(18)F-FAMT PET showed higher specificity for detecting malignant lesions than (18)F-FDG PET. The uptake of (18)F-FAMT by OSCC cells can be determined by the presence of LAT1 expression and tumour cell proliferation.

Ferroptosis is a newly recognized mechanism of regulated cell death. It was reported to be highly associated with immune therapy and chemotherapy. However, its mechanism of regulation in the tumor microenvironment (TME) and influence on oral squamous cell carcinoma (OSCC) therapy are unknown. We identified a ferroptosis-specific gene-expression signature, an FPscore, developed by a principal component analysis (PCA) algorithm to evaluate the ferroptosis regulation patterns of individual tumor. Multi-omics analysis of ferroptosis regulation patterns was conducted. Three distinct ferroptosis regulation subtypes, which linked to outcomes and the clinical relevance of each patient, were established. A high FPscore of patients with OSCC was associated with a favorable prognosis, a ferroptosis-related immune-activation phenotype, potential sensitivities to the chemotherapy and immunotherapy. Importantly, a high FPscore correlated with a low gene copy number burden and high immune checkpoint expressions. We validated the prognostic value of the FPscore using independent immunotherapy and pan-cancer cohorts. Comprehensive evaluation of individual tumors with distinct ferroptosis regulation patterns provides new mechanistic insights, which may be clinically relevant for the application of combination therapies in OSCC.

The accurate depiction of both biologic and anatomic profiles of tumors has long been a challenge in PET imaging. An inflammation, which is innate in the carcinogenesis of oral squamous cell carcinoma (OSCC), frequently complicates the image analysis because of the limitations of 18 F-FDG and maximum standardized uptake values (SUV max ). New PET parameters, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as well as 18 Ffluoro-α-methyltyrosine ( 18 F-FAMT), a malignancy-specific amino acid-based PET radiotracer, are considered more comprehensive in tumor image analysis. Here, we showed the substantial effects of the intratumoral inflammatory process on 18 F-FDG uptake and further study the possibility of MTV and TLG to predict both tumor biology (proliferation activity) and anatomy (pathologic tumor volume). Methods: 18 F-FDG and 18 F-FAMT PET images from 25 OSCC patients were analyzed. SUV max on the tumor site was obtained. PET volume computerized-assisted reporting was used to generate a volume of interest to obtain MTV and TLG for 18 F-FDG and total lesion retention (TLR) for 18 F-FAMT. The whole tumor dissected from surgery was measured and sectioned for pathologic analysis of tumor inflammation grade and Ki-67 labeling index. Results: The high SUV max of 18 F-FDG was related to the high inflammation grade. The SUV max ratio of 18 F-FDG to 18 F-FAMT was higher in inflammatory tumors (P , 0.05) whereas the corresponding value in tumors with a low inflammation grade was kept low. All 18 F-FAMT parameters were correlated with Ki-67 labeling index (P , 0.01). Pathologic tumor volume predicted from MTV of 18 F-FAMT was more accurate (R 5 0.90, bias 5 3.4 ± 6.42 cm 3 , 95% confidence interval 5 0.77-6.09 cm 3 ) than that of 18 F-FDG (R 5 0.77, bias 5 8.1 ± 11.17 cm 3 , 95% confidence interval 5 3.45-12.67 cm 3 ). Conclusion: 18 F-FDG uptake was overestimated by additional uptake related to the intratumoral inflammatory process, whereas 18 F-FAMT simply accumulated in tumors according to tumor activity as evaluated by Ki-67 labeling index in OSCC.

(18)F-FAMT PET/CT was useful and more specific than MRI or (18)F-FDG PET/CT in the detection of bone marrow invasion of OSCC and may contribute to minimize the extent of resection in oral surgery patient.

Purpose To evaluate the expression of alanine-serine-cysteine-transporter 2 (ASCT2) and L-type amino acid transporter1 (LAT1) in prostate cancer (PCa) and their impact on uptake of 18 F-1-amino-3-fluorocyclobutane-1-carboxylic acid ( 18 F-fluciclovine) which is approved for the detection of recurrent PCa. Methods Twenty-five hormone-naïve patients with histologically confirmed PCa underwent PET/CT before prostatectomy. Dynamic imaging was performed immediately after injection of 368 ± 10 MBq of 18 F-fluciclovine and the uptake in PCa was expressed as SUV max at six sequential 4-min time frames and as tracer distribution volume ( V T ) using Logan plots over 0–24 min. The expression of ASCT2 and LAT1 was studied with immunohistochemistry (IHC) on a tissue microarray (TMA) containing three cores per carcinoma lesion. The TMA slides were scored independently by two trained readers based on visual intensity of ASCT2/LAT1 expression on a four-tiered scale. The correlations between ASCT2/LAT1 staining intensity, SUVmax/ V T , and Gleason grade group (GGG) were assessed using Spearman’s rank correlation coefficient ( ρ ). Results Forty tumor foci (> 0.5 mm in diameter, max. 3 per patient) were available for TMA. In visual scoring, low, moderate, and high staining intensity of ASCT2 was observed in 4 (10%), 24 (60%), and 12 (30%) tumors, respectively. No tumors showed high LAT1 staining intensity while moderate intensity was found in 10 (25%), 25 (63%) showed low, and the remaining 5 (12%) were negative for staining with LAT1. Tumors with GGG > 2 showed significantly higher uptake of 18 F-fluciclovine and higher LAT1 staining intensity ( p < 0.05). The uptake of 18 F-fluciclovine correlated significantly with LAT1 expression ( ρ = 0.39, p = 0.01, for SUV max at 2 min and ρ = 0.39, p = 0.01 for V T ). No correlation between ASCT2 expression and 18 F-fluciclovine uptake or GGG was found. Conclusions Our findings suggest that LAT1 is moderately associated with the transport of 18 F-fluciclovine in local PCa not exposed to hormonal therapy. Both high and low Gleason grade tumors express ASCT2 while LAT1 expression is less conspicuous and may be absent in some low-grade tumors. Our observations may be of importance when using 18 F-fluciclovine imaging in the planning of focal therapies for PCa.

Objectives L-3-[ 18 F]-Fluoro-α-methyl tyrosine (FAMT), an amino acid positron emission tomography (PET) tracer, complements [ 18 F]-fluorodeoxyglucose (FDG) in the diagnosis of malignancies. We compared the predictive ability of FAMT PET versus FDG PET regarding metastatic oral squamous cell carcinoma (OSCC) outcomes for distant metastasis, including lymph node metastasis, and identified the relevant metabolic parameters for each. Methods We enrolled 160 patients with OSCC who underwent PET/computed tomography using FDG and FAMT before treatment. Outcomes were assessed using clinicopathological characteristics such as the standardized uptake value (SUV max , SUV peak ), metabolic tumor volume (MTV), and total lesion glycolysis or total lesion retention. Univariate and multivariate Cox proportional hazards models were used to identify the independent predictors of disease-free survival (DFS) and overall survival (OS) during an average follow-up time of 1401.7 and 1646.0 days, respectively. Areas under the receiver operating characteristic curves were analyzed for the accuracy and predictive value of imaging parameters. Results Clinical parameters (excluding age) and PET metabolic parameters were significantly associated with OS. Multivariate analysis showed that an infiltrative growth pattern [ p = 0.034, hazard ratio (HR) = 2.30], and the FDG-measured SUV peak ( p = 0.045, HR = 2.45) were independent risk factors for DFS and that lymph node metastasis ( p = 0.03, HR = 2.57) and the FAMT-measured MTV ( p = 0.004, HR = 3.65) were independent risk factors for OS. Conclusions In patients with OSCC, FDG PET predicted DFS, whereas FAMT predicted OS. The two PET tracers, combined with clinical parameters, provide complementary, outcome-related diagnostic information in OSCC.

Background/Aim: Postoperative pneumonia is a serious complication of major oesophageal surgery. We aimed to clarify the association between the degree of improvement in oral hygiene by perioperative oral care and postoperative pneumonia in oesophageal cancer patients. Patients and Methods: Oesophageal cancer patients (n=129) who underwent esophagectomy received perioperative oral care. Their oral hygiene was evaluated using the Oral Assessment Guide (OAG). The relationship between perioperative OAG scores and postoperative complications was analysed. Results: The average OAG scores before starting oral care, pre-operation, and post-operation were 11. 0±1.7, 9.1±1.5, and 11.2±3.0, respectively (p<0.001). An increase in preoperative OAG scores was independently associated with postoperative pneumonia on multivariate analysis (p=0.027). Conclusion: Preoperative oral care improves oral hygiene in patients undergoing oesophageal cancer surgery. No improvement in oral hygiene despite preoperative oral care was an independent predictor of postoperative pneumonia.Oesophageal cancer (EC) is the sixth most common cause of cancer-related death worldwide (1). Although the development of various treatment methods, such as surgical techniques, neoadjuvant therapy, adjuvant therapy, and perioperative management have improved the prognosis of patients with EC (2-8), esophagectomy is correlated with high morbidity and mortality rates (9). Postoperative complications adversely affect the outcome after esophagectomy; hence, it is essential to decrease postoperative complications to improve prognosis (10-12). Among postoperative complications, postoperative pneumonia is one of the most frequent and serious complications of major oesophageal surgery. Perioperative oral care has been reported to be useful in preventing postoperative pneumonia (13,14). However, in these studies, patients who received oral care were compared with those who did not. No studies have analysed the association between oral hygiene and postoperative outcomes among patients who received oral care. Thus, little is known about the association between the degree of improvement in oral hygiene and postoperative pneumonia in EC patients.The Oral Assessment Guide (OAG), developed by Eilers et al., is an oral health assessment tool widely used by dentists, dental hygienists, and nurses (15,16). Knöös et al. reported the usefulness of the OAG in patients receiving radiotherapy to the head and neck region (17), and Saito et al. showed the effectiveness of the OAG for evaluating chemotherapy-induced oral mucositis in breast cancer patients (18). A unique feature of the OAG is that is allows the assessment of the degree of oral hygiene using a numerical value.In this study, we hypothesised that the degree of oral hygiene is associated with the development of postoperative pneumonia in EC patients. To investigate this hypothesis, we examined the relationship between the degree of oral hygiene, as evaluated by the OAG, and the development of postoperative complications.

The pecan weevil, Curculio caryae (Horn) (Coleoptera: Curculionidae), is a key pest of pecans Carya illinoinensis ([Wangenh.] K. Koch) (Fagales: Juglandaceae). Control recommendations rely on broad spectrum chemical insecticides. Due to regulatory and environmental concerns, effective alternatives for C. caryae control must be sought for pecan production in conventional and organic systems. We explored the use of microbial biopesticides for control of C. caryae in Georgia pecan orchards. Three experiments were conducted. The first investigated an integrated microbial control approach in an organic system at two locations. Three microbial agents, Grandevo (based on byproducts of the bacterium Chromobacterium subtsugae Martin, Gundersen-Rindal, Blackburn & Buyer), the entomopathogenic nematode Steinernema carpocapsae (Weiser), and entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin, were applied to each treatment plot (0.6 ha) at different times during the season. A second experiment compared the effects of S. carpocapsae and B. bassiana applied as single treatments relative to application of both agents (at different times); survival of C. caryae was assessed approximately 11 mo after larvae were added to pots sunk in an organic pecan orchard. In a conventional orchard (with 1.0 ha plots), the third experiment compared Grandevo applications to a commonly used regime of chemical insecticides (carbaryl alternated with a pyrethroid). All experiments were repeated in consecutive years. The combined pest management tactic (experiment 1) reduced C. caryae infestation relative to non-treated control plots in both locations in 2014 and one of the two locations in 2015 (the other location had less than 1% infestation). In experiment 2, no differences among combined microbial treatments, single-applied microbial treatments or different numbers of application were observed, yet all microbial treatments reduced C. caryae survival relative to the control. In the third experiment, both Grandevo and standard chemical insecticide applications resulted in lower weevil infestation than the control (both years) and there was no difference between the insecticide treatments in 2014 although the chemical insecticide regime had slightly lower infestation in 2015. These results provide evidence that microbial biopesticides can substantially reduce pecan weevil infestations in organic and nonorganic systems.