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.

Nasopharyngeal Carcinoma Treated With Photoimmunotherapy.

Photoimmunotherapy is a new treatment modality in which a tumor-targeting monoclonal antibody is combined with a photoactivated dye and a laser is applied to destroy tumor cells. In Japan, insurance reimbursement for this treatment started in January 2021 for unresectable locally advanced or locally recurrent head and neck cancer. We used photoimmunotherapy to treat two patients with recurrent nasopharyngeal squamous cell carcinoma (NPSCC). The first patient was diagnosed with NPSCC (T1N0M0) and treated with definitive radiotherapy, leading complete response. A local recurrence was observed and treated with photoimmunotherapy. Seven months have passed, complete response is archived. The second patient was diagnosed with NPSCC (cT2N1M1). Multimodal therapy led to a complete response for all lesions. A local recurrent lesion appeared, and photoimmunotherapy has been repeatedly performed. The lesion was controlled as a stable disease for about one year. Photoimmunotherapy could be an effective treatment for local recurrence of NPSCC after radiotherapy.

Eligibility for Photoimmunotherapy in Patients with Unresectable Advanced or Recurrent Head and Neck Cancer and Changes before and after Systemic Therapy.

Photoimmunotherapy is a novel cancer treatment that recently became covered by national health insurance in Japan, but treatment decision-making remains challenging for unresectable advanced or recurrent head and neck cancer. We aimed to clarify the characteristics of patients for whom photoimmunotherapy was indicated by a retrospective chart review. Patients aged ≥20 years diagnosed with advanced or recurrent head and neck cancer who started receiving systemic therapy at the National Cancer Center Hospital East from January 2016 through December 2020 were retrospectively analyzed. Before and after first-line systemic therapy, patients were classified into 3 groups according to eligibility for photoimmunotherapy: eligible, potentially eligible, and ineligible. In total, of 246 patients evaluated-194 after exclusions were analyzed-108 were deemed ineligible for treatment. Of the remaining 86 patients, 8 were considered potentially eligible and 9 eligible. Of the nine eligible patients, four became ineligible after receiving first-line systemic therapy due to disease progression. Our results suggest that the indication of photoimmunotherapy should be considered before, during, and after systemic therapy for unresectable locally advanced or recurrent head and neck cancer.

Clinical outcome of endoscopic-assisted transoral surgery for superficial cancer of pharyngo-esophageal junction.

BACKGROUND: Endoscopic-assisted transoral surgery (TOS) for superficial cancer of the pharyngo-esophageal junction (PEJ) is risk of stricture, and therapeutic outcomes are unclear. This study aimed to evaluate clinical outcomes of endoscopic-assisted TOS for superficial PEJ cancers. METHODS: We retrospectively compared clinical outcomes of endoscopic-assisted TOS for superficial PEJ cancers (group A) and of other sites in the hypopharynx (group B). RESULTS: The group A comprised 12 lesions in 12 patients, and group B comprised 198 lesions in 146 patients. Group A and group B exhibited en bloc resection rates of 100% and 99%. Median operative times were 82 and 37 min (p < 0.001). The frequency of stricture and local recurrence in group A was significantly higher in group B (42% vs. 1%, p < 0.001; 25% vs. 6%, p = 0.036). All adverse events could be managed with conservative treatments. CONCLUSIONS: Endoscopic-assisted TOS is not ideal for treating superficial PEJ cancers compared to other sites.

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.

Human papillomavirus-related multiphenotypic sinonasal carcinoma.

Human papillomavirus-related multiphenotypic sinonasal carcinoma (HMSC) is a rare primary tumor of the sinonasal tract that has been reported recently. It is reportedly associated with human papillomavirus infection. The tumor presents with glandular cyst-like histology, but some cases exhibit squamous epithelialization and are positive on p16 immunohistochemical staining. The clinical picture and treatment of this disease have not been established. However, this report describes a recurrent case of this disease treated with salvage surgery. The patient was a 61-year-old woman who presented to the previous doctor with a chief complaint of nasal obstruction. A localized tumor was found in the left nasal cavity and was resected under endoscopic guidance. The postoperative pathological diagnosis was HMSC. Twenty-one months after the surgery, local recurrence was observed, and the patient was referred to our hospital. Since the recurrent lesion had widely infiltrated outside the nasal cavity, extensive resection and reconstructive surgery were performed. Postoperative radiotherapy was performed as an additional treatment. Notably, 13 months have passed since the salvage surgery, and no recurrence has been observed to date.

Comparison between three age-stratified cohorts reveals poor prognosis of young patients with tongue carcinoma.

Objectives: Investigation of the prognosis of young patients with tongue carcinoma has been the focus of several recent studies aimed at improving future precision treatment. Most studies have been two-cohort investigations comparing young and older patients, who have wide discrepancies in prognosis. Older patients, especially those aged >70 years, often have a poor general condition. This affects the prognosis of the older cohort and accounts for the discrepancies observed in two-cohort studies. Accordingly, in this study, older patients (aged ≥71 years) were separated and compared to young and middle-aged patients. Methods: A total of 257 patients with oral tongue carcinoma referred during 2011-2017 were analyzed. Patients were sorted into young (aged ≤40 years), middle-aged (aged ≥41 and ≤70 years), and older (aged ≥71 years) groups. Overall survival (OS) and disease-free survival (DFS) were compared among the groups. Furthermore, patterns of recurrence rates were compared. Results: Compared with young patients, there was no difference in OS or DFS for older patients (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.5-2.7 and HR: 0.7, 95% CI: 0.4-1.2, respectively) in a multivariate analysis. There was also no difference in OS (HR: 0.6, 95% CI: 0.3-1.3) for middle-aged patients. However, middle-aged patients had low recurrence rates (HR: 0.5, 95% CI: 0.3-0.8). With respect to the recurrence type, middle-aged patients had a low local recurrence rate (HR: 0.3, 95% CI: 0.1-0.7). Conclusion: Three-cohort studies should be conducted to evaluate whether the prognosis of young patients with tongue carcinoma is truly poor in terms of future precision treatment.

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.

Is elective neck dissection necessary for patients with cT3-4N0 parotid gland cancer?

OBJECTIVE: Management of the cervical lymph nodes in patients with cT3-4N0 parotid gland cancer (PGC) has been controversial. This study investigated the need for elective neck dissection (END) in patients with cT3-4N0 PGC. METHODS: We retrospectively examined cervical lymph node metastasis, overall survival (OS), and disease-free survival (DFS) rates in 40 patients with cT3-4N0 PGC according to whether or not END was performed. RESULTS: Cervical lymph node metastasis occurred in 27.5% of patients and level II was the most common area. Recurrence could be treated by salvage neck dissection. There was no significant difference in OS (P=0.581) or DFS (P=0.728) between the group that underwent END and the group that did not. CONCLUSION: END at level II is worth performing because of the occult lymph node metastasis rate. The area of neck dissection should be limited because there is no evidence that END improves the prognosis of cT3-4N0 PGC.

A phase I, single-center, open-label study of RM-1929 photoimmunotherapy in Japanese patients with recurrent head and neck squamous cell carcinoma.

BACKGROUND: To determine the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of a single cycle of RM-1929 photoimmunotherapy, an anti-EGFR antibody cetuximab conjugated with a light-activatable dye (IRDye®700DX), in Japanese patients with recurrent head and neck squamous cell carcinoma (rHNSCC). METHODS: Patients received a single fixed dose (640 mg/m2) of RM-1929 and a fixed light treatment dose (50 J/cm2 for superficial illumination; 100 J/cm fiber diffuser length for interstitial illumination). Safety, tumor response (modified RECIST v1.1 by central radiology review), pharmacokinetics, and immunogenicity were evaluated. RESULTS: Three Japanese patients were enrolled who had failed ≥ 3 prior lines of therapy including radiation, chemotherapy, cetuximab, and immunotherapy. Target lesions were: submental lesion; right superficial cervical node lesion and oropharynx lesion; and external auditory canal lesion. All patients experienced ≥ 1 treatment-emergent adverse event (TEAE), but none were considered dose-limiting. TEAEs were mild to moderate in severity except for one grade 3 application-site pain, which was transient, resolved without sequelae within 24 h, and did not affect study treatment administration. Thirteen of 17 TEAEs reported were possibly or probably related to study treatment. Three patient reports of application-site pain and localized edema were deemed probably related to study treatment. Objective response was observed in two patients (both partial responses). The third patient had disease progression. RM-1929 concentrations and pharmacokinetic parameters were similar in all patients. No patients tested positive for anti-drug antibodies. CONCLUSIONS: RM-1929 photoimmunotherapy showed a manageable safety profile in rHNSCC. Tumor response in these heavily pre-treated patients was clinically meaningful and warrants further investigation. CLINICAL TRIAL REGISTRATION: The trial was registered with the Japanese registry of clinical trials as jRCT2031200133.

Extent of salvage neck dissection following chemoradiation for locally advanced head and neck cancer.

BACKGROUND: Salvage neck dissection (ND) is the only treatment modality for persistent or recurrent nodal disease after chemoradiotherapy (CRT) for locally advanced head and neck cancer. However, the optimal extent of ND at salvage surgery after definitive CRT is controversial. METHODS: Our salvage ND procedure is targeted extirpation of nodal disease with resection of only involved areas of nonlymphatic structures. A retrospective analysis of the data indicated a total of 28 targeted NDs performed in 28 patients following definitive CRT. The efficacy of targeted ND was evaluated based on survival rate, regional control rate, complications, and shoulder syndromes. RESULTS: Over a median follow-up period of 30 months, cervical disease recurred in 7 patients but did not lead to death, and 2 patients died of pulmonary metastasis. The 3-year disease-specific survival rate was 66%. CONCLUSION: The targeted ND procedure was effective as an intervention for patients with cervical disease recurrence (149/150).

Salvage Reconstructive Surgery During Nivolumab Therapy for a Patient With Hypopharyngeal Cancer.

OBJECTIVES: Nivolumab, a fully IgG4-programmed death-1 inhibitor antibody, led to improved overall survival compared with single-agent therapy in patients with platinum-refractory recurrent head and neck cancers. In general, nivolumab is used in inoperable patients. To the best of our knowledge, there have been no reports of salvage surgery during nivolumab therapy for patients with head and neck cancer. We report the case of a woman treated with salvage reconstructive surgery during nivolumab therapy. METHOD: Case report and literature review. RESULTS: The patient underwent nivolumab therapy for recurrent primary and neck disease after induction chemotherapy, followed by concurrent chemoradiation therapy. The neck disease shrunk, whereas the primary disease temporarily shrunk but later progressed again. Recurrent primary disease led to a narrowing of her airway, and she required airway management. We performed total pharyngolaryngectomy with free jejunal reconstruction, and her quality of life improved. The surgery was performed without complications and the postoperative course was uneventful. She was discharged postoperative day 18 with oral intake function and a safer airway. CONCLUSION: As far as we know, this is the first report of salvage surgery during nivolumab therapy for patients with head and neck cancer. The salvage reconstructive surgery in this case proceeded uneventfully.

Comparison of salvage surgery for recurrent or residual head and neck squamous cell carcinoma.

OBJECTIVE: Concomitant chemoradiation therapy is a standard treatment for head and neck cancer. Thus, salvage surgery has become a necessary treatment. The aim of the study was to evaluate the results of salvage surgery by each site of the head and neck, especially the oropharynx, hypopharynx and larynx. METHODS: This was a retrospective, single-institute study. The primary endpoint was overall survival. Secondary endpoints were disease-free survival, the locoregional control rate after salvage surgery, the indication rate for salvage surgery, the reasons for contraindications to salvage surgery, the post-operative complication rate and the predictors of survival. RESULTS: Three-year overall survival after salvage surgery was 58.8% in the salvage surgery group and 8.59% in the other treatment group (P < 0.0001). Regarding overall survival and disease-free survival after salvage surgery, there was no difference among sites. Regarding locoregional control rate among sites, there was no significant difference. The oropharyngeal cancer group had the lowest rate of salvage primary resection. Surgical margin and local and regional recurrence or residual disease were predictors on univariate and multivariate analyses. CONCLUSIONS: Salvage surgery is effective for recurrent or residual cases after concomitant chemoradiation therapy. For oropharyngeal cancer, local control is important, and for oropharyngeal cancer and hypopharyngeal cancer, distant metastasis is important.

Treatment results of 99 patients undergoing open partial hypopharyngectomy with larynx preservation.

OBJECTIVE: Hypopharyngeal cancers frequently go undetected until advanced stages. However, recent advances in endoscopic technology have enabled earlier detection of hypopharyngeal cancer. We evaluated the effectiveness of larynx-preserving surgery for hypopharyngeal cancer. METHODS: We retrospectively analyzed 99 patients with hypopharyngeal squamous cell carcinoma who underwent partial hypopharyngectomy with larynx preservation between September 1992 and December 2009 at the National Cancer Center Hospital East. Of these, 91 patients underwent larynx-preserving surgery as initial treatment; eight patients underwent salvage surgery for recurrent disease after previous radiotherapy. Also, 9 of our patients had undergone previous radiotherapy in the head and neck for a different cancer. Before surgery, the TNM stage and tumor location was recorded. Free-flap reconstruction was performed in 60 patients, while the hypopharyngeal mucosa was closed without a free flap in 39 patients. RESULTS: The 5-year overall survival rate in our cohort was 66.9%, and 59 patients are currently alive without recurrence. Thirty-three patients died due to primary recurrence (n = 5), regional recurrence (n = 10), distant metastasis (n = 9), postoperative death (n = 1), and unrelated disease (n = 8). Laryngeal function could not be preserved in 19 patients, 2 of whom had undergone previous radiotherapy, and 7 of whom had undergone both previous radiotherapy and other salvage surgeries. CONCLUSION: Partial hypopharyngectomy can preserve laryngeal function in patients with pharyngeal cancer with careful patient selection.

The role of elective neck dissection for cT4aN0 glottic squamous cell carcinoma.

OBJECTIVE: The indication for elective neck dissection for patients with clinically T4aN0 (cT4aN0) glottic cancer is not established. The objective of this study was to evaluate the role of elective neck dissection for patients with cT4aN0 glottic cancer. METHODS: We assessed patients with cT4aN0 laryngeal squamous cell carcinoma who underwent total laryngectomy between 1998 and 2014 and conducted a retrospective analysis. We considered occult neck metastasis positive when confirmed by histological analysis. When patients with late neck metastases did not undergo therapeutic neck dissection, the presence of occult neck metastasis was judged on the basis of computed tomography. The validity of elective neck dissection for patients with cT4aN0 glottic cancer was assessed from comparisons the rates of occult neck metastases of supraglottic and subglottic cancers, which are generally recommended for elective neck dissection. The distribution of occult neck metastases in glottic cancer is described according to nodal levels. RESULTS: The rate of occult neck metastasis of cT4aN0 laryngeal cancer was 36% (14/39). There were no significant differences among the rates of glottic 7/21 (33%), supraglottic 3/8 (38%) and subglottic 4/10 (40%) cancers. Patients with glottic cancer did not have bilateral Level IIB and ipsilateral Level IV metastasis. One patient had contralateral Level IV metastasis. The metastases rates of ipsilateral Levels IIA, III, and VI were >10%. CONCLUSIONS: We think that elective neck dissection is valid for cT4aN0 glottic cancer. Ipsilateral Levels IIA, III and VI should be dissected. The omission of neck dissection for bilateral Levels IIB and IV can be considered when there is a need to avoid complications.

Swallowing disorder following salvage total pharyngo-laryngo-esophagectomy with free jejunum reconstruction.

For recurrent cases or residual cases following concomitant chemo-radiation therapy (CCRT), salvage surgery is a frequently used treatment options. A swallowing disorder is one of the major complications of CCRT. The purpose of the present study was to evaluate the effect of CCRT on swallowing function in patients who underwent salvage total pharyngo-laryngo-esophagectomy (TPLE), and to evaluate the importance of pharyngeal constriction in patients who underwent TPLE. Between 2008 January and 2014 May, 54 patients were treated with salvage TPLE following CCRT or TPLE at the National Cancer Center Hospital East, Chiba, Japan and were included in the present study. A total of 14 patients underwent salvage TPLE following CCRT for recurrence or residual tumor (the salvage TPLE group), and 40 patients underwent TPLE as initial treatment (the TPLE group). The pharyngeal constriction score and the post-swallowing oropharyngeal residue rate were evaluated, and inadequate velopharyngeal closure was assessed by videofluorography. The pharyngeal constriction score of the salvage TPLE group was poorer than that of the TPLE group (P<0.05). The bolus residue in the oropharynx was significantly larger in the salvage TPLE group than in the TPLE group (P<0.05). With regards to inadequate velopharyngeal closure, there was no significant difference between the TPLE group and the salvage TPLE group (P>0.99). The results of the present study indicate that the swallowing function of patients who undergo salvage TPLE may be affected by CCRT.

Effectiveness of steroid injections for bamboo nodules: A case report.

Vocal nodules are generally caused by vocal abuse, and conservative treatments such as voice therapy have been advocated as a first-choice treatment for vocal nodules. Reports of vocal fold lesions related to autoimmune diseases, such as bamboo nodules, are rare in the literature. Here we report a very rare case of bamboo nodules in a 30-year-old woman treated by steroid injection into the vocal folds by videoendoscopic laryngeal surgery in an outpatient setting. She was successfully treated without further recurrence. This report indicates that a steroid injection into bamboo nodules might be a useful treatment option, especially in patients who have not shown any improvement after conservative treatments.

[A Case of Severe Hyponatremia Caused by Renal Salt Wasting Syndrome in Oropharyngeal Cancer].

Hyponatremia is one of the electrolyte abnormalities frequently encountered in cancer therapy. Cisplatin is a well-known drug which can raise various adverse events, including hyponatremia. A male with advanced oropharyngeal cancer is presented in the present report, who was treated with radiotherapy with concurrent administration of cisplatin and who underwent a total of three episodes of severe hyponatremia in the course of therapy. The first two attacks of hyponatremia following cisplatin administration were accompanied by dehydration and excessive urination, and the patient recovered in one week with rehydration and salt supplementation. Excessive loss of salt in urine confirmed that these events were caused by renal salt wasting syndrome after cisplatin administration. On the other hand, the third attack was due to the syndrome of inappropriate antidiuretic hormone secretion after surgery for a bone fracture. Estimation of the extracellular fluid volume and salt intake/output balance is always believed to be necessary for the diagnosis and proper management of severe hyponatremia after chemotherapy-based treatment with cisplatin.

Restricted infection of murine cytomegalovirus (MCMV) in neonatal mice with MCMV-induced sensorineural hearing loss.

BACKGROUND: Congenital infection with human Cytomegalovirus (HCMV) is known to be a causative agent of sensorineural hearing loss (SNHL). OBJECTIVES: To clarify the nongenetic etiology of SNHL by identifying the Cytomegalovirus (CMV)-infected region in the cochleae. STUDY DESIGN: We established an animal model of SNHL by injecting neonatal Balb/c mice with intracerebral murine Cytomegalovirus (MCMV) within 24h after delivery. RESULTS: At 3 weeks of age, unilateral and bilateral SNHL were observed in 24% (5/21) and 29% (6/21) of the mice, respectively. SNHL thereafter progressed, with 79% of mice developing bilateral SNHL by 6 weeks of age. MCMV antigens and DNA were detected in the spiral ganglion, and cells surrounding the meninges and scala tympani at 1 week of age. However, both MCMV antigens and DNA had completely disappeared by 2 weeks of age. It is possible that the MCMV reached the spiral ganglion via cerebrospinal fluid as the result of meningitis, as the stria vascularis was found to be MCMV antigen negative. Myosin VI expression in the outer hair cells was lost at 3 weeks of age. MCMV and myosin VI expression disappeared before and during SNHL progression, respectively. CONCLUSIONS: There was a definite lag time between the period in which MCMV antigens/DNA-positive cells were observed and that in which SNHL developed and myosin VI-negative hair cells were observed. Further study is needed to explore the role of MCMV in the loss of myosin VI expression in the outer hair cells.