Multicentre randomized clinical trial on robot-assisted versus video-assisted thoracoscopic oesophagectomy (REVATE trial).

BACKGROUND: Surgery for oesophageal squamous cell carcinoma involves dissecting lymph nodes along the recurrent laryngeal nerve. This is technically challenging and injury to the recurrent laryngeal nerve may lead to vocal cord palsy, which increases the risk of pulmonary complications. The aim of this study was to compare the efficacy and safety of robot-assisted oesophagectomy (RAO) versus video-assisted thoracoscopic oesophagectomy (VAO) for dissection of lymph nodes along the left RLN. METHODS: Patients with oesophageal squamous cell carcinoma who were scheduled for minimally invasive McKeown oesophagectomy were allocated randomly to RAO or VAO, stratified by centre. The primary endpoint was the success rate of left recurrent laryngeal nerve lymph node dissection. Success was defined as the removal of at least one lymph node without causing nerve damage lasting longer than 6 months. Secondary endpoints were perioperative and oncological outcomes. RESULTS: From June 2018 to March 2022, 212 patients from 3 centres in Asia were randomized, and 203 were included in the analysis (RAO group 103; VAO group 100). Successful left recurrent laryngeal nerve lymph node dissection was achieved in 88.3% of the RAO group and 69% of the VAO group (P < 0.001). The rate of removal of at least one lymph node according to pathology was 94.2% for the RAO and 86% for the VAO group (P = 0.051). At 1 week after surgery, the RAO group had a lower incidence of left recurrent laryngeal nerve palsy than the VAO group (20.4 versus 34%; P = 0.029); permanent recurrent laryngeal nerve palsy rates at 6 months were 5.8 and 20% respectively (P = 0.003). More mediastinal lymph nodes were dissected in the RAO group (median 16 (i.q.r. 12-22) versus 14 (10-20); P = 0.035). Postoperative complication rates were comparable between the two groups and there were no in-hospital deaths. CONCLUSION: In patients with oesophageal squamous cell carcinoma, RAO leads to more successful left recurrent laryngeal nerve lymph node dissection than VAO, including a lower rate of short- and long-term recurrent laryngeal nerve injury. Registration number: NCT03713749 (http://www.clinicaltrials.gov).

Oesophageal cancer often requires complex surgery. Recently, minimally invasive techniques like robot- and video-assisted surgery have emerged to improve outcomes. This study compared robot- and video-assisted surgery for oesophageal cancer, focusing on removing lymph nodes near a critical nerve. Patients with a specific oesophageal cancer type were assigned randomly to robot- or video-assisted surgery at three Asian hospitals. Robot-assisted surgery had a higher success rate in removing lymph nodes near the important nerve without permanent damage. It also had shorter operating times, more lymph nodes removed, and faster drain removal after surgery. In summary, for oesophageal cancer surgery, the robotic approach may provide better lymph node removal and less nerve injury than video-assisted techniques.

Learning Curve of Robot-Assisted Lymph Node Dissection of the Left Recurrent Laryngeal Nerve: A Retrospective Study of 417 Patients.

OBJECTIVE: Left recurrent laryngeal nerve (no.106recL) lymph node dissection is a challenging procedure, and robotic-assisted minimally invasive esophagectomy (RAMIE) may have some advantages. This study aimed to determine the learning curve of no.106recL lymph node dissection. METHODS: The data of 417 patients who underwent McKeown RAMIE between June 2017 and June 2022 were retrospectively analyzed. The lymph node harvest of no.106recL was used to determine the learning curve, and the cumulative sum (CUSUM) method was employed to obtain the inflection point. RESULTS: A total of 404 patients (404/417, 96.9%) underwent robotic surgery. Based on the number of no.106recL lymph nodes harvested, the CUSUM learning curve was mapped and divided into three phases: phase I (1‒75 cases), phase II (76‒240 cases), and phase III (241‒404 cases). The median (IQR) number of no.106recL lymph node harvests were 1 (4), 3 (6,) and 4 (4) in each phase (p < 0.001). The lymph node dissection rate gradually increased from 62.7% in phase I to 82.9% in phase III (p = 0.001). The total and thoracic lymph node harvest gradually increased (p < 0.001), whereas operation time (p = 0.001) and blood loss gradually decreased (p < 0.001). Moreover, the incidence of total complication (p = 0.020) and recurrent laryngeal nerve injury (p = 0.001) significantly decreased, and the postoperative hospital stay gradually shortened (p < 0.001). CONCLUSION: Robotic no.106recL lymph node dissection has some advantages for patients with esophageal cancer. In this study, perioperative and clinical outcomes were significantly improved over the learning curve. However, further prospective studies are required to confirm our results.

Connection between Osteoarthritis and Nitric Oxide: From Pathophysiology to Therapeutic Target.

Osteoarthritis (OA), a disabling joint inflammatory disease, is characterized by the progressive destruction of cartilage, subchondral bone remodeling, and chronic synovitis. Due to the prolongation of the human lifespan, OA has become a serious public health problem that deserves wide attention. The development of OA is related to numerous factors. Among the factors, nitric oxide (NO) plays a key role in mediating this process. NO is a small gaseous molecule that is widely distributed in the human body, and its synthesis is dependent on NO synthase (NOS). NO plays an important role in various physiological processes such as the regulation of blood volume and nerve conduction. Notably, NO acts as a double-edged sword in inflammatory diseases. Recent studies have shown that NO and its redox derivatives might be closely related to both normal and pathophysiological joint conditions. They can play vital roles as normal bone cell-conditioning agents for osteoclasts, osteoblasts, and chondrocytes. Moreover, they can also induce cartilage catabolism and cell apoptosis. Based on different conditions, the NO/NOS system can act as an anti-inflammatory or pro-inflammatory agent for OA. This review summarizes the studies related to the effects of NO on all normal and OA joints as well as the possible new treatment strategies targeting the NO/NOS system.

Evaluating the effect of methotrexate on the rate of renal fibrosis by elastography and fibrosis-related gene expression.

Methotrexate is mainly used to treat diseases such as rheumatoid arthritis (RA), but its potential for nephrotoxicity has always been a significant concern on the use of this medication. This study aimed to determine the rate of renal fibrosis using transient elastography and its relationship with cumulative dose and duration of drug use in patients with rheumatoid arthritis treated with methotrexate. TGFß gene expression was also assessed for further evaluation. Patients with rheumatoid arthritis who received methotrexate for more than six months were included. Renal fibrosis was determined by measuring the stiffness of the kidney by elastography (FiberScan Device). RA patients were divided into two groups based on kidney stiffness measurement with and without renal fibrosis, and demographic, clinical, and biochemical parameters were compared to investigate the relationship between cumulative dose and duration of methotrexate treatment and renal fibrosis. Also, in this study, 50 controls (healthy people) and 50 cases (RA patients) were used to evaluate the expression of the TGFß gene by real-time PCR method. The existence of kidney fibrosis was observed in 10 patients. There was no significant relationship between renal fibrosis and the cumulative dose (P = 0.21) and duration of methotrexate (P = 0.30). Multivariate regression analysis showed that the chances of developing renal fibrosis in patients increase with increasing serum ALT levels (P = 0.01). The results of the TGFß gene expression showed that the expression of this gene in the group of RA patients with fibrosis was higher than the control group (healthy people) and the group of RA patients without fibrosis (P <0.01). These results showed that evaluation of renal fibrosis by elastography method is recommended for scanning RA patients while they are being treated with methotrexate, which is also confirmed by the results of the fibrosis-related-gene expression.

A nomogram to predict lymph node metastasis risk for early esophageal squamous cell carcinoma.

BACKGROUND: A nomogram was developed to predict lymph node metastasis (LNM) for patients with early-stage esophageal squamous cell carcinoma (ESCC). METHODS: We used the clinical data of ESCC patients with pathological T1 stage disease who underwent surgery from January 2011 to June 2018 to develop a nomogram model. Multivariable logistic regression was used to confirm the risk factors for variable selection. The risk of LNM was stratified based on the nomogram model. The nomogram was validated by an independent cohort which included early ESCC patients underwent esophagectomy between July 2018 and December 2019. RESULTS: Of the 223 patients, 36 (16.1%) patients had LNM. The following three variables were confirmed as LNM risk factors and were included in the nomogram model: tumor differentiation (odds ratio [OR] = 3.776, 95% confidence interval [CI] 1.515-9.360, p = 0.004), depth of tumor invasion (OR = 3.124, 95% CI 1.146-8.511, p = 0.026), and tumor size (OR = 2.420, 95% CI 1.070-5.473, p = 0.034). The C-index was 0.810 (95% CI 0.742-0.895) in the derivation cohort (223 patients) and 0.830 (95% CI 0.763-0.902) in the validation cohort (80 patients). CONCLUSIONS: A validated nomogram can predict the risk of LNM via risk stratification. It could be used to assist in the decision-making process to determine which patients should undergo esophagectomy and for which patients with a low risk of LNM, curative endoscopic resection would be sufficient.

Lymph node dissection around left recurrent laryngeal nerve: robot-assisted vs. video-assisted McKeown esophagectomy for esophageal squamous cell carcinoma.

OBJECTIVE: This study investigated the advantages of robot-assisted McKeown esophagectomy (RAME) for extensive superior mediastinal lymph node dissection (LND) versus video-assisted McKeown esophagectomy (VAME). METHODS: The cases of 184 consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent minimally invasive McKeown esophagectomy (109 with RAME, 75 with VAME) performed by a single surgical group between June 2017 and December 2019 were retrospectively reviewed. RESULTS: Overall, 59.8% (110/181) patients (70 treated with RAME, 40 treated with VAME; 64.2% vs. 53.3%, respectively, p = 0.139) underwent complete LND around the left recurrent laryngeal nerve (RLN) by pathological assessment. Cumulative sum plots showed increased numbers of LND around the left RLN (3.6 ± 2.0 vs. 5.4 ± 2.7, p = 0.008) and a decreased incidence of recurrent nerve injury (27.9% vs. 7.4%, p = 0.037) after RAME learning curve. Despite similar overall LND results (30.6 ± 10.2 vs. 28.1 ± 10.2, p > 0.05), RAME yielded more LND (5.4 ± 2.7 vs. 4.4 ± 2.2, p = 0.016) and a greater proportion of lymph node metastases (37.0% vs. 7.5%) around the left RLN but induced a lower proportion of recurrent nerve injuries (7.4% vs. 22.5%, p = 0.178) compared with VAME. Further analysis revealed that the complete LND around the left RLN was associated with recurrent nerve injury in the RAME (20.0% vs. 5.1%, p = 0.035) and VAME (22.5% vs. 5.7%, p = 0.041) groups but did not affect other clinical outcomes including surgical duration, intraoperative blood loss, postoperative intensive care unit stay, hospital stay, and other complications. CONCLUSIONS: For patients with ESCC, RAME has great advantages in LND around the left RLN and recurrent nerve protection after learning curve of robotic esophagectomy.

Extracellular Vesicles Allow Epigenetic Mechanotransduction between Chondrocytes and Osteoblasts.

MicroRNAs (miRNAs) can be transported in extracellular vesicles (EVs) and are qualified as possible messengers for cell-cell communication. In the context of osteoarthritis (OA), miR-221-3p has been shown to have a mechanosensitive and a paracrine function inside cartilage. However, the question remains if EVs with miR-221-3p can act as molecular mechanotransducers between cells of different tissues. Here, we studied the effect of EV-mediated transport in the communication between chondrocytes and osteoblasts in vitro in a rat model. In silico analysis (Targetscan, miRWalk, miRDB) revealed putative targets of miRNA-221-3p (CDKN1B/p27, TIMP-3, Tcf7l2/TCF4, ARNT). Indeed, transfection of miRNA-221-3p in chondrocytes and osteoblasts resulted in regulation of these targets. Coculture experiments of transfected chondrocytes with untransfected osteoblasts not only showed regulation of these target genes in osteoblasts but also inhibition of their bone formation capacity. Direct treatment with chondrocyte-derived EVs validated that chondrocyte-produced extracellular miR-221-3p was responsible for this effect. Altogether, our study provides a novel perspective on a possible communication pathway of a mechanically induced epigenetic signal through EVs. This may be important for processes at the interface of bone and cartilage, such as OA development, physiologic joint homeostasis, growth or fracture healing, as well as for other tissue interfaces with differing biomechanical properties.

The Interaction between microRNAs and the Wnt/ß-Catenin Signaling Pathway in Osteoarthritis.

Osteoarthritis (OA) is a chronic disease affecting the whole joint, which still lacks a disease-modifying treatment. This suggests an incomplete understanding of underlying molecular mechanisms. The Wnt/ß-catenin pathway is involved in different pathophysiological processes of OA. Interestingly, both excessive stimulation and suppression of this pathway can contribute to the pathogenesis of OA. microRNAs have been shown to regulate different cellular processes in different diseases, including the metabolic activity of chondrocytes and osteocytes. To bridge these findings, here we attempt to give a conclusive overview of microRNA regulation of the Wnt/ß-catenin pathway in bone and cartilage, which may provide insights to advance the development of miRNA-based therapeutics for OA treatment.

Safety and Efficacy of Apatinib Monotherapy for Unresectable, Metastatic Esophageal Cancer: A Single-Arm, Open-Label, Phase II Study.

LESSONS LEARNED: Patient compliance with the oral dosage treatment was good, with no need for hospitalization. Patients with tracheal and esophageal fistulas can take crushed apatinib by nutrient tube, with the same bioavailability and efficacy. Apatinib may be an effective and safe second- or further-line treatment for advanced esophageal cancer. BACKGROUND: Apatinib is an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2), which is thought to play a role in esophageal cancer progression. Our goal was to evaluate the efficacy and safety of apatinib in patients with unresectable esophageal cancer and to examine whether VEGFR2 expression influenced the clinical response. METHODS: This single-arm, open-label, investigator-initiated phase II study enrolled patients with advanced squamous cell carcinoma (SCC) or adenocarcinoma of the esophagus or esophagogastric junction who were admitted to Tianjin Medical University Cancer Institute and Hospital between August 2017 and January 2019. Apatinib monotherapy (500 mg/day) was given orally or via an enteral tube until disease progression, unacceptable toxicity, withdrawal, or death. Patients were followed until treatment was discontinued or death. The main endpoints were tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS: Among 32 patients screened for inclusion, 30 were included in the safety and survival analyses (i.e., received apatinib), and 26 were included in the efficacy analysis (at least one imaging follow-up). Median follow-up time and exposure to apatinib were 5.34 months and 72 days, respectively. Among 26 patients included in the efficacy analysis, 2 had a partial response (PR; 7.7%) and 14 had stable disease (SD; 53.8%). The overall response rate (ORR) was 7.7%, and the disease control rate (DCR) was 61.5%. Median PFS and OS were 4.63 months (95% confidence interval, 2.11-7.16 months) and 6.57 months (4.90 months to not estimable), respectively. Fifteen patients (50.0%) experienced treatment-related AEs, most commonly hypertension (26.7%), diarrhea (20.0%), and hand-foot-skin reaction (10.0%). No patients had grade ≥4 treatment-related AEs. CONCLUSION: Apatinib was effective as second- or further-line treatment for advanced esophageal cancer.

Influence of Induction Therapy on Robot-Assisted McKeown Esophagectomy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: The present study was to investigate the influence of induction therapy on robot-assisted McKeown esophagectomy (RAME) with radical superior mediastinal lymph node dissection for esophageal squamous cell carcinoma in a high-volume cancer center. METHODS: A consecutive patient cohort who underwent RAME from January 2017 to May 2019 were reviewed. The perioperative outcomes of patients with induction therapy were compared with those who had surgery alone. RESULTS: In total, 118 patients underwent RAME during the study period. The average age was 59.1 ± 7.5 years, including 100 male and 18 female patients. Thirty patients (25.4%) had induction therapy, and 88 patients did not receive induction therapy. The average age of the patients treated with induction therapy was younger than those received surgery alone (56.8 ± 6.1 vs. 59.5 ± 7.6 years, p = 0.039). There were no statistically significant differences in the mean operative time and estimated blood loss between both groups. Complications occurred in 46 (39.0%) patients. There were no statistically significant differences in the rates of any complications between both groups (p = 0.951). There were no deaths in either group. The hospital stay was prolonged in patients with induction therapy than those in the surgery-alone group (20.8 ± 8.9 vs. 16.8 ± 6.0, p = 0.048). There was no statistically significant difference in the average number of dissected lymph nodes in total and both recurrent laryngeal nerve stations between both groups. CONCLUSION: For patients with esophageal squamous cell carcinoma, induction therapy has no influence on RAME with radical superior mediastinal lymph node dissection.

The predictive value of a preoperative systemic immune-inflammation index and prognostic nutritional index in patients with esophageal squamous cell carcinoma.

Growing evidence indicates that systemic inflammation response and malnutrition status are correlated with survival in certain types of solid tumors. The aim of this study is to evaluate the association between the systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) and overall survival (OS) in patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. A consecutive series of 655 patients with resected ESCC who underwent esophagectomy were enrolled in the retrospective study. The preoperative SII was defined as platelet × neutrophil/lymphocyte counts. The PNI was calculated as albumin concentration (g/L) + 5 × total lymphocyte count (109 /L). The optimal cut-off values of SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and PNI were determined by receiver operating characteristic analysis. Survival analysis was performed using the Kaplan-Meier method with a log-rank test, followed by a multivariate Cox proportional hazards model. A high SII was significantly related to tumor size, histological type, invasion depth, and TNM stage (p < 0.05). A low PNI was significantly associated with age, tumor size, invasion depth, lymph node metastasis, and TNM stage (p < 0.05). Univariate analysis revealed that age, smoking history, tumor size, invasion depth, lymph node metastasis, SII, NLR, PLR, and PNI were predictors of OS (p < 0.05). Multivariate analysis identified age (p = 0.041), tumor size (p = 0.016), invasion depth (p < 0.001), lymph node metastasis (p < 0.001), SII (p = 0.033), and PNI (p = 0.022) as independent prognostic factors correlated with OS. There was a significant inverse relationship between the SII and PNI (r = 0.309; p < 0.001). The predictive value increased when the SII and PNI were considered in combination. Our results demonstrate that the preoperative high SII and low PNI are powerful indicators of aggressive biology and poor prognosis for patients with ESCC. The combination of SII and PNI can enhance the accuracy of prognosis.

Vav1 expression is increased in esophageal squamous cell carcinoma and indicates poor prognosis.

Recently, Vav1 has been suggested to play an essential role in the progression of human cancers. However, the correlation between Vav1 expression and prognosis of esophageal squamous cell carcinoma (ESCC) is still unknown. The aim of this study was to investigate Vav1 expression and its prognostic value in ESCC. The expression of Vav1 was detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting in ESCC tissues and matched nontumorous tissues. Immunohistochemistry (IHC) was carried out to detect Vav1 expression in paraffin samples from 112 primary ESCC patients. Survival analysis was performed using Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to evaluate the correlation of Vav1 expression with prognosis of ESCC patients. The expression levels of Vav1 mRNA and protein in ESCC tissues were both significantly higher than those in adjacent nontumorous tissues. High Vav1 expression was significantly correlated with larger tumor size (P = 0.015), depth of tumor invasion (P = 0.023), lymph node metastasis (P = 0.008) and TNM stage (P < 0.001). The rate of overall survival (OS) was significantly lower in patients with high Vav1 expression than those with low Vav1 expression (P = 0.014). Multivariate Cox analysis indicated that Vav1 expression is an independent prognostic factor for OS (HR = 1.660, 95%CI = 1.058-2.607, P = 0.028). In summary, our findings demonstrate that Vav1 may be a candidate molecular prognostic marker for patients with ESCC.

High Body Mass Index Worsens Survival in Patients with Esophageal Squamous Cell Carcinoma after Esophagectomy.

AIMS: To investigate the prognostic significance of body mass index (BMI) on the survival of patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. METHODS: Between 2005 and 2008, 291 patients with ESCC who met the inclusion criteria were included in the study. The BMI cut-off values were as follows: 18.5-23 kg/m2 for normal weight; 23-27.5 kg/m2 for overweight; and ≥27.5 kg/m2 for those with obesity. Univariate and multivariate analyses were performed to identify prognostic factors for long-term survival. RESULTS: Patients were divided into 3 groups: normal weight (n = 138), overweight (n = 103), and obese (n = 50). The median survival time was 56 months. The 5-year overall survival (OS) rates were 40.8, 44.7, and 20.8% for normal weight, overweight, and obese patients respectively (p < 0.05). Multivariate analysis identified BMI as an independent prognostic factor for OS (p < 0.05). For 179 patients without lymph node metastasis, the 5-year OS rates were 46.5, 50.7, and 27.0% for normal weight, overweight, and obese patients respectively (p < 0.05). CONCLUSIONS: A BMI ≥27.5 kg/m2 has a distinctly adverse impact on the long-term survival of ESCC patients after esophagectomy. High BMI is a potential predictor of worse prognosis in ESCC patients, particularly in patients without lymph node metastasis.

Chondrogenic effect of cell-based scaffold of self-assembling peptides/PLGA-PLL loading the hTGFß3 plasmid DNA.

With the application of tissue engineering to tissue regeneration, additional new complexes have been made in response to the challenge of cartilage-injury repair. This study was performed to construct a rat precartilaginous stem cells-based scaffold of self-assembling peptides RADA16-I/PLGA-PLL (poly-L-lysine coated PLGA) as extracellular matrix loading the NLS-TAT as a peptide-based carrier for a plasmid DNA containing hTGFß3. After composites were cultured for 1, 2, 3 and 4 weeks, respectively, the results showed that the levels of chondrogenic-related gene expression were higher in the experimental group with and hTGFß3 gene by reverse transcription-polymerase chain reaction, and with higher histochemical and immunohistochemical expression. hTGFß3 protein expression had increased at 4 weeks based on western blot analysis. The results of this study show that a complex may be a suitable scaffold for cartilage repair and offer a strategy for tissue regeneration through the use of tissue engineering.

Acute Fatty Liver of Pregnancy: Analysis on the Diagnosis and Treatment of 15 Cases.

OBJECTIVE: To describe our experience with the diagnosis and management of acute fatty liver of pregnancy (AFLP). STUDY DESIGN: The medical records of pregnant women with AFLP were reviewed for symptoms, laboratory findings, treatment, and maternal and fetal outcomes during a 10-year period between January 2003 and December 2013. RESULTS: During the study period 15 women had AFLP as their discharge diagnosis. The mean gestational age at onset was 36 ± 1 weeks. Eleven cases were primigravidas, and 2 had multiple gestations. All patients presented with nausea, vomiting, and epigastric distress followed by jaundice in the third trimester of pregnancy. Raised transaminases and serum bilirubin as well as coagulopathy were found in all patients (100%), while hypoglycemia was found in 8 patients (53%). Ultrasound examination showed enhanced echo or fatty liver in 11 patients. Maternal morbidity included hepatic encephalopathy (n = 1), renal failure (n = 3), ascites (n = 6), hypoglycemia (n = 8), postpartum hemorrhage (n = 6), upper gastrointestinal hemorrhage (n = 1), and preeclampsia (n = 1). Emergency cesarean section was performed in 12 cases and supracervical hysterectomy was performed in 1 patient due to postpartum hemorrhage and disseminated intravascular coagulation (DIC); all patients survived. All neonates survived except for 2 fetal death cases before admission. CONCLUSION: Early diagnosis and prompt progressive management, including early termination of pregnancy and comprehensive supportive care, are crucial for improving the prognoses of both mother and newborn.

Verrucous Carcinoma of the Vulva: A 20 Year Retrospective Study and Literature Review.

OBJECTIVE: The aim of the study was to assess the clinicopathological characteristics of patients with verrucous carcinoma (VC) of the vulva. MATERIALS AND METHODS: We reviewed data on the age, disease course, clinical manifestation, pathologic diagnosis, treatment, and follow-up of patients with vulvar VC who were treated at Tianjin Medical University General Hospital and cases that were reported in the Chinese and English literature during the past 20 years. RESULTS: Six cases were identified in Tianjin Medical University General Hospital, the mean age of patients was 55 years, and their mean disease course was 26 months. Primary symptoms were exophytic neoplasm with pruritus and/or pain. Surgical treatment included wide local excision, simple vulvectomy, and radical vulvectomy with or without lymph node dissection in the groin. Vulvar VC occurred simultaneously with vulvar intraepithelial neoplasia in 2 cases and well-differentiated squamous cell carcinoma in 2 cases. The mean follow-up was 16.8 months with no recurrence in those 6 cases. During the 20-year period, 20 and 41 cases were reported in Chinese and English literature, respectively. Three cases were misdiagnosed with giant condyloma acuminatum in China. One case (1/20) was reported with coexistent squamous carcinoma in Chinese literature and 8 cases (8/41) in the English literature. The recurrence rate was 12.5% (2/19) and 17.5% (7/40) in Chinese and English literature, respectively. CONCLUSIONS: Vulvar VC is a distinct type of slow-growing, nonmetastatic tumor with unclear etiology. These tumors should be distinguished from giant condyloma acuminatum and well-differentiated squamous cell carcinoma. Surgery is the most effective treatment.

Comparison of lymph node metastasis pattern from esophagogastric junction adenocarcinoma versus very low thoracic esophageal squamous cancer: a propensity-matched analysis.

Background: The anatomical locations of esophagogastric junction adenocarcinoma (AEG) and very low thoracic esophageal squamous cell carcinoma (ESCC) are similar. This study aimed to evaluate the difference in lymph node metastasis (LNM) distribution between AEG and very low thoracic ESCC. Methods: Data from 156 Siewert I-II AEG patients and 120 ESCC patients with proximal edges located within 5 cm of the esophagogastric junction (EGJ) and underwent curative surgery from 2010 to 2015 were retrospectively analyzed using propensity score matching (PSM). Five or six baseline variables were included in PSM separately. All patients underwent curative transthoracic surgery and systematic lymphadenectomy. After PSM, LNM rates of major stations were compared using the chi-squared test or Fisher's exact test. Results: After PSM was performed with covariates (age, sex, T stage, grade, tumor length), 60 pairs of patients were included. The lower mediastinal and total thoracic LNM rates of ESCC were significantly higher than those of AEG (18.3% vs. 3.3%, P=0.019; 25% vs. 3.3%, P=0.002). After further addition of the N stage as a variant to the previous PSM model, we found that the paracardial LNM distribution was significantly different between ESCC and AEG patients (36.1% vs. 19.7%, P=0.043). Among all tumor characteristics, only the T stage was positively correlated with paracardial LNM in ESCC (P=0.010), but not in AEG. In AEG, the median survival was poor for patients with thoracic LNM. Conclusions: Patients with very low thoracic ESCC exhibit stronger metastatic ability in the lower mediastinal and paracardial nodes than Siewert I-II AEG. However, the pathological metastasis of AEG in thoracic nodes was associated with poor survival outcomes.

Corrigendum: Comparison of Ceramic-on-Ceramic vs. Ceramic-on-Polyethylene for Primary Total Hip Arthroplasty: A Meta-Analysis of 15 Randomized Trials.

[This corrects the article DOI: 10.3389/fsurg.2021.751121.].

The Application of Extracellular Vesicles Mediated miRNAs in Osteoarthritis: Current Knowledge and Perspective.

Osteoarthritis (OA) is a whole joint disease characterized by synovitis, cartilage destruction, and subchondral bone sclerosis and cyst. Despite decades' study, effective treatment is rare for this chronic disease. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptosis bodies, are nano-sized vesicles with a cargo containing biologically active agents, such as nucleic acids, lipids, and proteins. As a group of short non-coding RNAs, microRNAs (miRNAs) can be delivered by parental cells secreted EVs. Negatively regulate the target mRNAs at the posttranscriptional level and regulate gene expression in recipient cells without modifying gene sequence. Recently, most studies focused on the function of EVs mediated miRNAs in the pathophysiological process of OA. However, all kinds of EVs specific and OA specific factors might influence the administration of EVs-miRNAs, especially the precise quantitative management. As a result, the flourishing of current research about EVs in the laboratory might not promote the relevant clinical transformation in OA treatment. In this review, we reviewed the present application of EVs-miRNAs in the therapeutic of OA and further analyzed the potential factors that might influence its application. Further progress in the quantitative management of EVs-miRNAs would accelerate the clinical transformation of miRNAs enriched EVs in the OA field.