The Current State of Robot-Assisted Minimally Invasive Esophagectomy (RAMIE): Outcomes from the Upper GI International Robotic Association (UGIRA) Esophageal Registry.

BACKGROUND: Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted in centers worldwide, with ongoing refinements to enhance results. This study aims to assess the current state of RAMIE worldwide and to identify potential areas for improvement. METHODS: This descriptive study analyzed prospective data from esophageal cancer patients who underwent transthoracic RAMIE in Upper GI International Robotic Association (UGIRA) centers. Main endpoints included textbook outcome rate, surgical techniques, and perioperative outcomes. Analyses were performed separately for intrathoracic (Ivor-Lewis) and cervical anastomosis (McKeown), divided into three time cohorts (2016-2018, 2019-2020, 2021-2023). A sensitivity analysis was conducted with cases after the learning curve (> 70 cases). RESULTS: Across 28 UGIRA centers, 2012 Ivor-Lewis and 1180 McKeown procedures were performed. Over the time cohorts, textbook outcome rates were 39%, 48%, and 49% for Ivor-Lewis, and 49%, 63%, and 61% for McKeown procedures, respectively. Fully robotic procedures accounted for 66%, 51%, and 60% of Ivor-Lewis procedures, and 53%, 81%, and 66% of McKeown procedures. Lymph node yield showed 27, 30, and 30 nodes in Ivor-Lewis procedures, and 26, 26, and 34 nodes in McKeown procedures. Furthermore, high mediastinal lymphadenectomy was performed in 65%, 43%, and 37%, and 70%, 48%, and 64% of Ivor-Lewis and McKeown procedures, respectively. Anastomotic leakage rates were 22%, 22%, and 16% in Ivor-Lewis cases, and 14%, 12%, and 11% in McKeown cases. Hospital stay was 13, 14, and 13 days for Ivor-Lewis procedures, and 12, 9, and 11 days for McKeown procedures. In Ivor-Lewis and McKeown, respectively, the sensitivity analysis revealed textbook outcome rates of 43%, 54%, and 51%, and 47%, 64%, and 64%; anastomotic leakage rates of 28%, 18%, and 15%, and 13%, 11%, and 10%; and hospital stay of 11, 12, and 12 days, and 10, 9, and 9 days. CONCLUSIONS: This study demonstrates favorable outcomes over time in achieving textbook outcome after RAMIE. Areas for improvement include a reduction of anastomotic leakage and shortening of hospital stay.

Analysis of Risk Factors for Recurrence after Transurethral Resection of Bladder Tumor in Patients with Non-Muscle Invasive Bladder Cancer: 2-Year Follow-Up Outcomes.

INTRODUCTION: The aim was to investigate the risk factors for recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) and to provide a basis for clinical prevention of recurrence of NMIBC. METHODS: From January 2012 to December 2020, 592 patients with NMIBC who underwent TURBT attending the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively included in this study. Patients were divided into relapse and relapse-free groups according to whether relapse occurred within 2 years. Ultimately, 72 patients were included in the relapse group and 350 patients were included in the relapse-free group. Observation indicators included age, sex, smoking, underlying disease (hypertension, diabetes, coronary heart disease), two or more lesions, tumor size, hematuria, pathology grading (low, medium, high), staging (Ta, T1), muscular invasion in initial pathology, tumor base (sessile, pedunculated), use of intravesical drug (pirarubicin, bacillus Calmette-Guerin [BCG], mitomycin, hydroxycamptothecin, gemcitabine). RESULTS: In this study, the 2-year recurrence rate of NMIBC patients after TURBT was 17.06%. There were significant differences in comparison of pirarubicin, BCG, and mitomycin treatment between the two groups (p < 0.05). To avoid missing risk factors for recurrence, factors with p < 0.1 were analyzed. The results of univariate logistic regression analysis showed that NMIBC patients with BCG treatment (OR = 5.088, 95% CI = 1.444-17.73, p = 0.012), high pathology grading (OR = 0.415, 95% CI = 0.197-0.880, p = 0.023), T1 stage (OR = 2.097, 95% CI = 0.996-4.618, p = 0.059), mitomycin treatment (OR = 5.029, 95% CI = 1.149-21.77, p = 0.031), and pirarubicin treatment (OR = 1.794, 95% CI = 1.079-3.030, p = 0.024) had significantly higher risk of recurrence within 2 years after TURBT. The results of multivariate logistic regression analysis showed that NMIBC patients with high pathology grading (OR = 0.4030, 95% CI = 0.1702-0.8426, p = 0.0241), pirarubicin treatment (OR = 1.961, 95% CI = 1.159-3.348, p = 0.0125), and BCG treatment (OR = 6.201, 95% CI = 1.275-29.73, p = 0.0190) had significantly higher risk of recurrence within 2 years after TURBT. CONCLUSION: Our study highlights the importance of postoperative surveillance and individualized treatment for patients with NMIBC. Our findings show that high pathology grading, pirarubicin treatment, and BCG treatment are independent risk factors for recurrence after TURBT in patients with NMIBC. However, caution is warranted when interpreting our findings due to the small sample size and the need for further research to confirm the negative impact of mitomycin and BCG on recurrence rates.

CT radiomics to predict pathologic complete response after neoadjuvant immunotherapy plus chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: To develop and validate a CT-based radiomics model to predict pathologic complete response (pCR) after neoadjuvant immunotherapy plus chemoradiotherapy (NICRT) in locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 105 patients with locally advanced ESCC receiving NICRT from February 2019 to December 2023 were enrolled. Patients were randomly divided into the training cohort and the test cohort at a 3:1 ratio. Enhanced CT scans were obtained before NICRT treatment. The 2D and 3D regions of interest were segmented, and features were extracted, followed by feature selection. Six algorithms were applied to construct the radiomics and clinical models. These models were evaluated by area under curve (AUC), accuracy, sensitivity, and specificity, and their respective optimal algorithms were further compared. RESULTS: Forty-eight patients (45.75%) achieved pCR after NICRT. The AUC values of three algorithms in 2D radiomics models were higher than those in the 3D radiomics model and clinical model. Among these, the 2D radiomics model based on eXtreme Gradient Boosting (XGBoost) exhibited the best performance, with an AUC of 0.89 (95% CI, 0.81-0.97), accuracy of 0.85, sensitivity of 0.86, and specificity of 0.84 in the training cohort, and an AUC of 0.80 (95% CI, 0.64-0.97), accuracy of 0.77, sensitivity of 0.84, and specificity of 0.69 in the test cohort. Calibration curves also showed good agreement between predicted and actual response, and the decision curve analysis further confirmed its clinical applicability. CONCLUSION: The 2D radiomics model can effectively predict pCR to NICRT in locally advanced ESCC. KEY POINTS: Question Can CT-based radiomics predict pathologic complete response (pCR) after neoadjuvant immunotherapy plus chemoradiotherapy (NICRT) in locally advanced esophageal squamous cell carcinoma (ESCC)? Findings The model based on eXtreme Gradient Boosting (XGBoost) performed best, with an AUC of 0.89 in the training and 0.80 in the test cohort. Clinical relevance This CT-based radiomics model exhibits promising performance for predicting pCR to NICRT in locally advanced ESCC, which may be valuable in personalized treatment plan optimization.

Safety and effectiveness of using Disposable Ultrasonic shears to coagulate 5-7 mm blood vessels: protocol for a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial.

BACKGROUND: The ultrasonic scalpel is widely used during surgery. It is safe and effective to close the pulmonary artery branch vessels of 7 mm or below with an ultrasonic energy device as reported. However, there have been no multicenter randomized clinical trial to assess the safety and effectiveness of using ultrasonic scalpel to coagulate 5-7 mm blood vessels in thoracic surgery. METHODS: This is a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial. A total of 144 eligible patients planning to undergo lung or esophageal surgery will be randomly allocated to the experimental group and the control group. The investigational product (Disposable Ultrasonic Shears manufactured by Reach Surgical, Inc.) and the control product (Harmonic Ace + 7, 5 mm Diameter Shears with Advanced Hemostasis) will be used in each group. The primary endpoint is the success rate of coagulating target blood vessels during surgery. Secondary endpoints include postoperative rebleeding, intraoperative bleeding volume, drainage volume, surgical duration, etc. Postoperative follow-up before and after discharge will be performed. DISCUSSION: This clinical trial aims to evaluate the safety and effectiveness of using the investigational product (Disposable Ultrasonic Shears manufactured by Reach Surgical, Inc.) and that of the control product (Harmonic Ace + 7, 5 mm Diameter Shears with Advanced Hemostasis) to coagulate 5-7 mm blood vessels in thoracic surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06002737. The trial was prospectively registered on 16 August 2023, https://www. CLINICALTRIALS: gov/study/NCT06002737 .

Robotic Versus Conventional Minimally Invasive Esophagectomy for Esophageal Cancer: A Meta-analysis.

OBJECTIVES: To give a comprehensive review of the literature comparing perioperative outcomes and long-term survival with robotic-assisted minimally invasive esophagectomy (RAMIE) versus minimally invasive esophagectomy (MIE) for esophageal cancer. BACKGROUND: Curative minimally invasive surgical treatment for esophageal cancer includes RAMIE and conventional MIE. It remains controversial whether RAMIE is comparable to MIE. METHODS: This review was registered at the International Prospective Register of Systematic Reviews (CRD42021260963). A systematic search of databases was conducted. Perioperative outcomes and long-term survival were analyzed and subgroup analysis was conducted. Cumulative meta-analysis was performed to track therapeutic effectiveness. RESULTS: Eighteen studies were included and a total of 2932 patients (92.88% squamous cell carcinoma, 29.83% neoadjuvant therapy, and 38.93% stage III-IV), 1418 underwent RAMIE and 1514 underwent MIE, were analyzed. The number of total lymph nodes (LNs) [23.35 (95% CI: 21.41-25.29) vs 21.98 (95% CI: 20.31-23.65); mean difference (MD) = 1.18; 95% CI: 0.06-2.30; P =0.04], abdominal LNs [9.05 (95% CI: 8.16-9.94) vs 7.75 (95% CI: 6.62-8.88); MD = 1.04; 95% CI: 0.19-1.89; P =0.02] and LNs along the left recurrent laryngeal nerve [1.74 (95% CI: 1.04-2.43) vs 1.34 (95% CI: 0.32-2.35); MD = 0.22; 95% CI: 0.09-0.35; P <0.001] were significantly higher in the RAMIE group. RAMIE is associated with a lower incidence of pneumonia [9.61% (95% CI: 7.38%-11.84%) vs 14.74% (95% CI: 11.62%-18.15%); odds ratio = 0.73; 95% CI: 0.58-0.93; P =0.01]. Meanwhile, other perioperative outcomes, such as operative time, blood loss, length of hospital stay, 30/90-day mortality, and R0 resection, showed no significant difference between the two groups. Regarding long-term survival, the 3-year overall survival was similar in the two groups, whereas patients undergoing RAMIE had a higher rate of 3-year disease-free survival compared with the MIE group [77.98% (95% CI: 72.77%-82.43%) vs 70.65% (95% CI: 63.87%-77.00%); odds ratio = 1.42; 95% CI: 1.11-1.83; P =0.006]. A cumulative meta-analysis conducted for each outcome demonstrated relatively stable effects in the two groups. Analyses of each subgroup showed similar overall outcomes. CONCLUSIONS: RAMIE is a safe and feasible alternative to MIE in the treatment of resectable esophageal cancer with comparable perioperative outcomes and seems to indicate a possible superiority in LNs dissection in the abdominal cavity, and LNs dissected along the left recurrent laryngeal nerve and 3-year disease-free survival in particular in esophageal squamous cell carcinoma. Further randomized studies are needed to better evaluate the long-term benefits of RAMIE compared with MIE.

Lymph Node Ratio Improves Prediction of Overall Survival in Esophageal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy: A National Cancer Database Analysis.

OBJECTIVE: This study aimed to propose a revised ypN (r-ypN) classification based on lymph node ratio (LNR) and to examine its prognostic value in postneoadjuvant esophageal cancer. BACKGROUND: A new postneoadjuvant pathologic (ypTNM) staging classification has been introduced for esophageal cancer. However, the ypN classification currently defined by the number of positive lymph nodes is influenced by the extent of lymphadenectomy. METHODS: Data on 7195 esophageal cancer patients receiving neoadjuvant chemoradiation were extracted from the National Cancer Database (NCDB). Four r-ypN stages were defined by 3 LNR thresholds (0%, 10%, and 20% using X-tile software). A revised ypTNM (r-ypTNM) classification was developed by solely changing N categories. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. Akaike information criterion (AIC) and Harrell's concordance index ( C -index) were used to compare the predictive performance of the current and the revised classification. External validation was performed using an independent cohort from the NEOCRTEC5010 clinical trial. RESULTS: Both ypN ( P <0.001) and r-ypN ( P <0.001) were independent prognostic factors of overall survival (OS) for esophageal cancer patients. Kaplan-Meier curves demonstrated a better discrimination with r-ypN than ypN categories. Within each ypN category (except ypN3), OS was significantly different comparing r-ypN strata; however, there were no differences between ypN strata within each r-ypN category (except r-ypN3). r-ypN (AIC: 60752 vs 60782; C -index: 0.591 vs 0.587) and r-ypTNM (AIC: 60623 vs 60628; C -index: 0.613 vs 0.610) showed better predictive performance than the current staging system, with a lower AIC (better calibration) and higher C -index (improved discrimination). This advantage was also confirmed by external validation using the NEOCRTEC5010 cohort. CONCLUSIONS: LNR showed better performance than ypN in predicting OS of esophageal cancer patients after neoadjuvant chemoradiation and may be an improvement on the current staging system.

The active phthalate metabolite, DHEP, induces proliferation and metastasis of prostate cancer cells via upregulation of ß-catenin and downregulation of KLF7.

Phthalates such as DHEP are among the widely used compounds in industry. It has been shown that DHEP can convey various biological consequences in mammalian cells, among them, the carcinogenic effects of DHEP are emphasized. The present study aimed to assess the impact of DHEP exposure on the proliferation and invasiveness of DU145 prostate cancer cells through in vitro and in vivo models. The DU145 cells were treated with increasing concentrations of DHEP and the tumorigenic parameters were analyzed. KLF7 as a probable mediator of the effect of DHEP was either overexpressed or knocked down in DU145 to evaluate the probable impact of KLF7 on the biological effects of DHEP. The effect of DHEP was also studied in a DU145 xenograft tumor model. The moderate doses of DHEP increased the proliferation and migration of DU145 cells. In the case of gene expression patterns, DHEP reduced the levels of p53 and KLF7 while elevated the expression of ß-catenin. The knock-down of KLF7 conveyed comparable effects to that of DHEP to some degree and increased the proliferation of DU145 cells, while the transduction of KLF7 increased the expressions of p53 and p21 along with controlling the tumor size. The present study demonstrated the potential of DHEP in increasing the tumorigenic properties of DU145 cells along with a focus on the underlying mechanisms. Sustained exposure to DHEP can cause a dysregulation in balance between oncogenes and tumor suppressor genes which is the hallmark of malignant transformation. Thus, special considerations seem necessary for the safe exploitation of phthalates.

Hybrid laparoscopic versus fully robot-assisted minimally invasive esophagectomy: an international propensity-score matched analysis of perioperative outcome.

BACKGROUND: Currently, little is known regarding the optimal technique for the abdominal phase of RAMIE. The aim of this study was to investigate the outcome of robot-assisted minimally invasive esophagectomy (RAMIE) in both the abdominal and thoracic phase (full RAMIE) compared to laparoscopy during the abdominal phase (hybrid laparoscopic RAMIE). METHODS: This retrospective propensity-score matched analysis of the International Upper Gastrointestinal International Robotic Association (UGIRA) database included 807 RAMIE procedures with intrathoracic anastomosis between 2017 and 2021 from 23 centers. RESULTS: After propensity-score matching, 296 hybrid laparoscopic RAMIE patients were compared to 296 full RAMIE patients. Both groups were equal regarding intraoperative blood loss (median 200 ml versus 197 ml, p = 0.6967), operational time (mean 430.3 min versus 417.7 min, p = 0.1032), conversion rate during abdominal phase (2.4% versus 1.7%, p = 0.560), radical resection (R0) rate (95.6% versus 96.3%, p = 0.8526) and total lymph node yield (mean 30.4 versus 29.5, p = 0.3834). The hybrid laparoscopic RAMIE group showed higher rates of anastomotic leakage (28.0% versus 16.6%, p = 0.001) and Clavien Dindo grade 3a or higher (45.3% versus 26.0%, p < 0.001). The length of stay on intensive care unit (median 3 days versus 2 days, p = 0.0005) and in-hospital (median 15 days versus 12 days, p < 0.0001) were longer for the hybrid laparoscopic RAMIE group. CONCLUSIONS: Hybrid laparoscopic RAMIE and full RAMIE were oncologically equivalent with a potential decrease of postoperative complications and shorter (intensive care) stay after full RAMIE.

DKK1 Ameliorates Myofibroblast Differentiation in Urethral Fibrosis in Vivo and in Vitro by Regulating the Canonical Wnt Pathway.

Background: Urethral stricture is a common disorder of the lower urinary tract in men. A complex network of pathways and interactions are involved in the pathogenesis of urethral fibrosis. However, the mechanisms underlying urethral fibrosis remain poorly understood. Objectives: To investigate the critical role of the canonical Wnt pathway in development of urethral fibrosis and explore DKK1, the endogenous inhibitor of Wnt pathway, as a potential target to prevent urethral fibrosis in vitro and in vivo. Methods: Urethral fibrosis tissue derived from patients and rat models were harvested to assess the activation of the canonical Wnt pathway by using western blot, qRT-PCR and immunohistochemistryWe performed histological staining, western blot, qRT-PCR and immunohistochemistry to examine the effects of DKK1 treatment on in vivo rat urethral fibrosis models. In vitro, human urethral fibroblasts (HUFs) were cultured to examine the effects of DKK1 in TGFß1-induced HUFs by CCK-8 assay, hydroxyproline assay, flow cytometry, cell migration assay, western blot, qRT-PCR and immunofluorescence. Results: The key components of Wnt signaling were upregulated in urethral fibrosis tissue derived from patients and rat models while DKK 1 was downregulated. DKK1 ameliorated TGFß1-induced urethral fibrosis in rats. TGFß1 induced myofibroblast differentiation by upregulating collagen I, collagen III, α-SMA, ß-catenin and p-GSK-3ß, while DKK1 was decreased. DKK1 significantly inhibited cell proliferation, collagen content, cell migration and promoted cell apoptosis in TGFß1-induced HUFs. DKK1 significantly suppressed myofibroblast differentiation of TGFß1-induced HUFs by downregulating collagen I, collagen III, α-SMA, ß-catenin and p-GSK-3ß with a mechanism independent of Smad2/3. Conclusions: Our study demonstrated that canonical Wnt pathway may be an essential mechanism underlying the pathogenesis of urethral fibrosis and explored the potential role of DKK1 participation in the development of urethral fibrosis.

MKRN3-mediated ubiquitination of Poly(A)-binding proteins modulates the stability and translation of GNRH1 mRNA in mammalian puberty.

The family of Poly(A)-binding proteins (PABPs) regulates the stability and translation of messenger RNAs (mRNAs). Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC). Recently, we have shown that MKRN3 epigenetically regulates the transcription of GNRH1 through conjugating poly-Ub chains onto methyl-DNA bind protein 3 (MBD3). Therefore, MKRN3-mediated ubiquitin signalling could control both transcriptional and post-transcriptional switches of mammalian puberty initiation. While identifying MKRN3 as a novel tissue-specific translational regulator, our work also provided new mechanistic insights into the etiology of MKRN3 dysfunction-associated human CPP.

The diverse role of RNA methylation in esophageal cancer.

Esophageal cancer is one of the major life-threatening diseases in the world. RNA methylation is the most common post-transcriptional modification and a wide-ranging regulatory system controlling gene expression. Numerous studies have revealed that dysregulation of RNA methylation is critical for cancer development and progression. However, the diverse role of RNA methylation and its regulators in esophageal cancer remains to be elucidated and summarized. In this review, we focus on the regulation of major RNA methylation, including m 6A, m 5C, and m 7G, as well as the expression patterns and clinical implications of its regulators in esophageal cancer. We systematically summarize how these RNA modifications affect the "life cycle" of target RNAs, including mRNA, microRNA, long non-coding RNA, and tRNA. The downstream signaling pathways associated with RNA methylation during the development and treatment of esophageal cancer are also discussed in detail. Further studies on how these modifications function together in the microenvironment of esophageal cancer will draw a clearer picture of the clinical application of novel and specific therapeutic strategies.

Urine metabolomic characteristics of female patients with occupational chronic cadmium poisoning after 15 years of treatment.

Occupational chronic cadmium poisoning (OCCP) can cause irreversible organ damage. Currently, no effective treatment is available for OCCP, and effective and sensitive biomarkers for treatment evaluation are still lacking. In this study, metabolomics techniques were used to analyze changes in endogenous metabolites in the urine of patients with OCCP after 15 years of treatment. Thirty urine samples from female patients with OCCP and healthy female controls (n = 15 per group) were assessed using gas chromatography-time-of-flight mass spectrometry and ultra-high-performance liquid chromatography-Q-Exactive mass spectrometry. The OCCP group had higher concentrations of blood urea nitrogen and urinary cadmium but near-normal urinary concentrations of ß2 -microglobulin and retinol-binding protein. Compared with the control group, the OCCP group had 66 significantly different metabolites with a variable importance in projection score >1 and p < 0.05. These differential metabolites were involved in various metabolic pathways, such as creatine metabolism, nicotinate and nicotinamide metabolism, the pentose phosphate pathway, d-glutamine and d-glutamate metabolism, and amino acid metabolism. Compared with the control group, the OCCP group had significantly higher urinary concentrations of creatine, glutamic acid, quinolinic acid and nicotinic acid. In a receiver operator characteristic analysis, the area under the curve of creatine was higher than those for glutamic acid, quinolinic acid and nicotinic acid, indicating that urinary concentrations of creatine could be used as a sensitive biomarker for the diagnosis and prognosis of OCCP and for monitoring its treatment.

Long-Term Survival and Prognostic Factors After Laparoscopic Radical Nephrectomy.

Purpose: Our study aims to investigate the long-term survival and prognostic factors of patients after laparoscopic radical nephrectomy. Methods: Totally, 245 patients with renal cell carcinoma in our hospital from January 2015 to February 2017 were analyzed retrospectively. The 5-year survival status of patients with renal cell carcinoma was under analysis and further based on univariate analysis, and its influencing factors were analyzed by Cox regression. Results: The average 5-year follow-up time of 245 patients with renal cell carcinoma was (4.88 ± 0.52) years. The mortality of 1 year, 3 years and 5 years were 2.45% (5/245), 6.35% (16/245) and 9.80% (24/245), respectively. The survival rates were 97.55% (239/245), 93.06% (228/245) and 90.61% (222/245). Univariate analysis showed that age, tumor diameter, hematuria, TNM stage and postoperative recurrence may be the influencing factors of 5-year survival of patients with renal cell carcinoma (P < .05). However, the following parameters, including gender, course of disease, and other clinical complications were not related to the 5-year survival of patients with renal cell carcinoma (P > .05). the influencing factors of 5-year survival status of patients with renal cell carcinoma were age, tumor diameter, hematuria, TNM stage, and postoperative recurrence. Conclusion: The study revealed the long-term survival of patients with renal cell carcinoma may be associated with age, tumor diameter, hematuria, TNM stage and postoperative recurrence.

Robot-assisted Versus Conventional Minimally Invasive Esophagectomy for Resectable Esophageal Squamous Cell Carcinoma: Early Results of a Multicenter Randomized Controlled Trial: the RAMIE Trial.

OBJECTIVE: To compare perioperative and long-term outcomes of robot-assisted minimally invasive esophagectomy (RAMIE) and conventional minimally invasive esophagectomy (MIE) in the treatment for patients with esophageal squamous cell carcinoma (ESCC). SUMMARY BACKGROUND DATA: RAMIE has emerged as an alternative to traditional open or thoracoscopic approaches. Efficacy and safety of RAMIE and MIE in the surgical treatment for ESCC remains uncertain given the lack of high-level clinical evidence. METHODS: The RAMIE trial was designed as a prospective, multicenter, randomized, controlled clinical trial that compares the efficacy and safety of RAMIE and MIE in the treatment of resectable ESCC. From August 2017 to December 2019, eligible patients were randomly assigned to receive either RAMIE or MIE performed by experienced thoracic surgeons from 6 high-volume centers in China. Intent-to-treat analysis was performed. RESULTS: Significantly shorter operation time was taken in RAMIE (203.8 vs 244.9 min, P<0.001). Compared with MIE, RAMIE showed improved efficiency of thoracic lymph node dissection in patients who received neoadjuvant therapy (15 vs 12, P = 0.016), as well as higher achievement rate of lymph node dissection along the left recurrent laryngeal nerve (79.5% vs 67.6%, P = 0.001). No difference was found in blood loss, conversion rate, and R0 resection. The 90-day mortality was 0.6% in each group. Overall complications were similar in RAMIE (48.6%) compared with MIE (41.8%) (RR, 1.16; 95% CI, 0.92-1.46; P = 0.196). Besides, the rate of major complications (Clavien-Dindo classification ≥ III) was also comparable (12.2% vs 10.2%, P = 0.551). RAMIE showed similar incidences of pulmonary complications (13.8% vs 14.7%; P = 0.812), anastomotic leakage (12.2% vs 11.3%; P = 0.801), and vocal cord paralysis (32.6% vs 27.1%, P = 0.258) to MIE. CONCLUSIONS: Early results demonstrate that both RAMIE and MIE are safe and feasible for the treatment of ESCC. RAMIE can achieve shorter operative duration and better lymph node dissection in patients who received neoadjuvant therapy. Long-term results are pending for further follow-up investigations. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT03094351.

Robotic-assisted Versus Video-assisted Thoracoscopic Lobectomy: Short-term Results of a Randomized Clinical Trial (RVlob Trial).

OBJECTIVE: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. SUMMARY OF BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550-1130 mL] vs 685 mL [IQR, 367.5-1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145-$13924) vs $8009 (IQR, $7014-$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8-15) vs 10 (IQR, 8-13), P = 0.02], higher number of N1 LNs [6 (IQR, 4-8) vs 5 (IQR, 3-7), P = 0.005], and more LN stations examined [6 (IQR, 5-7) vs 5 (IQR, 4-6), P < 0.001]. CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).

Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy).

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .

Immature rat testis sustained long-term development using an integrative model.

BACKGROUND: Xenotransplantation has been primarily performed using fresh donor tissue to study testicular development for about 20 years, and whether the cultured tissue would be a suitable donor is unclear. In this study, we combined testicular culture and xenotransplantation into an integrative model and explored whether immature testicular tissue would survive and continue to develop in this model. METHODS: In the new integrative model group, the testes of neonatal rats on postnatal day 8 (PND 8) were cultured for 4 days ex vivo and then were transplanted under the dorsal skin of castrated nude mice. The xenografted testes were resected on the 57th day after xenotransplantation and the testes of rats in the control group were harvested on PND 69. The survival state of testicular tissue was evaluated from morphological and functional perspectives including H&E staining, immunohistochemical staining of 8-OH-dG, immunofluorescence staining, TUNEL assay, ultrastructural study, gene expression and protein analysis. RESULTS: (a) We found that complete spermatogenesis was established in the testes in the new integrative model group. Compared with the control in the same stage, the seminiferous epithelium in some tubules was a bit thinner and there were vacuoles in part of the tubules. Immunofluorescence staining revealed some ACROSIN-positive spermatids were present in seminiferous tubule of xenografted testes. TUNEL detection showed apoptotic cells and most of them were germ cells in the new integrative model group. 8-OH-dG immunohistochemistry showed strongly positive-stained in the seminiferous epithelium after xenotransplantation in comparison with the control group; (b) Compared with the control group, the expressions of FOXA3, DAZL, GFRα1, BOLL, SYCP3, CDC25A, LDHC, CREM and MKI67 in the new integrative model group were significantly elevated (P < 0.05), indicating that the testicular tissue was in an active differentiated and proliferative state; (c) Antioxidant gene detection showed that the expression of Nrf2, Keap1, NQO1 and SOD1 in the new integrative model group was significantly higher than those in the control group (P < 0.05), and DNA methyltransferase gene detection showed that the expression of DNMT3B was significantly elevated as well (P < 0.05). CONCLUSION: The new integrative model could maintain the viability of immature testicular tissue and sustain the long-term survival in vivo with complete spermatogenesis. However, testicular genes expression was altered, vacuolation and thin seminiferous epithelium were still apparent in this model, manifesting that oxidative damage may contribute to the testicular development lesion and it needs further study in order to optimize this model.

Review of Approaches to Developing Intersegmental Plane during Segmentectomy.

In recent years, with the popularity of computed tomography (CT) scanning, early lung cancer has been found in a large number of patients, and segmentectomy has been widely used in clinical practice. The development of intersegmental plane is the most critical step in segmentectomy. At present, there are many methods to identify the intersegmental plane. Also, dissection of the intersegmental plane has been a challenge for thoracic surgeons for decades because of the complicated anatomic variations. This study focuses on the safety and efficacy of relevant methods in both identification and dissection of the intersegmental plane in segmentectomy.

Effects of preoperative nutrition on postoperative outcomes in esophageal cancer: a systematic review and meta-analysis.

Postoperative enteral nutrition has been widely implemented in esophageal cancer, but the efficacy and safety of preoperative nutrition, particularly immune-enhancing nutrition (IEN), remain controversial. This meta-analysis aims to provide a quantitative synthesis of whether preoperative nutrition improves postoperative morbidity and mortality in patients with resectable esophageal cancer. A systematic search was conducted in Medline, Embase, Cochrane, and databases of clinical trials dated up to December 2019. Randomized controlled trials and observational studies comparing postoperative outcomes between esophageal cancer patients with and without preoperative nutritional support were included. Random-effects model was applied in the meta-analysis of primary outcomes (overall complication rate, in-hospital mortality) and secondary outcomes (infectious complication rate, anastomotic leak rate, length of postoperative hospital stay). Complications of feeding tube access and perioperative weight loss were evaluated by qualitative synthesis. Subgroup analyses were performed by stratifying immunonutrition and standard nutrition before surgery. Subgroup analysis of randomized controlled trials alone was also done. A total of 15 studies enrolling 1864 participants were included. The overall meta-analysis found that preoperative nutrition could reduce infectious complications (odds ratio [OR] = 0.51, 95% confidence interval [CI] [0.26, 0.98]; I2 = 48%) and length of hospital stay (mean difference = -2.10 day, 95% CI [-3.72, -0.47]; I2 = 78%) after esophagectomy, whereas no significant difference was revealed in the incidence of overall complications (OR = 0.76, 95% CI [0.52, 1.11]; I2 = 32%), in-hospital mortality (OR = 1.03, 95% CI [0.41, 2.61]; I2 = 12%), and anastomotic leak (OR = 1.05, 95% CI [0.69, 1.58]; I2 = 0%). Subgroup of preoperative immunonutrition showed more prominent benefits. The complication rate of feeding tube access was low (1.6-16%). In conclusion, preoperative nutrition is safe in esophageal cancer, but benefits are observed in infectious complication rate and length of stay on a limited scale. IEN holds more advantages over standard nutrition. Randomized trials in the context of nutritional support during neoadjuvant therapy are in demand.

Learning curve for robot-assisted Ivor Lewis esophagectomy.

This study aimed to demonstrate the learning curve of robot-assisted minimally invasive esophagectomy (RAMIE). A retrospective analysis of the first 124 consecutive patients who underwent RAMIE with intrathoracic anastomosis (Ivor Lewis) by a single surgeon between May 2015 and August 2020 was performed. An risk-adjusted cumulative sum (RA-CUSUM) analysis was applied to generate a learning curve of RAMIE considering the major complication rate, which reflected the technical proficiency. The overall 30-day morbidity rate was 38.7%, while the major complication rate was 25.8%. The learning curve was divided into two phases based on the RA-CUSUM analysis: phase I, the initial learning phase (cases 1-51) and phase II, the proficiency phase (cases 52-124). As we compared the proficiency phase with the initial learning phase, significantly decreased trends were observed in relation to the major complication rate (37.3% vs. 18.7%, P = 0.017), total operation time (330.9 ± 55.6 vs. 267.3 ± 39.1 minutes, P < 0.001), and length of hospitalization (10 [IQR, 9-14] days vs. 9 [IQR, 8-11] days, P = 0.034). In conclusion, the learning curve of RAMIE consisted of two phases, and at least 51 cases were required to gain technical proficiency.