Evaluation of aesthetic outcomes of mandibular reconstruction using artificial intelligence.

BACKGROUND: Although vascularized bone graft (VBG) transfer is the current standard for mandibular reconstruction, reconstruction with a mandibular reconstruction plate (MRP) and with a soft-tissue flap (STF) alone remain crucial options for patients with poor general conditions. However, objective aesthetic outcome evaluations for these methods are limited. METHODS: In a retrospective analysis of 65 patients (VBG, 33; MRP, 19; and STF, 13), mandibular asymmetry value was calculated for each patient's photograph using facial recognition AI, with a higher value indicating worse asymmetry. RESULTS: The MRP group had a value comparable to the VBG group regardless of mandibular defect types. The STF group had a significantly higher value than the VBG group. CONCLUSIONS: Regarding cosmesis, STF was inferior to VBG, whereas MRP was comparable to VBG, even for anterior defects for which rigid reconstruction is mandatory. However, MRP's risks of plate-related complications limit its use to cases where VBG is contraindicated or with poor prognosis.

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.

Sema6D forward signaling impairs T cell activation and proliferation in head and neck cancer.

Immune checkpoint inhibitors (ICIs) are indicated for a diverse range of cancer types, and characterizing the tumor immune microenvironment is critical for optimizing therapeutic strategies, including ICIs. T cell infiltration and activation status in the tumor microenvironment greatly affects the efficacy of ICIs. Here, we show that semaphorin 6D (Sema6D) forward signaling, which is reportedly involved in coordinating the orientation of cell development and migration as a guidance factor, impaired the infiltration and activation of tumor-specific CD8+ T cells in murine oral tumors. Sema6D expressed by nonhematopoietic cells was responsible for this phenotype. Plexin-A4, a receptor for Sema6D, inhibited T cell infiltration and partially suppressed CD8+ T cell activation and proliferation induced by Sema6D stimulation. Moreover, mouse oral tumors, which are resistant to PD-1-blocking treatment in wild-type mice, showed a response to the treatment in Sema6d-KO mice. Finally, analyses of public data sets of human head and neck squamous cell carcinoma, pan-cancer cohorts, and a retrospective cohort study showed that SEMA6D was mainly expressed by nonhematopoietic cells such as cancer cells, and SEMA6D expression was significantly negatively correlated with CD8A, PDCD1, IFNG, and GZMB expression. Thus, targeting Sema6D forward signaling is a promising option for increasing ICI efficacy.

Extracting interpretable features for pathologists using weakly supervised learning to predict p16 expression in oropharyngeal cancer.

One drawback of existing artificial intelligence (AI)-based histopathological prediction models is the lack of interpretability. The objective of this study is to extract p16-positive oropharyngeal squamous cell carcinoma (OPSCC) features in a form that can be interpreted by pathologists using AI model. We constructed a model for predicting p16 expression using a dataset of whole-slide images from 114 OPSCC biopsy cases. We used the clustering-constrained attention-based multiple-instance learning (CLAM) model, a weakly supervised learning approach. To improve performance, we incorporated tumor annotation into the model (Annot-CLAM) and achieved the mean area under the receiver operating characteristic curve of 0.905. Utilizing the image patches on which the model focused, we examined the features of model interest via histopathologic morphological analysis and cycle-consistent adversarial network (CycleGAN) image translation. The histopathologic morphological analysis evaluated the histopathological characteristics of image patches, revealing significant differences in the numbers of nuclei, the perimeters of the nuclei, and the intercellular bridges between p16-negative and p16-positive image patches. By using the CycleGAN-converted images, we confirmed that the sizes and densities of nuclei are significantly converted. This novel approach improves interpretability in histopathological morphology-based AI models and contributes to the advancement of clinically valuable histopathological morphological features.

Machine learning approach to predict tracheal necrosis after total pharyngolaryngectomy.

BACKGROUND: Tracheal necrosis is a potentially severe complication of total pharyngolarynjectomy (TPL), sometimes combined with total esophagectomy. The risk factors for tracheal necrosis after TPL without total esophagectomy remain unknown. METHODS: We retrospectively reviewed data of 395 patients who underwent TPL without total esophagectomy. Relevant factors associated with tracheal necrosis were evaluated using random forest machine learning and traditional multivariable logistic regression models. RESULTS: Tracheal necrosis occurred in 25 (6.3%) patients. Both the models identified almost the same factors relevant to tracheal necrosis. History of radiotherapy was the most important predicting and significant risk factor in both models. Paratracheal lymph node dissection and total thyroidectomy with TPL were also relevant. Random forest model was able to predict tracheal necrosis with an accuracy of 0.927. CONCLUSIONS: Random forest is useful in predicting tracheal necrosis. Countermeasures should be considered when creating a tracheostoma, particularly in patients with identified risk factors.

Enhanced recovery pathways for head and neck surgery with free tissue transfer reconstruction.

The enhanced recovery after surgery (ERAS) pathway is designed to facilitate recovery after surgery by packaging evidence-based protocols specific to each aspect of the perioperative period, including the preoperative, intraoperative, postoperative, and post-discharge periods. The ERAS pathway, which was originally developed for use with colonic resection, is now being expanded to include a variety of surgical procedures, and the ERAS Society has published a consensus review of the ERAS pathway for head and neck surgery with free tissue transfer reconstruction (HNS-FTTR). The ERAS pathway for HNS-FTTR consists of various important protocols, including early postoperative mobilization, early postoperative enteral nutrition, abolition of preoperative fasting, preoperative enteral fluid loading, multimodal pain management, and prevention of postoperative nausea and vomiting. In recent years, meta-analyses investigating the utility of the ERAS pathway in head and neck cancer surgery have also been presented, and all reports showed that the length of the postoperative hospital stay was reduced by the implementation of the ERAS pathway. The ERAS pathway is now gaining traction in the field of head and neck surgery; however, the details of its efficacy remain uncertain. We believe the future direction will require research focused on improving the quality of postoperative patient recovery and patient satisfaction. It will be important to use patient-reported outcomes to determine whether the ERAS pathway is actually beneficial.

Dose-Finding and Efficacy Confirmation Trial of the Superselective Intra-arterial Infusion of Cisplatin and Concomitant Radiation Therapy for Locally Advanced Maxillary Sinus Cancer (JCOG1212): Results of the Efficacy Confirmation Phase in Patients with T4aN0M0.

PURPOSE: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment, but this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiation therapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas. We herein report the results of the efficacy confirmation phase in the T4a cohort. METHODS AND MATERIALS: Patients received 100 mg/m2 cisplatin intra-arterially weekly for 7 weeks with concomitant radiation therapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (OS), comparing RADPLAT with the historical control for 3-year OS in surgery (80%). RESULTS: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 men and 11 women with a median age of 64 years (range, 40-78 years) and Eastern Cooperative Oncology Group performance status 0/1 (58/7). After excluding 1 ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3-year OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (grade ≥3), neutropenia (grade ≥3), increased creatinine (grade ≥2), hearing impairment (grade ≥2), and stroke (grade ≥2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported. CONCLUSIONS: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 maxillary sinus squamous cell carcinomas compared with the historical control for 3-year OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients.

Second free jejunum transfer after flap loss does not affect oral intake: A retrospective case-control study.

PURPOSE: Free jejunum transfer is one of the standard procedures for restoring oral intake after total pharyngo-laryngo-esophagectomy. Flap loss leading to a second free jejunum transfer rarely occurs. This study investigated the impact of a second free jejunum transfer on post-operative oral intake. METHODS: A retrospective review was conducted on patients who underwent a first free jejunum transfer between July 1998 and December 2019. A total of 367 patients were included in the study. Among them, 17 patients who underwent a second free jejunum transfer because necrosis constituted the second free jejunum transfer group, whereas 350 patients who did not require a second free jejunum transfer formed the first free jejunum transfer group. The incidence of dysphagia requiring tube feeding and post-operative complications was compared between the two groups. Moreover, risk factors for dysphagia and complications were estimated. RESULTS: There were no statistically significant differences in the incidence of dysphagia post-operation between the two groups. A second free jejunum transfer was a statistically significant factor for complications at 2- and 6-months post-operation; however, there were no significant differences in complication rates at the 12-month follow-up. Furthermore, there were no significant differences in the incidence of severe complications between the two groups. CONCLUSION: Although a second free jejunum transfer increases early complications, it is not associated with major complications and does not negatively impact oral intake. These findings support the conclusion that free jejunum transfer is safe and helps maintain post-operative quality of life.

Accelerated three-dimensional conformal radiotherapy for early-stage glottic cancer in reducing dose to the internal carotid artery and pharyngeal constrictor muscles.

BACKGROUND: We evaluated clinical and dosimetric outcomes of radiotherapy using two anterior oblique portals (AOP), to reduce the dose to the bilateral internal carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) during early-stage glottic cancer (ESGC) treatment. METHODS: We identified patients with ESGC who underwent definitive radiotherapy between June 2014 and May 2020. RESULTS: Among the 66 patients, 32 (48%) underwent radiotherapy using AOP, and the remaining underwent typical radiotherapy using parallel opposed lateral portals (POLP). The median follow-up duration was 53 months. No significant differences were observed in the 5-year local failure (0%/9.4%), progression-free survival (90.6%/90.8%), and overall survival (90.6%/91.0%) rates between the two groups. The grade ≥2 acute mucositis incidence rate was significantly lower in the AOP group (44%/85%). Radiotherapy using AOP maintained an adequate dose coverage to the target while markedly reducing the CAs and PCM doses. CONCLUSION: Radiotherapy with AOP resulted in favorable clinical and dosimetric outcomes.

Long-term outcomes of patients with oral cavity cancer receiving postoperative radiotherapy after salvage neck dissection for cervical lymph node recurrence.

BACKGROUNDS: We aimed to clarify the outcomes of postoperative radiotherapy (PORT) after salvage neck dissection for cervical lymph node (LN) recurrence in oral cavity cancer. METHODS: We retrospectively evaluated overall survival (OS), recurrence-free survival (RFS), recurrence patterns, and adverse events of 51 patients with high-risk features receiving PORT after salvage neck dissection between 2009 and 2019. RESULTS: After a median follow-up of 7.4 years from PORT initiation, the 7-year OS and RFS rates were 66.3% (95% CI: 54.0-81.3) and 54.6% (95% CI: 42.1-70.9), respectively. Age <70 years and isolated LN recurrence were significantly associated with longer OS and RFS. Among the 22 patients who experienced recurrence, 14 experienced recurrence within the radiation field. PORT-related grade 3 acute mucositis (35%) and late adverse events (osteoradionecrosis [4%] and laryngeal stenosis [2%]) were observed. CONCLUSIONS: PORT after salvage neck dissection for cervical LN recurrence achieved good survival with acceptable toxicity.

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.

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.

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).

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.

Anatomical classification of pharyngeal and laryngeal endoscopic images using artificial intelligence.

BACKGROUND: The entire pharynx should be observed endoscopically to avoid missing pharyngeal lesions. An artificial intelligence (AI) model recognizing anatomical locations can help identify blind spots. We developed and evaluated an AI model classifying pharyngeal and laryngeal endoscopic locations. METHODS: The AI model was trained using 5382 endoscopic images, categorized into 15 anatomical locations, and evaluated using an independent dataset of 1110 images. The main outcomes were model accuracy, precision, recall, and F1-score. Moreover, we investigated focused regions in the input images contributing to the model predictions using gradient-weighted class activation mapping (Grad-CAM) and Guided Grad-CAM. RESULTS: Our AI model correctly classified pharyngeal and laryngeal images into 15 anatomical locations, with an accuracy of 93.3%. The weighted averages of precision, recall, and F1-score were 0.934, 0.933, and 0.933, respectively. CONCLUSION: Our AI model has an excellent performance determining pharyngeal and laryngeal anatomical locations, helping endoscopists notify of blind spots.

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.

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.

The area of residual tumor predicts esophageal squamous cell carcinoma prognosis following neoadjuvant chemotherapy.

PURPOSE: To clarify the utility of the area of residual tumor for patients with esophageal squamous cell cancer treated with neoadjuvant chemotherapy. METHODS: We enrolled 186 patients with esophageal squamous cell cancer who underwent surgical resection following neoadjuvant chemotherapy at our hospital. Using digital images, we measured the area of residual tumor at the maximum plane of the specimen and divided the patient into three groups as follows: 0 (area = 0 mm2), low (area = 0-40 mm2), and high (area ≥ 40 mm2). The clinicopathological factors and prognosis were compared among these groups. RESULTS: The median area of the residual tumor was 15.0 mm2　(range 0-1,448.8 mm2). Compared with the 0 and low group, the high group was significantly associated with poorer recurrence-free survival (all P < .001) and overall survival (P < .001 [vs. 0] and P = .017 [vs low]). The area of residual tumor, ypN, tumor regression grade, and lymphovascular invasion were independent predictors of recurrence-free survival. By dividing the patients using a combination of the area of residual tumor and lymphovascular invasion, the high and/or lymphovascular invasion ( +) group displayed significantly poor recurrence-free survival than the 0 group and low/lymphovascular invasion ( -) group. However, there was no significant difference in the recurrence-free survival between the 0 group and low/lymphovascular invasion ( -) group. CONCLUSION: The area of residual tumor is a promising histopathological prognostic factor for patients with esophageal squamous cell cancer treated with neoadjuvant chemotherapy. Moreover, it is a possible candidate histopathological factor for postoperative chemotherapy selection.

Immunohistochemical Analysis of Common Cancer Antigens in Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: The prognosis of recurring and metastatic head and neck squamous cell carcinoma (HNSCC) is poor. Although immune checkpoint inhibitors have expanded the treatment options for HNSCC, the response rates are low. Alternatively, cancer vaccines and T-cell therapies are being developed. Identification of useful common cancer antigens and confirmation of human leukocyte antigen (HLA) class I expression are required. MATERIALS AND METHODS: Immunohistochemistry analyses were performed for 10 antigens (FOXM1, TGFBI, SPARC, HSP105α, WT1, AFP, GPC3, PP-RP, KIF20A, KM-HN-1) and HLA class I using specimens of 56 surgical cases. Staining intensity, percentage of stain-positive areas, and localization of staining in the tumor cells and normal tissue were evaluated. RESULTS: Staining of FOXM1, TGFBI, SPARC, and HSP105α was more predominant in tumor cells than that in normal cells. The expression rates of these antigens in tumor cells were 60.7%, 58.9%, 73.2%, and 50.0%, respectively. Regarding sites, the expression rates of these antigens in oral cancer were high at 57.1%, 71.4%, 81.0%, and 66.7%, respectively. Furthermore, the expression of HLA class I was 83.9% in all cases. Of these, 68.1% showed expression on the plasma membrane. CONCLUSION: FOXM1, TGFBI, SPARC, and HSP105α could be useful common cancer antigens, and HLA class I is expressed on the plasma membrane of cancer cells in many cases. The results suggest that cancer vaccines and T-cell therapy may be clinically viable options for HNSCC treatment.