Changes in the recent three decades and survey on the current status of surgical treatment for esophageal cancer in China.

BACKGROUND: To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. METHODS: We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. RESULTS: A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. CONCLUSIONS: Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

Heterogeneous Uptake of 68 Ga-DOTATATE and 18 F-FDG in Initial Diagnosed Neuroendocrine Tumors Patients : Which Patients Are Suitable for Dual-Tracer PET Imaging?

PURPOSE: This study was designed to assess the uptake heterogeneity in neuroendocrine tumor (NET) patients at initial diagnosis with dual-tracer PET imaging and the staging changes and prognostic value it brings to explore the indication of the use of dual-tracer PET. METHODS: Fifty-one newly diagnosed patients with pathologically confirmed NET who underwent 18 F-FDG and 68 Ga-DOTATATE PET imaging between January 2020 and September 2022 were enrolled. Dual-tracer uptake patterns were classified into 3 groups: A. 68 Ga-DOTATATE positive and 18 F-FDG negative, B. 68 Ga-DOTATATE positive and 18 F-FDG positive, and C. 68 Ga-DOTATATE negative and 18 F-FDG positive. Descriptive statistics were used to evaluate the heterogeneity of dual-tracer uptake patterns among different grading (G) groups, between primary and metastatic lesions, and staging changes. Moreover, dual-tracer uptake patterns, grade, age, sex, and stage were compared with progression-free survival (PFS) by Cox regression. RESULTS: In the different G groups, none of the patients with dual-tracer uptake pattern A had grade 3 histology, but 57% of patients with grade 1 disease had FDG avidity (25% of them resulting in dual-tracer uptake pattern C). Patients with no metastasis were well differentiated, but one of them presented with dual-tracer uptake pattern C. Different uptake patterns were also observed between primary and metastatic lesions, particularly 44% of patients with dual-tracer uptake pattern A of primary with FDG avidity of metastases. Moreover, 9 (17.6%) had new lesions detected by additional 18 F-FDG PET imaging, and 3 of them (5.9%) had clinical stage changed accordingly. The Cox regression test showed that the dual-tracer uptake patterns were significantly correlated with PFS by univariate and multivariate analyses ( P = 0.026 and 0.039, respectively), whereas the grade and stage did not correlate with survival (all P >0.05). CONCLUSION: The current study has proven the uptake heterogeneity of the NET at initial diagnosis and demonstrated the staging and prognostic value of dual-tracer PET imaging. Our preliminary results have confirmed the importance of dual-tracer imaging modalities and concluded that dual-tracer PET imaging could be considered as prognostic tool for all patients with an initial diagnosis of NET.

Long-Term Survival and Recurrence Patterns in Locally Advanced Esophageal Squamous Cell Carcinoma Patients with Pathologic Complete Response After Neoadjuvant Chemotherapy Followed by Surgery.

BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

Spatiotemporal distribution and pollution control of pollutants in a Cr(VI)-contaminated site located in Southern China.

Soil and groundwater Cr(VI) pollution resulting from improper disposal and accidental spills is a critical problem worldwide. In this study, a comprehensive study was conducted to assess the hydrogeological conditions of a contaminated site, obtain spatiotemporal distribution and trend forecasts of pollutant Cr(VI), and determine the feasibility of applying clayey engineered barriers for pollution control. The results showed that the hydraulic conductivity (K) of the clayey barrier (1.56E-5 m/d) is several orders of magnitude lower than that of the stratum beneath the contaminated site, with K values ranging from 0.0014 to 4.76 m/d. Cr(VI) exhibits high mobility and a much higher concentration in the vadose zone, with maximum values of 6100 mg/kg in topsoil and 2090 mg/L in the perched aquifer. The simulation results indicated that the groundwater in the vicinity of the contaminated site, as well as downstream of the Lianshui River, is seriously threatened by Cr(VI). Notably, the pollution plume could occur downstream of the Lianshui River after 8 years. The retention efficiency of clayey engineered barriers will decrease over time, at 61.6% after 8 years and 33% after 20 years. This work contributes to an in-depth understanding of Cr(VI) migration at contaminated sites.

Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer.

BACKGROUND: Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone. METHODS: We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety. RESULTS: A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24-month overall survival was 80.9% in the pembrolizumab group and 77.6% in the placebo group (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of the participants in the pembrolizumab group and in 11.0% of those in the placebo group (difference, 19.2 percentage points; 95% CI, 13.9 to 24.7; P<0.0001; threshold, P = 0.0001), and a pathological complete response occurred in 18.1% and 4.0%, respectively (difference, 14.2 percentage points; 95% CI, 10.1 to 18.7; P<0.0001; threshold, P = 0.0001). Across all treatment phases, 44.9% of the participants in the pembrolizumab group and 37.3% of those in the placebo group had treatment-related adverse events of grade 3 or higher, including 1.0% and 0.8%, respectively, who had grade 5 events. CONCLUSIONS: Among patients with resectable, early-stage NSCLC, neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared with neoadjuvant chemotherapy alone followed by surgery. Overall survival did not differ significantly between the groups in this analysis. (Funded by Merck Sharp and Dohme; KEYNOTE-671 ClinicalTrials.gov number, NCT03425643.).

Prognostic role and predictors of lymph node involvement in pancreatic neuroendocrine tumors.

PURPOSE: To define the prognostic role of lymph node involvement (LNI) in patients with pancreatic neuroendocrine tumors (PNETs) and identify predictors of LNI using a comprehensive multifactor analysis focusing on preoperative radiological features. METHODS: This study included 236 patients with preoperative computed tomography who underwent radical surgical resection of PNETs at our hospital between 2009 and 2019. Univariate and multivariable logistic regression analyses were performed to investigate the risk factors associated with LNI and tumor recurrence. The disease-free survival (DFS) rates with and without LNI were compared. RESULTS: Forty-four of the 236 patients (18.6%) had LNI. Biliopancreatic duct dilatation (odds ratio [OR], 2.295; 95% confidence interval [CI], 1.046-5.035; p = 0.038), tumor margin (OR, 2.189; 95% CI, 1.034-4.632; p = 0.041), and WHO grade (G2: OR, 2.923; 95% CI, 1.005-8.507; p = 0.049; G3: OR, 12.067; 95% CI, 3.057-47.629; p < 0.001) were independent risk factors of LNI in PNETs. Multivariable analysis showed that LNI (OR, 2.728; 95% CI, 1.070-6.954; p = 0.036), G3 (OR, 4.894; 95% CI, 1.047-22.866; p = 0.044), and biliopancreatic duct dilatation (OR, 2.895; 95% CI, 1.124-7.458; p = 0.028) were associated with PNET recurrence in patients after surgery. Patients with LNI had a significantly worse DFS than those without LNI (3-year DFS: 85.9 vs. 96.7%; p < 0.001; 5-year DFS: 65.1 vs. 93.9%; p < 0.001). CONCLUSION: LNI was associated with decreased DFS. Biliopancreatic duct dilatation, irregular tumor margins, and grades G2 and G3 were independent risk factors for LNI.

The differential effects of sarcopenia and cachexia on overall survival for pancreatic ductal adenocarcinoma patients following pancreatectomy: A retrospective study based on a large population.

OBJECTIVES: Both cachexia and sarcopenia have been considered adverse predictors for prognosis in patients with pancreatic cancer; although sarcopenia and cachexia share some similarities, they are still defined as distinct nutritional conditions. We aimed to explore the differential impacts of sarcopenia and cachexia on prognosis for pancreatic ductal adenocarcinoma (PDAC) patients following radical excision. METHODS: From January 2015 to May 2022, 614 patients undergoing surgery for PDAC were retrospectively included. Sarcopenia was defined as the L3 total skeletal muscle index below 52.4 cm2 /m2 (men) and 38.5 cm2 /m2 (women). Cachexia was classified according to the following criteria: involuntary weight loss >5% over the past 6 months, or weight loss >2% and BMI <20 kg/m2 , or weight loss >2% and sarcopenia. RESULTS: Of the 614 patients included in the analysis, 62% and 48% were diagnosed with sarcopenia and cachexia, respectively. Kaplan-Meier analysis showed that sarcopenia and/or cachexia were significantly associated with worse overall survival (OS) rather than worse recurrence-free survival (RFS). Moreover, Cox regression analysis revealed that cachexia rather than sarcopenia was an adverse factor for OS in all PDAC patients. For poorly differentiated PDAC, both cachexia and sarcopenia were significantly associated with shorter OS. However, for moderately/well-differentiated PADC, cachexia was an independent factor for adverse OS, but not sarcopenia. CONCLUSIONS: Sarcopenia and cachexia have different effects on OS for PDAC patients undergoing radical excision. This difference may provide some important information for preoperative management.

Toward regulating biodegradation in stages of polyurethane copolymers with bicontinuous microphase separation.

For typical biodegradable polymers, their overall performance almost declines exponentially to the degradation degree, which inevitably leads to a dilemma between the requirements of service life and retention time in the environment (both in vitro and in vivo). It is a great challenge to develop a biodegradable polymeric device with relatively stable performance in service while rapidly degrading out of service. Herein, we demonstrate an effective strategy to control degradation of biodegradable polymers in stages by constructing separated bicontinuous microphases with very different microphase degradation rates. First, polyurethane copolymers (PCL-b-CrP-U) containing two blocks, i.e., semicrystalline poly(ε-caprolactone) (PCL) blocks and amorphous random copolymer blocks (CrP) based on ε-CL and p-dioxanone (PDO), were synthesized. The microscopic morphology of PCL-b-CrP-U is investigated by an alkali-accelerated degradation experiment, which also demonstrates that the chain cleavage-induced crystallization during degradation resulted in a self-reinforcement by forming degradation residues with a scaffold-like morphology. The tensile test shows that PCL-b-CrP-U has excellent mechanical properties (1500% of elongation at break, a tensile strength of about 7.5 MPa, and an elastic modulus of 40.0 MPa). The degradation experiments with artificial pancreatic juice as a working medium reveal that PCL-b-CrP-U samples containing relatively high PDO units exhibit a three-stage degradation, i.e. an induction stage, a steady degradation stage and an accelerated degradation stage. The CrP phase preferentially hydrolyzes to form some microchannels due to its amorphous nature and relatively high hydrophilicity, effectively accelerating the entry of water and enzymes into the inner parts of the sample. Meanwhile, at this stage, those originally amorphous PCL segments gradually crystalize owing to their enhanced chain mobility induced by the chain cleavage, forming a "scaffold"-like structure, which effectively reinforces the sample to resist the damage from external force and therefore guarantees a relatively stable mechanical performance of PCL-b-CrP-U during service. With the further depletion of the CrP phase, the intermediate "scaffold"-like structure is also very beneficial to accelerate the degradation of residues owing to its large specific surface area, which is expected to be beneficial for preventing long-term retention of the implantation devices.

Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-mutant non-small-cell lung cancer: final overall survival analysis of the EMERGING-CTONG 1103 randomised phase II trial.

EMERGING-CTONG 1103 showed improved progression-free survival (PFS) with neoadjuvant erlotinib vs. chemotherapy for patients harbouring EGFR sensibility mutations and R0 resected stage IIIA-N2 non-small cell lung cancer (NSCLC) (NCT01407822). Herein, we report the final results. Recruited patients were randomly allocated 1:1 to the erlotinib group (150 mg/day orally; neoadjuvant phase for 42 days and adjuvant phase to 12 months) or to the GC group (gemcitabine 1250 mg/m2 plus cisplatin 75 mg/m2 intravenously; 2 cycles in neoadjuvant phase and 2 cycles in adjuvant phase). Objective response rate (ORR), complete pathologic response (pCR), PFS, and overall survival (OS) were assessed along with safety. Post hoc analysis was performed for subsequent treatments after disease recurrence. Among investigated 72 patients (erlotinib, n = 37; GC, n = 35), the median follow-up was 62.5 months. The median OS was 42.2 months (erlotinib) and 36.9 months (GC) (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.47-1.47; p = 0.513). The 3- and 5-year OS rates were 58.6% and 40.8% with erlotinib and 55.9% and 27.6% with GC (p3-y = 0.819, p5-y = 0.252). Subsequent treatment was administered in 71.9% and 81.8% of patients receiving erlotinib and GC, respectively; targeted therapy contributed mostly to OS (HR, 0.35; 95% CI, 0.18-0.70). After disease progression, the ORR was 53.3%, and the median PFS was 10.9 months during the EGFR-TKI rechallenge. During postoperative therapy, grade 3 or 4 adverse events (AEs) were 13.5% in the erlotinib group and 29.4% in the GC group. No serious adverse events were observed. Erlotinib exhibited clinical feasibility for resectable IIIA-N2 NSCLC over chemotherapy in the neoadjuvant setting.

Laboratory investigation on the retention performance of a soil-bentonite mixture used as an engineered barrier: insight into the effects of ionic strength and associated heavy metal ions.

Soil-bentonite (S-B) materials are promising backfill materials for use as engineered barriers in heavy metal-contaminated sites. The effects of contaminant exposure on the retention performance of the S-B barrier remain unrevealed. In this study, based on the pollution status of an abandoned ferroalloy factory located in southern China, the retention performance of the S-B mixture toward Cr(VI) and Zn(II) was studied through adsorption and diffusion experiments sequentially; the separate effect of ionic strength (binary solution) and the combined effect of ionic strength and associated heavy metal ion (ternary solution) were discussed. In NaCl-Cr(VI)/Zn(II) binary solutions, the adsorption of Zn(II) onto the S-B mixture is larger than that of Cr(VI). Kd, Qmax, and ɛacc (accessible porosity) of Cr(VI) increase through increasing ionic strength, while Zn(II) shows the opposite trend; De (effective diffusion coefficient) values for both Cr(VI) and Zn(II) increased with increasing ionic strength and follow a sequence of Cr(VI) > Zn(II), indicating a better retention performance of the S-B mixture to Zn(II). For a given ionic strength, the adsorption of Zn(II) was larger than that of Cr(VI), which can be attributed to the retention specificity of the S-B mixture to anion and cation. In Cr(VI)-Zn(II)-NaCl ternary solutions, the adsorptions of Cr(VI) and Zn(II) are enhanced in varying degrees when compared with their binary solution, which probably could be attributed to the ion bridge role of Cr(VI)/Zn(II) to connect each other that relatively increased the adsorption capacity of S-B material. This work will contribute to an in-depth understanding of the retention performance of the S-B mixture in complicated chemical environments and facilitate the selection of future remediation strategies.

Plain language summary of the CheckMate 816 study results: nivolumab plus chemotherapy given before surgery for non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: In this article, we summarize results from the ongoing phase 3 CheckMate 816 clinical study that were published in The New England Journal of Medicine in 2022. The goal of CheckMate 816 was to find out if nivolumab, an immunotherapy that activates a person's immune system (the body's natural defense system) to fight cancer, plus chemotherapy works better than chemotherapy alone when given before surgery in people with non-small-cell lung cancer (NSCLC) that can be removed surgically (resectable NSCLC). WHAT HAPPENED IN THE STUDY?: Adults who had not previously taken medications to treat NSCLC and whose cancer could be removed with surgery were included in CheckMate 816. During this study, a computer randomly assigned the treatment each person would receive before surgery for NSCLC. In total, 179 people were randomly assigned to receive nivolumab plus chemotherapy, and 179 people were randomly assigned to receive chemotherapy alone. The researchers assessed whether people who received nivolumab plus chemotherapy lived longer without the cancer geting worse or coming back and whether there were any cancer cells left in the tumor and lymph nodes removed by surgery. The researchers also assessed how adding nivolumab to chemotherapy affected the timing and outcomes of surgery and whether the combination of these drugs was safe. WHAT WERE THE RESULTS?: Researchers found that people who took nivolumab plus chemotherapy lived longer without the cancer getting worse or coming back compared with those who took chemotherapy alone. More people in the nivolumab plus chemotherapy group had no cancer cells left in the tumor and lymph nodes removed by surgery. Most people went on to have surgery in both treatment groups; the people who took nivolumab plus chemotherapy instead of chemotherapy alone had less extensive surgeries and were more likely to have good outcomes after less extensive surgeries. Adding nivolumab to chemotherapy did not lead to an increase in the rate of side effects compared with chemotherapy alone, and side effects were generally mild and manageable. WHAT DO THE RESULTS OF THE STUDY MEAN?: Results from CheckMate 816 support the benefit of using nivolumab plus chemotherapy before surgery for people with resectable NSCLC. Clinical Trial Registration: NCT02998528 (ClinicalTrials.gov).

Clinicopathological features and long-term prognosis of purely cystic pancreatic neuroendocrine tumors: A single-center experience.

BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) are heterogenous neoplasms, of which the prognosis varies widely. Purely cystic pancreatic neuroendocrine tumors (C-pNETs) are a small subset of pNETs in which data are extremely rare. This study aimed to compare clinicopathological and long-term survival differences between C-pNETs and solid pNETs (S-pNETs). METHODS: A retrospective review of 242 patients with pNETs underwent resection in our institution from 2009 to 2019 was conducted. Demography characteristics, clinicopathological features and long-term outcomes of them were analyzed. RESULTS: Sixteen out of 242 patients (6.6%) were identified as C-pNETs. Compared with S-pNETs, C-pNETs were more frequently non-functional (75% vs 45%, P = 0.02), and the median tumor diameter of C-pNETs was smaller (36 mm vs. 47 mm, P = 0.001). And the accuracy of preoperative diagnosis of C-pNETs was significantly lower (31% vs 78%, P = 0.001). Of note, the majority of C-pNETs were well-differentiated with G1 (81% vs 35%, P = 0.001). And there were no G3 (0 vs 7%, P = 0.001) in C-pNETs. No T4 stage or R1/R2 surgical margin detected in C-pNETs. And only one C-pNETs (6%) had regional lymph node metastasis (N) or synchronous distant metastasis (M). Additionally, only one patient with C-pNETs (6%) suffered tumor recurrence, compared with 24 (13%) for S-pNETs. And survival analysis showed the patients with C-pNETs seemed to be with better disease-free survival (P = 0.26). CONCLUSION: C-pNETs are rare subtype with possibly less aggressive behavior comparing with their solid counterparts. Recurrence and tumor-related death still occurs in patients with resected C-pNETs, although they tend to be with more favorable prognosis.

Pre-operative oil ingestion reduces the probability of thoracic duct trunk ligation during esophagectomy.

Chylothorax is an important complication after esophagectomy. Ligation of the injured thoracic duct is the main method to prevent chylothorax after esophagectomy, but may be associated with adverse effects. Whether ligation of the injured tributary alone, keeping the main trunk intact, may suffice to prevent post-operative chylothorax is not well known. Since March 2017, 40 mL of olive oil was administered to patients posted for esophagectomy. We compared patients admitted between March 2017 and December 2019 with patients admitted between July 2014 and February 2017, who had not received pre-operative oil. The outcome measures were the need for thoracic duct main trunk or tributary ligation, development of chylothorax and missed ligation. There were 371 patients in the oil ingestion group and 308 patients in the standard control group. Chylothorax in the oil ingestion group was significantly lower than that in the standard control group (1.3% vs. 4.5%, P = 0.012). Chyle leak from thoracic duct tributaries was diagnosed in a significantly higher percentage (5.7% vs. 0.0%, P < 0.001) and missed ligation of the injured thoracic duct was significantly lower (0.3% vs. 3.9%, P = 0.002) in the oil ingestion group compared with the standard control group. The incidence of post-operative chylothorax was not statistically different (6.3% vs. 10.0%, P = 1.000) between the tributary and the trunk ligation group. Pre-operative oil ingestion can help visualize the thoracic duct trunk and its tributaries during esophagectomy. Thus, non-selected thoracic duct trunk ligation and missed ligation during esophagectomy can be reduced. Precise ligation of the injured tributary while the main trunk is intact can also prevent post-operative chylothorax.

Feasibility of same-day discharge following endoscopic submucosal dissection for esophageal or gastric early cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an established technique for the treatment of early gastrointestinal neoplasia. Generally, multi-day (M-D) admission is required for patients undergoing ESD due to potential complications. AIM: To evaluate the feasibility of a same-day (S-D) discharge strategy for ESD of the esophagus or stomach. METHODS: The data of patients who underwent esophageal or gastric ESD were retrospectively collected from January 2018 to December 2021 at Peking University Cancer Hospital. The propensity score matching (PSM) method was applied to balance the unevenly distributed patient baseline characteristics between the S-D and M-D groups. Intraoperative and postoperative parameters were compared between the matched groups. RESULTS: Among the 479 patients reviewed, 470 patients, including 91 in the S-D group and 379 in the M-D group, fulfilled the inclusion and exclusion criteria. Following PSM, 78 patients in each group were paired using the 1:1 nearest available score match algorithm. No significant difference was found between groups with respect to intraoperative and postprocedural major adverse events (AEs). Tumor size, complete resection rate, and procedural duration were comparable between the groups. The S-D group demonstrated a significantly shorter length of hospital stay (P < 0.001) and lower overall medical expenses (P < 0.001) compared with the M-D group. CONCLUSION: The S-D discharge strategy may be feasible and effective for esophagogastric ESD, and the procedural-related AEs can be managed successfully.

IGFBP1hiWNT3Alo Subtype in Esophageal Cancer Predicts Response and Prolonged Survival with PD-(L)1 Inhibitor.

PD-(L)1 inhibitor could improve the survival of locally advanced esophageal cancer (ESCA) patients, but we cannot tailor the treatment to common biomarkers. WNT signaling activation was associated with primary resistance to immunotherapy. In this study, we used our two clinical cohorts (BJCH n = 95, BJIM n = 21) and three public cohorts to evaluate and verify a new immunotherapeutic biomarker based on WNT signaling in ESCA patients. Our findings showed that WNT signaling-related genes stratified TCGA patients into Cluster 1, 2, and 3, among which, Cluster 3 had the worst prognosis. The most up- and down-regulated genes in Cluster 3 were IGFBP1 and WNT3A. Further analysis validated that IGFBP1hiWNT3Alo ESCA patients had significantly poor RFS and OS in the TCGA and BJCH cohorts. Interestingly, IGFBP1hiWNT3Alo patients had a good response and prognosis with immunotherapy in three independent cohorts, exhibiting better predictive value than PD-L1 expression (signature AUC = 0.750; PD-L1 AUC = 0.571). Moreover, IGFBP1hiWNT3Alo patients may benefit more from immunotherapy than standard treatment (p = 0.026). Immune cell infiltration analysis revealed a significant increase in DC infiltration in IGFBP1hiWNT3Alo patients post-immunotherapy (p = 0.022), which may enhance immune response. The IGFBP1hiWNT3Alo signature could predict patients who benefited from PD-(L)1 inhibitor treatment and may serve as a biomarker in ESCA.

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.