RESUMO
Head and neck squamous cell carcinoma (HNSCC) has a low five-year survival rate because of its high rate of recurrence and metastasis. After surgical resection or radiation, the main treatments for HNSCC, patients sometimes experience functional or aesthetic disorders. Therefore, there is a great demand for the development of non-surgical treatment strategies to improve clinical outcomes and patients' quality of life. One such non-surgical treatment is mild hyperthermia (mHT). Many studies have investigated combination treatments with mHT and immune checkpoint inhibitors in preclinical settings. However, there have been no detailed reports on the effects of mHT on immune checkpoint molecules. Here, we investigated the effects of mHT on the tumor microenvironment (TME), particularly on programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1), in SCCVII cells and a squamous cell carcinoma mouse model. First, we found that PD-L1 mRNA levels and surface PD-L1 expression significantly increased after mHT. Second, a single tumor model was used to determine the effect of HT on the TME. mHT enhanced the accumulation of CD4+ and CD8+ T cells, elevated PD-L1 expression in the TME, and decreased the PD-1 positive rate of CD4+ T cells. Finally, using a bilateral tumor model, we found that anti-PD-L1 monotherapy and combination therapy resulted in longer survival than the isotype control or mHT monotherapy. Moreover, the combination therapy resulted in a significantly higher survival rate than anti-PD-L1 monotherapy. In conclusion, our findings elucidate changes in PD-L1 expression in the TME and strengthen the rationale for mHT and PD-L1 blockade combination therapy.
Assuntos
Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Microambiente Tumoral , Animais , Microambiente Tumoral/efeitos dos fármacos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Camundongos , Linhagem Celular Tumoral , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Regulação para Cima/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Hipertermia Induzida/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Modelos Animais de DoençasRESUMO
This systematic review aims to determine whether the presence of human papillomavirus (HPV) influences the immunohistochemical expression of programmed cell death-1 ligand (PD-L1) in oropharyngeal squamous cell carcinoma (OPSCC). PD-L1 immunohistochemical expression varies in OPSCC, and the presence of HPV is a plausible explanation for this variability. Comprehending these findings is crucial, as high PD-L1 expression in the tumor microenvironment of OPSCC can help identify patient subgroups that could be suitable for immunotherapy. Therefore, a systematic review was conducted following PRISMA guidelines (CRD42023437800). An electronic literature search was performed without time or language restrictions. The search included PubMed/MEDLINE, Embase, Scopus, Web of Science, https://clinictrials.gov, and relevant journals. A meta-analysis was performed using RStudio. Fourteen studies involving 1,629 participants were included. The sample consisted predominantly of males (81.26%) with a mean age of 58.3 years. Concerning clinical and pathological characteristics, the most frequently described anatomical location was the tonsils (68.54%), and most participants were either current or former smokers (78%) and alcohol users (79%). Advanced TNM IV was the most common stage. Regarding histopathological characteristics, HPV 16 was the only type mentioned, and half of the cases were detected through immunohistochemistry. The SP142 clone (35.7%) and the pattern of membrane immunostaining in tumor cells (71%) were the most commonly employed methods. The most prevalent findings were positive expression of PD-L1 (64.28%) and negative HPV status (57.14%). The association between PD-L1 positivity and HPV positivity (78.57%) was confirmed by meta-analysis. The conclusion was that HPV-positive status has an impact on immunohistochemical expression of PD-L1 in OPSCC.
Assuntos
Antígeno B7-H1 , Carcinoma de Células Escamosas , Imuno-Histoquímica , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Antígeno B7-H1/análise , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Masculino , Feminino , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/patologia , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , PapillomaviridaeRESUMO
BACKGROUND: Locally advanced oral cavity squamous cell carcinoma (OCSCC) presents a significant clinical challenge despite being partially responsive to standard treatment modalities. This study investigates the prognostic implications of programmed death-ligand 1 (PD-L1) expression in these tumors, focusing on its association with treatment outcomes and the immune microenvironment. METHODS: We assessed tumor-infiltrating lymphocytes (TILs) in 132 patients with OCSCC to evaluate their impact on survival. Multiplex immunohistochemistry staining for CD3, CD68, CD11c, PD-L1, and P40 was used to explore correlations with clinical outcomes in patients with early-stage (n=22) and locally advanced (n=36) OCSCC. These initial findings were validated through differential gene expression analysis, gene set enrichment, and immune cell deconvolution in a The Cancer Genome Atlas cohort of 163 locally advanced OCSCC tumors. Additionally, single-cell RNA sequencing (scRNA-seq) on a smaller cohort (n=10) further characterized the PD-L1hi or PD-L1lo cancer cells in these tumors. RESULTS: Elevated PD-L1 expression was associated with poor outcomes in patients with locally advanced OCSCC undergoing standard adjuvant therapy, irrespective of "hot" or "cold" classification based on TILs assessment. PD-L1hi tumors exhibited an active immune response phenotype, enriched with M1 macrophages, CD8+ T cells and T regulatory cells in the tumor microenvironment. Notably, the negative impact of PD-L1 expression on outcomes was primarily attributed to its expression by cancer cells, rather than immune cells. Furthermore, scRNA-seq revealed that immune interactions were not essential for PD-L1 upregulation in cancer cells, instead, complex regulatory networks were involved. Additionally, PD-L1lo locally advanced tumors exhibited more complex pathway enrichment and diverse T-cell populations compared with those in the early-stage. CONCLUSION: Our findings underscore the prognostic significance of PD-L1 expression in locally advanced OCSCC, and unveil the complex interplay between PD-L1 expression, immune responses, and molecular pathways in the tumor microenvironment. This study provides insights that may inform future therapeutic strategies, including the possibility of tailored immunotherapeutic approaches for patients with PD-L1hi locally advanced OCSCC.
Assuntos
Antígeno B7-H1 , Linfócitos do Interstício Tumoral , Neoplasias Bucais , Microambiente Tumoral , Humanos , Antígeno B7-H1/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/imunologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , Masculino , Feminino , Pessoa de Meia-Idade , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Idoso , Prognóstico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Adulto , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/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/mortalidadeRESUMO
The morphology of the choriocarcinomatous variant of cervical squamous cell carcinoma (SCC) suggests an undifferentiated aggressive biological behaviour and a poor outcome, for which standard treatment has not been established. In addition, cases are rarely reported, with only five cases of patients with cervical carcinoma with choriocarcinoma reported previously in the literature. This current case report describes in detail a patient who was diagnosed with cervical SCC mixed with choriocarcinomatous differentiation. The case report includes details of the diagnosis, pathology, short tandem repeat genotyping, treatment and follow-up of this patient. As there is no standard treatment for this variant, the patient underwent surgery followed by radiotherapy. Unfortunately, 4 months after therapy discontinuation, radiological evaluation and laboratory tests documented a recurrence of the disease and the patient died. This report also systematically reviews the literature on cervical cancer associated with choriocarcinomatous differentiation and the five previous cases. It provides the most up-to-date summary of this disease, including its clinical manifestations, histopathology, diagnosis, treatment and prognosis.
Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico , Diferenciação Celular , Pessoa de Meia-Idade , Coriocarcinoma/patologia , Coriocarcinoma/diagnóstico , Coriocarcinoma/cirurgia , Evolução Fatal , AdultoRESUMO
Near-total to total lower lip defects present significant challenges for reconstructive surgeons, requiring restoration of oral competency, maximization of oral aperture, and cosmetic appearance. This report explores a novel reconstructive option addressing all three needs. Traditionally, local flap options restore cosmesis and oral competency by recruiting local tissue of similar thickness, pliability, and appearance, but often result in microstomia. Conversely, free flaps prevent microstomia but can lead to bulky and cosmetically unacceptable reconstructions. We present the first case of using a super-thin superficial circumflex iliac artery perforator (SCIP) free flap for near-total, full-thickness lower lip reconstruction. The patient was a 66-year-old female with recurrent squamous cell carcinoma of the lower lip, requiring wide local excision and resulting in an 80% full-thickness defect with unilateral oral commissure loss. An 8 cm × 5 cm × 5 mm SCIP flap was raised with a 4.5-cm pedicle length and anastomosed to the facial artery and vein. Clear fluids were commenced 7 days postoperatively, wounds healed 2 weeks postoperatively, and a normal diet was resumed at this time. The SCIP flap offers an excellent additional option for managing full-thickness near-total to total lower lip defects. Its thin, pliable nature and minimal donor site morbidity help restore oral competency, maximize oral aperture, and achieve a pleasing cosmetic result.
Assuntos
Carcinoma de Células Escamosas , Retalhos de Tecido Biológico , Artéria Ilíaca , Neoplasias Labiais , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Humanos , Feminino , Idoso , Neoplasias Labiais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Artéria Ilíaca/cirurgia , Artéria Ilíaca/transplante , Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/transplante , Carcinoma de Células Escamosas/cirurgia , Retalhos de Tecido Biológico/transplante , Retalhos de Tecido Biológico/irrigação sanguínea , Lábio/cirurgiaRESUMO
OBJECTIVE: This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis. METHODS: A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups' progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared. RESULTS: The surgical staging group started radiotherapy 10.2 days (range 9-12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively). CONCLUSION: Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs.
Assuntos
Excisão de Linfonodo , Linfonodos , Metástase Linfática , Pelve , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/mortalidade , Excisão de Linfonodo/métodos , Pessoa de Meia-Idade , Adulto , Seguimentos , Taxa de Sobrevida , Linfonodos/patologia , Linfonodos/cirurgia , Pelve/patologia , Pelve/cirurgia , Prognóstico , Idoso , Estudos Retrospectivos , Quimiorradioterapia/métodos , Estadiamento de Neoplasias , Aorta/patologia , Aorta/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundárioRESUMO
Background: Microangiogenesis and lymphangiogenesis are essential for tumor growth in the tumor microenvironment, contributing to tumor invasion and metastasis. Limited literature exists on these processes in esophageal squamous cell carcinoma (ESCC). Therefore, the purpose of this study is to explore the impacts of microangiogenesis and lymphangiogenesis on the occurrence, progression, and prognosis assessment of ESCC. Methods: Surgical specimens and paraffin-embedded human tissues were procured from ESCC patients, encompassing 100 ESCC tissues and 100 cancer-adjacent normal (CAN) tissues. CD34 and D2-40 were utilized as markers for microvessel endothelial cells and lymphatic vessel endothelial cells, respectively. Microvascular density (MVD) and lymphatic vessel density (LVD) were evaluated through immunohistochemical quantification. Results: We found that tumor tissues in ESCC patients had significantly higher MVD and LVD than cancer-adjacent normal (CAN) tissues. High MVD and LVD were associated with lymph node metastasis and advanced tumor clinical stages. Additionally, both high MVD and high LVD were strongly linked to poorer prognosis among cancer patients. Furthermore, a positive correlation was found between high MVD and high LVD (p < 0.05). The presence of these markers individually indicated a worse prognosis, with their combined assessment showcasing enhanced prognostic value. Conclusions: Overall, the increased MVD and LVD indicates higher invasion and metastasis of ESCC, closely correlating with unfavorablefor poor prognosis of ESCC patients.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Vasos Linfáticos , Densidade Microvascular , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/irrigação sanguínea , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Vasos Linfáticos/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/irrigação sanguínea , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/irrigação sanguínea , Metástase Linfática/patologia , Linfangiogênese/fisiologia , Idoso , Neovascularização Patológica/patologia , Microvasos/patologia , Antígenos CD34/metabolismo , Imuno-HistoquímicaRESUMO
Part II of the S3 guideline report deals with the surgical treatment of hypopharyngeal carcinoma, neck dissection for oropharyngeal and hypopharyngeal carcinomas and adjuvant therapy options. Primary surgical therapy ± adjuvant radio- or radiochemotherapy and primary radio- or radiochemotherapy are established as primary therapies for local-regional hypopharyngeal carcinomas. Direct randomized comparisons of both basic therapeutic procedures were never conducted. Available registry data show a worse prognosis of hypopharyngeal carcinoma compared to oropharyngeal carcinomas in all locoregional tumor stages, regardless of the treatment method. For T1N0-T2N0 squamous cell carcinoma of the hypopharynx, there are no relevant differences in overall survival and locoregional relapse rate between primary surgical and primary non-surgical treatment. Primary surgical therapy ± adjuvant radiotherapy or radiochemotherapy and primary radiotherapy or radiochemotherapy are established as primary therapies for advanced but locoregionally limited hypopharyngeal carcinomas. Neck dissection is an integral part of the primary surgical treatment of oropharyngeal and hypopharyngeal cancer. There are only a few randomized studies on non-surgical organ preservation for advanced hypopharyngeal cancer as an alternative to pharyngolaryngectomy, but these have led to the recommendation of alternative concepts in the new guideline. The indication and implementation of postoperative adjuvant radiotherapy and radiochemotherapy for hypopharyngeal carcinoma do not differ from those for HPV/p16-negative and -positive oropharyngeal carcinoma.
Assuntos
Neoplasias Hipofaríngeas , Esvaziamento Cervical , Estadiamento de Neoplasias , Neoplasias Orofaríngeas , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Hipofaríngeas/terapia , Humanos , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia , Radioterapia Adjuvante , Terapia Combinada , Quimiorradioterapia Adjuvante , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Taxa de Sobrevida , PrognósticoRESUMO
OBJECTIVE: This study aimed to develop a prognostic cell death index (CDI) based on the expression of genes related with various types of programmed cell death (PCD), and to assess its clinical relevance in lung squamous cell carcinoma (LUSC). METHODS: PCD-related genes were gathered and analyzed in silico using the transcriptomic data from the LUSC cohorts of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Differentially expressed PCD genes were analyzed, and a prognostic model was subsequently constructed. CDI scores were calculated for each patient, and their correlations with clinical features, survival outcomes, tumor mutation burden, gene clusters, and tumor microenvironment were investigated. Unsupervised consensus clustering was performed based on CDI model genes. Furthermore, the correlation of CDI for sensitivity of targeted drugs, chemotherapy efficacy, and immunotherapy responses was assessed. RESULTS: Based on 351 differentially expressed PCD genes in LUSC, a CDI signature comprising FGA, GAB2, JUN, and CDKN2A was identified. High CDI scores were significantly associated with poor survival outcomes (p < 0.05). Unsupervised clustering revealed three distinct patient subsets with varying survival rates. CDKN2A exhibited significantly different mutation patterns between patients with high and low CDI scores (p < 0.01). High CDI scores were also linked to increased immune cell infiltration of specific subsets and altered expression of immune-related genes. Patients with high-CDI showed reduced sensitivity to several chemotherapeutic drugs and a higher Tumor Immune Dysfunction and Exclusion (TIDE) score, indicating potential resistance to immunotherapy. CONCLUSION: The CDI signature based on PCD genes offers valuable prognostic insights into LUSC, reflecting molecular heterogeneity, immune microenvironment associations, and potential therapeutic challenges. The CDI holds potential clinical utility in predicting treatment responses and guiding the selection of appropriate therapies for patients with LUSC. Future studies are warranted to further validate the prognostic value of CDI in combination with clinical factors and to explore its application across diverse patient cohorts.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Masculino , Feminino , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Idoso , Apoptose/genética , TranscriptomaRESUMO
OBJECTIVES: This study aimed to analyse the value of pre-operative 18F-fluorodeoxyglucose positron emission tomography (PET)-computed tomography that can predict tumour pathological complete response, tumour histology grade, overall survival, and recurrence-free survival in patients with locally advanced oesophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy (NCRT) followed by surgery. METHODS: We retrospectively reviewed the cases of patients with locally advanced oesophageal squamous cell carcinoma undergoing NCRT followed by surgery. Patients who did not undergo PET within 3 months of surgery were excluded. We set a pre-operative PET maximum standardised uptake value (SUVmax) of > 5 as the threshold and classified the patients into two groups. We analysed the tumour response and histology grade, and compared the overall survival and recurrence-free survival between the two groups. RESULTS: This cohort included 92 patients with oesophageal squamous cell carcinoma who underwent NCRT followed by surgery; 49 patients had a pre-operative PET SUVmax < 5, and 43 patients had a pre-operative PET SUVmax > 5. The patients' pre-operative PET SUVmax correlated with tumour histology, ypT stage, and tumour response. Patients with a pre-operative SUVmax < 5 had better 2-year-overall survival (78% vs. 62%, P < 0.05) and 2-year recurrence-free survival (62% vs. 34%, P < 0.05) than those with a pre-operative SUV > 5. CONCLUSIONS: Pre-operative SUVmax may be useful to predict tumour response, survival, and recurrence in patients with locally advanced oesophageal squamous cell carcinoma who undergo NCRT followed by surgery.
Assuntos
Neoplasias Esofágicas , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Compostos Radiofarmacêuticos , Terapia Neoadjuvante , Esofagectomia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgiaRESUMO
PURPOSE: Our objective was to investigate the association between programmed death-ligand (PD-L1) immunoexpression measured as a combined positive score and clinical outcomes in penile SqCC. MATERIALS AND METHODS: We retrospectively reviewed all penile SqCC cases diagnosed in our institution between 2018 and 2023. PD-L1 immunohistochemistry was performed as a qualitative assay. Immunoexpression in both tumor and immune cells equal or superior to 1 was considered positive. RESULTS: A total of 34 patients with conventional penile SqCC were included. Eleven cases were HPV-associated (32.4%). Twelve cases were PD-L1 CPS < 1 and twenty-two were PD-L1 CPS ≥ 1. Nine cases (32.4%) were PD-L1 CPS ≥ 1 and p16 positive, but this did not translate in worse clinicopathological features. Larger tumors (3.0 cm in PD-L1 CPS ≥ 1 vs 2.5 cm in PD-L1 CPS < 1; p = 0.662), vascular invasion (36.4% in PD-L1 CPS ≥ 1 vs. 25.0% in PD-L1 CPS < 1; p = 0.705) and perineural invasion (40.9% in PD-L1 CPS≥1 vs. 16.7% in PD-L1 CPS < 1; p = 0.252) were associated with PD-L1 expression. Among the high-risk features, only lymph node involvement had statistical significance, with 14 out of 22 PD-L1 CPS ≥ 1 patients (63.6%) having lymph node metastases when lymphadenectomy was performed (p = 0.031). With a median follow-up of 16 months (IQR 27.5), PD-L1 CPS ≥ 1 patients had worse overall survival (53.4 months vs 75.9 months), but no statistical significance could be inferred (p = 0.188). CONCLUSIONS: It is noteworthy the clinical significance of lymph node involvement in PD-L1 CPS ≥ 1 cases and a trend towards worse overall survival in this group of patients.
Assuntos
Antígeno B7-H1 , Carcinoma de Células Escamosas , Metástase Linfática , Neoplasias Penianas , Humanos , Masculino , Neoplasias Penianas/patologia , Neoplasias Penianas/metabolismo , Antígeno B7-H1/metabolismo , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Idoso de 80 Anos ou mais , Adulto , Imuno-HistoquímicaRESUMO
PURPOSE: This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma. METHODS AND MATERIALS: Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m2, once weekly for 5 weeks), radiotherapy (45-50.4 Gy/25-28 Fx, 5 fractions weekly), followed by brachytherapy (24-30 Gy/3-5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS). RESULTS: All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient experienced grade V AEs. The objective response rate (ORR) was 100%. At the data cutoff (June 30, 2023), the median follow-up was 31.8 months (9.5 to 37.8 months). The 2-year PFS rate was 81.8%. The 2-year LC and local regional control rates were both 95.5%, and the 2-year OS rate was 90.9%. CONCLUSIONS: Toripalimab combined with CCRT achieved good tolerance and showed promising anti-tumor effects in patients with locally advanced cervical cancer.
Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células Escamosas , Quimiorradioterapia , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Idoso , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Histopathologically, oral squamous cell carcinoma (OSCC) consists of well-defined interfaces with adjacent non-cancerous epithelium. Previously, we found that SCC tissues expressed higher levels of specific proteins at this interface. Ladinin-1 (LAD1) is one of the specific molecules that has increased expressions in cancer fronts; however, its function in OSCC is unknown. Therefore, this study aimed to elucidate the function of LAD1 in human OSCC cells. LAD1 was localized on the actin arc at the distal periphery of cell clusters in the OSCC cell lines HSC-2, HSC-3, and HSC-4. When LAD1 was knocked down, cellular migration was repressed in wound scratch assays but was reversed in three-dimensional collagen gel invasion assays. Characteristic LAD1 localization along actin arcs forming the leading edge of migrating cells was diminished with loss of filopodia formation and ruffling in knockdown cells, in which the expression levels of cell motility-related genes-p21-activated kinase 1 (PAK1) and caveolin-1 (CAV1)-were upregulated and downregulated, respectively. LAD1 expression was also associated with the downregulation of vimentin and increased histological differentiation of OSCC. These results suggest that LAD1 is involved in actin dynamics during filopodia and lamellipodia formation, and in maintaining the epithelial phenotype of OSCC cells.
Assuntos
Actinas , Carcinoma de Células Escamosas , Movimento Celular , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Actinas/metabolismo , Quinases Ativadas por p21/metabolismo , Quinases Ativadas por p21/genética , Vimentina/metabolismo , Vimentina/genética , Caveolina 1/metabolismo , Caveolina 1/genética , Regulação Neoplásica da Expressão Gênica , Fenótipo , Células Epiteliais/metabolismo , Células Epiteliais/patologiaRESUMO
BACKGROUND: A variety of solid tumours, including oral squamous cell carcinoma (OSCC), can cause coagulation abnormalities, and this phenomenon is known as tumour-associated hypercoagulation. We aimed to explore the preoperative thromboelastography (TEG) parameter profiles of OSCC patients, and to investigate their trends in relation to tumour stage progression, and to evaluate their value for predicting cervical lymph node metastasis. METHODS: Data on thromboelastographic parameters and conventional coagulation indices were retrospectively collected, and comparisons were performed among preoperative primary OSCC patients (n = 311), recurrent/metastatic OSCC patients (n = 44) and a control group (n = 71). Among primary OSCC patients, the correlation with tumour stage and the predictive role of cervical lymph node metastasis were analyzed. RESULTS: Hypercoagulability occurred in OSCC patients and tended to become more pronounced as the tumour progressed. The whole-time phase of coagulation increased with increasing T stage, while the early phase of coagulation increased with increasing N stage. CONCLUSIONS: Preoperative TEG parameters are closely related to tumour stage and progression, suggesting that TEG can be used as an important indicator for predicting tumour stage and as a potential biomarker.
Assuntos
Carcinoma de Células Escamosas , Metástase Linfática , Neoplasias Bucais , Estadiamento de Neoplasias , Tromboelastografia , Humanos , Tromboelastografia/métodos , Masculino , Feminino , Neoplasias Bucais/patologia , Neoplasias Bucais/sangue , Neoplasias Bucais/cirurgia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Prognóstico , Período Pré-OperatórioRESUMO
BACKGROUND: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.
Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Queratina-19 , Leucoplasia Oral , Neoplasias Bucais , Fibrose Oral Submucosa , RNA Mensageiro , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Neoplasias Bucais/sangue , Neoplasias Bucais/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/diagnóstico , Masculino , RNA Mensageiro/sangue , Fibrose Oral Submucosa/sangue , Fibrose Oral Submucosa/genética , Feminino , Leucoplasia Oral/sangue , Leucoplasia Oral/genética , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Queratina-19/sangue , Adulto , Líquen Plano Bucal/sangue , Líquen Plano Bucal/genética , Estudos de Casos e Controles , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Detecção Precoce de Câncer/métodos , Idoso , Reação em Cadeia da Polimerase em Tempo Real , Curva ROCRESUMO
BACKGROUND: The Surgical Tool for Auditing Records scoring system [STAR] focuses on surgical record auditing with promising outcomes. It offers a structured approach to evaluating the quality of surgical notes. AIMS AND OBJECTIVES: This study aimed to assess the effectiveness of the STAR in evaluating oral surgical records and identifying areas for improvement in documentation practices. MATERIALS AND METHODS: The data was obtained from the Dental Information Archival Software (DIAS) of our institution. The sample size was determined using G*Power 3.1.9.4 software. Fifty consecutive oral surgery clinical records of oral squamous cell carcinoma patients were evaluated using STAR. Each record was reviewed for adherence to documentation standards including Initial Assessment (10 points), Follow-up Entries (8 points), Consent Documentation (7 points), Anesthesia Report (7 points), Surgical Log (9 points), and Discharge Synopsis (9 points). compiling a total STAR score (50 points). The data was tabulated in Google Sheets. The descriptive statistics with inter-observer agreement and the mean score were recorded. RESULTS: We observed that each of the 50 records received a score of 49/50 points on the STAR. Deductions were necessary in the Operative record section due to the lack of information regarding the sutures used. CONCLUSION: To summarize, this study emphasizes the effectiveness of the STAR scoring system in evaluating the quality of oral surgical records. Identifying deficiencies, particularly in documenting operative details, can improve the completeness and accuracy of patient records. It can ultimately enhance patient care and facilitate better communication among healthcare professionals.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Documentação/normas , Procedimentos Cirúrgicos Bucais/normas , Registros Odontológicos/normasRESUMO
Solid organ transplant recipients (SOTRs) are at high risk of cutaneous squamous cell carcinoma (cSCC) metastasis. Despite prior studies identifying risk factors, mortality remains high. Understanding additional risk factors may aid in reducing mortality in this population. This study aimed to investigate risk factors and predictive variables for metastatic cSCC in SOTRs. The primary goal was to accurately identify transplant patients at increased risk of metastatic cSCC. A retrospective case-control study in a single institution of 3576 cases of organ transplants were identified from January 1991 to July 2022. A cohort of metastatic cancer patients and two randomly generated age and organ matched control cohorts were identified. 16 SOTR patients developed metastatic cSCC. The majority were male, with high-risk tumor sites. Tumor depth varied and half exhibited perineural invasion. Cylex® (p = 0.05) and white blood cell counts (p = 0.04) were significantly lower in these patients compared to control. Lung transplants were at highest risk relative to other solid organ transplants. Voriconazole exposure was also associated with increased metastatic risk (p = 0.04). Small sample size at a single institution. Close monitoring of SOTR, especially those with lung transplants given their increased risk, reducing immunosuppression, and limiting exposure to voriconazole can improve outcomes in SOTRs with metastatic cSCC.
Assuntos
Centros Médicos Acadêmicos , Carcinoma de Células Escamosas , Transplante de Órgãos , Neoplasias Cutâneas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/secundário , Fatores de Risco , Estudos Retrospectivos , Transplante de Órgãos/efeitos adversos , Estudos de Casos e Controles , Idoso , Centros Médicos Acadêmicos/estatística & dados numéricos , Transplantados/estatística & dados numéricos , AdultoRESUMO
BACKGROUND: Radiotherapy (RT) is used in head and neck squamous cell carcinoma (HNSCC) with excellent effectiveness, but it is burdened by important side effects, which may negatively impact patients' quality of life (QoL). In particular when associated with chemotherapy (CT), that has a radiosensitising effect (and its own toxicities), it is responsible for several adverse events, causing social discomfort and lower QoL, in patients who are already experiencing several tumor-related discomforts. Prehabilitation is a healthcare intervention consisting of several specialist visits prior to the start of treatment, with the aim of improving the patient's health status, resolving symptoms that interfere with treatment and impact QoL, and finally to better avoid or overcome complications. Of all cancer patients, HNSCC patients are among those who could benefit most from prehabilitation, both because of the high number of symptoms and toxicities and their difficult management. Despite this and the emerging data, prehabilitation is not often considered for the majority of patients undergoing (C)RT. In this review, we tried to understand what are the main areas in which interventions can be made prior to the (C)RT start, the possible side effects of the treatment, the effectiveness in their prevention and management, and the impact that prehabilitation may have in adherence to therapy and on the principal survival outcomes, providing important guidance for the planning of future studies. EVIDENCES AND CONCLUSIONS: Although there is no strong data evaluating multidisciplinary prehabilitation strategies, evidence shows that optimizing the patient's health status and preventing possible complications improve the QoL, reduce the incidence and severity of adverse events, and improve treatment adherence. While cardiology prehabilitation is of paramount importance for all patients undergoing concomitant CRT in the prevention of possible side effects, the remaining interventions are useful independently of the type of treatment proposed. Geriatricians have a key role in both elderly patients and younger patients characterized by many comorbidities to comprehensively assess health status and indicate which treatment may be the best in terms of risk/benefit ratio. Collaboration between nutritionists and phoniatrics, on the other hand, ensures adequate nutritional intake for the patient, where possible orally. This is because optimizing both body weight and muscle mass and qualities has been shown to impact key survival outcomes. Finally, HNSCC patients have the second highest suicide rate, and the disease has side effects such as pain, dysfiguration, and sialorrhea that can reduce the patient's social life and create shame and embarrassment: A psychological intake, in addition to the usefulness to the patient, can also provide current support to caregivers and family members. Therefore clinicians must define a personalized pathway for patients, considering the characteristics of the disease and the type of treatment proposed, to optimize health status and prevent possible side effects while also improving QoL and treatment adherence.
Assuntos
Quimiorradioterapia , Neoplasias de Cabeça e Pescoço , Qualidade de Vida , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Quimiorradioterapia/métodos , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Exercício Pré-Operatório , Carcinoma de Células Escamosas/terapiaRESUMO
BACKGROUND: SEPT9 is a pivotal cytoskeletal GTPase that regulates diverse biological processes encompassing mitosis and cytokinesis. While previous studies have implicated SEPT9 in tumorigenesis and development; comprehensive pan-cancer analyses have not been performed. This study aims to systematically explore its role in cancer screening, prognosis, and treatment, addressing this critical gap. METHODS: Gene and protein expression data containing clinical information were obtained from public databases for pan-cancer analyses. Additionally, clinical samples from 90 patients with lung squamous cell carcinoma (LUSC) were used to further experimentally validate the clinical significance of SEPT9. In addition, the molecular docking tool was used to analyze the affinities between SEPT9 protein and drugs. RESULTS: SEPT9 is highly expressed in various cancers, and its aberrant expression correlates with genetic alternations and epigenetic modifications, leading to adverse clinical outcomes. Take LUSC as an example, additional dataset analyses and immunohistochemical experiments further confirm the diagnostic and prognostic values as well as the clinical relevance of the SEPT9 gene and protein. Functional enrichment, single-cell expression, and immune infiltration analyses revealed that SEPT9 promotes malignant tumor progression and modulates the immune microenvironments, enabling patients to benefit from immunotherapy. Moreover, drug sensitivity and molecular docking analyses showed that SEPT9 is associated with the sensitivity and resistance of multiple drugs and has stable binding activity with them, including Vorinostat and OTS-964. To harness its prognostic and therapeutic potential in LUSC, a mitotic spindle-associated prognostic model including SEPT9, HSF1, ARAP3, KIF20B, FAM83D, TUBB8, and several clinical characteristics, was developed. This model not only improves clinical outcome predictions but also reshapes the immune microenvironment, making immunotherapy more effective for LUSC patients. CONCLUSION: This is the first study to systematically analyze the role of SEPT9 in cancers and innovatively apply the mitotic spindle-associated model to LUSC, fully demonstrating its potential as a valuable biomarker for cancer screening and prognosis, and highlighting its application value in promoting immunotherapy and chemotherapy, particularly for LUSC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Simulação de Acoplamento Molecular , Septinas , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Septinas/genética , Septinas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Prognóstico , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/imunologia , Masculino , FemininoRESUMO
Line-field confocal optical coherence tomography (LC-OCT) is a new technology for skin cancer diagnostics. However, the interobserver agreement (IOA) of known image markers of keratinocyte carcinomas (KC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as precursors, SCC in situ (CIS) and actinic keratosis (AK), remains unexplored. This study determined IOA on the presence or absence of 10 key LC-OCT image markers of KC and precursors, among evaluators new to LC-OCT with different levels of dermatologic imaging experience. Secondly, the frequency and association between reported image markers and lesion types, was determined. Six evaluators blinded to histopathologic diagnoses, assessed 75 LC-OCT images of KC (21 SCC; 21 BCC), CIS (12), and AK (21). For each image, evaluators independently reported the presence or absence of 10 predefined key image markers of KCs and precursors described in an LC-OCT literature review. Evaluators were stratified by experience-level as experienced (3) or novices (3) based on previous OCT and reflectance confocal microscopy usage. IOA was tested for all groups, using Conger's kappa coefficient (κ). The frequency of reported image marker and their association with lesion-types, were calculated as proportions and odds ratios (OR), respectively. Overall IOA was highest for the image markers lobules (κ = 0.68, 95% confidence interval (CI) 0.57;0.78) and clefting (κ = 0.63, CI 0.52;0.74), typically seen in BCC (94%;OR 143.2 and 158.7, respectively, p < 0.001), followed by severe dysplasia (κ = 0.42, CI 0.31;0.53), observed primarily in CIS (79%;OR 7.1, p < 0.001). The remaining seven image-markers had lower IOA (κ = 0.06-0.32) and were more evenly observed across lesion types. The lowest IOA was noted for a well-defined (κ = 0.07, CI 0;0.15) and interrupted dermal-epidermal junction (DEJ) (κ = 0.06, CI -0.002;0.13). IOA was higher for all image markers among experienced evaluators versus novices. This study shows varying IOA for 10 key image markers of KC and precursors in LC-OCT images among evaluators new to the technology. IOA was highest for the assessments of lobules, clefting, and severe dysplasia while lowest for the assessment of the DEJ integrity.