[Non-targeted renal metabolomics reveals multi-target effects of Dahuang Zhechong Pills on renal aging in rats].

This study aims to observe the effects of the traditional Chinese medicine prescription Dahuang Zhechong Pills(DHZCP on renal aging and explore its potential multi-target effects. Rats were assigned into the normal, model, DHZCP, and vitamin E(VE)groups. Firstly, the rat model of D-galactose(D-gal)-induced renal aging was established. During the modeling period, the rats in the 4 groups were administrated with double distilled water, double distilled water, DHZCP suspension, and VE suspension, respectively,by gavage every day. On day 60 of intervention, the indicators of renal aging and injury in rats were measured, including the function,histopathological characteristics, senescence-associated ß-galactosidase( SA-ß-gal) staining, and expression levels of Klotho and proteins associated with cell cycle arrest and senescence-associated secretory phenotype(SASP) in the renal tissue. Moreover, nontargeted metabolomic analysis of the renal tissue was performed for the 4 groups of rats to screen out the potential biomarkers and metabolic pathways. Finally, the signaling pathways of key targets were preliminarily validated. The results showed that DHZCP and VE significantly improved the renal function, histopathological features of renal tubular/interstitial tissue, and degree of SA-ß-gal staining, up-regulated the expression level of Klotho, and down-regulated the expression levels of proteins associated with cell cycle arrest and SASP in the renal tissue of the aging rats. In addition, DHZCP and VE regulated the metabolites in the renal tissue of the aging rats. There were 21 common differential metabolites. Among them, 5 differential metabolites were significantly increased in the aging rats and recovered after DHZCP or VE treatment, and they were involved in the lipid metabolism and energy metabolism pathways. The areas under the curves of the groups in comparison varied within the range of 0. 88-1. DHZCP regulated multiple signaling pathways, such as the adenosine monophosphate-activated protein kinase(AMPK), cyclic guanosine monophosphate-protein kinase G( c GMP-PKG), cyclic adenylic acid( c AMP), phosphatidylinositol-3-kinase-protein kinase B( PI3K-Akt), mammalian target of rapamycin(mTOR), and autophagy signaling pathways. In addition, it affected the multiple metabolic pathways, such as renin secretion, longevity regulation pathway, diabetic cardiomyopathy, and niacin and nicotinamide metabolism. DHZCP and VE significantly up-regulated the expression level of the key proteins in the AMPK signaling pathway in the renal tissue of the aging rats. In all, DHZCP and VE could mitigate renal aging and injury. DHZCP exerted multi-target effects via multiple signaling pathways and metabolic pathways in the kidney, in which the AMPK signaling pathway may be one of the key targets for action.

Mapping of lymph node metastasis from esophageal squamous cell carcinoma after neoadjuvant treatment: a prospective analysis from a high-volume institution in China.

The study aimed to describe the prevalence of lymph node metastases per lymph node station for esophageal squamous cell carcinoma (ESCC) after neoadjuvant treatment. Clinicopathological variables of ESCC patients were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. A two-field lymphadenectomy was routinely performed, and an extensive three-field lymphadenectomy was performed if cervical lymph node metastasis was suspected. According to AJCC/UICC 8, lymph node stations were investigated separately. The number of patients with metastatic lymph nodes divided by those who underwent lymph node dissection at that station was used to define the percentage of patients with lymph node metastases. Data are also separately analyzed according to the pathological response of the primary tumor, neoadjuvant treatment regimens, pretreatment tumor length, and tumor location. Between January 2019 and March 2023, 623 patients who underwent neoadjuvant therapy followed by transthoracic esophagectomy were enrolled. Lymph node metastases were found in 212 patients (34.0%) and most frequently seen in lymph nodes along the right recurrent nerve (10.1%, 58/575), paracardial station (11.4%, 67/587), and lymph nodes along the left gastric artery (10.9%, 65/597). For patients with pretreatment tumor length of >4 cm and non-pathological complete response of the primary tumor, the metastatic rate of the right lower cervical paratracheal lymph nodes is 10.9% (10/92) and 10.6% (11/104), respectively. For patients with an upper thoracic tumor, metastatic lymph nodes were most frequently seen along the right recurrent nerve (14.2%, 8/56). For patients with a middle thoracic tumor, metastatic lymph nodes were most commonly seen in the right lower cervical paratracheal lymph nodes (10.3%, 8/78), paracardial lymph nodes (10.2%, 29/285), and lymph nodes along the left gastric artery (10.4%, 30/289). For patients with a lower thoracic tumor, metastatic lymph nodes were most frequently seen in the paracardial station (14.2%, 35/247) and lymph nodes along the left gastric artery (13.1%, 33/252). The study precisely determined the distribution of lymph node metastases in ESCC after neoadjuvant treatment, which may help to optimize the extent of lymphadenectomy in the surgical management of ESCC patients after neoadjuvant therapy.

Impact of deep muscle invasion on nodal status and survival in patients with pT2 esophageal squamous cancer.

BACKGROUND: Whether T2 esophageal squamous cell carcinoma should be subclassified remains controversial. We aimed to investigate the impact of the depth of muscularis propria invasion on nodal status and survival outcomes. METHODS: We identified patients with pT2 esophageal squamous cell carcinoma who underwent primary surgery from January 2009 to June 2017. Clinical data were extracted from prospectively maintained databases. Tumor muscularis propria invasion was stratified into superficial or deep. Binary logistic regression was used to determine risk factors for lymph node metastases. The impact of the depth of muscularis propria invasion on survival was investigated using Kaplan‒Meier analysis and a Cox proportional hazard regression model. RESULTS: A total of 750 patients from three institutes were investigated. The depth of muscularis propria invasion (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 2.46-6.35; p < 0.001) was correlated with lymph node metastases using logistic regression. T substage (hazard ratio [HR]: 1.37, 95% CI: 1.05-1.79; p < 0.001) and N status (HR: 1.51, 95% CI: 1.05-2.17; p < 0.001) were independent risk factors in multivariate Cox regression analysis. The deep muscle invasion was associated with worse overall survival (HR: 1.52, 95% CI: 1.19-1.94; p = 0.001) than superficial, specifically in T2N0 patients (HR: 1.38, 95% CI: 1.08-1.94; p = 0.035). CONCLUSIONS: We found that deep muscle invasion was associated with significantly worse outcomes and recommended the substaging of pT2 esophageal squamous cell carcinoma in routine pathological examination.

The prognostic impact of preoperative body mass index changes for patients with esophageal squamous cell carcinoma who underwent esophagectomy: A large-scale long-term follow-up cohort study.

Background: This study aims to investigate the relationship between preoperative body mass index changes (ΔBMI) and prognosis in patients with esophageal squamous cell carcinoma who underwent esophagectomy. Methods: We identified 1,883 patients with esophageal squamous cell carcinoma who underwent curative resection in our department between January 2005 and December 2013. Patients were grouped into a stable body mass index (ΔBMI = 0) group and a decreased body mass index (ΔBMI < 0) group. Risk factors for ΔBMI were assessed using logistic regression analysis. The impact of ΔBMI on survival was investigated using Kaplan-Meier curves and Cox regression. A nomogram for survival prediction was constructed and validated. Results: The results showed that T stage (OR: 1.30, 95% CI: 1.16-1.45, P < 0.001) and N stage (OR: 1.24, 95% CI: 1.11-1.38, P < 0.001) were independent risk factors for ΔBMI. The ΔBMI < 0 group had worse overall survival than the stable body mass index group (HR: 1.25, 95% CI: 1.08-1.44, P = 0.002). When stratified by stage, ΔBMI had the greatest prognostic impact in stage I tumors (HR: 1.82, 95%: 1.05-3.15, P = 0.033). In addition, multiple comparisons showed that decreasing ΔBMI correlated with worse prognosis. The ΔBMI-based nomogram presented good predictive ability with a C-index of 0.705. Conclusion: This study demonstrates that ΔBMI < 0 had an adverse impact on the long-term survival of patients with esophageal squamous cell carcinoma undergoing esophagectomy. These results may support further investigation of preoperative nutrition support.

Effect of circumferential resection margin status on survival and recurrence in esophageal squamous cell carcinoma with neoadjuvant chemoradiotherapy.

Background: The aim of this study was to investigate whether circumferential resection margin (CRM) status has an impact on survival and recurrence in esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy. Methods: We screened patients with esophageal squamous cell carcinoma who underwent esophagectomy from January 2017 to December 2019. The CRM was reassessed. Patients were grouped into a CRM of 1 mm or less (0 < CRM ≤ 1 mm) and a CRM greater than 1 mm (CRM>1 mm). The impact of CRM on survival was investigated using Kaplan-Meier analysis and Cox regression modeling. The optimal CRM cut point was evaluated using restricted cubic spline curve. Results: A total of 89 patients were enrolled in this study. The CRM status was an independent risk factor for the prognosis (HR: 0.35, 95% CI: 0.16-0.73). Compared with a CRM of 1 mm or less, a CRM greater than 1 mm had better overall survival (HR: 0.35, 95% CI: 0.16-0.73, log-rank P = 0.011), longer disease-free survival (HR: 0.51, 95% CI: 0.27-0.95, log-rank P = 0.040), and less recurrence (HR: 0.44, 95% CI: 0.23-0.85, log-rank P = 0.015). We visualized the association between CRM and the hazard ratio of survival and identified the optimal cut point at 1 mm. Conclusions: A CRM greater than 1 mm had better survival and less recurrence compared to a CRM of 1 mm or less. A more radical resection with adequate CRM could benefit survival in patients with esophageal squamous cell carcinoma after neoadjuvant therapy.

Is Tumor Regression Grade Sufficient to Predict Survival in Esophageal Cancer with Trimodal Therapy?

BACKGROUND: This study aimed to assess the predictive value of tumor regression grade (TRG) and nodal status on survival in esophageal carcinoma with neoadjuvant chemoradiotherapy (nCRT). METHODS: Tumor pathologic regression and nodal status were assessed. Differences in survival stratified by TRG or nodal status were analyzed using the Kaplan-Meier method and log-rank test. The prognostic value of TRG and nodal status were analyzed using univariate and multivariate Cox proportional hazards methods. RESULTS: From July 2016 to June 2019, 253 patients with esophageal cancer underwent nCRT followed by surgery. Significant differences were presented in survival according to nodal status but not TRG. Multivariate analysis showed that nodal status and not TRG was the only independent predicter for overall survival (HR: 3.550, 95% CI: 2.264-5.566, P < 0.001) and disease-free survival (HR: 2.801, 95% CI: 1.874-4.187, P < 0.001). The modified TRG system combining tumor regression with nodal status stratified patients survival with good discrimination. CONCLUSIONS: Lymph node status impacts more importantly than TRG on survival for patients with esophageal cancer undergoing nCRT plus esophagectomy. The modified TRG system may facilitate postoperative treatment decisions and survival surveillance.

Limited-stage small cell carcinoma of the esophagus treated with curative esophagectomy: A multicenter retrospective cohort study.

BACKGROUND: This study aimed to investigate the efficacy of surgery in the treatment of small cell carcinoma of the esophagus (SCCE) and explore potential prognostic factors. METHODS: We screened patients with SCCE who underwent esophagectomy from 2010 to 2018 at three institutes. Differences in survival were analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were identified using univariate and multivariate analyses. RESULTS: A total of 69 patients were included. Multivariate analysis showed that TNM stage (hazard ratio [HR]: 4.10, 95% confidence interval [CI]: 1.57-10.75, p = 0.004) and adjuvant therapy (HR: 0.28, 95% CI: 0.16-0.51, p < 0.001) were independent prognostic factors. Stage I, stage IIA, and stage IIB disease were merged into the surgery response disease (SRD), whereas stage III disease into the surgery nonresponse disease (SNRD). The SRD group had significantly improved survival compared to the SNRD group (HR: 0.33, 95% CI: 0.19-0.58, p < 0.001). In addition, adjuvant therapy increased survival benefit in the SNRD group (p < 0.001) but not in the SRD group (p = 0.061). CONCLUSIONS: Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group.

Safety and Feasibility of Esophagectomy Following Neoadjuvant Immunotherapy Combined with Chemotherapy for Esophageal Squamous Cell Carcinoma.

Background: This study aimed to investigate the safety and feasibility of esophagectomy after neoadjuvant immunotherapy and chemotherapy for esophageal squamous cell carcinoma. Methods: We retrospectively identified patients who received neoadjuvant immunotherapy combined with chemotherapy (n = 38) in our center between 2020 and 2021. The primary end point was the risk of major complications (grade ≥3) according to the Clavien-Dindo classification. Secondary end points were surgical details, 30-day mortality, and 30-day readministration. Results: The most commonly used regimens of immunotherapy were camrelizumab (36.8%), pembrolizumab (31.5%), tislelizumab (15.8%), sintilimab (13.2%), and toripalimab (2.6%). The median interval to surgery was 63 days (range, 40-147). Esophagectomy was performed in 37 of 38 patients who received neoadjuvant immunotherapy and chemotherapy. All procedures were performed minimally invasively, except for 1 patient who was converted to thoracotomy. Of 37 surgical patients, R0 resection was achieved in 36 patients (97.3%). Pathologic complete response was observed in 9 patients (24.3%). Tumor regression grade I was identified in 17 patients (45.9%). Morbidity occurred in 12 of 37 patients (32.4%). The most common complication was pneumonia (16.2%). There were no deaths or readministration within 30 days. Conclusions: Esophagectomy following neoadjuvant immune checkpoint inhibitor plus chemotherapy for patients with resectable esophageal squamous cell carcinoma appears to be safe and feasible, with acceptable complication rates.

Short- and Long-Term Outcomes of Totally Versus Hybrid Minimally Invasive Ivor Lewis Oesophagectomy for Oesophageal Cancer: A Propensity Score-Matched Analysis.

Background: Few objective studies have compared totally minimally invasive Ivor Lewis oesophagectomy with hybrid procedure. Here we investigated whether the choice between totally and hybrid minimally invasive Ivor Lewis oesophagectomy influenced short-term outcomes and long-term patient survival. Methods: Patients who underwent totally or hybrid minimally invasive Ivor Lewis oesophagectomy between January 2014 and December 2017 were propensity score matched in a 1:1 ratio. The short- and long-term outcomes between the two groups were compared before and after matching. Results: Of 138 totally and 156 hybrid minimally invasive oesophagectomy patients were eligible, 104 patients from each group were propensity score matched. Totally minimally invasive oesophagectomy was associated significantly with less blood loss (median(IQR) 100(60-150) vs 120(120-200) ml respectively; P < 0.001), pneumonia (13.5 vs 25.0%; P = 0.035), pleural effusion (3.8 vs 13.5%; P = 0.014), and chest drainage (7.5(6-9) vs 8(7-9) days; P = 0.009) than hybrid procedure. There was no significant difference in 3-year overall survival rate and 3-year disease-free survival rate between the two group. Conclusions: Totally minimally invasive Ivor Lewis oesophagectomy may improve short-term outcomes and specifically reduce the incidence of pulmonary complications compared with hybrid procedure. The long-term overall survival and disease-free survival rates between the two groups were similar.

A Novel Technique to Optimize Uniportal Thoracoscopic Right Middle Lobectomy.

The study aimed to describe a novel port design and simple surgical strategy for uniportal thoracoscopic right middle lobectomy. In this approach, a 3- to 4-cm incision was created at the sixth intercostal space posterior to the scapular line. The surgery was performed by serial division of the anterior oblique fissure, vein, bronchus, artery, and horizontal fissure. Based on our preliminary experience, this approach could provide an appropriate direction and angle for dissection and stapling, solving the challenge of conventional uniportal right middle lobectomy.

A rare cause of chronic dysphagia: pulmonary inflammatory myofibroblastic tumor with distal esophagus invasion.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is rare intermediate tumor, which happens mostly in children and young adults. CASE PRESENTATION: Reported is the successful treatment of a 29-year-old man presented with progressively dysphagia and weight loss. No other abnormal symptoms were observed. The contrast enhanced computed tomography (CT) revealed a dumbbell-shaped lesion between lung and esophagus. Finally, it was pathologically diagnosed as pulmonary IMT invading to the distal esophagus after operation. The patient underwent partial esophagectomy and left lower lobectomy, and was discharged on 10th postoperative day. CONCLUSIONS: IMT is a rare lesion that usually occurs in the lung, but pulmonary IMT with distal esophagus invasion has not been described previously. Discriminating untypical symptom, completed resection, pathological expertise and closed follow-up will reach the successful diagnosis and treatment.

A rare Bochdalek hernia in an adult: a case report.

BACKGROUND: Symptomatic Bochdalek hernias are found mainly in infants in respiratory distress and occur rarely in adults. CASE PRESENTATION: We report a rare case of Bochdalek hernia associated with developmental abnormalities in an adult who exhibited acute chest pain and dyspnea on exertion. CONCLUSIONS: This case highlights the importance of the differential diagnosis of acute left-sided chest pain and antenatal examination.

The Clinical Application of Neoantigens in Esophageal Cancer.

Esophageal cancer (EC) is a common malignant tumor with poor prognosis, and current treatments for patients with advanced EC remain unsatisfactory. Recently, immunotherapy has been recognized as a new and promising approach for various tumors. EC cells present a high tumor mutation burden and harbor abundant tumor antigens, including tumor-associated antigens and tumor-specific antigens. The latter, also referred to as neoantigens, are immunogenic mutated peptides presented by major histocompatibility complex class I molecules. While current genomics and bioinformatics technologies have greatly facilitated the identification of tumor neoantigens, identifying individual neoantigens systematically for successful therapies remains a challenging problem. Owing to the initiation of strong, specific tumor-killing cytotoxic T cell responses, neoantigens are emerging as promising targets to develop personalized treatment and have triggered the development of cancer vaccines, adoptive T cell therapies, and combination therapies. This review aims to give a current understanding of the clinical application of neoantigens in EC and provide direction for future investigation.