervention in patients with MMHN. MATERIALS AND METHODS: The study included 34 patients with MMHN who underwent surgical resection as initial treatment at 10 institutions in Japan between July 2005 and June 2015. Results: The 5-year overall survival (OS), local control rate (LCR), disease-free survival (DFS), and disease-specific survival (DSS) rates were 48.7%, 53.4%, 32.4%, and 55.1%, respectively. Based on multivariate analysis, no independent prognostic factors for the 5-year OS and DSS were found. Based on univariate analysis, the 5-year LCR was worse in patients with lesions in the nasal cavity and paranasal sinuses than in the oral cavity and pharynx. However, no differences in oncological outcomes were identified in relation to primary sites, and postoperative radiotherapy (PORT) and adjuvant systemic therapy did not contribute to improvements in the 5-year OS. CONCLUSIONS: No independent prognostic factors for the 5-year OS or DSS were identified. Regional or distant recurrences are often identified, regardless of local control with surgical resection. Difficult control of MMHN with conventional therapeutic strategies, such as surgical intervention, PORT, and systemic therapy, has been suggested.

Impact of cervical lymph node metastasis on transoral surgery for hypopharyngeal squamous cell carcinoma: A retrospective multicenter study.

BACKGROUND: Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. METHODS: We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. RESULTS: Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035). CONCLUSIONS: In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater.

Local recurrence and metachronous multiple cancers after transoral nonrobotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

BACKGROUND: Late laryngopharyngeal cancers after transoral surgery include not only local recurrences but also metachronous multiple cancers. METHODS: We compared clinical information, surgical outcomes, and late laryngopharyngeal cancers in patients who underwent transoral nonrobotic surgery for laryngopharyngeal squamous cell carcinoma without lymph node metastases between 2015 and 2021 in a multicenter retrospective study. RESULTS: Four hundred and fifty-seven patients were included. Positive surgical margins were found in 121 patients (26.5%). Twenty-two patients (4.8%) received additional treatment. Positive horizontal margins of invasive carcinoma (p = 0.003) and positive horizontal margins of carcinoma in situ only (p = 0.032) were independent risk factors for local recurrence, and prior radiotherapy (p = 0.001) for metachronous multiple cancers. Local control was significantly worse without additional treatment (p = 0.049), but there was no significant difference in survival. CONCLUSIONS: Patients with positive margins had an increased frequency of local recurrence, but salvage therapy was effective.

Parathyroid carcinoma: impact of preoperative diagnosis on the choice of surgical procedure.

The operative procedure in the surgical treatment of parathyroid carcinoma differs from that of benign hyperparathyroidism. However, preoperative differentiation is often difficult. This study elucidated how clinicians diagnose parathyroid carcinoma and the relationship between preoperative diagnosis and the operative course. Using a retrospective chart review, twenty cases of parathyroid carcinoma from nine participating centers were examined. In 11 cases with preoperative suspicion of malignancy, at least one of these three features was found: elevated serum calcium level (>14 mg/dL), palpable mass, and irregular margin on ultrasonography. Although an intact parathyroid hormone (iPTH) threshold to suspect malignancy has not been established, six cases showed marked iPTH elevation exceeding 8.0 times the upper limit of normal. One case was excluded from analysis due to hemodialysis. Compared with the four cases that showed calcium elevation, the iPTH threshold might represent better sensitivity. Among 9 cases of benign preoperative diagnosis, six cases were performed with pericapsular resection. In three cases where malignancy was suspected in the middle of the operation, the recommended en bloc resection with ipsilateral thyroid lobectomy was not performed but a parathyroidectomy with surrounding soft tissue. In contrast, 10 preoperatively suspected cases underwent en bloc resection, and one case underwent pericapsular resection followed by supplementary ipsilateral hemithyroidectomy due to the uncertain pre- and intraoperative findings to determine the diagnosis. In conclusion, the surgical procedure for parathyroid carcinoma strongly depends on the preoperative diagnosis. The presence of excessive iPTH levels might contribute to improved preoperative diagnostic sensitivity for parathyroid carcinoma.

Characteristics of oral squamous cell carcinoma focusing on cases unaffected by smoking and drinking: A multicenter retrospective study.

BACKGROUND: Some oral squamous cell carcinoma (OSCC) cases are unaffected by smoking or drinking. This study aimed to clarify distinctive groups among OSCC patients and examine the characteristics of multiple primary carcinomas (MPCs). METHODS: We analyzed data from 970 patients. The patients were divided into three groups: all individuals <45 years (<45 y), smokers/drinkers ≥45 years (SD ≥45 y), and non-smokers/non-drinkers ≥45 years (NSND ≥45 y). RESULTS: Tongue cancers were more common in the <45 y group than in the other groups (p < 0.001). The NSND ≥45 y group was significantly older and more likely to be female than the SD ≥45 y group (p < 0.001). MPCs in the upper aerodigestive tract were more common in men and smokers/drinkers, whereas women were at risk for multiple primary OSCCs (p = 0.022). CONCLUSIONS: The "young tongue" and "elderly female" subgroups and characteristics of MPCs suggest carcinogenic factors of OSCC other than smoking and drinking.

A multi-institutional retrospective study of 340 cases of sinonasal malignant tumor.

OBJECTIVE: Sinonasal malignant tumors (SNMT) are relatively rare among head and neck malignant tumors. Most are squamous cell carcinomas, and malignant melanomas, olfactory neuroblastomas, adenoid cystic carcinomas, sarcomas, and others also occur. The most common primary site of nasal sinus squamous cell carcinoma is the maxillary sinus. In recent years, a decrease in incidence of maxillary sinus squamous cell carcinoma (MSSCC) has been reported along with a decrease in the incidence of sinusitis. MSSCC is treated with a combination of surgery, radiation, and chemotherapy. Treatment decisions are made according to the progression of the disease, the patient's general condition, and the patient's own wishes. There are variations in treatment policies among facilities due to the specialty of staff and cooperation with other departments at each facility. We conducted a multi-institutional retrospective study to compare outcomes by treatment strategy. METHODS: In this study, 340 patients with SNMT who were treated at 13 Hospitals (Head and Neck Oncology Group (Kyoto-HNOG) ) during the 12-year period from January 2006 to December 2017 were included. There were 220 patients with squamous cell carcinoma, 32 with malignant melanoma, 21 with olfactory neuroblastoma, and 67 with other malignancies. Of the squamous cell carcinomas, 164 were of maxillary sinus origin. One hundred and forty cases of MSSCC that were treated radically were included in the detailed statistical analysis. RESULTS: There were 5 cases of cStage I, 9 cases of cStage II, 36 cases of cStage III, 74 cases of cStage IVa, and 16 cases of cStage IVb. There were 92 cases without clinical lymph node metastasis (cN(-)) and 48 cases with clinical lymph node metastasis(cN(+)). Primary tumors were treated mainly by surgery in 85 cases (Surg) and by radical radiation therapy (with or without chemotherapy) of 6-70 Gy in 55 cases(non-Surg). The 5-year overall/disease-free survival rate (OS/DFS) for MSSCC was 65.1%/51.6%. Old age, renal dysfunction, and clinical T progression were independent risk factors for OS, and renal dysfunction was an independent risk factor for DFS. In cN(-) patients, OS and DFS were significantly better in Surg group than in non-Surg group. In cN(+) patients, there was no significant difference in OS and DFS between Surg and non-Surg groups. CONCLUSION: For patients with MSSCC without lymph node metastasis, aggressive surgery on the primary tumor contributes to improved prognosis.

Real-world 2-year long-term outcomes and prognostic factors in patients receiving nivolumab therapy for recurrent or metastatic squamous cell carcinoma of the head and neck.

OBJECTIVE: Real-world outcomes and prognostic factors in Japanese patients receiving nivolumab therapy for recurrent or metastatic head and neck carcinoma (RMHNC) with an observation period of 1 year have been previously reported. The 1-year follow-up data have been subsequently accumulated, and the long-term real-world outcomes have been analyzed. This study aimed to investigate the 2-year long-term outcomes and prognostic factors associated with the response to nivolumab. METHODS: This was a multi-institutional retrospective study. In total, 88 RMHNC Japanese patients with squamous cell carcinoma who received nivolumab between May 2017 and May 2018 were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and best overall response (BOR) were evaluated. Univariate and multivariable analyses were performed to identify the prognostic factors. RESULTS: The median follow-up periods for monitoring OS and PFS were 73.1 and 48.1 weeks, respectively. The median OS was 74.1 weeks, and the 2-year survival rate was 33.4%. The median PFS was 18.5 weeks, and the 2-year PFS rate was 22.5%. The BOR rate was 10.2%, 19.3%, 25.0%, and 44.3% in patients who achieved complete response, partial response, stable disease, and progressive disease (PD), respectively. Among the 88 patients with RMHNC, a total of 40 immune-related adverse events (irAEs) were reported in 30 patients. Four patients continued nivolumab, while 84 patients discontinued nivolumab at the data cut-off date. The most common reason for discontinuation was PD in 61 patients, irAEs in 14 patients, and patients' wishes in 7 patients. Of the 61 patients who discontinued nivolumab because of PD, 28 patients received subsequent treatment. Statistical analyses revealed radiotherapy history, performance status, platinum-refractory carcinoma, irAEs, age, and post-nivolumab treatment as the important prognostic factors associated with OS in patients with RMHNC, and the magnitude of BOR was significantly associated with OS. Additionally, patients with subsequent treatment, including molecular targeted therapy and/or chemotherapy, had significantly prolonged OS compared to patients without subsequent treatment in cases with nivolumab discontinuation because of PD. CONCLUSION: These findings could be a useful guide for future treatment strategies for head and neck carcinoma. Considering the limitations of our cohort, further larger-scale studies with long-term follow-up are needed to substantiate the results of this study.

Clinicopathological Characteristics and Survival Outcomes of Patients with Buccal Squamous Cell Carcinoma: Results of a Multi-Institutional Study.

Background and Objectives: To investigate clinicopathological characteristics and survival outcomes of patients with buccal cancer in Japan. Materials and Methods: This study was conducted using a database of 1055 patients with oral cancers treated between 2010 and 2017 at 12 institutions in Japan. Ninety-two patients (8.7%) with primary buccal cancer were extracted and clinicopathological characteristics and survival outcomes were compared between patients with buccal cancers and patients with other oral cancers. Results: Ages were significantly higher in the patients with buccal cancer (73 years old vs. 69 years old). Buccal cancer had less advanced cT stage and cN stage than other oral cancers. Overall 5-year survival (OS) was 80.6%, and recurrence-free 5-year survival (RFS) of buccal cancers was 67.8%, and there were no significant differences in survival compared with other oral cancers in terms OS or RFS (5y-OS: 82.5%, 5y-RFS: 74.4%). However, patients with stage IV buccal cancer showed poorer prognosis in terms of OS and RFS compared with the same stage patients with other oral cancer. Advanced T stage was the only factor independently associated with both OS and RFS of patients with buccal cancer in this study. Conclusions: Postoperative radiotherapy or chemoradiotherapy should be considered to improve survival outcome of buccal cancer patients, especially for the patients with advanced primary site disease or a higher cancer stage.

Lingual Lymph Node Metastases as a Prognostic Factor in Oral Squamous Cell Carcinoma-A Retrospective Multicenter Study.

Backgrounds and Objectives: The epidemiology and prognostic role of lingual lymph node (LLN) metastasis in patients with oral squamous cell carcinoma (OSCC) remain unclear. Here, we aimed to analyze the clinicopathological features, risk factors, and prognostic role of LLN metastasis in patients with OSCC. Materials and Methods: In total, 945 patients with OSCC were retrospectively analyzed. Clinicopathological features were compared between patients with and without LLN metastasis. The risk factors of LLN metastasis and its effects on survival outcomes were evaluated using multi-variate analysis. Results: LLN metastasis was noted in 67 patients (7.1%). Habitual alcohol consumption and clinical neck node metastasis were independent risk factors for LLN metastasis. LLN metastasis was an independent prognostic factor for disease-free and overall survival, although LLN dissection did not improve survival outcomes. Conclusion: LLN metastasis is an independent adverse prognostic factor. Further prospective studies are needed to fully assess the extent of LLN dissection required in OSCC patients.

A retrospective multicenter study of sublingual gland carcinoma in Japan.

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.

Survival in patients with submandibular gland carcinoma - Results of a multi-institutional retrospective study.

OBJECTIVE: Clinical studies demonstrating the prognostic factors in submandibular gland carcinoma are limited because the tumor is relatively rare. The aim of this study was to identify clinical outcomes and prognostic factors in submandibular gland carcinoma. METHODS: The study included 65 patients with submandibular gland carcinoma who underwent initial surgical treatment at the Kyoto University and its affiliated hospitals. RESULTS: The 3-year overall survival (OS), disease specific survival, locoregional control (LRC), and no distant metastasis (NDM) rates were 74.2%, 74.2%, 90.0%, and 64.8%, respectively. In the current follow-up study, 16 patients died of the disease, 5 patients were alive with recurrence, 43 patients were alive without disease, and 1 patient died of unrelated disease without recurrence. All patients who died of the disease had developed distant metastasis. Based on univariate analysis, tumor grade (high grade) and lymph node metastases (≥N2) were significant prognostic factors for OS and LRC. It also revealed tumor grade (high grade), T classification (≥T3), and lymph node metastases (≥N2) were significant for distant metastasis. Multivariate analysis showed the following significant prognostic factors: lymph node metastases (≥N2) for OS, LRC, and NDM, and high tumor grade for NDM. CONCLUSION: Our study suggested death of submandibular gland carcinoma occurred mainly due to distant metastasis. The significant predictors of distant metastasis were lymph node metastases (≥N2) and tumor grade (high grade).

Unknown primary squamous cell carcinoma of the head and neck: retrospective analysis of 80 cases.

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.

Survival in patients with parotid gland carcinoma - Results of a multi-center study.

BACKGROUND: Parotid gland carcinoma is a rare malignancy, comprising only 1-4% of head and neck carcinomas; therefore, it is difficult for a single institution to perform meaningful analysis on its clinical characteristics. The aim of this study was to update the clinical knowledge of this rare disease by a multi-center approach. METHODS: The study was conducted by the Kyoto University Hospital and Affiliated Facilities Head and Neck Clinical Oncology Group (Kyoto-HNOG). A total of 195 patients with parotid gland carcinoma who had been surgically treated with curative intent between 2006 and 2015 were retrospectively reviewed. Clinical results including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), local control rate (LCR), regional control rate (RCR), and distant metastasis-free survival (DMFS) were estimated. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: The median patient age was 63years old (range 9-93years), and the median observation period was 39months. The OS, DFS, DSS, LCR, RCR, and DMFS at 3years were 85%, 74%, 89%, 92%, 88%, and 87%, respectively. Univariate analysis showed age over 74, T4, N+, preoperative facial palsy, high grade histology, perineural invasion, and vascular invasion were associated with poor OS. N+ and high grade histology were independent factors in multivariate analysis. In subgroup analysis, postoperative radiotherapy was associated with better OS in high risk patients. CONCLUSION: Nodal metastases and high grade histology are important negative prognostic factors for OS. Postoperative radiotherapy is recommended in patients with advanced high grade carcinoma.

Adenoid cystic carcinoma of the head and neck: a retrospective multicenter study.

BACKGROUND: Adenoid cystic carcinoma of the head and neck (ACCHN) is rare and difficult to study effective treatment at one institute. Our aim is to identify prognostic factors for this disease by conducting a multicenter study at 11 institutions in Japan. METHODS: A retrospective multicenter study of ACCHN was performed. One hundred and three patients were identified between 2006 and 2015. The overall survival (OS) rate for all patients was calculated, and OS, locoregional control (LRC) rate, or no distant metastasis (NDM) rate was calculated for patients in that the surgery was performed without distant metastasis (DM). Statistical analyses were performed. RESULTS: A significant difference with multivariate analysis was observed in patients in sublingual glands, stage IV and the use of radiation therapy ≥60Gy (sufficient RT) in OS for all patients. A significant difference was observed in the use of sufficient postoperative RT in the OS and the LRC rate, and in pathological surgical margins in the NDM rate. CONCLUSION: Sublingual glands or stage IV was a poorer, and sufficient RT was a better prognostic factor for ACCHN. Sufficient RT was effective to prevent local recurrence after surgical resection. Positive surgical margins caused an increase in DM.