Wenlu Li

This study aimed to compare the clinical response of suprabony and intrabony defects to non-surgical periodontal therapy (NSPT) and evaluate the influence

Background: Conventional classification of surgical margins is inadequate for head and neck squamous cell carcinoma (HNSCC) treated with neoadjuvant immunochemotherapy (NICT), as it fails to capture the complex biological changes in the tumor microenvironment. This study aimed to develop a novel definition of a negative margin. Methods: We conducted a retrospective analysis of treatment-naïve, HPV-negative HNSCC patients who completed NICT followed by surgery. Surgical margins underwent multi-modal assessment, including histopathology (tertiary lymphoid structures), tumor burden (Pan-CK, Ki-67), molecular profiling (driver mutations, PD-L1 RNA), and immune contexture (CD8+/FoxP3+ ratio, Granzyme B). A Margin Risk Index (MRIx) was developed by weighting these domains based on their prognostic impact for locoregional control (LRC) and distant metastasis-free survival (DMFS). The MRIx was externally validated in an independent cohort. Results: The study included a training cohort of 144 patients and an independent validation cohort of 100 patients. The MRIx integrated four domains into a continuous score, stratifying patients into low, intermediate, and high-risk categories. The MRIx significantly outperformed traditional margin assessment, with superior discrimination for both LRC (C-index=0.72) and DMFS (C-index=0.75). External validation confirmed its prognostic power, demonstrating significant risk stratification (log-rank p<0.001 for both LRC and DMFS) and an independent hazard ratio for high-risk patients (HR = 2.95 for LRC; HR = 3.22 for DMFS, both p<0.001). Conclusion: The proposed MRIx provides a biologically-grounded tool that redefines margin status following NICT. It accurately identifies patients at high risk of recurrence who may benefit from treatment intensification and those with low-risk margins suitable for de-escalation, enabling personalized adjuvant therapy.

Background: To clarify the impact of the number of positive lymph nodes (LNs) on the prognosis of parotid mucoepidermoid carcinoma (MEC).Methods: Patients who underwent neck dissection for parotid MEC were retrospectively enrolled. The primary outcome variable was overall survival (OS). Associations between OS and LN factors, including the AJCC N stage, intraparotid LN metastasis, number of positive LNs, LN size, and extranodal extension (ENE), were evaluated using Cox proportional hazard regression analyses.Results: A total of 720 patients were included with a mean age of 56 ± 16 years. There was no additional survival compromise until two positive LNs were presented. After adjusting for the number of positive LNs, intraparotid LN metastasis, ENE, and LN size were not related to prognosis. Our proposed N stage based on the number of metastatic LNs (0/1 vs. 2–4 vs. 5+) showed a superior C‐index to the AJCC N stage in OS prediction.Conclusion: Quantitative LN burden was an important determinant of prognosis, and the proposed N stage provided better OS stratification than the AJCC N stage.

Objectives: To explore the possible risk factors of orocutaneous fistula (OCF) development in free flap reconstruction of the tongue/floor of the mouth (TFOM).Methods: Data of patients who underwent free flap reconstruction of the TFOM were retrospectively analyzed. The association between clinicopathologic variables and OCF occurrence was analyzed using univariate and multivariate analyses.Results: Altogether, 469 patients were enrolled. OCF occurred in 43 patients with a rate of 9.2%. The univariate analysis revealed the negative effects of smoking, preoperative albumin level, cachexia, T4 stage, neck dissection, entire resection of the floor of the mouth (FOM), segmental mandibulectomy, and surgical site infection on OCF occurrence. The multivariate analysis confirmed the independence of cachexia (p<0.001, 4.386[1.883–9.472]), tumor stage (p<0.001, 2.738[1.482–6.629]), entire FOM resection (p<0.001, 6.332[2.110–14.432]), and surgical site infection (p<0.001, 5.376[1.998–11.218]) in affecting the OCF development.Conclusions: OCF development following free flap reconstruction of the TFOM was relatively uncommon, but significantly associated with presence of cachexia, T4 stage, entire FOM resection, and surgical site infection.

Oral squamous cell carcinoma (OSCC) is a common malignant cancer with unfavorable prognosis, and the epithelial‐to‐mesenchymal transition (EMT) is a critical contributor to OSCC metastasis. Recently, we have shown that sirtuin 7 (Sirt7) is associated with EMT and OSCC metastasis by acetylating small mother against decapentaplegic 4 (Smad4). Nonetheless, the mechanism of Sirt7 downregulation in OSCC cells remains unknown. This study analyzed the potential microRNAs that were predicted to regulate Sirt7 expression by online databases. We identified miR‐770 as an upstream regulator of Sirt7 that targets its 3′‐untranslated region. The expression of miR‐770 was observed to be negatively correlated with the mRNA expression of Sirt7 in metastatic OSCC tumors, and higher miR‐770 expression was correlated with poorer OSCC patient survival. Our in vitro data indicated that miR‐770 promoted OSCC cell migration and invasion, and this process was dependent on Sirt7/Smad4 signaling. Furthermore, in vivo metastasis experiments indicated that miR‐770 overexpression led to more prominent OSCC metastasis and downregulated Sirt7 expression. Collectively, our results revealed a new role of Sirt7 downregulation in metastatic OSCC and suggested that miR‐770 is a potential target in counteracting OSCC metastasis.

Background. The aim of this study was to evaluate quality of life of free anterolateral thigh flap (ALTFF) for reconstruction of tissue defects of total or near-total glossectomy. Methods. Quality of life was assessed by means of the University of Washington Quality of Life (UW-QOL) and the 14-item Oral Health Impact Profile (OHIP-14), after 12 months postoperatively. Results. 65 of 79 questionnaires were returned (82.27%). In the UW-QOL, the best-scoring domain was “shoulder,” whereas the lowest scores were for “chewing” and “pain.” In the OHIP-14, the lowest-scoring domain was “handicap,” followed by “Social disability” and “Psychological disability.” Conclusion. Free anterolateral thigh perforator flaps for reconstruction of total or near-total glossectomy defects after cancer resection would have significantly influenced the patients’ oral functions and quality of life.

Background: Claudin 8 (CLDN8), an integral membrane protein that constitutes tight junctions in cell membranes, was recently implicated in tumor progression. However, its roles in colorectal cancer (CRC) progression and metastasis remain unknown. Methods: In this study, we examined the effect of CLDN8 on the progression of CRC, including cell proliferation, migration, and invasion, and determines its underlying molecular mechanism using in vitro CRC cell lines and in vivo mouse xenograft models. Results: We found that CLDN8 expression in human CRC tissues was significantly higher than that in adjacent normal tissues. The knockdown of CLDN8 markedly suppressed the proliferation, migration, and invasion of SW480 and HT-29 CRC cells, whereas the overexpression of CLDN8 notably promoted tumor progression in SW480 and HT-29 CRC cells. Mechanistic studies revealed that CLDN8 upregulated p-ERK (p-PKB/AKT) and MMP9 in CRC cells. Notably, the MAPK/ERK inhibitor PD98095 dramatically attenuated the effects of CLDN8 on p-ERK and MMP9. Moreover, PD98095 remarkably blocked the tumor-promoting activity of CLDN8. The knockdown of CLDN8 also inhibited the in vivo tumor growth in a nude mouse xenograft model. Collectively, CLDN8 promoted CRC cell proliferation, migration, and invasion, at least in part, by activating the MAPK/ERK signaling pathway. Conclusion: These findings suggest that CLDN8 exhibits an oncogenic effect in human CRC progression.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and has a poor prognosis. The epithelial-to-mesenchymal transition (EMT) is crucial for increasing the metastasis of OSCC. Recently, studies have indicated that sirtuin7 (SIRT7) is implicated in tumor genesis; however, the potential role of SIRT7 in the EMT and metastasis of OSCC has not been reported. We investigated the cellular responses to SIRT7 silencing or overexpression in OSCC cell lines by wound healing assay, migration and invasion assay, western blotting, immunofluorescence and immunohistochemistry. In the present study, we found that SIRT7 was significantly downregulated in OSCC cell lines and human OSCC/OSCC tissues with lymph node metastasis. Overexpression of SIRT7 decreased the proliferation and invasion of OSCC cells in vitro, whereas SIRT7 knockdown significantly increased OSCC cell growth and invasion. Upregulation of SIRT7 concomitantly increased the expression of E-cadherin, and decreased the expression of mesenchymal markers. SIRT7 overexpression also reduced the level of acetylated SMAD4 in OSCC cells. Moreover, SIRT7 overexpression significantly inhibited OSCC lung metastasis in vivo. Together, these findings suggested that SIRT7 suppressed EMT in OSCC metastasis by promoting SMAD4 deacetylation.