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Background: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. Methods: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. Conclusion: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.
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Neoplasias de Cabeça e Pescoço , Nivolumabe , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Masculino , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Feminino , Idoso , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/genética , Estudos Retrospectivos , Biomarcadores Tumorais/genética , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Resultado do Tratamento , Adulto , Antígeno B7-H1/genética , Idoso de 80 Anos ou mais , Mutação , Genômica/métodosRESUMO
BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.
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Cholangiocarcinoma is a fatal disease with limited therapeutic options. We screened genes required for cholangiocarcinoma tumorigenicity and identified FADS2, a delta-6 desaturase. FADS2 depletion reduced in vivo tumorigenicity and cell proliferation. In clinical samples, FADS2 was expressed in cancer cells but not in stromal cells. FADS2 inhibition also reduced the migration and sphere-forming ability of cells and increased apoptotic cell death and ferroptosis markers. Lipidome assay revealed that triglyceride and cholesterol ester levels were decreased in FADS2-knockdown cells. The oxygen consumption ratio was also decreased in FADS2-depleted cells. These data indicate that FADS2 depletion causes a reduction in lipid levels, resulting in decrease of energy production and attenuation of cancer cell malignancy.
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OBJECTIVES: Acute kidney injury (AKI) represents a major toxicity associated with cisplatin. We developed a risk prediction model for cisplatin-induced AKI in patients with postoperative high-risk head and neck cancer who received chemoradiotherapy during a randomized phase II/III trial, JCOG1008. MATERIALS AND METHODS: Two hundred and fifty-one patients received radiotherapy with weekly cisplatin at 40 mg/m2 (weekly arm) or 3-weekly cisplatin at 100 mg/m2 (3-weekly arm). AKI was defined using the AKI Network classification/staging system as increased serum creatinine of ≥0.3 mg/dL or a ≥1.5-fold increase from baseline 30 days after completing chemoradiotherapy. The Akaike information criterion was used to explore the optimal model by combining explanatory variables at registration. RESULTS: Among the 251 patients (210 men and 41 women (median age; 62 years)), 94 (37.5 %) developed cisplatin-induced AKI. The optimal cisplatin-induced AKI risk prediction model comprised four factors, including a primary site of hypopharynx/larynx (vs. oral cavity/oropharynx), 3-weekly arm (vs. weekly arm), serum albumin of ≤3.5 g/dL (vs. >3.5 g/dL) and creatinine clearance (CCr) of <90 mL/min (vs. ≥90 mL/min). The incidence of cisplatin-induced AKI rose with cumulative count of the four factors. When the cumulative count was ≥2, the positive predictive value for cisplatin-induced AKI was 50.3 %. CONCLUSIONS: We developed a risk prediction model for cisplatin-induced AKI in patients with head and neck cancer who received postoperative chemoradiotherapy using primary site, cisplatin administration method, serum albumin, and CCr. Patients with risk factors unrelated to the cisplatin administration method should adopt a weekly cisplatin regimen.
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Injúria Renal Aguda , Quimiorradioterapia , Cisplatino , Neoplasias de Cabeça e Pescoço , Humanos , Cisplatino/efeitos adversos , Cisplatino/administração & dosagem , Masculino , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia , Feminino , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/terapia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Idoso , Adulto , Antineoplásicos/efeitos adversos , Medição de Risco , Fatores de RiscoRESUMO
RNAs, such as noncoding RNA, microRNA, and recently mRNA, have been recognized as signal transduction molecules. CD271, also known as nerve growth factor receptor, has a critical role in cancer, although the precise mechanism is still unclear. Here, we show that CD271 mRNA, but not CD271 protein, facilitates spheroid cell proliferation. We established CD271-/- cells lacking both mRNA and protein of CD271, as well as CD271 protein knockout cells lacking only CD271 protein, from hypopharyngeal and oral squamous cell carcinoma lines. Sphere formation was reduced in CD271-/- cells but not in CD271 protein knockout cells. Mutated CD271 mRNA, which is not translated to a protein, promoted sphere formation. CD271 mRNA bound to hnRNPA2B1 protein at the 3'-UTR region, and the inhibition of this interaction reduced sphere formation. In surgical specimens, the CD271 mRNA/protein expression ratio was higher in the cancerous area than in the noncancerous area. These data suggest CD271 mRNA has dual functions, encompassing protein-coding and noncoding roles, with its noncoding RNA function being predominant in oral and head and neck squamous cell carcinoma.
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Neoplasias de Cabeça e Pescoço , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B , Neoplasias Bucais , Proteínas do Tecido Nervoso , RNA Mensageiro , Receptores de Fator de Crescimento Neural , Carcinoma de Células Escamosas de Cabeça e Pescoço , Feminino , Humanos , Masculino , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismoRESUMO
BACKGROUND: Total pharyngolaryngectomy (TPL) is standard treatment for hypopharyngeal cancer. However, extensive thyroidectomy and paratracheal nodal dissection (PTND) can cause hypoparathyroidism. We sought to determine the optimum extent of resection. METHODS: We analyzed the clinicopathological information of 161 pyriform sinus cancer patients undergoing TPL from 25 Japanese institutions. Rates of recurrence and risk factors for hypoparathyroidism, as well as incidence of pathological contralateral level VI nodal metastasis and stomal recurrence, were investigated. RESULTS: The extent of thyroidectomy and nodal dissection were not independent risk factors for recurrence. Incidences of contralateral level VI nodal involvement and stomal recurrence were 1.8% and 1.2%, respectively. Patients undergoing hemithyroidectomy/ipsilateral PTND did not develop stomal recurrence and had the lowest incidence of hypoparathyroidism. Prognosis in patients without tracheostomy prior to hemithyroidectomy/ipsilateral PTND was comparable to that with more extensive resections. CONCLUSIONS: Hemithyroidectomy/ipsilateral PTND may be sufficient for pyriform sinus cancer cases without tracheostomy.
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Hipoparatireoidismo , Neoplasias Hipofaríngeas , Seio Piriforme , Neoplasias da Glândula Tireoide , Humanos , Tireoidectomia/efeitos adversos , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Hipofaríngeas/patologia , Esvaziamento Cervical , Estudos Retrospectivos , Seio Piriforme/cirurgia , Seio Piriforme/patologia , Excisão de Linfonodo/efeitos adversos , Hipoparatireoidismo/etiologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologiaRESUMO
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.
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Assistência ao Convalescente , Recuperação Pós-Cirúrgica Melhorada , Humanos , Alta do Paciente , Manejo da Dor , Tempo de Internação , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND: Pain and post-operative nausea and vomiting are the main factors that impair the quality of recovery after surgery. Very few reports have analyzed patient-reported outcomes to investigate the efficacy of an enhanced recovery after surgery protocol to alleviate these symptoms after head and neck surgeries with free tissue transfer reconstruction. METHODS: We investigated post-operative pain and post-operative nausea and vomiting in 47 patients who underwent head and neck surgeries with free tissue transfer reconstruction with enhanced recovery after surgery support between February 2021 and August 2022. Patient-reported outcomes were assessed using the visual analog scale and Japanese version of the Quality of Recovery-40. RESULTS: Significant increases in the mean visual analog scale scores for pain and post-operative nausea and vomiting were observed only on post-operative Day 1 compared with preoperative values (pain: 3.19 ± 2.78 vs. 1.96 ± 2.42, P = 0.0408; post-operative nausea and vomiting: 1.52 ± 2.09 vs. 0.54 ± 1.37, P = 0.0194). From post-operative Day 2, there were no significant differences between the pre- and post-operative visual analog scale scores, and no significant increases in the incidences of moderate or severe pain and post-operative nausea and vomiting compared with preoperatively. The Japanese version of the Quality of Recovery-40 score for post-operative pain showed no significant deterioration compared with preoperatively, while the Japanese version of the Quality of Recovery-40 score for post-operative nausea and vomiting showed significant deterioration compared with the preoperative value on post-operative Days 2, 4 and 7. CONCLUSIONS: The visual analog scale and Japanese version of the Quality of Recovery-40 scores for post-operative pain and visual analog scale score for post-operative nausea and vomiting suggested that the enhanced recovery after surgery strategy favorably controlled pain and post-operative nausea and vomiting after head and neck surgeries with free tissue transfer reconstruction. However, as the post-operative Japanese version of the Quality of Recovery-40 score for post-operative nausea and vomiting was lower than the preoperative value, there is still a need for further improvement of the enhanced recovery after surgery pathway.
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Recuperação Pós-Cirúrgica Melhorada , Humanos , Náusea e Vômito Pós-Operatórios/etiologia , Manejo da Dor , Dor Pós-Operatória/etiologiaRESUMO
OBJECTIVE: Occurrence of hyperactive postoperative delirium (POD) with agitation after head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) is associated with the risk of life-threatening complications. The relationships between occurrence of hyperactive POD after HNS-FTTR and inflammatory markers reflecting the surgical stress response, represented by postoperative interleukin-6 levels, are not fully understood. METHODS: A retrospective study was conducted on 221 consecutive patients who underwent HNS-FTTR at our department between September 2016 and December 2021. Potential risk factors for POD were examined, including age, operation time, intraoperative blood loss, and postoperative serum levels of blood parameters such as interleukin-6, C-reactive protein, and neutrophil-to-lymphocyte ratio. RESULTS: Hyperactive POD with agitation was observed in 54 subjects (24.4%). The postoperative hospital stay in the POD group was significantly longer than that in the non-POD group (median: 32.5 days vs. 28 days; p=0.0129). Multivariate logistic regression analysis identified age (in years) (odds ratio: 1.102; p<0.0001), operation time (min) (odds ratio: 1.004; p=0.0359), and postoperative serum interleukin-6 level (pg/mL) (odds ratio: 1.005; p=0.0384) as significant risk factors for development of POD. In a receiver operating characteristic curve and area under the curve analysis, the cut-off value for postoperative serum interleukin-6 level to predict POD development was 82.5 pg/mL. The postoperative serum interleukin-6 ≥82.5 pg/mL group developed hyperactive POD with agitation significantly more often than the postoperative serum IL-6 <82.5 pg/mL group (odds ratio: 4.400; p<0.0001). The postoperative serum IL-6 ≥82.5 pg/mL group also had significantly longer postoperative hospital stay (41.58 ± 33.42 days vs. 31.73 ± 22.89 days; p=0.0151), older age (68.60 ± 9.99 years vs. 64.30 ± 12.58 years; p=0.0054), and longer operation time (625.4 ± 114.05 min vs. 575.5 ± 98.73 min; p=0.0009) than the postoperative serum IL-6 <82.5 pg/mL group. CONCLUSION: Postoperative serum interleukin-6 level, as well as age and operation time, were identified as significant independent risk factors for development of hyperactive POD with agitation after HNS-FTTR. Inflammation is a potential target for the prevention and treatment of POD after HNS-FTTR.
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Delírio , Interleucina-6 , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Delírio/etiologia , Delírio/complicaçõesRESUMO
BACKGROUND: The 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. METHODS: We 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. RESULTS: The preoperative IL-6 ≥ 8 pg/mL group had a significantly worse prognosis than the preoperative IL-6 < 8 pg/mL group (overall survival [OS]: hazard ratio [HR] 3.098, P = 0.0006; disease-specific survival [DSS]: HR 3.335, P = 0.0008). In multivariate analysis, IL-6 ≥ 8 pg/mL and age ≥ 70 years were independent poor prognostic factors for OS (HR 1.860, P = 0.0435 and HR 1.883, P = 0.0233, respectively). The only independent poor prognostic factor for DSS was IL-6 ≥ 8 pg/mL (HR 2.052, P = 0.0329). Serum albumin was significantly lower and serum C-reactive protein and neutrophil-to-lymphocyte ratio were significantly higher in the IL-6 ≥ 8 pg/mL group than in the IL-6 < 8 pg/mL group (all P < 0.0001). CONCLUSIONS: Preoperative 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.
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Neoplasias de Cabeça e Pescoço , Interleucina-6 , Idoso , Humanos , Neoplasias de Cabeça e Pescoço/cirurgia , Prognóstico , Estudos Retrospectivos , Síndrome de Resposta Inflamatória SistêmicaRESUMO
CD271 (also referred to as nerve growth factor receptor or p75NTR) is expressed on cancer stem cells in hypopharyngeal cancer (HPC) and regulates cell proliferation. Because elevated expression of CD271 increases cancer malignancy and correlates with poor prognosis, CD271 could be a promising therapeutic target; however, little is known about the induction of CD271 expression and especially its promoter activity. In this study, we screened transcription factors and found that RELA (p65), a subunit of nuclear factor kappaB (NF-κB), is critical for CD271 transcription in cancer cells. Specifically, we found that RELA promoted CD271 transcription in squamous cell carcinoma cell lines but not in normal epithelium and neuroblastoma cell lines. Within the CD271 promoter sequence, region + 957 to + 1138 was important for RELA binding, and cells harboring deletions in proximity to the + 1045 region decreased CD271 expression and sphere-formation activity. Additionally, we found that clinical tissue samples showing elevated CD271 expression were enriched in RELA-binding sites and that HPC tissues showed elevated levels of both CD271 and phosphorylated RELA. These data suggested that RELA increases CD271 expression and that inhibition of RELA binding to the CD271 promoter could be an effective therapeutic target.
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Neoplasias Hipofaríngeas , Humanos , Adapaleno , Proliferação de Células/genética , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismoRESUMO
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.
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Neoplasias Nasofaríngeas , Espondilite , Infecções Estreptocócicas , Humanos , Carcinoma Nasofaríngeo/complicações , Neoplasias Nasofaríngeas/complicações , Espondilite/diagnóstico por imagem , Infecções Estreptocócicas/microbiologia , StreptococcusRESUMO
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.
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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.
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Esôfago de Barrett , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Adapaleno , Animais , Anticorpos Monoclonais/metabolismo , Esôfago de Barrett/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Glicosilação , Imuno-Histoquímica , Camundongos , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/metabolismoRESUMO
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.
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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.
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Nutrição Enteral , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica , Idoso , Feminino , Cabeça/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/cirurgia , Estudos Retrospectivos , Fatores de TempoRESUMO
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.
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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.
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Neoplasias de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Incidência , Japão , Laringe , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural , Segunda Neoplasia Primária/epidemiologia , Duração da Cirurgia , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida , Carga TumoralRESUMO
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.
Assuntos
Antineoplásicos/análise , Antineoplásicos/farmacologia , Descoberta de Drogas , Células-Tronco Neoplásicas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Antineoplásicos/química , Linhagem Celular Tumoral , Ensaios de Triagem em Larga Escala , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.