Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

Fibroblast growth factor (FGF), FGF receptor (FGFR), and cyclin D1 (CCND1) DNA methylation in head and neck squamous cell carcinomas is associated with transcriptional activity, gene amplification, human papillomavirus (HPV) status, and sensitivity to tyrosine kinase inhibitors.

BACKGROUND: Dysregulation of fibroblast growth factor receptor (FGFR) signaling pathway has been observed in head and neck squamous cell carcinoma (HNSCC) and is a promising therapeutic target for selective tyrosine kinase inhibitors (TKIs). Potential predictive biomarkers for response to FGFR-targeted therapies are urgently needed. Understanding the epigenetic regulation of FGF pathway related genes, i.e. FGFRs, FGFs, and CCND1, could enlighten the way towards biomarker-selected FGFR-targeted therapies. METHODS: We performed DNA methylation analysis of the encoding genes FGFR1, FGFR2, FGFR3, FGFR4, FGF1-14, FGF16-23, and CCND1 at single CpG site resolution (840 CpG sites) employing The Cancer Genome Research Atlas (TCGA) HNSCC cohort comprising N = 530 tumor tissue and N = 50 normal adjacent tissue samples. We correlated DNA methylation to mRNA expression with regard to human papilloma virus (HPV) and gene amplification status. Moreover, we investigated the correlation of methylation with sensitivity to the selective FGFR inhibitors PD 173074 and AZD4547 in N = 40 HPV(-) HNSCC cell lines. RESULTS: We found sequence-contextually nuanced CpG methylation patterns in concordance with epigenetically regulated genes. High methylation levels were predominantly found in the promoter flank and gene body region, while low methylation levels were present in the central promoter region for most of the analyzed CpG sites. FGFRs, FGFs, and CCND1 methylation differed significantly between tumor and normal adjacent tissue and was associated with HPV and gene amplification status. CCND1 promoter methylation correlated with CCND1 amplification. For most of the analyzed CpG sites, methylation levels correlated to mRNA expression in tumor tissue. Furthermore, we found significant correlations of DNA methylation of specific CpG sites with response to the FGFR1/3-selective inhibitors PD 173074 and AZD4547, predominantly within the transcription start site of CCND1. CONCLUSIONS: Our results suggest an epigenetic regulation of CCND1, FGFRs, and FGFs via DNA methylation in HNSCC and warrants further investigation of DNA methylation as a potential predictive biomarker for response to selective FGFR inhibitors in clinical trials.

Infection by High-Risk Human Papillomaviruses, Epithelial-to-Mesenchymal Transition and Squamous Pre-Malignant or Malignant Lesions of the Uterine Cervix: A Series of Chained Events?

Wound healing requires static epithelial cells to gradually assume a mobile phenotype through a multi-step process termed epithelial-to-mesenchymal transition (EMT). Although it is inherently transient and reversible, EMT perdures and is abnormally activated when the epithelium is chronically exposed to pathogens: this event deeply alters the tissue and eventually contributes to the development of diseases. Among the many of them is uterine cervical squamous cell carcinoma (SCC), the most frequent malignancy of the female genital system. SCC, whose onset is associated with the persistent infection of the uterine cervix by high-risk human papillomaviruses (HR-HPVs), often relapses and/or metastasizes, being resistant to conventional chemo- or radiotherapy. Given that these fearsome clinical features may stem, at least in part, from the exacerbated and long-lasting EMT occurring in the HPV-infected cervix; here we have reviewed published studies concerning the impact that HPV oncoproteins, cellular tumor suppressors, regulators of gene expression, inflammatory cytokines or growth factors, and the interactions among these effectors have on EMT induction and cervical carcinogenesis. It is predictable and desirable that a broader comprehension of the role that EMT inducers play in SCC pathogenesis will provide indications to flourish new strategies directed against this aggressive tumor.

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.

Impact of molecular surgical margin analysis on the prediction of pancreatic cancer recurrences after pancreaticoduodenectomy.

BACKGROUND: Pancreatic cancer is one of the lethal cancers among solid malignancies. Pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage, invisible field cancerization and skipped lesions like tumor budding. As a result, tumor recurrences sometimes occur even from the pathologically negative surgical margins. METHODS: We applied molecular surgical margin (MSM) analysis by tissue imprinting procedure to improve the detection sensitivity of tiny cancerous cells on the surgical specimen surface after pancreatoduodenectomy. Surgical specimens were collected from 45 pancreatic cancer cases who received subtotal stomach preserving pancreatoduodenectomy at Nagoya University Hospital during 2017-2019. Quantitative methylation-specific PCR (QMSP) of the original methylation marker panel (CD1D, KCNK12, PAX5) were performed and analyzed with postoperative survival outcomes. RESULTS: Among 45 tumors, 26 cases (58%) were QMSP-positive for CD1D, 25 (56%) for KCNK12 and 27 (60%) for PAX5. Among the 38 tumors in which at least one of the three markers was positive, CD1D-positive cancer cells, KCNK12-positive cancer cells, and PAX5-positive cancer cells were detected at the surgical margin in 8 cases, 7 cases and 10 cases, respectively. Consequently, a total of 17 patients had at least one marker detected at the surgical margin by QMSP, and these patients were defined as MSM-positive. They were associated with significantly poor recurrence-free survival (p = 0.002) and overall survival (p = 0.005) than MSM-negative patients. Multivariable analysis showed that MSM-positive was the only significant independent factor for worse recurrence-free survival (hazard ratio: 3.522, 95% confidence interval: 1.352-9.179, p = 0.010). On the other hand, a significant proportion of MSM-negative cases were found to have received neoadjuvant chemotherapy (p = 0.019). CONCLUSION: Pancreatic cancer-specific methylation marker panel was established to perform MSM analysis. MSM-positive status might represent microscopically undetectable cancer cells on the surgical margin and might influence the postoperative long-term outcomes.

Evaluating the prognostic contributions of TNM classifications and building novel staging schemes for middle ear squamous cell carcinoma.

BACKGROUND: A universally acknowledged cancer staging system considering all aspects of the T-, N-, and M-classifications for middle ear squamous cell carcinoma (MESCC) remains absent, limiting the clinical management of MESCC patients. MATERIALS AND METHODS: A total of 214 MESCC patients were extracted from the SEER (the Surveillance, Epidemiology, and End Results) database between 1973 and 2016. The relationships between patient's characteristics and prognoses were analyzed by Kaplan-Meier and Cox proportional hazards regression models. Novel staging schemes for MESCC were designed by adjusted hazard ratio (AHR) modeling method according to the combinations of Stell's T-classification and the eighth AJCC N- and M-classifications, of which performances were evaluated based on five criteria: hazard consistency, hazard discrimination, explained variation, likelihood difference, and balance. RESULTS: T-classification was the most significant prognostic factor for MESCC patients in multivariable analysis (p = 0.021). The N- and M-classifications also had obvious prognostic effect but were not statistically significant by multivariate analysis due to the limited metastasis events. Three novel staging schemes (AHR-Ⅰ-Ⅲ models, different combination of T- and N-classifications) and ST (solely derived from Stell's T-classification) were developed, among which the AHR-Ⅰ staging scheme performed best. CONCLUSIONS: Tumor extension, quantified by Stell's T-classification, is the most significant prognostic factor for MESCC patients. However, our AHR-Ⅰ staging scheme, a comprehensive staging scheme that integrating T-, N-, and M-classifications, might be an optimal option for clinical practitioners to predict MESCC patients' prognosis and make proper clinical decisions.

A rapid response of lung squamous cell carcinoma following treatment with sintilimab combined with recombinant humane endostatin injection and nab-paclitaxel in an elderly patient: A case report.

RATIONALE: At present, the prognosis of patients with giant lung squamous cell carcinoma (LSCC) is poor, and there is no safe and effective treatment for elderly patients with large LSCC. PATIENT CONCERNS: Here, we reported a 77-year-old man admitted to the hospital with cough for 3 months and significant chest pain. Computed tomography (CT) imaging showed a large mass in the left lung with pleural effusion. DIAGNOSES: Chest CT scan revealed a 12.5 cm × 7.3 cm mass in the left upper lobe adjacent to the pulmonary vein, with left pleural effusion. Pulmonary tumor markers were significantly elevated, and CT-guided percutaneous lung mass biopsy specimens showed LSCC. INTERVENTIONS: After diagnosis, the patient was treated with sintilimab combined with endostar and nab-paclitaxel. After 2 cycles of treatment, the lung mass in the patient shrank rapidly and the clinical symptoms were relieved. OUTCOMES: The patient's tumor dramatically shrank, and the pleural effusion was decreased after 4 cycles of treatment without any adverse effects. Meanwhile, the high-level tumor marker resumed normal. LESSONS: Sintilimab combined with endostar and nab-paclitaxel may be a good treatment option for lung squamous cell cancer, especially for that in elderly patients.

Model of Human Tongue Squamous Cell Lines Stably Transfected with Human Papillomavirus (HPV)16 E6 and E7 Genes and Biological Characteristic Analysis.

BACKGROUND: Human tongue squamous cell carcinoma (TSCC) is the most common oral cancer with the highest human papillomavirus (HPV) infection rate in oral cancer. The purpose of this study was to research the correlation between HPV and TSCC. METHOD: Plasmid pEGFP/HPV16 E6E7 and plasmid pEGFP/no HPV16 E6E7 were constructed. TSCC cell lines SCC9 and SCC15 were infected by liposome transfection and would be highly selected by antibiotic. Fluorescence imaging, PCR, and Western blot were used to detect the expression of HPV16 E6E7 in cells. The biological characteristics were detected by CCK-8, wound healing assay, qRT-PCR, and Western blot. RESULT: TSCC cell lines transfected with HPV16 E6E7 gene were successfully established and identified. And the proliferation and migration ability of the TSCC cell lines infected with HPV16 E6E7 gene were significantly stronger than that of the blank group. CONCLUSION: TSCC cell lines infected with HPV16 E6E7 with significantly higher ability of proliferation and migration were more malignant than those not infected with HPV16 E6E7.

Temporal analysis of type 1 interferon activation in tumor cells following external beam radiotherapy or targeted radionuclide therapy.

Rationale: Clinical interest in combining targeted radionuclide therapies (TRT) with immunotherapies is growing. External beam radiation therapy (EBRT) activates a type 1 interferon (IFN1) response mediated via stimulator of interferon genes (STING), and this is critical to its therapeutic interaction with immune checkpoint blockade. However, little is known about the time course of IFN1 activation after EBRT or whether this may be induced by decay of a TRT source. Methods: We examined the IFN1 response and expression of immune susceptibility markers in B78 and B16 melanomas and MOC2 head and neck cancer murine models using qPCR and western blot. For TRT, we used 90Y chelated to NM600, an alkylphosphocholine analog that exhibits selective uptake and retention in tumor cells including B78 and MOC2. Results: We observed significant IFN1 activation in all cell lines, with peak activation in B78, B16, and MOC2 cell lines occurring 7, 7, and 1 days, respectively, following RT for all doses. This effect was STING-dependent. Select IFN response genes remained upregulated at 14 days following RT. IFN1 activation following STING agonist treatment in vitro was identical to RT suggesting time course differences between cell lines were mediated by STING pathway kinetics and not DNA damage susceptibility. In vivo delivery of EBRT and TRT to B78 and MOC2 tumors resulted in a comparable time course and magnitude of IFN1 activation. In the MOC2 model, the combination of 90Y-NM600 and dual checkpoint blockade therapy reduced tumor growth and prolonged survival compared to single agent therapy and cumulative dose equivalent combination EBRT and dual checkpoint blockade therapy. Conclusions: We report the time course of the STING-dependent IFN1 response following radiation in multiple murine tumor models. We show the potential of TRT to stimulate IFN1 activation that is comparable to that observed with EBRT and this may be critical to the therapeutic integration of TRT with immunotherapies.

Longitudinal changes in skeletal muscle mass in patients with advanced squamous cell lung cancer.

BACKGROUND: Skeletal muscle depletion (sarcopenia) is associated with poor prognosis in patients with lung cancer. We analyzed changes in skeletal muscle area using serial computed tomography (CT) until the death of patients with advanced squamous cell lung cancer (SQCLC). METHODS: This retrospective study comprised 70 consecutive patients who underwent palliative chemotherapy for SQCLC. The cross-sectional area of the skeletal muscle at the level of the first lumbar vertebra (L1) was measured using chest CT. An artificial intelligence algorithm was developed and used for the serial assessment of the muscle area. Sarcopenia was defined as an L1 skeletal muscle index <46 cm2 /m2 in men and < 29 cm2 /m2 in women. RESULTS: The median age was 69 years; 62 patients (89%) had metastatic disease at the time of initial diagnosis. Sarcopenia was present in 58 patients (82.9%) at baseline; all patients experienced net muscle loss over the disease trajectory. The median overall survival was 8.7 (95% confidence interval 5.9-11.5) months. The mean percentage loss of skeletal muscle between the first and last CT was 16.5 ± 11.0%. Skeletal muscle loss accelerated over time and was the highest in the last 3 months of life (p < 0.001). Patients losing skeletal muscle rapidly (upper tertile, >3.24 cm2 /month) had shorter overall survival than patients losing skeletal muscle slowly (median, 5.7 vs. 12.0 months, p < 0.001). CONCLUSIONS: Patients with advanced SQCLC lose a significant amount of skeletal muscle until death. The rate of muscle area reduction is faster at the end of life.

Inflammatory Response Mechanisms of the Dentine-Pulp Complex and the Periapical Tissues.

The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.

Assessment and treatment strategies for occult contralateral lymph node metastasis in hypopharyngeal squamous cell carcinoma patients with ipsilateral node-positive necks.

Hypopharyngeal squamous cell carcinoma (HSCC) is an aggressive disease with poor prognosis, yet studies have largely been more qualitatively focused. Our study aims to quantitatively predict the risk of occult contralateral lymph node metastasis (cLNM) for HSCC patients with ipsilateral lymph node metastasis (iLNM). This will be based on pre- and post-operative indexes to guide the selection of prophylactic contralateral lymph node dissection (cLND) and postoperative adjuvant treatments. Multivariate analyses of 462 primary HSCC patients with iLNM showed that the age of patients, subregions of tumor, pathological T (pT) stage, ipsiateral MLS and metastatic lymph node number (MLN), and lymph nodal necrosis were independent cLNM risk factors. These were used to construct two nomograms that can effectively predict the contralateral neck involvement in HSCC patients with ipsilateral positive lymph nodes. The first nomogram (pre-model) provides quantitative assessment on the necessity of cLND, while the second nomogram (post-model) informs regions of interest for therapeutic radiation. Overall, patients deemed high-risk of cLNM by pre-model should receive cLND. Post-operation, patients deemed high-risk of cLNM by post-model should receive therapeutic radiation targeting contralateral neck lymph nodes, moderate-risk group warrants comparatively lower dose contralaterally, while low-risk group requires only follow-up.

Comparison of different lymph node staging systems in patients with positive lymph nodes in oral squamous cell carcinoma.

OBJECTIVES: The evaluation of neck lymph node metastasis is critical for predicting survival after head and neck cancer treatment. However, traditional pathological N staging does not completely correlate with survival; the total number of lymph nodes resected during surgery affects staging, and a minimal number of nodes must be resected to achieve a superior outcome. Thus, the prognostic abilities of various lymph node staging systems for oral cavity squamous cell carcinoma (OSCC)-positive lymph nodes were compared. MATERIALS AND METHODS: Data for 639 patients with OSCC-positive nodes who were treated and monitored at the Changhua Christian Hospital were retrospectively analyzed. The different N staging systems were compared to evaluate their disease-free survival (DFS) predictability. RESULTS: The areas under the receiver operating characteristic curve were as follows: 0.551 for the traditional American Joint Committee on Cancer (AJCC) N staging, 0.60 for lymph node density (LND), 0.596 for log odds of positive lymph nodes (LODDS), and 0.597 for the number of metastatic lymph nodes (nmLN). The LND, LODDS, and nmLN systems could predict DFS better than AJCC N staging. Multivariable analysis for DFS revealed that extranodal spread, level IV or V positive nodes, and tumor invasion deeper than 13 mm were independent prognostic factors in these four models. LND and LODDS predicted DFS better than pathological N staging. CONCLUSION: LND and LODDS staging predicted DFS better than AJCC N staging for OSCC-positive nodes. In the future, the prognostic ability of AJCC staging may be strengthened by LND or LODDS staging.

Difference in tumor mutation burden between squamous cell carcinoma in the oral cavity and larynx.

OBJECTIVES: This study aimed to evaluate the difference in tumor mutation burden (TMB) between oral cavity squamous cell carcinoma (OCSCC) and larynx squamous cell carcinoma (LSCC). MATERIALS AND METHODS: Patients with OCSCC or LSCC were identified from datasets within The Cancer Genome Atlas. Somatic mutations and clinical information were included in the analysis. A Poisson regression model was used to evaluate the association of TMB with the primary cancer sites. RESULTS: We identified 5 datasets that included 396 OCSCC patients and 143 LSCC patients. Patients with LSCC had a significantly higher TMB than patients with OCSCC (crude risk ratio: 0.60, 95% confidence interval: 0.51-0.70, P < 0.001; adjusted risk ratio: 0.57, 95% confidence interval: 0.49-0.66, P < 0.001).Subgroup analyses suggested that this difference was independent of dataset, age, sex, race, alcohol drinking, smoking status, pathological risk, tumor grade, and tumor stage. Sensitivity analyses confirmed the robustness of this finding. CONCLUSION: To the best of our knowledge, this is the first study to identify a significant difference in TMB between OCSCC and LSCC. Though preliminary, these findings might have implications for guiding the development of trials for examining the response of head and neck carcinomas to immune checkpoint inhibitor treatments.

Pathophysiological relationship between hypoxia associated oxidative stress, Epithelial-mesenchymal transition, stemness acquisition and alteration of Shh/ Gli-1 axis during oral sub-mucous fibrosis and oral squamous cell carcinoma.

Oral sub-mucous fibrosis (OSF) is a pathophysiological state of oral cavity or oropharynx having a high chance of conversion to oral squamous cell carcinoma (OSCC). It involves fibrotic transformation of sub-epithelial matrix along with epithelial abnormalities. The present work aims to unveil the mechanistic domain regarding OSF to OSCC conversion exploring the scenario of hypoxia associated oxidative stress, epithelial-mesenchymal transition (EMT), metastasis and stemness acquisition. The study involves histopathological analysis of the diseased condition along with the exploration of oxidative stress status, assessment of mitochondrial condition, immunohistochemical analysis of HIF-1α, E-cadherin, vimentin, ERK, ALDH-1, CD133, Shh, Gli-1 and survivin expressions in the oral epithelial region together with the quantitative approach towards collagen deposition in the sub-epithelial matrix. Oxidative stress was found to be associated with type-II EMT in case of OSF attributing the development of sub-epithelial fibrosis and type-III EMT in case of OSCC favoring malignancy associated metastasis. Moreover, the acquisition of stemness during OSCC can also be correlated with EMT. Alteration of Shh and Gli-1 expression pattern revealed the mechanistic association of hypoxia with the phenotypic plasticity and disease manifestation in case of OSF as well as OSCC. Shh/ Gli-1 signaling can also be correlated with survivin mediated cytoprotective phenomenon under oxidative stress. Overall, the study established the correlative network of hypoxia associated oxidative stress, EMT and manifestation of oral pre-cancerous and cancerous condition in a holistic approach that may throw rays of hope in the therapeutic domain of the concerned diseases.

Cellular heterogeneity and microenvironmental control of skin cancer.

Healthy tissues harbour a surprisingly high number of cells that carry well-known cancer-causing mutations without impacting their physiological function. In recent years, strong evidence accumulated that the immediate environment of mutant cells profoundly impact their prospect of malignant progression. In this review, focusing on the skin, we investigate potential key mechanisms that ensure tissue homeostasis despite the presence of mutant cells, as well as critical factors that may nudge the balance from homeostasis to tumour formation. Functional in vivo studies and single-cell transcriptome analyses have revealed a tremendous cellular heterogeneity and plasticity within epidermal (stem) cells and their respective niches, revealing for example wild-type epithelial cells, fibroblasts or immune-cell subsets as critical in preventing cancer formation and malignant progression. It's the same cells, however, that can drive carcinogenesis. Therefore, understanding the abundance and molecular variation of cell types in health and disease, and how they interact and modulate the local signalling environment will thus be key for new therapeutic avenues in our battle against cancer.

Free-breathing radial volumetric interpolated breath-hold examination sequence and dynamic contrast-enhanced MRI combined with diffusion-weighted imaging for assessment of solitary pulmonary nodules.

OBJECTIVE: To test the performance of free-breathing Dynamic Contrast-Enhanced MRI (DCE-MRI) using a radial volumetric interpolated breath-hold examination (VIBE) sequence combined with diffusion-weighted imaging (DWI) for quantitative solitary pulmonary nodule (SPN) assessment. METHODS: A total of 67 SPN cases receiving routine MRI routine scans, DWI, and dynamic-enhanced MRI in our hospital from May 2017 to November 2018 were collected. These cases were divided into a malignant group and a benign group according to the characteristics of the SPNs. The quantitative DCE-MRI parameters (Ktrans, Kep, Ve) and apparent diffusion coefficient (ADC) values of the nodules were measured. RESULTS: The Ktrans and Kep values in the malignant group were higher than those in the benign group, while the ADC values in the malignant group were lower than those in the benign group. Furthermore, the Ktrans value of adenocarcinoma was higher than that of squamous cell carcinoma and small cell carcinoma (P < 0.05). The Ve value was significantly different between non-small cell carcinoma and small cell carcinoma (P < 0.05). With an ADC value of 0.98 × 10-3 mm2/s as the threshold, the specificity and sensitivity to diagnose benign and malignant nodules was 90.6% and 80%, respectively. CONCLUSION: High-temporal-resolution DCE-MRI using the r-VIBE technique in combination with DWI could contribute to pulmonary nodule analysis and possibly serve as a potential alternative to distinguish malignant from benign nodules as well as differentiate different types of malignancies.

Patient-Reported Quality of Life After Resection With Primary Closure for Oral Tongue Carcinoma.

OBJECTIVES/HYPOTHESIS: For early-stage oral tongue carcinoma and carcinoma in situ (ESOTCCIS), we evaluated patient-reported quality-of-life (QOL) outcomes following resection with primary closure (R-PC). STUDY DESIGN: Retrospective review at an academic cancer center. METHODS: Thirty-nine ESOTCCIS patients (Tis, T1, T2) who underwent R-PC without radiation completed the University of Washington Quality of Life Questionnaire Version 4 (UW-QOL) at least 6 months since R-PC (mean = 2.39 years; range = 0.5-6.7 years). We compared UW-QOL scores for pain, swallowing, chewing, speech, and taste to established normative population scores. Multivariable regression analysis evaluated factors associated with QOL impairment. RESULTS: ESOTCCIS patients who underwent R-PC in comparison to the normative population reported significantly worse mean speech (87.7 vs. 98, P < .001) and taste (85.6 vs. 95, P = .002) scores and no significant differences in mean pain (91.7 vs. 86, P = .96), swallowing (100 vs. 98, P = .98), chewing (97.4 vs. 94, P = .98) scores. For speech and taste, 59% (23/39) reported no postoperative change from baseline, whereas 41% (16/39) and 35.9% (14/39) reported mild impairment, respectively. Overall, postoperative QOL was reported as good, very good, or outstanding by 87.2% (34/39). Higher American Society of Anesthesiologists class, cT1 compared to CIS, and ventral tongue involvement were independently associated with worse speech. Age < 60 years was independently associated with worse taste. CONCLUSIONS: ESOTCCIS patients who undergo R-PC without radiation can expect long-term swallowing, chewing, and pain to be in the normative range. Although a majority of patients can expect to achieve normative speech and taste outcomes, R-PC carries the risks of mild speech and/or taste impairments. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:312-318, 2021.

Predictors of Stricture and Swallowing Function Following Salvage Laryngectomy.

BACKGROUND: Long-term functional outcomes are poorly characterized for salvage laryngectomy. We identified predictors of esophageal stricture and swallowing function after salvage laryngectomy in a large cohort. METHODS: A retrospective study of 233 patients who underwent salvage total laryngectomy for recurrent/persistent squamous cell carcinoma of the larynx or hypopharynx after radiation (XRT) or chemoradiation (CRT) was performed. Primary outcomes were esophageal dilation within 1 year, time to dilation, and gastrostomy tube dependence. Multivariate logistic and Cox regressions were used for statistical analysis. RESULTS: Dilation was performed in 29.9% of patients. Dilation was twice as likely in patients with post-operative fistula compared to those without (Hazard Ratio (HR) 2.10, 95% Confidence Interval (CI) 1.06-4.13, P = .03). Every year between XRT/CRT and salvage was associated with 10% increase in dilation (HR 1.09, 95% CI 1.03-1.17, P = .01). No factors were associated with dilation by 1 year. About 10% of patients were at least partially gastrostomy tube-dependent 1 year post-operatively. At last follow-up (median 29 months), this rate was 13%. Patients with supraglottic recurrence had an increased risk of gastrostomy tube dependence at 1 year compared to glottic (OR 16.7, 95% CI 1.73-160, P = .02). For every 10 pack years pre-salvage, the OR of requiring tube feeds at last follow-up was 1.24 (95% CI 1.04-1.48, P = .02). CONCLUSIONS: Fistula and pre-salvage smoking were associated with stricture post-salvage laryngectomy. No factors were associated with dilation by 1 year. Supraglottic recurrence and smoking were associated with gastrostomy tube dependence. These findings are important for pre-operative counseling prior to salvage laryngectomy. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 131:1229-1234, 2021.