Head and Neck Osteosarcoma: Perineural Invasion is Associated With Disease-Free Survival and Tumor Metastasis.

BACKGROUND: Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI) is a notable indication of aggressive tumor behavior, which includes the phenomenon of tumor cells invading any of the 3 layers of the nerve sheath or tumor cells gathering, encircling one-third of the nerve circumference, and infiltrating and metastasizing along the nerve. PNI has been reported in various malignant tumors and is considered to be linked to poor prognosis. PURPOSE: The study's purpose is to measure the association between PNI and survival outcomes in patients with HNOS. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study focused on HNOS patients who underwent surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University, from January 1, 2019 to December 31, 2021. Patients who did not undergo complete surgical resection of the tumor, did not receive a conventional osteosarcoma diagnosis, and had positive surgical margins were eliminated. PREDICTOR VARIABLE: The predictor variable is PNI status. The pathological section of the tumor was consistent with any of the PNI features, which was considered PNI-positive. MAIN OUTCOME VARIABLE(S): The primary outcome variables were 3-year disease-free survival (DFS) and 3-year overall survival. Secondary outcomes were 3-year tumor local recurrence and 3-year metastasis (MT). COVARIATES: Covariates were categorized into the following categories: demographic variables (age, sex), clinical variables (tumor region, primary tumor), and treatment variables (chemotherapy, radiotherapy). ANALYSES: Analytic statistical methods were used for the data analysis. Pearson χ2 or Fisher's exact test was used to describe the baseline data. Kaplan-Meier is used to calculate survival rates. The Cox regression model was adapted for univariate and multivariate analysis. A P value less than .05 indicated statistical significance. RESULTS: The study sample comprised 70 patients; 33 (47.1%) were male, and the mean age was 42.2 (standard deviation: 16.7) years. There were 15 (21.4%) cases of PNI. The 3-year DSF rate and OS rate were 67.3% and 82.0%, respectively. PNI-positive resulted in higher risk for MT (P ＜ .01, hazard ratio: 5.95, 95% confidence interval: 1.62-21.86) and negative impact on DFS (P < .01, hazard ratio: 6.35, 95% confidence interval: 2.11-19.17) for HNOS patients. CONCLUSION AND RELEVANCE: Positive PNI status was associated with decreased DFS and increased risk of MT.

Prospective observational study of surgery alone for locally advanced oral squamous cell carcinoma: a real-world study.

INTRODUCTION: A prospective observational study was modified to assess the efficacy of surgery alone for the treatment of locally advanced oral squamous cell carcinoma. (LA-OSCC) MATERIALS AND METHODS: This prospective, single-institution, single-arm study involved 174 patients who underwent major surgery for LA-OSCC. Participating patients did not receive postoperative radiation. After initial curative treatment, patients were routinely monitored via clinical examination and imaging. The follow-up period was 3-70 months. Tumour recurrence and death were considered as the Clinical End Point in Research. RESULTS: The 5-year overall survival (OS), disease-free survival (DFS), and locoregional control rates for 174 patients were 66.7% (95% confidence interval [CI], 59.8 to 73.6), 66.1% (95% CI, 59.2 to 73.0), and 82.4% (95% CI, 76.5 to 88.3), respectively. CONCLUSION: A study of patients with LA-OSCC treated with surgery alone may have the optimal therapeutic impact for LA-OSCC, as evidenced by solid data for our next RCT trial. This conclusion still needs to be validated in higher-level RCTs.

Changes of Oral Flora, Inflammatory Factors, and Immune Function Indicators in Patients with Chronic Periodontitis and Their Clinical Significance.

This research focuses on investigating the changes of oral flora, inflammatory factors, and immune function indicators in patients with chronic periodontitis (CP) and their clinical significances. Clinical indices such as gingival index (GI) and sulcus bleeding index (SBI) of the study subjects were recorded. The levels of oral flora, inflammatory factors and T lymphocyte subsets in gingival crevicular fluid (GCF) of the study subjects were measured. To analyze the correlation between GI and gingival SBI and oral flora, inflammatory factors, and immune function indicators, Pearson correlation analysis was performed. Porphyromonas gingivalis, Streptococcus digestiveis, Prevotella intermedia, Veronococcus, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, CD3+, CD4+, and CD4+/CD8+ had a positive correlation with GI and SBI, while IL-10 and CD8+ were negatively correlated with GI and SBI. Oral flora, inflammatory factors and immune function indicators levels are largely elevated in patients with CP and they are correlated with CP clinical indicators.

Three-dimensional assessment of tongue cancer prognosis by preoperative MRI.

PURPOSE: To obtain the relative volume by measuring the tongue volume and the lesion volume, and further explore its relationship with the prognosis of patients, hoping to supplement the TNM staging with a new index. METHODS: ITK-SANP software was used to outline the patients' MRI. After MRI reconstruction and measurement, slicer software was used to estimate tumor volume. RESULTS: A total of 64 patients with tongue cancer who met the inclusion criteria were included in the study. The estimated tumor volume after MRI reconstruction revealed a significant and robust correlation with tumor stage (p < 0.05, Rs = 0.6207) and a substantial and medium correlation with early lymph node metastasis (p < 0.05, Rs = 0.4873). CONCLUSIONS: We classified tongue cancer into three grades based on tumor volume (Stage I, tumors smaller than 1500 mm³; Stage II, tumors 1500-9000 mm³; and Stage III, tumors larger than 9000 mm³), and such grading could be used as a reference for tumor staging, lymph node metastasis, and patient prognosis to a certain extent.

Head-and-neck dermatofibrosarcoma protuberans: Survival analysis and Clinically relevant immunohistochemical indicators.

BACKGROUND: Head and neck dermatofibrosarcoma protuberans (HNDFSP) is extremely rare and not entirely understood. OBJECTIVE: To investigate the clinicopathological features of HNDFSP and identify the expression of its clinically relevant indicators, with the expectation of improving the existing treatment strategies. METHODS: A long-term follow-up of patients with HNDFSP who received treatment between 2000 and 2021 at Shanghai Ninth People's Hospital was conducted. The clinical, histological, and immunohistochemical data of the patients were retrieved and analyzed. The endpoint of the study was the incidence of significant disease-related clinical events (recurrences or metastasis). RESULTS: A total of 49 patients with HNDFSP were included in the study, with males (92.7%) predominating than females (7.3%). Eighteen patients developed recurrent disease (36.8%) after surgery, and the median time of recurrence was 48 months (interquartile, 20-74 months). Metastasis occurred in two cases (4.1%). Two patients died during follow-up, both with local recurrence, and one of them with intestinal metastasis. Post-operation radiotherapy was administered to eight patients (16.3%) and the effect in local control was remarkable. Age, tumor size, and negative margins with sufficient safety width were the main independent factors affecting the disease-free survival. Several potential targeted therapeutic indicators, including EZH2 (80.0%), EGFR (91.4%), PDGF (97.1%), PD-L1 (77.1%), and VEGF (77.1%), were positively expressed in most tumor samples. CONCLUSION: HNDFSP is rare, significantly challenging to control locally, and has a worse prognosis with current treatment strategies. Wide local excision and long-term follow-up are needed. Radiotherapy could improve the prognosis of patients with HNDFSP.

Application of anatomy unit resection surgery for lateral basicranial surgical approach in oral squamous carcinoma.

BACKGROUND: The basicranial region lacks definite boundaries and includes various anatomical units. We developed a novel concept of the posterior oral anatomical complex (POAC) to identify these anatomical units in the basicranial region. OSCC with POAC involvement is termed posterior oral squamous cell carcinoma (POSCC) with poor prognosis. The principal aim of this study was to evaluate the effect of anatomy unit resection surgery (AUSR) on patients with POSCC. METHODS: A total of 120 POSCC patients who underwent radical surgical treatment were recruited for this study. These POSCC patients were treated with conventional surgery or AUSR. According to the extent of primary tumor resection in the AUSR group, the lateral basicranial surgical approach can be subdivided into four types: face-lateral approach I, face-lateral approach II, face-median approach or face-median and face-lateral combined approach. Facial nerve function was evaluated according to the House-Brackmann Facial Nerve Grading System. RESULTS: The overall survival rate was 62.5% and 37.5% in the AURS group and conventional group (hazard ratio: 0.59; p < 0.0001), respectively. The disease-free survival rate was 62.5% and 34.3% in the AURS group and conventional group (hazard ratio: 0.43; p = 0.0008), respectively. The local disease control rate in the AURS group (71.4%) was significantly better than that in the conventional group (34.4%) in present study (p < 0.0001). Compared to the conventional group, all the patients undergoing AURS were classified as T4 stage and presented with more lymph node metastasis (71.4%). A total of 20 patients (face-lateral approach I and face-lateral combined approach) were temporarily disconnected from the temporofacial branch of the facial nerve. Fifteen patients exhibited slight paresis, and five patients presented with moderate or severe paresis. The survival rate of zygomatic arch disconnection was 94.6% (54 of 56 patients). CONCLUSION: This lateral basicranial surgical approach based on AUSR improves the survival rate and enhances the local control rate while also preserving a good prognosis without damaging the nerve and zygomatic bone. This surgical approach based on AUSR provides a novel and effective surgical treatment to address POSCC with better prognosis, especially for patients without metastatic lymph nodes.

Unicystic ameloblastoma: A retrospective study on recurrent factors from a single institute database.

OBJECTIVE: Unicystic ameloblastomas are a variant of ameloblastoma with a definite recurrence rate because of the biological behaviours of the tumour. The risk factors associated with disease recurrence were analysed in this retrospective study. METHODS: A total of 132 patients with primary unicystic ameloblastoma reported in a tertiary hospital from 2005 to 2015 were analysed to identify the clinic-pathological and radiological factors associated with recurrence using univariate and multivariate Cox regression analyses. RESULTS: The mean volume was 30.54cm3  ± 12.55 cm3 , and this value differed significantly according to recurrence (p < 0.001). Root resorption and bone cortex/soft tissue invasion were also significantly associated with recurrence among unicystic ameloblastoma patients (p = 0.017 vs. p < 0.001, respectively). A new stage classification system was developed to predict disease recurrence of patients. The multivariate Cox regression analysis revealed that the new stage classification system was the only predictor of disease recurrence in unicystic ameloblastoma patients (p < 0.001), regardless of root resorption, position and site characteristics. CONCLUSIONS: Volume, root resorption and bone cortex/soft tissue invasion were risk factors for disease recurrence among unicystic ameloblastoma patients. The new stage classification was an independent predictor of disease recurrence in patients with unicystic ameloblastoma.

Postoperative radiotherapy may not be necessary for locally advanced head and neck squamous cell carcinoma: a case-match multicentre study.

BACKGROUND: Some head and neck cancer surgeons found that many patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) without postoperative radiotherapy (PORT) also have a good prognosis. The purpose of this study was to determine the effect of PORT on survival in patients with LA-HNSCC. METHODS: A case-match cohort analysis was performed at two institutions on patients with LA-HNSCC. Patients who received surgery alone were case-matched 1: 1 with patients treated by surgery plus PORT based on pT, pN, tumor subsite etc. RESULTS: 114 patients were matched into 57 pairs, with a median follow-up period of 40.2 months. No difference in overall survival (OS, HR 0.88; 95% CI 0.50-1.58; P = 0.79) or disease-specific survival (DFS, 0.86; 95% CI 0.50-1.50; P = 0.76) was observed with no PORT. CONCLUSIONS: PORT isn't necessary for patients with LA-HNSCC who are treated for the first time as long as the head and neck cancer surgeon adhere to appropriate surgical concepts. The indications of PORT for patients with LA-HNSCC need to be further discussed.

Trends in the incidence of diabetes mellitus: results from the Global Burden of Disease Study 2017 and implications for diabetes mellitus prevention.

BACKGROUD: Diabetes mellitus is a common chronic disease and a severe public health issue. The incidence trends for type 1 diabetes (TIDM) and type 2 diabetes (T2DM) have rarely been studied on a global scale. We aimed to determine the temporal and geographical trends of diabetes globally. METHODS: Data on diabetes mellitus, including incidence, prevalence from 1990 to 2017 were obtained from the 2017 Global Burden of Disease study. We calculated the estimated annual percentage changes (EAPCs) in age-standardized incidence rate (ASIR) of diabetes mellitus according to sex, region, and disease type. RESULTS: The worldwide incident cases of diabetes mellitus has increased by 102.9% from 11,303,084 cases in 1990 to 22,935,630 cases in 2017 worldwide, while the ASIR increased from 234 /100,000 persons (95% UI, 219-249) to 285/100,000 persons (95% UI, 262-310) in this period [EAPC = 0.87, 95% confidence interval (CI):0.79-0.96]. The global ASIRs of T1DM and T2DM both demonstrated significant increase during 1990-2017, with EAPCs of 0.34 (95% CI,0.30-0.39) and 0.89 (95% CI,0.80-0.97), respectively. The ASIR trends also varied considerably by regions and countries. The increase in ASIR was greatest in high sociodemographic index regions (EAPC = 1.05, 95% CI:0.92-1.17) and lowest in low-SDI regions (EAPC = 0.79, 95% CI:0.71-0.88). CONCLUSIONS: Both the number of incident cases and ASIR of diabetes mellitus increased significantly during 1990-2017 worldwide, but the temporal trends varied markedly across regions and countries.

Nonvascularized Iliac Bone Reconstruction for the Mandible Without Maxillofacial Skin Scarring.

PURPOSE: There are many methods to reconstruct the mandible, but they are often accompanied by trauma, which can lead to scarring of the maxillofacial skin. The purpose of this study was to show the utility of a minimally invasive method for reconstruction of the mandible with nonvascularized iliac bone grafts without a skin scar, as well as to evaluate the success rate and complications. PATIENTS AND METHODS: This was a retrospective case series. We retrospectively analyzed patients who underwent transoral resection of benign mandibular pathologies, followed by nonvascularized iliac bone graft reconstruction. The primary outcome variable was the success rate of the bone grafts. Secondary outcome variables were postoperative complications at the grafted bone recipient and donor sites, the long-term absorptivity of grafted bone, and the type of mandibular defect. We computed descriptive statistics or performed the χ2 test for each variable. RESULTS: Overall, 54 patients were included in the study, including 21 male and 33 female patients, with an age range of 10 to 65 years. The complete survival rate was 87.0% (47 of 54 patients), and the partial survival rate was 98.1% (53 of 54). The average bone absorption rate 3 years after surgery was 1.8 to 30.7%. We propose a new classification method for mandibular defects based on the extent of the tumor, location of the osteotomy, and degree of surgical difficulty. CONCLUSIONS: Intraoral nonvascularized iliac bone grafting is a highly successful minimally invasive method for mandibular reconstruction. It is also one of the best methods for mandibular reconstruction in patients with benign mandibular tumors without soft tissue involvement.

Differential expression of matrix metalloproteinases and miRNAs in the metastasis of oral squamous cell carcinoma.

BACKGROUND: Our study aimed to reveal the regulatory mechanisms of miRNAs and matrix metalloproteinases (MMPs) in oral squamous cell carcinoma (OSCC). METHODS: The mRNA and miRNA expression profiles of six metastatic tumour samples, six nonmetastatic tumour samples, and six normal tissue samples were used for microarray analysis. Moreover, the important genes and miRNAs were validated by published profiles in Oncomine and by qRT-PCR. RESULTS: MMP7, MMP13, and MMP10 were upregulated, and MMP12 and MMP9 were downregulated in metastatic tumours compared with nonmetastatic tumours. MMP7 was regulated by miR-4697-5p and miR-7109-5p. MMP7 and MMP13 were upregulated in OSCC samples compared with normal samples in Oncomine. Moreover, qRT-PCR revealed that the expression of miR-7109-5p and miR-34b was decreased in metastatic tumours compared with nonmetastatic tumours. CONCLUSIONS: Our study suggested that miR-7109-5p and miR-34b might play important roles in the metastasis of OSCC by regulating MMP7 and MMP13 expression, respectively.

Drain fluid amylase as a predictor of postoperative salivary fistula in cases with benign parotid tumours.

BACKGROUND: Late diagnosis of a salivary fistula increases the risk of wound infection and scarring. The purpose of the present study was to identify a quantitative predictor of postoperative salivary fistula for cases treated with surgery. METHODS: Demographic, intraoperative and postoperative parameters for 57 cases that received surgery for benign parotid tumours were recorded from June 2017 to June 2018, of which 18 cases developed salivary fistulas. These data were analysed using univariate and binary logistic regression analyses as well as receiver operating curve analysis. RESULTS: Drain fluid amylase concentration was positively correlated with salivary fistula development (p <  0.001), with an odds ratio of 1.14 for a 1 KU/L increase in concentration and an optimal receiver operating curve cut-off value of 51,100 U/L for predicting salivary fistula development. Cases wherein the parotid-masseteric fascia remained intact were associated with a lower risk of salivary fistula development (p = 0.006). CONCLUSION: Drain fluid amylase concentration may be a valuable predictor of postoperative salivary fistula in cases with benign parotid tumours.

Inhibiting MT2-TFE3-dependent autophagy enhances melatonin-induced apoptosis in tongue squamous cell carcinoma.

Autophagy modulation is a potential therapeutic strategy for tongue squamous cell carcinoma (TSCC). Melatonin possesses significant anticarcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in TSCC are unclear. Herein, we show that melatonin induced significant apoptosis in the TSCC cell line Cal27. Apart from the induction of apoptosis, we demonstrated that melatonin-induced autophagic flux in Cal27 cells as evidenced by the formation of GFP-LC3 puncta, and the upregulation of LC3-II and downregulation of SQSTM1/P62. Moreover, pharmacological or genetic blockage of autophagy enhanced melatonin-induced apoptosis, indicating a cytoprotective role of autophagy in melatonin-treated Cal27 cells. Mechanistically, melatonin induced TFE3(Ser321) dephosphorylation, subsequently activated TFE3 nuclear translocation, and increased TFE3 reporter activity, which contributed to the expression of autophagy-related genes and lysosomal biogenesis. Luzindole, a melatonin membrane receptor blocker, or MT2-siRNA partially blocked the ability of melatonin to promote mTORC1/TFE3 signaling. Furthermore, we verified in a xenograft mouse model that melatonin with hydroxychloroquine or TFE3-siRNA exerted a synergistic antitumor effect by inhibiting autophagy. Importantly, TFE3 expression positively correlated with TSCC development and poor prognosis in patients. Collectively, we demonstrated that the melatonin-induced increase in TFE3-dependent autophagy is mediated through the melatonin membrane receptor in TSCC. These data also suggest that blocking melatonin membrane receptor-TFE3-dependent autophagy to enhance the activity of melatonin warrants further attention as a treatment strategy for TSCC.

Prediction of Flap Compromise by Preoperative Coagulation Parameters in Head and Neck Cancer Patients.

PURPOSE: Studies on coagulation parameters (including activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen [FIB], platelet count, and D-dimer) in flap compromise are limited. The aim of the present study was to compare coagulation parameter variables in patients with and without flap compromise. MATERIALS AND METHODS: In this retrospective cohort study, patients were recruited from the Department of Oral and Maxillofacial Surgery at the Second Xiangya Hospital (Changsha, Hunan, China) from July 2016 through July 2017. The primary predictor variable was a set of coagulation parameters. The primary outcome variable was flap compromise. The other variables were age, gender, tumor stage, smoking, and prior radiotherapy. Descriptive, bivariate, receiver operating characteristic (ROC) curves and regression statistics were computed. Statistical significance was set at less than .05 with 95% reliability. RESULTS: A total of 503 patients with 42 compromised flaps were identified in this study. Venous thrombosis, arterial thrombosis, or no confirmed reason for compromise was observed in 28, 5, or 9 compromised flaps, respectively. Only FIB was associated with flap compromise or venous thrombosis at adjusted analyses, although the predictive values were low at ROC analysis. For patients with D-dimer lower than 0.4 µg/mL, the likelihood of venous thrombosis was greater than that for patients with D-dimer of at least 0.4 µg/mL (P = .0414). For patients with FIB lower than 3.5 g/L, the likelihood of venous thrombosis was greater than that for patients with FIB of at least 3.5 g/L (P = .0336). CONCLUSION: Decreased FIB was associated with a higher rate of flap compromise. In patients with D-dimer lower than 0.4 µg/mL or FIB lower than 3.5 g/L, the risk of venous thrombosis was higher.

Clinical Application of an Original Vascular Anastomosis: A Clinical Multicenter Study.

PURPOSE: Vascular anastomosis is the most important technical step required for the possibility of free tissue transfer, and mismatch of the donor and recipient vessel size is the most common surgical challenge. As recent reports have described a new method (Ren anastomosis) to resolve this challenge, the goal of this study was to assess these newly described microvascular anastomosis methods. PATIENTS AND METHODS: The study was conducted at 2 institutes in China in different periods. Patients were recruited from the Second Xiangya Hospital between February and May 2013 and from the Shanghai Ninth People's Hospital between March and May 2015. All patients who participated in this study needed free flaps for oral and maxillofacial defects. Patients were divided into the experimental group and the control group. In the experimental group, isometric double-notch end-in-end microvascular anastomosis (Ren anastomosis) was performed, whereas end-to-end anastomosis was performed in the control group. Statistical differences were assessed by use of χ2 and t tests. RESULTS: A total of 148 patients (108 men and 40 women) were treated over the course of this study. There was a statistically significant difference (P < .001) in the operation time for the microscopic artery anastomosis between the experimental group (70 cases; 5.6 ± 1.8 minutes) and the control group (78 cases; 14.6 ± 3.7 minutes). In each group, 1 case of artery compromise was observed. CONCLUSIONS: The Ren anastomosis was time-saving, straightforward, efficient, and easy to learn, with a high patency rate.

Longitudinal Contraction Venoplasty in Prevention of Internal Jugular Vein Thrombosis After Free Flap Vascular Anastomosis.

PURPOSE: The vascular anastomosis of free flap with the internal jugular vein stump is susceptible to thrombosis, thus resulting in flap compromise or failure. This study aims to explore the method of longitudinal contraction venoplasty in the prevention of internal jugular vein stump thrombosis after free flap vascular anastomosis and its feasibility. PATIENTS AND METHODS: A retrospective review was performed of 16 patients who underwent internal jugular vein resection because of cancer ablation and longitudinal contraction venoplasty to prevent internal jugular vein stump thrombosis after free flap vascular anastomosis from January 2013 through December 2014 at Second Xiangya Hospital. The methods for longitudinal contraction venoplasty and its efficacy are reported. RESULTS: Venous anastomosis of all flaps was performed with the internal jugular vein stump, and single venous anastomosis was made in all cases. Postoperatively, all flaps survived completely, without vascular compromise. All the patients were followed for approximately 9 to 33 months, and they were satisfied with the esthetic and functional results of the donor and recipient sites after reconstruction. CONCLUSIONS: Longitudinal contraction venoplasty may be an effective new method for prevention of internal jugular vein thrombosis after free flap vascular anastomosis.

Transfer of anterolateral thigh flaps in elderly oral cancer patients: complications in oral and maxillofacial reconstruction.

PURPOSE: Although a promising approach, the use of anterolateral thigh (ALT) free flaps has been limited in the reconstruction of oral and maxillofacial defects in elderly patients. The aim of this study was to estimate the frequency of postoperative complications and identify factors associated with complications. PATIENTS AND METHODS: The authors designed and implemented a retrospective study on the frequency of postoperative complications in elderly patients. They enrolled a sample composed of patients who underwent ALT free flap transfers for the repair of defects created during oral and maxillofacial cancer surgery from February 2002 to March 2013. The χ(2) test, t test, and multivariate regression model were used. RESULTS: A total of 1,100 patients were studied (859 men and 241 women). One hundred four patients (9.5%) were at least 70 years old (elderly group) at the time of surgery; the other 996 patients were younger than 70 years (younger group). The overall success rate of ALT free flap transfer was 97.2% (97.0% in the younger group, 99.0% in the elderly group; P > .05). The overall complication rate was 27.5% (27.2% in the younger group, 29.8% in the elderly group; P = .572). Multivariate analysis showed that operation time, American Society of Anesthesiologists class, and comorbidity were independent risk factors for postoperative complications in elderly patients. CONCLUSIONS: Oral and maxillofacial reconstruction using ALT free flaps in elderly patients can achieve outcomes similar to those obtained in younger patients. Limiting the operation time is important for improving surgical outcomes.