Stage Squamous Cell Carcinoma Research Articles

Imaging for the Initial Staging and Post-Treatment Surveillance of Penile Squamous Cell Carcinoma.

Although relatively rare in the United States, penile squamous cell carcinoma is encountered worldwide at a higher rate. Initial diagnosis is often made on clinical exam, as almost all of these lesions are externally visible and amenable to biopsy. In distinction to other types of malignancies, penile cancer relies heavily on clinical nodal staging of the inguinal lymph node chains. As with all cancers, imaging plays a role in the initial staging, restaging, and surveillance of these patients. The aim of this manuscript is to highlight the applications, advantages, and limitations of different imaging modalities in the evaluation of penile cancer, including ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography.

Assessment of epidermal growth factor receptor in histological, clinical and pathological staging of oral squamous cell carcinoma.

Oral squamous cell carcinoma is an invasive epithelial neoplasm with varying degrees of squamous differentiation that arises from the following anatomic sites: the oral cavity, particularly oral soft tissues including the gingival and alveolar mucosa, floor of the mouth, tongue, soft and hard palate, tonsils and oropharynx. In normal epithelium EGFR is localized to basal cell layer, while its expression beyond basal localization in cancerous tissue suggest that correlation of EGFR and tumor progression might exist. The present study aimed to assess epidermal growth factor receptor in histological, clinical and pathological staging of oral squamous cell carcinoma. The current study was performed on subject with confirmed histological diagnosis of oral squamous cell carcinoma of age group between 35 and 70 years reported to Kempe-Gowda Institute of Medical Science and Hospital, Department of Oral and Maxillofacial Surgery, Vokkaligara Sangha Dental College and Hospital Bangalore and KIDWAI Memorial Institute of Oncology, Bangalore between December 2019 and March 2021. Total of 30 subjects included in the study of age group between 35 and 70 years. In the selected subject for the study, tumor was resected and preserved in 10% formalin, which was sent to department of pathology for analysis and PTNM was recorded. Immunohistochemical evaluation of EGFR was done. Total score of EGFR of each subject was co-related with pathological prognostic factor. Correlation of EGFR with adjuvant therapy and histological grading, P values were 0.001 and 0.005, respectively. The obtained results were tabulated statistically using Chi square test and significance was set at P < 0.05. A preventive approach and assessment of EGFR in early stage of SCC provide better results. Subjects with higher EGFR value have poor prognosis and have to undergo postsurgical adjuvant therapy for long term-survival.

Comparative Study of Conventional and Ultrahigh-resolution Optical Coherence Tomography Imaging in Esophageal Neoplasia

Early diagnosis of esophageal cancer can be enhanced by the application of optical coherence tomography (OCT) to gastrointestinal endoscopy. One of the most salient examples is the use of OCT to augment the detection of dysplasia during Barrett's esophagus (BE) surveillance, the established precursor to esophageal adenocarcinoma (EAC). 1 Reid BJ Li X Galipeau PC et al. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010; 10: 87-101https://doi.org/10.1038/nrc2773 Crossref PubMed Scopus (303) Google Scholar , 2 Pohl H Welch HG The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005; 97: 142-146https://doi.org/10.1093/jnci/dji024 Crossref PubMed Scopus (1069) Google Scholar A previously commercially available balloon-based imaging catheter system, also known as volumetric laser endomicroscopy (VLE), was designed to provide circumferential esophageal imaging at the time of endoscopy. The VLE system uses a 1300 nm wavelength-swept laser and provides images with an axial resolution of 7 µm up to a depth of 3 mm. VLE is capable of resolving microarchitectural features associated with early neoplasia in BE including irregular glandular morphology and increased surface signal intensity. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Scoring systems that incorporate these features are associated with a sensitivity of 76-83% and specificity of 71-79% in the diagnosis of BE neoplasia. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar , 4 Swager AF Tearney GJ Leggett CL et al. Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett’s esophagus using high-quality histological correlation. Gastrointest Endosc. 2017; 85: 918-926.e7https://doi.org/10.1016/j.gie.2016.09.012 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Similarly, esophageal OCT has been used in the diagnosis and staging of squamous cell carcinoma (ESCC) where layer effacement predicts the depth of invasion. 5 Trindade AJ Benias PC Inamdar S et al. Use of volumetric laser endomicroscopy for determining candidates for endoscopic therapy in superficial esophageal squamous cell carcinoma. United European Gastroenterol J. 2018; 6: 838-845https://doi.org/10.1177/2050640618761701 Crossref PubMed Scopus (5) Google Scholar In the last decade, ultra-high resolution (UHR) OCT systems that operate at 800 nm and achieve an axial resolution closer to 2.5 µm have been developed. Our group previously described a super-achromatic OCT capsule designed for UHR esophageal imaging. 6 Li K Liang W Mavadia-Shukla J et al. Super-achromatic optical coherence tomography capsule for ultrahigh-resolution imaging of esophagus. J Biophotonics. 2019; 12e201800205https://doi.org/10.1002/jbio.201800205 Crossref PubMed Scopus (16) Google Scholar In the present study, we compare the imaging capability of UHR OCT to VLE in distinguishing microarchitectural features associated with esophageal neoplasia by imaging ex vivo esophageal resection specimens obtained from patients undergoing clinical endoscopy.

The influence of HIV status on the duration of chemoradiotherapy for anal squamous cell carcinoma

The HIV epidemic has changed the demographic of patients with anal squamous cell carcinoma. The influence of HIV status on the ability to complete standard chemoradiotherapy was studied.A retrospective analytic observational study was conducted of all patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital radiation oncology department with anal squamous cell carcinoma from January 2014 to December 2016. Standard chemoradiotherapy was offered to all patients. Stage of anal squamous cell carcinoma, HIV status and cluster of differentiation 4 (CD4) levels were measured and compared in groups. We considered a maximum of 42 days as complete therapy without delay.Ninety-two patients with anal squamous cell carcinoma were identified, of whom 67 were seen with the intention to treat and had known HIV status, of whom 59 received chemoradiotherapy. Eighty-eight per cent were people living with HIV (PLWH). PLWH were younger (p < 0.001) and less likely to receive full-dose chemotherapy (63%, p = 0.41). No patients presented in stage 1. More than 60% presented in stage 3. Fifty-six per cent of PLWH and 57% of HIV-negative patients were able to complete the 50 Gy radiation in 42 days (p = 1.0). CD4 above 200 did not impact therapy (p = 0.71).HIV status of anal squamous cell carcinoma has minimal impact on the duration of chemoradiotherapy.

MMP-9, MMP-2, VEGF and VEGFR-2 as Factors of Invasion and Angiogenesis in Squamous Cell Carcinoma of the Cervix

Tissue destruction and angiogenesis play an important role in malignant tumor progression. They are responsible for the tumor growth and progress and its ability to invade and metastasize. The key role in the destructive processes belongs to matrix metalloproteinases (MMPs), which are able to cleave almost all components of the extracellular matrix (ECM). Gelatinases MMP-2 and MMP-9 hydrolyze type IV collagen, the main component of basement membranes, thereby releasing various biologically active molecules from ECM, including vascular endothelial growth factor (VEGF). VEGF is a key regulator of angiogenesis. The main mediator of the biological action of VEGF is its receptor VEGFR2. This study was aimed at assessing the relationship between the expression of the main factors of tissue destruction and angiogenesis - MMP-2, MMP-9, VEGF and VEGFR2 in the early and later stages of cervical squamous cell carcinoma (CSCC). The work was performed using samples of tumor and surrounding morphologically normal tissue, obtained from patients with or without metastases to regional lymph nodes. We have shown that MMP- 9 is significantly expressed in tumors in CSCC already at the early stages of tumor progression. At later stages of the disease (when metastases to regional lymph nodes are detected in patients), the expression of MMP-2, VEGF and VEGFR2 increases markedly both in the tumor and in the morphologically normal tissue surrounding the tumor and makes an additional contribution to the processes of destruction, angiogenesis and metastasis. We assume that MMP-2, VEGF and VEGFR2 can be considered as negative markers of the course of CSCC.

The incidence and risk factors for ovarian metastasis and overall survival with ovarian preservation for early-stage adenocarcinoma of the cervix-A meta-analysis

Objective: To compare the incidence of ovarian metastasis (OM) in early stage adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the cervix, evaluate the overall survival with ovarian preservation and determine risk factors of OM for early stage AC. Data sources, methods of study selection: We searched the Cochranes database, Embase, and PubMed for publications to November 2020. The articles reporting the incidence, risk factors and overall survival of OM in AC were included. Articles that lacked sufficient data of the odds ratios (ORs) and 95% confidence intervals (CIs) were excluded. A fixed effects model was used to calculate OR and 95% CIs. Eggers test and Funnel plot were used to test the publication bias. Forest plots was used to present and synthesise results. Tabulation, integration and results: In the meta-analysis, the incidence of OM of AC was higher than that of SCC (OR 5.68, 95% CI 4.40–7.32, I2 = 28.1%) in stage IA-IIB. The incidence of OM was 0% in stage IA, 2.72% in stage IB, 5.95% in stage IIA, and 12.86% in stage IIB AC. Ovarian preservation was not significantly associated with OS (OR 0.53, 95% CI 0.35–0.80, I2 = 37.8%) in early stage of AC. We found seven risk factors for OM: deep stromal invasion (OR 8.80, 95% CI 3.20–24.23, I2 = 0%), corpus uteri invasion (OR 6.29, 95% CI 3.36–11.77, I2 = 21.8%), tumor size &gt;&gt;4 cm (OR 3.78, 95% CI 1.86–7.69, I2 = 30.5%), FIGO stage IIA (OR 3.67, 95% CI 1.98–6.81, I2 = 0%), FIGO stage IIB (OR 4.31, 95% CI 2.74–6.77, I2 = 0%), FIGO stage II (OR 3.99, 95% CI 2.49–6.41, I2 = 0%) and lympho-vascular space invasion (OR 2.90, 95% CI 1.36–6.17, I2 = 0%). Conclusions: Ovarian preservation is only recommended in stage IA and stage IB AC without risk factors, but not reasonable for stage IIA and IIB AC. Both stage IIA and IIB are risk factors for OM in early stage AC.

High-Dose-Rate Brachytherapy Boost Following External Radiotherapy in a Case of Carcinoma External Ear

Squamous cell carcinoma of the external ear is rare and the combination of external beam radiotherapy and brachytherapy has been beneficial for tumors in this location due to the advantage of organ preservation and thereby cosmesis. The incorporation of brachytherapy allows the delivery of doses large enough for the eradication of tumor and the advantage of rapid dose fall off due to brachytherapy minimizes the radiation damage to the nearby organs at risk. Herein we report a case of elderly male with early stage squamous cell carcinoma of external ear treated with a combination of external beam radiation with brachytherapy. An eighty nine year old male reported to our hospital with the complaints of left sided ear ache the presence of some mass in the left external ear. A diagnostic Contrast enhanced Computed Tomography (CECT) scan of head and neck showed a 1.6*1.5*1.4 cm mass lesion (maximum diameter) involving anterior cartilaginous part of left external auditory canal and preauricular soft tissue, thereby staged as T2N0, stage II. Patient was planned for External Beam Radiotherapy (EBRT) using 3D CRT(Conformal Radiotherapy) technique by 6 MV photon beam to a dose of 50 Gy in 25 fractions (2 Gy/#) and following this, a gap of seven days was given and after that four fractions of HDR brachytherapy using Iridium 192 of 3 Gy/# keeping a gap of six hours between two fractions on a single day, Two flexible plastic tubes were used for radiation delivery. The size of the catheter used for radiation delivery was 6 French. Planning CT scan was taken and target volume defined as PTV and a dose of 3 Gy per fraction to a total of 4 fractions was prescribed to the target volume. The spike of intravenous site was used for fixing the plastic tube in the mould. The tumor responded ver well to radiotherapy. Brachytherapy is an effective modality to boost high risk areas without significant damage to the surrounding area. External Beam Radiotherapy in case of early stage carcinoma external auditory canal combined with brachytherapy boost can be considered as a better modality with less severe side effects and better cosmesis.

Clinical management of squamous cell carcinoma in an 8-year-old White Arewa Stallion: A case Report

An 8- year- old white Arewa stallion was hospitalized in our facility (Veterinary Teaching Hospital, Ahmadu Bello University, Zaria) with the primary complaints of fleshy growth on the lower eyelid of the right eye and unilateral left scrotal enlargement. Biopsies were taken via fine needle aspirate from the growth and sent to the histopathology laboratory of the Department of Veterinary Pathology, Ahmadu Bello University Zaria. Histo-pathology results confirmed 3rd stage of squamous cell carcinoma (SCC). Treatment was instituted using vincristine sulphate at a dose rate of 0.025mg/kg and a cyclo-oxygenate 2 inhibitor, diclofenac sodium at a dose rate of 0.5mg/kg for 6 cycles. The surgery was shelved because of the outcome of the therapy. The tumour regressed and the scrotum returned to normal size. The patient recovered and was discharged 2 weeks after the 6 weeks of therapy. The clinical relevance of note is that the above cocktail might be employed in managing early stage of SCC therapy where surgery is not required.

FOUR DIFFERENT STAINING METHODS FOR DETECTION OF MITOTIC FIGURES IN ORAL SQUAMOUS CELL CARCINOMA

In the diagnosis and prognosis of oral squamous cell carcinoma (OSCC) and oral epithelial dysplasia, evaluation of mitotic figures (MFs) is often performed. Numerous techniques, like microscopy, flow cytometry, nucleotide radio labelling, as well as immuno-histochemistry, have been developed throughout time to evaluate the MFs. The most modern techniques are more precise for everyday usage, but because of time and money constraints, they are less practical. In the current research, mitotic figures in various stages of oral squamous cell carcinoma were examined using Haematoxylin and Eosin stain, Crystal Violet stain, Giemsa stain and Toluidine Blue stain. Based on statistical comparison, the number of mitotic figures seen in each of the four distinct stains was compared.

Immunohistochemical evaluation of CD31 and D2-40, expression in oral squamous cell carci-noma

Background: The present study was carried out to evaluate the relation between angiogenesis, and tumor stage of oral squamous cell carcinoma (OSCC).Materials and methods: Thirty formalin-fixed paraffin embedded blocks were used, ten of them were previously diagnosed as well differentiated OSCC, ten moderately differentiated OSCC and ten poorly differentiated OSCC. To determine the expression of CD31 and D2-40 proteins, streptavidin-biotin immunoperoxidase staining technique was used. The areas with the most vascular density (hot spots) were determined. The stained vessels were counted independently in intratumoral and peritumoral stroma. Results: CD 31 protein showed positive expression in the peritumoral and intratumoral blood vessels subjacent to the malignant invading nests. D2-40 expression was positive in lymphatic vessel in the peritumoral and intratumoral stroma subjacent to the invading nests. The highest mean values of both CD31 and D2-40 proteins expression were recorded in poor differentiated OSSC followed by moderate differentiated OSSC then well differentiated OSSC. There was statistically significant difference found between the three studied groups regarding CD31 and D2-40 levels. Also there was statistically significant positive correlation found between CD31 level and D2-40 level.Conclusion: CD31 and D2-40 are related to stage of OSCC and are consistent with angiogenesis in tumor progression.

Systemic Inflammatory Markers as Predictors of Postoperative Complications and Survival in Patients With Advanced Head and Neck Squamous Cell Carcinoma Undergoing Free-Flap Reconstruction

The aim of this study was to determine the prognostic value of systemic inflammatory indices as factors for postoperative complications and survival in patients with advanced stages of p16-negative head and neck squamous cell carcinoma undergoing free-flap reconstruction. This was a retrospective cohort study. The primary predictor variables were inflammatory markers such as neutrophil, lymphocyte, monocyte, and platelet count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, lymphocyte-monocyte ratio, derived NLR, systemic immune-inflammatory index, and systemic inflammatory marker index (SIM). Multivariate regression analyses were used to measure the associations between systemic inflammatory indices and overall and disease-free survival as a primary outcome and occurrence of postoperative complications as a secondary outcome measure. The sample was composed of 69 male (76.67%) and 21 female (23.33%) patients, with an average age of 61.15±9.79years. The median follow-up time was 24months, and 73 of 91 (66.43%) patients were alive during the median follow-up. Overall disease survival correlated with systemic immune-inflammation (P=.022, cutoff >1,005.3, sensitivity 67.1%, and specificity 70.6%) and SIM (P=.0001, cutoff >4.05, sensitivity 90.4%, and specificity 41.2%), preoperative platelets (P=.036, cutoff <194, sensitivity 28.8%, and specificity 94.1%), and postoperative lymphocytes (P=.012, cutoff <0.6, sensitivity 38%, and specificity 76.5%), whereas increased SIM (P=.042, cutoff >4.05, sensitivity 91.3%, and specificity 38.1%), NLR (P=.031, cutoff >13.2, sensitivity 56.9%, and specificity 60%), and preoperative platelets (P=.006, cutoff <244, sensitivity 52.3%, and specificity 76%) were associated with adverse disease-free survival. The cumulative postoperative complication rate was 34.5%, of which 13.3% accounted for major complications, whereas derived NLR (P=.013, degrees of freedom 1, χ2 test 6.161, cutoff >2.3) and postoperative lymphocytes (P=.009, DF 1, χ2 test 6.756, cutoff <1) correlated with occurrence of complications. Inflammatory indices as measures of inflammation-related systemic dysfunction may be associated with adverse survival in patients with head and neck squamous cell carcinoma and occurrence of postoperative complications and with specific cutoff values.

ARL14 as a Prognostic Biomarker in Non-Small Cell Lung Cancer.

PurposeNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. The mechanisms underlying NSCLC initiation and progression require further investigation. The purpose of this study was to investigate the role of ADP ribosylation factor-like GTPase 14 (ARL14) related to the progression of NSCLC.Patients and MethodsWe analyzed the correlation between clinical characteristics and ARL14 expression using data from The Cancer Genome Atlas (TCGA). Kaplan–Meier analysis was conducted to evaluate the prognostic value of ARL14 in NSCLC. Functions of ARL14 were identified by enrichment analysis. The relationship between ARL14 expression and immune cell infiltration was also studied. Furthermore, ARL14 expression was examined using immunohistochemistry, and its clinical significance was analyzed in 120 patients with NSCLC.ResultsOur study revealed that the expression level of ARL14 in patients with NSCLC was higher than that in normal tissues. Using TCGA data, higher ARL14 expression in lung adenocarcinoma was associated with residual tumor (P = 0.017), while it was associated with age (P = 0.003) and N stage (P = 0.009) in lung squamous cell carcinoma. Similar results were obtained from 120 patients with NSCLC. High ARL14 expression was associated with poor overall survival and progression-free survival in NSCLC. Multivariate analysis revealed that ARL14 was an independent risk factor for patients with NSCLC. Functional enrichment analysis indicated that ARL14 was related to the occurrence and development of tumors.ConclusionIncreased ARL14 expression was considerably correlated with poor survival in NSCLC, and it might be a promising prognostic biomarker for NSCLC.

NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P < 0.05) epithelium thickness in the cancer groups as compared to the vehicle and control groups at both the PM and M. Overall, this study discovered that NTCU is capable of developing PM and M lung SCC in mice model at appropriate weeks and the vehicle group was suggested to be adequate as control group for future research.

Cutaneous squamous cell carcinoma staging may influence management in users: A survey study.

PurposeThis study aims to determine whether there is consensus regarding staging and management of cutaneous squamous cell carcinoma (CSCC) across the various specialties that manage this disease.Materials and MethodsA survey regarding CSCC high‐risk features, staging, and management was created and emailed to cutaneous oncology experts including dermatology, head and neck surgery/surgical oncology, radiation oncology, and medical oncology.ResultsOne hundred fifty‐six (46%) of 357 invited physicians completed the survey. Depth of invasion (92%), perineural invasion (99%), histologic differentiation (85%), and patient immunosuppression (90%) achieved consensus (>80%) as high‐risk features of CSCC. Dermatologists were more likely to also choose clinical tumor diameter (79% vs. 54%) and histology (99% vs. 66%) as a high‐risk feature. Dermatologists were also more likely to utilize the Brigham and Women's Hospital (BWH) staging system alone or in conjunction with American Joint Committee on Cancer (AJCC) (71%), whereas other cancer specialists (OCS) tend to use only AJCC (71%). Respondents considered AJCC T3 and higher (90%) and BWH T2b and higher (100%) to be high risk and when they consider radiologic imaging, sentinel lymph node biopsy, post‐operative radiation therapy, and increased follow‐up. Notably, a large number of respondents do not use staging systems or tumor stage to determine treatment options beyond surgery in high‐risk CSCC.ConclusionThis survey study highlights areas of consensus and differences regarding the definition of high‐risk features of CSCC, staging approaches, and management patterns between dermatologists and OCS. High‐risk CSCC is defined as, but not limited to, BWH T2b and higher and AJCC T3 and higher, and these thresholds can be used to identify cases for which treatment beyond surgery may be considered. Dermatologists are more likely to utilize BWH staging, likely because BWH validation studies showing advantages over AJCC were published in dermatology journals and discussed at dermatology meetings. Additional data are necessary to develop a comprehensive risk‐based management approach for CSCC.

PELI1 promotes radiotherapy sensitivity by inhibiting noncanonical NF‐κB in esophageal squamous cancer

The low sensitivity of radiotherapy is the main cause of tumor tolerance against ionizing radiation (IR). However, the molecular mechanisms by which radiosensitivity is controlled remain elusive. Here, we observed that high expression of pellino E3 ubiquitin protein ligase 1 (PELI1) was correlated with improved prognosis in human esophageal squamous cell carcinoma stage III patients that received adjuvant radiotherapy. Moreover, we found PELI1‐mediated IR‐induced tumor cell apoptosis in vivo and in vitro. Mechanistically, PELI1 mediated the lysine 48 (Lys48)–linked polyubiquitination and degradation of NF‐κB–inducing kinase (NIK; also known as MAP3K14), the master kinase of the noncanonical NF‐κB pathway, thereby inhibiting IR‐induced activation of the noncanonical NF‐κB signaling pathway during radiotherapy. As a consequence, PELI1 inhibited the noncanonical NF‐κB–induced expression of the anti‐apoptotic gene BCL2 like 1 (Bclxl; also known as BCL2L1), leading to an enhancement of the IR‐induced apoptosis signaling pathway and ultimately promoting IR‐induced apoptosis in tumor cells. Therefore, Bclxl or NIK knockdown abolished the apoptosis‐resistant effect in PELI1‐knockdown tumor cells after radiotherapy. These findings establish PELI1 as a critical tumor intrinsic regulator in controlling the sensitivity of tumor cells to radiotherapy through modulating IR‐induced noncanonical NF‐κB expression.

A clinical case of treatment of a patient with laryngeal granular cell (Abrikossoff) tumor

The study objective – present a clinical case of radical surgical treatment of a laryngeal granular cell tumor with invasion of cricoid cartilage and thyroid gland and show the importance of pathomorphological diagnosis.Case report. A 47‑year-old woman of European origin complained of progressive hoarseness that lasted for 8 months. We analyzed her clinical, laboratory, radiological, and pathomorphological data. At the preoperative stage, the tumor was classified as well differentiated squamous cell carcinoma (stage cT4aN0M0). Endoscopic examination revealed the exophytic part of the tumor with an infiltrative base and tuberous surface, pinkish, with signs of dyskeratosis and tumor invasion to the cartilage. Pathomorphological examination of biopsy specimens demonstrated well differentiated keratinizing squamous cell carcinoma. The patient has undergone laryngectomy, thyroidectomy, and selective cervical lymph node dissection. Pathomorphological and immunohistochemical examinations of surgical material verified granular cell tumor of the larynx (Abrikosov’s tumor) that was excised within healthy tissues (R0). Conclusion. The presented clinical case of such a rare pathology as a granular cell tumor of the larynx shows the importance of pathomorphological diagnosis and the use of additional immunohistochemical research methods for making an accurate diagnosis and differential diagnosis of squamous cell carcinoma and Abrikossoff tumor.

Prognostic Value of Telomeric Zinc Finger-Associated Protein Expression in Adenocarcinoma and Squamous Cell Carcinoma of Lung.

Background and Objectives: Telomeric zinc finger-associated protein (TZAP) is a telomere regulation protein, previously known as ZBTB48. It binds preferentially to elongated telomeres, competing with telomeric repeat factors 1 and 2. TZAP expression may be associated with carcinogenesis, however; this study has not yet been performed in lung cancer. In this study, we examined the clinicopathological and prognostic values of TZAP expression in non-small cell lung cancer (NSCLC). Materials and Methods: Data were collected from The Cancer Genome Atlas. The clinical and prognostic values of TZAP for NSCLC were examined in adenocarcinoma (AD) and squamous cell carcinoma (SCC). Results: TZAP expression significantly increased in NSCLC tissues compared with normal tissues. In AD, TZAP expression was lower in patients with higher T stage (p = 0.005), and was associated with lymph node stage in SCC (p = 0.005). Survival analysis showed shorter disease-free survival in AD patients with lower TZAP expression (p = 0.047). TZAP expression did not have other clinical or prognostic value for AD and SCC. Conclusions: TZAP expression is a potential prognostic marker for NSCLC, especially in patients with AD.

Analysis of M2 macrophage infiltration and its clinical significance in 44 patients with multiple primary cancers of the head and neck

Objective: To investigate and analyze the characteristics of M2 macrophage infiltration and the clinical significance in patients with multiple primary cancers (MPCs) of head and neck in order to explore its role in the diagnosis and prognosis for patients with MPCs. Methods: RNA-seq data were downloaded from the Genomic Data Commons data portal (TCGA) and the R software v4.0.3 was used to statistically analyze the differences. A retrospective analysis was conducted by screening the clinical data of 44 patients (17 males and 27 females) with MPCs in head and neck from July 1998 to February 2016 in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. Clinical data from a batch of 41 patients (28 males and 13 females) with gingival cancer and without MPCs from August 2013 to December 2015 were collected and analyzed. The number of CD163 positive cells and the expression patterns in immunohistochemically panoramic slices were observed under high magnification. Chi-square test and Spearman correlation analysis were used to compare the difference and correlation between the CD163 positive counts and/or depths of invasion and the number of incidences. The descriptive statistics on the clinical features was performed by SPSS 25.0. Results: TCGA database analysis showed that the infiltration of macrophage in patients with squamous cell carcinoma of head and neck (HNSCC) was increased compared to the para-cancer sites. A total of 142 tissue samples from 44 patients with MPCs were selected in the present single-center retrospective research. The number of CD163-positive cells in MPCs patients [90.9% (40/44)] was significantly increased compared to single gingival cancer patients [61.0%(25/41)] (r=0.353, P=0.001), which was related to the number of occurrence (r=0.368, P=0.001). The ratio of the CD163 counts in primary tumor to the depths of invasion was positively correlated with the number of onsets (r=0.331, P=0.03). In terms of clinical features, the 44 patients with MPCs were mainly female, non-smoking, no alcohol addiction, no systemic history, Tis-T2 stage and N0 stage squamous cell carcinoma. The number of incidences ranged from two to eight. The incidence of cancer relative to synchronous cancer increased with the increased occurrence of MPCs. The primary cancer mainly occurred in tongue, gingiva and buccal sites, while the proportion of onset sites in gingiva, buccal and palate areas increased with the increased occurrence. Conclusions: M2 type macrophage counts and/or ratio to depth of infiltration were associated with the occurrence of MPCs, which could be used as a clinical indicator to distinguish single and MPCs in HNSCC. For early stage of HNSCC, patients with clinical characters of women, non-smoking, no alcohol addiction, no systemic medical history and sites of tongue, gingiva, and buccal should be paid more attention on their follow-up plan. The findings in the present study was also helpful to explore new treatment methods for the patients with MPCs.

Effectiveness of photodynamic therapy on treatment response and survival of patients with recurrent oral squamous cell carcinoma: a systematic review protocol.

This review aims to systematically examine the effectiveness of photodynamic therapy for the treatment of patients with recurrent oral squamous cell carcinoma. Oral squamous cell carcinoma is a significant public health problem, and is the seventh most common cancer. Its incidence is mainly due to tobacco use, alcohol consumption, and HPV infection. The survival rates are poor due to diagnosis at advanced stages, with high recurrence rates. Although current evidence does not point to photodynamic therapy as a first-line option, this treatment might be suitable for treating recurrent stages of the cancer where conventional treatments were ineffective. Despite the potential of photodynamic therapy, there is a need to verify the scientific evidence to support its indication for the treatment of recurrent oral squamous cell carcinoma. This review will consider studies on any stage of recurrent oral squamous cell carcinoma treated with photodynamic therapy after receiving first-line conventional treatments. Patients of any age, gender, and geographic location will be included. The primary outcomes will be to evaluate response to treatment, focusing on remission, recurrence, change in size of the lesion, alleviation of symptoms, and survival. Secondary outcomes will be postoperative complications, presence of necrosis, patient quality of life after treatment, and patient satisfaction. Studies will be searched using a combination of index terms and keywords in MEDLINE, Cochrane Central, Web of Science, Embase, and ClinicalTrials.gov. No date limits will be applied. Articles written in English, French, Spanish, or Portuguese will be considered. Findings will be provided as a narrative synthesis, structured around the photodynamic therapy protocol used. A meta-analysis is planned and subgroup analysis will be conducted if possible. The certainty of findings will be assessed. PROSPERO CRD42020141075.

Chemoradiation With or Without Metformin in Locally Advanced Cervical Cancer: Phase II Randomized Trial

Tumor hypoxia is associated with poor response to radiation (RT) and chemotherapy, and worse treatment outcome. We previously discovered a novel mechanism of metformin in a xenograft model: enhancing tumor RT response by inhibiting tumor cell oxygen consumption. Our population-based study showed that cumulative dose of metformin after cervical cancer diagnosis was independently associated with a decreased risk of cervical cancer-specific mortality in diabetic women. Based on the pre-clinical and retrospective data, we hypothesized that metformin would decrease tumor hypoxia and improve tumor response to RT in locally advanced cervical cancer.A window-of-opportunity, phase II randomized trial was performed in women with stage IB-IVA cervical adenocarcinoma, squamous cell or adenosquamous carcinoma. Patients underwent screening positron emission tomography (PET) imaging with hypoxia tracer fluoroazomycin arabinoside (FAZA). Those with non-hypoxic tumor (no FAZA uptake) were excluded. Patients with FAZA uptake were randomized centrally in a 2:1 ratio (in favor of metformin) to receive either metformin in combination with standard chemoRT or standard chemoRT alone. Metformin was started at 850mg once daily x 3 days, followed by 850mg twice daily throughout the entire duration of external radiotherapy. A second FAZA-PET/CT scan was performed after 1 week of metformin or no intervention in control group, just before start of chemoRT. The hypoxic volume was defined as all voxels within a tumor with standardized uptake values (SUVs) greater than 3 standard deviations (SD) from the mean gluteus maximus muscle SUV value. The hypoxic fraction (HF) was defined as the ratio of the number of hypoxic voxels to the total number of tumor voxels. The primary endpoint was absolute mean change in HF between the two FAZA-PET scans, compared using the Wilcoxon sign rank test. Disease-free survival (DFS) was defined as the duration of time from randomization to the time of relapse or death and compared using the log-rank test. Target accrual was 48 patients; the study was closed early to accrual due to FAZA availability and the COVID-19 pandemic.Of the twenty patients who consented, 6 were excluded due to no FAZA uptake and 1 withdrew. The median age of the 13 enrolled patients was 52; 8 (62%) had squamous cell carcinoma and 8 had stage IIB disease. HF of the 10 patients in the metformin arm decreased by an average of 10.2% (from 44.4% to 34.2%) ± SD 16.9% after 1 week of metformin, compared to an average increase of 4.7% (from 29.1% to 33.8%) ± 11.5% for the 3 patients in the control arm (P = 0.027). With a median follow-up of 2.8 years, the 2-year DFS was 67% for the metformin arm vs 33% for control (P = 0.09).Metformin decreases cervical tumor hypoxia with a trend towards improved DFS in this trial. A larger confirmatory trial is warranted.