To investigate T lymphocyte, neutrophil/lymphocyte ratio (NLR) and their impact on patients with radiation-induced oral mucositis (RIOM) after intensity-modulated radiotherapy for head and neck cancer. The clinical data of 148 patients diagnosed with head and neck cancer from January 2016 to January 2019 were retrospectively analyzed. Patients were divided into RIOM group (n = 42 cases) and non-RIOM group (n = 106 cases), based on whether they developed RIOM after intensity-modulated radiation therapy. The T lymphocyte and NLR of the 2 groups were analyzed before and after treatment; The correlation between T lymphocyte and NLR in RIOM group was analyzed. We used RTOG grading system to evaluate and scale the RIOM. The relationship between the grade of RIOM, T lymphocyte and NLR in RIOM group was analyzed. After treatment, the proportion of CD3 +, CD4 +, and CD8 + T lymphocytes in the 2 groups after treatment were decreased, and the RIOM group was significantly lower than non-RIOM group, P < .05. NLR in RIOM group was significantly higher than that in non-RIOM group, P < .05. The data of overall survival showed no significant differences between 2 groups (HR = 0.82, 95% CI: 0.43-1.59). Compared with RIOM group, patients in non-RIOM group showed a longer progress-free survival (HR = 0.57, 95% CI: 0.33-0.99). In RIOM group, NLR was negatively correlated with CD3 + (r = -0.433, P = .004), CD4 + (r = -0.644, P < .001) and CD8 + T cells (r = -0.665, P < .001). RIOM was positively correlated with NLR (R = 0.621, P < .001), negatively correlated with CD4 + T cell ratio (r = -0.449, P = .003) and CD8 + T cell ratio (r = -0.307, P = .048), but RIOM did not correlate with CD3 + T cell ratio (r = -0.225, P = .152). For patients with RIOM after intensity-modulated radiotherapy for head and neck cancer, T lymphocyte showed a downward trend, and NLR showed an upward trend. In addition, T lymphocyte and NLR are closely related to the RIOM, indicating that clinicians should be aware of the importance of T lymphocyte and NLR on patients received radiotherapy.

BACKGROUND: In free jejunum transfer, knowing the ischemic tolerance time of the jejunum is crucial. It helps determine the need for reharvesting if an unexpected situation prolongs the ischemic time. The current ischemic tolerance time in humans is unknown. We investigated the relationship between ischemic time and postoperative complications in head and neck cancer patients who underwent free jejunum transfer.
METHODS: The study included 76 patients with available medical records out of 103 patients who underwent free jejunum transfer between 2009 and 2023. The association between the surgical procedure, including ischemic time, and patient\'s background, and flap engraftment, stenosis of the intestinal anastomosis, the swallowing function, and other complications was investigated.
RESULTS: The ischemic time for jejunal flaps ranged from 1 h 24 min to 6 h, with a mean of 197 ± 55.5 min. In 72 patients, the jejunum was successfully engrafted, but vascular occlusion occurred in another four patients. In three of these patients, jejunal necrosis occurred, and there was no specific trend in ischemic time. Stenosis of the intestinal anastomosis occurred in 17 cases (22%), with ischemic time (≥3 h) and age (≥75 years) being significant factors for stenosis (ischemic time: 30% vs. 10%, p = 0.048, age: 50% vs. 15%, p < 0.01). No significant correlations were observed with other complications or the swallowing function.
CONCLUSIONS: There was no specific trend between ischemic time and jejunal survival rate, indicating that an ischemic time within 6 h may not have affected engraftment. Although we have recently performed intestinal anastomosis prior to vascular anastomosis, the choice of surgical technique should be adapted to the patient\'s age and background.

BACKGROUND: Recent randomized phase III trials have demonstrated the efficacy of anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in treating patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). However, a large proportion of such patients still have poor response. This study aimed to identify biomarkers for predicting anti-PD-1 ICI treatment outcomes .
METHODS: We retrospectively analyzed 144 patients with RMHNSCC who received anti-PD-1 ICIs after progression to platinum-based chemotherapy between January 2017 and December 2022 at Kaohsiung Chang Gung Memorial Hospital. Data on clinicopathological parameters, albumin levels, calcium levels, and other pretreatment peripheral blood biomarkers, including total lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI) were collected and correlated with the treatment outcome of anti-PD-1 ICIs.
RESULTS: Low tumor proportion score (TPS), low combined positive score (CPS), NLR ≥ 5, PLR ≥ 300, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly correlated with poor response of ICIs. The overall response rates were 25% and 3% in patients with calcium < 10 mg/dL and calcium ≥ 10 mg/dL, respectively (P = 0.007). The overall response rates were 6% and 33% in patients with albumin < 4 g/dL and albumin ≥ 4 g/dL, respectively (P < 0.001). Univariate survival analysis showed that low TPS, low CPS, NLR ≥ 5,, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly associated with worse progression-free survival (PFS) and inferior overall survival (OS). Multivariate analysis revealed that calcium ≥ 10 mg/dL and albumin < 4 g/dL were independent poor prognosticators for worse PFS and inferior OS. The two-year OS rates were 26% and 9% in patients with calcium < 10 mg/dL and ≥ 10 mg/dL, respectively (P < 0.001). The two-year OS rates were 10% and 33% in patients with albumin < 4 g/dL and ≥ 4 g/dL, respectively (P < 0.001).
CONCLUSIONS: Hypercalcemia and hypoalbuminemia can potentially predict poor treatment outcomes of anti-PD-1 ICIs in patients with RMHNSCC. Blood calcium and albumin levels may be helpful in individualizing treatment strategies for patients with RMHNSCC.

OBJECTIVE: Metallic taste (MT) is frequently observed during head and neck cancer treatments, but very little is known about its impact on nutritional status. The aim of this study was to explore the impact of MT on the quality of life and nutritional status in patients with head and neck cancer expressing MT.
METHODS: Questionnaires on quality of life, MT, weight, and food intake were filled out by 44 patients with head and neck cancer before, during, and up to 1 year after their treatment. Patients were divided into two groups based on their reported experience of MT.
RESULTS: MT was commonly observed (n = 12, 27.2%), always during the treatment phase, and mostly linked with radiotherapy or radiochemotherapy. Reported MT intensity was moderate (n = 6, 40%) to high (n = 4, 26.7%). MT had a significant negative impact on quality of life linked to dysgeusia (p = 0.025). The negative impacts of MT on food intake and on weight were not significant, possibly due to a combination of sample size, dropouts, and duration of observation. Further research in this area could provide additional insights into how to better address the issue related to MT and enhance the quality of care provided to this patient population.
CONCLUSIONS: Metallic taste, experienced by 27.2% of the 44 patients with head and neck cancer, contributes to dysgeusia and results in a significant decline in quality of life associated with dysgeusia.
BACKGROUND: ClinicalTrials.gov trial registration number: NCT03558789.

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Immune checkpoint inhibitors are approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) but the response rate is only 13-18%. For an effective antitumor immune response, trafficking of immune cells to the tumor microenvironment (TME) is essential. We aimed to better understand immune cell migration as well as the involved chemokines in HNSCC. A transwell assay was used to study immune cell migration toward TME-conditioned medium. While T cell migration was not observed, conventional dendritic cell (cDC) migration was induced by TME-conditioned media. cDC migration correlated with various proteins in the TME secretome. CCL8, CXCL5, CCL13 and CCL7 were tested in validation experiments and addition of these chemokines induced cDC migration. Using single cell RNA-sequencing, we observed expression of CCL8, CXCL5, CCL13 and CCL7 in cancer-associated fibroblasts (CAFs). Depleting fibroblasts led to reduced cDC migration. Thus CAFs, while often seen as suppressors of antitumor immunity, play a role in attracting cDCs toward the head and neck cancer TME, which might be crucial for effective antitumor immunity and response to therapies. Indeed, we found RNA expression signatures of the indicated chemokines, cDC and CAF subpopulations, to be significantly higher in baseline tumor specimen of patients with a major pathological response to pre-surgical anti-PD-1 treatment compared to non-responding patients.

The aim of this study was evaluated the influence of radiation as well as of new formulations of artificial saliva on the development of root dentin lesions. Bovine root samples were divided into: irradiated (70 Gy) dentin or not; the type of biofilm (from irradiated patient-experimental or non-irradiated patient-control) and the type of artificial saliva (for the condition irradiated dentin/biofilm from irradiated patient): Control Artificial Saliva (inorganic); Control Saliva + 1 mg/ml hemoglobin; Control Saliva +0.1 mg/ml cystatin; Control Saliva + hemoglobin + cystatin; Bioextra (positive control) and deionized water (DiW, negative control) (n = 12/group). Biofilm was produced using human biofilm and McBain saliva (0.2 % of sucrose, 37o C and 5 % CO2); the treatments were done 1x/day, for 5 days. Colony-forming units (CFU) counting was performed; demineralization was quantified by transversal microradiography. Two-way ANOVA/Bonferroni or Sidak test for the comparison between biofilm x dentin and ANOVA/Tukey or Kruskal-Wallis/Dunn for comparing artificial saliva were done (p < 0.05). The type of biofilm had no influence on CFU and demineralization. Sound dentin under control biofilm presented the lowest Lactobacillus ssp. and Streptococcus mutans CFU and the lowest mean mineral loss (R) (25.6 ± 2.2; 23.7 ± 2.9 %) compared to irradiated dentin (26.1 ± 2.8; 28.1 ± 3.3, p < 0.004) for both types of biofilms (experimental and control, respectively). Bioextra was the only artificial saliva that reduced R (10.8 ± 2.5 %) and Lesion Depth (LD) (35 ± 15 μm) compared to DiW (17.3 ± 3.3 %, 81 ± 18 μm, p < 0.0001). Irradiation has impact on caries development; the experimental saliva were unable to reduce its occurrence.

HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.

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