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.

Low concentrations of TNF-α in vitro transform the phenotype of vascular smooth muscle cells and enhance their survival in a three-dimensional culture system.

BACKGROUND: Vascular smooth muscle cells (VSMCs) are commonly used as seed cells in tissue-engineered vascular constructions. However, their variable phenotypes and difficult to control functions pose challenges. This study aimed to overcome these obstacles using a three-dimensional culture system. METHODS: Calf VSMCs were administered tumor necrosis factor-alpha (TNF-α) before culturing in two- and three-dimensional well plates and polyglycolic acid (PGA) scaffolds, respectively. The phenotypic markers of VSMCs were detected by immunofluorescence staining and western blotting, and the proliferation and migration abilities of VSMCs were detected by CCK-8, EDU, cell counting, scratch, and Transwell assays. RESULTS: TNF-α rapidly decreased the contractile phenotypic markers and elevated the synthetic phenotypic markers of VSMCs, as well as markedly increasing the proliferation and migration ability of VSMCs under two- and three-dimensional culture conditions. CONCLUSIONS: TNF-α can rapidly induce a phenotypic shift in VSMCs and change their viability on PGA scaffolds.

Insulin-transferrin-selenium promote formation of tissue-engineered vascular grafts in early stage of culture.

To create tissue-engineered vascular grafts (TEVGs) in vitro, vascular smooth muscle cells (VSMCs) must function effectively and produce sufficient extracellular matrix (ECM) in a three-dimensional space. In this study, we investigated whether the addition of insulin-transferrin-selenium (ITS), a medium supplement, could enhance TEVG formation. PGA fabric was used as the scaffold, and 1% ITS was added to the medium. After two weeks, the tissues were examined using electron microscopy and staining. The ITS group exhibited a denser structure and increased collagen production. VSMCs were cultured in two dimensions with ITS and assessed for collagen production, cell growth, and glucose metabolism. The results showed that ITS supplementation increased collagen production, cell growth, glucose utilization, lactate production, and ATP levels. Furthermore, reducing the amount of fetal bovine serum (FBS) in the medium did not affect the TEVGs or VSMCs when ITS was present. In conclusion, ITS improves TEVG construction by promoting VSMCs growth and reducing the need for FBS.

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.

Three-arm phase II trial comparing camrelizumab plus chemotherapy versus camrelizumab plus chemoradiation versus chemoradiation as preoperative treatment for locally advanced esophageal squamous cell carcinoma (NICE-2 Study).

BACKGROUND: Preoperative chemoradiotherapy (CRT) with CROSS regimen has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to preoperative CRT may further improve oncologic results. Preoperative camrelizumab plus chemotherapy has been demonstrated as a promising treatment modality based on results of the phase II NICE study (ChiCTR1900026240). METHODS: The NICE-2 study is designed as a three-arm, multicenter, prospective, randomized, phase II clinical trial, comparing camrelizumab plus chemotherapy (IO-CT) and camrelizumab plus CRT (IO-CRT) versus CRT as preoperative treatment for locally advanced ESCC. A total of 204 patients will be recruited from 8 Chinese institutions within 1.5 years. The primary endpoint is pathological complete response (pCR) rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events. DISCUSSION: This is the first prospective randomized controlled trial to explore commonly used neoadjuvant treatments in clinical practice, which will provide high-level evidence of neoadjuvant treatment for patients with locally advanced ESCC. The purpose of this study is to establish the optimal modality of IO-CT, IO-CRT and CRT as preoperative treatment for locally advanced ESCC. The Institution Review Committee approved this study protocol in August 2021 and patient enrollment was started in September 2021. TRIAL REGISTRATION: ClinicalTrial.gov: NCT05043688 (August 29, 2021). The trial was prospectively registered.

Dermoscopic characteristics of membranous aplasia cutis congenita: Report of 56 cases.

BACKGROUND: Membranous aplasia cutis congenita (MACC) presents at birth characterized by oval epidermis defect. Skin lesions with MACC have various clinic manifestations. In recent years, the usefulness of trichoscopy (scalp dermoscopy) has been reported for hair loss diseases. However, the dermoscopic features of MACC were mostly reported by case reports. OBJECTIVES: To summarized the obvious dermoscopic characteristics of MACC. MATERIALS & METHODS: These 56 cases met the clinical diagnostic criteria for MACC without forceps delivery complications or other birth injuries. To find the dermoscopic characteristics of MACC by summarizing 56 infants' dermoscopic pictures. RESULTS: The dermoscopic manifestation of MACC are characterized by hair follicle openings and hair deficiency in the center of skin lesions, translucent epidermis, hair root and hair bulb arranged along the margins of skin lesion. CONCLUSION: The typical dermoscopic characteristics of MACC could help clinicians to early diagnose and differential diagnosis.

Role of BCLAF-1 in PD-L1 stabilization in response to ionizing irradiation.

Programmed cell death ligand 1 (PD-L1) is a major immunosuppressive checkpoint protein expressed by tumor cells to subvert anticancer immunity. Recent studies have shown that ionizing radiation (IR) upregulates the expression of PD-L1 in tumor cells. However, whether an IR-induced DNA damage response (DDR) directly regulates PD-L1 expression and the functional significance of its upregulation are not fully understood. Here, we show that IR-induced upregulation of PD-L1 expression proceeds through both transcriptional and post-translational mechanisms. Upregulated PD-L1 was predominantly present on the cell membrane, resulting in T-cell apoptosis in a co-culture system. Using mass spectrometry, we identified PD-L1 interacting proteins and found that BCLAF1 (Bcl2 associated transcription factor 1) is an important regulator of PD-L1 in response to IR. BCLAF1 depletion decreased PD-L1 expression by promoting the ubiquitination of PD-L1. In addition, we show that CMTM6 is upregulated in response to IR and participates in BCLAF1-dependent PD-L1 upregulation. Finally, we demonstrated that the ATM/BCLAF1/PD-L1 axis regulated PD-L1 stabilization in response to IR. Together, our findings reveal a novel regulatory mechanism of PD-L1 expression in the DDR.

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.

Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study.

BACKGROUND: After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. METHODS: Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value. DISCUSSION: If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial). TRIAL REGISTRATION: The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).

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.

CMISG1701: a multicenter prospective randomized phase III clinical trial comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) (NCT03001596).

BACKGROUND: Neoadjuvant chemoradiation is not recommended as an approach for treatment of esophageal squamous cell carcinoma due to its significant postoperative mortality. However, it is assumed the combination of neoadjuvant chemoradiation with minimally invasive esophagectomy (MIE) may reduce postoperative mortality, which can revive preoperative chemoradiation. No randomized controlled studies comparing neoadjuvant chemoradiation plus MIE with neoadjuvant chemotherapy plus MIE have been performed so far. The present trial is initiated to obtain valid information whether neoadjuvant chemoradiation plus MIE yields better survival without worse postoperative morbidity and mortality in the treatment of locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0). METHODS/DESIGN: CMISG1701 is a multicenter, prospective, randomized, phase III clinical trial, investigating the safety and efficacy of neoadjuvant chemoradiation plus MIE compared with neoadjuvant chemotherapy plus MIE. Patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) are eligible for the study. A total of 264 patients are randomly assigned to neoadjuvant chemoradiation (arm A) or neoadjuvant chemotherapy (arm B) with a 1:1 allocation ratio. The primary outcome is overall survival assessed with a minimum follow-up of 36 months. Secondary outcomes are progression-free survival, recurrence-free survival, postoperative pathologic stage, treatment-related complications, postoperative mortality as well as quality of life. DISCUSSION: The objective of this trial is to identify the superior protocol with regard to patient survival, treatment morbidity/mortality and quality of life between neoadjuvant chemoradiation plus MIE and neoadjuvant chemotherapy plus MIE. TRIAL REGISTRATION: NCT03001596 (December 17, 2016).

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.

Clinical outcomes of the robot-assisted Ivor Lewis procedure for adenocarcinoma of the esophagogastric junction with semi-instrument overlap intrathoracic anastomosis.

Background: The main difficulty of minimally invasive Ivor Lewis (IL) procedure for adenocarcinoma of the esophagogastric junction (AEGJ) is the intrathoracic esophagogastric anastomosis (IEA). We aimed to assess the safety and feasibility of the IL procedure with the da Vinci surgical system for treatment of AEGJ with semi-mechanical intrathoracic IEA. Methods: The cohort included 72 patients with AEGJ who received treatment at the Department of Minimally Invasive Esophagus Surgery of the Tianjin Medical University Cancer Institute and Hospital from August 2020 to March 2023. Of these 72 patients, 17 received neoadjuvant chemo-immunotherapy. The robot-assisted minimally invasive IL procedure was performed using a linear stapler for overlap side-to-side intrathoracic anastomosis and the stapler defect was closed with double full-layer continuous sutures by robotic hand-sewn (semi-mechanical) IEA. Results: Of the 72 AEGJ patients, 2 were converted to exploration, 7 were converted to laparotomy and thoracotomy for circular-stapled intrathoracic anastomosis, and 6 were converted to thoracotomy for circular-stapled anastomosis, which included 2 cases of extensive pleural adhesion and 4 cases of overlap anastomosis failure, whereas 57 underwent the robot-assisted minimally invasive IL procedure with semi-mechanical IEA. Among the 9 patients converted to laparotomy, the laparotomy rate was closely related to the Siewert classification (P<0.005) and preoperative use of neoadjuvant therapy (P<0.05). Among the 57 patients who underwent the robot-assisted minimally invasive IL procedure with semi-mechanical IEA, there were 2 cases of anastomotic leakages (2/57, 3.5%), no case of anastomotic stricture, 5 cases of postoperative pneumonia (5/57, 8.77%), 2 cases of intensive care unit admission (2/57, 3.5%), and 1 case of readmission within 30 days (1/57, 1.75%). None of the patients died within 30 days after surgery. Conclusions: The robot-assisted minimally invasive IL procedure with semi-mechanical IEA is both safe and feasible for AEGJ. However, caution is advised for patients with Siewert type III AEGJ and those who have already received preoperative neoadjuvant therapy.

Neoadjuvant chemoimmunotherapy followed by robot esophagectomy has no effect on short-term results compared with surgery alone.

BACKGROUND: To determine the safety and efficacy of robot-assisted minimally invasive esophagectomy (RAMIE) for locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoimmunotherapy (NCI). METHODS: Data from patients who underwent RAMIE between January 2020 and June 2022 were retrospectively analyzed. The oncological and operative outcomes of the NCI and surgery-only (S) groups were compared by both unmatched and 1:1 propensity score-matched (PSM) analysis. RESULTS: A total of 201 patients with ESCC who underwent three-incision RAMIE were included in this study (143 patients in the S group and 58 patients in the NCI group). Of the 58 patients who underwent NCI, a pathologically complete response (pCR) (ypT0N0) was identified in 14 (24.1%) patients. The patients in the NCI group were younger than those in the S group (p = 0.017), and had more advanced cT (p < 0.001) and cN stage diseases (p = 0.002). After 1:1 PSM of the confounders, 55 patients were allocated to each of the NCI and S groups. No significant differences were found in oncological and operative results, including surgical blood loss, operative time, and lymph node harvest (all p > 0.05). However, the NCI group exhibited a lower rate of pulmonary complications than the S group (3.6% vs. 14.5%, p = 0.047). No significant difference between the groups was found for other complications (all p > 0.05). CONCLUSION: These findings indicate that NCI could result in a high pCR rate without increased complications in locally advanced ESCC. RAMIE is safe and feasible in patients with ESCC after NCI.

[Retracted] Upstream transcription factor 1 prompts malignancies of cervical cancer primarily by transcriptionally activating p65 expression.

[This retracts the article DOI: 10.3892/etm.2018.6758.].

PEG 300 Promotes Mesodermal Differentiation in iPSC-Derived Embryoid Body Formation In Vitro.

Embryoid bodies (EB) are sensitive to changes in the culture conditions. Recent studies show that the addition of PEG 300 to culture medium affects cell growth and differentiation; however, its effect on the embryoid body is unclear. This study aims to understand the role of PEG 300 in the process of EB formation and germ layer differentiation. EBs formed more efficiently and differentiated toward the mesoderm when cultured in a medium supplemented with appropriate concentrations of PEG 300. The expression of T/Bry, a marker of mesodermal differentiation, increases in EBs in the PEG group, and the expression of TUBB3 generally decreases, showing a quantitative relationship with PEG. Furthermore, further differentiation of PEG-pretreated EB into vascular smooth muscle cells (VSMCs) by directional induction shows that PEG 300-pretreated induced VSMCs have higher expression of phenotypic markers and greater secretory and contractile functions. This study highlights the role of PEG 300 in the culture medium during EB differentiation, which can significantly enhance mesodermal gene expression and the efficiency of subsequent differentiation into smooth muscle cells and other target cells.

Carrageenan maintains the contractile phenotype of vascular smooth muscle cells by increasing macromolecular crowding in vitro.

BACKGROUND: The contractile phenotype of vascular smooth muscle cells (VSMCs) results in good diastolic and contractile capacities, and its altered function is the main pathophysiological basis for diseases such as hypertension. VSMCs exist as a synthetic phenotype in vitro, making it challenging to maintain a contractile phenotype for research. It is widely recognized that the common medium in vitro is significantly less crowded than in the in vivo environment. Additionally, VSMCs have a heightened sense for detecting changes in medium crowding. However, it is unclear whether macromolecular crowding (MMC) helps maintain the VSMCs contractile phenotype. PURPOSE: This study aimed to explore the phenotypic, behavioral and gene expression changes of VSMCs after increasing the crowding degree by adding carrageenan (CR). METHODS: The degree of medium crowding was examined by a dynamic light scattering assay; VSMCs survival and activity were examined by calcein/PI cell activity and toxicity and CCK-8 assays; VSMCs phenotypes and migration were examined by WB and wound healing assays; and gene expression was examined by transcriptomic analysis and RT-qPCR. RESULTS: Notably, 225 µg/mL CR significantly increased the crowding degree of the medium and did not affect cell survival. Simultaneously, CR significantly promoted the contraction phenotypic marker expression in VSMCs, shortened cell length, decreased cell proliferation, and inhibited cell migration. CR significantly altered gene expression in VSMCs. Specifically, 856 genes were upregulated and 1207 genes were downregulated. These alterations primarily affect the cellular ion channel transport, microtubule movement, respiratory metabolism, amino acid transport, and extracellular matrix synthesis. The upregulated genes were primarily involved in the cytoskeleton and contraction processes of VSMCs, whereas the downregulated genes were mainly involved in extracellular matrix synthesis. CONCLUSIONS: The in vitro study showed that VSMCs can maintain the contractile phenotype by sensing changes in the crowding of the culture environment, which can be maintained by adding CR.