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

Head and neck cancer involving the carotid artery is usually unresectable. Such involvement often leads to exposure of the carotid artery and the risk of its blow-out. Carotid covered stent placement may be effective in preventing carotid blow-out; however, thus far, there are few published reports of this procedure. We here present a 65-year-old man who developed neck node recurrence of laryngeal cancer involving the carotid artery, which eventually resulted in exposure of that artery and its impending blow-out. A balloon occlusion test was performed to confirm that the circle of Willis was complete. A covered stent was inserted simultaneously into the affected carotid, enabling us to perform en block resection of the tumor and involved carotid artery as an elective procedure. The patient remained alive and disease-free with no complications or sequelae 10 years after this operation. Despite carotid blow-out being considered imminent, insertion of an endovascular covered stent into the affected carotid artery allowed us to investigate the feasibility of carotid resection while simultaneously preventing that artery’s rupture. Aggressive surgical resection may lead to maintenance of quality-of-life and long-term survival in selected patients.

Objective Early enteral nutrition is essential for enhancing recovery after surgery. However, to date, no detailed study has been conducted on the feasibility of early enteral nutrition in patients undergoing head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) and the risk factors for difficulty with early enteral nutrition. Methods We retrospectively analyzed 102 patients who underwent HNS-FTTR at our institution; 61 underwent free jejunal reconstruction (FJ) and 41 did not. We investigated the achievement of early enteral nutrition within 24 and 48 h after surgery and the discontinuation of enteral nutrition after its initiation within 7 days after surgery. Results Enteral nutrition could be started in 81/102 (79.4%) and 99/102 (97.1%) patients within 24 and 48 h, respectively. Cases of difficulty with early enteral nutrition accounted for 21/102 (20.6%) patients. The multivariate analysis revealed that FJ was a significant independent risk factor for difficulty with early enteral nutrition (odds ratio: 4.054, P = 0.042). The risk factors for difficulty with early enteral nutrition in patients who underwent FJ were also investigated, and the multivariate analysis showed that blood loss of ≥158 mL was a significant independent risk factor (odds ratio: 3.505, P = 0.044). Conclusions Early enteral nutrition seemed to be provided with no problems in patients without FJ. FJ was a significant risk factor for difficulty with early enteral nutrition. Increased intraoperative blood loss was a significant risk factor for difficulty with early enteral nutrition in patients undergoing FJ; therefore, patients’ abdominal symptoms and gastric residual volume should be carefully monitored in such cases.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real‐world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1–75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2–357). Adverse events occurred in 12.7%. Life‐threatening complications occurred in 0.5%, but there were no treatment‐related deaths. During a median follow‐up period of 46.1 months (range 1–113), the 3‐year overall survival rate, relapse‐free survival rate, cause‐specific survival rate, and larynx‐preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276., This is the first report on nationwide survival data and pathological criteria of superficial head and neck cancer. Transoral surgery for superficial head and neck cancer was safe and offered highly curative minimally invasive treatment preserving organs and their function. Subepithelial invasion was clinically useful predictor of recurrence after transoral surgery.

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

BackgroundThe outcome of head and neck cancer has improved in recent years but survival is not yet satisfactory. Interleukin (IL)-6 is a representative inflammatory cytokine and inducer of systemic inflammatory response. It is not known whether preoperative serum level of IL-6 is a prognostic factor in head and neck cancer surgery.MethodsWe studied 181 consecutive patients who underwent head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) between September 2016 and December 2020. Whether preoperative serum IL-6 level was a prognostic risk factor was retrospectively investigated by univariate and multivariate analyses. We also investigated the association between preoperative IL-6 level and representative systemic inflammatory response markers.ResultsThe preoperative IL-6 ≥ 8 pg/mL group had a significantly worse prognosis than the preoperative IL-6 ConclusionsPreoperative serum IL-6 level is an independent poor prognostic factor for both OS and DSS after HNS-FTTR, reflecting the degree of preoperative systemic inflammatory response.

CD271 is a common receptor for all neurotrophins that is localized to neurons, endothelial cells, and the basal layer of the epithelium in normal tissue. Recently, we and others reported that CD271 plays essential roles in the development of squamous cell carcinoma, especially in tumor-initiating cells. Since little is known about how CD271 regulates cancer cell initiation and proliferation, antibodies that recognize different domains of CD271 are needed to enable investigation. Therefore, this study aimed to develop an antihuman CD271 antibody by immunizing mice with a CD271 antigen produced by a baculovirus. The antibody was named hCD271mAb#13, and it recognized cysteine-rich domain 1 with a higher affinity than the commercially available antibody ME20.4. We determined that hCD271mAb#13 is suitable for flow cytometry, Western blotting, immunocytochemistry, and immunohistochemistry of formalin-fixed paraffin-embedded tissue. Use of hCD271mAb#13 for CD271 labeling could enable detailed analyses of cancer cell regulation and other biological processes.

In the treatment of head and neck cancer, radiation therapy is an effective modality and is often used in routine clinical practice. Although rare, pyogenic spondylitis has been reported as a complication of radiation therapy. Here, we report a case of nasopharyngeal carcinoma resulting in pyogenic spondylitis from a catheter-related bloodstream infection after chemoradiotherapy. The initial symptoms were fever and posterior cervical pain. Streptococcus dysgalactiae subspecies equisimilis was detected in blood cultures. Magnetic resonance imaging showed abnormal enhancement of the C6 and C7 vertebrae and an anterior epidural abscess. The infection was successfully treated with antibacterial therapy.

Cardiac metastases from head and neck cancers are sometimes found at autopsy, but are rarely found before death; therefore, case reports are uncommon. In this report, we describe a case of cardiac metastasis from head and neck cancer. Although asymptomatic at the time of detection, positron emission tomography–computed tomography was effective in ascertaining the diagnosis. However, patients with cardiac metastases usually have a poor prognosis, and unfortunately, the patient died shortly after detection. At autopsy, the patient had a “hyperdense armored heart” owing to a huge pericardial metastases. Here, we report the imaging and autopsy findings of a hyperdense armored heart owing to cardiac metastases from head and neck cancer.

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

We report here a patient with a massive lymphatic metastasis involving the internal jugular-subclavian venous (IJ-SCV) junction that was safely resected with a new surgical procedure without significant complications. The patient, a 57-year-old man, had advanced hypopharyngeal cancer that had metastasized to the left IJ-SCV junction with a considerable invasion of the vessels, seemingly precluding a conventional surgical intervention. We, therefore, devised a new minimally invasive surgical approach involving resection of the margin of the medial clavicle, which provided an open view of the operation field. This enabled severance of both subclavicular and brachiocephalic veins and removal of the tumor. All procedures were accomplished safely and there were no postoperative circulatory disturbances, including arm edema and compartment syndrome, in the ipsilateral arm. Additionally, postoperative adjuvant chemoradiotherapy was completed uneventfully.

Background: Biomarkers predicting therapeutic response to immunotherapy have been widely explored via monitoring the liquid and tissue-derived components. Increasing treatment options for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) mandates prediction of the therapeutic response of anti-PD-1 antibody alone as well as optimization of the treatment sequence. In view of improving biomarkers predicting the efficacy of immunotherapy for R/M HNSCC, we hypothesized that biomarkers can be personalized depending on clinicopathological backgrounds and treatment sequence. Methods: In this study, we retrospectively included formalin-fixed paraffin-embedded (FFPE) samples, peripheral blood cell counts at treatment, clinicopathological information, and outcome data for patients with R/M HNSCC receiving nivolumab across 22 institutions in Japan (N = 100). FFPE samples were subjected to 14-marker multiplex immunohistochemistry (IHC) and image cytometry analysis (Tsujikawa T et al. Cell Reports, 2017) to quantitatively evaluate CD8+ T cells, helper T cells, regulatory T cells, B cells, natural killer (NK) cells, macrophages, dendritic cells, CD66b+ granulocytes, mast cells, programmed death ligand 1 (PD-L1) and PD-1 expression in a single slide. Intratumoral and circulating immune cell frequencies were comparatively analyzed between responders (CR, n = 14; PR, n = 39) and non-responders (SD, n = 2; PD, n = 45). Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-L1 expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. Next, focusing on the history of prior therapy, stratified analysis revealed that the frequency of NK cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Furthermore, stratified analysis by patient age revealed that nivolumab response was significantly associated with high CPS and lymphoid-inflamed profiles based on cell densities of nine immune cell lineages in the group aged 65 years or older, but not in the group under 65 years of age. On the contrary, the neutrophil/lymphocyte ratios (NLR) in peripheral blood counts at nivolumab treatment were significantly lower in responders (mean 4.96) than those in non-responders (mean 10.46) in the group under 65 years of age, but not in those over 65 years of age (7.41 versus 8.47). Conclusions: Using peripheral blood data and tumor tissue profiling stratified by patient age and prior treatment might provide better predictive biomarkers in nivolumab response to HNSCC. Further preclinical and clinical studies elucidating immune mechanisms in different patient backgrounds will be warranted. Citation Format: Takahiro Tsujikawa, Kazuchika Ohno, Sumiyo Saburi, Junichi Mitsuda, Kanako Yoshimura, Alisa Kimura, Hiroki Morimoto, Gaku Ohmura, Akihito Arai, Hiroshi Ogi, Saya Shibata, Yosuke Ariizumi, Akihisa Tasaki, Ryosuke Takahashi, Yumiko Tateishi, Hiroaki Kawabe, Sadakatsu Ikeda, Kei-ichi Morita, Tatsuhiko Tsunoda, Takumi Akashi, Morito Kurata, Issei Imoto, Yasushi Shimizu, Akihito Watanabe, Yukinori Asada, Ryuichi Hayashi, Yuki Saito, Hiroyuki Ozawa, Kiyoaki Tsukahara, Nobuhiko Oridate, Arata Horii, Takashi Maruo, Nobuhiro Hanai, Hidenori Inohara, Hiroshi Iwai, Takashi Fujii, Ken-ichi Nibu, Shigemichi Iwae, Tsutomu Ueda, Ryuji Yasumatsu, Hirohito Umeno, Muneyuki Masuda, Kyoko Itoh, Shigeru Hirano, Takahiro Asakage. Tumor immune characterization identifies age-stratified biomarkers for nivolumab in patients with head and neck squamous cell carcinoma: A nationwide collaborative study in Japan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5210.

We report a very rare case of an ectopic thyroid in the superior mediastinum, which was detected incidentally using imaging. The case was a 50-year-old woman patient. She had an orthotopic thyroid and normal thyroid function. This superior mediastinum mass obviously lacked continuity with the orthotopic thyroid. Its computed tomography density was lower than that of the orthotopic thyroid, and an enhancement was heterogeneously observed. In the cytodiagnosis, only large and small lymphocytes were observed, and malignant diseases such as malignant lymphoma could not be ruled out, so surgical resection was performed through a cervical incision. Combined resection of the thyroid was unnecessary, and ligation of the feeding vessels from the thorax side was able to be carried out without incident.

Neck dissection results in a high probability of postoperative shoulder functional impairment, even when the spinal accessory nerve is preserved. Therefore, surgeons must inform patients about the expected functional and qualitative recovery of shoulder function after surgery.The present study included a prospective cohort of 66 patients (85 neck dissection sides) who underwent neck dissection between December 2015 and July 2017 at a single institution. The active shoulder abduction angles of the affected side and the patient-reported shoulder-specific quality-of-life recovery score of the Western Ontario Rotator Cuff (WORC) questionnaire were examined at 1, 3, 6, 9, and 12 months postoperatively. Additionally, the association between these outcomes and risk factors for shoulder impairment were investigated.The average active shoulder abduction angles were significantly improved at 3 and 6 months postoperatively compared with 1 month postoperatively (96.5 ± 4.3° at 1 month versus 110.1 ± 4.7° at 3 months, p = 0.035, and versus 142.0 ± 4.6° at 6 months, p 0.0001). The proportion of patients who were unable to abduct their shoulders by 150° or more was significantly lower at 6 months postoperatively (41.5%) compared with 1 month postoperatively (82.4%, p 0.0001). The WORC score significantly improved from 60.4 ± 2.4% at 1 month postoperatively to 67.9 ± 2.6% at 6 months postoperatively (p = 0.036). Multivariate analysis revealed that postoperative radiotherapy was a significant risk factor for shoulder impairment at 3 and 6 months postoperatively (p = 0.003 and p = 0.027, respectively), and that level V dissection and head and neck irradiation were significant risk factors for a worse shoulder outcome at 6 and 9 months postoperatively (respective p values for level V dissection and head and neck irradiation were p = 0.049 and p = 0.030 at 6 months postoperatively, and p = 0.016 and p = 0.013 at 9 months postoperatively).Satisfactory functional and qualitative recovery of shoulder function was achieved at 6 months after neck dissection. Postoperative radiotherapy was a predictor of poor shoulder function in the early postoperative period; both level V dissection and head and neck irradiation were predictors of poor shoulder function at 6 and 9 months after neck dissection.

Objective the pandemic of coronavirus disease 2019 (COVID-19), hospitals worldwide are at risk of nosocomial infection. Preoperative identification of COVID-19 in patients who are scheduled to be admitted to the hospital is essential to preventing the collapse of medical facility. In Japan, the preoperative observation and screening tests with the RT-PCR testing for the new coronavirus (SARS-CoV-2) and chest CT scan are recommended for head and neck cancer surgery during the COVID-19 pandemic. Method We conducted surveys of the current situation in Japan through the internet. Results Chest CT scan was fully performed (90%), but the RT-PCR testing was not adequately performed (51%). Conclusion Although the current screening system can be considered effective to a certain extent, we recommend further widespread use of pre-admission RT-PCR testing not only for patients with head and neck cancer surgery but also for all the hospitalized patients, in order to promote safer treatments, during the COVID-19 pandemic.

Enhanced Recovery After Surgery (ERAS) protocols promote recovery after various invasive surgeries. Likewise, preoperative glucocorticoid administration can reduce complications after some surgeries. However, the effects of ERAS protocols and glucocorticoid administration in patients undergoing major surgery for head and neck cancer have not been well described. The aim of this study was to evaluate the effect of an ERAS protocol with preoperative glucocorticoid administration in major surgery for head and neck cancer.This retrospective study included 28 patients who underwent major head and neck surgery with free tissue transfer reconstruction at our institution from September 2016 to May 2017, after implementation of an ERAS protocol with preoperative glucocorticoid administration. Outcomes in that group were compared with those in a control group that underwent surgery from January 2015 to September 2016, before implementation of the protocol.Analysis revealed significantly less body weight fluctuation, lower C-reactive protein levels, higher albumin levels, and lower body temperature in the ERAS group than in the control group postoperatively.Patients undergoing major surgery for head and neck cancer who were treated with the ERAS protocol and preoperative glucocorticoid administration had evidence of better hemodynamic stability and less inflammatory response than control patients.

Hypopharyngeal cancer is a head and neck cancer with a poor prognosis, and most cases show metastases on diagnosis. Cervical lymph node (LN) metastasis is a poor prognostic factor in hypopharyngeal cancer patients. The identification of risk factors for LN metastasis can help guide surgical treatment strategies for these patients.This retrospective study included 93 superficial hypopharyngeal cancer patients with 109 histopathologically examined lesions treated by endoscopic resection between January 2007 and December 2017. Tumor thickness quantification, quantification of budding nests, immunostaining and other histopathological analyses in paraffin-embedded, formalin-fixed tissue sections (3-μm) of surgical specimens were performed by a certified pathologist.Cervical LN metastasis was positive in 18 out of 93 cases (19.3%) and 18 out of 109 lesions (16.5%). No differences were detected in patient characteristics between LN-positive and LN-negative cases, except for tumor thickness, which was significantly larger in LN-positive cases (3119.4±602.2μm vs. 1015.5±129.6μm, respectively; p0.0001). Univariate analysis showed that tumor thickness ≥1000μm (odds ratio: 5.559, p=0.003), lesions with high budding grade (odds ratio: 5.188, p=0.01) and vascular invasion (odds ratio: 12.710, p=0.007) were significantly associated with cervical LN metastasis. Multivariate analysis revealed tumor thickness≥1000μm as the most significant risk factor for cervical LN metastasis in superficial hypopharyngeal cancer (odds ratio: 3.639, p=0.04).We demonstrate for the first time that high budding grade may serve as powerful predictors of LN metastasis and tumor thickness ≥1000μm is a significant risk factor for LN metastasis of superficial hypopharyngeal cancer. These results should be further examined in future larger scale studies.

Background There are few reports on Enhanced Recovery After Surgery (ERAS)-based perioperative management following head and neck surgery with free tissue transfer reconstruction (HNS-FTTR). Here, we prospectively evaluated our ERAS program involving preoperative glucocorticoid administration in HNS-FTTR. Methods This prospective study included 60 patients who underwent HNS-FTTR at the Miyagi Cancer Center from June 2017 to December 2018. Their treatment plan included receiving perioperative management in accordance with our head and neck ERAS program. Major outcomes of hospitalization periods, early mobilization, early enteral nutrition, and patient satisfaction were assessed, and blood date and vital signs were compared with control patients who underwent HNS-FTTR from January 2014 to September 2016 at our institution before ERAS was implemented. Results The duration of hospital stay and the duration until completion of the discharge criteria was a median of 25 days and 17 days, respectively. Early mobilization was achieved in 86.0% of the patients at postoperative-day (POD)1 and 96.5% at POD2. Enteral nutrition was started in 80.1% at POD1 and 100% at POD2. Postoperative pain was controlled at mean VAS scores of 1.51–3.13. Clavien–Dindo grade II or higher postoperative complications were evident in 27.6% of the patients. The mean QOR40 score was 179.6 preoperatively, 146.1 at POD3, and 167.8 at POD7. Compared with the control group, there were significantly lower C-reactive protein levels, higher albumin levels, a lower body temperature, a lower neutrophil-to-lymphocyte ratio, less body weight fluctuation, and fewer incidences of decreased blood pressure in the ERAS group. Conclusion Patients who underwent HNS-FTTR with ERAS-based perioperative management achieved early mobilization, early enteral nutrition, favorable pain control, remarkable recovery of patient satisfaction at POD7, and there was evidence of better hemodynamic stability and less inflammatory response compared with control patients.

CD271, known as a neurotrophin receptor, is expressed in various cancers such as hypopharyngeal cancer (HPC) and melanoma. We recently reported that CD271 is a cancer-stem-cell biomarker of HPC, and that its expression is essential for cancer-cell proliferation and is correlated with a poor prognosis in this disease. Here, to develop a therapeutic antibody to CD271, we established a humanized anti-CD271 monoclonal antibody (hCD271 mA b). hCD271 mA b bound to the cysteine-rich domain 1 (CRD1) of human CD271 with high affinity (KD = 1.697 × 10−9 M). In vitro, hCD271 mA b exerted antibody-dependent cell-mediated cytotoxicity (ADCC) activity against SP2/0-CD271 (human CD271-transduced mouse cell line). Treatment with hCD271 mA b also exerted anti-tumor activity in graft models of three cell lines (HPCM2 (patient-derived xenograft cell line of hypopharyngeal cancer), MeWo-Luc (melanoma cell line), and SP2/0-CD271) in mice, resulting in smaller tumors compared to controls and reduced numbers of CD271-positive cells. Collectively, these data suggest that an antibody targeting CD271 is a promising therapeutic strategy.

Background: Extensive resection and free-flap reconstruction surgery has become the standard treatment for locally advanced head and neck cancer. Surgical site infection (SSI) is one of the serious complications of this treatment. This study aimed to investigate the risk factor for onset of SSI, particularly focusing on whether preoperative professional oral health care in cooperation with general dental clinics is effective in reducing the occurrence of SSI. Methods: From March 2003 to August 2011, 183 patients who underwent head and neck free-flap reconstructive surgery by the same plastic surgeon at Miyagi Cancer Center for Head and Neck Surgery were investigated retrospectively. Results: Of the 183 patients, 135 and 48 were men and women, respectively, with a mean age of 62 (range, 29-82) years. The tumor was located in the oral cavity (n = 76), hypopharynx (n = 55), oropharynx (n = 28), and others (n = 24). Clinical stages were stage I/II in 18, stage III/IV in 164 patients, and benign tumor in one patient, based on UICC classification. SSI occurred in 66 patients (36.1%). Based on multivariate analysis, professional oral health care [P = 0.0076, odds ratio (OR) = 0.39] and radiation therapy history (P = 0.0214, OR = 2.820) were shown as factors that are significantly related to SSI. Conclusion: This study identified history of radiation therapy as a significant risk factor for SSI from univariate and multivariate analysis and revealed that patients receiving preoperative professional oral health care at general dental clinics reduce the risk of SSI. Preoperative professional oral health care in cooperation with general dental clinics has been shown to reduce SSI of head and neck free-flap reconstructive surgery.

Summary:. Reconstruction following total laryngopharyngectomy with total glossectomy (TLPTG) is challenging. To reconstruct this extended range of mucosal defect, it is necessary to overcome the remarkable discrepancy of apertures of oral and esophageal sides. We report a case of reconstruction surgery for total laryngopharyngectomy with total glossectomy with a funnel-shaped rectus abdominis musclocutaneous flap. The patient recovered without major complications and could keep a relatively good swallowing function. We believe this simple method should contribute to cases with complicated ablation.

For locally advanced laryngeal cancers, the standard treatment of choice is chemoradiotherapy if organ function needs to be conserved. Surgical treatment with larynx preservation is conducted only for limited cases. For locally advanced laryngeal cancers such as those with vocal cord fixation and/or cricoid cartilage destruction, there is no apparent standardized organ-preserving surgery keeping the essential laryngeal functions, viz. the airway, deglutition and articulation, uncompromized. Recently, our surgical team saw a patient with T4a advanced laryngeal cancer with vocal cord fixation who aspired to maintain his laryngeal function. Driven by his eagerness, we contrived novel techniques for laryngeal function preservation and performed a two-staged operation. In the first stage, extended vertical partial laryngectomy was conducted including resection of the affected thyroid, arytenoid, and cricoid cartilages, followed by local closure of the hypopharynx. Additionally, laryngeal suspension surgery and cricopharyngeal myotomy were performed in addition to suturing the epiglottis with the intact arytenoid cartilage to enhance swallowing function. In the second stage, airway reconstruction was performed using a local skin flap. As of 10 months after operation, there has been no tumor recurrence, and the reconstructed larynx has been working satisfactorily. In this report we describe an innovative operation that was especially contrived for laryngeal function preservation.

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

Free jejunal transfer is the main technique used for reconstructing a circumferential defect caused by total pharyngo-laryngo-cervical-esophagectomy in certain cancer cases. We report a rare case of severe late-onset dysphagia caused by autonomous spastic peristalsis, which led to complete obstruction of the free jejunal route. A 70-year-old man underwent treatment for hypopharyngeal cancer involving total pharyngolaryngectomy with free jejunal transfer. After uneventful peri- and postoperative recovery, he developed sudden-onset severe dysphagia 22 months later. Gastrografin fluoroscopy revealed abnormal peristalsis and contraction of the transferred jejunum, leading to complete obstruction. Nutritional treatment, application of depressants of peristalsis, and xylocaine injection into the outer space of the jejunal mucosa all failed to alleviate the dysphagia. Surgical treatment involving a longitudinal incision of the jejunal graft, and interposing a cutaneous flap, as a fixed wall, between the incised jejunal margins to prevent obstruction was performed. After further reconstructive surgery involving using a pectoralis major musculocutaneous flap and a split-thickness skin graft to close a refractory jejunum-skin fistula, the dysphagia was permanently alleviated. To our knowledge, this is the first report of severe dysphagia caused by peristalsis of a free jejunal graft.

喉頭温存・下咽頭喉頭部分切除術で，適切な再建術選択の指針は確立されていない。そこで2004年4月より当科で本術式を行った23例を対象として，切除範囲と再建法について検討を行った。一側の披裂喉頭蓋襞と梨状陥凹に留まる切除なら一期縫縮が可能であった。一側の梨状陥凹を越えて後壁や輪状後部に達する切除や，一側の披裂喉頭蓋襞を越えて披裂上半分を含む切除では空腸パッチ再建が必要であった。T3・T4進行癌でも，喉頭温存手術の可能な症例が認められた。一期縫縮例では平均2週間，再建症例では平均3週間で術後経口再開が可能であった。完全喉頭機能温存が約8割の症例で成され，疾患特異的生存率が約9割であった。

We report an extremely rare case of primary clear cell carcinoma (CCC), not otherwise specified (NOS) of the nasal cavity. An 80-year-old woman was referred to our hospital with left nasal obstruction caused by a nasal cavity tumor. The tumor was resected completely with lateral rhinotomy approach. Histopathological examination revealed CCC. CCC metastasis from renal cell carcinoma (RCC), which is at the top of differential diagnosis, was ruled out by the absence of renal tumor at computed tomography (CT). Also, immunohistochemical results of the specimen with vimentin negative and CK7 focally positive excluded the possibility of RCC metastasis. The patient is free from recurrence 1 year after the surgery, and there is no evidence of RCC. In this report histopathological characteristics, especially immunohistochemical properties of primary CCC, NOS of the nasal cavity are presented together with some clinical features of this rare tumor. Also, we refer to histopathogenesis of primary CCC of nasal cavity in relation to myoepithelial carcinoma. Histopathological discussion is further extended to include other CCC and CCC-resembling histologies to confirm the uniqueness of the present case.

【対象と方法】1993年～2005年に我々が行った喉頭部分切除術（PL）24例と下咽頭喉頭部分切除術（PPL）症例14例を同時期の超選択的動注化学放射線療法（iaCRT）症例17例と比較した。また1999年～2003年に放射線治療を行った下咽頭癌20例に対して喉頭温存手術が可能であるか検討した。【結果】喉頭癌でのKaplan-Meier法による疾患特異的5年生存率はPL症例が81.3%でiaCRT症例は87.5%（N.S.）であり，下咽頭癌での生存率はPPL症例が39.5%でiaCRT症例が55.6%（N.S.）であった。放射線治療を行った下咽頭癌に対して，喉頭温存手術は20例中12例で可能であると判断された。【結論】喉頭癌や下咽頭癌での喉頭温存手術の適応となる症例は放射線治療の良い適応でもある。