Effect of oral intake initiation-establishment interval on hospital stay after oral cancer surgery.

OBJECTIVES: To clarify the effect of the period between initiation of oral intake (IOI) and establishment of oral intake (EOI) on length of hospital stay. METHODS: This retrospective study included postoperative oral cancer patients. The number of days from surgery to IOI and EOI and between IOI and EOI were recorded. We performed intergroup comparisons and Cox regression analysis using the number of days until discharge, representing hospital stay length as the dependent variable. RESULTS: The median number of days between IOI and EOI was 3 days for eligible patients and 4.5 and 1.5 for older and younger patients, respectively. The median number of days from surgery to IOI was 15 days. There was a significant correlation between the period between IOI and EOI and the length of hospital stay (r = 0.40, p < 0.01). The period between IOI and EOI was a significant independent variable for the length of hospital stay (HR [95% confidence interval] = 0.45 [0.28-0.72]). CONCLUSIONS: Shortening the IOI to EOI intervals was identified as an independently associated factor for shortening hospital stay, even in older postoperative patients with dysphagia who struggled with early oral intake initiation. Professional, step-by-step dysphagia rehabilitation tailored to the patient's condition yields beneficial outcomes.

Retrospective analysis of odontogenic myxoma and odontogenic myxofibroma in the oral and maxillofacial region: a fibrous tissue-related differentiation.

The clinical differences between odontogenic myxoma (OM) and odontogenic myxofibroma (OMF), and the clinical significance of their classifications, remain unclear. This study reviewed the clinicopathological characteristics of patients with OM or OMF and evaluated the fibrous component of the specimens. Medical records of 21 patients with OM or OMF who underwent tumour resection were reviewed. The percentage of fibrous tissue on the representative sections was evaluated using haematoxylin and eosin- and Masson's trichrome-stained specimens. Histopathological diagnoses included 11 OMs and 10 OMFs with no tumour recurrence except for two cases in which the dredging method was applied. More cortical bone perforation was observed in OM than in OMF cases, without significant differences. Location-locularity and apparent diffusion coefficient value (ADC)-cortical bone perforation were significantly correlated in all OM and OMF cases. The percentage of fibrous tissue in specimens showed bimodal distribution bordered by 45%. There was a significant association between diagnosis based on 45% fibrous tissue criterion and the final pathological diagnosis. Our study showed a tendency for cortical bone perforation in OM compared to OMF and correlation between ADC and cortical bone perforation. According to the histopathological analyses, the fibrous component of each case was bimodal with 45%, which may be a criterion to distinguish between OM and OMF. Accumulating knowledge, such as significant differences in prognosis, may allow for minimal surgical treatment options based on the diagnosis according to this novel histopathological criterion.

Maximum standardized uptake value in 11C-methionine positron emission tomography may predict the prognosis of patients with oral squamous cell carcinoma.

The present study aimed to elucidate the correlation between the uptake of 11C-methionine (MET) by a primary tumor and the survival of patients with oral squamous cell carcinoma (OSCC). This study enrolled 31 patients who underwent radical surgery for OSCC. The patients underwent pretreatment MET-positron emission tomography (PET) scanning. We analyzed correlations between the maximum standardized uptake value (SUVmax) of MET-PET in a primary tumor and the clinicopathological features. Further, we compared overall survival (OS), disease-specific survival (DSS), and loco-regional recurrence (LRR) rates between the two groups according to SUVmax of MET-PET. SUVmax of MET-PET in a primary tumor was higher in patients with advanced T-classification and advanced clinical stage, with significant differences (P = 0.001 and P = 0.016, respectively). The patients with SUVmax of MET-PET ≥ 4.4 showed significantly lower DSS rates and higher LRR rates than those with SUVmax of < 4.4 (P = 0.015 and P = 0.016, respectively). SUVmax of MET-PET and OS rates showed no significant correlation (P = 0.073). The present study revealed that SUVmax of MET-PET may predict clinical outcomes and prognosis in patients with OSCC who underwent radical surgery.

Significance of radiation therapy in the myxoid round-cell liposarcoma treatment regimen.

BACKGROUND AND PURPOSE: Because myxoid liposarcomas are more radiosensitive than other soft tissue sarcomas, there have been several reports of 50 Gy preoperative radiation therapy combined with surgery, but the wound complication rate is reportedly high. We have performed preoperative irradiation at a reduced dose of 40 Gy and definitive radiation therapy for unresectable cases. This study aimed to report the tumor reduction rate and oncological results with a reduced dose of preoperative irradiation and the outcome of definitive irradiation for unresectable cases. MATERIALS AND METHODS: Forty-one patients with myxoid liposarcoma treated in our institution between 2002 and 2021 were included. We examined the tumor volume shrinkage rate with preoperative radiation, compared complications and oncological outcomes between preoperative radiation and surgery-only cases, and investigated the prognosis and tumor shrinkage of definitive radiation cases. RESULTS: The total dose irradiated was 40 Gy except in two cases. The mean tumor volume reduction rate was 52.0%. A decreased dose of preoperative radiation did not worsen clinical outcomes with fewer complications. The total dose of definitive radiation was approximately 60 Gy. The mean tumor volume reduction rate was 55.0%. The tumor shrinkage maintenance rate was 100% in a median follow-up period of 50.5 months. CONCLUSION: Preoperative radiation therapy for myxoid liposarcoma near vital organs is a good approach because even with a reduced dose of 40 Gy, significant tumor reduction and excellent results were achieved. Definitive radiation therapy is the recommended treatment for older patients with serious comorbidities or inoperable patients.

Transforming growth factor-ß signals promote progression of squamous cell carcinoma by inducing epithelial-mesenchymal transition and angiogenesis.

At present, the molecular mechanisms driving the progression and metastasis of oral squamous cell carcinoma (OSCC) remain largely uncharacterized. The activation of transforming growth factor-ß (TGF-ß) signaling in the tumor microenvironment has been observed in various types of cancer and has been implicated their progression by enhancing the migration and invasion of epithelial cancer cells. However, its specific roles in the oral cancer progression remain unexplored. In this study, we examined the effects of TGF-ß signaling on the murine squamous cell carcinoma, SCCVII cells in vitro and in vivo. The incubation of SCCVII cells with TGF-ß induced the activation of TGF-ß signals and epithelial-mesenchymal transition (EMT). Notably, the motility of SCCVII cells was increased upon the activation of the TGF-ß signaling. RNA sequencing revealed upregulation of genes related to EMT and angiogenesis. Consistent with these in vitro results, the inhibition of TGF-ß signals in SCCVII cell-derived primary tumors resulted in suppressed angiogenesis. Furthermore, we identified six candidate factors (ANKRD1, CCBE1, FSTL3, uPA, TSP-1 and integrin ß3), whose expression was induced by TGF-ß in SCCVII cells, and associated with poor prognosis for patients with head and neck squamous cell carcinoma. These results highlight the role of TGF-ß signals in the progression of OSCC via multiple mechanisms, including EMT and angiogenesis, and suggest novel therapeutic targets for the treatment of OSCC.

Complications including dysphagia following transoral non-robotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

OBJECTIVE: Transoral surgery is a minimally invasive treatment but may cause severe dysphagia at a lower rate than chemoradiotherapy. METHODS: We compared clinical information, surgical complications, and swallowing function in patients who underwent transoral nonrobotic surgery for laryngo-pharyngeal squamous cell carcinoma between 2015 and 2021 in a multicenter retrospective study. RESULTS: Six hundred and forty patients were included. Postoperative bleeding was observed in 20 cases (3.1%), and the risk factor was advanced T category. Postoperative laryngeal edema was observed in 13 cases (2.0%), and the risk factors were prior radiotherapy, advanced T stage, and concurrent neck dissection in patients with resected HPC. Dysphagia requiring nutritional support was observed in 29 cases (4.5%) at 1 month postoperatively and in 19 cases (3.0%) at 1 year postoperatively, respectively. The risk factors for long-term dysphagia were prior radiotherapy and advanced T category. Short-term risk factors for dysphagia were prior radiotherapy, advanced T category, and concurrent neck dissection, while long-term risk factors for dysphagia were only prior radiotherapy and advanced T category. CONCLUSION: Prior radiotherapy, advanced T stage, and concurrent neck dissection increased the incidence of postoperative laryngeal edema and short-term dysphagia, but concurrent neck dissection did not affect long-term dysphagia. Such features should be considered when considering the indication for transoral surgery and postoperative management.

Clinicopathological analysis of 134 patients with squamous cell carcinoma of the mandibular gingiva.

Objective: The accurate assessment of the involvement of mandibular gingival squamous cell carcinoma (SCC) is essential for determining the extent of resection and is also useful for predicting lymph node metastasis and prognosis. The purpose of this study was to investigate the factors for predicting the prognosis. Study design: We reviewed 134 patients with mandibular gingival SCC treated between 2008 and 2017. The clinical findings, TN stage, relationship between radiographical type and histological pattern, and factors affecting the survival rate were investigated. Results: The moth-eaten radiographic type was significantly associated with histologically infiltrative pattern. For all 134 cases, the 5-year OS was 89.5 %, and 5-year DSS was 93.9 %. The 5-year DSS was 95.0 % for cN0 and/or pN0 cases and 90.3 % for pN (+) cases, with a significant difference. The significant risk factors for lymph node metastasis were teeth extractions by previous physicians and moth-eaten radiographic type. Conclusion: The risk factor for poor prognosis was lymph node metastasis. In addition, teeth extractions by previous physicians and moth-eaten radiographic type were the risk factors for lymph node metastasis. It is recommended that these cases be treated considering the possibility of cervical lymph node metastasis.

Impact of cervical lymph node metastasis on transoral surgery for hypopharyngeal squamous cell carcinoma: A retrospective multicenter study.

BACKGROUND: Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. METHODS: We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. RESULTS: Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035). CONCLUSIONS: In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater.

Inhibition of transforming growth factor-ß signals suppresses tumor formation by regulation of tumor microenvironment networks.

The tumor microenvironment (TME) consists of cancer cells surrounded by stromal components including tumor vessels. Transforming growth factor-ß (TGF-ß) promotes tumor progression by inducing epithelial-mesenchymal transition (EMT) in cancer cells and stimulating tumor angiogenesis in the tumor stroma. We previously developed an Fc chimeric TGF-ß receptor containing both TGF-ß type I (TßRI) and type II (TßRII) receptors (TßRI-TßRII-Fc), which trapped all TGF-ß isoforms and suppressed tumor growth. However, the precise mechanisms underlying this action have not yet been elucidated. In the present study, we showed that the recombinant TßRI-TßRII-Fc protein effectively suppressed in vitro EMT of oral cancer cells and in vivo tumor growth in a human oral cancer cell xenograft mouse model. Tumor cell proliferation and angiogenesis were suppressed in tumors treated with TßRI-TßRII-Fc. Molecular profiling of human cancer cells and mouse stroma revealed that K-Ras signaling and angiogenesis were suppressed. Administration of TßRI-TßRII-Fc protein decreased the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), interleukin-1ß (IL-1ß) and epiregulin (EREG) in the TME of oral cancer tumor xenografts. HB-EGF increased proliferation of human oral cancer cells and mouse endothelial cells by activating ERK1/2 phosphorylation. HB-EGF also promoted oral cancer cell-derived tumor formation by enhancing cancer cell proliferation and tumor angiogenesis. In addition, increased expressions of IL-1ß and EREG in oral cancer cells significantly enhanced tumor formation. These results suggest that TGF-ß signaling in the TME controls cancer cell proliferation and angiogenesis by activating HB-EGF/IL-1ß/EREG pathways and that TßRI-TßRII-Fc protein is a promising tool for targeting the TME networks.

A multi-institutional retrospective study of 340 cases of sinonasal malignant tumor.

OBJECTIVE: Sinonasal malignant tumors (SNMT) are relatively rare among head and neck malignant tumors. Most are squamous cell carcinomas, and malignant melanomas, olfactory neuroblastomas, adenoid cystic carcinomas, sarcomas, and others also occur. The most common primary site of nasal sinus squamous cell carcinoma is the maxillary sinus. In recent years, a decrease in incidence of maxillary sinus squamous cell carcinoma (MSSCC) has been reported along with a decrease in the incidence of sinusitis. MSSCC is treated with a combination of surgery, radiation, and chemotherapy. Treatment decisions are made according to the progression of the disease, the patient's general condition, and the patient's own wishes. There are variations in treatment policies among facilities due to the specialty of staff and cooperation with other departments at each facility. We conducted a multi-institutional retrospective study to compare outcomes by treatment strategy. METHODS: In this study, 340 patients with SNMT who were treated at 13 Hospitals (Head and Neck Oncology Group (Kyoto-HNOG) ) during the 12-year period from January 2006 to December 2017 were included. There were 220 patients with squamous cell carcinoma, 32 with malignant melanoma, 21 with olfactory neuroblastoma, and 67 with other malignancies. Of the squamous cell carcinomas, 164 were of maxillary sinus origin. One hundred and forty cases of MSSCC that were treated radically were included in the detailed statistical analysis. RESULTS: There were 5 cases of cStage I, 9 cases of cStage II, 36 cases of cStage III, 74 cases of cStage IVa, and 16 cases of cStage IVb. There were 92 cases without clinical lymph node metastasis (cN(-)) and 48 cases with clinical lymph node metastasis(cN(+)). Primary tumors were treated mainly by surgery in 85 cases (Surg) and by radical radiation therapy (with or without chemotherapy) of 6-70 Gy in 55 cases(non-Surg). The 5-year overall/disease-free survival rate (OS/DFS) for MSSCC was 65.1%/51.6%. Old age, renal dysfunction, and clinical T progression were independent risk factors for OS, and renal dysfunction was an independent risk factor for DFS. In cN(-) patients, OS and DFS were significantly better in Surg group than in non-Surg group. In cN(+) patients, there was no significant difference in OS and DFS between Surg and non-Surg groups. CONCLUSION: For patients with MSSCC without lymph node metastasis, aggressive surgery on the primary tumor contributes to improved prognosis.

Summary of Japanese clinical practice guidelines for head and neck cancer - 2022 update edited by the Japan society for head and neck cancer.

The aim of the "Japanese Clinical Practice Guidelines for Head and Neck Cancer - 2022 Update" is to review the latest evidence regarding head and neck cancer and to present the current standard approaches for diagnosis and treatment. These evidence-based recommendations were created with the consensus of the Guideline Committee, which is composed of otorhinolaryngologists and head and neck surgeons, together with radiologists, radiation oncologists, medical oncologists, plastic surgeons, dentists, palliative care physicians, and rehabilitation physicians. These guidelines were created by the Clinical Practice Guideline Committee of the Japan Society for Head and Neck Cancer based on the "Head and Neck Cancer Treatment Guidelines 2018 Edition," and the revised draft was compiled after evaluation by the Assessment Committee and public comments. The 'Clinical questions and recommendations' section consists of 13 categories, and 59 clinical questions are described in total. Here we describe 6 clinical questions specific to other sets of guidelines with recommendations and comments.

Outcomes of regenerative treatment for over 200 patients with tympanic membrane perforation.

OBJECTIVE: To evaluate outcomes of a regenerative treatment (RT) for over 200 patients with tympanic membrane perforation (TMP). The RT-TMP method involves a gelatin sponge, basic fibroblast growth factor (bFGF) and fibrin glue. METHODS: The study population included 216 patients and 234 ears (male: female =100:116; age 1-93 years). All enrolled patients were treated with RT-TMP in which TMP edges were disrupted mechanically and a gelatin sponge immersed in bFGF was inserted into the perforation. Fibrin glue was then dripped over the sponge. Patient outcomes including TMP closure rates, change in hearing level, and complications were obtained from retrospective medical chart reviews. The TMP was examined three or more weeks after surgery. The treatment was repeated up to 4 times until complete TMP closure was achieved. RESULTS: After mechanical disruption, the perforation size was Grade I, ≤1/3 of entire TM area in 22 ears (9.4 %), Grade II, 1/3-2/3 of entire TM in 77 ears (32.9 %) and Grade III, ≥2/3 of entire TM area in 135 ears (57.7 %). The overall TMP closure rates were 97.0 % (227/234). Complete TMP closure was achieved in 68.8 % (161/234), 22.6 % (53/234), 4.7 % (11/234) and 0.9 % (2/234) of ears after 1, 2, 3 and 4 treatments, respectively. In 7 of 234 ears (3.0 %), the TMPs were not closed completely after 4 treatments. There was no correlation between TMP size after mechanical disruption and number of treatments required to achieve complete closure (Fisher's exact test p = 0.70). The mean air-conduction hearing threshold at low frequency improved from 57.3 ± 16.7 dB before treatment to 37.3 ± 16.0 dB (p < 0.0001) after closure of TMPs. For middle and high frequencies, the improvement was 49.0 ± 19.3 dB to 36.9 ± 17.9 dB (p < 0.0001) and 57.7 ± 22.9 dB to 49.2 ± 23.3 dB (p < 0.0001), respectively. The mean air-bone gaps also improved significantly, and were within 10 dB at 250 Hz, 500 Hz and 1 kHz, and 11 dB at 2 kHz. One or more complications occurred in 32 patients (32/216; 14.8 %). The most common complication was formation of an epithelial pearl (16 ears; 6.8 %), followed by severe TM retraction (9 ears; 3.8 %) and otitis media with effusion (6 ears; 2.6 %). There were no serious complications that caused deterioration of the patient's general condition. CONCLUSION: Our results showed that RT-TMP had high success rates for TMP closure and good hearing improvement and produced no severe complications that could affect general health status. This novel therapy is simple, safe and minimally invasive, and could help improve the quality of life in patients with TMP.

Local recurrence and metachronous multiple cancers after transoral nonrobotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

BACKGROUND: Late laryngopharyngeal cancers after transoral surgery include not only local recurrences but also metachronous multiple cancers. METHODS: We compared clinical information, surgical outcomes, and late laryngopharyngeal cancers in patients who underwent transoral nonrobotic surgery for laryngopharyngeal squamous cell carcinoma without lymph node metastases between 2015 and 2021 in a multicenter retrospective study. RESULTS: Four hundred and fifty-seven patients were included. Positive surgical margins were found in 121 patients (26.5%). Twenty-two patients (4.8%) received additional treatment. Positive horizontal margins of invasive carcinoma (p = 0.003) and positive horizontal margins of carcinoma in situ only (p = 0.032) were independent risk factors for local recurrence, and prior radiotherapy (p = 0.001) for metachronous multiple cancers. Local control was significantly worse without additional treatment (p = 0.049), but there was no significant difference in survival. CONCLUSIONS: Patients with positive margins had an increased frequency of local recurrence, but salvage therapy was effective.

The Efficacy of Immunotherapy and Clinical Utility of Comprehensive Genomic Profiling in Adenoid Cystic Carcinoma of Head and Neck.

Background and Objectives: Adenoid cystic carcinoma (ACC) of the head and neck is generally slow-growing but has a high potential for local recurrence and metastasis to distant organs. There is currently no standard pharmacological treatment for recurrent/metastatic (R/M) ACC, and there are cases in which immune checkpoint inhibitors (ICIs) are administered for ACC according to head and neck squamous cell carcinoma (HNSCC). However, the efficacy of ICIs for ACC remains unclear, and the predictive biomarkers need to be elucidated. Materials and Methods: The Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database enabled the retrospective but nationwide analysis of 263 cases of ACC of the head and neck. Then, we examined and reported four cases of ACC that received ICIs and comprehensive genomic profiling (CGP) in our institution. Results: The C-CAT database revealed that 59 cases out of 263 received ICIs, and the best response was 8% of objective response rate (ORR) and 53% of disease control rate (DCR) (complete response, CR 3%, partial response, PR 5%, stable disease, SD 44%, progressive disease, PD 19%, not evaluated, NE 29%). The tumor mutational burden (TMB) in ACC was lower overall compared to HNSCC and could not be useful in predicting the efficacy of ICIs. Some cases with MYB structural variants showed the response to ICIs in the C-CAT database. A patient with MYB fusion/rearrangement variants in our institution showed long-term stable disease. Conclusions: ICI therapy is a potential treatment option, and the MYB structural variant might be a candidate for predictive biomarkers for immunotherapy in patients with R/M ACC.

A case of sclerosing odontogenic carcinoma of the mandible with a review of the literature.

Sclerosing odontogenic carcinoma (SOC) is a very rare malignant odontogenic tumor characterized by sclerotic stroma and single-file cord-like tumor cell structures. A 38-year-old man presented with extraoral swelling and right mental region paralysis. Panoramic radiography revealed an ill-defined radiolucent lesion extending from the right mandibular ramus to the right lower canine. Magnetic resonance imaging showed tumor invasion into the right inferior alveolar nerve and masseter muscle. Hemimandibulectomy, bilateral neck dissection, and mandibular reconstruction were performed using a rectus abdominis musculocutaneous flap and a titanium plate. Histopathology and immunohistochemistry confirmed SOC diagnosis. No recurrence occurred in the 1-year follow-up. In this paper, a case of SOC with a high Ki-67 labeling index was reported. Since SOC is prone to nerve invasion, treatment is resection with an appropriate surgical margin.

Invasion of the bucco-mandibular space by oral squamous cell carcinoma: histopathological analysis of invasion pattern.

Background: This study aimed to determine the patterns of invasion of oral squamous cell carcinoma (OSCC) into the bucco-mandibular space (BMS) using detailed histopathological analysis and to assess clinical outcomes. Methods: Patients with OSCC who underwent segmental mandibulectomy or hemi-mandibulectomy combined with resection of the BMS between 2012 and 2021 were included. The invasions of the BMS were classified into three patterns. Pattern A was defined as a horizontal invasion, Pattern B as a vertical invasion, and Pattern C as an expansive invasion. Results: In total, 109 patients were reviewed. Of these 109 patients, the primary tumor affected the lower gingiva in 78 patients, the buccal mucosa in 18 patients, and was a primary intraosseous carcinoma of the mandible in 13 patients. Invasion of the BMS was significantly associated with a higher pathological T stage, positive/close margins, and lower disease-free survival (DFS) rates. The DFS rates were 86.7% and 66.0% in the BMS non-invasion and invasion groups, respectively. The DFS rates for each type of invasion were 82.1% for Pattern A, 67.4% for Pattern B, and 48.0% for Pattern C (P=0.277). Conclusion: Patients with BMS invasion have a poorer prognosis than those without invasion of the BMS. Therefore, adjuvant therapy is necessary, especially in Patterns B and C. Evaluation of preoperative BMS invasion patterns is important for predicting the prognosis of OSCC.

Efficacy and safety of bone management agents administered at 12 weeks vs. 4 weeks in patients with bone metastases: A systematic review.

BACKGROUND: Bone modifying agents (BMAs) have been used to prevent skeletal-related events (SRE) in cancer patients with bone metastases. In this meta-analysis, efficacy and adverse events (AEs) were studied based on a de-escalation strategy in which the BMA dosing interval was prolonged from 4 to 12 weeks. METHODS: PubMed, Cochrane, ICHUSHI, and CINAHL were searched for articles on BMA dosing intervals from outcomes measured were the incidence of SRE and related various AEs. A quantitative meta-analysis was performed using a random-effects model to calculate relative risk ratios (RRs) and 95% confidence intervals (CIs). RESULT: The meta-analysis included three randomized controlled studies (RCTs) of Zoledronic acid hydrate (ZA) (n = 2663) and six RCTs (n = 141) on BMA other than ZA. There was no difference in the incidence of SREs when comparing the dosing frequency of 12 versus 4 weeks for BMA (RR = 1.21, 95% CI [0.82-1.78], p = 0.33). Further, AEs related to treatment discontinuation were significantly less frequent with ZA given every 12 weeks than when given every 4 weeks (RR = 0.51 [0.30-0.89], p = 0.02). In particular, renal dysfunction leading to grade ≥3 or discontinuation of treatment with ZA occurred significantly less frequently with every 12-week dosing (RR = 0.33 [0.12-0.91], p = 0.33). CONCLUSION: This meta-analysis showed no influence of BMA de-escalation on the incidence of SRE; nevertheless, AEs appeared to reduce with the de-escalated usage of ZA.

Cr (VI) and Pb (II) Removal Using Crosslinking Magnetite-Carboxymethyl Cellulose-Chitosan Hydrogel Beads.

Heavy metals, such as chromium (VI) and lead (II), are the most common pollutants found in wastewater. To solve these problems, this research was intended to synthesize magnetite hydrogel beads (CMC-CS-Fe3O4) by crosslinking carboxymethyl cellulose (CMC) and chitosan (CS) and impregnating them with iron oxide (Fe3O4) as a potential adsorbent to remove Cr (VI) and Pb (II) from water. CMC-CS-Fe3O4 was characterized by pHzpc, scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR). Batch removal experiments with different variables (CMC:CS ratio, pH, initial metals concentration, and contact time) were conducted, and the results revealed that CMC-CS-Fe3O4 with a CMC:CS (3:1) ratio had the best adsorption capacity for Cr (VI) and Pb (II) at pH levels of 2 and 4, respectively. The findings of this research revealed that the maximum adsorption capacity for Cr (VI) and Pb (II) were 3.5 mg/g and 18.26 mg/g, respectively, within 28 h at 30 ℃. The adsorption isotherm and adsorption kinetics suggested that removal of Cr (VI) and Pb (II) were fitted to Langmuir and pseudo-second orders. The highest desorption percentages for Cr (VI) and Pb (II) were 70.43% and 83.85%, achieved using 0.3 M NaOH and 0.01 M N·a2EDTA, respectively. Interestingly, after the first cycle of the adsorption-desorption process, the hydrogel showed a sudden increase in adsorption capacity for Cr (VI) and Pb (II) until it reached 7.7 mg/g and 33.0 mg/g, respectively. This outcome may have certain causes, such as entrapped metal ions providing easy access to the available sites inside the hydrogel or thinning of the outer layer of the beads leading to greater exposure toward active sites. Hence, CMC-CS-Fe3O4 hydrogel beads may have potential application in Cr (VI) and Pb (II) removal from aqueous solutions for sustainable environments.

Role of Stromal Fibroblast-Induced WNT7A Associated with Cancer Cell Migration Through the AKT/CLDN1 Signaling Axis in Oral Squamous Cell Carcinoma.

Wnt signaling plays a crucial role in the progression of various cancers, including oral squamous cell carcinoma (OSCC). However, the tumor microenvironment (TME) regulating Wnt signaling has not yet been fully elucidated. In this study, we investigated whether cancer-associated fibroblasts (CAFs), the primary components of the TME, activate Wnt signaling and promote tumor progression in OSCC. We conducted a Transwell coculture assay using human OSCC cell lines and normal human dermal fibroblasts (NHDFs). NHDFs stimulated WNT7A expression in several OSCC cell lines, especially HO-1-N-1 and HSC-5. An immunohistochemical study using 122 human OSCC samples indicated that high WNT7A expression in tumor cells was significantly associated with invasion depth and poor prognosis. Moreover, WNT7A expression in OSCC cells was positively correlated with α-smooth muscle actin expression in CAFs. WNT7A knockdown in OSCC cells demonstrated that OSCC cells cocultured with NHDFs significantly promoted tumor cell migration and invasion, which was dependent on WNT7A expression in OSCC cells. We also isolated HSC-5 cells from the coculture and conducted microarray analysis to investigate the factors that promote tumor progression induced by WNT7A. Among the various differentially expressed genes, we identified a downregulated gene encoding CLDN1 and confirmed that WNT7A negatively regulated CLDN1 expression in OSCC cells and CLDN1 knockdown in OSCC cells promoted their migration. Phosphokinase array analysis showed that WNT7A activates protein kinase B (AKT) phosphorylation. Activating AKT signaling using the SC79 agonist induced CLDN1 downregulation in OSCC cells. In the coculture assay, the AKT inhibitor MK2206 significantly recovered CLDN1 expression downregulated by WNT7A, resulting in OSCC cell migration suppression. These results suggest that CAFs stimulate OSCC cells to produce WNT7A, following CLDN1 expression downregulation by activating AKT signaling, promoting cancer cell migration. These findings highlight the importance of molecular therapies targeting the TME in OSCC.

Application of Box-Behnken Design to Optimize Phosphate Adsorption Conditions from Water onto Novel Adsorbent CS-ZL/ZrO/Fe3O4: Characterization, Equilibrium, Isotherm, Kinetic, and Desorption Studies.

Phosphate (PO43-) is an essential nutrient in agriculture; however, it is hazardous to the environment if discharged in excess as in wastewater discharge and runoff from agriculture. Moreover, the stability of chitosan under acidic conditions remains a concern. To address these problems, CS-ZL/ZrO/Fe3O4 was synthesized using a crosslinking method as a novel adsorbent for the removal of phosphate (PO43-) from water and to increase the stability of chitosan. The response surface methodology (RSM) with a Box-Behnken design (BBD)-based analysis of variance (ANOVA) was implemented. The ANOVA results clearly showed that the adsorption of PO43- onto CS-ZL/ZrO/Fe3O4 was significant (p ≤ 0.05), with good mechanical stability. pH, dosage, and time were the three most important factors for the removal of PO43-. Freundlich isotherm and pseudo-second-order kinetic models generated the best equivalents for PO43- adsorption. The presence of coexisting ions for PO43- removal was also studied. The results indicated no significant effect on PO43- removal (p ≤ 0.05). After adsorption, PO43- was easily released by 1 M NaOH, reaching 95.77% and exhibiting a good capability over three cycles. Thus, this concept is effective for increasing the stability of chitosan and is an alternative adsorbent for the removal of PO43- from water.